The COVID Commentaries A Chronicle of a Plague Personal Commentaries on COVID-19 from January 2020 to December 2021
WILLIAM A. HASELTINE, PhD
Copyright © 2023 by William A. Haseltine, PhD All rights reserved. No part of this book may be used or reproduced by any means, graphic, electronic, or mechanical, including photocopying, recording, taping, or by any information storage retrieval system, without the written permission of the publisher except in the case of brief quotations embodied in critical articles and reviews. All author proceeds from the sale of the COVID Commentaries will be donated to the nonprofit global think tank ACCESS Health International.
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Thank you for purchasing the COVID Commentaries: A Chronicle of a Plague. This book is a Living eBook. It will be updated regularly with new resources and information about COVID-19. When you purchased this book, you also purchased access to every subsequent edition of the book, as it is released. To access future editions, please visit: www.williamhaseltine.com/commentaries You’ll be taken to a special section of our website where you can download the most up to date version.
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Introduction In early 2020, I was working on the final chapters of my autobiography, My Lifelong Fight Against Disease. It was then that I heard the first rumblings of concern about a new pneumonia-like illness coming from Wuhan, China. COVID-19 has gone on to infect at least twenty five million people worldwide and, as of this writing, can be tied to nearly one million deaths. Despite the breadth of damage COVID-19 has already wrought, we are only beginning to glimpse what its long term toll might be. There is no doubt though that the impact of the pandemic will be massive, indelibly imprinting and changing the behaviors of our rising generations. My personal losses have been far fewer than what many have suffered. Yet COVID-19 has still completely upended my life. From the very beginning of the outbreak, my friends and colleagues have come to me for counsel. Some wanted to know the best way to protect their families. Some wanted to discuss the science behind the virus itself. Still others sought to commiserate over how poorly our leaders seemed to grasp the seriousness of the pandemic. In most all cases, I found I had something to offer. Today after a lifetime spent in science, medicine and pursuing better public health, I find myself once again logging eighteen hour days battling a new and still somewhat unknown disease. I am working closely with three generations of students—my former students, their former students and those who studied under them— to understand the virus and what makes it tick. Together, and along with many in the private sector I have worked with over the years, we are doing what we can to create new diagnostic tests, new drugs and new vaccines. I have also been asked by governments all over the world – in Europe, Asia, the Middle East, Africa and here in the United States – for advice on the best policies and containment measures. Equally important is my effort to advance the public’s understanding of SARS-CoV-2 and how to defeat it. On January 22, a day after the first COVID-19 case was diagnosed in the United iv
States, President Donald Trump declared on national television that the U.S. had the virus “totally under control.” In fact, no coordinated plan was in place to contain an outbreak that by then might have been spreading within our borders for weeks. A week after that hollow declaration, I published an article in Scientific American, “Want to Prevent Another Coronavirus Epidemic? We need to treat it as the deadly biological threat that it is.” Since then, my opinions about ongoing news, research and other developments in the pandemic have been sought regularly, many times a week, in live conversations with anchors at major cable news networks MSNBC, CNN, Fox and international networks like Bloomberg Asia and CGTV. My commentaries on COVID-19 have been published online and in print at the Washington Post, Los Angeles Times, Project Syndicate, CNN.com, Forbes.com and Psychology Today. I have interviewed dozens of physicians, scientists and economists as they published new research or proposed new ideas. Suggestions I offered on their approaches often enabled me to discover new details that in turn deepened my understanding of the virus, our attempts to contain it and the long term effects now unfolding. The COVID Commentaries contain a collection of my writings, research and interviews on COVID-19. This is a Living eBook, updated regularly with new information on the disease and our response as it unfolds. It is organized into three sections. The first contains my published commentaries on the outbreak, giving you an in-depth account of the most pressing topics at the time. The second section provides links to my media interviews and mentions in news articles. Finally, at the end of the book, you’ll find a collection of my social media posts, offering a quick, spur of the moment glimpse into my thinking day to day. For a robust assemblage of COVID-related news, medical and scientific research papers, webinars and online resources from other organizations, feel free to head over to my website: https://covid19resources.org/ I first coined the term Living eBook when I published A Family Guide to COVID: Questions & Answers for Parents, Grandparents & Children in June 2020. At the time, I was acutely aware of how frustrated, confused and frightened many people were over what was happening in the world, their world. My goal in writing the book v
was to simplify the science and make as much information as possible available to anyone looking for answers to those questions and others like them. I also wanted to make sure that the information in the book was as accurate as possible. I knew that as the science and our understanding of the virus evolved, so too would my recommendations of how best to protect ourselves and those we love against infection. I soon found that no publishing house would be able to deliver a book as quickly as we needed or update it as regularly as I wanted so I created a new genre of books. The Family Guide and my subsequent book, A COVID Back To School Guide: Questions and Answers for Parents and Students, were the first books published as Living eBooks. They are free on the ACCESS Health website and available in print on Amazon. Each time new discoveries happen, we update the books immediately on our website and within a few days through the major retailers. The Commentaries follow the same format. When this pandemic is finally over, as it no doubt will be one day, my hope is that my Commentaries will provide the historical perspective to help us reckon with mistakes we have made, especially in the United States, and provide insights into how we might better contain the next contagion and reduce the number of lives ultimately, needlessly lost—a modern day version of Samuel Pepys’s Plague Diary.
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Table of Contents Introduction ................................................................ iv Personal Commentaries ................................................. 1 January 2020 ..................................................................................... 2 What Makes This Coronavirus Different—And What We Can Do About It ........................................................................................ 3 Want to Prevent Another Coronavirus Epidemic? ......................... 6 The US Isn’t defenseless Against The Coronavirus, But It Is Unprepared ................................................................................... 9 What Governments Must Do To Deliver An Anti Coronavirus Drug Within Months ...................................................................12 February 2020 ..................................................................................14 Escalate Federal Action Against The Coronavirus Before It’s Too Late..............................................................................................15 Solving The Coronavirus Identity Crisis: A Strategy For Prevention ............................................................17 Why Are We So Fearful of the New Coronavirus? .......................19 Scientists Warned About Coronavirus For Years But Got Nowhere. Here’s How To Fix That .............................................................22 U.S. Hospitals Are Unprepared For The Spread Of Coronavirus. Here’s What They Should Do ......................................................25 March 2020 .....................................................................................27 Four Coronavirus Prevention Steps We Can All Take ..................28 Coronavirus Mismanagement Is Risking American Lives ..............30 Social Workers Have A Key Role To Play In The War Against Coronavirus .................................................................................32 Coronavirus Pandemic Could End In These Ways – Maybe Sooner Than We Expect ..........................................................................34 Wondering What A Coronavirus Quarantine Is Really Like? ........37 Terrified of Quarantine? Here’s What It Actually Looks Like ........42 Hydroxychloroquine Is Ineffective In Treatment Of Patients Hospitalized With COVID-19, According To Small Controlled Trial From Shanghai .....................................................................45 Study Shows Hydroxychloroquine Is Ineffective Against COVID19 — So What Now? ...................................................................47 Is This Coronavirus Epidemic The Big One? ................................49 Why America Is Losing to COVID-19 .........................................51
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April 2020 ....................................................................................... 52 Why Don’t We Have A Coronavirus Drug Yet—And How We Can Develop One As Soon As Possible ........................................ 53 Why Researchers Are Exploring Antibodies From Recovered Patients For Possible Treatment And Prevention Of COVID-19 .. 59 How Antibody Tests Can Be Used To Fight COVID-19 ............. 64 Opportunity Lost: Avoiding Further Missteps With COVID-19 And Future Biothreats .................................................................. 67 Can We Really Develop A Safe, Effective Coronavirus Vaccine? .. 70 Beyond Flattening The Curve, Here's How To End The Pandemic ...................................................................... 74 Tests For COVID-19 Are Expensive, But They Don’t Have To Be .............................................................. 77 A Troubling Tale Of Two Children In The Time Of COVID-1979 The Challenges Of Testing For COVID-19 ................................. 81 How Do We Reduce Our In Hospital Death Rates? .................... 83 We Need To Crush The Curve Now—Or COVID-19 Will Come Back To Haunt Us ....................................................................... 88 19% Of People Infected With COVID In The US Are Healthcare Professionals. Almost Three Quarters Of Them Are Women ........ 91 New Study Finds 15% Of Pregnant Women At Two New York Hospitals Tested Positive For COVID-19 .................................... 92 A New Normal For Hospital Care ............................................... 94 Why COVID? Nature’s Code Cracking Machine Intelligence ...... 96 What Did We Know And When Did We Know It? Disease Surveillance: Past, Present And Future ........................................ 100 How Many Tests Do We Really Need? ..................................... 107 In Some Hospitals, Surviving COVID Is Almost Twice As Likely ......................................................................... 109 This Is How You Can Return To Work Safely .......................... 111 Monoclonal Antibodies Could Help Fight Against Coronavirus .. 114 How Business Leaders Can Respond COVID-19 ....................... 117 Reopening America Will Require This Key Thing That's Been Ignored ...................................................................................... 121 A Vaccine Candidate Protects Non-Human Primates From SARSCoV-2 Infection ........................................................................ 123 A Letter To Congress: Four Principles For A Safe Economic Reopening ................................................................................. 125 Reducing The Risk Of In Flight COVID-19 Transmission ........ 127 Urging Caution On Remdesivir................................................. 128 An Urgent Need To Reopen Medical Care For All.................... 130
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May 2020 ...................................................................................... 133 Remdesivir: A Non-Antiviral Antiviral Drug? ............................ 134 COVID Immunity: How Protected Are You? ............................ 136 Responsible Reopening: A Lesson From NYU Shanghai ............ 138 Can America Handle A Second Wave? ....................................... 140 A Walk With Death ................................................................... 141 Blood Clotting And COVID-19: How Serious Is It? .................. 143 Putting COVID-19 Behind Us: A Research Agenda To Prepare For The Next Pandemic ................................................................... 145 Hong Kong Doctors See Progress In Treatment Of COVID-19 . 149 Why Haven’t We Seen The Data On Remdesivir? ..................... 151 Which COVID-19 Antivirals Actually Work? ............................ 153 Why Weren’t We Ready For The Coronavirus? ........................ 155 Rapid, Accessible, Affordable, Ubiquitous Tests For SARS-CoV-2 Are On The Way ....................................................................... 157 One Step Closer To Understanding The Origin Of SARS-CoV-2..................................................... 160 Progress And Possibilities For Treating COVID-19 .................... 162 COVID-19 Among Children ..................................................... 165 What AIDS Taught Us About Our Coronavirus Response ......... 166 Did The Oxford COVID Vaccine Work In Monkeys? Not Really ................................................................................. 167 MIS-C: A New Name For COVID Kawasaki/Toxic Shock In Young People ............................................................................ 170 Moderna’s Claim Of Favorable Results In Its Vaccine Trial Is An Example Of ‘Publication By Press Release’ ................................. 173 What Happens If We Can’t Find A Coronavirus Vaccine That Works?....................................................................................... 176 It’s Too Early For The US Government To Place Risky, Billion Dollar Bets On COVID Vaccines ............................................... 178 Remdesivir Revealed ................................................................. 180 Will Memorial Day 2020 Be Remembered As The Holiday When COVID-19 Got The Upper Hand? ............................................ 183 The Way That COVID-19 Tricks The Immune System Could Result In More Severe Illness ..................................................... 186 Key Protein That Leads To COVID-19 Infection May Be Less Common In Children, Researchers Find .................................... 189 Confronting Barriers To COVID-19 Vaccine Acceptance .......... 191 June 2020 ...................................................................................... 193 COVID-19 In Children: A Detailed Study Of 10 Italian Children .......................................................................... 194 Two Weeks And Ten Million COVID Tests In Wuhan ............. 197
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COVID-19 In Kids: A Reason To Be Wary Of COVID Vaccines ....................................................................... 200 A Warning From Sweden’s Coronavirus Response ..................... 202 Human COVID-19 Vaccine Trials Are Unnecessary, Uninformative, And Unethical ................................................... 204 The Role Of Blood Type In COVID-19 Infection And Respiratory Failure ....................................................................................... 205 Wounded In Action From COVID-19 ...................................... 207 A Mutation Shows Why the Coronavirus Is Such A Formidable Foe ...................................................................... 208 A New CDC Report Shows COVID Disproportionately Affects Those With Underlying Disease And Disadvantaged Minorities .. 209 Traveling By Air In The Time Of COVID ................................ 212 Dexamethasone Reduces Mortality In Seriously Ill COVID-19 Patients—And So Do Other Treatments .................................... 214 More Publication By Press Release, This Time From Sinovac On A COVID Vaccine ........................................................................ 216 Are Children Less Easily Infected By SARS-CoV-2? Maybe Yes And Maybe No .......................................................................... 218 Immunity To COVID-19 Infection May Fade Quickly .............. 220 Successful Reopening: It's Not What You Think ....................... 223 The Risks Of Rushing A COVID-19 Vaccine ........................... 226 Protecting Pregnant Women From COVID-19.......................... 229 A Tale Of Four Cities: Wuhan, Seattle, New York, Chicago ..... 231 Progress In Monoclonal Antibodies For The Treatment And Prevent-Of-COVID-19 ............................................................. 233 COVID-19 Ping-Pong: Animal To Human, Human To Animal, Animal To Human Transmission. How Great A Danger? ........... 236 We’re Making Exciting Progress In Developing COVID-19 Drugs ...................................................................... 238 The Other Shoe Drops: Gilead’s Outrageous Pricing Of Remdesivir ............................................................... 241 Women’s Health And The Ripple Effect Of The COVID-19 Pandemic ................................................................ 243 July 2020 ....................................................................................... 245 Lessons For COVID-19 From The Early Days Of AIDS ............ 246 Even Without A COVID-19 Vaccine, There's Reason For Hope ...................................................................... 250 Is Wearable Technology The Savior We’ve Been Waiting For? .. 251 Is It Too Soon To Restart Sports? .............................................. 255
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Midsummer For The Season—But Not The Coronavirus: A Case In Poor Leadership, The U.S. Containment Strategy Has Lacked Clarity, Consistency, Credibility, And Compassion ..................... 257 We're Wasting Time Talking About Herd Immunity.................. 261 What Does Disappearing Immunity To COVID-19 Mean For A Vaccine?..................................................................................... 262 A Key To Understanding The Race For A COVID-19 Vaccine . 266 COVID-19 Might Be Far More Widespread Than We Think. Here’s What We Can Do About It ............................................. 270 The Complex Pathogenesis Of COVID-19 ................................ 272 What If There’s No COVID Vaccine? ....................................... 274 An Investigation Into The Basis For The Loss Of Smell As An Early Symptom Of COVID-19 ........................................................... 275 India Approves Antigen Test To Speed Detection And Management Of SARS-CoV-2 Infections ....................................................... 278 New Evidence Suggests Young Children Spread COVID-19 More Efficiently Than Adults ............................................................... 281 August 2020................................................................................... 283 The Flu Could Send Our Healthcare System Into Overdrive This Winter. This Drug Offers Some Hope. ....................................... 284 Two-Step Testing Could Slow COVID-19 Transmission Dramatically ............................................................................... 285 Will Reopening Gyms Improve Our Well-Being Or Put Us At Risk?.......................................................................................... 287 Back To School: A Tipping Point In US Politics ........................ 290 What Restarting Sports And Reopening Schools Have In Common .................................................................................................. 292 Cheap, Daily Home Tests Are The First Step To Containing The Pandemic ................................................................................... 295 The Moral Trauma of COVID-19: How the failures of our national leaders have torn the moral fabric of our lives ............................. 299 Why Most Voters Oppose Schools Reopening ........................... 305 Deregulating COVID-19 Treatment Sets Dangerous Precedent for Vaccine Approval ....................................................................... 307 New CDC Guidelines Decrease Coronavirus Testing For Those Who Need It Most..................................................................... 310 September 2020 ............................................................................. 313 Containing COVID—American Style ........................................ 314 How We Can Contain COVID-19 Without A Vaccine ............. 320 Herd Immunity: Reckless And Ineffective Strategy ..................... 321 The Case For Safer Emergency Use Authorizations .................... 323
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Why Suspension Of The AstraZeneca Vaccine Trial Matters ...... 325 A Defense of Self-Testing and Supported Self-Isolation .............. 327 The University Of Illinois’s COVID-19 Control Shows That Mass Testing Is The Answer ............................................................... 330 Paused AstraZeneca Trials Emphasize Need For Vaccine Transparency ............................................................................. 332 Why We Can’t Rely On Natural Immunity To Protect Us From COVID-19 ................................................................................ 335 Herd Immunity Is A Fantasy ...................................................... 337 Lessons From AIDS For The COVID-19 Pandemic: We Can Learn From Parallels Between The Coronavirus And HIV Crises ......... 338 Beware Of COVID-19 VaccineTrials Designed To Succeed From The Start.................................................................................... 348 What COVID-19 Reinfection Means For Vaccines.................... 351 COVID-19 Vaccine Protocols Reveal That Trials Are Designed To Succeed ..................................................................................... 356 To Contain COVID-19, Combine Mass Testing With Social And Economic Assistance .................................................................. 360 October 2020 ................................................................................ 363 Eroding Faith In Public Health Leaders ...................................... 364 The Encounter Was Inevitable. Trump Meets The Coronavirus. 367 Herd Immunity Will Not Defeat COVID-19 ............................. 370 All The President’s Medicine ..................................................... 373 The Difference Between COVID-19 And HIV/AIDS ............... 376 COVID-19 Traumatic Stress Disorder: A Definition Of A New Disease: CVTSD. ....................................................................... 378 This Is Trump’s Last, Best Chance To Tell The Truth About The Virus .......................................................................................... 381 White House Continues To Choose Political Gain Over Public Health........................................................................................ 384 Federal Health Agencies Push Back Against Political Interference 386 What The Pause In The Johnson & Johnson And Eli Lilly COVID Drug Trials May Mean ............................................................... 389 How US Public Health Failed You And Me .............................. 391 Herd Immunity Is A Double Tragedy In The Making ................ 395 Compromised Type I Interferon Response Common Among Severe COVID-19 Patients ........................................................ 397 Eli Lilly Plant Set To Manufacture COVID-19 Therapy Cited For Breaching FDA Regulations ....................................................... 400 Massive COVID-19 Drug Trial Underscores Importance Of Controlled Clinical Studies ......................................................... 403
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Underfunding Public Health Harms Americans Beyond COVID-19 ................................................................................ 406 More Troubling Events In The Rush To Find COVID-19 Vaccine ................................................................... 410 Vaccine Transporters Feel Unprepared For The Distributive Effort Ahead ........................................................................................ 413 Three Takeaways From Major FDA Advisory Meeting On COVID-19 Vaccines .................................................................. 416 Despite Conflicting Evidence, FDA Approves COVID-19 Drug Remdesivir ................................................................................ 419 Restructuring The Federal Response To A Pandemic ................. 421 In Brazil, New Study Shows The Poor And Indigenous Suffer The Most From COVID-19 .............................................................. 426 Britain's Moral Bankruptcy Over COVID-19 Vaccines ............... 430 Large Contact Tracing Study Reveals Efficient COVID Transmission Within All Age Groups From 5-10 Years On Up .. 433 Eli Lilly Stops Antibody Trial In Hospitalized COVID-19 Patients ................................................................... 437 New Study Offers More Evidence That Immunity To COVID-19 Fades Quickly ............................................................................ 440 The FDA Will Not Inspect Vaccine Production Plants ............... 443 New Research On Flu Vaccines Sheds Light On COVID-19 Vaccines ..................................................................................... 445 November 2020 ............................................................................. 447 New York City Limits The Chances For In-Person Learning For Students ..................................................................................... 448 Kushner Comments Suggest COVID-19 Decisions Are Politically Motivated .................................................................................. 450 What Are Autoantibodies? The Latest Risk Factor For Severe COVID-19 ................................................................................ 452 Lancet Study Suggests U.S. Is Massively Undercounting COVID-19 Cases .......................................................................................... 455 Lancet Study Concludes That Public Health Interventions Reduce Viral Transmission ...................................................................... 457 How Obesity Puts You At Risk For COVID-19 ........................ 460 A More Transparent And Trusted COVID Vaccine .................... 462 Pregnant Women Are At Higher Risk For Severe COVID-19 And Death ......................................................................................... 464 Are Frozen Foods A Risk For COVID-19 Infection? Possibly. ... 467 One Tenth Of Americans Infected By COVID-19 Are Children 469 This Nasal Spray Could Be The Breakthrough We Need To End COVID-19 ................................................................................ 471
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Long Lasting HIV Drugs Hold Lessons For Us All ...................... 473 A Ray Of Hope For Treatment Of COVID-19 ......................... 476 “COVID-19 Has Laid Bare The Inequities In Our Health System. What Are We Going To Do About It?” ..................................... 479 A Note Of Caution On Moderna’s Promising COVID-19 Vaccine News ......................................................................................... 482 Build A Plan For COVID-19 Home Testing On Reason, Not Speculation Or Politics ............................................................... 485 Do Not Ignore COVID-19 Safety This Thanksgiving ................ 489 China Aims To Eliminate COVID-19 With New Testing Policy ............................................................................ 492 We Finally Have Rapid At-Home COVID-19 Tests. What Happens Now? .......................................................................... 494 To Guarantee Safety Of COVID-19 Vaccines, Prioritize LongTerm Studies ............................................................................. 497 COVID-19 Reinfection Is Possible And Should Inform Pandemic Priorities Moving Forward ......................................................... 500 How Is COVID-19 Impacting The Preparedness Of The US Military? .................................................................................... 503 Don’t Assume A 14-Day Quarantine Is Enough ......................... 506 One Man, One Plane, Seven Infections And Counting: A Cautionary Tale For All Those Planning Air Travel.................... 508 The Mental Health Toll Of COVID-19 ..................................... 510 Why The Biden Team Must Prioritize Cheap COVID-19 Rapid Test Production And Distribution .............................................. 513 Put An End To Publication By Proclamation For COVID Vaccines ....................................................................... 515 December 2020 ............................................................................. 517 Why Most Countries Won't Benefit From Moderna And Pfizer’s Covid-19 Vaccines ..................................................................... 518 These Forms Of Covid-19 Transmission May Be Rare, But Can’t Be Ignored ................................................................................. 521 America Needs a COVID-19 Reckoning ................................... 524 UK Vaccine Approval Sets Worrying Precedent For World Leaders ........................................................................... 528 Modified CDC Guidelines Grant Covid-19 Patients Discretion To Leave Quarantine Early .............................................................. 530 New Study Shows Deep Impact Of Climate Change On Human Health........................................................................................ 532 Cancer Rates Are On The Rise In Adolescents And Young Adults New Study Shows...................................................................... 535 COVID-19: An Investment in Our Economy ............................ 538
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How Will A Covid-19 Vaccine Impact Travel? .......................... 542 Even With A Vaccine, We Still Need Rapid Tests To End Covid-19 ................................................................................... 544 The Trouble With Herd Immunity And Covid-19 Vaccines....... 547 The Covid-19 Pandemic Is Threatening Decades Of Progress In Global Health ............................................................................. 550 Covid-19 Is Preventing Sustainable Investment In Developing Nations ...................................................................................... 553 Why Covid-19 Is Overwhelming California ............................... 555 Covid-19 Home Tests Should Be Much Cheaper ....................... 558 The Mouse That Roared: What The US Can Learn From Andorra About Covid-19 Testing ............................................................ 561 When Implementing Or Easing Restrictions For Covid-19, Transparency Is Paramount ......................................................... 564 The Moderna Vaccine’s Antibodies May Not Last As Long As We Hoped........................................................................................ 569 Urban Flight Due To Covid-19 Is Temporary, Not Permanent .. 572 Here's what's worrying about the coronavirus variant .................. 575 Why Most Countries Won't Benefit From Moderna and Pfizer’s Covid-19 Vaccines ..................................................................... 576 There Will Be No Quick COVID Fix ....................................... 579 It’s Time To Recalibrate: New Covid-19 Strains Will Only Make The Pandemic Worse ................................................................. 583 How The US Military Is Handling Covid-19 And What We Can Learn From Their Experience .................................................... 586 January 2021 .................................................................................. 589 Vaccines Need To Be Cheap And Accessible Worldwide ........... 590 The Risks Of Delaying Or Diluting Covid-19 Vaccines ............. 592 New Covid-19 Variants In One Country Pose A Threat To All Countries ................................................................................... 594 How The Covid-19 Virus Changes ............................................ 596 How To Decipher The New Pfizer Study On Vaccines And Variants ...................................................................................... 599 Why The U.S. Needs To Step Up Covid-19 Genome Sequencing .................................................................. 602 Who Are The Vaccinated That Still Become Infected? ............... 605 Are We Creating Immune Resistant Variants Of SARS-CoV-2? 608 How The Vaccine Rollout Went Wrong And What To Do Next .................................................................................................. 611 How New Covid-19 Variants Might Impact Vaccines ................ 614 New Covid-19 Variants Reshape Our Understanding Of Reinfection ................................................................................ 617
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Researchers Identify New Covid-19 Variant In Ohio ................. 619 Why America Should Look To China To Contain Covid-19 ..... 622 When Society Returns To Normal Post-Pandemic, Common Viruses Will Return In Droves ................................................... 624 Can SARS-CoV-2 Become Even More Troublesome Than The U.K. And South African Variants? .............................................. 627 The US Must Develop A National Vaccine Registry .................. 630 Billions In Low-Income Nations Will Not Receive Their Covid-19 Vaccine Anytime Soon............................................................... 632 Biden’s Covid-19 Plan Is A Welcome Relief — But It Needs To Go Further................................................................................. 634 For Insight On New Covid-19 Variants, Look To Natural History Of Coronaviruses ....................................................................... 639 Why Patterns In Covid-19 Variation Might Resemble Seasonal Flu ............................................................... 644 This Devastating Covid-19 Outbreak In Brazil Is A Warning To The Rest Of The World ............................................................ 647 Opinion: “A Great Moment For Science” .................................. 650 A Tale Of Two Viruses .............................................................. 653 Autoantibodies May Be A Driver Of Severe Covid-19 Reactions ................................................................... 657 Israeli Study Shows A Majority Of Those Vaccinated Can Be Infected By SARS-CoV-2 After The First Shot .......................... 660 SARS-CoV-2 Immunity: A Moving Target ............................... 663 Eli Lilly’s Latest Combination Antibody Therapy Yields Strong Effectiveness Against Covid-19................................................... 665 February 2021................................................................................ 667 Will Population (Herd) Immunity To Covid-19 Be Permanent Or Seasonal? .................................................................................... 668 Travel Bans Won’t Stop The Spread Of New Variants — Travel Restrictions Might ..................................................................... 673 Concerns Grow Over The Newly Discovered Southern California Covid-19 Variant ....................................................................... 676 COVID Control American Style ................................................ 679 Covid-19 Could End Up Like The Flu—Or Worse ................... 683 Weighing Biden's First Executive Orders to Address COVID-19 691 Persistently Infected Covid-19 Patients: A Potential Source For New Variants ............................................................................. 696 Rapid Spread Of Variants Across Europe Is A Dire Warning For The U.S..................................................................................... 700 This Region Of The Covid-19 Virus Is One We Can’t Ignore... 703
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How One Covid-19 Patient’s Infection Foreshadowed The Rise Of New Variants ............................................................................. 706 How will the Coronavirus Evolve? ............................................. 710 What Are The 677 Mutations? New Covid-19 Variants Found In The US ...................................................................................... 713 UK Approves Human Challenge Trials For Covid-19, But At What Cost? .......................................................................................... 716 NBA Study Reveals The UK Variant May Last Longer In Human Hosts.......................................................................................... 718 Variants Could Cause A Rapid Rise In Covid-19 Cases In The U.S. Unless We Implement These Public Health Measures ................. 721 Beware The Next Wave: What To Expect From Covid-19 ........ 726 Questions The FDA Must Ask Drug Makers As It Considers Full COVID-19 Vaccine Approval .................................................... 730 New SARS-CoV-2 Variant Discovered In Japan Nearly Identical To Dangerous Brazilian Variant .................................................. 732 The Spread Of New Variants Calls For Extending Quarantine Guidelines .................................................................................. 735 What To Make Of Covid-19 Infections In French Daycare Centers ......................................................................... 738 Opinion: “How To Redesign Covid-19 Vaccines So They Protect Against Variants” ........................................................................ 740 Pfizer/BioNtech And Moderna MRNA Covid-19 Vaccines Closely Mimic The Immune Response Of Natural SARS-CoV-2 Infections ............................................................ 743 If I Had Covid-19, Should I Still Get Vaccinated? Absolutely ..... 747 A New Covid-19 Variant From Nigeria Raises Increased Concerns For Containment And Vaccination ............................................. 750 Identification of a Novel Covid-19 Variant Cluster Isolated from a Sick Newborn in US Capital ...................................................... 753 New York Finds Its Own Covid Variants. The News Is Not Good ............................................................. 756 Covid-19 Cases Are Rising Again Globally................................. 759 Self-Testing: A Route To School Re-Opening – The Austrian Example ..................................................................................... 761 Should Anticoagulants Be Used Early Or Late In Patients Hospitalized With Covid-19: Two Conflicting Answers ............. 763 The California Variant Is More Transmissible, Evokes Worse Symptoms, And May Resist Vaccines ......................................... 766 Schools Must Reconsider Accelerating Plans To Reopen In Light Of Dangerous New Covid-19 Variants ....................................... 769
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March 2021 ................................................................................... 772 Italian Scientists Create Live SARS-CoV-2 Neutralization Escape Variant ....................................................................................... 773 New York Covid-19 Variants Are Causing Concern .................. 776 How COVID-19 Could Make Us Healthier .............................. 779 Variants: Forewarned Is Forearmed— For Those Who Listen ..... 782 More Cause For Concern Around Covid-19 And Schools .......... 785 Opinion: “Covid-19 Variants and the Safety of Students” ........... 787 Lessons From The Past And Present For Controlling Covid-19: Polio .......................................................................................... 790 T-Cell Responses Hold Up Against SARS-CoV-2 Variants, Study Finds .......................................................................................... 795 The Covid Syndemic: The Mental Health Crisis Of Mental Health Workers ..................................................................................... 798 Covid-19 Reinfections Are Real And Serious—All The More Reason To Be Vaccinated .......................................................... 801 New Study Using Live Virus Explores Whether Pfizer-BioNTech Vaccine Protects Against Variants ............................................... 804 New Hope For A Covid-19 Vaccine That Protects Against All Variants...................................................................................... 807 Clearer COVID-19 Guidelines Cause Less Stress for Us All ........ 810 Novavax Covid-19 Vaccine Performs Well In Clinical Trials, But Variants Remain A Threat ......................................................... 814 Molnupiravir: A New Hope For Prevention And Treatment Of Covid-19 And Other Dangerous Viruses .................................... 816 COVID-19 Survivors At Risk Of Depression And Other Disorders .................................................................. 819 The Covid Pandemic Is Not Over: The Past May Be Prologue .. 822 AstraZeneca Vaccine Fails To Protect Against The South African Variant ....................................................................................... 826 A New Variant In The Philippines ............................................. 829 Can America Beat COVID-19?.................................................. 833 Science will save us in our battle against COVID-19 .................. 836 Preventing Fecal-Oral And Fecal-Aerosol Transmission Of Covid-19 .............................................................................. 839 Controversy Over OSHA Proposals To Create A Covid-19 Safe Workplace ................................................................................. 845 What Can We Learn From Australia’s Covid-19 Response? ....... 848 New Study Predicts Immune Protection May Vary For Different Covid-19 Vaccines ..................................................................... 853 Spring Break Could Trigger A National Surge In Cases Fueled By Variants...................................................................................... 857
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From Cats And Dogs To Minks And Mice, Covid-19 Variants Are Infecting The Ecosystem ............................................................ 860 Covid-19 Has Exacerbated Child Poverty, Forcing A Long Overdue Policy Focus ................................................................ 864 Persistence Of Covid-19 Antibodies Varies Widely From Person To Person ........................................................................................ 868 Moderna And Pfizer Vaccines Prevent Infection As Well As Disease: Key Questions Remain .............................................................. 873 Why Was CDC Director Rochelle Walensky Fighting Back Tears? .................................................................................................. 876 New Belgian Variant Illustrates The Versatility Of SARS-CoV-2 In Escaping Immune Suppression .................................................... 878 April 2021...................................................................................... 881 Despite Progress, Protecting The Population Against Covid-19 Variants Remains Complex ........................................................ 882 Pfizer’s New Oral Protease Inhibitor Could Possibly Treat And Prevent Covid-19 ...................................................................... 884 HBO Doc ‘The Last Cruise’ Gives Insight Into Nightmarish Covid19 Outbreak ............................................................................... 888 Rapid Home Testing: If The UK Can Do It, Why Can’t We? ... 891 An Indian SARS-CoV-2 Variant Lands In California. More Danger Ahead? ....................................................................................... 894 Covid-19 Increases Stress And Traumatic Stress Disorders Including Drug Abuse And Fatal Overdoses ............................................... 897 A Dangerous New Covid-19 Variant Detected In Oregon.......... 900 Young People Hit Hardest By Loneliness And Depression During Covid-19 ................................................................................... 903 New Tanzanian Variant Detected In Angola From An Entirely New Branch Of SARS-CoV-2 ........................................................... 907 How Covid-19 Impacts The Digestive System ........................... 911 The Recent Rise of Indian Covid-19 Cases Display The Dangers Of SARS-CoV-2 Variants .......................................................... 914 Opinion: “The Common Good Of Gun Control And Covid Control” .................................................................................... 917 New Antibody Therapy And Prophylactic Shows Promise In Defending Against SARS-CoV-2 Variants Of Concern .............. 919 Written From The Frontlines Of The Pandemic, Rachel Clarke’s Memoir ‘Breathtaking’ Is A Must Read ...................................... 922 Understanding The Neurological And Psychological Effects Of Covid-19 ................................................................................... 926 An Antibody Cocktail To Lay Low A Mighty Foe ..................... 929 How Fintech Can Help Break The Health Poverty Trap ............ 934
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May 2021 ...................................................................................... 936 Covid-19 And Tuberculosis: A Deadly Combination — We Can Do Better!.................................................................................. 937 The Logic And Practice Of Strict Border Control In Covid-Free Countries ................................................................................... 940 The Logic And Practice Of Strict Border Control In Covid-Free Countries ................................................................................... 945 A New Approach To Treat And Prevent Covid-19 .................... 950 New Antiviral Drug Cocktail Could Help India Control Brutal Covid-19 Surge ......................................................................... 953 Vaccines Vs Variants: Three Studies Provide New Insight........... 956 mRNA Vaccine Booster Shots Likely Required Within Six Months To Protect Against Covid-19 Variants ........................................ 959 Newly Discovered Antibody Neutralizes Covid Variants By Locking Receptor-Binding Domain In A Closed Position .......... 962 A Possible Cure For ‘Bubble Baby’ Disease And Hope For More Discoveries To Come ................................................................ 966 A New Twist To Antibody Cocktails To Prevent And Treat Covid-19 ................................................................................... 969 A Third SARS-CoV-2 Variant Of Interest (Potentially Concern) Emerges From Sub-Saharan Africa ............................................. 974 Making The Best Of A Tough Situation: How To Respond To The CDC's New Mask Guidance ............................................... 978 Discovery Of A Novel Monoclonal Antibody That Neutralizes A Broad Range Of Coronaviruses .................................................. 982 The Premonition By Michael Lewis Highlights A Longstanding Need For Structural Reform Of The US Public Health Service .. 987 Singapore’s Outbreak Highlights A Challenging Road Ahead For Covid-19 Containment .............................................................. 991 How COVID Changed Science ................................................. 993 June 2021 ...................................................................................... 998 United Kingdom Data Show Population Based Rapid Antigen Tests Are A Potent Covid Control Tool ............................................. 999 Don’t Let Children Be The Casualties Of Covid-19 Complacency ........................................................... 1001 New Drug May Bypass SARS-CoV-2 Blockade Of Innate Immune Response ................................................................................. 1004 Can We End the Pandemic?..................................................... 1008 Pediatric Mental Health Is In Crisis .......................................... 1017 Hepatitis-C Drugs And A Remdesivir Metabolite As New AntiCovid-19 Drugs: The Viral Protein NSP3 Emerges As A New Target. ..................................................................................... 1020
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Baseline Temperature Dropped Over 100 Years: The Importance Of Knowing Your Normal Temperature To Detect Fever........ 1033 Restoring Vision To The Blind. Regenerative Medicine Offers New Hope For Retinitis Pigmentosa ........................................ 1035 The Perils Of Covid Complacency ........................................... 1038 Success And Challenges In Mass Screening For Covid-19 Control: The Andorra Story ................................................................... 1044 Will COVID-19 Improve Long Term Care? ............................ 1046 We Need to Prioritize Mental Health for Healthcare Workers .. 1049 How COVID-19 Changes Our Understanding of Mental Health .......................................................................... 1054 Infection Through “Fleeting Contact” With The Delta Variant Leads To Lockdowns Across Australia ...................................... 1058 July 2021 ..................................................................................... 1062 The Delta Dilemma: Loosening Covid-19 Controls At A Time Of Increased Danger ...................................................................... 1063 An Argument For Covid-19 Booster Shots To Protect The Vulnerable................................................................................ 1066 Λ!!: A New Threat On The Rise In South America .................. 1069 Keep it local: How America can meet its vaccine challenge ....... 1074 New Studies Highlight Promising Candidates For SecondGeneration Covid-19 Vaccines ................................................. 1077 The UK's Dangerous And Deadly Gamble................................ 1082 Potential New Biomarker To Guide Treatment For Severe Covid-19 ...................................................................... 1085 Liberté, Egalité, Fraternité, Rationalité: Covid Control French Style ..................................................... 1088 Humanizing Healthcare: A Model For Consumer-Based Care .. 1091 Overwhelmed U.S. Hospital Systems: A Look Into The Future 1094 A Situation Update On Covid-19 Variants And Vaccines ......... 1097 New Hope On The Horizon For Many Women With Breast Cancer ..................................................................................... 1105 Ventilated Classrooms Are Critical To Protecting Our Children .......................................................... 1109 What We Need To Know About The Future Of Variants ........ 1112 How to End the Pandemic ....................................................... 1117 August 2021................................................................................. 1122 A New Study Documents Efficient COVID-19 Transmission From Infected Children And Adolescents To Household Contacts ..... 1123 A Warning About The Future Of Covid-19 From The Scientific Advisory Group For Emergencies Of The United Kingdom ..... 1126
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Opinion: Be careful about covid-19 optimism. There are still plenty of ways for things to go wrong. ................................................ 1131 Healing Ruptured Eardrums With A New 3-D Printed Graft ... 1134 How Peer Counseling Can Address Barriers to Student Mental Health...................................................................................... 1136 It Is Time To Pay Close Attention To The Lambda Variant Now Devastating South America ...................................................... 1139 We Must Support The Children Orphaned By Covid-19 ......... 1144 The Delta Variant: A Guide To Evaluating Personal Risk ......... 1146 Busting 12 Covid-19 Myths That Could Kill............................ 1150 Israel’s Recent Surge Confirms We Need A Multimodal Strategy To Fight Covid-19 .................................................................. 1155 A New Killer On The Loose: B.1.621...................................... 1158 How SARS-CoV-2 Evades And Suppresses The Immune System (Part One)................................................................................ 1164 How SARS-CoV-2 Evades And Suppresses The Immune System (Part Two) ............................................................................... 1167 How SARS-CoV-2 Evades And Suppresses The Immune System (Part Three) ............................................................................. 1171 Study Shows Covid-19 Can Be Detected In A Single Asymptomatic Person Through Wastewater Surveillance ................................. 1176 Covid-19, No End In Sight ..................................................... 1180 How SARS-CoV-2 Evades And Suppresses The Immune System (Part Four) ............................................................................... 1183 How SARS-CoV-2 Evades And Suppresses The Immune System (Part Five) ................................................................................ 1187 Children Born During Pandemic Show Lower Cognitive Scores ........................................................... 1191 How SARS-CoV-2 Evades And Suppresses The Immune System (Part Six).................................................................................. 1193 Babies And Toddlers Are Highly Contagious For Covid-19 ..... 1200 How SARS-CoV-2 Evades And Suppresses The Immune System (Part Seven) ............................................................................. 1202 Decoding The Gordian Knots At The Ends Of The SARS-CoV-2 Genome................................................................................... 1207 Depression And Anxiety Double In Youth Compared To PrePandemic ................................................................................. 1218 How The Pandemic Is Fueling Eating Disorders In Young People...................................................................... 1221 How SARS-CoV-2 Evades And Suppresses The Immune System (Part Eight) ............................................. 1224
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The Mystery Of The False Start At The 5’ End Of SARS-CoV-2 .............................................................. 1232 How SARS-CoV-2 Evades And Suppresses The Immune System (Part Nine) ............................................................................... 1237 September 2021 ........................................................................... 1241 One Fifth Of Adults Report A Relationship Breakdown During The Pandemic .......................................................................... 1242 Is This The Next Variant Of Concern— C.1.2? ....................... 1244 How SARS-CoV-2 Evades And Suppresses The Immune System (Part 10) ................................................................................... 1255 How SARS-CoV-2 Evades And Suppresses The Immune System (Part 11) ................................................................................... 1258 How SARS-CoV-2 Evades And Suppresses The Immune System (Part 12) ................................................................................... 1263 Animal Reservoirs Of Covid-19 May Trigger New Rounds Of Human Disease ........................................................................ 1267 I'm an Infectious Disease Expert and Warn You Don't Go Here ................................................................. 1272 The Covid virus is sneaky. Booster shots can protect us from it . 1276 A Second East African Variant: A.23.1 ...................................... 1280 What US policymakers can learn from the UK's COVID-19 response ................................................................................... 1288 Kids & Covid: What You Need To Know About Schools, Vaccines, And Risk .................................................................. 1291 A New US/Japan Variant To Watch ........................................ 1294 Pandemic Cycles Of Covid-19: SARS-CoV-2 Immune Suppression Helps Us Understand Repeated Cycles Of Viral Infection And Vaccine Breakthrough .............................................................. 1302 How SARS-CoV-2 Evades And Suppresses The Immune System (Part 13) ................................................................................... 1312 A Missed Opportunity: A Decision To Regret ......................... 1316 A Snapshot Of SARS-CoV-2 Evolution: Observed Increase Of Infectivity In The Covid-19 Virus ............................................ 1320 October, 2021 ............................................................................. 1329 A Neanderthal Gene That Protects Us From Covid-19 (Part 14) ................................................................... 1330 Making the Transition from an Academic to a Biobusiness Entrepreneur ............................................................................ 1337 Origin: Very Close Relatives Of SARS-CoV-2 Identified In Laotian Bats.............................................................................. 1341 Successful Multimodal Covid Control In Summer Camps ......... 1346
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Will Covid Overwhelm Our Vaccines? .................................... 1350 Anti-Covid Drugs Are Coming, But At What Cost? ................ 1354 Covid-19 Variation: Past, Present, And Future ......................... 1357 Blockchain Technology, A Practical Solution To Vaccine Verification Systems ................................................................. 1363 Covid-19 Variation: What Comes Next? The Amazonas Experience ....................................................... 1368 The Growing Threat Of The Delta Pluses At Home And Abroad ............................................................................. 1378 The Role Of Nucleases In Innate Immune Escape (Part 15) ..... 1384 The Next Big One: Drug-Resistant Airborne Tuberculosis ...... 1388 An Approaching Storm: What To Expect With Covid This Winter................................................................... 1392 November, 2021.......................................................................... 1395 Supercharging New Viral Variants: The Dangers Of Molnupiravir (Part 1) ............................................................... 1396 The Urgent Need For Increased Surveillance Of Variants That Arise From Chronic Covid ............................................................... 1400 Defeating death from COVID: Here's a comprehensive strategy 1404 Nature Has Gifted Humans With Intelligence That Can Relegate Covid-19 If Not A Disease Of The Past, Then One That Rarely, If Ever, Is Fatal ............................................................................ 1407 Harming Those Who Receive It: The Dangers Of Molnupiravir (Part 2) .......................................................... 1410 UK Approval Of Molnupiravir May Create New And More Dangerous Covid-19 Variants .................................................. 1414 New Data Suggests mRNA Vaccines Work Best As A Three-Dose Regimen.................................................................................. 1417 A Single Point Mutation In The Nucleocapsid Protein Increases Covid Virus Infectivity By More Than 100 Times.................... 1420 Spike And Nucleocapsid Protein Mutations In Tanzanian And Ugandan Strains Of SARS-CoV-2 Demand Attention ............. 1426 HPV Vaccine Should Be Universal For Boys And Girls, Ages 9-14................................................................ 1432 Epidemiology Answers Key Questions About Delta Variant Transmissibility And Lethality .................................................. 1435 Stimulating Innate Immunity Stops SARS-CoV-2 Infection ..... 1439 Detailed Description Of A Highly Potent SARS-CoV-2 Neutralizing Antibody: Bamlanivimab ...................................... 1442 Covid Ear: Virus Implicated ..................................................... 1447 Intramuscular Injection Of Monoclonal Antibodies Simplifies Covid Treatment ................................................................................ 1451
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Science Talk: Hope and concern for two novel Covid-19 antivirals ................................................................................................ 1455 Hong Kong Demonstrates Effective Use Of Covid Public Health Mitigation ................................................................................ 1458 A New Monoclonal Antibody That Has The Potential To Neutralize All Viral Variants ..................................................... 1460 December, 2021 .......................................................................... 1465 Frequent Rapid Testing Is The Key To Controlling Covid-19 Transmission In Universities And In Our Communities ............ 1466 Can Our Success with HIV Serve as a Guide for Antiviral Drug Development for Covid-19? ..................................................... 1468 Omicron Origins...................................................................... 1475 Buckling Up for Omicron ........................................................ 1480 Brain Fog and Seizures: Is Covid-19 to Blame? ......................... 1483 Omicron: The Sum Of All Fears! ............................................. 1487 What Is The Meaning Of Omicron?......................................... 1494 FDA Approves Anti-SARS-CoV-2 Monoclonal Antibodies For The Vaccine Insensitive Immune Suppressed Population........... 1497 Omicron: The Sum Of All Fears! Part 2 ................................... 1499 How Omicron Evades Natural Immunity, Vaccination, And Monoclonal Antibody Treatments ............................................ 1508 Non-Spike Proteins Contribute To Transmission And Virulence Of Sars-Cov-2 ............................................................................... 1517 Another Variant Emerges From An Immunocompromised Patient ............................................. 1521 Omicron Evades Most But Fortunately Not All Monoclonal Antibodies ................................................................................ 1526 Pfizer’s New Antiviral Drug Could Transform The Pandemic, But Challenges Still Lie Ahead ........................................................ 1532 Fight COVID-19 with lessons learned from HIV...................... 1535 New Evidence Of Immune Suppression By SARS-CoV-2 ....... 1539
Media Inerviews ...................................................... 1544 January 2020 ................................................................................ 1545 Interview With Health Professional Radio ................................ 1546 Interview With NBC News Radio ........................................... 1551 Interview With Alzheimer’s Speaks Radio ................................ 1553 March 2020 ................................................................................. 1571 Interview With Bloomberg Asia ............................................... 1572 Fireside Chat on COVID-19 at the Swedish-American Chamber of Commerce ............................................................................... 1576
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Interview With MSNBC The Beat With Ari Melber ............... 1583 Interview With MSNBC Stephanie Ruhle ............................... 1592 Interview With MSNBC Morning Joe ..................................... 1593 Interview With China Global Television Network ................... 1594 April 2020 ................................................................................... 1595 Interview With Houston Matters: Special Edition..................... 1596 Interview With Michael Davidson, CEO Of Gen Next, Inc. .... 1604 Interview with Asia Pacific Biotech News ................................ 1626 Interview With Fox News Daily Briefing With Dana Perino .... 1630 Interview With Chicago's Morning Answer ............................. 1631 Interview With Olivia Messer, Daily Beast ............................... 1632 Interview With The Heat ........................................................ 1641 Interview With Jared Hopkins, Wall Street Journal ................... 1646 Interview With Houston Matters: Special Edition..................... 1663 Interview With Dana Perino, FOX News ................................ 1676 Interview With The Heat ........................................................ 1679 May 2020 .................................................................................... 1680 Interview With Bloomberg News ............................................ 1681 Interview With Thomson Reuters ........................................... 1682 Interview With CNBC ............................................................ 1683 Interview With NBC Nightly News ........................................ 1684 Interview With The Intercept .................................................. 1685 Interview With Bloomberg News ............................................ 1693 Interview With Chinese TV..................................................... 1699 Interview With German TV..................................................... 1705 Interview With NTV Wie Ticket Amerika .............................. 1716 June 2020 .................................................................................... 1717 Interview With HBO Sports .................................................... 1718 Interview With Bud Mishra, Hightech COVID Group, and Charles Cantor ..................................................................................... 1729 Interview With University Of Miami Business School .............. 1741 Interview With VuMedi .......................................................... 1761 Interview with Bloomberg Businessweek (Podcast)................... 1769 Interview With Bloomberg Markets: The Close ....................... 1774 Interview With Dong Lyu ....................................................... 1778 Interview With Bloomberg News ............................................ 1785 Interview With FOX News Dana Perino ................................. 1786 Interview With CNN Anderson Cooper .................................. 1787 Interview With MSNBC Stephanie Ruhle ............................... 1793 Interview With Caixin Chinese News Service .......................... 1796
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July 2020 ..................................................................................... 1810 Interview with CNN Chris Cuomo Prime Time ...................... 1811 Interview with CNN Anderson Cooper ................................... 1815 Interview With CNN Poppy Harlow ....................................... 1820 Interview with Don Lemon...................................................... 1824 Interview With CNN Don Lemon........................................... 1827 Interview With CNN Anderson Cooper .................................. 1830 Interview With KNX News Radio .......................................... 1833 Interview With Houston Matters Ernie Manouse...................... 1834 Interview With CNN Erin Burnett .......................................... 1854 Interview With Thrive Global .................................................. 1857 Interview With CNN Anderson Cooper .................................. 1863 Interview With CNN John Berman ......................................... 1867 Interview With CNN Don Lemon........................................... 1870 Interview with CNN Don Lemon............................................ 1873 Interview With CNN Jake Tapper ........................................... 1876 Interview With MSNBC Stephanie Ruhle ............................... 1879 Interview With CNN John Berman ......................................... 1881 Back To School? ...................................................................... 1885 Interview With CNN Erin Burnett .......................................... 1886 Interview With CNN Anderson Cooper .................................. 1889 Interview With CNN John Berman and Alisyn Camerota ........ 1893 Interview With CNN Jake Tapper ........................................... 1895 August 2020................................................................................. 1898 ‘Second Opinion,’ Episode 1: COVID-19’s resurgence ............. 1899 An Interview With Thrive Global ............................................ 1900 Interview With Bloomberg Radio Carol Massar ....................... 1906 The Randy Tobler Show ......................................................... 1910 Interview With Abi Millar ........................................................ 1912 Interview With Nik Zecevic .................................................... 1914 Interview With CGTN Mike Walter........................................ 1915 September 2020 ........................................................................... 1917 20% of Coronavirus Infections Are Asymptomatic But Still Contagious ............................................................................... 1918 Interview With TRT World and Ghida Fakhry ........................ 1920 Interview With Mark Masselli And Margaret Flinter ................. 1921 Interview With Hedy Phillips ................................................... 1922 Interview On CGTN America ................................................. 1923 Interview With Reuters Marilynn Larkin.................................. 1924 Interview With Equal Parts ...................................................... 1925 Interview With Houston Public Media Ernie Manouse ............. 1934
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Interview With George Citroner .............................................. 1935 Interview With Houston Public Media Ernie Manouse ............ 1936 Interview With TRT World and Ghida Fakhry........................ 1937 October 2020 .............................................................................. 1938 Interview with CNN Don Lemon ........................................... 1939 Interview with VuMedi ........................................................... 1941 Interview with CNN Digital Holly Yan ................................... 1942 White House Nearing Deadline for Fiscal Stimulus (Podcast) .... 1944 Interview With KNX News Radio .......................................... 1945 Interview with CNN New Day ............................................... 1946 Interview BioInnovation Summit Fireside Chat With Yu GuoLiang ......................................................... 1950 Interview with CNN Don Lemon ........................................... 1966 Interview with VuMedi ........................................................... 1968 Interview with CNN Digital Holly Yan ................................... 1969 White House Nearing Deadline for Fiscal Stimulus (Podcast) .... 1971 Interview With KNX News Radio .......................................... 1972 Interview with CNN New Day ............................................... 1973 Interview BioInnovation Summit Fireside Chat With Yu GuoLiang ................................................................................................ 1977 November 2020 .......................................................................... 1993 Interview with KIRO Radio ................................................... 1994 Interview with Seattle Morning News ...................................... 1995 Interview with David Ross ...................................................... 1996 Interview with Houston Public Media...................................... 1997 Interview on Bloomberg.com .................................................. 1998 Interview on Health Matters Radio .......................................... 1999 Interview with KIRO Radio ................................................... 2017 Interview with Seattle Morning News ...................................... 2018 Interview with David Ross ...................................................... 2019 Interview with Houston Public Media...................................... 2020 Interview on Bloomberg.com .................................................. 2021 Interview on Health Matters Radio .......................................... 2022 Interview with Vera Scuderi, Consultant, Innovation & Technology Hub at The European House-Ambrosetti Part I........................ 2040 Interview with Gloria Pallares Global health and development reporter & writer, El Pais ......................................................... 2057 December 2020 ........................................................................... 2075 Interview with NHK World - Japan......................................... 2076 Q&A Session: COVID-19 Vaccines And Newest Updates with Dr. William Haseltine .................................................................... 2077
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Interview with IE University’s Insights: Viruses Not Only Kill People. They Kill Economies. .................................................. 2078 Interview on Town Square with Ernie Manouse - The Year in COVID ................................................................................... 2084 Interview on CBC’s Current: Even if new variant of COVID-19 isn't in North America, we might have made our own: expert .. 2085 Interview on CNN with Bianna Golodryga: To Discuss U.S. Hitting Record COVID Hospitalizations.................................. 2089 Interview on ‘MSNBC Live’ with Lindsey Reiser To Discuss Coronavirus Vaccine ................................................................ 2092 Interview on CNN’s ‘The Lead With Jake Tapper’ To Discuss COVID ................................................................................... 2097 Interview with CNN’s Don Lemon To Discuss COVID Vaccination .............................................................................. 2100 Interview on CNN’s ‘New Day’ To Discuss COVID ............... 2103 Interview on ‘MSNBC Live’ to Discuss COVID Vaccinations Host: Yasmin Vossoughian, John Torres and William Haseltine ......... 2107 January 2021 ................................................................................ 2110 Interview with Bloomberg Radio ............................................. 2111 Interview on CNN’s ‘New Day’ Alliyson Camerota : Discuss Record Number of U.S. COVID Deaths ................................. 2112 Interview on NDTV "There Will Be No Quick Fix For Coronavirus": US Scientist ....................................................... 2115 Interview with The Heat: US Battles COVID-19 Crisis Host: Anand Naidoo Dr. William Haseltine Gavin Macgregor-Skinner, Director of Global Biorisk Advisory Council Dr. Kate Tulenko, CEO and Founder of Corvus Health Katie Barlow, An attorney and Media Editor for SCOTUSblog ............................................... 2116 Interview with CBC Radio - The Current ............................... 2129 Future Of Biotech & Global Vaccine Landscape | Nathealth Thought Leadership Series | NewsX ........................................ 2133 Interview with Margaret Hamburg : Roosevelt House Public Policy Institute at Hunter College ....................................................... 2157 Interview on CNN’s ‘New Day’ To Discuss COVID ............... 2159 Interview on NHK: Biden's Coronavirus Strategy..................... 2162 Interview on CNN Tonight With Don Lemon to Discuss Covid-19 Vaccinations ............................................................................. 2163 February 2021 .............................................................................. 2166 Interview on CNN’s ‘New Day’ To Discuss COVID ............... 2167 Interview on CNN’s ‘Erin Burnett OutFront’ To Discuss COVID ....................................................................... 2170
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Interview with Conversation on Health Care: COVID-19 Is ShapeShifting: Dr. William Haseltine Warns Variants & Lack of Containment May Weaken Vaccine Efficacy ............................ 2172 Interview with Erin Burnett on CNN ...................................... 2173 Interview on ‘CNN Newsroom with Michael Holmes’ To Discuss COVID ................................................................................... 2175 Interview on Euronews To Discuss Covid-19 .......................... 2177 Interview on WGN Infectious Disease Expert William Haseltine Discusses COVID-19 Variant Concerns ................................... 2179 Interview on CNN’s ‘Erin Burnett’ To Discuss COVID Vaccine ...................................................................... 2180 Interview on ‘CNN Tonight with Don Lemon’ To Discuss Winter Storms Delay Vaccine Shipments.............................................. 2184 Interview with Global News Radio: Covid-19 vaccine’s global approval process and efficacy .................................................... 2186 Interview on ‘MSNBC Live’ To Discuss Covid ....................... 2193 March 2021 ................................................................................. 2195 Interview on CNN’s ‘New Day’ To Discuss Covid and Measures ................................................................. 2196 Interview with Susan Ryan of The Green House Project: A Sobering Look at COVID-19, Variants & Immunity ................ 2198 Interview on Bloomberg Daybreak: Australia: Dr. Haseltine Says It's Too Soon to Relax Covid Measures ........................................ 2221 Interview with CGTN The Heat Covid-19 battle. Third wave hits Europe ..................................................................................... 2222 April 2021 ................................................................................... 2223 Interview with CGTN: The Heat: Vaccine inequality and Brazil battles COVID-19 ................................................................... 2224 Interview with HPM-Houston Public Health Radio A Lifelong Fight Against Disease: Dr. William Haseltine Talks About Global Health, From AIDS To COVID-19 ......................................... 2235 May 2021 .................................................................................... 2254 The Heat: China leads multilateralism talks at UN .................... 2255 Interview with Bloomberg: TSMC Stuck in Middle of Global Panic Over Chips (Podcast) ............................................................... 2256 Interview with Minor Memorial Library: COVID 101: How will the Virus Evolve? with Dr. William Haseltine .......................... 2257 The Heat: Coronavirus pandemic — more than 1.7 billion vaccine doses given globally .................................................................. 2258
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June 2021 .................................................................................... 2259 Houston Public Radio: Reflecting On 40 Years Of The HIV/AIDS Epidemic.................................................................................. 2260 July 2021 ..................................................................................... 2282 Interview for GLOBAL TEEN MEDICAL SUMMIT (The Health Museum).................................................................................. 2283 Interview with BBC World News ............................................ 2307 Interview with MBN’s ‘Alhurra Tonight’ ................................. 2309 August 2021................................................................................. 2312 The Benefits of Being Vaccinated If You Still Get COVID....... 2313 Interview with Don Lemon...................................................... 2330 The Black Stallion; Dear Me: Letters to Myself, For All of My Emotions – an interview with Dr. William A. Haseltine ........... 2332 U.S. To Offer Covid-19 Boosters in September ....................... 2334 'That's Insanity': Former Harvard Medical Professor Responds to No Plan for Covid-19 Measures in School ...................................... 2340 Infectious Disease Researcher Calls for Strict Public Health Measures for Back-to-school to Protect Kids from Delta Variant ............................................................ 2344 September 2021 ........................................................................... 2348 Doctor warns of the toll this pandemic is taking on our mental health and the hangover is longterm ......................................... 2349 The Heat: 40 million COVID-19 cases in the U.S.................... 2352 “The Power of Science” // Interview with Neal Howard ........ 2364 COVID-19: Finding A Way Forward....................................... 2369 COVID-19: Finding a Way Forward: Houston Doctor “Optimistic” COVID-19 Vaccines For Young Children Could Be Approved Before Halloween .................................................... 2371 Covid PTSD - It’s vital we can all receive support for both the individual adversity and communal stress of Covid-19 with Dr William Haseltine ..................................................................... 2378 October 2021 .............................................................................. 2392 Heat: U.S. battles Covid-19 ..................................................... 2393 A proposal for long-term COVID-19 control ........................... 2394 Dr. William Haseltine // Interview with Bloomberg Businessweek ......................................................... 2418 ‘We are not done with the virus. And the virus is not done with us,’ says global health expert about omicron .................................... 2419
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Media Mentions .......................................................2421 January 2020 ................................................................................ 2422 Could The Coronavirus Scare Have Been Avoided? One Leading Health Authority Thinks So ..................................................... 2423 Is America Ready? ................................................................... 2424 February 2020.............................................................................. 2425 World Should Have Been More Prepared For Coronavirus, Says US Scientist William Haseltine ....................................................... 2426 Coronavirus Death Toll Hits 564; Infant Infections Add Troubling New Element To Outbreak ..................................................... 2427 The Gross And Uncomfortable Way Doctors Test For The Coronavirus ............................................................................. 2428 First Coronavirus Case Of Unknown Origin Confirmed In US. What Does That Mean? ........................................................... 2429 Coronavirus May Explode In U.S. Overnight Just Like In Italy 2430 Is This Coronavirus ‘The Big One’? ......................................... 2431 March 2020 ................................................................................. 2432 China Constructed New Hospitals In Days, And Other Lessons From Their Response To The Coronavirus ............................. 2433 Pull The Pieces Together And Find The Soul .......................... 2434 Could Widespread Coronavirus Testing Make Things Worse? Prevention Seen As Key ........................................................... 2435 What To avoid In NYC This Weekend If You’re Worried About Coronavirus ............................................................................. 2436 Coronavirus Vaccine at Least a Year Away, But Treatment Could be Here in Months ................................................................... 2437 Is The U.S. wasting The window Of opportunity To Contain COVID-19? ............................................................................ 2438 Norwegian Cruise Line Managers Reportedly Pressured Employees To Lie To About Coronavirus Danger ..................................... 2439 What Aggressive Coronavirus Lockdown Might Look Like In The U.S. ......................................................................................... 2440 Exclusive: A Spike In Coronavirus Cases Could Overwhelm U.S. Hospitals By The End of March, Defense Department Monitoring Shows ...................................................................................... 2441 Four Ways Experts Say Coronavirus Nightmare Could End ..... 2442 Asymptomatic Carriers May Still Transmit Coronavirus, Says New Research .................................................................................. 2443 Does Taking Ibuprofen Make Coronavirus Worse? Here's What Experts Have To Say................................................................ 2444
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Social Distancing, Self-Quarantining, Under Lockdown: Here's What Each Term Means ........................................................... 2445 Here’s How to Tell If That Sneeze Is Coronavirus, The Flu Or Just A Cold ..................................................................................... 2446 Public Health Experts Say Trump Is Bungling The Coronavirus Response ................................................................................. 2447 Docs Buck Bosses To Beg Cuomo For Coronavirus Protective Gear .................................................... 2449 April 2020.................................................................................... 2450 Should You Be Wiping Down Your Groceries When You Get Home from the Store? Experts Are Divided.............................. 2451 Tucker Carlson: Not Job Of Public Health Officials To Make "Big Decisions" About COVID-19 Response ................................... 2452 Medical Expert Gives Fox News A Stern Fact-Check About Unproven Coronavirus Drug ................................................... 2453 How The Very Rich Are Different In The COVID-19 Fight ... 2455 Fox guest describes malaria drug as 'quack cure' for coronavirus 2456 Top Biologist To Fox News Host Dana Perino: Unproven Drug Treatment Hyped By Trump Is A "Quack Cure" ..................... 2458 Trump Lashes Out At Fox News Reporter: You should Say "Great Job Instead Of Being So Horrid" .............................................. 2459 For Fox News hosts, The Hydroxychloroquine Controversy Is Fuel For The Culture War ............................................................... 2460 Experts Fear Coronavirus Vaccine May Only Provide "Short-Term" Immunity From Virus .............................................................. 2461 Here’s How We Extricate Ourselves From This Lockdown ...... 2463 Limbaugh Falsely Claims Criticisms Of Trump's Coronavirus Preparedness Are "A Political Hit Job" ...................................... 2464 Rickter Scale: In Search Of The Lost Cure............................... 2465 Was That Cold I Had In November Or December Coronavirus? ........................................................... 2467 Arizona Has Done 51,000 COVID-19 Tests. The State Needs Double That Each Month To Safely Reopen, Expert Says ........ 2468 How To Avoid A Pandemic Patriot Act ................................... 2470 Fox News Hosts Go Mum On The COVID-19 Drug They Spent Weeks Promoting .................................................................... 2472 Coronavirus diary – Part 3 ........................................................ 2474 Arizona Has Worst Day Of Confirmed Coronavirus Cases Yet . 2476 Early Funding Key To Finding Drugs That Will Fight COVID-19 ................................................................................................ 2477
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May 2020 .................................................................................... 2478 Challenges, Opportunities, And Innovations In The Health And Well-being Of Tthe World’s Aging Citizens ............................ 2479 Science Without The Luxury Of Time .................................... 2484 Kellyanne Conway Criticizes Anti-Trump Group Co-Founded By Husband .................................................................................. 2485 New York’s Antibody Testing Spree Could Be A Game Changer ..................................................................... 2487 WHO Says Some COVID-19 Medicines Can Shorten Illness — But .............................................................. 2490 Hydroxychloroquine Is Ineffective ........................................... 2490 Here's How That Rumor That Smokers Can't Get COVID-19 Got Started ..................................................................................... 2492 Trial Coronavirus Vaccine Only ‘Partially Effective In Monkeys – As It Fails To Stop Spread’ ....................................................... 2494 Fighting Coronavirus Conspiracy Theories ............................... 2496 Doubts Over Oxford COVID-19 Vaccine After Animals Tested Catch Virus .............................................................................. 2497 Stocks surge after Moderna announces promising early vaccine results ...................................................................................... 2499 Let’s Remember That The Coronavirus Is Still A Mystery........ 2500 Global report: Don't Count On Vaccine, US Scientist Warns, As Cases Pass 5M .......................................................................... 2501 U.S. Raises Ante in Vaccine Race With $1.2 Billion for Astra .. 2503 Coronavirus Is Vanishing So Quickly In Britain that Oxford University's vaccine trial only has a 50% chance of success, professor leading project warns................................................................ 2504 June 2020 .................................................................................... 2506 Researchers Race For Corona Vaccine But Question Effectiveness ............................................................. 2507 Biotech Pioneer Calls For Transparency In Coronavirus Vaccine Development ........................................................................... 2509 ‘All of a Sudden It Blows Up’: Arkansas’ COVID Problem Is Just Getting Started ......................................................................... 2512 Worried About a Second Lockdown? Pray Things Work Out in NYC ....................................................................................... 2514 July 2020 ..................................................................................... 2516 How A Chinese Firm Jumped To The Front Of The Virus Vaccine Race ........................................................................................ 2517 Interview with Poppy Harlow .................................................. 2519
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Phoenix Mayor's Office Clarifies Hospital Capacity Comment On Cable TV Interview ................................................................. 2521 The GOP is a suicide cult ......................................................... 2522 Moderna Fires Up COVID Vaccine Race With Promising Early Results ..................................................................................... 2523 COVID-19 Vaccine Trial Produces Antibodies In Everyone Tested, Report Says.............................................................................. 2524 Moderna’s Coronavirus Vaccine Produced Antibodies In All Patients Tested ......................................................................... 2525 Should I Get Tested For Coronavirus? Here's What Parents Need To Know ................................................................................. 2526 10 Tips For Returning To Work In The Midst Of A Pandemic 2527 An e-Book For Families Provides Answers To Important Questions About COVID-19 ................................................................... 2528 The Inside Story Of How A Sleep Tracker Became The Hottest Device Of The Pandemic ......................................................... 2530 12 Back-To-School Essentials Every Kid Will Need During A Pandemic ................................................................................. 2531 Quartet Of COVID-19 Vaccine Candidates Head Toward The Homestretch ............................................................................ 2532 The US Reported More COVID-19 Cases In The Last Two Weeks Than It Did For All Of June ..................................................... 2534 How COVID-19 Coronavirus May Affect Your Heart, Here Are Two New Studies .................................................................... 2535 Why You Should Stay Away From Bars During COVID-19, According To Experts .............................................................. 2536 Even the Best-Case U.S. Coronavirus Scenario Is Horrific ........ 2537 August 2020................................................................................. 2538 For Homemade Face Masks, 3 Layers Are Better Than 1 .......... 2539 3 Steps To Take Before Going To A Newly Reopened Restaurant ............................................................... 2540 September 2020 ........................................................................... 2541 If You Have No Choice But To Wear A Disposable Mask Again, Take These Doctors' Advice ..................................................... 2542 5 Experts Lay Out How They'll Determine Whether A Coronavirus Vaccine Is Really Safe And Effective — Here's What To Know To Evaluate The Data For Yourself ................................................ 2543 October 2020 .............................................................................. 2544 Doc Rips White House Embrace Of ‘Herd Immunity’ To CNN: ‘Another Word For Mass Murder’ ............................................ 2545
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"Herd Immunity Is Another Word For Mass Murder," Expert Says .............................................................................. 2547 U.S. Health Experts Warn Against 'Herd Immunity' Policy To Fight COVID-19 .............................................................................. 2548 Suite Talk: Dr. William A. Haseltine, Chairman And President, Access Health International ...................................................... 2549 What Fans Of ‘Herd Immunity’ Don’t Tell You ...................... 2552 Feds To Let 15,000 Worship On National Mall—Masks Be Damned ................................................................................... 2553 Drive? Fly? Stay home? The Hard Decisions Behind Pandemic Holiday Gatherings .................................................................. 2555 Scientists Debate How Much To Lower The Bar On COVID-19 Vaccine Potential ..................................................................... 2557 November 2020 .......................................................................... 2558 Why A Top Infectious-Disease Expert Says It's Too Soon To Celebrate Pfizer's Coronavirus Vaccine ..................................... 2559 Pfizer's Covid-19 vaccine promising, but many questions remain ................................................................................................ 2562 Abortion Reversal’ Evangelist Enlists in the COVID Wars ....... 2563 In an Attempt to Keep Schools Open, Some Parents Are Refusing to Test their Kids for COVID-19 ............................................. 2564 December 2020 ........................................................................... 2565 HIV lessons for covid-19 .......................................................... 2566 January 2021 ................................................................................ 2568 Simpler guidelines may speed rollout ........................................ 2569 As new Covid vaccines near U.S. debut, here’s what you need to know about the shots ............................................................... 2571 February 2021.............................................................................. 2575 Moral Injury: Pandemic's Fallout for Healthcare Workers ......... 2576 Experts split on delaying COVID-19 vaccine second doses. Here's why ......................................................................................... 2578 "Pathogen porn": Two papers about a New York coronavirus strain spark a scientific war of words .................................................. 2579 The Heat: One scientist’s fight against disease & Racism against Asian-Americans ...................................................................... 2581 April 2021 ................................................................................... 2582 Trump-Touted Drug Lives On as Covid Therapy Despite Trial Flops ........................................................................................ 2583 Months after recovering from COVID-19, millions may suffer from "brain or psychiatric disorders" ................................................. 2584
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What’s Actually Safer? Flying Commercial or Taking a Private Jet? ................................................................................................ 2587 India's 'double mutation' covid virus variant is worrying the world ................................................................................................ 2589 GLOBAL TRAVELER: Six vaccinated medical experts reveal their summer travel plans .................................................................. 2590 Vaccine Hoarding May Backfire on Rich Nations as India Reels ................................................................................................ 2592 May 2021 .................................................................................... 2594 Will summer see a ‘travel window’ before fall infections rise? Here’s what medical experts say........................................................... 2595 What Does a Future Without Herd Immunity Look Like? ........ 2597 What’s the difference between full FDA approval for a vaccine and emergency use authorization? ................................................... 2599 July 2021 ..................................................................................... 2600 England’s Covid unlocking is threat to world, say 1,200 scientists ................................................................... 2601 UK govt plan to end virus orders queried as cases top 50,000 .... 2603 August 2021................................................................................. 2606 The war against COVID-19 was fought with weapons developed to battle HIV ................................................................................ 2607 'Draconian measures' needed vs virus – expert........................... 2608 September 2021 ........................................................................... 2609 Researcher says COVID variant R.1 is ‘something really to watch’ .................................................................................. 2610 October 2021 .............................................................................. 2611 Top Covid experts privately urge Biden admin to scale back booster campaign .................................................................................. 2612 November 2021 ........................................................................... 2613 A prominent virologist warns COVID-19 pill could unleash dangerous mutants. Others see little cause for alarm .................. 2614 A COVID pill from Merck called Molnupiravir is narrowly backed by FDA for future use, but there are risks ................................. 2616 December 2021 ........................................................................... 2617 Scientists puzzle over Omicron’s origins as variant spreads ......... 2618 The U.S. Faces Another Covid Christmas as Omicron Fuels a Rise in Cases .................................................................................... 2619 'Drug cocktail' may be needed as COVID variants attack immune system on multiple fronts .......................................................... 2620
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"Sick madness": The public reacts to the CDC's decision to cut COVID-19 self-isolation time in half ....................................... 2621 Is Omicron Just Covid “Evolving to Become the Common Cold”? ..................................................................... 2623
Social Media ............................................................2625 January 2020 ................................................................................ 2626 February 2020.............................................................................. 2629 March 2020 ................................................................................. 2634 April 2020 ................................................................................... 2642 May 2020 .................................................................................... 2664 June 2020 .................................................................................... 2679 July 2020 ..................................................................................... 2692 August 2020 ................................................................................ 2707 September 2020 ........................................................................... 2717 October 2020 .............................................................................. 2731 November 2020 .......................................................................... 2753 December 2020 ........................................................................... 2774 January 2021 ................................................................................ 2802 February 2021.............................................................................. 2823 March 2021 ................................................................................. 2838 April 2021 ................................................................................... 2850 May 2021 .................................................................................... 2857 June 2021 .................................................................................... 2865 July 2021 ..................................................................................... 2879 August 2021 ................................................................................ 2889 September 2021 ........................................................................... 2899 October 2021 .............................................................................. 2905 November 2021 .......................................................................... 2910 December 2021 ........................................................................... 2917
Acknowledgements ..................................................2924 xxxviii
Personal Commentaries
1
January 2020
2
What Makes This Coronavirus Different—And What We Can Do About It Forbes | January 28, 2020 | Article
To date, more than 4,500 people have contracted 2019-nCoV, the new coronavirus that first appeared in Wuhan, China and has spread to numerous countries around the world. The first death from the severe viral respiratory disease was announced January 11, and of those infected 100 more have died since. Although 2019-nCoV isn’t the first disease of its kind, the world as we know it in 2020 is not the same as it was in 2002 or 2012, when the previous two coronavirus outbreaks, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), made their mark. The World Health Organization may not have declared a state of public health emergency just yet, but it’s critical moments like these when the changing nature of twenty first century health systems comes into sharp relief. Technology, geopolitics, socioeconomic conditions—these colliding spheres of influence have always impacted human health, and they will no doubt shape the global response to 2019-nCoV. SARS, the foremost of the coronavirus epidemics, originated in southern China in November 2002. By the time it was declared contained in July 2003, the number of documented cases exceeded 8,000; the number of fatalities, over 800. Epidemiologists deemed the Chinese horseshoe bat the most likely reservoir of the disease, which was next contracted by the palm civets bought and sold in exotic markets across Guangdong Province. Traders who handled infected civets became the first human hosts of the coronavirus— and from there, it quickly spread person to person throughout China. Although cases of SARS were reported in countries near, like Vietnam and Singapore, and far, like Canada, nearly 90 percent occurred in China and Hong Kong. The pneumonia like symptoms common to most cases of SARS remained consistent with those of the next lethal coronavirus to 3
emerge: MERS, which was thought to be transmitted from bats to camels to humans. Beginning in Saudi Arabia in fall 2012, the disease infected less people than SARS—about 2,500, to be exact—but claimed a proportionately larger number of lives across the Arabian Peninsula. (The mortality rate of MERS was triple that of SARS.) MERS reached 26 countries, including a notable 2015 outbreak in South Korea that killed dozens, before slowing down indefinitely. A new case of SARS hasn’t been reported since 2004, and MERS has been on the decline since 2016. Since only time will tell just how viral and lethal the latest coronavirus outbreak can be, most comparisons between SARS, MERS, and today’s 2019-nCoV are purely speculative. What we do know, however, is that the world is more interconnected—and its people more on the move—than ever before. In 2018, six times as many people flew in and out of China on a daily basis than in 2012—and that’s to say nothing of the cooccurrence of 2019-nCoV with the lunar new year, a time when permanent living situations are suspended and countrywide travel surges stretch the limits of global infrastructure. Assuming the rough and tumble of itinerant travelers can be kept in check, whether infectious disease management is easier or more difficult under increasingly globalized conditions still remains to be seen. The Chinese government, to be sure, is taking deliberate steps to avoid the mistakes of responses past, such as cooperating with the World Health Organization and deploying biosecurity systems to surveil and apprehend the spread of 2019-nCoV. But it would do everyone some good, no matter their location or their travel plans, to exercise vigilance and practice basic hygiene. For me, that means taking precautions like avoiding crowds. Washing my hands often with soap. Avoiding face touching, a bad habit that occurs on average a few times each hour and accumulates over the course of a day. Wearing gloves and swiping surfaces with sterile cleaning wipes when taking public transport. Using nasal spray or a bit of petroleum jelly to maintain resistance to infection while traveling. Until trusted health institutions deliver their verdicts on what comes next, we’ll have to rely on small protective measures like these for peace of mind.
4
This article originally appeared in Forbes and is available online here: What Makes This Coronavirus Different—And What We Can Do About It
5
Want to Prevent Another Coronavirus Epidemic? Scientific American | January 29, 2020 | Article
Once again we stand unprepared as the third epidemic of a new and deadly coronavirus races around the world. This need not have been the case. We should have learned from the SARS epidemic of 2003, which claimed nearly 800 lives, that coronaviruses can turn deadly. Until then, most health officials and scientists regarded coronaviruses simply as one of many causes of the common cold; some 30 percent of common colds start from coronaviruses. Then came the MERS epidemic in the Middle East in 2012, a coronavirus that killed 858 people. The irrefutable lesson from SARS and MERS: coronaviruses can spread quickly and be deadly. Why, then, is there no way to prevent or treat the disease in 2020? Science had the tools in the immediate aftermath of the previous two epidemics to develop the drugs to control future outbreaks. But health officials, scientists and governments, especially but not only in the United States and China, dropped the ball. There is no doubt that coronaviruses are wily opponents. Like all viruses of this type, the coronavirus mixes and matches components to create novel versions of itself. Bats are the natural hosts of the virus. There are more than 1,100 species of bats, each infected with one or more coronavirus variants. Think of the virus as a genetic safecracker, constantly evolving new combinations to extend its range and find new host species. Humans are on that menu. Each infection, deadly or not, is different from the last, which makes an effective vaccine or cure for the whole family of coronaviruses highly unlikely. Though we may not be able to develop a cure for those already ill, we can develop drugs that will prevent the disease from spreading. If we had done so after SARS and MERS, governments could have stockpiled the drugs years in advance of this latest outbreak and within one-day delivery to all locations where the virus 6
has been detected or suspected. All patients, hospital workers and any other persons suspected of contact would have been treated to stop the epidemic in its tracks. I led the effort to develop an effective drug to prevent and treat anthrax following the 2001 attack and was a pioneer for the concept of using drugs to prevent transmission of HIV/AIDS from mother to child and between adults. Assessing the genome of this new virus, I see what we describe as a “target-rich” environment; that is, a virus that has many vulnerabilities to antiviral drugs, similar to those that have been exploited successfully for the treatment of HIV, hepatitis B and herpes viruses. The drugs, or combinations of drugs, that control those diseases bind and block the enzymes the viruses need to grow. These enzymes are very similar to one another in all coronaviruses. This is a critical point. This common molecular pattern of all coronaviruses makes the challenge of identifying drugs to control coronaviruses less daunting. Scientists design drugs to inhibit the growth of specific virus enzymes. Once the genetic code of a virus has been sequenced, the targets for effective drugs appear. We now have witnessed three deadly coronavirus outbreaks in humans within 17 years. Once this new epidemic has faded into memory, will it be five or 10 years until the next one? We can and must develop, test and stockpile combinations of drugs that can protect against what is certain to be another coronavirus outbreak. In the wake of the 9/11 attacks, the U.S. government established the legal authority and executive process to do this. Known as BioShield, the program authorized funding to develop and stockpile effective means to prevent and treat “new and emerging biological threats.” BioShield works. At Human Genome Sciences we developed the drug Anthrax to prevent and cure anthrax infections after the 2001 attacks. That drug is now stockpiled by the government. BioShield created the market for our work, committing many millions of dollars in purchase orders. The coronavirus is not now and has never been on BioShield’s approved list of “new and emerging biological threats.” It should have been added after SARS, then again after MERS. It should be added now. We have been forewarned. The departments of Homeland Security, Health and Human Services, and Defense should convene a working group immediately 7
to add coronaviruses to the BioShield agenda. The Centers for Disease Control and National Institutes of Health then can initiate contractual discussions with the biopharmaceutical industry. Biopharmaceutical companies have the expertise to create the drugs we need quickly to prevent a fourth outbreak. Collectively, scientists at these agencies and companies then can, and will, soon identify the drugs and produce the stockpiles that we need, that the world needs, to prevent a fourth deadly outbreak from a coronavirus, any coronavirus. This article originally appeared in Scientific American and is available online here: Want to Prevent Another Coronavirus Epidemic?
8
The US Isn’t defenseless Against The Coronavirus, But It Is Unprepared Quartz | January 30, 2020 | Article
“We have it totally under control.” “It’s going to be just fine.” Those were the words of US president Donald Trump when he recently weighed in on news of the potential spread of the new coronavirus, dubbed the 2019-novel coronavirus, or 2019-nCoV, to the United States. He’s wrong. It’s true, we’re not defenseless in the face of this disease. But we are unprepared. Wuhan, the capital of China’s Hubei province where the coronavirus has broken out, is a major transportation hub. The city is larger than New York in both population and size. I was in Wuhan recently chairing the US-China Health Summit. I can assure you that in the US we are, like those in Wuhan were, woefully unprepared. I’ve led research teams assembled in the wake of two previous US public-health crises: the HIV/AIDS epidemic in the 1980s and the 2001 anthrax attacks. In both instances, lives were lost due to our inability to coordinate and execute a proactive response. It’s baffling to see that the US might fail, once again, to learn from the past. Déjà vu? This isn’t the first time we’ve seen a coronavirus epidemic of this kind. In 2003, SARS appeared. In 2012, we saw MERS break out. These epidemics have sickened and killed thousands, seemingly attacking every eight to 10 years. The coronaviruses we’re facing today has been found to be both highly transmissible and highly lethal—a particularly dangerous combination. Over a course of eight months, SARS spread to about 8,100 people and killed nearly 800. It was highly contagious, but 9
weakly lethal. MERS, on the other hand, infected about 2,500 and killed 858—not as sweeping, but far more deadly. The 2019-nCoV is spreading fast—so fast that from Jan. 27 to Jan. 28 alone, the number of confirmed cases jumped by almost 60%. The disease has traveled beyond China to reach countries including Japan, Singapore, South Korea, Thailand, and the United States. So far, 2019-nCoV has claimed the lives of more than 100 people, a figure that is sure to increase with every passing day. Economic risk of epidemics The 2019-nCoV outbreak is not just a threat to public health, but to the global economy. It is fully within the power of a country like the United States to leverage scientific knowledge and resources into a solution that protects populations from further exposure. Going about business as usual will only serve to intensify the economic ramifications of the crisis, not mitigate them. Ignorance, denial, and complacency are as much an enemy to human health today as 2019-nCoV itself. All three are endemic human traits. All three proved deadly with HIV/AIDS and the previous coronavirus outbreaks and likely may do so again. Being forewarned is being forearmed. We have been warned by nature time and time again. Now is the time to arm ourselves against this new threat. Drugs and money The first step is to focus on finding a drug or, more likely, a combination of drugs that will not just treat coronaviruses but protect those exposed from infection. As many companies don’t see a market for such therapeutic drug seems to have bred inertia in the pharmacology field, however. There’s also the challenge that the window of time when therapeutic drugs would work occurs before a patient even knows they’re sick. To drive action, we need to train our sights not only on treating those infected but also on prophylactic drugs. For example, the same cocktail of drugs used to treat HIV can prevent mother to child transmission and protect exposed adults. When it comes to funding, it’s up to the government to lead the way. Like the Cooperative Drug Development Grants program the 10
US government invested in for the treatment of cancer and HIV/AIDS, the government should create cooperative programs between academic laboratories and the biopharmaceutical industry to discover, develop, and bring to market new drugs to attack coronaviruses. The US already has the tools to do this. Bioshield, the US program that protects people against bioterrorism, legislates a rapid response to “new and emerging biological threats,” whether natural or man-made. I can tell you from a life of experience that threats from nature are far more dangerous to humans than humans are to each other. Today, we are at war not with a foreign country, nor with terrorist factions, but with nature itself. There is an old adage, “Fool me once: Shame on you. Fool me twice, shame on me.” Nature has warned us three times now: First with SARS, then with MERS, and now with 2019-nCoV. Fool me thrice, shame on all of us. This article originally appeared in Quartz and is available online here: The US isn’t defenseless against the coronavirus, but it is unprepared
11
What Governments Must Do To Deliver An Anti Coronavirus Drug Within Months Forbes | January 31, 2020 | Article
The world needs an anti coronavirus drug as soon as possible—and there is something the United States government can do right now to achieve that. STAT News recently reported that most big pharma companies have been reluctant to join the search for a vaccine that treats 2019nCoV, the new coronavirus that originated in Wuhan, China and has quickly spread around the globe. Given that the costs of vaccine manufacturing tend to run high—and the chances of profit, much lower—their lack of interest was to be expected. But there is a bigger issue at play. While 2019-nCoV may be the disease making headlines today, coronaviruses as a whole present a much more formidable threat to human health. This is the third coronavirus, after SARS and MERS, to attack us, and we’ll no doubt be hit again. Big pharma should be focused on finding a drug to prevent and treat the family of coronaviruses. Instead, they’ve taken a back seat. Our government leaders could change that. It is well within the power of the United States government to issue an open contract at this very minute that guarantees, to whichever pharmaceutical companies willing and able, a sizeable purchase order for one broad spectrum, anti coronavirus drug. Other countries, China especially, could follow suit. In targeting the coronavirus more generally, rather than a single strain, such a drug could be deployed for immediate use and stockpiled for future outbreaks. Authorized financing for the contract could feasibly come from Project BioShield Special Reserve Fund, a program established in the wake of the September 11 attacks. In the fifteen years since, Project BioShield has functioned as a means of buoying up the Strategic National Stockpile with medical products and treatments
12
that can protect Americans from “modern, evolving health security threats”—including new and emerging diseases. Imagine what would happen if the United States government actually took initiative and pursued this strategy, enlisting major players like the National Institutes of Health, the Food and Drug Administration, and the Centers for Disease Control and Prevention to help shepherd it forward. Pharmaceutical companies, allured by the promise of profit, would apply for the contract in droves, emptying out everything in their freezers for testing. Once clinical research is complete and safety requirements met, government and public health authorities would accelerate review and production to swiftly bring the drug to market. I predict that within two months—three months tops—an anti coronavirus treatment would be available. This proposal isn’t without precedent, and the journey from lab to market of azidothymidine (AZT), the first AIDS treatment approved by the Food and Drug Administration, provides an excellent case in point. AZT began as a cancer drug that, in the 1960s, was shelved indefinitely after mice trials proved ineffective. When it became evident two decades later that AIDS was an incredibly lethal infectious disease, pharmaceutical company Burroughs Wellcome & Company resurrected the drug as part of their effort to identify anti HIV agents. In 1987, states secured $30 million in emergency funding from Congress to distribute the drug as fast as possible. Had the United States government, big pharma, and public health agencies not eventually triangulated their efforts to stop the spread of AIDS, the nationwide rollout of AZT would have come much later than it did. Now, we need to do the same—not just for a 2019-nCoV vaccine, but a broad spectrum anti coronavirus drug. This article originally appeared in Forbes and is available online here: What Governments Must Do To Deliver An Anti Coronavirus Drug Within Months
13
February 2020
14
Escalate Federal Action Against The Coronavirus Before It’s Too Late Forbes | February 4, 2020 | Article
The 2019 coronavirus, otherwise known as 2019-nCoV, is spreading faster and further each day. This past Sunday, infectious disease experts told The New York Times that a full blown pandemic is increasingly likely, if not inevitable. Why, then, is the response of the United States government lagging so far behind? To date, the White House has assembled a task force, called for airport health screenings, and issued a variety of travel restrictions. Most recently, Alex Azar, Secretary of the Department of Health and Human Services, declared the coronavirus outbreak to be a public health emergency. None of those measures, however, confronts the epidemic for what it is: a danger to national health security, and to human health at large. One federal agency that specializes in neutralizing threats of this sort is the Biomedical Advanced Research and Development Authority, or BARDA for short. Established in 2006 and directed by Deputy Assistant Secretary for Preparedness and Response Dr. Rick Bright, BARDA presides over the discovery, development, and stockpiling of medical countermeasures that protect Americans against health security threats. This includes not just biological agents of warfare, but new and emerging infectious diseases—like the coronavirus. Medical products capable of effectively countering the coronavirus, such as novel drugs or vaccines, lack the immediate market that usually lures major players in the pharmaceutical industry. BARDA bypasses the laws of supply and demand by allowing none other than the federal government to pour hundreds of millions of dollars into procuring and advancing promising products. Project BioShield, one of several programs in the BARDA arsenal, is tasked with funding and fast tracking countermeasures from early to late development. Once FDA approved, the federal 15
government can either deploy the countermeasures or send them to the Strategic National Stockpile, where they will remain until another occasion for deployment arises. Were BARDA, with the support of other federal agencies like the National Institutes of Health and the Centers for Disease Control and Prevention, to open up the Project BioShield pipeline to a broad spectrum drug that targets the entire coronavirus family, any leftover quantities would be diverted to the Stockpile in case of future coronavirus outbreaks. The financial health of BARDA and Project BioShield is sound, with both institutions faring better budgetarily than in 2019. BARDA was recently allotted a $562 million in public health emergency appropriations for the fiscal year of 2020, while Project BioShield received $735 million. Is it so much to ask that the United States government commit a fraction of these funds to targeting a soon to be pandemic? Countering threats to national health security like the coronavirus, after all, is the reason BARDA and Project BioShield were created, which means this intervention would be continuous with legislative action against outbreaks past. In fifteen years, Project BioShield has amassed a portfolio of 27 products. Among the countermeasures procured by BARDA and shuttled to the Strategic National Stockpile through Project BioShield are an anthrax vaccine and two anthrax antitoxins. As one of the researchers who, in the wake of the 2001 anthrax attacks, led the development of these drugs, I can say with confidence that the United States government is fully capable of acting swiftly in the face of a public health crisis. It is in the best interest of the White House Coronavirus Task Force—and the health of the nation—to add an anti coronavirus drug to the Project BioShield portfolio. If the federal government waits too long to leverage the rapid response capabilities at its disposal, we will not only be vulnerable to 2019-nCoV, but epidemics to come. This article originally appeared in Forbes and is available online here: Escalate Federal Action Against The Coronavirus Before It’s Too Late
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Solving The Coronavirus Identity Crisis: A Strategy For Prevention Forbes | February 7, 2020 | Article
The new coronavirus, like its predecessors, is a beast to be reckoned with. And yet its working name, 2019 novel coronavirus (2019nCoV), is curiously tame. So technical and nondescript a label is hardly befitting of an epidemic that will not only harm thousands, but also demands an urgent, timely response. At a time when onlookers must be spurred into action, a name like 2019-nCoV inspires the opposite impulse: to forget or file away. We need a name that is both memorable and searchable. It must be capable of anchoring an ongoing conversation between scientists, government officials, and the general public—one in which crucial information about safety and protection is routinely relayed. Severe acute respiratory syndrome (SARS), the name of the first outbreak, did the trick. Why can’t we do the same now? Government and public health officials, to be fair, aren’t keen to repeat the mistake they made with Middle East respiratory syndrome (MERS): creating a lasting association between an infectious disease and its place of origin. MERS traveled to countries well beyond the Middle East, and the new coronavirus is following suit. The longer they hesitate, however, the longer media outlets and their audiences will continue to fall back on “Wuhan coronavirus” and, even worse, “Wu flu” as shorthand for the disease. Wuhan is not the enemy. The coronavirus is. Unless we give the new strain a name that suggests continuity with the outbreaks of decades prior, we risk losing sight of our target. In this vein, the name I propose is Coronavirus Acute Respiratory Syndrome Epidemic 3, or CARS-3. Like SARS, it rolls off the tongue. Unlike SARS, it reminds us that this is the third time we’ve suffered from a fatal coronavirus attack. If we want it to be our last, we can’t let it slip from our collective memory. Something has to stick—and it’s not going to be 2019-nCoV. 17
This article originally appeared in Forbes and is available online here: Solving The Coronavirus Identity Crisis: A Strategy For Prevention
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Why Are We So Fearful of the New Coronavirus? Psychology Today | February 14, 2020 | Article
In the thick of a disease outbreak, the line between panic and preparedness can feel perilously thin. For individuals living with comorbidities like chronic lung and immunodeficiency diseases, the new coronavirus is deadly. To protect them, certain precautions are, indeed, necessary, including the lockdowns enforced by the Chinese government and the temporary travel restrictions placed in the United States and elsewhere. For those who don’t fall into that category, there is little reason to fear—and a lot of evidence to suggest that even if infection occurs, chances of recovery are high. So far, the mortality rate outside Wuhan, the epicenter of the new coronavirus, has remained below 1 percent. But the anxiety and panic induced by the disease seem as contagious as the disease itself, depleting the surgical mask supply of pharmacies worldwide. Plenty of health challenges lurk at our doorstep that do more damage and take more lives than the coronavirus. Take seasonal influenza or the flu. So far, there have been no less than 19 million cases of flu-related illnesses recorded this flu season, as well as 10,000 deaths. The new coronavirus, on the other hand, has sickened upwards of 64,000 and killed almost 1,400. The raw numbers cast the flu as a mightier foe—and yet the coronavirus, if its continuing domination of headlines is any indication, has it overshadowed by a wide margin. Why does the 2019-nCoV outbreak rile our fears so? The discrepancy has to do with how humans perceive risks. Novel threats provoke anxiety in a way that everyday threats do not, triggering a fear response that begins with the part of the brain known as the amygdala and travels via activation of “fight or flight” motor functions throughout the body.
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While this evolutionarily honed instinct for the unfamiliar and foreboding can sharpen the senses—a sort of physiological priming for confrontation with a predator—it can also confuse the mind. Many of us, for example, fear plane crashes more than car crashes, even though death by automobile is far more likely. Reminding ourselves of this fact, however, does little to undo the knot that forms deep in the stomach as the plane prepares for takeoff. If we can’t trust our gut reactions to guide our response to the 2019-nCoV outbreak, then what can we trust? One option is to rely on de facto voices of authority: in this case, national governments. But in today’s world, this is easier said than done. In China, suspicion of misinformation, intentional rumormongering, and questionable leadership decisions are crippling the lines of communication that run between the Chinese people and their ruling party. The same could be said of the relationship between the President and the people of the United States, where “alternative facts” have become a recurring theme in political discourse. There is one thing the United States government could do not just to halt further transmission of the new coronavirus, but alleviate the fears surrounding it. Leveraging existing funding mechanisms, like Project BioShield, to develop and stockpile a broad-spectrum, anti-coronavirus drug would both curb the current coronavirus outbreak and prepare populations for outbreaks to come. Unfortunately, until federal commitments of this caliber are made, it will be up to individuals and their communities to find ways to avoid panic in the face of certain doubt. Some of the more concrete, universally applicable strategies for managing outbreak-related fear and anxiety are safety and prevention-oriented, such as washing your hands regularly, handling food with care, and practicing good hygiene in general. Other methods might involve education and mindful media consumption—for example, seeking out updates from credible health institutions, like the World Health Organization and the Centers for Disease Control and Prevention, rather than media outlets more likely to circulate incomplete or false information. Last but not least, we should keep in mind that even if the coronavirus outbreak demands some degree of social distancing or isolation, staying connected with friends, family, and loved ones— 20
whether it’s through Skype, social media, or a simple phone call—is one of the best ways to cope. Instead of allowing fear to drive us further apart, we can choose instead to reach out, band together, and hold out hope that this novel threat, like so many others before, will be overcome. This article originally appeared in Psychology Today and is available online here: Why Are We So Fearful of the New Coronavirus?
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Scientists Warned About Coronavirus For Years But Got Nowhere. Here’s How To Fix That Washington Post | February 18, 2020 | Article
Nature is teaching us a heavy lesson with this latest coronavirus outbreak. It warned us first with SARS and then with MERS, but we didn’t heed the warnings. If we willfully ignore nature this third time, our global community risks paying an unimaginable price. In 2003, when SARS was first reported, the origins of the virus were a mystery. Scientists suspected it may have come from bats, but it wasn’t until 2012, when the second major coronavirus outbreak was spreading across borders, that researchers confirmed its provenance. At the time of their discovery, they warned us of the outbreak potential of coronaviruses, urging the global community “to learn from our past to help us prepare.” But we didn’t pay attention. In the wake of the previous outbreaks, we scrambled to find a vaccine to prevent SARS and MERS specifically. But the coronavirus, much like the flu, is constantly evolving. In the same way that a flu vaccine doesn’t work across multiple strains over multiple years, a vaccine for one coronavirus outbreak is unlikely to help us stop a new one. What was needed then and what is needed now is not just a new vaccine, but a drug — or more likely a combination of drugs — that can act against the family of coronaviruses. Since the SARS and MERS outbreaks, scientists have decried the lack of interest and funding for the study of coronaviruses as whole. While financing was available in the midst of the outbreaks, it petered out after each outbreak ended. Funding from the National Institute of Allergy and Infectious Diseases, for example, leveled off at around $27 million a year — peanuts in the world of drug development. The biopharmaceutical industry could have stepped in, but, so far, it has been loath to act. The intermittent nature of the outbreaks 22
and the relatively small market for an anti-coronavirus drug means pharmaceutical companies have little incentive to pursue a solution. With scientists and researchers shackled by a lack of funds, and biopharmaceutical companies unwilling to step in without potential for profit, the government is the only one with the agency to act. There are concrete actions our government can take today to drive progress against the current coronavirus epidemic and to prevent future epidemics from occurring — a near certainty now according to scientists and researchers. The first step toward a solution is to list the coronavirus under the Biomedical Advanced Research and Development Authority (BARDA) and its Project BioShield. BARDA presides over the discovery, development and stockpiling of medical countermeasures to protect Americans against health security threats. This includes not just biological agents of warfare, but new and emerging infectious diseases — such as the coronavirus. BARDA bypasses the laws of supply and demand by allowing the federal government to pour hundreds of millions of dollars into procuring and advancing promising products. Listing the coronavirus as an emerging biothreat will create a market for an anticoronavirus drug that doesn’t currently exist. In the wake of the 2001 anthrax attacks, I worked through Project BioShield to develop ABthrax, a drug to treat and prevent anthrax infections. I can say with confidence that the U.S. government is fully capable of acting swiftly in the face of a publichealth crisis. But it must choose to act now. To date, we have been lucky — insofar as one can use that term when lives are on the line — as none of the coronaviruses that have jumped to humans have been both highly transmissible and highly lethal. There will come a time though when a coronavirus outbreak will spread quickly and kill abundantly. When that happens, we will not be talking about deaths in the hundreds or thousands, but in numbers far greater. It is our collective responsibility to ensure that our government leverages the rapid response capabilities at its disposal to protect the health of our nation, now and for generations to come.
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This article originally appeared in the Washington Post and is available online here: Scientists Warned About Coronavirus For Years But Got Nowhere. Here’s How To Fix That
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U.S. Hospitals Are Unprepared For The Spread Of Coronavirus. Here’s What They Should Do Los Angeles Times | February 24, 2020 | Article
When the new coronavirus COVID-19 first broke out, China’s healthcare system was unprepared. Hospital waiting rooms were so packed with prospective patients that hundreds more had no choice but to line up outside. Many waited several hours, only to be turned away and urged to self-quarantine. More troubling, experts say, is that the chaos of this initial surge likely did more to spread the disease than stop it. The same fate awaits us here if the new virus becomes a global pandemic. Hospitals in the United States are already so overburdened, and their staffs so overworked, that one bad flu season is enough to push them over capacity. Just two years ago, during a particularly bad season in California, patients seeking treatment for the flu instead found themselves in “war zones.” Hospitals turned away ambulances, imported nurses from elsewhere and erected parking lot tents when they ran out of beds. Surgeries had to be canceled and hospitals ran out of supplies. If the new coronavirus gains momentum here, infecting thousands, the outlook would be even grimmer. To be sure, we are better prepared than we were for the last coronavirus outbreak in 2009. Our hospitals now have pandemic plans to ensure that enough equipment, protective gear and administrative controls are available to deal with a surge of new patients. But, on their own, these measures are not enough. First, we must do more to make sure that if an outbreak occurs, we can keep and treat people where they are safest — in their homes. That will require leveraging or boosting the telehealth capabilities of local clinics to enable remote diagnosis of emergent coronavirus cases. Such virtual consultations would divert pressure away from hospitals and limit the transmission of infections in crowded waiting rooms. 25
Second, we must ensure that any added costs of protection and prevention are covered for patients. Currently, payment by insurance companies for virtual urgent care is not federally mandated, and many plans don’t cover it. Without a guarantee that their costs will be covered, patients may still head to hospitals to avoid the fees. Finally, we must prepare our hospitals and our health systems now for future crises even greater than the one we may face with COVID-19. This latest coronavirus is, by all appearances so far, more benign than some previous ones. Though it is highly transmissible, it has a low mortality rate, with the vast majority of those infected surviving whether they are treated at home or in a hospital. But there will come a time when a coronavirus outbreak or other biothreat emerges that is more lethal and widespread than anything previously seen. Our hospital-centric health system isn’t equipped to handle such a crisis. We must forge a new path toward a health system of distributed care, where patients receive care where they need it most — not just in hospitals, but in the home and community. The United States is home to some of the world’s best health providers and technological innovations. But we still hold to an antiquated notion that advanced healthcare is best delivered in hospitals. Countries like Singapore have shown that distributed care can be achieved on a national scale, and if they can do it, so can we. This article originally appeared in the Los Angeles Times and is available online here: U.S. Hospitals Are Unprepared For The Spread Of Coronavirus. Here’s What They Should Do
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March 2020
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Four Coronavirus Prevention Steps We Can All Take FOX News | March 1, 2020 | Article
With the first fatality recorded here in the United States, there is heightened alarm around what may lie ahead for all of us. In truth, there is no telling what damage this force of nature may leave in its wake. But that is not to say that there is nothing we can do to weaken its impact. Protecting ourselves from the virus is a collective responsibility that requires action from each of us to varying degrees. First, we must consider how each of us respond personally to the threat of an outbreak. There are basic handwashing and hygiene techniques than can limit our chances of infection and help us prevent the spread of the disease if we are unknowingly infected. We can avoid large crowds, wash our hands regularly, cover our mouths when we cough or sneeze, and start preparing our homes for the possibility that we’ll fall ill and need to stay home while sick. Second, we must think of how we will respond as a community and what we do collectively to ready ourselves. If you work in health, make sure frontline healthcare workers have a steady supply of protective equipment and that protocols are in place to meet a surge in demand. Bolster telehealth capabilities now so that in the event of an outbreak we can counsel patients remotely and direct them to the right level of care for their medical needs. If you work outside of the healthcare community, prepare your workplace environment to protect yourself and all employees. Ask leaders at your schools, places of worship, and other public gathering places how they will respond in the event that the virus spreads. The third effort we must focus on may lie beyond most of our individual domains but is equally important for us to understand and support – the scientific effort towards a medical solution. Efforts to develop a combination of drugs that can treat those who are newly 28
infected and prevent them from passing the infection on to others should be paramount. The onus for this work does not lie solely with scientists and researchers, but also with the pharmaceutical industry and government who must provide researchers with the necessary resources. One of the best steps we can take now to spur action on both sides is to list the coronavirus as an emerging biothreat under the Biomedical Advanced Research and Development Authority (BARDA) and its Project BioShield. Such a move would create a market for an anti-coronavirus drug that doesn’t currently exist. Finally, and perhaps most importantly, we must consider how we talk about the potential threat we face. We do not yet know the trajectory of this outbreak but even the most sanguine among us will admit to at least a hint of fear of what may come. Clear, concise, and credible public health communications is imperative in this time of crisis. If we can’t trust what our leaders are telling us to do or – worse yet – if they leave us confused about the possible risk, we leave ourselves fully exposed to the forces of nature and all the worst that this virus can bring. This article originally appeared in FOX News and is available online here: Four Coronavirus Prevention Steps We Can All Take
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Coronavirus Mismanagement Is Risking American Lives Forbes | March 9, 2020 | Article
It is now clear that the U.S. response to the potential dangers of the coronavirus infection is inadequate, confused, and—worst of all— putting us all at much greater risk than we need to be. Our first mistake was in choosing to develop our own diagnostic testing kits, instead of following the available WHO guidelines. It took more than a month since the beginning of the outbreak for the CDC to deliver tests to a handful of labs across the country, only to discover that the kits that were sent were flawed. The second mistake was in determining who qualified for testing. Initially only patients with recent travel to China and who showed symptoms of COVID-19 were approved for testing. It was only this week, on Tuesday, when the administration relented and allowed all Americans to be tested, if needed. But even with this step forward, our mistakes continue. Our government is now punting the testing problem down to the States. While finally allowing States to develop their own FDA approved testing kits to make testing more available, the government is now holding States solely accountable for tracking the number of people tested. On Monday, the CDC stopped reporting national numbers of people tested on their website, claiming that now that States were conducting tests themselves the CDC no longer had the most up to date figures. Without clear reporting from the CDC or transparent communication from the administration, the scope of the outbreak in America is still a complete unknown. A new analysis out of the Fred Hutchinson Cancer Research Center in Seattle suggests that this new strain of coronavirus has been spreading unseen and undetected in the area for weeks. Some models suggest up to 1,500 people could already be infected in the greater Seattle area alone. Calling out the government for their failures isn’t about politicizing public health—it’s about protecting our nation from a 30
growing danger. The mistakes we made allowed COVID-19 to come to our country unseen and undetected. The mistakes allowed the virus to spread to places like the Life Care Center, where more than 50 residents and staff continue to struggle with the disease, and seven residents—the oldest and most vulnerable among us—have died. And the mistakes we continue to make in shielding the facts from Americans is making it harder for us to make the tough decisions around possible self-quarantines, social distancing measures, and school or business related shutdowns. It is astounding that while China can now distribute more than a million tests per week and South Korea has rolled out drive-thru testing clinics and disinfecting drones, we have no one in government who can give us clear numbers around how many Americans have been tested and how many patients are under investigation for the disease. We can and should do better. The administration, Congress, and our entire government leadership must be called on to deliver a more transparent, a more effective, and a more robust response than what we have done to date. This article originally appeared in Forbes and is available online here: Coronavirus Mismanagement Is Risking American Lives
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Social Workers Have A Key Role To Play In The War Against Coronavirus FOX News | March 10, 2020 | Article
As the number of Americans critically ill from coronavirus mounts, one thing is becoming increasingly clear: it’s the oldest among us who are most vulnerable. Among the most recent deaths reported in the United States were a 69-year-old man, a man and a woman, each in their 70s, and another woman in her 80s. Their deaths reflect a wider story that those tracking the lethality of this new disease are just beginning to understand – in the fight against COVID-19, the younger fare far better than the old. Early research by the Chinese Center for Disease Control and Prevention has shown that the fatality rate of this new disease differs widely by age. For those confirmed cases between the ages of 10 and 39, only 0.2 percent die. For those 80 or older, the fatality rate is 14.8 percent. So while health care workers in hospitals and clinics may be the first line of defense for those feeling ill, it is the social workers and caregivers in our nursing homes and long-term care centers who are truly on the front lines of this outbreak. And yet, our national response has all but ignored this critical community. To redress our oversight, we must work immediately to integrate social workers and long-term care providers into our overall response to the outbreak. Social workers are the ones who will be able to identify those most at risk, who can alert authorities at the first sign of a patient falling ill, and who can pinpoint the patients who are likely to have the most severe and fatal reactions to COVID-19. Beyond simply linking social workers to the wider effort, we must also ensure that they have the knowledge, training and equipment to deliver immediate care for those in need – including the protective equipment in such scarce supply today. Without such equipment, social workers risk spreading infections to other patients 32
and are at serious risk themselves as they move about facilities where the scope of the outbreak may not yet be fully understood. Now that testing kits are becoming increasingly available across the United States, long-term care facilities across the country and especially in communities with known cases should be the first among those to receive them. When a medical solution becomes available, we must prioritize these facilities as well, as they are home to the most vulnerable among us. History has taught us how critically important social workers can be in the face of a public health epidemic. They were the messengers who first warned us about the spread of tuberculosis in Victorian slums. They were the ones to first understand and advocate for AIDS patients in the earliest years of the epidemic. Today, they are the ones who can help us push back the boundaries of this epidemic and help prevent it from spreading across our country. This article originally appeared in FOX News and is available online here: Social Workers Have A Key Role To Play In The War Against Coronavirus
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Coronavirus Pandemic Could End In These Ways – Maybe Sooner Than We Expect FOX News | March 21, 2020 | Article
The way public life has changed in the wake of the coronavirus pandemic may feel new and frightening to many. But the older among us have lived through similar times and similar fears. There is one thing we know that may bring solace: there will be an end to this pandemic and - if we take advantage of the most promising drug options available today - the end may come sooner than most think. Those of us who have lived long lives can remember the intense panic that summer used to bring, as "polio season" approached. Pools were shut down, movie theatres emptied, and most of us were isolated from the majority of our friends. Our fear was not unfounded. In 1952, nearly 60,000 children were infected with the virus and more than 3,000 died. Thousands who survived were left paralyzed by the disease. But a year later, researchers announced a new vaccine had been successfully tested in humans. Eventually, thanks to their work and the work of many other scientists and public health leaders, the epidemic was contained. The current coronavirus pandemic will end as well, despite how heavily it besieges us today. The only question is how. There are four possible ways: If the coronavirus proves to be seasonal in temperate climates, meaning that new infections eventually decline on their own as the weather warms. But in this scenario, the coronavirus would return when cold weather returns - although we hope that by then our health system is better prepared to help those who fall severely ill to recover. Through herd immunity, where a significant percentage of the population becomes infected, recovers and develops a natural immunity. The challenge is that reaching herd immunity will take a
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significant amount of time. While we wait, it's possible that as many as 200,000 to 1.7 million Americansmay die. Development of a vaccine that would be made widely available. There are at least five vaccines currently in some phase of development, with one starting clinical trials just this week. That's a promising development, but just the first phase of a lengthy process. Even in the best-case scenario, it will still be many months before a successful vaccine is available to the general public. Accelerated development of therapeutic drugs that treat infections and, depending on the drug, prevent further infection from occurring. One option in this scenario is an antiviral drug combination that targets the RNA at the center of the coronavirus responsible for the pandemic sweeping across the world today. In the midst of the SARS and MERS outbreaks, a number of drug candidates that target key proteins in coronaviruses underwent lengthy laboratory and preclinical study. But the drugs were never advanced to clinical trials. That's because there was no market for them and no government was willing to step in to guarantee the market with a commitment to stockpile the drugs. Thankfully, there is renewed interest today in these therapeutic solutions, with some antiviral drugs currently moving through clinical testing. There are also clinical studies now underway of other drugs that treat the respiratory consequences of infection but not the virus directly. With the right leadership and opportunity on our side, we may be able to begin moving toward the end of the current pandemic. But when this happens, we shouldn't turn away from the lessons we are learning today. Someday there will be another lethal coronavirus epidemic. There will also be another highly lethal and transmissible strains of influenza, a global spread of antibiotic-resistant tuberculosis and antibiotic-resistant bacteria. The biological threats we face are not unknown - just like the current coronavirus outbreak was not unexpected among scientists. This outbreak is yet another lesson from the natural world - one we have ignored in the past and ignore in the future at our peril. If you live in an earthquake zone, you build earthquake-proof houses. If you live near a volcano, you pay close attention to the local seismometer and clear out when it goes off. 35
Now we are on the alert today to take actions to protect ourselves against a dangerous virus. But will we forget again tomorrow? We will we ready for the next viral epidemic or pandemic? It is up to us to hold our leaders accountable now and in the future to step in and bring lifesaving drugs to market when others won't or can't. This article originally appeared in FOX News and is available online here: Coronavirus Pandemic Could End In These Ways – Maybe Sooner Than We Expect
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Wondering What A Coronavirus Quarantine Is Really Like? Forbes | March 20, 2020 | Article
Quarantine is an often disquieting term. From the mid 1300s to today, the word has evoked images of the sick and defenseless being dragged from their homes and locked away with dozens if not hundreds of potentially infectious strangers. The reality in the age of coronavirus though is far different. I had the opportunity this week to speak to a friend of mine who was forced into quarantine, along with his wife, in Shanghai. Many news outlets have reported on the Draconian measures introduced by China, describing “hazmat suit-clad goons dragging people from their homes”. Yet for my friends, the picture they paint of life under quarantine is different. Their journey to quarantine started in late February, when they hopped a plane from Europe back to their home in Shanghai. The city they were traveling from had yet to report a single confirmed case of COVID-19 and Europe overall hadn’t yet been dubbed a hot spot of infection. Upon their arrival at the Shanghai airport, they were screened like all other travelers — they walked through an infrared temperature check, they filled out a form describing where they had traveled, then they grabbed their suitcases, hopped into a waiting car, and headed home to their apartment. The next day, when my friend went down to his lobby’s front desk, the clerk examined him with friendly suspicion. “He was asking me where I had been, since he hadn’t seen me or my wife around the apartment for a few weeks. Once I told him I’d been traveling, his whole attitude changed. The only thing he wanted to talk about from then on was self-isolation.” In China, there are three levels of isolation and quarantine. The first is self-isolation, which means you stay home, monitor your temperature, and record it via a mobile app that helps the city monitor the health of people in isolation from afar. You can go out to buy groceries and for walks, but other than that you are meant to 37
confine yourself to your home. The second level is home quarantine, where you’re still at home but cannot step outside your home. And the third is controlled quarantine, where you are taken out of your home and sent to a supervised quarantine facility. The government of Shanghai had asked all those traveling into the city from elsewhere to voluntarily self-isolate for two weeks to be sure they weren’t unknowingly spreading infections. There was no doubt that my friend and his wife would comply. “For the next three days, we stuck very close to home. We could leave to get groceries if we needed to, but mostly my wife and I ordered in. But even ordering food was different than it used to be before the outbreak. Instead of bringing the food to our apartment, the delivery people had to leave it on a set of tables and shelves that had been temporarily placed by the front gate. At least we could go down to pick it up, since we were only self-isolating. If you’re told to self-quarantine you can’t leave your apartment — someone from the building has to bring it up to you.” “Then that Tuesday, three days after we’d arrived back in Shanghai, everything changed. Our phone rang incessantly that day — the police, the Shanghai Center for Disease Control, and the district CDC all called us to let us know that a passenger on our flight to Shanghai had tested positive for infection. But that isn’t really what shocked us — what alarmed us the most is when they told us we would have to finish out the rest of our fourteen day period of self-isolation in a controlled quarantine facility. They wanted to take us from our home.” “The word quarantine was terrifying. I was thinking of quarantine as somehow a lot of very, very sick people locked up together. Not, you know, a rational thing. Sort of like solitary confinement — you are cut off in some sense from the rest of the world. I even checked with the American consulate to see if it was really necessary. But they told us there was no other option, we would have to accept the forced quarantine or risk the consequences of noncompliance.” “That night we each packed a suitcase of our personal things and a bag with our laptops and tablets then the next morning we went downstairs at 11:00am, as they’d asked. A person comes in wearing a mask and some sort of surgical gown and walks us over to a van. Then he drove us over to a local hotel. Oddly enough, we looked it up later and found out it was actually a three star hotel when it was operational.” Much like the quarantine motels set up in Washington State here in the United States, the Chinese government had taken over 38
hundreds of hotels to use as quarantine facilities to help contain the spread of the disease. “When we arrived, there was another person in a hazmat suit standing outside waiting for us. It was nothing like the usual hotel check in process. We walked inside and were greeted by a very nice woman in a surgical mask and gown sitting behind a card table with forms and instructions. She politely but firmly explained that we would have to stay in separate rooms. She gave me a form which included rules for the next eleven days of our stay. We couldn’t leave our rooms. We couldn’t receive guests. And when we received our three meals a day — at 8:30am, 12:00pm and 6:00pm — we would listen for a knock on our door then wait thirty seconds before opening the door, getting our food as quickly as possible, and shutting the door behind us.” “It was all a bit unnerving at first. We asked if we could room together, but they said no — no exceptions. Even though I don’t speak Chinese, they assured me it wouldn’t be a problem. They did at least put us in two rooms on the same floor. They handed us each a thermometer, showed us how to use it, then told us that we would have to take our own temperature twice a day. We’d also have to submit to daily medical inspections and allow people to enter each day to clean and disinfect our rooms.” “There was one last set of directions before we went into our rooms. A hazmat-suited woman handed my wife and I a couple tiny bottles of shampoo and shower gel, and a couple bars of soap. Then she handed us each a big blue bucket and a jar of disinfectant tablets and said, ‘This is for toilets.’ My eyes grew wide in horror as I tried to figure out what she was asking me to do. Then she realized what I was thinking and burst into laughter. ‘No, no, no, no, no, no,’ she said. ‘I don’t want you to use the bucket as a toilet, I want you to dissolve the tablets in water in the bucket, then dump the mixture into the toilet before you flush. I was so relieved. They wanted us to dissolve six disinfectant tablets into one liter of water then pour it down the toilet after urinating. It was two liters of water and twelve tablets for other types of bathroom visit.” “The first day was a bit disconcerting. The person in the room beside mine had a pretty nasty cough that sounded like a barking dog. But the next day was substantially better, as my wife and I figured out a routine. Internet bandwidth was good and we could connect an unlimited number of devices. So we started a video conferencing session which we left on all the time, so we could ‘share; the experience. We could still order food for delivery, which they’d drop off at meal times in front of our doors. And friends were allowed 39
to send care packages as well: little bottles of Evian and Perrier, fresh fruit, wine and cheese, and chocolates all made it seem much less like the kind of experience I previously associated with the word ‘quarantine’.” “The hotel staff was kind and friendly. I especially enjoyed the disinfectant guys in the hazmat suits who came to my room each day to clean out the room – they were my two minutes of same-room conversation each day. I could see them visit my wife’s room before mine each day, so I always knew when they were on their way. I never exchanged names with them but they were my best buddies, because they were really my only buddies. I suppose they were also my worst buddies too. They were everything.” Thankfully, my friend and his wife were cleared and released at the end of their eleven days in controlled quarantine. Now, in Shanghai as in the rest of China, there have been no new infections due to local transmission. “What I would say now is that quarantine today, in the age of the internet with continuous video conferencing, is very different from what it probably used to be. With the care packages, and video conferencing and continuing to work remotely, I did not feel cut off from the world. I felt isolated in the sense that I was alone, but I did not feel cut off.” In addition to bringing relief to any afraid of what quarantine may bring, my friend’s story highlights the steps we need to take in the United States as well to prepare ourselves for the inevitable onslaught of new cases. We need to be ready to test those who we suspect are infected, trace all those they came in contact with, and have a plan in place not just for medical care but also for selective isolation and quarantine. This is the only way to slow the spread of this disease and buy ourselves time for a medical solution. This story illustrates one other important aspect of our response, which we dare not lose sight of: maintaining a sense of dignity and humanity in how we care for each other. Even as he sat alone in his room, there were moments of kindness and compassion throughout my friend’s experience that he will not soon forget. He told me one story, from his third day of quarantine, when he received an unexpected package of kiwi fruit, coffee, and tea from the Shanghai Municipal Foreign Affairs Office. The package came with a note in poorly translated English that read, “My dear friend, the inconvenience for the time being, it is for the health of you, of me, and of everybody. So thank you for everything. Quarantine against virus is no isolation of warm hearts. We are right here with you.” 40
This article originally appeared in Forbes and is available online here: Wondering What A Coronavirus Quarantine Is Really Like?
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Terrified of Quarantine? Here’s What It Actually Looks Like Psychology Today | March 23, 2020 | Article
There have been many unfortunate moments in America’s quarantine history, from the forced confinement of Typhoid Mary to the barbed wire strung around parts of San Francisco’s Chinatown in the midst of an outbreak of bubonic plague. But quarantine in the time of coronavirus will likely have no barbed wire moments. Still, even the possibility of forced quarantines have provoked fear among many. Recently a friend of mine and his wife were forced to quarantine in Shanghai. It was late February and they were returning from Europe back to their home in Shanghai. The city they were traveling from had yet to report a single confirmed case of COVID-19 -though they would do so just a day later -- but upon their return, they agreed to two weeks of voluntary isolation in their homes. This experience was much like what many of us are doing here in New York -- they went for walks and bought their groceries, but they stayed home most of the time. They were required to take their temperature twice a day and upload the results to an app so authorities could monitor their health from afar. Roughly 90% of people infected with COVID-19 experience a fever as one of the symptoms. Three days later, all that changed. My friends received calls from the police, the Shanghai Center for Disease Control (CDC) and their district CDC telling them a passenger on their flight had tested positive for infection and my friend and his wife were to be moved to a controlled quarantine location. This is different from selfquarantine, where you are asked not to leave your home, even to go out for food. With controlled quarantine measures, you are taken from your home and taken to a secure location for monitoring. A day later, my friend and his wife were taken by van to a three star hotel in the city, which had been taken over by authorities for quarantined individuals -- not dissimilar to the quarantine motels set 42
up in Washington State as the outbreak unfolded there. With suitcases in hand, they were taken to two separate rooms on the same floor and told they would be separated for the duration of their quarantine. Food would be brought to them three times a day and left in front of their doors. And once a day, their trash would be cleared and their room disinfected. With access to the internet and cell service, life on the inside was not all that different than life on the outside. They woke up, exercised, ate breakfast, and went on with their day, working remotely from a table in their rooms. They kept a video feed on with each other throughout the day so they could check in and group chat with friends. And they were even allowed to receive care packages with fresh fruit, wine, and other items that made life much more manageable, like warmer clothes, comfortable linens, and books to pass the time. While perhaps not enjoyable, in this case quarantine was most definitely liveable. Their story will hopefully bring relief to those who are afraid of what quarantine might bring. But despite the good news inherent in their story, there is still reason for a judicious amount concern. Quarantine was bearable for my friends because their government was prepared. They tested the traveller who was initially infected, traced all his contacts, and had a plan in place for quarantine. Rules for quarantine were given to my friends at the hotel’s front door, along with a thermometer, soap, and even a bucket with dissolving disinfectant tablets that they were to use after going to the bathroom to prevent ongoing infection. Would that be our experience here? The answer is unclear. Already our healthcare leaders and health systems are scrambling to keep up with a surge in demand. In places where we have set up similar quarantine facilities there have been reports of inadequate controls to keep those who may be infected in place. Each of us have a responsibility to ourselves and each other to stay as safe and healthy as possible, even if it means we are inconvenienced and forced out of our daily routines. Only by alleviating the pressure on our health system now can we free up resources to ensure that our response to this outbreak and the support for those infected is as smooth and efficient as it was for my friends. This article originally appeared in Psychology Today and is available online here: Terrified of Quarantine? Here’s What It Actually Looks Like 43
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Hydroxychloroquine Is Ineffective In Treatment Of Patients Hospitalized With COVID-19, According To Small Controlled Trial From Shanghai Forbes | March 25, 2020 | Article
Results from a controlled clinical trial from China on the use of hydroxychloroquine as a treatment for COVID-19 have shown no significant differences in health outcomes between the control group and patients who received the experimental drug. Thirty patients hospitalized for COVID-19 participated in the trial. Fifteen were treated with 400mg of chloroquine for five days and fifteen received the standard supportive care. On Day 7 of the trial both groups were evaluated The results: CT scans showed there was little difference in the progression of the disease for those given the hydroxychloroquine treatment and those who received conventional care. Of the thirty patients, only one patient progressed to severe stages of the disease -- that patient had received hydroxychloroquine as part of their treatment. 93% of patients in the control group tested negative for COVID19 after seven days compared to 86.7% of patients in the hydroxychloroquine treated group. It took those in the control group between 1 and 4 days from the start of treatment before testing negative for the disease. It took those in the hydroxychloroquine treated group between 1 and 9 days from the start of treatment before testing negative. The results were statistically indistinguishable, meaning there was no measurable difference in outcomes among the groups who received the hydroxychloroquine treatment and those who didn’t. What does this all mean? The researchers who conducted the study, a team from the Shanghai Public Health Clinical Center in China, acknowledge that 45
their clinical trial was small and a larger study would be necessary to confirm the results. The study also raises questions that remain unanswered about whether different dosages of hydroxychloroquine might bring different results. Still, despite its limitations, the study results are important -helping us curb false hopes that may be encouraging us to abandon the more aggressive actions that we need to take to stop the spread of this disease. These results must also be considered in light of the real potential harmful side effects of hydroxychloroquine. The full study in Chinese with a short English summary is available here: http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43 f8625d4dc74e42bbcf24795de1c77c.pdf This article originally appeared in Forbes and is available online here: Hydroxychloroquine Is Ineffective In Treatment Of Patients Hospitalized With COVID-19, According To Small Controlled Trial From Shanghai
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Study Shows Hydroxychloroquine Is Ineffective Against COVID-19 — So What Now? Forbes | March 25, 2020 | Article
Results from a controlled clinical trial from China on the use of hydroxychloroquine as a treatment for COVID-19 have shown no significant differences in health outcomes between the control group and patients who received the experimental drug. Thirty patients hospitalized for COVID-19 participated in the trial. Fifteen were treated with 400mg of chloroquine for five days and fifteen received standard supportive care. A week after the treatments started both groups were evaluated and results showed that no measurable difference in the progression of the disease. There are still important lessons to draw from the results. We must redouble our efforts towards the best and quickest medical solution -- the development of therapeutic antiviral drugs that treat infection and prophylactic antiviral drugs that prevent infection. In the wake of the SARS and MERS outbreaks, a number of highly promising drug candidates emerged, though none of them were brought to fruition due to a glaring lack of funding and flagging interest in coronaviruses once each outbreak ended. Now, with renewed interest and resources, these drug candidates are moving quickly to clinical trials. Recently a small trial was held to determine whether lopinavir-ritonavir, a combination HIV treatment that inhibits coronavirus proteases, would deter the virus in COVID-19 patients. Unfortunately, as researchers recently reported in an article for the New England Journal of Medicine, the drug failed to cure or diminish infection. But those early and unimpressive results aren’t conclusive and, more importantly, the clinical trial only focused on only one of the virus’ most promising targets, the protease. SARS-CoV-2 has favorable targets for antiviral drugs: the proteases, the helicase, and the RNA-dependent RNA polymerase. A second takeaway from the Shanghai hydroxychloroquine study is also critical -- while medical solutions are promising, they 47
are no guarantee. It is far too soon for us to abandon more aggressive actions that can be implemented immediately and effectively to slow the spread of COVID-19 in the United States. To date, our response to COVID-19 has been among the worst in the world. Testing per capita here lags far behind other developed nations -- including countries like Italy and the United Kingdom who are faring poorly in the face of this disease. In countries like Singapore and South Korea, aggressive contact tracing combined with widespread testing and selective isolation and quarantine has contained their outbreaks, dragging down the number of new infections each day and helping those countries avoid the extreme lockdown measures that have been used elsewhere, including here the United States. There are now more than 55,000 cases of COVID-19 in the United States. In New York, the number of cases is doubling every three days. Thousands lie in hospital beds. Hundreds have already lost their lives. This is not the time for excuses or inaction - we must test, we must trace the contacts of those infected, and we must isolate all those at risk of spreading the disease further. And while we do so, we wait for a medical solution that will hopefully soon be at hand. Tara Haelle discussed the Chinese hydroxychloroquine study in an earlier post today. This article originally appeared in Forbes and is available online here: Study Shows Hydroxychloroquine Is Ineffective Against COVID-19 — So What Now?
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Is This Coronavirus Epidemic The Big One? Forbes | March 31, 2020 | Article
When a friend asked me if this was the big one two weeks ago, I was not sure. Today I can answer: Yes. This is a big one in terms of lives that will be affected and lost, and economies destroyed. But… It is a big one, not as a consequence of an intrinsic property of the virus, but entirely the result of human action and inaction. The course of the epidemic in China shows that the epidemic can be controlled without an effective vaccine or antiviral drug. Rigorous people to people contact control can halt the spread of infection. Lack of short-term and long-term preparedness has doomed both the US and Europe and may well devastate other continents as well. Forewarned long in advance that a pandemic respiratory infection from an influenza or coronavirus was inevitable, our government failed to prepare and to support the research needed to create the vaccines and drugs needed to prevent and treat infections. We also failed to develop the necessary health system infrastructure needed to cope. This despite repeated warnings over the last thirtyfive years since the advent of HIV/AIDS that this day would surely come. Failures over the past three months are of a different sort. They are failures of leadership and of government. We are plagued by a President who, more than three quarters through his term, still claims that the buck stops with Obama. He is deaf to the agonized pleas of our health care professionals who, unprotected, must risk their lives and those of their family to treat the ill. The economic toll is yet to be measured but surely will include an unprecedented global depression, bankruptcies of national and state governments, businesses large and small and untold millions of people around the world that depend on their jobs for food and shelter. 49
What may mount to well more than 100 trillion dollars in economic damage could have been prevented by a few billion dollars of investments in research and a few hundred billions in health infrastructure. I fear ten years from now (one, two, three Presidencies hence) we will revert to our natural state of complacency, distracted by present exigencies and fail to prepare for nature’s next inevitable big one. This article originally appeared in Forbes and is available online here: Is This Coronavirus Epidemic The Big One?
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Why America Is Losing to COVID-19 Project Syndicate | March 31, 2020 | Article
Kentucky Senator Rand Paul’s behavior over the past two weeks is exactly what’s wrong with America’s response to COVID-19. Paul has a compromised lung, so he decided that he should be tested for the disease out of an abundance of caution. From the time of his test until he was confirmed positive six days later, Paul did nothing to protect those around him. On the contrary, he met with other senators, cast votes on the Senate floor, played a round of golf at a private club, and even squeezed in a few laps at the Senate pool. In the countries that have contained the coronavirus outbreak, such irresponsible behavior has not been tolerated, and even could have landed Paul in jail. As a physician (ophthalmologist), he, more than anyone, should know that if he was concerned enough about COVID-19 to be tested for it, he should have been equally concerned about the risk he was posing to others. This article originally appeared in Project Syndicate. The full article is available here: Why America Is Losing to COVID-19
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April 2020
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Why Don’t We Have A Coronavirus Drug Yet— And How We Can Develop One As Soon As Possible Forbes | April 3, 2020 | Article
How will the new coronavirus pandemic end? It could prove to be seasonal, meaning it peters out with the weather with a chance of returning at this time next year. A significant plurality of all people on Earth could contract the disease—prolonging its duration, slowing it over time through a gradual buildup of herd immunity, and inevitability leading to the death of millions. Or one of the many pharmaceutical companies hard at work on inventing a vaccine could succeed and administer their product widely and cheaply, though at least a year will go by before this comes to pass. Our best option—the option that will save the most lives in the least amount of time—is to accelerate the development of therapeutic antiviral drugs that treat infection and prophylactic antiviral drugs that prevent infection. Two approaches can realistically achieve this. The first is to repurpose existing antivirals. The second is to develop de novo, from scratch. Pharmaceutical companies and national health agencies have begun to pursue both strategies aggressively as the COVID-19 outbreak intensifies. Lucky for them, a massive corpus of laboratory studies conducted around past coronavirus outbreaks already exists—remnants of drug discovery efforts marshaled around SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) that never came to fruition. Much of the preclinical and phase I clinical trials showed promise and, had they advanced to the stages required for FDA approval, we might have had therapeutic or even prophylactic antivirals in our possession on the eve of COVID-19. What happened to halt the pipeline then, and how can we accelerate it now? SARS & MERS: Why a drug was never developed 53
The origins of the SARS outbreak can be traced back to November 2002, when cases of an “atypical pneumonia” first appeared in the Guangdong Province of southern China. Come February 2003, similar reports were surfacing in regions as near as Hong Kong and countries distant as Canada. These outbreaks, previously thought to be isolated, began to occur with more frequency in March, mainly in hospital settings and therefore mainly infecting healthcare workers. By early April, a slew of research groups had determined a novel coronavirus to be the epidemic’s likeliest causative agent. Initially, the international research response was robust. Once the virus was identified, diagnostic assays and profiles of its clinical, virological, and epidemiological characteristics soon followed. Potential antiviral candidates were investigated, animal models were developed—mice, macaque monkeys, and Golden Syrian hamsters among them—and vaccine strategies were charted and advanced, sometimes as far as phase I clinical trials. In the meantime, most patients infected with the disease were treated using experimental combinations of ribavirin, interferons, steroids, and antibiotics, though it was never proven at the time whether these therapeutic interventions corresponded with actual rates of recovery. In July 2003, around 8,000 cases and 800 fatalities later, SARS was deemed to be officially contained. Efforts to research the SARS coronavirus, of which much remained unknown, continued, motivated by the certainty that it wouldn’t be the first to wreak havoc on human life. The lack of knowledge around the molecular biology of SARS-CoV, i.e. ideal targets for entry and replication inhibitors, that impeded drug development during the outbreak was largely resolved in its wake. All the pieces needed to bring new antivirals to the finish line were falling into place. All except for one: the money. The funding streams funneled by pharmaceutical companies, governments, and nongovernmental organizations into labs around the world had all but dried up by 2006. No cases of SARS had been reported since 2004, and previously invested parties were losing interest. Thousands of scientific papers had been published on SARS, and yet nearly a decade later, when MERS first appeared in Saudi Arabia in late 2012, not a single antiviral drug was available for public consumption.
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Since some of the more promising inhibitors identified in the SARS literature had yet to undergo large scale testing for toxicity, healthcare workers treating MERS stricken patients up and down the Arabian Peninsula reverted back to the experimental therapies administered to SARS patients—even though they were ultimately found to yield “little to no clinical benefit.” The MERS epidemic went on to infect fewer people than its predecessor—around 2,500, to be exact—but racked up a mortality rate triple that of SARS. At first, it seemed like the momentum for finding antivirals had mounted anew. Calls came more urgently not just for a MERS vaccine, but a broad spectrum antiviral that could successfully neutralize future coronavirus threats. Yet by 2016, the year MERS cases definitively began to dwindle, the antiviral drug to make it furthest down the pipeline was only just entering phase I dose escalation trials. Three years later, that number had increased to three. The estimated date of completion? Ten years from now. COVID-19: Paying for our past mistakes and avoiding new ones As of March 23, COVID-19 has infected nearly 350,000 and killed more than 15,000. The tally has increased so exponentially that it has become difficult to keep track. From the beginning, it has already been too late; we had almost two decades to prepare ourselves and instead met our enemy unarmed. Back when SARS research was still ongoing, the Singapore based biomedical research hub Biopolis commissioned a sculpture for their central plaza. SARS Inhibited (2006), the winning design conceived and actualized by artist Mara G. Haseltine, was erected as an homage to the notable contributions that Biopolis scientists made to the coronavirus drug discovery and development front. While their findings were unduly shelved, they are now seeing the light of day. The COVID-19 coronavirus is called SARS-CoV-2 for a reason. While their genomes aren’t exactly identical, the two coronaviruses have between 80 to 90 percent of the same genetic material. Like SARS-CoV, SARS-CoV-2 penetrates a human lung cell by binding to ACE2, a receptor protein located on its surface. In an effort to expedite the search for efficient therapies, scientists 55
are revisiting most—if not all—of the molecular targets identified some fifteen years ago in preclinical studies for SARS antivirals. Three targets emerged as particularly viable then that remain so today: the helicase, the RNA-dependent RNA polymerase, and the protease, depicted in SARS Inhibited. The protease of coronaviruses is crucial to its replication, breaking down viral proteins into the functional units the virus needs to speedily copy itself. A clinical trial was held to determine whether lopinavir-ritonavir, a combination HIV treatment that inhibits coronavirus proteases, would deter the virus in COVID-19 patients. Unfortunately, as the researchers recently reported in an article for the New England Journal of Medicine, the drug failed to cure or diminish infection. That said, the unimpressive results aren’t conclusive, and testing of lopinavir-ritonavir will continue under the auspices of the World Health Organization multinational SOLIDARITY trial set to take place in Iran, South Africa, Switzerland, and elsewhere. The RNA-dependent RNA polymerase is the target of Remdesivir, a broad spectrum antiviral invented by Gilead Sciences ten years ago. Remdesivir is designed to keep the RNA-dependent RNA polymerase from making copies of the virus’s genetic material. The drug was unsuccessful in stopping this process in the cells of Ebola patients, but its known safety in humans helped fast track clinical trials testing its efficacy for COVID-19 to phase III. Despite this, its prospects remain hazy; a Gilead analyst described the pipeline as “risky” and the outlook as “unclear.” Along with lopinavirritonavir, Remdesivir awaits further vetting via the SOLIDARITY trial, while the first outcomes of the trials taking place in the United States and China are due for an April release. Several other drugs are being tested, though none specific to SARS-C0V-2. Current evidence suggests they will be weakly effective in preventing and treating the infection at best. Like the protease and RNA-dependent RNA polymerase, the helicase makes an ideal target due to the multifaceted role it plays in viral replication. While the body of knowledge on effective helicase inhibitors has been passed over in favor of more developed therapies, they still merit further investigation—as do the many other proteins that allow the coronavirus to commandeer our cellular machinery, whether they originally belong to the virus or the host. Already hot 56
on this trail are hundreds of scientists who joined forces to map the interactions that individual parts of SARS-CoV-2 have with individual parts of our lung cells. If the coronavirus uses these components to replicate, navigate, or otherwise destroy our cells’ defenses, then a drug that interferes with those interactions—of which there are reportedly more than 300—might be effective in stopping infection altogether. On Sunday, March 22, several of the scientists published a preliminary report of their findings that identified 69 drugs that might perform this function. Of these, 32 are undergoing preclinical development, 12 are in clinical trials, and 25 are already FDA-approved. For now, it is ultimately these FDA-approved drug candidates— both those targeting viral proteins and those targeting human proteins—that offer us the most rapid solution. However, for now we do not have enough evidence to confirm their effectiveness as a treatment for COVID-19. In my view, the best solution would be a combination of virus specific antiviral drugs that inhibit the mechanisms the virus needs to reproduce itself. If one or more drugs, alone or in combination, are shown to be effective in treating infection, those same drugs should also be used to prevent infection in the first place. This practice has a wellestablished precedent in antimalaria drugs, which are prescribed to people traveling to or stationed in countries where malaria is prevalent, and the combination antiviral drugs for HIV known as PrEP, recommended for populations at risk. There is much reason to believe that antivirals that effectively treat coronavirus infection will also be effective in preventing the infection of those exposed. The horizon for vaccine development is too distant to even speak of, and though investigations of plasma derived and antibody based therapies are in the mix, whether these can be produced and deployed en masse is, for now, highly uncertain. The efficacy of drugs like chloroquine, which treat the respiratory consequences of infection but don’t attack the virus directly, is also not yet known. We cannot allow a broad spectrum antiviral drug that targets all coronaviruses, not just COVID-19, to lay waste to the same fate that befell SARS and MERS. The laws of nature are not dictated by market forces—any snapshot of the global economy from the last few weeks will say as much. If we wish to survive this pandemic and the next, we must leverage federal agencies like BARDA and 57
emergency funding mechanisms like Project BioShield to accelerate the effort now and continue it even when COVID-19 is well behind us. Otherwise, it won’t truly be the end—it will be just the beginning of many pandemics to come. This article originally appeared in Forbes and can be found online here: Why Don’t We Have A Coronavirus Drug Yet—And How We Can Develop One As Soon As Possible
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Why Researchers Are Exploring Antibodies From Recovered Patients For Possible Treatment And Prevention Of COVID-19 Forbes | April 6, 2020 | Article
Is there a COVID-19 treatment that can treat critically ill, hospitalized patients, on the one hand, and protect healthcare workers on the other? Passive immune therapy has the potential to do both—immediately, and with major improvements over time. Broadly speaking, it involves giving antibodies, in this case specific to COVID-19 virus SARS-CoV-2, to people who need them. The first stage is sera from convalescents. The second is purified antibody fractions that are safer and more potent, but also achievable—hopefully by summer. The third is monoclonal antibodies, which will take more time but is already on the fast track. Each approach mobilizes antibodies against SARS-CoV-2 in unique ways, with varying degrees of safety, speed, and efficacy—and all three must be explored. A primer on antibodies When the body is under attack, the immune system’s B cells produce antibodies specific to the invading organism that fit its viral proteins with utmost precision. This hand-and-glove binding mechanism either marks the target for destruction via other white blood cells, inhibits basic biological activity, or targets the invading organism for clearance from the body. Some virus-specific antibodies linger on in the body long after infection has cleared. While immunoglobulin M (IgM) antibodies, the largest and first to be produced, disappear shortly after their role as the initial line of defense has been fulfilled, immunoglobulin G (IgG) antibodies remain in abundance in all bodily fluids, ready to leap into action should the virus ever return. If a patient makes a full recovery from COVID-19, the IgG antibodies their immune system
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weaponized to fight the virus will retain a memory of the disease at least for many months. Shortest term solution: convalescent sera In the event of an infectious disease outbreak for which neither a cure nor a vaccine yet exists, such as the current pandemic, medical practitioners can transfer the antibody-rich blood plasma of recently recovered patients to those critically ill. Collected at least a few weeks after the donor has been discharged, this convalescent plasma, also known as convalescent sera, still contains antibodies against the virus that can treat patients in critical condition. Treatment, not protection, is the purpose of convalescent sera, which buys enough time for some to stabilize and recover. Use of convalescent sera dates back to the 1900s but has more contemporary precedents that suggest its viability as a somewhat reliable stopgap measure against emerging infectious diseases. From H1N1 influenza to Ebola to COVID-19’s foremost predecessor, SARS, medical practitioners have repeatedly turned to this basic form of passive immune therapy and, in several cases, reported back promising reductions in mortality and viral load. Combined with small studies recently conducted with COVID-19 patients, the evidence is favorable enough that convalescent sera transfers, as of March 24, are FDA approved for emergency cases in the United States. That said, there are many valid reasons why convalescent sera therapy is still considered experimental and reserved for emergencies only. Although modern blood banking technology does a fine job of filtering rogue substances out of plasma donations, the principle worry is infection from hepatitis and other viruses. Patients with certain immunodeficiencies or lung-related comorbidities, among the most vulnerable to COVID-19, may be ineligible. With so many lives on the line, and so few options in the way of treatment, these risks may be worth it—but there are safer alternatives worth pursuing. Shorter term solution: hyperimmune globulins In New York City, the new epicenter of the pandemic, the New York Blood Center has already started to collect blood plasma 60
donations from convalescent COVID-19 patients for therapeutic use. The ultimate distribution of donors and donations will be determined by patterns in caseload and recovery, with convalescent sera moving between hospitals accordingly. As both the number of recovered patients and the number of infected patients continue to rise, a good portion of incoming donations received by the 380 licensed plasma collection centers across the country should be pooled for the creation of a cleaner, more concentrated, and more effective passive immune therapy: hyperimmune globulins. Unlike convalescent sera, which is processed and circulated through a network of hospitals and clearinghouses, the preparation of hyperimmune globulins—especially at a commercial scale— requires proper manufacturing infrastructure. First, in designated labs and manufacturing plants, samples of collected plasma are assessed for their potency. The goal is to locate and quantify highly neutralizing antibodies, those most adept at fighting the virus, and concentrate them into a clinical grade solution. Once identified, the highly neutralizing antibodies are pooled, purified, and incubated in large batches over the course of several weeks. If all goes well, the resulting hyperimmune globulin preparations should be safer and less variable than a dose of convalescent sera. They can be administered to critically ill patients as treatment and healthcare workers as protection. Hyperimmune globulins have already been produced for diseases like cytomegalovirus, H1N1, and hepatitis. They were even prepared for SARS, though these, like so many other potential coronavirus therapies, never left the lab. The process of industrial purification may be more labor intensive and time consuming, but with enough resources and facilities mobilized, it can also be accelerated. At this point, the coronavirus pandemic is so widespread that recruiting enough plasma donors for rapid manufacturing—usually one of the most significant challenges in yielding high volumes of hyperimmune globulins—will only grow in feasibility. Another technique that has demonstrated success in the past is the collection and refinement of equine plasma. Groups of horses would be immunized with a killed version of SARS-CoV-2, the COVID-19 virus, and develop antibodies in response. Because horses are larger animals, they produce more plasma than humans 61
that can, in turn, be purified just as we purify that of convalescents. Either way, hyperimmune globulins would take longer to prepare than convalescent sera, but not nearly as much time as vaccines or antiviral drugs—meaning they’re well worth the effort. Long term solution: Monoclonal antibodies The final, most advanced, and most specific of the passive immune therapies being explored for COVID-19 are monoclonal antibody drugs. These treatments are engineered using a single cell that produces a single, highly neutralizing antibody, one that is replicated over and over again at a large scale. Monoclonal antibodies have the purity and consistency of a synthetically generated product but remain wholly human and potentially very effective. To date, more than 80 pharmaceutical products that use this technology to treat cancer, infectious diseases like Ebola, and other health conditions have received FDA approval. The main downside to monoclonal antibody drugs is that they’re difficult and expensive to make. Luckily, research was conducted on monoclonal antibodies against SARS and MERS that were never brought to market, but are now of use to scientists developing drugs for COVID-19. In the case of SARS and MERS, the considerable investment of time, money, and labor needed to produce monoclonal antibody drugs exceeded any conceivable benefits. Today, with initiatives like Bill Gates’ COVID-19 therapeutics accelerator pouring funds into multiple avenues of immunotherapy discovery, prospects may still be uncertain, but they’re also more promising than they’ve ever been. Meanwhile, as we await the verdict on more ambitious therapies, here are five steps we can take to get what is already at our disposal— and what could be, within weeks—into the hands of healthcare workers, extremely ill patients, and any other high priority groups in dire need of protective immunity. First, find convalescents eligible for plasma donation. This should be a nationwide effort. Second, identify the plasma that contains the highest concentration of neutralizing antibodies that can either be administered in emergencies as convalescent sera, or pooled for the production of hyperimmune globulins. 62
Third, purify these potent antibody fractions into hyperimmune globulins. Fourth, after testing for safety and efficacy, ramp up production. And last but not least, give the finished product to the patients who need it most and the healthcare workers who need it to continue their efforts. To recap, the broader strategy would be to use convalescent sera today to treat critically ill patients. Then, to use hyperimmune globulins to both treat critically ill patients and to protect healthcare workers. Lastly, to use monoclonal antibodies both as treatment and as prevention for increasingly broad segments of the population. The first monoclonal antibodies are likely to be protective for three to four weeks. It is possible, through genetic engineering, to extend that period for up to four months. Once passive immune therapies have been administered, we don’t know how many weeks we can expect the antibodies to persist. At the end of the day, we can only buy time—for the COVID-19 patients in acute condition, and the healthcare workers putting themselves on the line to save them. But until more long term solutions emerge as viable, we’ll need every minute and every hour we can get. This article originally appeared in Forbes and is available online here: Why Researchers Are Exploring Antibodies From Recovered Patients For Possible Treatment And Prevention Of COVID-19
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How Antibody Tests Can Be Used To Fight COVID-19 Forbes | April 6, 2020 | Article
There is a new antibody test that will change the landscape of COVID-19 testing as we know it. There are now two ways to test for COVID-19: one that measures the actual virus, and one that measures the body’s reaction to the virus. The first is a genome test that detects the presence of viral genes in the body using a swabbed sample, usually taken from the nose and throat. The sample must then be sent to a lab where it can be replicated and analyzed in a PCR machine. Results could take anywhere from one day to a week and a half to deliver. Point-ofcare genome tests have also been developed that can potentially shorten this waiting period to mere minutes. The second, which only recently has received FDA approval in the United States, is an antibody test, or serology test, that detects the presence of SARS-CoV-2 specific antibodies in the blood. Instead of a nasopharyngeal swab, results are obtained using a finger prick blood test. Like the point of care genome tests, antibody tests are a rapid diagnostic that will give users a verdict within minutes. One potential use of antibody tests is to measure the extent of the pandemic at the population level. Our understanding of the disease and its projected impact in the United States is weakened by our inability to monitor its spread amongst people with either mild symptoms or none at all. Another use is to measure the progress of individual infection. Antibody tests quantify the number of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in the blood. The presence of more IgM antibodies, which are the first to appear and mobilize against an invading organism, indicates more recent exposure to the virus. It is through this result that an asymptomatic carrier of the virus could be identified—a feature of no small importance, since “silent carriers” have played a major role in transmission. 64
More IgG antibodies, which are virus specific and produced in later stages of infection, would lead a person to test positive for immunity, implying recovery. This unfortunately doesn’t guarantee full protection. The test won’t reveal how neutralizing, or how potent, these IgG antibodies are; nor can it determine how long they will last. With certain families of coronaviruses, including the beta coronavirus family that includes SARS-CoV-2, reinfection has been found to occur, and for now it remains a possibility. Even with this taken into account, the advantages of antibody tests as a tool against infectious disease are still numerous—their low cost not least among them. Antibody tests can be administered for less than $10 each in the United States, and even less in other countries. The price is but a fraction of the PCR tests, which hover around $50 for Medicare patients. No special assembly or training is required; tests could be given in clinics and pharmacies, or at schools and popup stations. Successful deployment of antibody tests, as The Economist so succinctly put it, will depend on their “sensitivity and specificity.” Sensitivity prevents false negatives, since a more sensitive test is more likely to actually detect it. Specificity, on the other hand, prevents false positives, since a less specific test may pick up on antibodies against a virus other than SARs-CoV-2. Either way, once an antibody test proves to be as sensitive and specific as constraints will allow, it must be distributed nationwide for maximum effect. If it is still difficult to imagine how one rapid diagnostic test could reach the majority of American citizens, consider the example of a country that has done it before: Egypt. Since October 2018, the Ministry of Health’s 100 Million Healthy Lives program has used serology tests to screen more than 60 million Egyptians 12 years of age or older for hepatitis C, diabetes, hypertension, and obesity. The tests cost about 50 cents per person and come back in as little as five minutes. Results are logged and correlated with factors like age, sex, weight, blood pressure, and so on. It would take a concerted effort, but in the United States we have the infrastructure and manpower it takes to conduct rapid antibody tests quickly, cheaply, and at a massive scale. The small European country of Andorra has plans to give antibody tests to its entire population. Compared to other resource rich nations, we’ve
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failed to answer the WHO director general’s call to “test, test, test.” That can change—but only if we act now, and act fast. This article originally appeared in Forbes and can be found online here: How Antibody Tests Can Be Used To Fight COVID-19
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Opportunity Lost: Avoiding Further Missteps With COVID-19 And Future Biothreats Forbes | April 6, 2020 | Article
This is a tragedy that did not have to happen” was Governor of New York Andrew Cuomo’s plaintiff cry at the end of a recent broadcast. I echo his sentiment, not only for the delayed and ineffective action of our federal government which Cuomo decried, but from a lifetime of experience in fighting disease. I know what is possible and am sad to say I have an intimate acquaintance of the decade and a half or our collective failures. Anti-coronavirus drugs and vaccines could have stopped COVID-19 dead in its tracks well before it spread beyond Wuhan, but those drugs and vaccines still lie many months in our future. This is a story of my colleagues and friends who developed the medical war chest we so badly need now, only to be stopped dead, halfway through their pioneering work, due to a lack of interest and funding. My friend Ron Crystal, MD, is a brilliant pulmonologist and researcher at Weill Cornell Medical School. Recognizing the threat of SARS and then MERS, Ron harnessed his team both in New York and Qatar to attack the problem. He demonstrated the ability of candidate vaccines he developed together with Jim Wilson, MD PhD, at the University of Pennsylvania to protect monkeys exposed to either SARS or MERS. First, he lost funding in the United States for his work on SARS, then from Qatar for his work on MERS, where he was dismissed with a curt note that read "MERS is no longer of interest." Stanley Perlman, MD PhD, who I first met in 1965 when he was a graduate student with my sister Florence at the Massachusetts Institute of Technology, has spent the past 40 years at the University of Iowa working on coronaviruses. That’s right, 40 years! Realizing that cold viruses can turn nasty (after all, the polio virus is a cold virus that too can be lethal) he began his work years before the SARS epidemic. He developed strains of mice that can be infected by SARS and MERS, necessary for the development of anti67
coronavirus drugs and vaccines, only to mothball them for lack of funding. He is now in a race to revive those colonies, but it will take time. Then there is Wayne Marasco, MD PhD, trained in the fight against HIV/AIDS in my own lab at Harvard’s Dana-Farber Cancer Institute. Realizing the pandemic potential of SARS and MERS, he rushed to China then Arabia and returned to his Harvard laboratories to develop monoclonal antibodies both to prevent and treat those exposed to the virus and to probe the virus for weaknesses in their defense against potential vaccines. Had his work been carried to fruition we might have a proven drug available to fight the current pandemic, given the similarity of the SARS and COVID-19 viruses and the known ability of some SARS monoclonal antibodies to bind to the COVID-19 virus. Wayne's work too was shelved for lack of interest and funding. Michael Farzan, PhD, Professor at Scripps Reserch Florida, is a star student of my star student Joe Sodroski. Together Joe and Michael spent years understanding the intricacies of how HIV evades the immune system. Once in his own lab he quickly applied lessons learned for HIV to identify the gateway that SARS uses—and as it happens it is the same one used by COVID-19 virus—to enter our body. He used this knowledge to design what may be the most effective approach to creating a vaccine. Had it worked for SARS in humans as it did in monkeys, the same vaccine might well work have worked against the COVID-19 virus. Had he been funded adequately to bring the vaccine to market, an anti COVID-19 vaccine might well have been approved and ready to use today. That was not to be, as the rug was pulled from under this work as it was for so many others. Rolf Hilgenfeld, PhD, from the University of Lübeck was excited when scientists at Singapore’s research powerhouse Biopolis used his high resolution structure of key components of the SARS virus to develop a chemical inhibitor that acted not only to stop the growth of the SARS virus but of all coronaviruses tested. This drug, like more than a dozen found by scientists around the world, would very likely stop the COVID-19 virus too. None reached the market for lack of funding. The good news is that they can be revived. The bad news is that it will take time, time we all wish we had.
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I write not to lament the past but to alert us all to what we must do to prepare for the future. This will not be our last pandemic. We know that pandemic flu will strike sooner or later, perhaps more lethal and vicious than that of 1918 with the potential to kill one to two billion people. We are unprepared. We know antibiotic resistant staphylococcus and tuberculosis can spread widely at any moment, yet we are unprepared. Hit thrice by a lethal coronavirus, we must be prepared for more to come. We are not defenseless. Science will eventually save us from COVID-19 but after how much needless suffering and economic ruin? Science can save us from what we know is on our doorstep but only if we invest in our future. Let us not have to cry again, "This tragedy need not have happened!" This article originally appeared in Forbes and can be found online here: Opportunity Lost: Avoiding Further Missteps With COVID-19 And Future Biothreats
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Can We Really Develop A Safe, Effective Coronavirus Vaccine? Scientific American | April 6, 2020 | Article
In the event of any infectious disease outbreak, our minds turn to vaccines—and they do so for good reason. They’re safe, relatively expensive and have worked well for diseases including smallpox, polio, yellow fever, and, most recently, Ebola. Will a vaccine come as easily for the novel coronavirus? The answer is maybe yes, maybe not. The “maybe yes” comes from the observation that in animal studies, coronaviruses stimulate strong immune responses, which seem capable of knocking out the virus. Recovery from COVID-19 may be in large part due to effective immune response. The “maybe not” comes from evidence just as strong, at least with earlier SARS and MERS viruses, that natural immunity to these viruses is short-lived. In fact, some animals can be reinfected with the very same strain that caused infection in the first place. This raises more crucial questions with equally ambiguous answers. If a vaccine does prove to be effective, would it be effective for long? At this point, we can’t be sure. How long will it take to develop in the first place? We can hope, but we can’t be certain that it will be developed rapidly. To understand this better, it’s important to understand how the body protects itself from invading organisms. How Your Body Protects You From Disease Certain physical and chemical barriers—skin, mucus, stomach acid—protect the body from infection around the clock. The first line of defense is innate immunity, an immediate and nonspecific immune response to the multitudes of foreign viruses and bacteria, or pathogens, we encounter every hour of every day. This includes defensins, the ancient antimicrobial proteins that mobilize cellular pathways in the fight against pathogens, and macrophages, the white 70
blood cells that scavenge and devour all things foreign. The ultimate goal of an innate immune response is to be broadly effective. In this regard it usually succeeds, but not always. The second line of defense is adaptive immunity, whereby the body develops a long-lasting protective response specific to what it has seen before. It weaponizes two branches of the immune system: antibody-producing B cells, and T cells that attack and kill invading microorganisms or cells affected by those microorganisms. In many cases adaptive immunity to a disease is long-lived—sometimes lasting a lifetime, often lasting 10 years or more. Other times the immune response is short-lived, which appears to be the case in early experiments with the novel coronavirus. Not everyone can bear to ride out the two to eight weeks it takes for adaptive immunity to phase into completion—which is where vaccination comes in. Vaccines prevent disease by simulating infection, teaching the immune system to recognize, remember and fight a given pathogen before actual infection occurs. Rather than unleashing virulent organisms into the body, a vaccine builds immunity using antigens, the virtually harmless molecules that dwell on pathogenic surfaces. Antigens are foreign enough to trigger antibody production, but not dangerous enough to cause disease. Thanks to vaccination, what the body would normally learn the hard way—unexpectedly, painfully, at great cost—it can absorb under controlled conditions with relative ease. Types of Vaccines There are many ways to develop a vaccine that successfully deters infectious disease. The first to be invented, the smallpox vaccine, used a live vaccinia virus—one similar enough to the original infectious agent, but not quite. Unlike its disease-causing counterpart, which killed about 300 million people in its heyday, the vaccinia virus caused only mild symptoms in healthy patients. This method can be replicated by identifying a “lookalike” virus that triggers the desired immune response without actually inflicting disease. An attenuated strain of the virus, used to develop the yellow fever vaccine, is another option. Because the virus is still alive, albeit weakened, it gives the body a lasting education on how to neutralize 71
it. The protective immunity that results could last decades. The main problem with this kind of vaccine is that not everyone has an immune system healthy enough to handle the live virus, no matter how feeble it has become. In killed vaccines like the polio vaccine, the virus has been inactivated and thus cannot replicate itself, meaning several doses usually must be administered over time. Subunit vaccines, such as those available for hepatitis B and the human papillomavirus (HPV), inject particular parts of the virus into the muscles. They are usually administered with adjuvants, the booster shots that strategically flood the injection site with immune cells by causing inflammation. Unlike other vaccine types, which can cause complications or even death in people with chronic immunodeficiencies or other comorbidities, nearly everyone can withstand the immune response triggered by a subunit vaccine. To securely deliver the viral pieces that constitute a subunit vaccine, scientists purify protein compounds and insert them into a harmless virus, one destined not to survive a perilous journey through the human body. Known as viral vectors, these were used to create the Ebola vaccine. In the case of the novel coronavirus, for instance, the adenovirus vector would make an apt choice. For many years, biotech companies have tried unsuccessfully to produce genetic vaccines, which use genetic code in lieu of the actual virus or its individual parts. One prominent COVID-19 vaccine candidate is based on RNA, which the virus uses as its genetic code; it’s unproven as yet. Because we’re in the area of the unknown, we don’t know which vaccine type will work—and the best strategy is to try them all, mounting a massive effort that is fortunately already underway. Why Vaccine Development Takes So Long Why does Anthony Fauci say that it could take 18 months to produce a safe, fully functioning vaccine? The difficulty is finding a vaccine that works against a very particular disease, on the one hand, and for all of humanity on the other. This is why vaccine development normally proceeds at a glacial pace compared to other pharmaceutical products—not for lack of trying or innovation, but because safety must be proven beyond a shadow of a doubt. 72
Therapeutic drugs are generally prescribed to sick people as needed; vaccines are generally given to healthy people en masse. It takes a couple days for scientists administering experimental treatments to hospitalized coronavirus patients to determine safety and efficacy; for those injecting vaccines into as yet unaffected test subjects, it could be years. Add the multipronged challenge of manufacturing and distributing a packaged good in a volatile global marketplace, factor in an estimated hundreds of millions of dollars in expenses, and voilà—you’ll see why many experts doubt we’ll have a COVID-19 vaccine as early as this fall. We know that some antibody responses can actually make a disease worse. This proved to be the case most recently for the dengue virus in the Philippines, and there is some hint that issues of this sort will arise with the novel coronavirus. If a vaccine is to be administered to a sizable portion of the human population, it falls on us to proceed with the utmost caution. We must still move as fast as we can with as many resources as we can, but we must do so carefully—or risk exacerbating the spread of the current pandemic. We need to rigorously test the dozens of vaccine candidates in the running to find one that works, and that will take some serious funding. On average, it may cost $25,000 or more per participant to put a vaccine through clinical trials. It may also take tens of thousands of participants to ensure that a vaccine candidate is effective and safe. That means it would cost upwards of $250 million just to recruit people for a single vaccine candidate. Multiply that $250 million by 10—the minimum number of vaccines, in my view, that must reach this stage—in addition to the costs of research and developing a manufacturing process, and the sum total could be somewhere in the neighborhood of 10 billion. Even $10 billion would be a low price to pay for developing a means to stop a pandemic that is paralyzing economies around the world. No matter how much money developing a viable vaccine takes, it will be worth it. We can’t afford not to. This article originally appeared in Scientific American and can be found online here: Can We Really Develop A Safe, Effective Coronavirus Vaccine?
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Beyond Flattening The Curve, Here's How To End The Pandemic FOX News | April 8, 2020 | Article
As America enters what the President warns will be its “toughest week”, many are hoping that lockdown measures introduced in cities and communities across the country will lessen the devastation we face. The strict social distancing guidelines are an attempt to flatten the curve, an approach that has been described as America’s best bet at drawing the coronavirus outbreak under our control. While it is true that flattening the curve is an important tactic, it may not be sufficient to end the epidemic quickly. In principal, “flattening the curve” slows the rate of new infections, but the total number of infections under the curve may remain the same. Our goal should be to reduce the total number of people exposed and infected, not just slow down the spread of the disease. There may be an important benefit to flattening the curve, even if the total number of infections remains the same. By relieving the immediate and acute burden on hospitals and health systems, healthcare workers have a shot at providing the best possible care for every patient, which may result in fewer deaths. But the downside of a singular focus on flattening the curve may be that we extend the duration of this epidemic over months and perhaps even years. The most likely scenario we face today with the lockdown measures we’ve introduced is a successive series of reinfections over a prolonged period of time. Think of it in terms of waves, with a surge in the outbreak like what we see today ebbing when the impact of social distancing measures takes effect, only to surge again when lockdowns are lifted and infections in other parts of the country reignite the spread of the virus in areas that had once had their outbreak under control. The effect of this prolongation on businesses, the economy, and for each of us as individuals remains obscure. Will any one of us feel comfortable re-entering normal life when we know the next wave of infection lurks just around the corner? Singapore for example, a 74
country that acted early and seemed to have brought its epidemic under control, is now shutting down, shifting most businesses and schools online. Cases in the country have doubled in the past ten days, in part due to citizens returning home with new infections carried back from abroad. Their experience is a bellwether of what may await us here. To end the epidemic, we must not focus solely on flattening the curve but completely extinguishing it. This means reducing, then eliminating, the number of new infections. A successful vaccine would bring a lasting end to the pandemic, but we know that such a solution is at minimum a year away and likely much longer. There are other options that could bring a quicker endpoint. Many existing antivirals to treat the disease and prevent further infection have been fast-tracked to clinical trials, while dozens of other potential candidates are in preclinical development. Passive immune therapies -- where manmade or laboratory made antibodies are given to the ill and to those at risk to boost their immune system responses -- have also shown potential. But we have yet to determine whether these approaches will work and, even if they do, it will still be many months before these options are widely available. The only thing we know now that can reduce infections immediately is widespread testing, exhaustive contact tracing, and mandatory quarantine of all of those known to be exposed, regardless of their test results. In addition, a two week quarantine should be mandatory for all travelers entering the country from abroad or traveling between cities in America. We know these measures work, as they have come close to extinguishing outbreaks in several East Asian countries. But here in the United States, only one state has launched a similarly robust contact tracing effort. In Massachusetts, Governor Charles Baker recently partnered with the global health nonprofit Partners in Health to establish a virtual call center, staffed with 1,000 contact tracers. The contact tracers will call people who test positive for COVID-19 to make sure they are not spreading the infection further and to find out where they went and who they met with over previous days. Then the tracers will contact all the people who crossed paths with the infected person to warn them of their potential exposure and, most importantly, to direct them to isolate 75
themselves immediately so that they don’t spread their potential infection on. One state out of fifty is not nearly enough, but at least it is a start. As we begin to see signs of hope that the outbreak in places like Washington state and New York is starting to slow, let us not be irrationally optimistic about the effect of our lockdowns and social distancing measures on the true scope of this epidemic. Without a change in our approach to testing and tracing, it may only take one new infection, undetected and unnoticed, for the next wave to be upon us. This article originally appeared in FOX News and can be found online here: Beyond Flattening The Curve, Here's How To End The Pandemic
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Tests For COVID-19 Are Expensive, But They Don’t Have To Be Forbes | April 8, 2020 | Article
There is a huge demand around the world to understand COVID19. Those experiencing symptoms need to know if they’re infected, while those recovered need to know if they’re able to return to work. The problem of developing technology that can address the crisis has already been solved. Genome amplification tests are available that measure the presence of the COVID-19 virus, SARS-CoV-2, over the course of the disease. Antibody tests, also known as serology tests, reveal whether you’ve been infected, the stage of infection, whether you’ve recovered, and whether you’re likely immune to further infection. What continues to be a problem is the availability of tests, on the one hand—and on the other hand, their cost. How much should COVID-19 tests cost? Fortunately, we have a measure from a universal screening program recently completed in Egypt that can give us a reasonable estimate. Through the 100 Million Healthy Lives program, from October 2018 onward, either genome or serology tests were performed on the majority of Egyptians 12 and over: a total of 65 million people. Although the main goal was to reduce rates of hepatitis C infection—Egypt had the highest in the world at the time—testing was also conducted for diseases like diabetes, hypertension, and obesity. Results were logged using handheld tablets that also recorded age, sex, and geographical data. In no small part due to this program, Egypt may become the first country to eliminate hepatitis C. The antibody test, a rapid diagnostic developed by Abbott Laboratories that requires a simple, single finger prick, takes five minutes to complete and cost Egyptians a mere 50¢. Genome tests developed by Roche, which were administered to nearly four million, cost no more than $5 each. That’s a sharp contrast to what 77
people are charging today to test for COVID-19—in some cases $10 to $20 for a serology test, and more than $100 for a genome test. Because testing and diagnosis leads to treatment for some, the expenses of both are intertwined—a factor the program took into account when calculating opportunities for cost reduction. The three month hepatitis C treatment offered to Egyptians who tested positive was only $45. Compare that number to the $85,000 Americans must pay for the same care regimen, and the danger of leaving COVID-19 testing and medication prices unregulated becomes all the clearer. We cannot afford to see that discrepancy replicated today. To prevent companies from profiting at the expense of others, three things must happen. First, governments around the world should agree to procure these tests at a cost that everyone, low income countries included, can afford. This will entail the same level of international coordination that is already being used to facilitate the sharing of medical equipment and protective gear across borders. To this end, the World Health Organization has already called for patent pooling on COVID-19 related products. Second, the United States Congress should ensure that each and every American has access to, and can afford, a test for COVID-19. Testing for infection and immunity is as important to protecting American livelihoods as the stimulus checks due to reach 175 million within the next week. Regulating the costs of COVID-19 tests would be consistent with the goals of some of the bipartisan prescription drug legislation already in the works—meaning there is sufficient political will and incentive to act now. Lastly, we must recognize that making low cost COVID-19 tests available to all is not just an achievable and necessary target, but the right thing to do. At such a critical juncture in the trajectory of the disease, it is unconscionable that some should be profiteering. To control the pandemic, save lives, and put the world’s economy back to work, we need to be able to see the spread of COVID-19 in its entirety. Otherwise, we will all suffer the consequences. This article originally appeared in Forbes and can be found online here: Tests For COVID-19 Are Expensive, But They Don’t Have To Be
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A Troubling Tale Of Two Children In The Time Of COVID-19 Psychology Today | April 9, 2020 | Article
This week, I heard a disconcerting story from a friend of a friend in Boston who was diagnosed with COVID-19. She is just a teenager, but one who has suffered since early childhood from chronic asthma. Just over a week ago, she started experiencing the symptoms all of us with underlying conditions have come to dread -- chest pains, difficulty breathing, and a dry, hacking cough that would not disappear. Initially, because there was no fever, she and her parents tried to manage the symptoms at home, hoping it may just be a regular cold or a mild flu and not a more serious case of COVID-19. But when one of her high school friends texted to say she had recently tested positive for COVID-19, they felt they had no choice but to be tested and seek proper care. Her mother drove her to her physician’s office where, after a clinical examination, the doctor said there was little doubt that she was positive for COVID-19 -- but there were no tests available to confirm the diagnosis. Instead, the young girl was given acetaminophen, a prescription for more asthma pumps, and told to go home and rest. Both mother and daughter were distraught and confused, left to manage a potentially lethal disease on their own, with the risk of the infection spreading to the rest of the family, some of whom have underlying conditions of their own, highly likely. Meanwhile, nearly 10,000 miles away in Singapore, one of my colleagues and her six year old daughter were struggling with a similar challenge. Her daughter woke one morning with a slight wheezing in her chest, not particularly alarming since the young girl was just getting over a mild cold and -- much like the teenager in Boston -- she suffered from asthma. Wheezing was to be expected. Still, they called a nearby walk-in clinic and within the hour, they were sitting in front of a local physician. After running through their daughter’s medical history, including her history of asthma and her 79
recent illness, the doctor referred her to the emergency department of the National University Hospital to verify that her asthma was under control and to swab her for COVID-19. At the emergency room, they were, once again, seen quite quickly, since most people in Singapore have been heeding warnings not to overcrowd ERs. The emergency room physician said the wheezing wasn't severe, but they would have her take a few rounds off an inhaler and if her condition didn't stabilize they would take a chest x-ray. The doctor isolated them in a separate room to avoid the risk of further infection in case she eventually tested positive for COVID-19. A few hours and many Peppa Pig episodes later, her daughter’s condition had stabilized. The doctor swabbed her throat to test for COVID and gave her steroid medications to take home in case her symptoms were to return or worsen. They also sent her home with a legally enforceable medical leave, which meant she was not allowed to leave the house for five days. The next morning, to my colleague’s great relief, they received a call that the test results were negative While I was comforted to hear my colleague’s good news, the moment was bittersweet. Here are two cases of vulnerable young children at risk of COVID-19, both of them being treated in highly developed nations. In one, the child is tested, cared for, and quarantined immediately, steps which ensure not only her safety but the safety of those around her. In the other, there are no tests, there is no knowing whether there is an infection, and there are no safety protocols in place to break the chains of transmission. What a troubling state of affairs for those of us here in the United States and our children. Without tests available to all those at risk of infection and without mandatory quarantine orders to prevent further spread, we stand no chance against this disease. Instead, we set the stage for an endless wave of infections that will befall us for months, years, or perhaps for generations to come. This article originally appeared in Psychology Today and can be found online here: A Troubling Tale Of Two Children In The Time Of COVID-19
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The Challenges Of Testing For COVID-19 Forbes | April 13, 2020 | Article
The accuracy of tests for SARS-CoV-2 is central to our ability to control the epidemic— knowing who is infected, who has been exposed, and who is immune. It is also central to our ability to reopen businesses and lift restrictive lockdown measures. Unfortunately, our tests are not up to the job, nor are they available and affordable to all those in need. But that does not mean we don’t have ways to blunt the damage that our testing failures may cause. As Bloomberg reported over the weekend, doctors trying to diagnose patients are saying that false negative results from coronavirus tests are becoming an increasing concern, impeding their ability to correctly diagnose patients and preventing us from truly understanding the spread of the disease. The tests for the presence of the virus itself can miss thirty to forty percent of those actually infected, sometimes even more. These false negatives are due in many cases to individual variation in the actual level of the virus, the technique used by the tester, and issues with the tests themselves. The antibody tests that detect prior infection also have issues. As the FDA package insert warns, these tests are not specific for SARSCoV-2. They also detect prior infection by coronaviruses that are not related to COVID-19, instead noting antibodies developed in response to milder coronaviruses that circulate among us causing symptoms more like the common cold. Also troubling is the observation from China that up to one third of convalescent patients—meaning those hospitalized but not placed in ICU isolation—do not have detectable antibodies, even though they are symptom free. There is also emerging evidence of virus reactivation or reinfection in convalescent populations. The consequences are that some asymptotic carriers will be missed and continue to spread the infection. Others who think they are immune will remain at risk for reinfection and some may continue to transmit the virus to others unknowingly. 81
The challenges with testing for COVID-19 infection are important to consider as cities and states plan strategies to reopen businesses and return to more of a sense of normal. Without more accurate tests, we must ensure repeated testing of those identified as having been exposed for traces of SARS-CoV-2 and continued long term follow-up screening of all convalescents for the presence of the virus. Erring on the side of caution and testing more often than some may deem necessary is imperative in order to mitigate the very real risk of a new outbreak emerging just as we begin to get the current outbreak under control.
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How Do We Reduce Our In Hospital Death Rates? Forbes | April 14, 2020 | Article
Never has it been more critical for Americans to understand the importance of in hospital death rates and survival rates associated with hospital stays. Hospitals and emergency rooms today are increasingly overcrowded with those who are critically ill, either from COVID-19 or from other acute illnesses that require immediate medical care. In these trying times, many are seeking and accepting care wherever they are used to receiving it, without any exploration of which hospital or emergency room will give them the best shot at survival. Yet the facts show that there is a significant difference – even among the best hospitals – in survival rates, with the chances of survival in some hospitals nearly twice as high as others. Even prior to the COVID-19 outbreak, more than 400 people died in US hospitals each day due to poor hospital performance, according to a 2019 report. Many of these deaths could be prevented—if hospitals were to prioritize saving the lives of their most ill and patients were to prioritize hospital performance in their choice of care. Hospital mortality rates, which include deaths that occur both on site and 30 days after discharge, are a visceral measure of hospital performance. But they are poorly understood by most patients, perhaps because of how hard the numbers are to track and how inconsistent those numbers can be. A recent article published in NEJM Catalyst observed that quite a few quality rating systems either ascribe mortality rates the same weight as readmissions or exclude them from their calculations altogether. Still, there are options for consumers who care about where they are tended to. US News and World Report includes hospital mortality rates in their annual rankings of the best hospitals in the nation, but there are few other patient facing websites that rank hospitals on the issue. 83
The omission is troubling because it signals to hospitals that reducing mortality is not of the utmost priority. What happens, then, when an institution decides that it is? Plummeting mortality rates Such was the case at the University of Pennsylvania Health System, otherwise known as Penn Medicine. After a targeted effort to reduce mortality rates, the risk adjusted mortality index—a ratio that accounts for how sick patients are prior to admission—of their flagship hospital dropped, over six years, by nearly 50 percent. Since 2015, the mortality index of the academic medical center as a whole has seen an impressive overall reduction of 21 percent. Two other academic medical centers committed to mortality reduction, NYU Langone Health and Rush University Medical Center, have achieved even greater gains. Between 2009 and 2019, according to data obtained from the Vizient Clinical Database, the mortality index at NYU Langone plunged from 1.18 to 0.53—more than half. Theirs remains by far the lowest of any hospital in New York City, as well as the lowest of any hospital in the U.S. News & World Report Top 10. Rush, which rose to the top of Vizient’s Quality and Accountability rankings this year but until recently maintained uneven mortality rates, reached a mortality index just below 0.50 in the first half of 2019. At Rush, NYU Langone, and Penn Medicine, the mortality index falls well beneath the national average of 0.90. While this is a far cry from the most dangerous hospitals in the United States, where the risk of preventable death is twice as high as normal, it bears mentioning that even accredited institutions of supposedly comparable caliber can do poorly when it comes to their mortality index. An investigation conducted in 2017 found this to be the case at hundreds of “gold star” hospitals—some with violations “so bad,” Ars Technica reported, that they were “likely to cause serious injury or death to patients.” Given that mortality reduction is, quite literally, a matter of life or death, their success—and, more specifically, how they achieved it—should not be taken for granted. In all three cases, it took several years of steadfast quality and safety improvements and widespread organizational change. 84
Identifying the problem Initially, if patients outside the intensive care units at NYU Langone showed signs of deterioration, the critical interventions they needed to recover came too little or too late. Claims records show that this continued even after the installation of rapid response teams, which healthcare teams could call upon to intervene before patients ended up in intensive care. Mortality rates dropped, but not nearly enough. No secret is it that physicians are generally reluctant to let other personnel, like the rapid response teams, “take over” patient care. For bedside nurses and novice nurses in particular, these misgivings dovetail with, in the words of a 2019 analysis, a common fear of “critical, intimidating, and judgmental” exchanges with rapid response teams to strongly discourage their activation. Physicians, in their defense, express concern that opening up a closed circuit of caregivers to colleagues unfamiliar with the patient’s condition would disrupt treatment and create more room for error. A valid qualm but certainly no excuse for perpetuating a culture of distrust that undervalues nursing staff, impedes collaboration, and allows patients to suffer. All members of a healthcare team have a part to play in administering care. Reaching a solution In fact, an “interdisciplinary care approach,” Penn Medicine declares on their website, is the main reason for their success in mortality reduction. Back in 2006, their flagship hospital tasked an interdisciplinary Mortality Review Committee with promoting a “collaborative problem solving culture” powerful enough to erode the reluctance of physicians and bolster the capabilities of nursing staff. The Penn Medicine 2017 – 2018 Quality and Patient Safety Report confirms that mortality reduction, like patient satisfaction, is a prominent “Shared Team Goal”—and that nurses are a driving force behind the assessments, non pharmacological interventions, and care coordination that power a diverse set of integrative clinical pathways. In the event that the condition of a patient worsens and their care must be escalated, specialized rapid response teams like the Pulmonary Embolism Response Team or Airway Rapid Response 85
Team deliver interdisciplinary support and expertise directly to their bedside. The problem with rapid response teams at NYU Langone was not necessarily their ability to perform, but their inability to beat the existing status quo. Like Penn Medicine, departments across hospitals had to develop escalation pathways, policies, and procedures that aligned with existing workflows—the whirlwind of decisions, interactions, and relationships that structure everyday life in the hospital—but explicitly rewarded healthcare teams who called for assistance sooner than later. After years of sustained education, training, and codification, healthcare teams across hospitals have learned to activate rapid response as soon as patients begin to deteriorate—and mortality rates have plummeted. According to Martha Radford, Chief Quality Officer at NYU Langone Medical Center, it is now “no longer acceptable not to call a response team when you first think one may be needed.” Rather than a culture of distrust, healthcare providers at NYU Langone uphold a culture of shared responsibility. For Rush, building a culture around a common set of values is one key to attaining a level of patient care high enough to prevent in hospital deaths. Another, which goes hand in hand with the first, is routine data collection and analysis. By framing a set of democratically selected quality metrics—mortality among them—as drivers of collective improvement, the analytics team at Rush gradually brought the competing goals of individual physicians and staff into alignment. Lastly, the adoption of lean management practices, which identify patient perspective as a central determinant of value, provides further basis for a shared vision. Thanks to these three measures combined, an old hierarchy and its attendant codes of professionalism is giving way to a new focus on quality and safety. All too often, hospitals attribute higher rates of mortality and preventable deaths to the social or environmental risk factors that affect the populations they serve, essentially claiming that the danger is beyond their control. But the methods deployed by NYU Langone, Rush, and Penn Medicine, while far from one size fits all, can be adapted from one hospital to the next. Both Tisch Hospital and NYU Langone Hospital – Brooklyn, formerly known as NYU Lutheran Medical Center, have a mortality rate that hovers around 0.5. Given that NYU Langone Hospital – Brooklyn is a safety net 86
hospital that serves a majority Medicaid population—a patient mix that differs significantly from that of Tisch Hospital—the equivalency is nothing short of remarkable. Insurance companies also have a role to play in dispelling the notion that hospital mortality is some kind of inevitability. They must be willing to cover the cost of extra quality and quantity of care that, in some cases, is the difference between a life saved and a life lost. When insurers are ready to pay more to save lives, and when hospitals are held accountable for the patients that die on their watch, a sense of shared responsibility over patient care becomes the new norm—just as it has at NYU Langone, Rush, and Penn Medicine. New norms and higher standards, especially regarding the quality and safety of service delivery, are what hospitals need to not just reduce in hospital deaths, but replace profit centered care with person centered care. This article originally appeared in Forbes and is available online here: The Challenges Of Testing For COVID-19
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We Need To Crush The Curve Now—Or COVID-19 Will Come Back To Haunt Us Forbes | April 15, 2020 | Article
In a bid to slow the spread of COVID-19, communities across the United States have taken action to “flatten the curve.” The curve in question represents the number of people predicted to contract the novel coronavirus over time, while attempts to flatten it have so far included various forms of social distancing, self-isolating, and frequent handwashing. As critical as these actions are, they’re still not enough—not nearly. Flattening the curve may lessen the burden of care for hospitals and healthcare workers, but it won’t necessarily decrease the number of people who fall ill. If we don’t act now to crush the curve completely, subsequent waves of reinfection will continue to haunt us long after the current pandemic has cleared out—each smaller in scope, maybe, but not without significant aftershocks to our health, our economy, and our psyches. To put a definitive end to this pandemic, the United States must follow the lead of countries like New Zealand and pivot from a containment strategy to an elimination strategy; to not just flatten the curve, but crush it. Deployed swiftly, aggressively, and in conjunction, the following three countermeasures may give us the momentum we need to reduce the total number of cases, shorten the length of the pandemic, and allow economic activity to resume. First, use widespread testing to identify everyone who has been infected. More funds and resources must be invested in the procurement and production of available COVID-19 tests, whether genomic or serological, as well as necessary implements like nasopharyngeal swabs. Clinical and community test sites must be established where low-cost, rapid diagnostic tests can be administered to all. In South Korea, one of the few countries to successfully bring down their COVID-19 caseload, an early effort to test half a million people—including those experiencing either mild symptoms or 88
none at all—allowed public health officials to predict the trajectory of the disease with greater accuracy and precision. Taiwan, another country where proactive testing led to greater prevention, went so far as to retest those whose results came back negative. Second, use contact tracing to identify everyone who has been exposed. Detecting where the virus is already present cannot sufficiently anticipate where it will go next. Federal health agencies tracking the pandemic from above must cooperate with local health authorities reacting to it on the ground to trace the links between those infected and those they interact with. Tools like privacy-protecting contact tracing apps can help expedite this search—a technique that proved especially fruitful in Singapore. In addition to organizing teams of contact tracers who interview coronavirus patients and track down the names, phone numbers, and addresses of those exposed, the Ministry of Health launched a TraceTogether app that uses Bluetooth wireless technology to monitor close contacts. Lastly, mandate quarantines for everyone who has been infected or exposed. While this component of the elimination strategy may be the hardest to stomach, a two-week period of mandatory quarantine and self-isolation for all exposed, regardless of test status, is needed to stop infection from spreading. For those entering the country from overseas, this is best done in hotel rooms where any development of symptoms can be closely observed. Like contact tracing, the efficacy of quarantine can be increased through technological means. When Wuhan, ground zero of the pandemic, was still under lockdown, China used mobile QR codes to monitor quarantined individuals. If scanned, green indicated clearance and the absence of infection; yellow, instructions to stay inside and self-isolate; and red, forcible quarantine. Today, the system is still in effect, though the QR codes now help regulate access to public transport. So far, the elimination strategy has yielded promising results in New Zealand, where mandatory quarantine has been in effect since March 25. As of Tuesday, New Zealand has reported more recoveries than new cases and only one death. Once implemented, these countermeasures cannot be relaxed until there is absolute certainty that the virus no longer among us.
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This article originally appeared in Forbes and is available online here: We Need To Crush The Curve Now—Or COVID-19 Will Come Back To Haunt Us
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19% Of People Infected With COVID In The US Are Healthcare Professionals. Almost Three Quarters Of Them Are Women Forbes | April 15, 2020 | Article
A report from the CDC found that 19% of people infected with COVID-19 in the United States are healthcare professionals. Women accounted for 73% of those infected, a shockingly high percentage given the preponderance of infection of men over women in the general population. The average age of the healthcare professionals infected is 42. Ninety-two percent of those identified as infected have one or more symptoms of the disease. Only 8% were symptom free. The ratio of symptomatic to non symptomatic carriers is much higher than that found in the general population, suggesting that the actual percentage of healthcare workers infected may be much higher. The good news is that the death rate in this population was very low, at 0.06%. It is likely that the great majority of infections occurred while caring for patients. More than half of those infected reported that their only known exposure was to a patient. Our healthcare workers are a limited and very precious resource. Everyday our healthcare workers take risks to save lives, endangering their own. These numbers provide a stark reminder of the risks they face both for themselves and their families. We know we must provide them all they need to protect themselves. Evidently it is not enough. This article originally appeared in Forbes and is available online here: 19% Of People Infected With COVID In The US Are Healthcare Professionals. Almost Three Quarters Of Them Are Women
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New Study Finds 15% Of Pregnant Women At Two New York Hospitals Tested Positive For COVID-19 Forbes | April 20, 2020 | Article
At long last, we have a relatively unbiased random sample of the true infection rate of COVID-19 in New York City. Last week, the New England Journal of Medicine reported the results of a screening that was conducted on 215 women admitted to New York City hospitals for delivery. About 15 percent tested positive for the COVID-19 virus. We know that the test missed up to one third of those infected, either because of the low virus levels in patients in the asymptomatic and pre-symptomatic phase, or because of test failures. The true rate may be higher—as much as 20 percent. If pregnant women are representative of the population as a whole, that means between 2.7 to 3.6 million of the 18.8 million people who live in the greater New York metropolitan area are infected. That figure is a far cry from the 242,000 confirmed cases that were reported on Sunday. If the magnitude of the infection is really so much greater, New Yorkers aren’t the only ones who should be prepared to observe social distancing guidelines more closely in the months to come. It’s in the best interest of residents of other hot spots like Chicago, Washington D.C., and New Orleans, as well as their respective state governments, to act under the assumption that reports of current caseloads greatly underestimate the extent of infection. The same goes for major cities that COVID-19 has yet to hit hard. Otherwise, rates of infection may skyrocket nationwide, making the possibility of a smooth return “back to normal” ever more remote.
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This article originally appeared in Forbes and is available online here: New Study Finds 15% Of Pregnant Women At Two New York Hospitals Tested Positive For COVID-19
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A New Normal For Hospital Care Forbes | April 21, 2020 | Article
Most hospitals and doctors offices are closed for business as usual. Many remain open for exceptional emergencies such as near fatal heart attacks and life threatening accidents. That leaves many of us without routine care or even care for serious chronic illness. For example, my follow up appointments for cancer care are cancelled indefinitely. Fortunately I am at very low risk for recurrence, but many people with serious chronic conditions are not so lucky. The best estimate suggests that the combined toll of the pandemic on deaths not directly related to infection may be as great as the number of deaths form COVID-19 itself. That data comes from measurement of monthly excess deaths in Western European countries. When we can return to hospitals and doctors offices for care, what will that care be like? Granted, telemedicine can fill part of the need, but certainly not all. We still need physical interactions with doctors. The Centers for Medicare and Medicaid Services recently offered guidance for what resuming medical care for non-COVID related illness should look like. A few takeaways: People should not return to hospitals for non-COVID care until the epidemic abates locally. Unfortunately, the criteria for abatement are not spelled out. When hospitals reopen, non-COVID patients must be rigorously separated from COVID cases. That means separate facilities (entrances, waiting and examination rooms). That gives great advantage to those hospital systems that presciently invested in outpatient care facilities separate from full service hospitals. Here in New York, NYU Langone Health has created a network of many hundreds of such facilities in local communities distant from their hospitals. Each patient must be screened for COVID before entering the hospital. That means a check for fever, cough, and other symptoms. 94
Ideally it means each person should be subject to a rapid virus detection test (those that take five to 10 minutes). Once identified, COVID positive patients must be re-routed to specialized care facilities. Of course, this will not happen until we solve the testing issues. All medical personnel must be regularly screened for infection. Whether screening should be daily or less frequently is not addressed. (The need for testing capabilities, highlighted again). Patients and doctors should be required to wear protective masks at all times. Again, the guidelines are somewhat vague for what patient masks should be. All facilities should be rigorously cleaned. Exactly how is also not specified. Issues for care of children in foster care, prisoners, those mentally ill and with cognitive impairment or physical disabilities is not addressed in the guidelines. These are and will remain pressing issues. Healthcare is an essential service for us all. Even after the pandemic, the experience of going to a hospital or even getting a checkup will not be what we remember it was for a long time. This article originally appeared in Forbes and is available online here: A New Normal For Hospital Care
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Why COVID? Nature’s Code Cracking Machine Intelligence Forbes | April 21, 2020 | Article
COVID-19 is a pandemic that never had to happen. To prevent another—or one even worse—we have to internalize a simple lesson about life on earth that we tend to forget. Nature, for all its beauty and wonder, is out to get us. We must use our intellect and technology to prepare, predict and act swiftly in the face of what is a continuing threat to our life and livelihood. We live in a sea of viruses. They have been a part of life since the beginning. These tiniest of all life forms adapt to exploit every available ecological niche. We humans, now numbering in the many billions, packed into cities and traveling the globe in ever increasing numbers, provide a target rich opportunity. Viruses have adapted to our way of life, learned how to crack our defensive code, invade our cells, and take full advantage of our weaknesses. These microscopic organisms don’t just attack the human body; they attack all the systems we’ve built to sustain modern life, including our complex, interlinked economies. As our systems have evolved, so too have our viruses, producing the likes of the smallpox, 1918 flu, Polio and HIV/AIDS. Now, we have COVID-19, and if we aren’t careful, it will be here to stay. The current era is the culmination of decades of rapid demographic, technological, and cultural change. What we call the twenty-first century is yet another environment in which viruses mutate, adapt and thrive. A world of viruses Think of viruses as nature’s own form of artificial intelligence, capable of something very like what we call machine learning. Everywhere in the world, at any given moment, trillions upon trillions of natural experiments are underway that, through random mutation, advance the survival of each virus. We should be so lucky 96
someday to engineer a machine, a quantum computer or otherwise, that rivals the collective activity and productivity that is the natural property of viruses. In the last hundred years alone, the human population has more than quadrupled in size. Many of us have flocked to the nearest urban centers, where we live and work in high density clusters. Beyond sheer numbers, our urban centers are home to cramped and unclean quarters, tantalizing targets for omnipresent viruses. We are not defenseless. Our immune system has adapted to meet this constant barrage of microorganisms. The usual result is a standoff. We are host to billions of bacteria and viruses that do little harm. For example, each year nonlethal human coronaviruses attack us like clockwork, entering and exiting our bodies under the more recognizable guise of the common cold. However multilayered and resilient our immune systems have become, they’re far from impenetrable. They’re also unpredictable. A hit and run virus like the one responsible for COVID, SARSCoV-2, can trigger an immune response so potent it overwhelms the body completely. In some cases this overreaction, also known as a cytokine storm, does more damage than the virus itself—enough to be fatal. That SARS-CoV-2 has sickened and killed so many isn’t purely a byproduct of biology. While global pandemics have threatened us at various points over the course of human history, each one is unique to its respective day and age. COVID-19 is no exception. This virus has not only successfully adapted to our bodily defenses, but also exploited flaws endemic to our twenty first century social, economic, and political systems. Chinks in our armor The first chink in our armor is simply how many of us there are—and how long we’re able to live. Life expectancy has reached new heights and shows no sign of dropping. Because our health systems haven’t evolved sufficiently to meet the needs of larger aging populations, older adults are among the most vulnerable to COVID19 and other viruses that prey on weaker or compromised immune systems.
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The second is our unprecedented global mobility. Global travel has risen exponentially. More than a billion international tourist visits were logged worldwide in 2018, compared to just a quarter of a million in 1950. It’s not just people that are more mobile, but the goods, services, information flows, and other transactions that fuel the global economy. Technology has made it easier than ever to move and communicate across borders—a shift that unfortunately applies to viral transmission, too. The third is social inequity. Some of us live in luxury, with high quality doctors and medicine at our beck and call, while some of us have huge underlying health conditions due to poverty. Cities inevitably incubate infection, but substandard living conditions exacerbate it—and viruses exploit the social determinants that shape our health and environments, like race and income, all too well. Already we know that COVID-19 disproportionately affects communities of color in the United States, and that existing disparities in rates of infection, recovery, and death will only grow. Last but not least is political philosophy. As the wide range of national responses to COVID-19 has shown us, the rhetoric and behavior of our political leaders can significantly impact how their citizens react. If an administration errs on the side of skepticism, their followers might be deterred from adhering to even basic safety protocol. The same goes for an impatience to return to work, the endorsement of medicines not yet proven clinically safe, or an inability or unwillingness to exercise the degree of control necessary to curb infection’s spread. A political philosophy that overemphasizes individual freedom over collective responsibility may also have similar consequences. Sometimes a virus exploits our weak spots too efficiently—to its own detriment. Malicious though a virus may seem, it is never in its best interest to kill its hosts. When they do, we fight back. Modern medicine as a weapon How do we fight an enemy we cannot see when so many of our failings as a society are conducive to its victory? We have our intellect, our logic. We have modern medicine.
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We are unleashing modern medicine against COVID-19, but only in due time can it take effect. Had we learned from SARS and MERS, very few would have had to die. Other dangerous diseases lurk. Climate change will bring malaria, dengue, and other tropical diseases to our shores. In particular we have to be prepared against the reoccurrence of something like the 1918 flu—a virus that is regrouping as we speak. Were this virus to infiltrate our bodies and our systems as COVID19 has done, it could easily kill one to two billion people if we remain as unprepared as we are today. The COVID-19 pandemic is a more serious threat than anything a laboratory worker could release by accident or a terrorist could unleash on purpose. No need to go there. Mother Nature is dangerous enough and harbors close lookalikes to the COVID-19 virus. We have created countermeasures against agents of biological warfare, but we haven’t adequately prepared ourselves against Nature—and Nature is far more efficient and constant a terrorist than any human ever could be. We can be prepared, and we have to be. Nature is out to get us, and it is smart. If you ever doubt the power of random chance, look around you and see what it has created. The same life force that built us is trying to destroy us. This article originally appeared in Forbes and is available online here: Why COVID? Nature’s Code Cracking Machine Intelligence
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What Did We Know And When Did We Know It? Disease Surveillance: Past, Present And Future Forbes | April 22, 2020 | Article
What can we know, when can we know it, and what can we do with what we know? As COVID-19 moves through our world wreaking destruction upon our social fabric, our lives, and our economies these questions return to haunt me. I have recently engaged in lengthy conversations with people whose life work is to develop the tools that allow us to understand what is happening in the world through “open source” information, that is information that can be gathered publicly via newspapers, television, and radio and ever so much more from our increasing wired world. Many of the people with whom I spoke are in commerce, using data to understand consumer trends, habits and desires. Others are from the political world, using publicly available demographic and digital footprints to predict voter behavior and to target political ads. Still others are from the world of intelligence, observing both friend and foe for hints of impeding danger. Data gathering, data analysis, and clear courses of recommended action can be inferred by surveillance systems of ever increasing power and sophistication and by people who know how to use them. My conclusion: We can predict impending epidemics and do so early on. We could have, and very likely did, observe the earliest traces of COVID-19 to accurately predict the gathering storm. Exactly when and how clearly the disaster was foreseen and by who will be, and should be, a subject of intense scrutiny. Surely we in the US and others around the world did not make good use of the information available in plain sight to protect us. My conversations have also convinced me that even now we are not using our resources anywhere near their full capacity, to identify communities in need and to predict with pinpoint accuracy where the next hot spot for infection will be, whether it be next door or halfway around 100
the world. Such information is gold, as we know now how important nipping the epidemic in the bud is to save lives. And for the future. Will we learn our lesson? Will we develop the institutions both public (governmental) and private (companies and non for profit organizations) with the capabilities not only to observe but to understand global disease trends and the threat they pose? Will our leaders understand that the natural world resembles a giant machine learning device constantly generating trillions upon trillions of variants of disease pathogens to crack humanities defensive code? Will we remember that nature is the greatest terrorist of all and make full use of the means we have to defend ourselves against this relentless foe? In what follows I summarize what I learned from these conversations. Disturbances in the Digital Ocean Internet connectivity has rendered transparent the behavior, perceptions and even thoughts and feeling of much of the human race. Almost half the people in the world today have cell phones, and those without cell phones - young children and some in remote corners of the globe, are usually connected to someone who does have a cell. Directly or indirectly, virtually every human on the planet is connected digitally. Emails, texts, internet searches, social media posts, blogs, news sites, e-commerce, video streaming, publicly available satellite images and web cams, as well as geo-positioning data from digital devices are rivers of information that flow into a vast digital ocean. When major events occur, such as civil unrest, natural calamities or presidential elections, these dynamic events plough through the digital ocean, creating bow waves, wakes, and ripples that can be observed, even when the event itself cannot be directly seen. Disease outbreaks are events with a distinctive fingerprint. They that can be spotted on the digital ocean, if you know where to look, when to look, and how to look. Bow Waves
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A bow wave indicates that a nascent epidemic is poised to “go exponential” before it is obvious, even to local authorities, that something is starting to go wrong. Examples of epidemic bow waves that can be observed in most countries include: A sudden rise in the cost of poultry Significant changes in mobility as observed and quantified by geo tracking of mobile phones. Such data is widely available and routinely used for targeted marketing and traffic reports. Less movement in some places (people staying home), more movement in others (people fleeing a hot zone) before it’s locked down, is data readily interpreted by those trained and watching. Increased internet searches on medically related topics such as symptoms, treatment and availability of western and traditional remedies. Shortages and online price increases of prescription and overthe-counter drugs, thermometers, and other medical equipment such as masks and personal protective coverings available to the public. Changes in travel patterns to season action spots. These are just some of the enormous sources of data that those with an eye on the clouds and an ear to the ground will understand to be the rumbling of impending storm. Digital Wakes Digital wakes of nascent epidemics are the faint traces detectable when a few people—usually local hospitals and government officials—know that a serious disease outbreak is imminent. Wakes can be found by observing changes in the behavior or pattern of life of individuals or groups who typically would be the first to know when a new outbreak has started. These people are the "carnies in the coal mine". Observing their behavior constantly and in real time may seem intrusive but it is consistent with widely practiced commercial and political marketing activities using publicly available data. The key to success is identifying in advance the individuals or groups in each locality in a position to know what is happening. These include health care workers, government officials and digital “connectors” (influencers, thought leaders with massive social 102
networks). The most promising indicators are to be found in anonymized cell location data that is sold by mobile operators to marketers, traffic reporters, urban planners and others. When a serious outbreak has started, handset data, which can be pinpointed to specific buildings, even floors of buildings in some cases, can tell a compelling story. Here are some examples: Workers in key disciplines and areas staying late, not going out for meals, working weekends, changing who they socialize with (spatio-temporal relationships among multiple users are possible and have been used recently for contact tracing, social distance monitoring.) Workers in key disciplines and areas changing their travel and sleeping patterns (sleep is inferred from stationary geo-positional data for five to eight hours in residential areas) Cancellation of medical and government conferences or absence of key attendees Other telling digital early warning signal include: "Radio silence” of normally active voices on general interest (not health related) blogs and social media (due to preemptive government censorship) Decreased traffic or pollution Decreased power consumption of manufacturing buildings Less heat in normally active factories seen from commercial satellite thermal imagery Empty parking lots in some places such as factories and malls, and full lots at others such as grocery stores. Unexplained road and school closures A marked decrease in normal discussion about medical issues and disease, due to censorship or fear of censorship. Websites and blogs going dark Firings or unexplained absences of key individuals in health care or Government, cancelled leaves of first responders Unexplained rise or fall of certain stocks resulting from insider trading of corrupt officials Emotional content of postings by influencers/connectors and, in some cases, news reporters. The use of words that connote strong emotion has historically indicated that some locals are aware of big pending social disruptions
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Such a degree of data collection, surveillance and analysis may seem surprising and intrusive to many. From my many conversations, I can tell you such activities are routine, perhaps not always for health, but for intelligence and commercial purposes— certainly. Ripples Unlike bow waves and wakes, which occur in or near the region of outbreak, ripples are phenomena that take place at a distance from the epicenter. Examples are: Decreased bookings for air travel out of a region or even into a region Uncensored rumors heard in the outside world from foreigners posted in the affected regions Supply chain disruptions in global industries, especially for parts or services specific to a given region Conversations and chats online between teleworkers who perform offshore contract work (software engineers, call center operators, customer service representatives). Local governments potentially monitor and censor such conversations, but offshore teleworkers do not always display good “communications discipline” and governments who might monitor the conversations have limited resources to detect and throttle bothersome communications Cover-up behavior by diplomats or commercial representatives from the affected region. Attempts to disguise, deflect or deceive regarding the severity of disease outbreaks, are–all by themselves— indicators that something is amiss. Diplomats are trained to use certain language, describe or minimize problems, and those skilled in interpreting this language can spot changes that might suggest a building problem. Conversations across multiple officials in embassies, consulates, and trade missions have a sameness to them that denote official “talking points” that have been circulated “Holes” in conversations: officials and commercial/trade representatives avoid topics that they would normally discuss Unexplained overseas purchase of personal protective equipment, drugs and medical equipment 104
Perplexing swings in some commodities markets Such a degree of sophistication by trained observers may strike many as an impractical. Believe me, it is not! When national security or commercial profits are at risk, many governments and large companies are willing to make the training and manpower investment needed— but to date, this is not the case in health. Digital Buoys Harnessing the predictive power of bow waves, wakes and ripples is enabled by sensors, digital buoys, that are set afloat on the digital ocean in advance of disease outbreaks to detect disease outbreaks wherever they might occur at earliest possible moment. It is the early actions which are most effective in containing a disease threat and minimizing its impact. For example, to sense ripples in changes in behavior of key health care workers and government officials, they must be identified in advance and their normal daily behavior recorded and analyzed. Such analysis, I am told, is commonplace for intelligence services and commercial entities that have long standing customer relationship marketing deals in place with mobile operators so that location and movement data of relevant groups can be observed and analyzed. Similarly, analytics and tools must be developed and prepositioned because big data analytics, machine learning, and pattern recognition artificial intelligence systems cannot be brought on line instantly. It takes time to train people to interpret and analyze a flood of data. These people will be digital first responders. Training by observing disease information flow from disease outbreaks in the recent past is essential. There is no better training set of data than COVID-19. Real time tests of predictive models are also necessary. For that, there is no time like the present. Many of my interlocutors warned me against danger of over reliance on fully automated analysis. Forming insights from digital data is very labor-intensive, requiring the knowledge and experience of highly skilled staff. Digital collection, archival and analytic systems can be developed and pre-deployed, but humans are needed to operate and analyze these systems. They must be in place before the next epidemic. The necessary knowledge and experience cannot be acquired on the spot. 105
From Information to Action Everyone I spoke with emphasized that the most important part of the equation is communication, making sure that information leads to productive action. We all know the myth of Cassandra. Her curse was to be able to see the future, to be heard, but not to be believed. Belief is the necessary precedent for action. Remember the fate of the Trojans. Cassandra correctly foresaw that there were Greeks in the gift of an outsized horse. Priam listened to her. He did not believe what he heard. He did not act and so lost his country and his life. A robust conduit for transfer of information to decision makers is of utmost importance, so is the credibility of the messenger. Perhaps most important of all is the selection of leaders, by whatever process a country may choose, that are receptive to hearing and acting on information in the interest of the people and the economy they serve. Yes, leaders the world over are besieged daily with an overload of data and must make decisions based on imperfect knowledge. That is why the information and analysis they receive must be of the highest quality. Both our commercial companies and intelligence services know how to plumb the depths of the digital ocean to extract the information they need. These tools must be fully deployed for disease surveillance so that our lives and economy are never again placed at such risk. This article originally appeared in Forbes and is available online here: What Did We Know And When Did We Know It? Disease Surveillance: Past, Present And Future
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How Many Tests Do We Really Need? Forbes | April 23, 2020 | Article
We are all eager to return to normal or at least a new normal. Today’s limits on the availability of tests is the key bottleneck to reopening We all know more tests are needed. But how many more? Given the urgency to restart our economy this is no time to be timid. Every public health official outlines three criteria for ending lockdown. Identification of those infected. Contract tracing to identify those exposed. Isolation of those exposed until there is no longer a risk of transmission. How many tests do we need? Ideally all 155 million workers should be tested before returning or continuing to work. People should not have to go to work fearing for themselves and their families. All 80 million students (K through 12 and college) should be tested before returning to classrooms, which are ideal settings for disease transmission. All those over the age of 65 (about 50 million) should be tested as they are at high risk. According to the Harvard Roadmap to Pandemic Resilience, we may need as many as 5 million tests a day by June and 20 million tests a day by July, that translates to 10 billion tests per year, in excess of my estimates here. Testing is not a one-off exercise. Each person should be tested a minimum of three times over a fifteen day period to account for low and undetectable virus in early stages of infection. Additional testing of all contacts of an infected person will be needed until an effective vaccine is developed and those vaccinated develop protective immunity. Developing and deploying a vaccine is estimated to take a year or more. Developing protective immunity once vaccinated may require another six months and repeated boosters, as is the case for most vaccines. Therefore, the capacity for large scale testing must be in place for many months and up to two years perhaps. This simple 107
math adds up to about one billion tests for the initial round and another billion tests over the next two years, about one to two thousand times as many tests as are currently planned. The need for two billion tests far outstrips any current capacity. Therefore, I call on the Federal Government to create a crash program to develop the instrumentation and materials necessary. Manufacturing the machines and producing the materials is a relatively simple engineering problem, as the technology already exists. We have the technology to provide results on site, within 5 to 10 minutes of the test. What is lacking is resolve and scale. We are America. We can do it! Once developed the instruments and all the necessary materials should be made available throughout the country at no cost. The tests themselves must be administered by local public health authorities. It will be the responsibility of each state, once provided the instruments and testing materials, to deliver the service to its people. I estimate that the cost per test, when done at scale, will be less than one dollar per test. It is a small investment relative to the cost of the economic shutdown. This article originally appeared in Forbes and is available online here: How Many Tests Do We Really Need?
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In Some Hospitals, Surviving COVID Is Almost Twice As Likely Forbes | April 23, 2020 | Article
Earlier this month I published a story in Forbes on the importance of reducing in-hospital death rates. Even among the “best” hospitals in Manhattan, the chances of leaving by the morgue instead of the front door are twice as high in some hospitals as compared to others. One explanation often bandied about concerns the patient population, with some hospitals claiming that their patients are more at risk of death before they even make it to the hospital because of the complexity of their conditions. But this “get me off the hook” excuse does not explain why some hospital systems have reduced in-hospital death rates by 50% over the past few years while others have not. Those that have improved all made concerted multiyear efforts to reduce their death rate and improve other outcomes across the board. COVID-19 adds new urgency to the issue as critically ill patients are flooding our hospitals. I was struck by one number in particular in a recent report on COVID-19 patient outcomes. In the largest hospital system in New York, Northwell Health, 88% of COVID19 patients placed on ventilators died. For those over 65, the number was even higher at 97%. These numbers are comparable to those reported from some Chinese hospitals. Shocked by these numbers I asked the CEOs of two hospital systems with better than average in-hospital death rates for their outcomes. At NYU Langone the current death rate for ventilated COVID-19 patients is 48%. For those at Rush in Chicago the death rate is slightly under 40%, even though Rush is a referral hospital for the most difficult COVID-19 cases in the city. I am not surprised that the hospitals that have made a significant effort in developing systems to improve patient outcomes and reduce in-hospital deaths also do better with critically ill COVID-19 patients. It is time for all our hospitals to learn from the best, so that
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all patients, no matter where they are treated and no matter what their disease, are given the best chance medicine can offer. This article originally appeared in Forbes and is available online here: In Some Hospitals, Surviving COVID Is Almost Twice As Likely
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This Is How You Can Return To Work Safely Forbes | April 23, 2020 | Article
Public health experts agree on the need for widespread testing to be in place before businesses can reopen and the economy restarts. But not every government official is on board. In May, there is a real risk that Americans will be asked to return to work before our public health infrastructure is in place to keep them safe. Workers desperate for a paycheck, have little recourse but to agree. So what can each of us do to protect ourselves in this scenario and help keep those around us safe? The answer depends in part on what group you fall into: those who have been infected and those who haven’t. If you’ve been infected with a lab-confirmed case of COVID19, chances are that you have some degree of immunity to the virus. But what level of immunity and how long it lasts is still a great unknown. It’s also unclear whether or not your infection will reemerge, even after you’ve recovered and tested negative. Given the current dearth of testing in the US, it’s likely that many Americans were infected but never had their cases confirmed. If this is your situation, be wary of assuming you were positively infected. A false belief in having been bestowed some sort of immunity could lead to more careless attention to handwashing and other proven approaches to avoiding the disease. Those who have never been infected will continue to be at high risk when lockdowns loosen and must be particularly diligent in their return to work. Though the surge in demand for healthcare services may have passed and hospitals may be better able to manage the needs of those most ill, there is still no treatment or cure for COVID-19 and the death rate for those infected remains far too high. While the Centers for Disease Control have issued guidance for returning to work, their recommendations do not go far enough to protect those at risk. For instance, an employee with COVID-19 symptoms who was told by their doctor to care for themselves at 111
home would be allowed to return to work just three days after recovery according to the CDC. This means that a sick employee would be back in the office after only three days without a fever or a cough, a recommendation which flies in the face of early evidence which has shown that some patients may be infectious for up to ten days after obvious symptoms have resolved. To protect yourself, your coworkers, and your loved ones who you return home to each night, here are a few tips I recommend all employees follow based on the science we know now: If you are sick with a fever or cough — no matter whether you were officially tested and diagnosed with COVID-19 — do not return to the workplace until at least 14 days since the onset of your symptoms and, ideally, up to 16 days. Work should be done remotely from quarantine to protect the health of all employees. When you do return to work, wear a mask, keep a safe distance from your colleagues, and be conscious of what you touch in common areas, wiping down surfaces after you touch them. If you are not sick but someone in your household is showing signs of COVID-19, do not go into work until your entire household has recovered. COVID-19 is highly infectious and everyone who has had significant exposure to someone with the infection, like in a home environment, needs to quarantine for the full 14 days. If you are healthy and commute to work via public transit, wear gloves to help you avoid getting the virus on your hands, do not touch your eyes, nose, or mouth, and leave your phone in your pocket throughout your commute to avoid transferring germs onto its surface. If you can, consider taking a bike or car to work instead, being careful to wipe down all surfaces with disinfectant sheets prior to touching any surface. If you have another medical condition that puts you at high risk for a severe case of COVID-19, ask your employer to provide you with reasonable low cost solutions to make the office space safer for you. This could include moving your work area away from others, limiting foot traffic around your work space, or using plexiglass, tables or other barriers to ensure a minimum distance between you and your coworkers. You may also want to ask your employer for a change in hours to help you avoid rush hour commutes and to limit the number of employees around you at the office. 112
Granted, not all of us will be so lucky to work for an employer who will be understanding of our needs. In these cases, it may be worthwhile to visit the US Department of Labor website and review the information they have provided under the Families First Coronavirus Response Act as some of these protections are now required by law. Employees and employers alike are all eager to return to normal, or at least a new normal. But our sense of urgency to restart our economy should not eclipse our sense of duty to our families and those around us who continue to be at grave risk. This article originally appeared in Forbes and is available online here: This Is How You Can Return To Work Safely
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Monoclonal Antibodies Could Help Fight Against Coronavirus Forbes | April 23, 2020 | Article
A group of Chinese scientists report the isolation of two human monoclonal antibodies with the potential to treat and to prevent SARS-CoV-2 infections, the causative agent of COVID-19. The work is described in a manuscript made available by Nature Cellular and Molecular Immunology. The two monoclonal antibodies block binding of the virus to the receptor preventing entry. Such antibodies hold great promise for treatment as they are expected to prevent the virus spreading from cell to cell. The antibodies are also likely to protect those exposed, especially healthcare workers, from infection at least for a limited time. In both cases, the drugs would be administered intravenously. No results demonstrating the activity of these potential drugs in animals or humans are reported. Nonetheless, previous experience with antivirus monoclonal antibodies of this type have been shown to be effective in treatment of both human and animal infections by viruses and other microorganisms. Monoclonal antibodies are among the most successful class of new drugs. Methods for manufacture and testing are well established. The FDA has approved more than 70 monoclonal antibodies for the treatment of human disease, including one for the treatment of respiratory syncytial virus a major cause of lower respiratory disease in children. Several key questions remain open: How soon will drugs be available? My guess, within three to four months for the first approvals. • It may take several weeks to demonstrate effectiveness in animals.
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Human safety studies can be done with no more than 30 people in about a month. These drugs are generally known to be safe though more testing for safety will be required.
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Tests of the drugs’ effect in reducing the viral load in infected patients should take no longer than a month.
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Most time consuming will be large scale manufacturing of the drugs, once approved.
Some of these steps are undoubtedly already in process at this moment. China has the necessary skills and capacity to complete the research and testing and to manufacture at scale, as do many other countries. I know whereof I speak as I developed a similar drug for the treatment of and protection from anthrax infection and a monoclonal antibody for the treatment of Lupus. Will the drugs work once patients become critically ill? The damage may already be too great to reverse. It is highly likely that the earlier the drug is administered post infection, the better. If given to healthcare workers to protect them from infection, how long will the protection last? Best estimates for first generation antibody drugs is from 3 to 6 weeks. Follow on prophylactic treatments will be needed. Subsequent preparations may provide protection for up to four months. There are several caveats. • Coronaviruses, specifically those closely related to the SARS virus, are known to mutate to escape monoclonal antibody neutralization. The drugs may work for a while before the virus develops immunity. One way to counteract virus escape is to treat with two or more antibodies simultaneously. •
The drugs are relatively expensive to manufacture. The first generation must be grown in cell culture. It should be
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possible to develop future generations of drugs that act similarly but are far less expensive to produce. •
The antibodies were isolated from COVID-19 convalescent blood. Of the 26 convalescent patients studied, only three had the potential to block binding of the virus to its receptor, the ACE2 surface protein. Cells that produce antibodies were isolated from these three patients.
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The genes that produce the antibodies were isolated from these cells and used to create the two new drug candidates.
The work was completed by a team of scientists working in four different cities from across the length and breadth of China. While still in its early phases, the discovery is significant. There has been much talk in recent weeks about the use of convalescent serum and hyperimmune globulins—essentially, collecting blood from patients who have recovered from COVID-19 and giving the plasma to people who are sick. This discovery offers us the hope of a purer and potentially safer form of this type of treatment. This article originally appeared in Forbes and is available online here: Monoclonal Antibodies Could Help Fight Against Coronavirus
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How Business Leaders Can Respond COVID-19 Psychology Today | April 24, 2020 | Article
Many management books talk about the importance of building trust with customers in order to succeed, but in the age of COVID, trust takes on new meaning. When businesses reopen, the behavior of customers will be critical to containing new outbreaks. Customers who keep a respectable distance, take care not to touch too many surfaces, and cover their mouths when they cough or sneeze will help reduce transmission of the virus. But those who stand too close, cough or sneeze too liberally, and neglect the need to keep common areas germ-free will contribute to its spread. So what makes a person more likely to behave in a manner that protects public health? Studies tell us that there are a few critical elements at play. When people understand the public health risk and believe that the recommendations to protect themselves and those around them are credible and sincere, they tend to comply with protective measures. On the other hand, when public health messages are inconsistent or there’s a perception that the crisis response is biased, incompetent or unfair, distrust and fear flourish and people are much less likely to follow the recommended rules. Businesses can’t control all the factors at play -- if people don’t trust the public health leaders and political players leading the national or statewide response to COVID-19, there is little that a single company can do. However, businesses can step in and create trust at a local level, which may have an outsize impact on the spread of the virus overall. Imagine two restaurants, side by side. The first looks like any restaurant pre-COVID: tables packed tightly together, waiters with bare hands taking orders and serving up meals, and bathrooms with a single sign beside the sink reminding employees to wash their hands.
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The second restaurant looks quite different: tables are spaced out, waiters wear disposable gloves, hand sanitizer is widely available, and signs in the bathroom and around the dining area remind customers of how regularly rooms and tables are sanitized and how important the health of customers and staff alike is to management. There is no doubt of the effect of each on customers. In the first, customers will follow the lead of the restaurant itself, gathering more closely together and likely becoming more careless with other protective measures, such as lengthy handwashing. In the second, customers would be more aware of their risk and more likely to modify their behavior to reduce the chance of infection. In the absence of clear national guidance, the onus is then on business leaders and managers to create environments that promote positive behavior change and safeguard the reopening of our communities. In normal times, as described in my book World Class, the hallmark of an effective leader is a person with a clear vision, a decisive strategy developed with input from the wider team, and the willingness to hold everyone, including themselves, accountable for results. Also critical is the ability to communicate clearly and effectively in order to rally support for the long term vision and shorter term goals. In times of crisis, these qualities become ever more important. In times of crisis, these qualities still matter greatly. But research has shown us that one quality matters above all the rest: trust. A lack of trust in leadership leads to disobedience and an unwillingness to follow public health measures that can save lives. The challenge for business leaders though is that trust is a delicate thing, hard to gain yet easy to lose. Once trust is lost, efforts to communicate information and promote better health behavior becomes ineffective. Fortunately, researchers have helped us identify six key determinants of trust that matter most in a public health crisis like the one we face today with COVID-19. Competency. Where people feel that those in charge possess the necessary knowledge and expertise. Objectivity. Where people feel that the information that is shared with them is reliable and not influenced by those with a particular agenda.
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Fairness. Where people feel that all relevant opinions are considered and included. Consistency. Where people feel messages and actions are predictable and aligned. Sincerity. Where people feel that the people delivering the message are transparent, honest and open. Empathy. Where people feel that those in charge are listening to them and genuinely want the best for them. This means to establish trust, leaders must help make people feel as though they are being dealt with competently and fairly, the information that is shared is trustworthy and consistent, and the message is delivered with honesty, empathy, and transparency. A perceived lack of any of these elements -- competency, fairness, consistency, objectivity, empathy, or sincerity -- will sow distrust and fear and lead to behaviors that will eventually result in new outbreaks and a renewed call to shut down businesses and stop the spread. To help leaders flourish in their new and, perhaps to some unwelcome, role as guardians of our health, the Dean of the University of Miami’s business school, John Quelch, developed what he termed the “7 C’s” of leadership during the coronavirus crisis: Calm. Commanding the situation with a level of composure that instills trust in employees and customers alike. Confidence. Projecting a managerial bearing that boosts the faith of stakeholders. Communication. Communicating relentlessly, keeping everyone informed and rumors at bay. Collaboration. Tapping into the resources and capabilities of their entire team to identify the best solutions. Community. Recognizing the role of the business within the community and leading by example. Compassion. Looking out both for the wellbeing of employees and also for members of the wider community in need. Cash. Preserving funds and ensuring that every step is taken to care for the financial needs of employees. Fostering these key elements of leadership, especially as more and more businesses reopen, is key to building the trust we need to win our battle against COVID-19, a battle that is likely to be long and 119
drawn out over many months and possibly years. No matter what happens at the national level, each of us have a responsibility in our communities to prevent future outbreaks. Businesses must lead by example, inspiring us to act in a way that will eliminate the risk of a new coronavirus outbreak. And as customers, we have a responsibility to support the businesses we trust have our health and the wellbeing of our communities at heart. This article originally appeared in Psychology Today and is available online here: How Business Leaders Can Respond COVID-19
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Reopening America Will Require This Key Thing That's Been Ignored FOX News | April 24, 2020 | Article
Returning to work and school after the coronavirus is urgent and necessary. Virtually all public health officials agree on the three capabilities necessary to reopen society: 1. Availability of tests to identify those actively infected and capable of infecting others. 2. Exhaustive contract tracing to identify those exposed and potentially infected. 3. Self-isolation of those exposed until they are no longer likely to infect others. The requirements for testing and contract tracing are the subject of much public debate. But missing from the conversation is another step central to our ability to reopen—the “Q” word, controlled quarantine. Identifying those exposed to the virus is important, but we make a grave mistake by stopping short with the recommendation only to self-isolate. We know what works from the experience of East Asia. Those exposed to the virus are placed under controlled quarantine. The preferred method is to isolate all those exposed in a special facility, for example in a single-occupancy hotel room. There, those in quarantine are allowed only fleeting contact with staff dressed in full hazmat gear for fourteen days from exposure. During that time, they are required to monitor and report their temperature and symptoms twice daily. Their status is monitored, recorded, and reflected on a personal QR code, green for clear, yellow for those exposed and not yet cleared, and red for actively infected. 121
Identifying those exposed to the virus is important, but we make a grave mistake by stopping short with the recommendation only to self-isolate. They are also required to disinfect all urine and feces after using the toilet and before flushing, as the COVID-19 virus is also transmitted by the oral/fecal route. Entry to all public spaces is dependent upon having a green QR code and normal temperature, measured on entry. Conditions of self-isolation are far less stringent. As practiced in the U.S., those exposed and even ill may reside at home, preferably in a separate room. The chances that they will expose others in the household, despite precautions, is very high. Those exposed who are not ill often feel free to enjoy a walk around the block, a visit to a local grocery store or even a run in a nearby park, all activities that may expose others should they be presymptomatic or even asymptomatic. The consequences of avoiding strict and controlled quarantine of those exposed will be prolonged person to person transmission. Rather than the epidemic reaching a peak and quickly subsiding— as has been the case for most East Asian countries—the infection rate will plateau and remain high for a prolonged period. We may flatten the curve via self-isolation only to find we have to climb again, though this time not to the top of a mountain peak but rather a long flat ascent, glimpsing the downslope only at a distance. That is what is happening in Europe and seems to be happening in high incidence cities in the United States today. We have the hotel space needed—the great majority of our hotels stand empty. What is absent is the will to utter the “Q” word and put controlled quarantine into action. Even the most ardent advocates of testing and contract tracing have not yet committed to such a move. Without quarantine, our suffering will only be prolonged, along with the continued disruption of our lives and livelihoods. This article originally appeared in FOX News and is available online here: Reopening America Will Require This Key Thing That's Been Ignored
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A Vaccine Candidate Protects Non-Human Primates From SARS-CoV-2 Infection Forbes | April 25, 2020 | Article
A pre-print in BioRxiv from a Beijing based biotechnology company company, Sinovac, describes protection of macaque monkeys from infection by SARS-CoV-2 by a vaccine candidate. The candidate is a “killed virus” vaccine prepared by inactivating live virus with beta-Propriolactone, a standard procedure used in inactivate other viruses for use as vaccines. Alum, used in many vaccines, was added to the killed virus preparation to elicit a stronger immune response. To my knowledge this is the first published report of protection of non-human primates by a COVID-19 vaccine candidate. Preparatory studies of the vaccine candidate were conducted in mice. The vaccine candidate administered day 0 and day 7 elicited strong antibody responses that neutralized all eleven strains of SARSCoV-2 isolated in China and several European countries. The majority of the antibodies were directed against the part of the spike protein, called the receptor binding domain, necessary for virus infection. Monkeys were injected with two different doses of the vaccine candidate at day 0, day 7 and day 14. All animals produced produced strong antibody responses to viral proteins including the spike protein. A separate group of animals were inoculated with a sham vaccine containing all ingredients of the vaccine except the inactivated virus. A third group was left untreated. Both doses of the vaccine induced strong neutralizing antibody responses by day 21. All the animals were challenged on day 22 by introducing live virus into the lung. As expected within 3-7 days all the animals inoculated with the sham vaccine as well as the untreated control animals were infected and fell ill. All the animals inoculated with the higher doses showed no signs of infection nor was virus detected in the fluids obtained from the throat, lung or rectum. Transient infection was observed in animals inoculated with the lower dose as 123
evidenced by isolation of live virus from the fluids in some of the animals. There has been a concern that an anti-coronavirus vaccine might enhance the disease, as was observed several years ago for a vaccine intended to protect cats from a coronavirus induced diarrhea (a virus unrelated to SARS-CoV-2). This phenomenon is called antibody dependent enhancement (ADE). The authors report that ADE was not observed in any of the vaccinated animals. These are the hoped for results for candidate vaccine for human trials. Sinovac has already initiated safety trials of the vaccine candidate in 144 volunteers in China. If successful, a trial involving 1,000 volunteers in planned for mid-May to evaluate efficacy of the vaccine. Sinovac has received support from the Chinese government both to conduct the trials and to scale up manufacturing capacity. Sinovac currently produces several other killed virus vaccines for the prevention of other diseases. This is by no means the only vaccine to enter human trials. According to the World Health Organization, as of this week there are seven vaccine candidates in human trials and many more are on the way. I am personally encouraged by the results presented. The vaccinated monkeys raised exactly the type of antibodies that are likely to be most protective and the most serious feared side effect, ADE, was not observed. The Sinovac vaccine may or may not be the one that eventually brings a halt to the pandemic but we are off to a very promising start. This article originally appeared in Forbes and is available online here: A Vaccine Candidate Protects Non-Human Primates From SARS-CoV-2 Infection
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A Letter To Congress: Four Principles For A Safe Economic Reopening Forbes | April 29, 2020 | Article
On Monday, a bipartisan group of public health leaders laid out four principles for the safe reopening of the US economy in a letter to Congress. In it, they argued that the key to reopening our economy would be to test, trace and self-isolate and they asked for an additional $46 billion in congressional funding for implementation. They introduced the four point proposal by emphasizing that central to reopening is the universal availability of rapid, accurate tests to identify those who are infected and those who are potential sources of contagion. Testing at this scale will require an adequate supply of new, high speed, accurate tests and their approval by the Food and Drug Administration. The letter does not address actions by Congress or the Administration needed to create this necessary capacity. Once the testing capacity is in place, the bipartisan group recommended four additional steps: 1. Expansion of a contract tracing workforce. They calculate 180,000 full time contract tracers would be needed until a vaccine is available. They estimated the cost for this new workforce at $12 billion dollars. 2. Establishment of voluntary self-isolation facilities using vacant hotels. They recommend self-isolation for all those exposed to a person who tested positive for COVID-19, thereby eliminating the risk of becoming a source for infection of others. Self-isolation means no contact with others for 14 days. The proposal is to use vacant hotel rooms to house all identified contacts of an infected person. The estimated cost is $4.5 billion. 3. Income support for voluntary self-isolation. They propose a $50 dollar per day income support for those in voluntary self-isolation. They calculate such a program would cost an additional $30 billion for the 18 months until a vaccine is available.
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4. Primary care provider referrals. They call for the creation of a referral code to be used by primary care doctors for COVID-19 patients. Such a code will enable payment for their referral services. The letter does not call for additional funds for such payments. The letter is a welcome and important contribution to the discussion of how to open our lives and businesses safely. It is unfortunate that at present time we do not have capacity to implement the testing precondition that is necessary to fully implement the four recommended steps. Nonetheless we can make significant progress by implementing steps one to four with the imperfect diagnostics and testing regimes in place now. The sticking point of the four step program is “the voluntary self-isolation in vacant hotel facilities.” As those who drafted the letter are aware, 14 days of isolation of all those exposed is necessary to reduce the contagion index below one. The contagion index for self-isolation at home with family, even when confined to one room or a basement, remains too high, above one. If this continues, so will the infection continue to spread throughout the community. The proposed program pins our hopes on the better part of human nature, that the great majority of those exposed will be willing to dramatically change their lives for 14 days, to stay alone in free hotel rooms with free meals and $50 dollars a day, for the good of the nation’s health and economy. Let’s hope we can! This article originally appeared in Forbes and is available online here: A Letter To Congress: Four Principles For A Safe Economic Reopening
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Reducing The Risk Of In Flight COVID-19 Transmission Forbes | April 29, 2020 | Article
All of us fly. Last year, more than 1.5 billion people took to the air. Flying both short and long distances has become a way of life not just for the privileged, but for the many. We always knew air travel was a good way to catch a cold. Many of us took pains to wipe down all surfaces we were likely to touch, including the seat belt buckle. In the end, what we were afraid of was the air. A passenger near us, one passing by, or even one further away might be spreading viruses. There is even risk of catching tuberculosis, the drug resistant kind, if you fly to and from India like I do. It turns out our fears, reinforced by our experience, were correct. Michael Laris of the Washington Post has written a deeply researched article on air travel contagion, and he only described the airplanes, not the airports. Contagion while flying is nothing new, even for the coronavirus. Transmission in flight of the SARS virus has been studied in detail. What have airlines done since? Precious little. The article emphasizes the use of person friendly, virus killing ultraviolet light as one approach. The scientist in me says sure, that should help—but it will not be enough. We should ask what the airlines, aircraft manufacturers, and their regulators are really doing to keep us safe. The time is now past when we just sit down, buckle up, and sneeze. This article originally appeared in Forbes and is available online here: Reducing The Risk Of In Flight COVID-19 Transmission
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Urging Caution On Remdesivir Forbes | April 30, 2020 | Article
There is palpable excitement today among many regarding the potential of remdesivir to help patients with severe COVID-19 recover. Many are saying there is clear cut evidence that it works, based on a news release issued yesterday by the National Institutes of Health (NIH). Yet, an equally important study about remdesivir was published the same day in the Lancet, with markedly different results and noticeably less attention paid. According to the NIH, preliminary data analysis from a randomized, controlled trial involving 1063 patients showed that patients who received remdesivir had a 31% faster time to recovery than those who received the placebo. It also suggested -- but didn’t statistically prove -- that there was a survival benefit to the drug, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group. The Lancet article describes results from a randomized, doubleblind, placebo-controlled trial involving 237 patients at ten hospitals in Hubei Province, China. That study found that patients who received remdesivir did not recover any faster than patients given the placebo. They also found that the 28-day mortality was similar between the two groups, with 22 patients (14%) who died in the Remdesivir group versus 10 (13%) in the placebo group. In such a time of despair, it is no wonder that we cling to the more positive results from the NIH trial and all but ignore the news from China. But our hope is premature and may be misplaced. The NIH has not released any comprehensive data from their trial, nor were their findings made public or peer reviewed before the public announcement. While I have enormous respect for the Institutes and their leaders, releasing the preliminary news without sharing the data behind it is highly irresponsible. We have, unfortunately, already seen what unfounded trust in an unproven medical solution can do, with the death of a man in Arizona who ingested chloroquine from 128
his fish tank in the hopes that it would protect him from COVID19. Remdesivir is not a drug without risk.The peer reviewed study out of China showed that 18 patients (12%) had to discontinue remdesivir because of adverse or serious adverse events. These adverse and potentially life-threatening events included gastrointestinal issues and liver function abnormalities -- side effects that we have known about for a while already. It is impossible to know with certainty why the NIH released unpublished preliminary results without accompanying comprehensive data on the same day that a definitive peer reviewed paper with disappointing results was being published. It is possible that they were aware of a credible beacon of hope and they wanted providers and patients alike to know. It is also possible that the decision was done for economic, geopolitical, or political reasons. But we should not allow hope, nor politics, nor economics to cloud our vision. Viruses do not care much for any of them. If we are to have drugs and vaccines to control this pandemic, we must keep an open mind regarding what works. But we must be equally open to what doesn’t and not base policy or actions on undocumented assertions that may put all of us more at risk than necessary. This article originally appeared in Forbes and is available online here: Urging Caution On Remdesivir
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An Urgent Need To Reopen Medical Care For All The Hill | April 30, 2020 | Article
Each day a new story of crowded hospital corridors and exhausted healthcare workers appears in our newspapers. But another story, equally tragic, is unfolding in the privacy of our homes. Countless Americans with chronic conditions and other serious illnesses languish in isolation without access to care. While hospitals have of course remained open for urgent care, patients with less critical needs have been relegated almost entirely to virtual visits. Many without illness are able to cope, but countless families have been permanently broken by the hospital closures. Take, for example, the blood cancer patient in Philadelphia who was desperately in need of chemotherapy. Unfortunately, blood supplies had been rationed for COVID patients and the patient couldn’t get enough transfusions to allow his chemotherapy to begin. His clinic visits were canceled, his condition worsened, and by the middle of April, he had passed away, a death expedited by COVID-19. Stories like this are just the tip of the iceberg. Doctors across the country have been reporting concerning trends among patients, with many delaying much needed care because of concerns about contracting COVID during an emergency room visit. A survey of nine major hospitals published earlier this month in the Journal of the American College of Cardiology found that the number of patients presenting with severe heart attacks had dropped by nearly forty percent since March. Vaccinations and well-child visits have seen a similar deterioration, with millions of children now at greater risk of infection of other preventable diseases due to the stark decline. All this reinforces the undeniable fact that the first facilities to reopen in our communities must be our hospitals. The Centers for Medicare & Medicaid Services (CMS) recently released guidance for reopening healthcare facilities for non-emergent cases, but the advice 130
included is vague at best. While it has recommendations for testing and screening of both patients and providers, it gives no concrete advice on how often to screen each group or what to do if a healthcare provider tests positive. Guidance from state departments of health is equally inadequate and, in some cases, downright dangerous. Some in the hardest hit areas suggest that healthcare professionals can return to work after testing positive for COVID-19, assuming they have been symptom free for just three days and seven days have passed since their symptoms first developed. This despite the fact that studies have shown that some people may be infectious for up to ten days after obvious symptoms have resolved. In the absence of more careful guidance, many medical centers have developed their own more stringent guidelines. In addition to designing their own strategies to protect healthcare workers, hospitals are also crafting their own plans to protect patients. Some hospital systems have created broad networks of ambulatory care centers that operate as outpatient facilities. Many hospital administrators think their best bet may be to funnel patients suspected of COVID-19 to the hospitals while maintaining a steady supply of high quality services for non COVID patients through the ambulatory care centers. This would keep hospital beds free for the worst COVID patients and still provide high quality care to other patients in need. All of this extra effort will require additional resources, something that is becoming a pivotal challenge for all hospitals large and small. Ever since facilities were forced to cancel these procedures to ramp up COVID care, they have been hemorrhaging cash in extraordinary amounts. In New York State alone, one of the Buffalo region’s smallest hospitals has said they are losing roughly $1 million each month. In New York City, some of the major medical centers are losing as much as $450 million. The only way these hospitals can survive is with an immediate infusion of money. True, there are some large hospitals with generous endowment funds that may be able to make it through the crisis without outside support. But smaller hospitals in rural communities and many safety net hospitals in larger cities are running out of cash already. We cannot charge patients more for the care they are receiving. A recent poll suggests that one in seven 131
Americans avoid seeking care because of the financial burden and potential cost. The onus is on our government to step in and support our hospitals as they reopen fully. It is quite simply a matter of life and death, not convenience or economic recovery. This article originally appeared in The Hill and is available online here: An Urgent Need To Reopen Medical Care For All
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Remdesivir: A Non-Antiviral Antiviral Drug? Forbes | May 1, 2020 | Article
There is an interesting line in the Chinese study on remdesivir that has gone almost entirely overlooked, one that introduces an interesting, and potentially serious, conundrum. The authors of the study wrote that "Remdesivir did not result in significant reductions in SARS-CoV-2 RNA loads or detectability in upper respiratory tract or sputum specimens in this study....” In short, what the authors are saying here is that remdesivir—an antiviral drug that is supposed to work by stopping the virus from replicating—did nothing to actually stop the virus from replicating. Patients who received remdesivir had the same viral load as those who didn’t. Remdesivir is purported to work by inhibiting virus growth by blocking an enzyme—RNA-dependent RNA polymerase—that the virus needs to reproduce itself. If the drug worked the way it’s supposed to, the amount of measurable virus in patients administered remdesivir should be many times lower than that in the untreated control patients. That was not observed in the controlled trial done in Hubei province and published in the journal the Lancet. That means that any benefit remdesivir has as a treatment is not related to its antiviral effect, because no such effect was observed. Many have critiqued the size of the China trial, saying it had too few enrollees to confidently assume the drug had no effect. But that argument does not apply in this case. The results from very few patients is all that is required to know whether a drug inhibits virus growth or not. Recall that AZT, the first effective treatment for HIV/AIDS, showed a very dramatic drop in virus load in a 36 patient study: 18 given the drug, 18 controls. An antiviral drug candidate that does not affect the virus load is not a promising therapy. Remdesivir is not the equivalent of what AZT was for HIV/AIDS, as some pundits have claimed—not by a long shot. If 134
Remdesivir is working to improve outcomes, data we are still waiting to see, it is not because it controls the virus. Most likely the Hubei study reached the appropriate conclusion—as the authors wrote, “Remdesivir is not associated with statistically significant clinical benefits.” This article originally appeared in Forbes and is available online here: Remdesivir: A Non-Antiviral Antiviral Drug?
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COVID Immunity: How Protected Are You? Forbes | May 4, 2020 | Article
If I have antibodies to the COVID-19 virus, or if I recovered from the disease, am I protected? These are the two burning questions workers and employers are asking today. The answer, at least from what we know today is bound to be unsatisfying—we don’t know. Mounting evidence from Italy and elsewhere raises serious unknowns about positive antibody tests for SARS-CoV-2. Not all people who recover from the virus make high levels of antibodies and in some cases, people make no antibodies at all. Even those who do make the antibodies may not make the right ones, the so-called neutralizing antibodies that inactivate the virus in the test tube. In some studies, only 15% of those who tested positive for SARS-CoV2 antibodies made these neutralizing antibodies. And even among those with the “right” type of antibody, there is a question over how long protection against a new infection might last, or if there is any real protection at all. All these questions make it difficult for employers to rely on an antibody test, or even successful convalescence, to determine the risk for infection in the workplace. To be sure, anyone who tests positive for an active infection—whether they are symptomatic or not— should be excluded from the workplace. That much is clear. But even someone who tests negative is not necessarily good to return to work, given how many tests fail to detect people who are actually infected and infectious. The only safe assumption any of us can make as long as COVID19 is present in our local populations, is to consider everyone is capable of infecting others and that everyone is susceptible to infection. That means every business must take precautions to avoiding workplace contagion. Reasonable precautions are: Measuring the temperature of everyone reporting to work and every person who enters a workplace. That is especially important 136
for consumer facing businesses, such as shops and restaurants. These temperature checks are not just for staff but should also include any customer who may enter the working space. Requiring everyone within the workplace to wear masks at all times. Removing a mask in a private office risks contaminating others who enter the space for business or cleaning. Reducing workplace density by creating staggered shifts, encouraging remote work, spacing work stations, and limiting the number of people in the working space, be they staff members, patrons, delivery persons, or otherwise. Instituting rigorous cleaning procedures designed to reduces workplace exposure and contamination. Ideally the cleaning process and its execution should monitored by an independent agency. Enforcing the rules to ensure compliance. It is unlikely that all workplaces will agree to institute the necessary precautions. The ability to stay open and to remain in business must depend on compliance. That means local, state and federal guidelines for reopening must be clear. It also means that all workplaces be subject to on the spot inspections. Those who don’t follow the guidelines should face the consequences and should be shut down immediately. Workers and employers should be allowed to file anonymous complaints against companies that are not following health and safety guidelines. These working conditions will not last forever. Eventually the pandemic will pass, and medicine will triumph. But until then, the only way to counter the disease, reopen our businesses, and resume our vibrant economy is vigilance by all. This article originally appeared in Forbes and is available online here: COVID-19 Immunity: How Protected Are You?
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Responsible Reopening: A Lesson From NYU Shanghai Forbes | May 4, 2020 | Article
This news clip is a glimpse of what reopening looks like for a small university in a country and city that has met the requirements for reopening, according to the Centers for Disease Control guidelines and US public health officials: 1. The number of new COVID-19 cases is small to none. 2. Rapid testing is easily available for those with symptoms. 3. Vigorous contact tracing exists. In this case, personal phone apps track location and certify local public health status: green means ok to enter public space, yellow means you have been exposed and isolation is required, red means infected. 4. Mandatory isolation in a supervised facility for all those exposed. To date this essential requirement is not part of US recommendations to contain the outbreak. Our emphasis is on voluntary self-isolation which has yet to be proven effective elsewhere. 5. Temperature reading required to enter all public spaces, including shops, restaurants, malls, and public transportation. Once the country and a city meet these requirements, a generally safe environment allows individual organizations to begin the slow and careful process of reopening. It’s a “try it and see” approach. If infection rates rise again, they are prepared to quickly implement harsher measures to reduce infections once again.
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This article originally appeared in Forbes and is available online here: Responsible Reopening: A Lesson From NYU Shanghai
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Can America Handle A Second Wave? Project Syndicate | May 4, 2020 | Article
Like surfers looking out for the next big breaker before the first one has passed, epidemiologists and public-health officials in the United States are bracing themselves for a fresh surge of COVID-19 infections later this year. The fear is that this second wave will coincide with the peak of the 2020-21 US influenza season, triggering a new flood of hospital patients in dire need of respiratory support The fear is justified, based on what we know about coronaviruses and influenza. For both, infections begin rising in November and peak at some point in December, January, or February, before subsiding by April. What is less certain is how high the waves for each infection will be. Although we understand influenza infection patterns much better than that of the SARS-CoV-2 virus that causes COVID-19, influenza remains a known unknown. Its strains vary from year to year in terms of both transmissibility and severity. In some years, the number of lives lost to influenza in the US can be as low as 12,000. But during the 2017-18 winter, a particularly lethal strain led to the death of an estimated 80,000 Americans – the highest such toll in at least 40 years. This article originally appeared in Project Syndicate. The full article is available here: Can America Handle A Second Wave?
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A Walk With Death
Medium | May 5, 2020 | Article
On Saturday I walked with death. The morning dawned bright, clear, a hint of summer warmth in the air. Magnolias and cherry blossoms were flying like fragrant snow, the wisteria and lilac blooming, adding subtle shades of lavender to tender new green of life reborn. We had been eager to enjoy a perfect day in early spring. As on most mid-afternoons, my wife and I strolled in Central Park. We were masked, gloved, intending to keep our distance. But not yesterday. Impossible. The park was packed. Some were masked, many bare-faced. Some were distant, most not. The crowds spilled into nearby streets. People clustered before the few take out windows, happily chatting, eager close personal contacts so long denied. Cars packed with people whizzed by — a nearly normal Saturday afternoon in the City. But these are not normal times. This is lockdown time. Social distancing or stay at home time. Time to prevent the spread of a deadly virus that each day harvests its tragic new toll; on this sunny day, 437 will die from COVID-19 in New York City. Yes, lockdown has slowed the spread, but it has not stopped contagion. We are learning as the days go by a tough lesson: America's loosely enforced self-isolation is not the match of disciplined quarantines -- at home or controlled -- practiced in East Asian countries. We are flattening the curve, no more. Not to climb down from a sharp mountain peak but to arrive at the top of a broad mesa, its down-slope only a distant vision. The infection smolders on... closing our businesses, cramping our lives — continuing on unless and until we do what is necessary. We do know how to stamp out this fire. Others have. We can too. Identify those infected (broadly available rapid virus detection) Identify all those exposed (vigorous contact tracing) 141
Isolate those exposed (controlled quarantine) Isolation of those exposed does not mean stay at home with others. It means isolation from all others for a minimum of two weeks in a supervised isolation facility, only contacting caregivers or other helpers who are fully garbed in hazmat suits. We are far from that. The words "controlled quarantine" are not even in our lexicon. Until we follow these straightforward rules we will not trust our neighbors, our co-workers or our friends. How can we? Will they know they carry the virus? We will continue to feel the fear that caused my wife and I to scurry home after our glimpse, jolting, unexpected, of the crowded park. Saturday had dawned bright, clear, a hint of summer warmth in the air. Magnolias and cherry blossoms were laying like fragrant snow, the wisteria and lilac blooming, adding subtle shades of lavender to tender new green of life reborn. We had been eager to enjoy a perfect day in early spring. Now, I felt that we were walking with death delayed. That two weeks from now we will measure this spring idle in rising numbers of body bags exiting homes and hospitals. A foreshadowing of deaths foretold, the mortician's harvest from a reopening without controlled quarantine. A haunting image of the medieval, our walk with the Grim Reaper in the Park. This article originally appeared in Medium and is available online here: A Walk With Death
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Blood Clotting And COVID-19: How Serious Is It? Forbes | May 7, 2020 | Article
With each passing day we learn more about SARS-CoV-2 and what it does to our cells and our bodies. It seems, according at least to anecdotal reports, that infection with SARS-CoV-2 can induce serious blood clots in COVID-19 patients, as well as those who are otherwise asymptomatic. Abnormal clotting has been reported in COVID-19 patients in China, the United Kingdom, Italy, and United States.The resulting heart attacks, strokes, and pulmonary clots can be fatal. From what we understand today, the blood clots appear to form in major vessels and migrate. Some are serious enough to require limb amputation. A recent paper in the New England Journal of Medicine reports 44 0f 216 COVID-9 patients had abnormalities in clotting time as measured by activated partial-thromboplastin time (aPTT). That’s 20% of those studied. Further investigation was done in 35 patients who had tested positive for aPTT. The patients ranged in age from 18-83, 24 male and 6 female. Lupus anticoagulant assays were performed in 34 patients. Of those tested, 91% (31 patients) tested positive. This factor is elevated in less than ten percent of matched historical controls. Despite its name, lupus anticoagulant is associated with increased blood clotting disorders. Lupus anticoagulant is an immunoglobulin that binds to a cell’s surface proteins and phospholipids. It is thought to act by binding to and aggregating platelets. A possible explanation for the elevated levels, not offered by the authors, is that antibodies related to SARS-CoV-2 itself, or to infected cells or cell debris, triggers an autoimmune reaction similar to that found in lupus patients. Other researchers have recently reported favorable outcomes in patients treated with anticoagulants. Management of COVID-19 patients will improve as physicians accumulate experience with the full range of symptoms associated 143
with SARS-CoV-2 infections. On Wednesday, a team out of Mount Sinai in New York reported better results for hospitalized COVID-19 patients who received anticoagulant drugs. Their findings aren’t definitive, but they do add evidence to the potential importance using blood thinners to reduce the potential for lifethreatening blood clots for COVID-19 patients. This article originally appeared in Forbes and is available online here: Blood Clotting And COVID-19: How Serious Is It?
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Putting COVID-19 Behind Us: A Research Agenda To Prepare For The Next Pandemic Forbes | May 8, 2020 | Article
Though many today are too young to remember, this is not the first time our nation has faced down a lethal pandemic. Indeed, this is the third time in my life the world has been overwhelmed by contagions that reshaped societies. The first, polio, struck parts of Europe and North America well before I was born and plagued countries for more than half a century before scientists discovered a vaccine. The second, HIV/AIDS, hit when I was an adult and when I was thankfully better placed to be an active part of the team of scientists and public health leaders working on our response. This third pandemic hit just as hard as the previous two — though it shouldn’t have. Unlike the others, we knew well in advance this one was coming. In the midst of two previous coronavirus outbreaks, SARS and MERS, scientists scrambling to find a medical solution warned us to prepare for the inevitability of another deadly outbreak of the virus. They started work on a number of promising drugs, some of which could act not just against a single strain of coronavirus, like MERS, but against the whole family of coronaviruses including today’s SARS-CoV-2. But once the SARS and MERS outbreaks were over, interest in developing these drugs all but disappeared. Pharmaceutical companies lost interest, governments forgot about the scientists’ warnings, and the rest of us went about our regular lives, having never had to face our worst fears. Someday — soon I hope — this outbreak too will be behind us. With an effective vaccine or treatment for COVID-19 in hand, we will, once again, return to daily life. And perhaps, just as we did after previous pandemics, we will begin to believe that the worst is behind us. But we will be wrong. There is a whole world of other biological threats lying in wait, more deadly and more transmissible than today’s SARS-CoV-2. These looming biothreats are far from unknown. In 2015, the World 145
Health Organization began prioritizing diseases that posed a threat to global health. By highlighting the diseases with the greatest risk, the thinking was that researchers and drug developers could prioritize efforts to tackle a solution. Among the diseases currently on the WHO list are SARS, MERS, and COVID-19, alongside other diseases of global renown, like Ebola and Zika. But there are many other threats beyond that list alone. Think of viruses as nature’s own form of artificial intelligence, constantly learning and adapting to find the best way to exploit their environment. Humans have created a rich environment indeed. In the last hundred years, our population has more than quadrupled, with many of us living and working in high density urban clusters where viruses can easily spread and thrive. Fold in our increasingly global way of life and you have the recipe for successive pandemics that will engulf us with more frequency than in the past. Our awareness of the threat of a new pandemic has become so widely acknowledged that Hollywood has even jumped on board, with movies like Contagion which essentially tells the story of what we are living today. The difference is that in Contagion, the virus killed 2.5 million. Today, we are not yet near those numbers, but that’s not to say the next virus won’t be deadlier. Whether it takes the form of a new coronavirus outbreak, a more dangerous strain of influenza, or a new germ that is resistant to all available antimicrobial drugs, it will be devastating — more devastating than anything we are witnessing today. Faced with the prospect of a whole host of potential pandemics, scientists have long advocated for the development of a global arsenal of panviral drugs — drugs that would work broadly across an entire family of viruses or even across multiple virus families instead of acting against a single disease. The oral polio vaccine of today, for example, works only against two of the three types of polioviruses we know of — WPV1 and WPV3. Introduce WPV2 — an eradicated strain — into the mix and the vaccine has no effect. Panviral drugs wouldn’t have the same problem. Instead of helping the body develop immunity against a disease caused by a particular virus, a panviral drug attacks the virus itself, preventing it from replicating or performing key functions. Simply put, If you understand the overall structure of a family of
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viruses and how they work, you can start targeting elements of their architecture and destroy their ability to function. The challenge is that developing a drug that targets a virus’ structure and processes is risky business. Any drug that works well at damaging the way an invading virus functions may also work far too well against the functioning of our own body’s cells. Creating safe and effective panvirals is a time-consuming and laborious process that takes years — sometimes decades — before bearing any fruit. So while we may have the knowledge and tools to develop these drugs as part of a pandemic preparedness watches, no scientist or laboratory has been given the time, the funding, and resources to take on the task. The lack of resources dedicated to this effort by major pharmaceutical companies and the private sector is somewhat understandable, though perhaps not endorsed. If we could accurately predict that a hemorrhagic fever-causing arenavirus would sweep the globe in 2025, killing tens of millions, every pharmaceutical company in the world would focus their efforts on an anti-arenavirus drug, knowing there was a market in place should they prove successful. But without knowing what the next pandemic will be or when it will hit, no company would sign up for the effort in advance. The onus then falls on governments to step in to fill the gap. Some governments have acknowledged the threat enough to create the programs that could now step in to help. The United States, for example, created the Biomedical Advanced Research and Development Authority (BARDA) in 2006. BARDA presides over the discovery, development, and stockpiling of medical countermeasures that protect Americans against health security threats. This includes biological agents of warfare, like anthrax, but also new and emerging infectious diseases, like the coronavirus. BARDA has a substantial $1.5 billion budget, split into three distinct areas: advanced research and development on emerging infectious diseases, pandemic influenza, and antimicrobial resistance; Project BioShield, a biodefense program to prepare for a bioterrorist attack; and a domestic influenza preparedness program. It’s potential is huge, but its funds are poorly targeted. With the abrupt firing of longtime director Rick Bright, its effectiveness is called into even greater question.
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In the absence of private sector or government leadership, new global partnerships among public, private, nonprofit organizations and by scientists themselves have taken root. The Coalition for Epidemic Preparedness Innovation was established in 2017 with substantial support from the Bill & Melinda Gates Foundation and the UK based Wellcome Trust, along with support from some major pharmaceutical players like GlaxoSmithKline. Their goal is to accelerate the development of vaccines against emerging infectious diseases and enable access to vaccines for all people in need during outbreaks. The Coalition represents exactly the kind of forward thinking research agenda that is needed to prepare us for the next pandemic. Yet, to date, only seven countries and the European Commission have committed ongoing funding for their work. Meanwhile, scientists at the Structural Genomics Consortium (SGC), the University of North Carolina at Chapel Hill and the Eshelman Institute for Innovation, recently announced a new initiative — the Rapidly Emerging Antiviral Drug Development Initiative (READDI) — which is raising $125 million to generate five new drugs in five years to ready our world for the next pandemic. These efforts are still not enough to prepare us entirely, but they are an important start. We should count ourselves lucky that SARSCoV-2 is not more deadly. We cannot forget — the bubonic plague killed 400 million, the 1918 flu killed 50 million, and the HIV/AIDS epidemic has killed more than 35 million, with numbers still rising. We may like to think we’ve gotten smarter and stronger since these outbreaks occurred — but for every advancement we have made, Nature has been right in step to match us. Let us not forget the warning she is giving us today. This article originally appeared in Forbes and is available online here: Putting COVID-19 Behind Us: A Research Agenda To Prepare For The Next Pandemic
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Hong Kong Doctors See Progress In Treatment Of COVID-19 Forbes | May 11, 2020 | Article
A group of Hong Kong Physicians report in Lancet that a cocktail of drugs approved for the treatment of other viral diseases significantly improved the clinical and laboratory outcomes of hospitalized COVID-19 patients. The symptoms of patients treated with the full four drug cocktail resolved more rapidly as compared to those treated by only two of the four drugs. All patients treated had mild to moderate disease. The four drugs used include lopinavir and ritonavir (anti-HIV drugs), ribavarin (a broad spectrum inhibitor of RNA viruses), and interferon-1 beta (a drug that stimulates antiviral immune responses). The control arm was treated with lopinavir-ritonavir alone, a combination previously shown to be no better than a placebo. The patients in the treatment group recovered much more rapidly. The average time to resolution of symptoms was reduced to 7 days from 12 days. Also encouraging is the measurable reduction in the virus load beginning day one post treatment and continuing throughout the treatment period. This is exciting news and, as far as I know, the first published report of symptom improvement along with a reduction in viral load. A published study of remdesivir shows no effect on patient improvement or viral load. An NIH study (still unpublished) claims improvement in symptoms but makes no mention of viral load reduction. The Hong Kong cocktail has another advantage. All the ingredients are available as generic formulations. This is especially important as the cost of medications will be an important factor in availability of the drugs, especially in resource limited settings. Knowledge of how effective the cocktail will be for a broader population is limited by the relatively small number of patients treated and the selection of patients with mild to moderate symptoms only. Viral load declined more rapidly in the treated versus control 149
group but did not drop dramatically as is the case for highly active antiviral drugs in other diseases. The authors correctly comment that this is at best an interim treatment until more effective antiviral drugs are developed. Despite these limitations this report is a ray of hope in a dark landscape. This article originally appeared in Forbes and is available online here: Hong Kong Doctors See Progress In Treatment Of COVID-19
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Why Haven’t We Seen The Data On Remdesivir? Forbes | May 11, 2020 | Article
Enthusiasm for remdesivir as the new standard of care for COVID19 has only grown since the release of preliminary results from the National Institute of Allergy and Infectious Diseases (NIAID) trial. But something is deeply wrong with the way the preliminary results were rolled out. Despite the hype, a vigorous examination of remdesivir studies suggests that something is amiss with how the drug is working. Remdesivir is an antiviral drug that is designed to target the center of SARS-CoV-2 and prevent it from replicating. Any positive effect should be apparent in a patient’s viral load. But a controlled clinical trial on remdesivir conducted in China and published in the Lancet suggests there is no such drop in viral load. Among the 237 patients in the study — 158 receiving remdesivir and 79 controls — there was no difference between the groups in viral load reduction. This means that if remdesivir is working, it is not because of its antiviral effect. Many have critiqued the size of the China trial, as too small to prove anything conclusively. But when it comes to antivirals, very few patients are needed to show whether a drug inhibits replication or not. The first effective treatment for HIV/AIDS — also an antiviral — was proven to work in a group of just 36 patients: 18 given the drug, 18 controls. Though laboratory tests were conducted as part of the NIAID study, reduction in viral load does not appear to be an integral part of the study. If it was included, that data should have been released along with the preliminary results. If it wasn’t included, we need to know why — reduction in viral load is a widely agreed upon marker of success for antiviral drugs. Were we to have access to the full data from the NIAID trial, we might be able to determine what impact remdesivir has on viral load and whether those effects have any impact on how effectively 151
the drug is working. But so far, all we have are those preliminary results. The makers of remdesivir recently secured FDA approval for their drug on the basis of the preliminary results. Now they are securing licensing agreements to ramp up global supply and determining how much they will charge for the drug — all without data from the largest controlled clinical trial on the effectiveness of the drug having been released. I would like to believe — as we all would — that there is nothing to be wary of in the way events are unfolding. But I can’t help but urge caution on remdesivir until the key question is answered: Where are the NIAID results? This article originally appeared in Forbes and is available online here: Why Haven’t We Seen The Data On Remdesivir?
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Which COVID-19 Antivirals Actually Work? Forbes | May 11, 2020 | Article
In emergency rooms around the world, doctors and nurses are writing the playbook for treatment of COVID-19. With so much about the virus, the disease, and effect of various treatments still evolving, doctors are improvising on the spot trying to figure out the approach that will give their patients the best shot at survival. Antiviral medications are among the options that doctors are considering as a way to treat the disease. The drugs work on SARSCoV-2 itself, targeting the functions of the virus and preventing it from replicating in the body. As I wrote about in a column earlier today, a group of physicians in Hong Kong recently reported success with a cocktail of antiviral drugs to treat COVID-19. The four drugs used include lopinavir and ritonavir (two antiHIV drugs), ribavarin (a broad spectrum inhibitor of RNA viruses), and interferon-1beta (a drug that stimulates antiviral immune responses). Their study shows that treatment with the cocktail can reduce recovery time from 12 days to 7 in patients with mild to moderate symptoms. This is much needed counsel for doctors struggling to keep their patients alive. Compare the information shared by these doctors with the data being shared on another antiviral drug currently being touted as the new standard of care: remdesivir. The data on remdesivir has been far less transparent. A controlled clinical study out of China suggests the drug brings no benefit to patients. Yet the National Institute of Allergy and Infectious Diseases said their study showed their was a benefit to patients, with recovery time reduced from 15 days to 11 days. The catch is that they have yet to release the full data from the study, nearly two weeks after they made the announcement of the preliminary results. The suspect nature of this lack of transparency aside, imagine what it means for doctors in emergency rooms today. Here you have two different antiviral treatment options available:
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One — remdesivir — has no track record of success, as it’s a new drug. Doctors have been given no access to the data proving it’s beneficial effects. There has also been no data shared about the drug’s ability to reduce a patient’s viral load, a key marker of success for an antiviral drug. The other — the four-drug cocktail tested in Hong Kong — has a proven track record from the use of these drugs on other viral diseases like HIV/AIDS. The data showing the cocktail’s benefits for COVID-19 have been shared widely and published in a respected, peer-reviewed journal. The data also shows the impact the drugs have on reducing a patient’s viral load, though perhaps not by as much as doctors might have hoped. The task facing our healthcare providers is difficult enough already without us clouding their view of the treatments that work. Remdesivir is still an unknown, despite the hype surrounding it. I have seen through the years the dangers of relying on unproven cures and the damage done to patients when we allow ourselves to be deceived by hope and ignore the data. This article originally appeared in Forbes and is available online here: Which COVID-19 Antivirals Actually Work?
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Why Weren’t We Ready For The Coronavirus? Forbes | May 12, 2020 | Article
The latest issue of the New Yorker asks the question that many of us have asked ourselves: Why weren’t we ready for the coronavirus? My reaction when I read the article was that those of us who have warned for years of coming respiratory pandemics were finally no longer alone. Though my colleagues and I each hold different fears of what nature has in store for us, my own pet fear is a reprise of an entirely new variant of influenza. Such an epidemic could kill 1 to 2 billion – not a misprint on the billion – assuming our post COVID-19 world looks much like what our pre-COVID world looked like. The New Yorker article traces the deep roots of inaction not only in the United States but throughout the world. After all, it was lack of preparedness in China that allowed the pandemic to emerge. That the virus has spread so widely is not China’s problem, it is the problem of all nations that ignored the persistent warnings that an outbreak was imminent, warnings delivered in powerful and popular books, films and TV programs, as well as in defense department and intelligence briefs. Post 9/11 and SARS, all of our defense agencies carried out war game equivalents to model a highly transmissible, lethal virus pandemic. The consequences we witness today were all predicted accurately. Even the movie Contagion got it right, right down to the bats being the cause of the contagion. Only the truly ignorant can argue that COVID-19 was unpredictable. The first warning I sounded of another pandemic came thirty five years ago in testimony to the United States Senate. It came at the beginning of the greatest pandemic of our time, HIV/AIDS, which has killed more than 30 million people and currently affects another 40 million worldwide. We are still not beyond that pandemic. For those of you who doubt its power, know that on a visit to Durban, South Africa three years ago I discovered that 70%
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(again not a misprint-70%) of young women between the ages of 25-25 were infected by HIV. To be one of many ignored prophets-in-our-own-time is not a happy feeling. It is deeply frustrating to know that very few, perhaps as few as ten people, needed to have died from COVID-19 before we could have stopped the infection in its tracks. If we had stockpiled one of the several anti-SARS drugs discovered in the early 2000s (as we stockpile drugs to protect us from bioterrorists) we could have administered it prophylactically to all those in contact with the first cases. That would have stopped the infection cold. China doesn’t have it handy. We don’t, no-one does. A massive collective failure. What happened? Those drugs lay dusty on the shelves in China, in Singapore, in Hong Kong, in Europe, in the United States, and in the Emirates and Saudi where they were discovered and shown to work in animal models of both SARS and MERS. We now know many work against SARS-CoV-2 at least in the test tube. Only now,15 years later are they being frantically resurrected. Talk about an opportunity missed. What hurts more is that those who developed that anti-SARS and anti-MERS drug knew what they had. They warned repeatedly that another coronavirus infection was imminent and that drugs, if stockpiled, could save us. How terrible that foreknowledge is as we see hundreds of thousands die and many millions infected. Governments and some of the most well-intentioned citizens around the world are good a saying “Let us never need say never again?” But we fail collectively in undertaking the necessary action to assure that predictable calamities do not strike again and yet again. This article originally appeared in Forbes and is available online here: Why Weren’t We Ready For The Coronavirus?
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Rapid, Accessible, Affordable, Ubiquitous Tests For SARS-CoV-2 Are On The Way Forbes | May 12, 2020 | Article
We need rapid, accessible, affordable and ubiquitous tests to detect those who are actively infected and can infect others. The good news is that they are coming soon. SARS-CoV-2 genome tests The first type of test to detect active infection measures the presence of the virus genome. These tests measure the presence of the virus in nasal and oral secretions or in sputum samples taken from the lung. The genome of SARS-CoV-2 is RNA which can be detected using several techniques. The advantage of genome tests is that can be very sensitive. Genome tests are also specific, that is they detect only SARS-CoV-2. The disadvantage of the first generation genome tests is that the samples must be sent to a laboratory for testing and that the materials and equipment for such tests are in short supply. This means there aren’t enough tests to go around and test results are too long in coming. The speed of viral genome tests can be improved to yield results in 5 to 15 minutes but at the sacrifice of sensitivity. The rapid genome tests now deployed may miss up to 25% of those actually infected. New CRISPR based tests to detect viral RNA may be fast but they are also less sensitive than the early laboratory based genome tests. SARS-CoV-2 antibody tests A second type of test measures antibodies to SARS-CoV-2. Antibodies are made by our body in reaction to the infection. Anti SARS-CoV-2 antibodies appear in the blood beginning one to two weeks after infection and may persist many months thereafter. Antibody tests are rapid, with results known within 5-20 minutes, and can be made inexpensively in large quantities. They are also easy 157
to use, with no complex machinery needed (think over-the-counter pregnancy tests). Such tests are now available. The US Food and Drug Administration is now assuring that only tests that meet their criteria for accuracy and reliability can be sold, resolving some the early issues with these tests. The disadvantage is that antibody tests do not measure the presence of the virus itself. They only measure the body’s reaction to the virus. Such tests will miss the early stages of infection, a time before symptoms appear when people are most likely to transmit the virus. What is needed is a test that combines the detection of the virus itself but is cheap to make and easy to use. SARS-CoV-2 viral protein tests (antigen tests) Tests for the presence of viral proteins satisfy the need to detect infection before the body has a chance to make antibodies and the need for easy to make, inexpensive rapid tests, tests that can even be self-administered. SARS-CoV-12 is made of proteins that protect the genome, provide the machinery for virus reproduction, and allow the virus to attach to and enter our cells. These proteins can be detected in nasal and oral secretions and in the sputum of the infected person. Typically, the protein detection tests employ antibodies that attach to the proteins. Such tests can be very accurate and rapid. They are also inexpensive to make and easy to use. The virus proteins are also called antigens because they cause the body to make antibodies. Such tests are often called antigen tests— not to be confused with antibody tests. Such protein based tests are currently used for the detection in blood (usually by finger stick) of the HIV, influenza, and dengue viruses and malaria. A potential disadvantage is the sensitivity of the tests. They may miss people who are actually infected but produce only a low level of virus. The sensitivity of such tests can be improved over time. I am pleased that these tests are now being developed by some the biggest diagnostic companies with years of experience in manufacturing and distribution, even in low resource settings,
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including Roche, Quidel, and Becton Dickenson. Several smaller companies are actively developing such tests as well. In an earlier story I estimated that the United States needs up to one billion virus detection tests per year. Others estimate the need at ten billion tests per year. SARS-CoV-2 protein detection tests are the only practical way to meet this demand. Thank goodness they are on the way. This article originally appeared in Forbes and is available online here: Rapid, Accessible, Affordable, Ubiquitous Tests For SARS-CoV-2 Are On The Way
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One Step Closer To Understanding The Origin Of SARS-CoV-2 Forbes | May 13, 2020 | Article
Whence SARS-CoV-2, the cause of so much human suffering in the US and around the world? The very first sequence of the virus genome told us much of the story. The virus resembled that which caused the original SARS epidemic (now called SARS-CoV-1) in 2002-2003. Both were members of the same family, beta-coronaviruses. Both had close, but different, relatives in bats from southern China. Both attach to human and animal cells via the same receptor, the ACE2 protein. Yet there are differences. SARS-2 is about 76% identical to SARS-1. SARS-2 is actually much closer to a previously isolated bat coronavirus than it is to SARS-1. The region that binds to the receptor much more closely resembles that of a pangolin coronavirus. Also the region preceding the part of the virus protein essential for penetrating cells, called the fusion peptide, contains an additional four amino acids, a feature that had not been previously observed for any other coronavirus including SARS-1. A recent paper in the journal Current Biology describing yet another coronavirus from a bat in Southern China adds valuable information to our understanding of SARS-2. The authors isolated 227 coronaviruses from bats in the southern province of Yunnan, China. One of the isolates, RmYN02 is remarkably similar to SARS-2 (93.3% overall). That part of the virus which specifies the enzymes required for replication showed an even greater similarity (97.2%). The region corresponding to the ACE2 receptor binding site of SARS-2 differs markedly from that of RmNY02. It is unlikely that RmYN02 uses the same receptor. The most remarkable finding was that like SARS-2, RmYN02 carries a four amino acid insertion in precisely the same location preceding the fusion peptide. These are the only two coronaviruses known to carry such an insertion. The inserted amino acids are 160
different between the two viruses, but share the same biochemical properties. This suggests that although the evolutionary origin of the insertion is different, the function is similar. These observations reinforce the close relationship between SARS-2 and other coronaviruses found in nature. Recombination among coronaviruses is well documented. A likely hypothesis is that a bat coronavirus very similar to that of RmYN02 recombined with another coronavirus, possibly of pangolin origin, to acquire the ACE2 receptor binding domain. What had been thought to be a unique feature of SARS-2, namely the four amino acid sequence preceding the fusion peptide, is now shown to be a feature of other naturally occurring coronaviruses. This work brings us one step closer to understanding the origins in nature of SARS-2. The study also reminds us that we must continue an intensive study of coronaviruses in bats and other animals. Recall that the coronavirus epidemic preceding COVID19 is thought to have originated from an Egyptian tomb bat that infected camels. That virus continues to infect humans who are in closely proximity to camels and sometimes spreads from human to human as well. It is a shame that the US administration ordered defunding of one of the premier groups of virus hunters because of their association with a Chinese lab, especially now when we need the information most. This article originally appeared in Forbes and is available online here: One Step Closer To Understanding The Origin Of SARS-CoV-2
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Progress And Possibilities For Treating COVID19 Forbes | May 14, 2020 | Article
Steady progress is being made in the treatment of patients hospitalized for COVID-19. The advances come together with the understanding that the disease is far more complex than a simple pneumonia. The most recent progress comes from a May 6th report in the Journal of the American College of Cardiology examining medical records of 2773 COVID-19 patients in five New York City hospitals. The study was initiated after the realization that COVID-19 disease includes the formation of life-threatening blood clots. These clots can cause heart attacks, strokes, kidney failure, and additional lung damage. Such clots are often the cause of death in younger patients too. The records were examined to determine what impact blood thinners had on a patient’s survival and the length of time to discharge or death. Of the patient records studied, 786 having received a full treatment dose of anticoagulants. Those patients were further divided into those who were intubated and those who were not. The most striking results were observed for those with the most serious disease who were intubated. The survival rate rate of intubated patients treated with anticoagulants was 70.9% as compared to 37.3% for who did not. The time to discharge from the hospital for those who did survive was also shorter for those who received anticoagulant therapy as compared to those that did not. This is very good news. Not long ago another New York hospital system reported that 88% of intubated COVID-19 patients died. Still, there is much more work to do. Several anticoagulants are approved for use. Which one and in what dose is best for what type of patient? Hospitals are beginning to be much more selective about which patients are intubated and which are not, recognizing the complex course of the disease.
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Infusing a patient with serum from a COVID-19 survivor has yielded promising results in preliminary trials. Efforts to improve serum based treatments by purifying and concentrating the responsible antibodies are in progress. These will be followed by administration of monoclonal antibodies, the best form of serum based therapies. I recently described an independent study from Hong Kong demonstrating the benefit of a four drug cocktail of antiviral drugs that both reduce the time to discharge and the viral load of patients with mild to moderate COVID-19 symptoms. All of the drugs in the "Hong Kong Cocktail” are approved for the treatment of viral diseases and, importantly, are generic and abundantly available. I have also reviewed the published evidence for some if the most highly touted drugs including hydroxchloroquine and remdesivir and do not find the data convincing. Fortunately, drugs and treatments that have statistically significant effects on the course of the disease are coming into view. Doctors around the world recognize that much of the damage to the lung and the organs is inflicted not by the virus directly but rather as a consequence of an overactive immune response called a cytokine storm. Many already approved drugs that modulate the immune response, including many used for the treatment of arthritis and other autoimmune diseases, are currently being tested in COVID-19 patients. Some have failed to make a difference but there are existing and new drugs still left to try. Once a drug is shown to improve outcomes the next course is clear: Learn to make the best use of that drug—determining who to give it to, when to give it, and in what dose. The next steps are also clear— combine two different treatments, for example the Hong Kong Cocktail with anticoagulant therapy. Add anti-cytokine storm drugs if and when they are shown to work. All this progress can and has made a real difference for COVID19 patient survival. The goal is to save as many lives as possible with existing drugs until such time as new drugs that specifically target SARS-CoV-2 come on line. This new generation of drugs should stop the virus altogether before it has a chance to cause much damage. Many such drugs are now entering human trials and there are many more to come. Then we can be confident that there is a cure for COVID. 163
This article originally appeared in Forbes and is available online here: Progress And Possibilities For Treating COVID-19
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COVID-19 Among Children Forbes | May 14, 2020 | Article
Recent reports that SARS-CoV-2 can cause serious life-threatening disease in young people is not good news. A few cases of a Kawasakilike vascular inflammation in kids age 2-15 were previously noted. As more cases have been identified, more than 100 in New York State alone, this aspect of the disease is coming into focus. The syndrome, now called pediatric multisystem inflammatory syndrome, appears to be a late sequela of infection in young people appearing anywhere from a week post first symptoms to at least as long as five weeks. Critical symptoms include high fever of 102-103 degrees, abdominal pain, diarrhea, and a rash (localized or whole body). Should these symptoms appear, regardless of prior disease or even known exposure, the child should be taken to the emergency room immediately for evaluation. The syndrome can be accompanied by heart disease, including cardiac arrest and aneurisms that can be life threatening. The disease has been described as a combination of Kawasaki-like symptoms and toxic shock, a syndrome which became familiar to many because of its association with tampon use. Previously, it was thought that children were mostly spared the ravages of this pandemic. But it seems they too are also at risk. There is no silver lining to this news. Our only hope is that this development may change calculus of premature reopening. Our churn are not spared the dangers of COVID. While some may have been willing to trade the life of the elderly for economic and electoral success, I doubt that few, if any, feel the same way about our children and our grandchildren. This article originally appeared in Forbes and is available online here: COVID-19 Among Children
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What AIDS Taught Us About Our Coronavirus Response Project Syndicate | May 15, 2020 | Article
Thirty-five years ago, in the midst of the new and still somewhat unknown AIDS epidemic, I warned in testimony to the US Congress that we were facing another deadly episode in the long battle between humankind and microbes. If asked to testify again I would say the same thing today. Just as it is impossible for us to control tsunamis, earthquakes, and volcanic eruptions, our ability to subdue contagious outbreaks is more limited than we like to admit. Despite what we often tell ourselves, we cannot always impose our will upon the natural world. This article originally appeared in Project Syndicate. The full article is available here: What AIDS Taught Us About Our Coronavirus Response
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Did The Oxford COVID Vaccine Work In Monkeys? Not Really Forbes | May 16, 2020 | Article
The day after data appeared from the vaccine maker Sinovac showed complete protection of rhesus monkeys by their vaccine candidate (whole inactivated SARS-CoV-2 virus particles), scientists from the Jenner Institute in Oxford issued a press release announcing that their vaccine (an adenovirus vector based vaccine that carried the SARSCoV-2 spike protein) worked to protect rhesus monkeys and that they were moving forward with large scale human safety trials. At the time, the substantiating data was not available. Now it is, in the form of a May 13 BioRxiv preprint. Does the data support the claim? Not really. All of the vaccinated monkeys treated with the Oxford vaccine became infected when challenged, as judged by recovery of virus genomic RNA from nasal secretions. There was no difference in the amount of viral RNA detected from this site in the vaccinated monkeys as compared to the unvaccinated animals. Which is to say, all vaccinated animals were infected. This observation is in marked contrast to the results reported from Sinovac trial. At the highest dose studied, no virus was recovered from vaccinated monkeys from the throat, lung, or rectum of the vaccinated animals. There is a second troubling result of the Oxford paper. The titer of neutralizing antibody, as judged by inhibition of virus replication by successive serum dilutions as reported is extremely low. Typically, neutralizing antibodies in effective vaccines can be diluted by more than a thousand fold and retain activity. In these experiments the serum could be diluted only by 4 to 40 fold before neutralizing activity was lost. Again, by contrast the titer of neutralizing antibodies in the serum of those vaccinated with whole inactivated SARS-CoV-2 was high. What then is the argument for pressing forward with the adenovirus vector SARS-CoV-2 spike protein vaccine?
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The authors present evidence to the effect that, although the vaccine did not protect the animals from infection, it did moderate the disease. The vaccinated and control animals were followed for clinical signs of infection for seven days post infection. One clinical sign of infection in rhesus monkeys is breathing rate. Monkeys ill from SARS-CoV-2 infection breathe more rapidly than normal. By this measure 3 of the 6 vaccinated monkeys were clinically ill, the remaining three were not clinically distinguishable from the unvaccinated animals. A second test is measurement of the amount of virus in the lungs (bronchial lavage). Viral RNA was detected in the bronchial lavage of 2 of the 6 vaccinated animals and in all three unvaccinated animals, again suggesting only partial protection. At day seven post challenge the animals were euthanized and examined for lung damage. Two of the three unvaccinated animals “developed some degree of interstitial pneumonia” as judged by pathological examination of the lungs. No such damage was observed in any of the vaccinated animals. It is encouraging that no evidence of vaccine induced disease enhancement was observed in either the Sinovac vaccine nor the Oxford trials. However, experience with other vaccines tells us that is not a firm guarantee that such will be the case for humans. What to make of this data? It is crystal clear that the vaccine did not provide sterilizing immunity to the virus challenge, the gold standard for any vaccine. It may provide partial protection. The question then becomes: Will partial protection be enough to control the COVID-19 pandemic? That is an open question. For an answer we can look to other diseases for which only partially effective vaccines exist—HIV, tuberculosis, and malaria. The answers are not encouraging, except perhaps for the protection of childhood malaria. What are the potential implications for other vaccine trials? We know adenovirus is a good vector for eliciting protective responses for protein coding genes of other viruses, in fact better than many others. This then raises the question of whether vaccine strategies based on the delivery of viral antigens by nucleic acids, be it DNA or RNA, will suffice. From the published data the nucleic acid of
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select viral genes and proteins delivery technology seems inferior to a whole killed virus vaccine approach. What then are the choices for the Oxford group? Steam ahead with a vaccine known to be partially effective at best, one which we already know elicits poor neutralizing responses? Work to improve the immunogenicity of the current vaccine? Attempt trials with combinations of two or more vaccines, a prime boost strategy? These questions are all the more fraught by what we already know about the complexities of antibody reposes to natural infections. For example, we know in the case of SARS and other coronavirus infections that even high titers of neutralizing antibodies fade quickly over time. How long can we expect weakly neutralizing antibodies to protect? We know what the public response is of the Oxford group and their collaborators. Proceed with full speed to human safety then efficacy trials. Time will tell if this is the best approach. I wouldn’t bet on it. This article originally appeared in Forbes and is available online here: Did The Oxford COVID Vaccine Work In Monkeys? Not Really
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MIS-C: A New Name For COVID Kawasaki/Toxic Shock In Young People Forbes | May 18, 2020 | Article
There is a new name for a recently recognized set of COVID-19 related symptoms in children and adolescents. The World Health Organization and the US Centers for Disease Control and Prevention have assigned the name Multisystem Inflammatory Syndrome in Children or MIS-C to this disease. The name attempts to encompass the many facets of the disease in young people. MIS-C symptoms may include skin rashes, reddening of the toes and fingers, shortness of breath, fever, diarrhea muscle aches and fatigue. The symptoms regularly appear late in the course of the disease. Young people who may have only mild symptoms following initial infection and then appear to fully recover, sometimes experience the symptoms of MIS-C several weeks later. Lifethreatening symptoms like heart failure may have a sudden and unexpected onset, requiring immediate life support. Initially young children, except those with serious underlying diseases, were thought to be largely unaffected or experience only mild symptoms following SARS-CoV-2 infection. That picture is rapidly changing with the realization of late onset life- threatening disease in children and adolescents. MIS-C is still believed to be an infrequent outcome of infection. This may or may not prove to be the case as we learn more about the long term effects of the disease in children in young people. The name MIS-C attempts to summarize our current understanding of the syndrome. The term Multisystem reflects the recognition that many organs in the body may be involved. The affected organ systems differ from person to person. Only one or many organs may be affected in a single individual. Organs affected include the heart, kidney, lung, skin, blood, blood vessels as well as gastrointestinal and nervous systems.
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The name Inflammatory reflects what many believe to be an underlying cause, inflammation of the organs and specific tissues. One hallmark of the disease is elevation of markers of generalized inflammation in the blood. Red toes and fingers may also reflect inflammation of blood vessels. Syndrome is a word used to describe a diverse set of signs and symptoms the cause of which is not definitely known. The term fits loosely here as the primary cause is infection by SARS-CoV-2, the virus that causes COVID-19. MIS is followed by “-C”. The C stands for child. The collection of symptoms has been observed mostly in young and adolescents 15 or younger. A similar set of late onset symptoms have been observed in young adults up to the age 30. It may be the “-C” will eventually be modified, as the late consequences of COVID-19 are only now being fully understood in patients of all ages. It is not uncommon for adults to continue to experience COVID related symptom for many weeks past initial recovery. Relapses with a complex sets of symptoms including fever and even continued virus detection have been noted. The realization that school age children and adolescents may also suffer serious and life-threatening consequences is causing some to reevaluate the wisdom of opening summer camps and re-opening schools in countries and communities were new infections persist. Let’s remember we are still less than half a year into the pandemic. Even so, we are beginning to learn it is far more complex than a simple pneumonia both in the short and long term. We have yet to understand the full impact of infection on a body any age. For those interested in learning more about our emerging understanding of MIS-C, consider the following resources: This article in the Guardian describes attempts to provide blood tests that will assist doctors in diagnosing young people who either have MIS-C or are at risk. They will test the blood of children known to be infected by SARS-CoV-2 for markers of inflammation. I suggest that this test be used for adults too. Please note that the article describes “hundreds” of children in Europe with MIS-C. This article from the Michigan Health Lab is a clear description of MIS-C. Required reading to understand the disease. This link is from the US Centers for Disease Control and Prevention and summarizes childhood COVID-19. 171
This story in the Washington Post describes a single instance of COVID in a child. Happily, this hair-raising story ends well. This story in the New York Times is a vivid description of what COVID related MIS-C can feel like to an adolescent. This is an important story for parents, grandparents, and everyone under 30 to read. This article originally appeared on Forbes and is available online here: MIS-C: A New Name For COVID Kawasaki/Toxic Shock In Young People
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Moderna’s Claim Of Favorable Results In Its Vaccine Trial Is An Example Of ‘Publication By Press Release’ Washington Post | May 19, 2020 | Article
Faith in medicine and science is based on trust. But today, in the rush to share scientific progress in combating COVID-19, that trust is being undermined. Private companies, governments and research institutes are holding news conferences to report potential breakthroughs that cannot be verified. The results are always favorable, but the full data on which the announcements are based are not immediately available for critical review. This is "publication by press release,” and it’s damaging trust in the fundamental methods of science and medicine at a time when we need it most. The most recent example is Moderna’s claim Monday of favorable results in its vaccine trial, which it announced without revealing any of the underlying data. The announcement added billions of dollars to the value of the company, with its shares jumping almost 20 percent. Many analysts believe it contributed to a 900-point gain in the Dow Jones industrial average. The Moderna announcement described a safety trial of its vaccine based on eight healthy participants. The claim was that in all eight people, the vaccine raised the levels of neutralizing antibodies equivalent to those found in convalescent serum of those who recovered from COVID-19. What to make of that claim? Hard to say, because we have no sense of what those levels were. This is the equivalent of a chief executive of a public company announcing a favorable earnings report without supplying supporting financial data, which the Securities and Exchange Commission would never allow. There is a legitimate question regarding what Moderna’s unsupported assertion means. The scientific and medical literature reports that some people who have recovered have little to no 173
detectable neutralizing antibodies. There is even existing scientific literature that suggests it is possible neutralizing antibodies may not protect animals or humans from infection or reinfection by coronaviruses. Such “publication by press release” seems to be a standard practice lately. The National Institutes of Health announced last month that the drug remdesivir offered a clear benefit to COVID19 patients with moderate disease, shortening the length of their hospital stay by several days. But did it really? Twenty days after the announcement, the supporting data has still not been published. Without the data, no doctor treating a patient can be sure they are doing the right thing. Another paper, published the same day, found that remdesivir had no measurable effect on patient survival or the amount of virus detectable in nasopharynx and lung secretions. What then should a practicing physician do? Follow the unsupported advice of a news announcement or a medical report published in a leading scientific journal? This is not an idle question: The NIH announcement triggered a global stampede for limited supplies of the drug. The case is more nuanced for the vaccine developed by the Jenner Institute at Oxford University, though the mileposts remain the same: It started with a public pronouncement of favorable results from an early study, this time in monkeys, well before any data was publicly released. An NIH scientist working on a trial of the Oxford vaccine gave an interview to the New York Times, claiming the drug was a success. But the data, released as a prepublication version more than two weeks after the story ran, didn’t quite live up to the early claim. All of the vaccinated monkeys became infected when introduced to the virus. Though there was some reduction in the amount of viral RNA detected in the lungs, there was no reduction in the nasal secretions in the vaccinated monkeys. So the positive result reported by the Oxford group turned out not to be protection from infection at all, something most would agree is what a successful vaccine would do. Instead, it lowered only the amount of virus recoverable from the vaccinated monkey’s lung. To the Jenner Institute’s credit, it does warn visitors to its website that there have been many false reports about the progress of its vaccine trial. Still, having a scientist working on the trial paint 174
preliminary results in such a positive manner without having yet released the full data is cause for concern. We all understand the need to share scientific and medical data as rapidly as possible in this time of crisis. But a media announcement alone is not enough. There are ways to share the data quickly and transparently: posting manuscripts before review or acceptance on publicly available websites or working with journals to allow an early view. Publishing in this manner allows doctors and scientists to reach their own conclusion, based on the evidence available. The media also bears responsibility. Asking experts to opine on unsubstantiated claims is not useful. Medicine and science are not matters of majority opinion; they are matters of fact supported by transparent data. This is the backbone of scientific progress and our only hope to end this pandemic. We can’t give up on our standards now. This article originally appeared in the Washington Post and is available online here: Moderna’s Claim Of Favorable Results In Its Vaccine Trial Is An Example Of ‘Publication By Press Release’
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What Happens If We Can’t Find A Coronavirus Vaccine That Works? Forbes | May 26, 2020 | Article
Last Friday, amidst all the heat, hype, and big bucks that greeted even the most modest advances in COVID-19 vaccine development in the United States, a far more sober assessment came from our friends across the pond: “Why We May Not Get a Coronavirus Vaccine.” Evidently British restraint, coupled with Boris Johnson's tangle with COVID, has infused a dose of reality into the country’s expectations of what a COVID vaccine might and might not do. This is a reality check for which the American government is long overdue. To repeat my own warnings on the subject, the question we must reckon with is not when, but if we will find a COVID vaccine that is safe and effective for everyone. If we acknowledge the reality that the vaccines currently being tested might fail or protect only some of us, what policy choices can our lawmakers and elected officials enact now that will ensure our protection no matter the outcome? If all vaccines fail, the answer is clear. Use what we know works to radically reduce infection in our populations. Identify those infected, symptomatically or via testing; identify those exposed through rigorous contract tracing; and mandate a period of 14-day controlled isolation for all those exposed. Then, continue the policy indefinitely to prevent re-occurrence during the pandemic. East Asian countries proved that is the best way to drive the infection rate to zero or near zero. We should all remember the entire pandemic began as a single infection in a faraway country. A single infection at home, absent a vaccine, could restart this terrible cycle. If the vaccine completely protects only the young and healthy, again, the answer is clear. Vaccinate everyone, without regard to age, economic income, or geography. Urge caution for the elderly and anyone else who may not respond because of preexisting 176
medical conditions. Understanding that the danger of a renewed epidemic is real, continue the policy of identification, contact tracing and mandatory isolation. If the vaccine partially protects the young and not the elderly, then we will be facing the most likely outcome. Current vaccines may protect the young from dying of lung disease but may not prevent nasal infections and possibly other complications. They may still transmit the virus. The most vulnerable populations will remain at high risk of dying. In that case, we will have no recourse other than to maintain a high level of vigilance and infection control via detection, contract tracing, and isolation. There is a very real possibility that we will develop effective antiviral drugs that both cure those ill and prevent infection of those exposed. I recently wrote about the 100 Million Healthy Lives program in Egypt. Over the course of one year, everyone in the country 12 years and older—a total of 65 million people—was screened for hepatitis C infection, a silent condition. Those with active viremia were treated and cured. Hepatitis C is now eliminated from Egypt. The cost was modest, less than $250 million for the entire program. That is a future we can look forward to if we are fortunate enough to have the drugs to do the job. Even so, until COVID is gone from the face of the earth, the policy of identify, trace and isolate must remain. Creating sound public policy in the face of uncertainty is difficult, but that it is the job of government. Governments exist to protect us all. Let’s hope that they are up to the challenge. This article originally appeared in Forbes and is available online here: What Happens If We Can’t Find A Coronavirus Vaccine That Works?
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It’s Too Early For The US Government To Place Risky, Billion Dollar Bets On COVID Vaccines Forbes | May 26, 2020 | Article
As American taxpayers, we are justified in asking why the United States government is giving a billion dollars to a British-Swedish pharmaceutical company, AstraZeneca, to develop a very early stage COVID-19 vaccine. Mind you, I am not particularly upset that AstraZeneca is British company, nor that the vaccine candidate was developed by an English research team. I have questioned government funding of Moderna, an American company, as well. My concerns are several. First, AstraZeneca is an incredibly profitable pharmaceutical company. Last year, their sales grew at a rate of 12 percent to a total of $23.5 billion. Profit margins on their proprietary pharmaceutical products are typically in the range of 80 percent. And their budget for advertising and promoting those products? Also in the billions. Given this, does AstraZeneca really need an additional business incentive of a billion dollars to fight a disease that has devastated economies the world over, and more particularly their own market for drugs? It is well documented that stay-at-home practices have significantly reduced doctor’s visits and pharmaceutical sales. Creating a vaccine would seem to be in the company’s best interest, as well as a public service for which they might be well paid. My second concern is that our government is placing a bet on very specific vaccine candidates. Why those vaccine candidates when more than 100 are in the running? Another company using technology nearly identical to that behind the AstraZeneca candidate already published the results of its first human trials—and they were decidedly mixed. Such was the case with the Oxford vaccine candidate recently tested in nonhuman primates, too. The data suggested that this class of vaccines may only protect us partially, reducing virus growth in the lungs, but not primary infection in the nose. 178
The United States government made a similarly speculative and risky bet when it gave nearly half a billion dollars to a well-funded American biotech company, Moderna, to test an unproven technology with no previously approved or marketed products. My third concern is transparency. Who made the decision to use taxpayer dollars in this way? On what basis was the decision made? What alternatives were considered? What was the justification for the amount allocated? Will the companies be held to strict reporting and accounting standards? Was the allocation of public funds open and transparent? I can’t answer any of these questions based on information available to the general public. Is it right? Is it even legal? I am in favor of government support of broad vaccine research and development. We also know that creating vaccines to protect against COVID is not likely to be easy. But why should the United States government pay companies with robust finances many hundreds of millions of dollars to do what is already in their best interest? Why place such early bets on such early stage products when the warning on the limitations of their approach are already flashing? It is rumored that Napoleon Bonaparte once said to his valet, “Dress me slowly, I am in a hurry.” Yes, we must proceed with a sense of urgency. But let’s be careful and strategic in how we use our valuable resources. This article originally appeared in Forbes and is available online here: It’s Too Early For The US Government To Place Risky, Billion Dollar Bets On COVID Vaccines
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Remdesivir Revealed
Forbes | May 26, 2020 | Article
The full data from the remdesivir trial by the National Institutes of Health (NIH) has finally been released, weeks after preliminary results were shared via press release. Those early results generated a great deal of hype and a world wide stampede for the drug. But the release of the full data tells a different story. The conclusion of the NIH study, published in The New England Journal of Medicine, states: “These preliminary findings support the use of remdesivir for patients who are hospitalized with COVID-19 and require supplemental oxygen therapy. However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient. Future strategies should evaluate antiviral agents in combination with other therapeutic approaches or combinations of antiviral agents to continue to improve patient outcomes in COVID-19.” There are a few problems this paragraph highlights. First, by opening with a reference to the data “preliminary findings” the authors are acknowledging the fact that this is not a definitive study. How could it be with such scant data? Ideally, this NIH trial and other remdesivir trials would continue to gather evidence to support the findings. But the NIH controversially ended their large trial of the drug and Gilead has suspended smaller trials. More study of the drug will still be conducted through the WHO Solidarity Trial and the Inserm DisCoVeRy Trial, so there is at least a glimmer of hope that we will eventually have robust and transparent data that shows the true impact of the drug on viral load. Second, the patients who benefit from the drug are those “who are hospitalized with COVID-19 and require supplemental oxygen therapy.” Why must patients be hospitalized to receive the drug? Because the drug has to be administered intravenously, through an in-dwelling catheter. This means that patients cannot take the drug from their homes. The data, preliminary though it is, shows that the drug only helps those with moderate COVID-19. If you view the 180
severity of COVID-19 on an eight point scale, with one being those not hospitalized and 8 being dead, the drug only helps those in groups 4 (hospitalized, but no need for extra oxygen) and 5 (hospitalized and needing oxygen). In other words, the drug is only useful for those who are likely to recover anyway, with or without remdesivir. The data here and in another published study shows the drug has no measurable effect in patients with serious disease. We also don’t have any proof that the drug prevented progression of the disease from serious to lethal. The next section contains a more ominous caveat and a dubious proposition. The caveat is included in the sentence that says “given the high mortality rate despite the use of remdesivir,” which suggests that patients who received a high dose of remdesivir intravenously for ten days continued to die at the same rate as the placebo group. This is troubling as it calls into question whether the enthusiasm for Gilead is justifiable in any sense, if the same number of people who fall ill with the disease will continue to die. The dubious proposition is in the section that says “it is clear that treatment with an antiviral drug alone is not likely to be sufficient. Future strategies should evaluate antiviral agents in combination with other therapeutic approaches or combinations of antiviral agents to continue to improve patient outcomes in COVID-19.” How can the authors be so sure that an antiviral drug alone won’t work against COVID-19 when antiviral cocktails can cure those with hepatitis C and treat those with HIV/AIDS? And why are they not explicitly suggesting remdesivir as part of a future strategy to evaluate antivirals with other therapeutic approaches? As far as conclusions go, this one does not give us much to hang our hats on. A deeper dive into the trial design, changed and truncated midcourse as it was, shows that “time to discharge” is one of the weakest criteria by which to gauge the success of a drug therapy. Rigorous criteria include reductions in mortality or, at a minimum for antivirals, reduction of viral load before and during treatment. That is how you know an antiviral drug is working as it is supposed to work. Apparently preventing death and measurement reduction of viral load was not part of the trial design. Is a skeptic allowed to ask why? Perhaps because the previously published study found no such effect. Is remdesivir the “fuzzy wuzzy drug” like the bear with no hair, an antiviral that has no antiviral effect in people? 181
Doctors and patients both have the right and the need to know how well the drug works and who it works for. Does this drug save lives and does it reduce viral loads? Impossible to know even with the full data from the NIH study which ended too soon. The need for urgency does not justify incomplete and poorly designed trials. Doctors and patients are hungry for clear, definite answers. NIH and Gilead know how to design and to present such trials that give comfort and guidance to practicing physicians. To do less is a dereliction duty. This article originally appeared in Forbes and is available online here: Remdesivir Revealed
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Will Memorial Day 2020 Be Remembered As The Holiday When COVID-19 Got The Upper Hand? Los Angeles Times | May 26, 2020 | Article
We may have the reason to remember Memorial Day 2020 as the holiday when COVID-19 exploded. Looking around the country over the weekend, there was little evidence that people were making the sacrifices needed to save their own lives and those of their friends and family. In preparation for a TV interview on Monday afternoon, I compared Sunday’s COVID case reports with those of a month ago. The numbers tell an interesting — and worrying — tale. First the good news: On March 30, New Jersey reported 3,250 new cases of COVID-19 to New York’s 9,000. No one who lives in Manhattan, as I do, will forget that day of constant sirens. On Saturday, two months later, the number of new cases in New Jersey was 1,050, down about 60% In New York, 1,772 new cases were reported on Saturday, down about 80% from March 30. Because of social distancing and mask wearing, which we now know work, the epidemic in both places, while far from over, is waning. Now the bad news: On March 30, the numbers of new cases for Illinois was 460 and for Wisconsin 109. On Saturday, Illinois reported 2,508 new cases, a more than fivefold increase. Wisconsin reported 400 new cases, a nearly fourfold increase. Yet on Monday’s holiday, in the midst of a rapidly growing epidemic in the state, Wisconsin lake shores were packed with maskless celebrants. Many Southern states are also seeing a rise in cases. Compared with March 30, COVID cases are up about threefold in Alabama, Arkansas and Texas. The epidemic has not abated in Georgia, Florida and Ohio, where the numbers of new cases is close to what it was two months ago. In California, COVID cases are still on the rise.
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When holiday revelers were asked on camera why they were out and about as normal over the weekend, the usual answers were some variation of “The cure is worse than the disease” or “The infection is rarely lethal, less than 1%.” Do these people remember that so far nearly 100,000 Americans have died? And that figure doesn’t even count the seriously ill. About 20% of those who get the virus get very, very sick. When you ask those survivors to talk about what they went through, it’s an alarming picture. They describe exquisite pain while acutely ill and long-term consequences after the virus has run its course. Some will be on kidney dialysis for the rest of their lives. Some of the young children who caught the virus will have permanently weakened hearts. And, weeks after recovering, many who had the virus are still having trouble catching their breath and recovering their energy. Because I am a biomedical scientist who has brought new drugs and vaccines to market, I am often asked when we will have a vaccine. By October? By the end of the year? By early next year? My experience tells me the actual question should be not when we will have a new vaccine, but if. Success is by no means assured. Thirty-five years ago I predicted it might be decades, if ever, before we would have an effective vaccine for HIV/AIDS. We still do not have one. I do not think making a vaccine to prevent COVID-19 will be as difficult as for AIDS, but neither is it a “slam dunk” that a vaccine will come to our rescue. Why? For one thing, the ability to respond to a new vaccine decreases sharply with age, and it is older people who are hardest hit. In other words, those who need it the most might benefit the least, even if a vaccine is developed quickly. Also, infections like COVID-19 contracted though the lining of the nose are very difficult to prevent. If we do get a vaccine soon, it is likely to be only partially effective for the young and may not be effective at all for the old. And remember, a vaccine that is to be given to hundreds of millions, or even billions, of healthy people must be demonstrably safe before it is brought to market. That is a very tall order for any medication. So without any certainty of a vaccine savior, what can we do? We know what works: aggressive social distancing — which means
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staying at home — coupled with widespread testing, contact tracing and mandatory 14-day isolation for those exposed to the virus. To give up what we know works while hoping for a distant and highly uncertain medical miracle is folly, and we will certainly pay for it with many more lives lost and widespread economic ruin. This article originally appeared in the Los Angeles Times and is available online here: Will Memorial Day 2020 Be Remembered As The Holiday When COVID-19 Got The Upper Hand?
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The Way That COVID-19 Tricks The Immune System Could Result In More Severe Illness Forbes | May 27, 2020 | Article
The virus that causes COVID-19, SARS-CoV-2 (SARS-2), has a nasty trick up its sleeve. Upon infection, most viruses trigger a vigorous immune response from both arms of the immune system: a lymphoid response and a myeloid response. Interferons released from infected cells trigger the lymphoid response, resulting in antivirus antibodies which bind to and eliminate the virus from the body. T cells are also activated that can recognize and eliminate infected cells. The myeloid pathway works differently. Myeloid cells attack the virus and the infected cells directly. Some myeloid cells engulf and destroy virus particles, others kill the infected cells directly, and others still induce a protective inflammatory response by release of compounds called cytokines. The way SARS-2 affects both arms of the immune response is different from other viruses. The lymphoid pathway is muted and the myeloid pathway hyperactive. This helps explain why some people who recover from COVID-19 have very low, sometimes undetectable levels of anti-SARS-2 antibodies, and others have undetectable levels of “neutralizing” antibodies capable of the inactivating virus in laboratory experiments. Failure to induce high levels of protective antibodies may also be related to a poor memory of prior infections. The upshot is the real possibility that protection following infection may be transient. We know that people who recover from coronavirus colds can be reinfected by the same strain of virus a year later. We will learn over time whether that is true of COVID-19 as well. A hyperactive myeloid response, on the other hand, can result in the famous cytokine storm associated with the rapid decline and death of COVID-19 patients. The two phenomena may in fact be linked. An ineffective or weak lymphoid response may lead to 186
prolific virus replication. Large amounts of virus can in turn trigger a violent myeloid response, in some cases violent enough to kill. Detailed studies reveal how SARS-2 virus pulls off this trick. In addition to the genes the virus needs to reproduce—the replicative enzymes and the proteins that comprise the outer and inner shells the virus—coronaviruses produce many other proteins. They all go by the generic name open reading frame gene (orf), followed by a number and sometimes an additional letter to distinguish one from the other. That’s because we don’t know much about them or what they do, besides the fact that most aren’t needed to grow the virus in a test tube. This reminds me of my earlier work with HIV-1, the virus that causes AIDS. My Harvard group discovered six such proteins. Two were absolutely required for virus replication in a test tube, but the other four were not. Years of extensive study revealed that in fact, these proteins provided HIV-1 with a bag of tricks that allowed it to survive not only in the test tube, but in the much more rigorous environment of our bodies. I’ll bet dollars to donuts that a similar focus on the so called “accessory genes" of the COVID-19 viruses will reveal another set of tools they use to do their dirty work. And there are a lot of them. After all, SAR-2 contains three times the amount of genetic information as HIV-1. We have a hint of how one of those genes, named orf3b, works. Initial studies of SARS-1, the virus that caused the earlier SARS epidemic, reveal that the protein made by the orf3b down regulates the production interferons needed to trigger the first arm of the immune system—the lymphoid pathway responsible for producing antibodies and killer T cells. A recent study shows that the orf3b protein of SARS-2 does the same thing, only better. The protein made by orf3b in most strains of SARS-2 is shorter and more potent in tamping down the interferon response than that of SARS-1. That may be one of the reasons SARS-2 can be transmitted more efficiently than SARS-1. A weaker antibody response means than more virus particles are made. There is an ominous twist to the story. Two strains of SARS-2 isolated from very ill patients carry yet a third variant of orf3B. This variant is longer than that of the original SARS-1 gene. When tested, it turns out to be more potent than either in its ability to compromise 187
the interferon response. The implication? This may be one of the first signs that a more transmissible and lethal strain of SARS-2 will emerge, one that accelerates the pandemic still further. Watch this space! In dampening the antibody response to infection and ramping up production of chemokines, SARS-2 is amplifying what happens to us naturally as our immune systems age. While our ability to mount an effective antibody and T cell response to new infections declines, the myeloid arm of the immune system becomes overactive. These features of the aging immune system account for both the decline in our response to new vaccines and to an increase in inflammatory auto-immune disease such as rheumatoid arthritis. In other words, infection by SARS-2 tips the balance of a misregulated immune system still further, explaining what we know all too well: older people are at far higher risk of serious disease and dying from COVID-19 than the young. Every day we learn more about this virus and the disease it causes. Thank heavens that international cooperation and data sharing is at an unprecedented high. It is clear that we have a lot more to learn about how the virus goes about its business and how our bodies react to it. With each new insight come fresh ideas of how to protect ourselves. For now, I will give you just one. If one of the problems is that the virus down-regulates interferon production, why not supplement those infected with interferons we already use in the treatment of other diseases? Well, one of the two drugs added to a four-drug regimen—what I call the "Hong Kong Cocktail”—that reduces viral load and hastens the healing of mild to moderately ill COVID-19 patients is... an interferon! We are in this for the long haul. The scientific journey is just getting underway. I am confident that we can beat this disease with a combination of enlightened public health policies, transparent rigorous clinical trials, and the power of our science. This article originally appeared in Forbes and is available online here: The Way That COVID-19 Tricks The Immune System Could Result In More Severe Illness
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Key Protein That Leads To COVID-19 Infection May Be Less Common In Children, Researchers Find Forbes | May 27, 2020 | Article
Once inside the body, the virus moves around by attaching to the same ACE2 protein on other tissues deep in the lungs, the heart, and the kidneys. The receptor can also be found in the lining of blood vessels, and possibly even the taste buds on our tongues. This is one reason why COVID-19 patients may present such a diverse set of symptoms. A paper recently published in JAMA examines one measure of the amount of receptors in the noses of children and adults. I say one measure because what is measured is not the protein responsible for attachment, but rather the RNA which directs its production. Usually but not always, the amount of RNA in cells determines the amount of the corresponding protein. The authors assume that is the case, and their conclusion depends on that assumption. With that caveat in mind, they report finding less ACE2 RNA in cells scraped from the noses of children than in those from adults. Participants in the study were divided into four age groups: less than ten, 10-17, 18-24, and older than 24. The first conclusion is there was no difference in the amount of ACE2 RNA detected according to gender or those with or without asthma. The second conclusion is that the amount of ACE2 RNA increases with each age group. The differences are relatively small and the error bars large. The average relative amount of RNA ranges from 2.4 for those less than 10 to 3.09 for those 25 and older. However, when the probable range is included, the results from the three older groups overlap, as do the results from the three younger groups. Can we conclude that such differences imply a difference in overall susceptibility to infection? Possibly, but not certainly. We do not know how many receptors are needed for the SARS-CoV-2 189
virus to successfully infect us. Clearly children, even very young children, can be infected. Additionally, we do not know the efficiency of the conversion of RNA to the stable ACE2 protein that serves as a receptor. Also unknown is whether or not there are age related biological and behavioral factors other than ACE2 which determine susceptibility to infection. Such is science. We must collect data, analyze it for accuracy, and infer its meaning. Our job is to do our best to disprove our favorite hypothesis, so that it remains the only explanation left standing. Does this paper “prove” children are less susceptible to COVID-19 infection? Alas, no. Does it advance our understanding of ACE2 expression in the noses of different age groups? Marginally, yes. This article originally in Forbes and is available online here: A Key Protein That Leads To COVID-19 Infection May Be Less Common In Children, Researchers Find
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Confronting Barriers To COVID-19 Vaccine Acceptance Forbes | May 28, 2020 | Article
One of the questions I’m asked most frequently is when we will have a COVID-19 vaccine. To that I say, the question is not when, but if. If we don’t have a vaccine, we don’t yet know how safe and effective it will be. Given our well-documented difficulty developing coronavirus vaccines for SARS and MERS, and now the less than promising data from recent studies involving humans and nonhuman primates, we can’t be so sure that the current race to produce a COVID-19 vaccine will end in certain success. We don’t know whether the vaccine will offer sterilizing, long lasting immunity—as hoped—or only transient, partial protection, as seems more likely. What we do know is that public acceptance of a COVID-19 vaccine will play an outsized role in our ability to get as many people vaccinated as possible—and to that end, it isn’t too early to begin planning our efforts to educate the public. As a new analysis published in JAMA makes clear, early planning and public education is a must. To proactively confront barriers to COVID-19 vaccine acceptance in the United States, its authors argue, we must ramp up public health education now. The authors begin with the premise that anything short of broad acceptance of vaccination risks failure. They write, "Given that certain individuals will be ineligible for COVID-19 vaccination due to age, immunocompromise, and other preexisting medical conditions, a vaccine refusal rate greater than 10% could significantly impede attainment of this goal.” The goal in question is that of population immunity, generally referred to by the unfortunate name of “herd immunity.” Why is such a high acceptance rate needed? A major consideration is that a COVID-19 vaccine, like most vaccines, is likely to be ineffective for older adults. As we age, the immune system loses its ability to respond to vaccines for new diseases. This is a problem, since in this 191
case it is the elderly who are most vulnerable to COVID-19—and most in need of protection. To help limit exposure of the elderly to COVID-19, a vaccine must limit the total number of infected people in the population from whom they may contract the virus. I believe that most people aren’t aware that the most vulnerable population is least likely to benefit directly from a COVID-19 vaccine, no matter how effective it may be. Their health and safety depend on low infection rates in the general population. The authors identified points of resistance to vaccine acceptance. These include: Questioning the necessity for a vaccine. Questioning the safety of a vaccine. Vaccination as a matter of freedom of choice. A general suspicion of the health care system. The authors did not mention the anti-vaccine movement explicitly, but its shadow looms large. Combined, these barriers have the power to prevent efforts to control the epidemic through any vaccine that may be developed, no matter how safe and effective it is. Consider also the projection of these issues onto the world stage. Availability and acceptance of the vaccine globally is as important as it is locally. Recall that the infection of one person many thousands of miles from our shores has infected more than 1.7 million Americans—and the count is still rising. This article originally appeared in Forbes and is available online here: Confronting Barriers To COVID-19 Vaccine Acceptance
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June 2020
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COVID-19 In Children: A Detailed Study Of 10 Italian Children Forbes | June 1, 2020 | Article
The current issue of the Lancet carries a study of 10 Italian children diagnosed with a Kawasaki-like syndrome, recently reclassified by the World Health Organization as Multisystem Inflammatory Syndrome—Children (MIS-C). The study compares the COVID19 related syndrome to that observed for 19 children with Kawasaki Syndrome in the same hospital over the past five years. Here are some of the take-home messages about MIS-C compared to previous, non-COVID-19 related Kawasaki cases: 1. MIS-C is a consequence of infection with SARS-CoV-2. 2. The average of of children with MIS-C is 8 years old as compared to 3 three years old for Kawasaki. The WHO definition of children includes all those between 0-20 years old. 3. MIS-C is more serious that Kawasaki Syndrome and frequently involves damage to the heart and lungs. 4. The disease is effectively treated with a combination of intravenous gamma globulin and high dose methylprednisone (10 of 10 positive responses). Methyl prednisone is usually not needed for the treatment of non COVID-19 related Kawasaki. What does this mean for parents? Here are the take home messages for those caring for young kids: 1. MIS-C is a rare life-threatening disease for your child. It can be treated but you must take your child to the hospital immediately at the first signs of the disease. 2. Be alert for signs and symptoms of MIS-C if anyone in your community is diagnosed as either SARS-CoV-2 infected or is ill with COVID symptoms.
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3. Be on high alert if anyone in your family or your child’s school is diagnosed with COVID-19, is SARS-CoV-2 infected or is ill with COVID-like symptoms. 4. Be aware that MIS-C occurs several weeks after exposure. The time to be on highest on alert is 2-4 weeks postdiagnosis of a close contact. 5. Symptoms include fever, rashes, reddened toes, diarrhea, fainting. A child may appear to be entirely normal one moment and faint the next. Kawasaki seems to be a mild form of MIS-C. MIS-C children display all the clinical and laboratory characteristics of Kawasaki and many more. Kawasaki is described as a general inflammation of the mediumsized blood vessels. Kawasaki patients have a constellation of blood abnormalities that have been designated as Kawasaki Disease Shock Syndrome (KDSS) and Macrophage Activation Syndrome (MAS). All are typical of children MIS-C. Both KDSS and MAS are characteristic of MIS-C. Clinical differences in case presentation: 1. Children with MIS-C are typically older than those with Kawasaki 2. MIS-C children often are in respiratory distress—low oxygen saturation 3. MIS-C children more often present with diarrhea 4. MIS-C children often have signs typical of encephalitis, meningeal symptoms—painful neck flex, and leg extension. Clinically, the presentations of the two diseases also vary: 1. Lung X-ray abnormalities 2. Cardiac aneurysms (ballooning of the arteries reflecting weakened blood vessel walls.) 195
3. Low levels of leucocytes and lymphocytes 4. Thrombocytopenia (low platelet levels) 5. Increased levels of ferritin (typical of abnormal inflammation) 6. High troponin levels (indicates cardiac damage, in the case of MIS-C myocarditis-inflammation of the heart). All of these abnormalities are typical of adult COVID-19. Five of the ten children were known to be exposed to COVID19 in the weeks before hospitalization. SARS-CoV-2 RNA was detected in two of the 10 children by nasal swabs. Three of the children tested positive for anti-SARSCoV-2 IgA or and eight for IgG indicating that they had been infected at least two weeks or more before infection. The authors speculated that Kawasaki Syndrome is also the late consequence of infection with a coronavirus and suggests that, like MIS-C, it is a late consequence of infection, accounting for the difficultly in isolating the causal agent. Like MIS-C, the virus may be long gone before the symptoms appear. If so, this paper provides the clues to unravel this longstanding mystery. This article originally appeared in Forbes and is available online here: COVID-19 In Children: A Detailed Study Of 10 Italian Children
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Two Weeks And Ten Million COVID Tests In Wuhan Forbes | June 1, 2020 | Article
Over the last two weeks of May, all residents over the age of 5 in Wuhan, China were tested for the presence of active SARS-CoV-2 virus replication. The tests identified 300 people with active infection. None of those tested show any signs of infection. All family members and close contacts of the 300 were also tested. None were found infected. The surfaces of the living spaces of those infected were also swabbed and tested. No viral nucleic acid was found on any of the nearby surfaces or doorknobs. Wuhan officials believe this to be evidence that those who tested positive weren’t highly infectious. Since the testing spree ended, no new COVID cases have been identified in Wuhan or in the entire province of Hubei. The mass testing initiative followed a small and isolated outbreak of new infections in the city, more than a month after the stay at home order was lifted in mid-April. The mass screening program was focused on breaking the chains of transmission and reassuring residents that the city was safe. At the peak of the testing campaign, one million people a day were tested. Testing stations were set up around the city. To speed up the testing process, samples were pooled and tested for up to five people. If one of those samples was found to be positive, all five were tested individually. Throat rather than nasal swabs were used for sample collection. Before the campaign began, residents were notified that it was their civic duty to take part in the program to protect themselves, their family, and their city. Signs posted around neighborhoods reminded residents that “A nucleic acid test is your responsibility to yourself, your family and society.” Yet, whether residents agreed it was their civic duty or not, participation was mandatory. According to reports, one official announcement read “You will receive a text from local health officials, along with your national ID, you will get 197
tested. If you test negative, you will receive this ‘health code’, and only then you can return to work,” he said. The health code refers to a color-coded system that people must display on their mobile phones, when asked to. Green is for those who are clear, yellow for those exposed, and red for virus-positive. If you were color-coded yellow, you could change from yellow to green, following a period of controlled quarantine. Or from red to green following recovery and a mandatory period of isolation under quarantine. A green, all clear, personal identification code is required for entry in public spaces. All the residents of a second city, Mundanjiang, are also being tested for active infection. This follows the discovery on June 3 that 15 people in the city were actively infected. Mudanjiang lies near the border of both Russia and South Korea. The infection may have entered the city from residents retuning overland from Russia. All of the 2.5 million residents over the age of five will be tested over the next six days. China’s efforts to contain COVID-19 are truly impressive. Once the disease was known to be easily transmissible among people and deadly consequence of infection understood, China put in place highly effective public health measures that reduced the number of new cases per day from the thousands in February, to hundreds in March, to below fifty in April, and to low single digits for the entire country in May. All this without a vaccine or drug to stop the spread of the virus. But what are we doing today in America to stop the epidemic? Practically nothing compared to what China has achieved. The Centers for Disease Control and Treatment used to share their count of the number of viral tests administered nationwide. In mid-May, they stopped that practice and started bundling viral tests—which test for active infection—with antibody tests, which can show a person has been previously infected. At the time, the number of viral tests administered since the start of the outbreak was at roughly 10 million. Less than what one city in China managed to do within two weeks. Now that the CDC is no longer sharing viral testing numbers publicly, it is impossible for us to know if we are increasing our testing enough to make a difference. What we do know is that we can make a difference. 198
The take-home message from Wuhan’s testing spree is simple: The epidemic can be stopped in its tracks with the public health measures we already have in hand. Governments that fail to implement these measures fail in their primary duty to protect the people of their nation. This article originally appeared in Forbes and is available online here: Two Weeks And Ten Million COVID Tests In Wuhan
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COVID-19 In Kids: A Reason To Be Wary Of COVID Vaccines Forbes | June 2, 2020 | Article
More than a dozen COVID vaccines are in development, with many of them already being tested in humans and many more to begin human trials soon. But what do we actually know about these potential vaccines and why might we be wary of them? Wary, of course, does not mean we stop testing them, but it does mean we must be careful, to fully understand what they do, what they don't do, and what harm they might cause to otherwise healthy adults and children. First, what don’t we know? We do not know if they are safe. No human safety data is available to the public as far as I am aware, though some companies have issued press releases claiming safety without releasing the data. This is a concern as we are contemplating eventually giving vaccines to two to three billion people or more. One adverse reaction will result in many millions either injured or killed. We don’t know if they will protect anyone from infection. Yes, they raise antibodies in experimental animals but it is still unclear whether the animals are protected. Data from studies with a very limited number of non-human primates (monkeys) is available for one type of vaccine (an adenovirus vector that carries the spike protein gene of SARS-CoV2). Vaccination failed to protect any of the monkeys from infection of the nasal but did lower the amount of virus as virus-associated damage to the lung. Similar results were found for experimental SARS and MERS vaccines. Extrapolation of the degree protection of the lung from monkey to human is difficult as SARS-CoV-2 does not cause serious disease in these animals. The failure to protect animals from nasal infection raises the possibility that vaccines will offer only partial protection, that is, they may reduce lung disease but not infection via the nasal mucosa, the
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primary route through which the virus enters the human body. Will such partial protection prevent SARS-CoV-2 disease? The experience with SARS-CoV-2 in children offers some insight. Most children infected by SARS-CoV-2 exhibit mild symptoms. Some may have a fever and cold-like symptoms. Few experience lung disease. Childhood resistance is likely the consequence of more active immune defenses, as compared to those 25 and older, and of a much lower concentration of the ACE-2 virus receptor in the lungs of children as compared to adults. Recent measures showed an increase in the density of ACE-2 on type II lung pneumocystis with age. That means very little virus is found in children’s lungs, similar to what was seen in the vaccinated monkeys. We now know the absence of lung disease in children does not mean that all are spared the life-threatening consequences of SARSCoV-2 infection. A new syndrome, Multisystem Inflammatory Syndrome-Children (MIS-C), is now recognized to be a late consequence of SARS-CoV-2 in children ages zero to twenty. MISC is characterized by generalized inflammation of the vascular system, inflammation of the heart (myocarditis)and aneurysms (ballooning of the vessels). Clotting abnormalities, often present in severely ill COVID-19 adults, may also occur among children. Children teach us that partially effective vaccines which spare the lung may not spare vaccinated adults (or children) from illness and death. This is all the more reason to proceed cautiously with COVID-19 vaccines. The rush to approval may endanger many more lives than does the disease itself. This article was originally appeared in Forbes and is available online here: COVID-19 In Kids: A Reason To Be Wary Of COVID-19 Vaccines
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A Warning From Sweden’s Coronavirus Response Forbes | June 4, 2020 | Article
Sweden now has among the highest per capita death rates from COVID-19 in the world. Why? The answer is simple. Sweden was lax in its implementation of protective measures in the face of the outbreak, refusing to implement broad stay at home orders for residents, or to enforce recommendations to wear masks or social distancing measures. Other than the government decision to shut down universities and high schools, compliance to public health recommendations was entirely voluntary. Early on, my Swedish friends seemed proud of their exceptionalism. They sent many of their children to school without many of the protections that are both in place and under consideration in many other countries. Outside the country, many voiced their praise of Sweden’s “common sense” approach, which they wagered would be less economically destructive than stricter measures and would not lead to any greater number of deaths. They were wrong. Even the chief architect of the Swedish anticoronavirus plan is able to admit it. In an interview translated by Reuters, Sweden’s chief epidemiologist told Swedish radio that the country clearly could have done better in fighting the virus and that there was “quite obviously a potential for improvement in what we have done.” In particular, he said Sweden should have started testing earlier and more extensively and they should have done more to protect older adults in Sweden’s long term care centers, where more than half of all Sweden’s coronavirus-deaths have occurred. For all the loss Swedes have endured, there has been no associated economic gain, which is what many claimed was the saving grace of the Swedish approach. According to the European Commission, Sweden’s economic forecast of a 6% reduction in GDP for 2020 is on par with its neighbors, Norway and Denmark who implemented much stricter lockdown measures. 202
Sweden’s story is a lesson for all of us around what happens when we pull back on social distancing and prudent epidemic control measures. Here in the United States, our epidemic control measures were already relatively relaxed, accounting for our near steady rate of about 20,000 newly diagnosed COVID-19 cases per day for more than two months. The data from Sweden tells us what is likely to happen next— an ever-accelerating increase in the rate of infection followed by a rising death toll. That, in turn, is very likely to be followed by continued restrictions on public gatherings, school openings, and public confidence in our government’s ability to protect us. With Operation Warp Speed, one can’t help but wonder if perhaps the plan is to pin all hopes on a vaccine rather than use the public health tools we know can work to control the pandemic. If that is the case, we should be aware that our hope in a vaccine is far brighter than preliminary public data suggests it should be. The current generation of vaccines are likely to offer only partial protection, and likely only to some of us not all. With the new vaccines will come new risks, and unknown safety profiles. As we contemplate easing public health measures even further thanks to unfounded hope in a vaccine, I ask each of us to contemplate whether the Swedish example is showing us what we will be risking with this approach—our lives, our economy, and our children. This article originally appeared in Forbes and is available online here: A Warning From Sweden’s Coronavirus Response
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Human COVID-19 Vaccine Trials Are Unnecessary, Uninformative, And Unethical Project Syndicate | June 4, 2020 | Article
I was recently stunned to learn of the serious consideration being given to deliberately infecting human volunteers with the SARSCoV-2 virus in order to assess the effectiveness of potential COVID19 vaccines. My first reaction was that the advocates of such “human challenge studies” had gone so mad with panic that they had forgotten the history and horrors of medical experimentation on humans. But on closer inspection, I saw that they included some of the world’s most respected vaccine researchers and medical ethicists, and even the World Health Organization. As far as I can tell, their principal argument is that waiting for an answer from naturally occurring infections will take too long. The new coronavirus has already infected 6.5 million people worldwide and killed more than 386,000, including 107,000 in the United States alone. And in the absence of safe, effective vaccines and treatments, measures aimed at controlling the virus’s spread are ruining economies around the world. The WHO’s recent white paper on the use of human subjects for vaccine research makes it clear that such trials are a desperate last resort. This article originally appeared in Project Syndicate. The full article is available here: Human COVID-19 Vaccine Trials Are Unnecessary, Uninformative, And Unethical
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The Role Of Blood Type In COVID-19 Infection And Respiratory Failure Forbes | June 10, 2020 | Article
Does having a certain blood type put you at higher risk of developing a severe case of COVID-19? A recent report doesn’t have all the answers, but it does offer some clues. The report, which analyzes the data of almost 2,000 patients hospitalized for COVID-19 in Italy and Spain, found that those with type A blood were at increased risk for respiratory failure. Type O blood, on the other hand, was found to have a protective effect. This apparent susceptibility and protection from respiratory failure is far from absolute. Some patients with blood type O still suffered respiratory failure, while some with type A did not. Infection by SARs-CoV-2 has led to respiratory failure in patients of all blood types, including types A, O, B, and AB. These findings, rather than being definitive, add to what was previously known about the role of blood types in susceptibility to infection by SARS-CoV-2. Groups in China, the United States, and Italy have all found that people with blood type A are overrepresented amongst those infected. These studies all highlight a set of six genes located on the chromosome near the region that encodes the ACE2 protein, the receptor of SARS-CoV-2. Curiously, although many variants of the receptor itself are known, none are yet associated with an increased risk of infection or respiratory failure. The proximity of this region to the ACE2 receptor prompts speculation that it may modify the receptor in some unknown way, influencing both infection by the virus and progression of the disease. How might we interpret the practical implications of these results? First, they do not tell us that those with blood type O aren’t at risk of contracting, falling ill, or dying from COVID-19. Neither do they tell us that everyone with blood type A who is infected will suffer respiratory failure. As far as we know, everyone—regardless of genetic type—is at risk of infection and disease. 205
The results do tell us that those who know their blood is type A must continue taking appropriate precautions to protect themselves from COVID-19. It also means healthcare workers should take note of the blood type of their patients and, if a patient is type A, be on high alert for signs of respiratory failure. In the future, it may be wise to test hospitalized COVID-19 patients for variants in and around the ACE2 locus for the same reason. Inherited predisposition is the latest of many factors associated with respiratory failure due to SARS-CoV-2, including age, heart disease, pulmonary disorders, diabetes, and smoking history. Every day we are learning more about the disease, how it is transmitted, who is most susceptible, and how it affects our bodies. With knowledge comes a deeper understanding of how to prevent transmission, and how to care for those who fall ill. As is the case with the findings around blood types described here, we benefit from the efforts of scientists and doctors working across many countries to understand, control, and treat this disease. This article originally appeared in Forbes and is available online here: The Role Of Blood Type In COVID-19 Infection And Respiratory Failure
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Wounded In Action From COVID-19 Forbes | June 10, 2020 | Article
In our battle against SARS-CoV-2, we have mobilized as if we were at war with an alien invader. But this enemy is not from outer space. We and SARS-CoV-2 spring from the same source, the deep reservoir of all life on earth. Each species, struggling to survive. With humans and SARS-CoV-2 that struggle binds us together, as we happen to be the choice ecological niche for this particular virus—conveniently numerous, crowded together, and traveling freely across continents. Normally when we enter into battle, we count both the dead and wounded. But in this struggle, we tally only the infected and the dead. Yet a far greater toll is being paid in those wounded by the virus, who will never be whole again. Rarely do we even mention this growing tide of suffering. Thanks to a recent story in the Washington Post we can now put faces to a few of our wounded survivors. Each is part of the COVID-19 recovery mosaic, lungs that will never breathe easy, foggy brains and paralyzed limbs, failing kidneys, hearts that swell and veins that burst. COVID-19 is no mild cold that kills just a few, nor is it a mirror of the flu from which most recover intact. It is a deadly disease to some, and the beginning of debilitating lifelong disability for many others. It is high time we heard the voices of our wounded and extended our hand to help. This article originally appeared in Forbes and is available online here: Wounded In Action From COVID-19
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A Mutation Shows Why the Coronavirus Is Such A Formidable Foe CNN | June 13, 2020 | Article
All living organisms mutate and adapt to maximize survival in their ecologic niche. For months, scientists have been looking into whether the novel coronavirus -- known as SARS-CoV-2 -- is mutating and becoming more transmissible or more lethal. Recent evidence points to a preliminary answer to half the question: yes, a study has found that the virus has mutated and the dominant strain today is now capable of infecting more human cells. But the scientists say more research is needed to show whether this changed the course of the pandemic, and it remains unclear whether this mutation is more lethal. Almost immediately after the outbreak emerged, researchers began looking for patterns of change among the tens of thousands of viral genome sequences of SARS-CoV-2. The search was made possible thanks to the willingness of researchers around the world to upload their data to a common database. The data is open source, meaning anyone with a computer can access and analyze the data. This article originally appeared on CNN. The full article is available here: A Mutation Shows Why the Coronavirus Is Such A Formidable Foe
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A New CDC Report Shows COVID Disproportionately Affects Those With Underlying Disease And Disadvantaged Minorities Forbes | June 16, 2020 | Article
COVID-19 discriminates against those who it sickens and kills. The disease discriminates both by ethnicity and by pre-existing disease. The two are likely to be synonymous given what we know about the social determinants of health. A newly released report by the CDC summarizes the stark differences in how SARS-CoV-2 infection impacts different populations. Risk of illness and death by pre-existing condition: The report reveals that of those with pre-existing conditions at the time of infection 45.4% percent were hospitalized and 19.5% died, as compared to 7.6% of those who were healthy who were hospitalized and 1.6% who died. To my knowledge this is an unprecedented difference for an infectious disease. Heart disease, diabetes, and lung disease are the primary illnesses that predispose a patient to death following infection. The most common underlying conditions reported in people with COVID-19 were: Heart Disease 32% Diabetes 30% Lung Disease 18% Other preexisting conditions included liver disease, kidney disease, neurodevelopmental or intellectual disability, and immunocompromised conditions. This reflects similar global findings published in the Lancet, which suggests that those with chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease are most at risk. Globally, about one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to these underlying health conditions. 209
Risk of illness and death by ethnicity: The report also reveals a profound difference in the impact of COVID-19 by ethnicity. Once infected, ethnic minorities have on average about twice the chance of becoming seriously ill and dying as compared to nonHispanic whites. Hispanics, who make up 18% of the population, account for 33% of those who become seriously ill or die from COVID-19. Blacks, who make up 13% of the population, account for 22% of the seriously ill or dead. And Native Americans and Alaskan Natives make up 1.7% of the population yet account for 2.6% of the seriously ill or dead. As dramatic as these differences are, they explain only part of the total picture. The incidence of infection also differs according to ethnicity. In some communities, the infection of black and Hispanic populations is four to five times greater than those of non-Hispanic whites. The incidence of infection is also very high in Native American peoples. The report also addresses the question of asymptomatic transmission—the fraction of infections that can be attributed to people who did not know they were infected at the time. The CDC estimates that asymptotic transmission may account for 41% of all infections. My first conclusion: People with these underlying health conditions and their families should be especially careful to avoid exposure. Schools and workplaces should provide exceptional protection for those who identify themselves as especially at risk. My second conclusion: The differences in illness and death can be directly attributed to social determinants of health. The difference in the underlying health of people of differing ethnicities in the United States corresponds closely to differences in the outcomes of COVID-19 infection. Health outcomes in the United States fall well below those of all other high income and OECD nations. The disparities in health revealed by COVID-19 are well known to all of us in the health industry and are a cause of great suffering. They are also one of the reasons the cost of healthcare in the United States is almost twice that of other nations. Health disparities are also one of the reasons we lead the world in COVID deaths. 210
My third conclusion: The high proportion of infection attributable to asymptomatic carriers reinforces he need for continued personal precautions. On average, slightly more than 20,000 people in the United States are discovered to be newly infected by SARS-CoV-2 each day, a number that has been near constant since April 1. If people are infectious on average for ten days that translates to a prevalence of 200,000 infectious people on any given day. The safest assumption, and the one I make, is that everyone I meet may be infected. Until the infection is dramatically reduced, I urge all to wear masks in public, follow social distancing guidelines, and to adhere to all other recommended precautions. This article originally appeared in Forbes and is available online here: A New CDC Report Shows COVID-19 Disproportionately Affects Those With Underlying Disease And Disadvantaged Minorities
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Traveling By Air In The Time Of COVID Forbes | June 16, 2020 | Article
Doubtless, many of you miss air travel for families, business or pleasure. I certainly do. Yet in this time of COVID, short of a hospital or nursing home, an airplane is a most dangerous place. When you’re in an enclosed space, there is a formula for probability of infection which I developed that looks like this: Probability of infection (PI) = Time of exposure (T), divided by distance between people (D), times the number of people in the space (N), times the number of people without a mask (NM), times the prevalence of the average daily infection in the population (P) over a period of ten days (incubation period). So the equation would look like this: PI= (T/D) x (N) x (NM) X (P x 10) The exact number you end up with is less important than whether or not the number is relatively low, under 100, or higher. If it’s a number that ends up in the thousands or, worse yet, in the millions, you should be extremely cautious. For air travel: The time of exposure is long. The distance between people is short. The number of people in the enclosed space is high. The number of people without masks will be variable but is almost definitely going to be greater than zero. The prevalence of the average daily infection within the population is rising. There are roughly 200,000 people in the US actively infected today and 1,250,000 across the world and the number is rising. Yesterday, the number of new cases of COVID-19 in the US was more than 25,000 and that number is steadily rising. Worldwide yesterday, there were 140,000 new infections – the largest number of new infections in any day since the start of the outbreak. In almost every case of air travel, the probability for infection is high. 212
If you must travel, you must be extra vigilant. Read through online resources for how to protect yourselves and those around you. The US Centers for Disease Control has created a website with issues you should consider before flying. While you can implement many protective measures—booking the window seat, wearing a mask, social distancing whenever possible, and maintaining good hand hygiene—you will not be able to eliminate the risk entirely. My advice, if you can, stay home and stay isolated. My mantra is: assume everyone you meet is infected because some surely are. Now is not the time for unnecessary air travel, it is a time for vigilance and caution. This article originally appeared in Forbes and is available online here: Traveling By Air In The Time Of COVID
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Dexamethasone Reduces Mortality In Seriously Ill COVID-19 Patients—And So Do Other Treatments Forbes | June 16, 2020 | Article
Each day doctors are battling to save lives with the limited resources they have. They hope, as do we, that medical science will soon lend them a strong helping hand. A group of doctors announced today they had completed a controlled study in which they compared the survival of patients seriously ill with COVID-19 with those on standard care. The seriously ill included those who need oxygen support and those in intensive care units with breathing assistance. More than 2,000 patients were treated with dexamethasone, a low-dose steroid. Their health outcomes were compared with more than 4,000 others who received standard care. The results are encouraging. Dexamethasone treatment reduced the death rate of those needing breathing assistance by 35% and those needing oxygen support by 20%. This report adds to other smaller studies supporting the use of steroids in COVID-19 patients requiring oxygen support. However, the Oxford team erroneously claimed that this was the first medication to improve the survival of seriously ill COVID-19 patients—a claim repeated in headlines around the world. Previously published studies show that treatment with anticoagulants has an even bigger effect in reducing COVID-19 patient death. What I have called the Hong Kong cocktail (lopinavir, ritonavir, ribavirin, and interferon-beta) also improves patient survival. Noticeably absent from this discussion is remdesivir, which in another published study was shown to have no measurable effect on patient survival despite current enthusiasm for its use.
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It is regrettable that these researchers announced their success in advance of the actual publication of their results—a tactic otherwise known as publication by press release. This article originally appeared in Forbes and is available online here: Dexamethasone Reduces Mortality In Seriously Ill COVID-19 Patients— And So Do Other Treatments
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More Publication By Press Release, This Time From Sinovac On A COVID Vaccine Forbes | June 17, 2020 | Article
Spreading almost as fast as COVID-19 itself are “publications by press release”. The latest comes from Sinovac, the same company that previously withheld comment on animal studies of its candidate COVID vaccine until the supporting data was available for review. Not so this time, for what they describe as phase I/II safety trials for their whole killed SARS-CoV-2 candidate called CoronaVax. The company says it expects "to share the data through academic publications.” Until then, we must rely on their credibility for evaluation of the data—an unfortunate state of affairs in the face of a crisis of such magnitude as the one now affecting many millions of people and entire economies. Sinovac does not tell us why they chose to comment on their results before the data can be viewed. Data transparency should be the rule, not the exception, for public announcements. The vaccine was administered in two doses two weeks apart and blood samples examined 14 days after the second dose. Sinovac claims that in studies of more than 700 hundred people, the vaccine was safe. This claim is made without supporting data regarding adverse events. It would be surprising if there were none. They also claim that more than 90% of those vaccinated as part of the phase II trial made neutralizing antibodies to SARS-CoV-2. They do not report the range of antibody response not discuss the antibody status of those who did not make neutralizing antibodies. Sinovac also announced that it is building new manufacturing facilities and has reached agreements to test the vaccine in Brazil, a seemingly good choice as infection in that country is high and accelerating. The most we can conclude from this report is that Sinovac is fully engaged in human trials of its COVID-19 vaccine. We must await the data which underlies any specific claim.
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This article originally appeared in Forbes and is available online here: More Publication By Press Release, This Time From Sinovac On A COVID Vaccine
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Are Children Less Easily Infected By SARSCoV-2? Maybe Yes And Maybe No Forbes | June 17, 2020 | Article
A recently published report in Nature Medicine by a group of British epidemiologists concludes that children are half as likely to be infected by SARS-CoV-2 as adults. The conclusion is based primarily on publicly available data from Wuhan and from five other countries including Canada, Italy, Japan, Singapore, and South Korea. Specifically, they estimate that those under the age of 20 have half the chance of infection as those 20 and older. They estimate that COVID-19 symptoms occur in about 20 percent of infections in children between the ages of 10 and 20 as compared to about 70 percent for those 70 and older. The conclusions are based solely on data analysis. The work does not describe direct observation of adult to adult, adult to child, and child to child transmission. Although the analytical methods may be sound, the conclusions may be affected by factors other than agerelated differences in infection susceptibility. For example, detection of infection in children may be influenced by what is already know about the absence of any disease symptom in children also documented in here, with the result that the actual number of children infected in undercounted. However another recent study provides more detail on whether and why the incidence of SARS-CoV-2 infection is lower in children than adults. The research seeks to confirm the hypothesis that the difference is due to a lower density of ACE2 receptors in the nasal epithelium of children as compared to adults. The reported relative densities of the ACE2 receptors are: Age Relative ACE2 Density <10yrs 2.4 10-17yrs 2.7 18-24yrs 3.02 25-60yrs 3.09 218
The significant difference in this study is reported to be between those under 17 and those aged 18-60. The authors speculate that this difference may account for the apparent difference in infection of children and adults. Several caveats to consider: How sure are we that there is an inherent difference in infection rates between adults and children? Many factors affect infection in adults which but not children confounding such studies. The authors acknowledge a weakness in the study as no one over 60 was included. Those 60 and above are those most affected by COVID-19. The density of ACE2 receptors may not be uniform throughout the nasal mucosa. Perhaps there are fewer differences in regions unlikely to have been sampled. SARS-CoV-2 may infect via the nasal mucosa by routes other than via attachment the ACE2 receptor, specifically via M cell transcytosis or via attachment to the exterior of migrating dendritic macrophages. Other respiratory viruses initiate infection by both alternative methods. I do not believe the literature shows that children are less susceptible to the NL63 cold-causing coronaviruses that also infects via the ACE2 receptor. No mention is made of oral/fecal transmission of SARS-CoV-2 which is also a confounding variable. Considerably more research is needed to validate both hypotheses: That children are indeed less infectable and that the reason for the difference is the density of nasal ACE2 receptors. What is clear is that the policy implications of the distinction between disease prevalence and age for susceptibility to infection are profound, as these observations may have implications relevant to school closings and to other public health control measures. This article originally appeared in Forbes and is available online here: Are Children Less Easily Infected By SARS-CoV-2? Maybe Yes And Maybe No
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Immunity To COVID-19 Infection May Fade Quickly Forbes | June 19, 2020 | Article
A new study published in Nature Medicine indicates that immunity to infection by SARS-CoV-2 may fade quickly, at least in people with no or moderate symptoms. The duration of protection from reinfection is a subject of intense interest both for convalescents returning to work and for vaccines. The study focused primarily on two groups of 37 people who had been infected by SARS-CoV-2, as determined by repeated tests for viral RNA. One group never displayed clinical signs and symptoms of COVID-19 (asymptomatic). The symptomatic group all displayed mild symptoms of COVID-19 as determined by examinations by several physicians. The groups were matched for age and sex. The first unexpected finding is that CAT-scans of the lung showed that two-thirds of those with no clinical signs of COVID19 had what are called ground-glass opacity abnormalities typical of COVID-19 in at least one lung, and one-third showed ground-glass opacities in both lungs. In simple terms, SARS-CoV-2 is damaging the lungs of the majority who seem symptom-free. The long term health effects of such injuries may be apparent in later life. A second somewhat unexpected finding is that the virus load upon initial detection was indistinguishable between the two infected groups. At least in the early stages of infection, the amount of virus detected in nasal swabs is not an indication of subsequent disease progression. Viral RNA was detected in the nasal swabs of those infected for an average of 19 days in those with no clinical symptoms and 14 days for those who fell ill. Viral RNA was present as long a 45 days in one asymptotic individual and up to 22 days in a symptomatic patient. Detection of viral RNA may not be equivalent to the shedding of live virus. Nonetheless, the possibility is not excluded that transmission may extend past the usual quarantine period of 14 220
days. In recent times people in Northern China may be quarantined for up to 21 days post-exposure. One purpose of the study was to measure the duration of the antibody response following infection in both the asymptomatic and symptomatic groups. The levels of Both IgG and IgM antibodies were measured 3-4 weeks post initial detection of infection and for two months thereafter. The first surprise is that roughly 20 percent of people in both groups made no detectable IgG response to SARS-CoV-2. For IgM, the number was even lower. Between 30 to 40 percent of those infected had no detectable levels of IgM. That raises the question of how the virus is cleared (as it eventually was in all those studied) without robust antibody responses. We can speculate that may be due to a non-specific response from cells of the myeloid lineage or via a T-cell mediated immune response. The levels of IgG neutralizing antibodies (as measured using a spike protein pseudotyped virus) were measured in both groups eight weeks after release from the hospital. The levels of IgG and neutralizing antibodies were significantly decreased in the majority of patients in both groups. The decrease in neutralizing antibodies was more pronounced in symptomatic as compared to asymptomatic patients. These are the most consequential results of this study. The finding that some people infected with SARS-CoV-2 infection do not make antibodies, added to the observation that neutralizing antibodies begin to drop noticeably a few weeks post-infection, raises the possibility that infection by SARS-CoV-2 does not establish long-lasting immunity, at least for those without symptoms or only mildly ill, more than 80% of all those infected by SARSCoV-2 Patients with serious COVID-19 experience a cytokine storm, the equivalent of total body inflammation. Chemokines are proteins which play an important role in immune cell recruitment during inflammation. To explore this aspect of the disease further, the researchers compared the asymptomatic and symptomatic groups with a control group of 37 healthy, uninfected people, also matched by age and sex. The levels of 18 chemokines were measured in all three groups. The levels of many (including TNF TRAIL, Mi-CSF, Gro-D. 221
GCSF, and Il-6) were significantly increased in patients who had been infected versus the uninfected matched controls. There was no detectable difference in the level of chemokines those with asymptomatic infections and uninfected controls. This observation strongly implicates chemokines as a causative agent of observed COVID-19 symptoms. Recall that SARS-CoV-2 damaged the lungs of the majority of those who were asymptomatic. The report also includes the curious observation that the levels of three proteins, stem cell factor, interleukin 3, and leukemia inhibitory factor were significantly higher in asymptomatic patients as compared to those with COVID-19 symptoms or were never infected. These are not inflammatory chemokines. As a group, these proteins promote blood cell formation and/or inhibit differentiation. Is this a hint of a protective response in those who never fall ill? Undoubtedly this is the first of what will be a wealth of similar studies with much larger numbers as we have the opportunity to observe many more patients in the weeks and months following infection. What little we know now does raise concerns about the protective immune response to SARS-CoV-2 infection, concerns with profound implications for public policy and vaccination strategies. This article originally appeared in Forbes and is available online here: Immunity To COVID-19 Infection May Fade Quickly
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Successful Reopening: It's Not What You Think Forbes | June 19, 2020 | Article
With most countries still in lockdown, some have started to reopen, and the world is watching. What does it mean to have a successful reopening, and have we witnessed it? Looking at the resurgence of COVID cases in China and in New Zealand, some may find it hard to label them as a success. However, what happened there is exactly what countries that achieve very low levels of infection can expect of a successful reopening, at least until the virus is eliminated worldwide. The first step in controlling the virus is to implement strict stayat-home procedures and to carry out a rigorous contact tracing effort. Tracing the contacts of all those known to be infected with SARS-CoV-2 allows the community to get ahead of the disease by quarantining anyone who might be infected and infectious, preventing them from further transmitting the virus. Massive testing and immediate contact tracing and mandatory isolation for those exposed is crucial for countries to break the chains of transmission. Wuhan, the city at the epicenter of this pandemic, once had a total of 68,135 confirmed cases. Today, the provincial health commission announced no new confirmed, asymptomatic or suspected COVID-19 across the entire province of Hubei, where Wuhan lies. The most recent outbreak in China was in Beijing. No infections were reported in Beijing for almost six weeks. Then on June 10 a man with no history of recent travel visited a doctor with a fever and chills. He tested positive for SARS-CoV-2 and was hospitalized the following day. While in hospital, public health officials discovered that he had visited a meat market on June 3. Within days, the city was under lockdown, a widespread testing initiative was underway, and thousands of contact tracers were trying to chase down potential new infections. Over a million people were tested within a week. More than 180 people as of Friday were found to be virus positive, all asymptomatic. 223
Thanks to this effort, a new cluster of infections was identified, all with links to the meat market. While it’s unknown how the SARS-CoV-2 virus was first introduced at the market, after a 55day run in which there was no known local transmission, the sheer volume of people passing through and the less than hygienic conditions may provide some of the explanation for the spread. It’s possible to argue that this re-emergence of locally transmitted infections demonstrates the failure of Beijing’s reopening. But in a globalized world where people from countries or communities with high rates of infection are still able to travel freely to communities that have their outbreak under control, the possibility of achieving zero new infections while the global infection rates are high is remote. A similar situation is occurred in New Zealand. After 17 days without any new infections, the country lifted its COVID-19 restrictions, only to be greeted by two new coronavirus cases just over a week later. Those cases came from two women who traveled from the UK to New Zealand, via Australia. Immediately upon detection they were lodged at an isolation hotel in Auckland and then monitored remotely as they traveled by car from Auckland to their home base in Wellington, where they have been in isolation ever since. As New Zealand’s director general of health said in a news conference, "A new case is something we hoped we wouldn't get but is also something we have expected and planned for…. That is why we have geared up, and continue to gear up, our contact tracing at a local level and national capacity and capability as well as having our excellent testing capability so we can respond rapidly." That is what a successful reopening looks like. It is not measured in the number of days without any new infections, but rather in the way the public health system responds to a spike in new infections. Until every country is rid of the virus, no country will ever be rid of the virus entirely. We have the measures at hand to ensure a successful reopening – widespread testing, rigorous contact tracing, and mandatory isolation for those who have been exposed to the virus. With that, we can control the current outbreak, bring infections down to manageable levels in every community, and prevent new outbreaks
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from overwhelming our healthcare system or leading unnecessary death and injury of those infected. This article originally appeared in Forbes and is available online here: Successful Reopening: It's Not What You Think
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The Risks Of Rushing A COVID-19 Vaccine Scientific American | June 22, 2020 | Article
The excitement and enthusiasm for a COVID-19 vaccine by the end of 2020 is both palpable and understandable. We all hope for a rapid end to the pandemic and an effective vaccine would be a surefire solution. But there are risks that come with a fast-tracked vaccine delivered end of this year, not the least of which are the risks related to the safety of the vaccine itself. Telescoping testing timelines and approvals may expose all of us to unnecessary dangers related to the vaccine. While preclinical trials to evaluate the potential safety and efficacy of vaccine candidates are likely to include tens of thousands of patients, it is still unclear whether that number will be large enough and a trial will last long enough to evaluate safety for a drug that would be administered to so many. The US alone plans to vaccinate hundreds of millions of people with the first successful candidate. One serious adverse event per thousand of a vaccine given to 100 million people means harm to 100,000 otherwise healthy people. Aside from questions of safety that attend any vaccine, there are good reasons to be especially cautious for COVID-19. Some vaccines worsen the consequences of infection rather than protect, a phenomenon called antibody-dependent enhancement (ADE). ADE has been observed in previous attempts to develop coronavirus vaccines. To add to the concern, antibodies typical of ADE are present in the blood of some COVID-19 patients. Such concerns are real. As recently as 2016, Dengavxia, intended to protect children from the dengue virus, increased hospitalizations for children who received the vaccine. Questions also arise around the efficacy of a potential vaccine. The little we know of the current generation of COVID-19 vaccines raises serious questions regarding their ability to protect people from infection. We know all the candidates tested to date in non-human primates failed to protect any of the monkeys from infection of the nasal passages, the primary route of human infection. Failure to 226
protect entirely from infection fits with all we know about attempts to protect monkeys from two other deadly coronaviruses, those that cause SARS and MERS. On a brighter note, at least some of the candidate vaccines did raise significant immune responses. How that translates to protection of humans is uncertain though as monkeys do not become noticeably ill or exhibit many of the life-threatening consequences of COVID-19, even when exposed to high doses of the virus via the nose, lung, and rectum simultaneously. As many of the most serious COVID symptoms do not appear until late in the disease course, sometimes four to five weeks following exposure, there is a possibility that we will not have sufficient time to judge efficacy of a new vaccine, even by the lower standard of symptom amelioration. An effective COVID-19 vaccine also faces several hurdles beyond our control. The older we get the poorer our ability to respond to vaccines. Resistance to vaccination begins early at age 30 and becomes progressively more profound with time. That is especially troubling as those over 60 are the population most at risk. Vaccination of the elderly may sometimes succeed by administering repeated doses and by increasing the potency of the vaccine with powerful adjuvants. But these adjuvants can be especially risky for the very old. It seems a folly then to rush our way towards a vaccine in 2020 if it is likely to have only limited benefit to the population most in need and may put otherwise healthy people at risk. The risk goes far beyond the dangers a COVID vaccine alone may hold. Public support for vaccines in general is already an issue. Trust in other lifesaving vaccines will be eroded even further if a COVID vaccine goes wrong and many more people—children especially—will be at risk if vaccination rates fall. Yes, we are all increasingly longing for an end to the outbreak. But a safe vaccine, effective for all those at risk, is worth the wait, especially when we have other solutions in hand. We already know from the experience of countries in Asia that the epidemic can be stopped in its tracks with basic public health measures: widespread testing, contact tracing, and mandatory controlled quarantine—not necessarily in a dismal public health facility as many imagine, but in our own homes with virtual supervision or in a hotel environment.
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These efforts alone could bring new infections down to almost zero within just weeks. In addition, I believe it will be possible before the end of this year to protect those most at risk from exposure with combinations of monoclonal antibodies or with truly effective antiviral drugs. These drugs could treat those who were ill and prevent further infection. In addition to pursuing a vaccine within a realistic timeframe, we should also be throwing our weight behind these other types of medical solutions which have historically been much quicker to bring to market safely. There is no doubt we need an urgent end to the pandemic. Economies around the world are crashing. Governments are piling up trillions of dollars in debt. And, in the US alone, tens of millions are without work or income. But there are still costs that are too great, even when compared to such numbers. When we have solutions to the pandemic in hand we cannot risk the potential lives lost of rushing a COVID vaccine to market. We must hold dear the central dictum of the medical community, first, do no harm. Trust that given the time science will deliver a medical solution in the form of a vaccine or a chemoprophylactic drug treatment, and in the meantime let us immediately implement the public health strategies that we know will work today to drive new infections down to nothing. This article originally appeared in Scientific American and is available online here: The Risks Of Rushing A COVID-19 Vaccine
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Protecting Pregnant Women From COVID-19 Forbes | June 22, 2020 | Article
Many months into the pandemic, we’re beginning to learn more— and in more detail—about how the COVID-19 is disrupting the health and wellbeing of specific populations. Yet for pregnant women and their unborn children, such information has been inconsistent, inconclusive, and altogether lacking. In late April, a group of researchers sounded a call to action in the Lancet imploring their peers, and the public health authorities they serve, to fill this glaring knowledge gap. Progress has been made since then, most notably in the form of a study published last week that pronounced it unlikely for the COVID-19 virus to be transmitted from mother to womb. Still, much remains unknown, and in the meantime, vigilance is needed. While no studies to date have shown that being pregnant increases the risk of COVID-19 infection or, once infected, severe symptoms, reports have started to trickle in that paint a more troubling picture. A case study published by JAMA in late April, for instance, describes a COVID-19 patient who had a spontaneous miscarriage in her second trimester. The placenta tested positive for the COVID-19 virus, prompting the question of whether infection had a role to play in inducing the adverse outcome. Adverse pregnancy outcomes documented during the previous two coronavirus pandemics, SARS and MERS, can’t be discounted either. One report suggests that pregnant women hospitalized with SARS were more likely to experience complications like sepsis and renal failure, require longer hospital stays, and end up in intensive care. We also know that pregnancy weakens the immune system, making pregnant women more susceptible to respiratory infections more broadly, not just those caused by coronaviruses. Such was the case during the 2009 outbreak of H1N1 influenza in the United States. According to another Lancet study, pregnant women developed severe pneumonia and deteriorated to the point of 229
needing mechanical ventilation at higher rates than nonpregnant women. Even high fever, a common symptom of COVID-19, is a harm for pregnant women to be wary of. Developed in too early a stage of pregnancy, high fever can lead to birth defects. Other risks don’t involve infection itself, but the public health measures we’ve adopted to prevent it. Stay-at-home orders and general fears of coming into contact with COVID-19 patients have prevented some women from completing their prenatal checkups as scheduled. Even more worryingly, these same conditions can keep women facing domestic violence from seeking help or safe refuge. To study and understand the full extent of the impact that COVID-19 and ensuing countermeasures have had—and will continue to have—on pregnant women around the world, research efforts will have to broaden in scope to include risks both medical and social. They will also have to expand across space and time, aiming for a global reach befitting of a global crisis. The researchers behind the Lancet article say as much, and yet many of their recommendations have gone unaddressed. They call for more expansive strategies of data collection that would track the impact of COVID-19 over the course of a woman’s pregnancy and into her child’s infancy. They also point to existing data reserves, like pregnancy registries, and research networks, like those formed to study the impact of the Zika virus on pregnancy, that could be mobilized to make the effort truly global. This pandemic isn’t likely to be the last, or even the most virulent. Understanding its impact on pregnant women won’t just benefit the children born in the throes of COVID-19, but their children’s children. We need more data transparency, coordination, and cooperation between countries on this urgent matter—or we risk leaving future mothers-to-be vulnerable once more. This article originally appeared in Forbes and is available online here: Protecting Pregnant Women From COVID-19
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A Tale Of Four Cities: Wuhan, Seattle, New York, Chicago Forbes | June 22, 2020 | Article
A new study from Northwestern University in Chicago, available as an unreviewed pre-print, identifies three distinct strains of SARSCoV-2 currently circulating in Chicago. The three strains, called clades, can be distinguished from one another by the sequence of viral RNA. The variant the authors call clade 2 was introduced into Chicago in mid-January 2020 by a traveler from Wuhan. It is the second earliest documented introduction of the virus into the United States. Despite the early introduction, Clade 2 viruses represent only 1 percent of strains circulating in The U.S. at the end of May 2020 and only 8 percent of the viral genomes analyzed in this study. The genome sequence of clade 2 very closely resembles strains originally found in Wuhan. Clade 1 is the most predominant in Chicago and the United States and accounts for almost 60 percent of all the viruses isolated in this study. Clade 1 arrived in Chicago in mid-March, having first migrated from China to Europe, from Europe to New York and from New York to Chicago. Subtle changes in the genome allow us to track the virus as it moves from one population to another. It is now the dominant strain in Europe, the eastern and central regions of the United States, and South America. Clade 2 has a different origin. It closely resembles variants in circulation in Seattle, WA and began circulating well before the appearance of clade 1 in New York and Chicago. It too originated in China. The authors measured the amount of viral RNA in nasopharyngeal samples of all patients when they were initially diagnosed and in the lungs by bronchoalveolar lavage in severely ill patients harboring clades 1 and 2. There is a statically significant difference in the amount of virus in the nasal passages depending on clade— high levels of virus were detected in patients infected with clade 1 viruses, moderate levels for those with clade 3 infections, and 231
the low levels for clade 2. There was no statically significant difference in the amount of virus in the lungs of severely ill patients infected with either clade 1or 2 variants. The amount of virus in the nasopharynx was consistently higher than that recovered from the lung in all patients. The authors report no difference in symptoms or severity of disease according to clade after normalizing for age, sex, or ethnicity of those infected. The authors speculate that clades 1, 2, and 3 differ in how readily they are transmitted from one person to another. They attribute differences in transmissibility to how much virus is present in the nasal passage. The correlation does appear to be good. After this manuscript was submitted, detailed studies of the effect of one of the variants in the spike protein of clade 1 viruses was shown to increase the infectivity of the virus by almost tenfold. On maturation, clade 1 virus retains far more of the exterior portion of the spike protein than viruses that lack this mutation. This observation validates the authors' speculation that the reason for the dominance of the clade 1 virus is that it is more transmissible, presumably because a much lower dose of virus is all that is needed. There is no biochemical understanding of why the clade 3 virus appears to be more infectious than that of clade 2 but less than the one of clade 1— an intriguing problem for further investigation. These findings open the possibility that the original outbreak in Wuhan and China might have been more easily controlled because the dominant virus was ten times less infectious than the dominant strain currently circulating in much of the world. Similarly, differences in the infectivity of the Wuhan (clade 2) and European/New York strains (clade 1) may account for the perception that COVID-19 was far less transmissible than it is today. The mutation that supercharges clade 1 first appeared in Europe in early March and quickly became the dominant strain, first in Italy, then the rest of continental Europe followed by the Eastern Central regions of the United States and throughout South America. As SARS-CoV-2 adapts to us we must improve our counterstrategies. This article originally appeared in Forbes and is available online here: A Tale Of Four Cities: Wuhan, Seattle, New York, Chicago
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Progress In Monoclonal Antibodies For The Treatment And Prevent-Of-COVID-19 Forbes | June 23, 2020 | Article
A team of scientists recently announced progress in the discovery of a pair of monoclonal antibodies that may be useful for the prevention and treatment of COVID-19. The work was described in the June 12th issue of Science Magazine. The scientists began the process by isolating live antibodyproducing cells from the blood of convalescent patients. They used a key fragment of the virus spike protein as bait to fish for cells that make the antibodies of interest. The bait fragment is the precise region of the spike protein that attaches to the ACE2 surface structure to begin the process of infection. The idea behind their choice was that antibodies that block the attachment of the virus to the cell will prevent infection altogether. Their fishing expedition was successful. They settled on four antibody-producing cells that met their criteria. The next step was to isolate the genes (the bits of DNA in the cell) that specify each of the antibodies. Again, they were successful. The next challenge was to develop each as a potential drug. To do so, they needed to insert the genes into a cell suitable for large scale production of the antibodies. This they also did. The first test of the four antibodies was to determine whether the antibodies attached to the SARS-CoV-2 spike protein as expected. All passed this test. The virus that causes SARS-CoV-1 also uses the ACE2 protein as a receptor but none of the four antibodies attached to the SARS-1 spike protein. The next question the researchers needed to answer was whether the antibodies blocked binding of the spike protein to the ACE2 receptor. Two of the four antibodies did and the other two did not. The team then focused their attention on the two ACE2-blocking antibodies. Did both blocking antibodies bind to the same part of the spike protein? If they did, binding of one should interfere with binding by 233
the other. What they found was the two antibodies did interfere with one another but only weakly, suggesting that they attach to overlapping but not identical regions of the spike. To understand exactly how the antibodies block binding to the ACE2 receptor, the atom-to-atom contacts of one of the antibodies to the spike protein was determined by X-ray crystallography of the antibody-spike protein complex. The result: the antibody studied binds to 18 of the 21 ACE2 attachment sites. In other words, when the antibody binds to the spike protein it almost completely covers the ACE2 attachment site. The next obvious question is, do the antibodies prevent infection? The hope is that if they do, two together should be more powerful than one alone. The experiments fulfilled that hope. Each of the antibodies on its own can neutralize the virus. The two together are more effective than either alone. The final experiment was to determine if the antibody acted against SARS-CoV-2 in an infected animal. They chose mice for convenience even though SARS-CoV-2 does not usually kill those animals. The antibodies were introduced in the mice 12 hours after the viral challenge. The experiment showed that the antibody treatment reduced the amount of virus in the animals by 32.8% for one of the antibodies and 26% for the other, when compared to a control group three days post-infection. The animals treated with each antibody also had fewer lung lesions than the placebo control animals. A next logical question, do the antibodies prevent infection of naive animals if not reported? It is likely that they will. Monoclonal antibodies used to treat respiratory syncytial virus protect very young children from infection. A monoclonal antibody that treats anthrax infections also prevents infection. The work is a tour de force not only for the clarity and completeness of the results but also for the speed with which all the many steps were accomplished. The work reveals the stepwise question and answer process of successful scientific experiments each performed in a clear logical progression. The work also attests to the power of modern bioscience as each of the steps is, in itself, demanding technical exercise. Apart from elegant science, the work offers hope that combinations of monoclonal antibodies can be used to treat and to 234
prevent COVID-19. As an aside, combinations of antiviral drugs often work better than drugs used alone as coronaviruses, like many other viruses, are known to develop resistance to single drugs. As a treatment, it is likely that combinations of monoclonal antibodies can prevent those infected from becoming ill, and if used early enough, may prevent those who are seriously ill from dying. Used as prophylactics, such antibodies may protect healthcare workers. They may also be used to prevent those exposed at home or in the workplace, and perhaps even those identified as exposed by contract tracing. One happy way to describe such a success is that monoclonal antibodies may be the equivalent of a short-acting vaccine. For now, all such good news must await human trials. The experiments described here demonstrate that success is in reach, not only for the effort of this group, but for many others who are on the same trail. This article originally appeared in Forbes and is available online here: Progress In Monoclonal Antibodies For The Treatment And Prevention Of COVID-19
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COVID-19 Ping-Pong: Animal To Human, Human To Animal, Animal To Human Transmission. How Great A Danger? Forbes | June 23, 2020 | Article
SARS-CoV-2 originally jumped from animals to humans. So too did the virus responsible for SARS and MERS. There is now abundant evidence that humans can transmit SARS-Cov-2 to domestic pets and other animals. The more people infected the greater the risk of creating a permanent animal reservoir of infection; one that may pose a threat for generations. Humans can infect other animals with the COVID-19 virus. Human can infect cats and dogs, lions and tigers, and now mink. Infected tigers can transmit the virus to lions. Min can transmit SARS-Cov-2 for one to another with devastating effects on entire colonies. Now it appears at least some animals can give the virus right back to us in what I call viral ping-pong. Beginning early April 2020, large scale infections occurred in at least two mink farms in the Netherlands. Sequence analysis of the viral genes showed that while the virus spread rapidly within farms, even among animals housed in separate cages, it did not spread between farms. Subsequent studies showed that cats in and around the mink farms were also infected. Whether all cats were infected by contact with mink feces or respiratory droplets or infected by contact with one another is not known. Then came the discovery that two mink farmworkers were infected. Genome sequencing established that the virus jumped back into humans from the infected mink What are the implications of intraspecies jumps? SARS-CoV-2 can infect mink, domestic cats and dogs, ferrets hamsters, tigers, lions, and bats and macaque monkeys. There is some evidence that pigs, mice, and rats may also be able to be infected. Likely, wild species closely related to these animals can also be infected including
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coyotes, wild dogs, feral feline species, wild boar, pangolins, and civets. With time I am certain that the list will grow. Should we worry about being infected by our pets and livestock? Perhaps. Soon more than ten million people worldwide will have been infected, each a possible source of animal infection. We know that the virus can jump from animals to humans, that is presumably how both SARS and COVID-19 infections began. Camels continue to infect humans with MERS eight years after the first cases were reported. We are fortunate that the MERS virus spreads slowly from person to person. There are too many unknowns to estimate the degree of risk of human infection from animal reservoirs of COVID-19. We do not know the efficiency of transmission for humans to animals although it appears to be low for dogs and cats. We do not know the efficiency of transmission between animals, although we have seen that for mink animal to animal transmission can be very efficient. We are uncertain about the routes of infection, whether it is airborne, oral/fecal, contaminated water, or all three. We are still learning about all the different types of animals that can be infected and transmit the virus back to us. What is clear is that there is a very real possibility that SARSCoV-2 may establish deep reservoirs of infection in our pets, livestock, and feral animals that live around us. It is time to begin detailed surveillance of animal populations for evidence of infection. It may be time to be wary not only of our fellow humans but our pets and livestock as potential dangers. This article originally appeared in Forbes and is available online here: COVID-19 Ping-Pong: Animal To Human, Human To Animal, Animal To Human Transmission. How Great A Danger?
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We’re Making Exciting Progress In Developing COVID-19 Drugs Forbes | June 29, 2020 | Article
Drugs specifically designed to prevent and treat COVID-19 are urgently needed. The good news is they are on their way. The winning strategy for several other viral diseases proved to be drugs that inhibit virus replication in patients. Drugs that treat HIV/AIDS, hepatitis C, and herpes simplex type 1 and 2 are wellknown examples. These drugs work by blocking the action of proteins the virus needs to reproduce itself. The most common targets are the enzymes a virus needs to copy their genome, the polymerases, and those they need to cut larger proteins into smaller functional fragments, the proteases. The discovery of anti-HIV proteases, combined with an anti-polymerase, paved the way for long term survival in people infected by HIV-1. Similarly, it was the discovery of anti-protease drugs that enabled the curative treatment of hepatitis C infections. The virus that causes COVID-19 is a beta-coronavirus, SARSCoV-2. Like all coronaviruses, SARS-CoV-2 makes a protease that is required for it to reproduce. Without an active protease, the virus cannot copy itself. To block the protease is to inhibit virus replication altogether—and to put a halt to the disease’s deep creep into the body. Two prior coronaviruses epidemics, SARS and MERS, triggered an intense hunt for anti-coronavirus drugs. Several researchers discovered chemicals capable of inhibiting the SARS and the MERS proteases, several of which prevent viral replication in the laboratory. Some even inhibit replication in infected laboratory animals. But when SARS was successfully contained, and when MERS proved to be a highly localized epidemic, interest in approving these drugs for human use waned. Now comes the best news—the discovery of drug candidates that specifically inhibit the SAR-CoV-2 protease. The researchers responsible for the discovery began with a leg up. Previous studies 238
elucidated the precise means by which drugs inhibit the SARS and MERS proteases, right down to the atom-to-atom contacts made between the drug and the protease. The SARS-CoV-2 protease closely resembles that of both the SARS and MERS enzymes, giving the drug developer a great guide. Using this information, the researchers designed two chemicals, designated 11a and 11b, they thought should do the job. Then, they conducted a series of experiments to test their idea, summarized in the series of questions below: Do 11a and 11b bind to the protease? Yes, they do—and tightly. Do 11a and 11b prevent the protease from cutting other proteins in test tube experiments? Yes, they do. Do 11A and B prevent virus replication in the lab? Yes, they do, and at very low concentrations. 11A is more potent 11B, but both work. Does the drug reach a level predicted to be effective? Both drugs do when injected into mice and dogs. 11a has a longer half-life and greater bioavailability than 11b. Is the drug toxic? No toxicity was observed in mice and dogs given what are considered to be therapeutic doses of 11a. No toxicity was observed in dogs given very high doses of 11a. For these reasons, the authors conclude that “11a is a good candidate for further clinical study.” What are the next steps? First, measuring the bioavailability and toxicity of 11a in macaque monkeys. Then, answering the following questions: Does 11a reduce the viral load of macaque monkeys infected with several different isolates of SARS-CoV-2, and if so at what dose? What’s the best dosing regime to assure permanent clearance of SARS-CoV-2 infection in macaque monkeys? If successful, 11a will then begin phase 1 safety trials in healthy humans. This will be a dose-escalation trial in which increasing doses of the drug are administered to healthy volunteers, most likely in groups of twenty to forty per dose. The bioavailability and half-life of the drug in humans will be measured, along with the analysis of the breakdown products blood and urine. Such a test should be completed within two months. I suspect that they are already in progress, if not already complete. 239
If the phase 1 trials are successful, the ability of 11a to decrease viral load in volunteers with active SARS-CoV-2 infection will be examined next. Again, small groups of SARS-CoV-2 positive volunteers will be given increasing doses of 11a. To monitor any reduction or drug-related toxicity, viral load will be measured using nasopharyngeal swabs, saliva, bronchoalveolar lavage, and feces. Within days, researchers should know whether or not 11a performs as hoped. Approving the drug for clinical use can take one of two possible routes. One is based on the ability to decrease viral load. Such was the case for approved anti-HIV drugs, for which reduction in the incidence of AIDS isn’t required. This is in part due to the long delay between infection and disease. The situation is different for COVID-19. The disease appears with mild symptoms within a week of infection, and with serious symptoms requiring hospitalization within two to three. Rather than a reduction of viral load, approval might be based on a reduction of mild to moderate symptoms (including chest x-rays to measure silent lung infection) or a significant decrease in the number of people who progress from infection to serious disease requiring hospitalization. Given the urgency of our need, I favor approval based only on the ability of the drug to decrease the viral load by several orders of magnitude in all samples. The good news is that regardless of the fate of 11a, this research group and many others are hot on the trail of a variety of drugs that will inhibit proteins needed for viral replication. I predict with confidence that by this time next year, cocktails of anti-viral drugs will be approved for use that effectively treat SARS-CoV-2 infections. I also predict that thereafter, long-acting anti-viral drug formulations will be developed to prevent infection. Such drugs would function as short-acting vaccines to protect our healthcare workers and household members who test SARS-CoV-2 positive. Lastly, I am confident that also by this time next year, an entirely different approach—use of anti-SARS-CoV-2 monoclonal antibodies—will be effective in tracing and preventing SARS-CoV2 infections. In any case, help is on the way! This article originally appeared in Forbes and is available online here: We’re Making Exciting Progress In Developing COVID-19 Drugs 240
The Other Shoe Drops: Gilead’s Outrageous Pricing Of Remdesivir Forbes | June 29, 2020 | Article
Gilead says it will charge governments $2,340 and private insurers $3,120 for a 5-day course of remdesivir, a treatment for COVID-19 patients. This is an outrageous price for a drug that has demonstrated little to no ability to save lives or lower viral loads in patients. The few benefits it supposedly has are supported by trials that can only be described as flimsy. Remdesivir is not even approved by the U.S. Food and Drug Administration, having received only emergency use authorization. As Peter Maybarduk, Public Citizen’s Access to Medicines Director, told the Financial Times, this is “a display of hubris and disregard for the public.” University of Liverpool Professor Andrew Hill is quoted in the same story saying: “Remdesivir does not have a proven survival benefit and the results have not been consistent between studies. It is not clear why 5 days of treatment should improve clinical responses, but not 10 days of treatment.” Earlier, Hill argued that the drug could be sold for as little as $9. By now it is no secret that Gilead charges exorbitant prices for its drugs. A curative three-month treatment of the company’s antihepatitis C drugs costs $35 in India, $45 in Egypt, and more than $80,000 dollars in the United States. Gilead has also been criticized for claiming that the high costs of its products reflect the cost of drug discovery and bringing drugs to market. In fact, neither remdesivir nor the anti-hepatitis drugs were discovered by Gilead. Notably, the company also did not pay the full cost of clinical trials resulting in approval or emergency use authorization. The time for governments to push back on Gilead’s pricing is now. A strong movement for control of pharmaceutical prices already exists in the United States. Little will be lost if Gilead drops 241
the drug altogether, as its benefit is marginal at best and generic manufacturers can easily satisfy whatever demand there may be. I am not opposed to paying reasonable prices for truly effective drugs that drop viral loads, save lives, and prevent disease progression. But remdesivir isn’t that—not even close. This article originally appeared in Forbes and is available online here: The Other Shoe Drops: Gilead’s Outrageous Pricing Of Remdesivir
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Women’s Health And The Ripple Effect Of The COVID-19 Pandemic Forbes | June 30, 2020 | Article
COVID-19 has upended every aspect of our lives, in ways both seen and unseen. Each day, we witness the damaging effects of the pandemic on our economies and healthcare systems, as businesses shut down and hospitals struggle to meet an overwhelming demand for intensive care services. But inside homes across the country, families are bearing witness to another impact of the epidemic, its effect on the sexual and reproductive health of women. A new report from the Guttmacher Institute released this week is shining first light on the plight of women in America in the midst of the COVID-19 pandemic. The institute surveyed 2,009 women over a two week period in late April and early May, asking questions related to their health, their physical and emotional safety, and their desire to have children. The responses give us a better understanding of the true scope of the impact of COVID-19 and a sense of the ripple effects that we will be navigating over generations to come. One of the most significant findings is that, because of the pandemic, one third of women surveyed now say they want to delay having children or they want fewer children overall. It has long been understood that a woman’s desire to have children is shaped in large part by the broader socioeconomic context in which she lives and the increase in financial and job-related worries created by today’s pandemic is already having an impact. Not surprisingly, the same percentage of women surveyed said their attitude towards contraception has also shifted because of the pandemic, with one third saying that they are now more careful than they used to be about using birth control. Unfortunately, the pandemic has created new challenges for women in need of contraception. One in three women surveyed said the pandemic has made it harder for them to access birth control or has delayed or forced cancellations of their doctor visits. Black and Hispanic women, two groups that have historically borne the 243
brunt of social inequalities, continue to face greater challenges to timely care than white women, with 38% of Black women and 45% of Hispanic women reporting issues with access to care, compared to 29% of white women. There were similar discrepancies in access to care for other marginalized groups like queer women (46%) when compared to straight women (31%). In addition to these fairly concrete questions around fertility and access to care, the survey also explored the social impact of COVID19 on women. Financial stress and economic hardship are often precursors to increases in domestic violence against women. One in five of the women surveyed said that they had been the victim of domestic abuse this year, either through verbal abuse, physical abuse, or forced sex. One third of those women said that the stay at home orders and social distancing measures in place in their communities were making it impossible for them to get the support needed in the face of such violence. It is hard to imagine any other global event having such an important impact on women. In the wake of the 2008 recession, the Guttmacher Institute conducted a similar survey which showed similar results. But those results appeared after a year of struggle and financial hardship. Today, the impact of the crisis has appeared much sooner and continued job losses and a slow economic recovery over the months to come is likely to compound the problem even further. Already, more than half of the women in the survey said they or someone in their household had lost their job or had their hours cut. And more than forty percent said they worried whether they would still be able to properly take care of their children. The challenges the survey exposes today will have an important effect on the America of tomorrow. As we begin to think about how we can rebuild from this crisis, which still has us firmly in its grasp, we must think about how we can create healthcare systems and social support systems that better meets the needs of women. Today’s outbreak has already had a disastrous effect on women’s sexual health and their physical wellbeing, reinforcing the disparities that already existed among marginalized communities. We need to do more and do better as we look ahead to the future. This article originally appeared in Forbes and is available online here: Women’s Health And The Ripple Effect Of The COVID-19 Pandemic On Fertility Choices 244
July 2020
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Lessons For COVID-19 From The Early Days Of AIDS Scientific American | July 6, 2020 | Article
Thirty-six years ago, we were, like today, in the midst of a new and still somewhat mysterious global pandemic. In the U.S. alone, more than one million people were infected with HIV, and 12,000 had already died of AIDS. At the time, we were just beginning to understand how the virus worked. But that didn’t stop some leaders from making wildly optimistic claims about an AIDS vaccine being delivered within two years. Now, with COVID-19, we are in a remarkably similar spot: 2.7 million people have been infected across the U.S., and 128,000 have died of the disease. Despite our limited understanding of how the novel coronavirus works and what it does to the human body, many are putting what I consider a disproportionate amount of faith in the possibility of a COVID-19 vaccine by 2021. My feelings today echo my feelings a third of a century ago: yes, a vaccine may be possible, but it is by no means a certainty. Every deadly virus tells a story. As each chapter unfolds, we learn more about the possibility of developing a vaccine. The poliovirus, for example, told us early on that a vaccine would be possible. When that virus enters the body, it responds by making antibodies that can clear the pathogen entirely. It’s a hit-and-run: The virus hits you hard, then runs away for good. Once you have the antibodies, it can’t cause you harm again. With HIV, the virus told us the road to a vaccine would be long and challenging. As the outbreak unfolded, we began tracking antibody levels and T cell counts of those infected. The high levels of both showed that patients were mounting incredibly active immune responses, more forceful than anything we’d seen for any other disease. But even working at its highest capacity, the body’s immune system was never strong enough to clear the virus. Unlike 246
a hit-and-run such as polio, HIV was a “catch it and keep it” virus— once you were infected, the pathogen stayed until your body had destroyed it. While that situation didn’t mean a vaccine would be impossible, it certainly meant developing one wouldn’t be easy. SARS-CoV-2 has echoes of both HIV and polio. We know from nearly 60 years of observing coronaviruses that a body’s immune system can clear the virus. But a coronavirus is a tricky thing. The virus distorts the immune system so that even after you clear it, the pathogen can reenter your system and cause illness again. It is not a hit-and-run or a catch and keep but a “get it and forget it” virus that is able to infect the same person multiple times. For those who are listening, SARS-CoV-2 is telling us the path to a vaccine is going to be filled with obstacles. While some people with COVID-19 make neutralizing antibodies that can clear the virus, not everybody does. So whether a vaccine will stimulate neutralizing antibodies in everyone is still unknown. Also unclear is how long those antibodies can protect someone from infection. Another challenge regards one of the ways SARS-CoV-2 enters the body: through the nasal mucosa. No COVID-19 vaccine currently in development has shown an ability to prevent infection through the nose. In nonhuman primates, some vaccines can prevent the disease from spreading to the lungs. But those studies don’t tell us much about how the same drugs will work in humans, because the disease in our species is very different from what it is in monkeys, who don’t become noticeably ill. A more serious obstacle is the potential safety of a vaccine. Many vaccines include powerful adjuvants that are meant to inflame the body’s immune system, making the vaccine itself work better. The adjuvants in some vaccines currently being tested have led to serious side effects among young and healthy patients, including at least one who landed in urgent care because of extremely high fever fainting as well. If that’s what a vaccine does to the young, imagine then the side effects for the old and infirm, who are the ones most in need of a viable drug. These are significant challenges for any vaccine developer and should give us pause before believing too readily in a safe and effective vaccine by 2021. The good news, though, is that even without a vaccine, we are not without hope. Other medical solutions may prove just as effective at breaking the chains of 247
transmission. Coronaviruses happen to be a target-rich environment for other types of drugs that can prevent viruses from multiplying. For other viral diseases, such as HIV/AIDS, hepatitis C, and herpes simplex virus types 1 and 2, antiviral drugs can both treat patients who are ill and prevent others from becoming infected. Thanks to these antivirals, new HIV infections in the U.S. have long been on a steady decline, and a positive HIV diagnosis is no longer a death sentence. Antivirals have two common targets: polymerases, the enzymes a virus needs to copy its genome, and proteases, those needed to cut larger proteins into smaller, functional fragments. SARS-CoV-2 requires an active protease to copy itself. A couple of months ago a group of scientists announced their discovery of a new drug candidate that inhibits that protease. In test-tube experiments, they found the chemical could bind to the protease and prevent replication. And early results in dogs and mice suggest that the drug is both effective and nontoxic. Though there is still much to be done before safety and efficacy in humans can be proved, the beauty of antivirals is that effectiveness can be determined much more easily than with a vaccine. Within a few days, you know your answer: either the drugs reduce the viral load in a patient, or they don’t. And you don’t need many people to prove it. Our first effective treatment for HIV was initially proved in a group of just 36 patients: 18 people who were given the drug and 18 controls. While I admit to lacking confidence in our ability to deliver a COVID-19 vaccine by 2021, I am convinced we will have antiviral drugs to prevent and treat SARS-CoV-2 infection by next year, if not sooner. And perhaps not only antivirals. In the June 12 issue of Science, researchers published important progress on another approach to treat and prevent SARS-CoV-2 infections. This approach used monoclonal antibodies that stick to the SARS spike protein and prevent it from binding to ACE2 receptors in our body. Here, too, success can be gauged much more quickly than with a vaccine. My hunger for a vaccine is as strong as the next person’s. My experience, however, tells me that hope for a quick COVID-19 vaccine may prove as misplaced as our hope for a quick HIV vaccine 36 years ago. I don’t doubt that it is possible. But while we wait on 248
a scientific breakthrough, we should not lose sight of the solutions that are more easily within our grasp. This article originally appeared in Scientific American and is available online here: Lessons For COVID-19 From The Early Days Of AIDS
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Even Without A COVID-19 Vaccine, There's Reason For Hope CNN | July 8, 2020 | Article
A lot of hope has been placed on the possibility of a COVID-19 vaccine by the end of this year. However, overcoming the technical challenges of developing a vaccine -- and the safety issues inherent in making one that works for the populations most at risk -- is no easy feat. While it may be possible to deliver a vaccine by the end of this year, absolutely every step of its development would have to go perfectly. From experience, I can tell you how rare that is. Vaccines don't act as impenetrable shields that prevent viruses from entering our bodies. Rather, they teach our bodies how to rapidly mobilize our immune defenses against a foreign invader. The rapid immune response helps us clear the virus from the body before it wreaks its damage. This article originally appeared on CNN. To read the full article, click here: Even Without A COVID-19 Vaccine, There's Reason For Hope
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Is Wearable Technology The Savior We’ve Been Waiting For? Forbes | July 9, 2020 | Article
The companies behind popular smart rings and wristwatches like the Oura ring, Fitbit, and Apple Watch are trying to program their products to detect early symptoms of COVID-19. If they succeed, wearables could potentially play a significant role in putting an end to this pandemic. Wearables are ideal for monitoring individual biometrics, an element that has been sorely lacking from disease control efforts in the United States and other countries where the pandemic rages on. They take around 250,000 measurements per day, including heart rate, sleeping patterns, and body temperature. Some measurements are particularly good for signaling the onset of sickness. When you fall ill, your resting heart rate (RHR) tends to increase. You sleep longer, and overall your bodily activity drops. Wearables can track all three of these variables—and notify the user to any abnormal changes. One study, published in January, took this function to task by investigating whether wearables that monitor sleep and RHR data could pick up on respiratory infections like influenza. The results are promising, showing that wearables could predict infections that we humans usually register two to three weeks too late. What if the same is true for early COVID-19 symptoms? Oura, the company behind the Oura Ring, is currently conducting research to see if the data their product collects, combined with daily user responses about symptoms, can predict COVID-19 infections at least three days before onset. More than 2,000 healthcare workers at the University of California, San Francisco will start wearing Oura Rings, joining the hundreds of health professionals and first responders at the West Virginia University Rockefeller Neuroscience Institute who test drove them back in May. Those initial runs produced Oura’s best results so far: accurately forecasting COVID-19 symptoms a full 24 hours before 251
they showed. While this falls short of their goal, with some improvements it could be within reach. The downside of most wearables is that they aren’t typically worn on body parts immediately relevant to an incoming COVID19 infection. Symptoms like fever, shortness of breath and coughing are among the most common, and wrists and fingers are the wrong place to monitor them. A group at Northwestern University is working on a more sophisticated device that can detect these common early symptoms. The device sits at the base of the throat and measures skin vibrations and temperature. It monitors coughs, detects labored respiration, and it sits close enough to the carotid artery to monitor heart rate. A recent addition to this device is a wearable pulse oximeter. The oximeter lets physicians detect low blood oxygen levels, an asymptomatic feature of the virus. Paired together, these two devices give a full picture of the disease and allow for better monitoring of its progression. Wearable technology: a solution for some or for all? Conventional wearables may not be ideal for detecting respiratory infections well in advance, but they do make great tracking devices once symptoms do appear. One of the main strategies that governments use to control the spread of the virus is contact tracing, and more specifically, contact tracing apps. The problem with these apps is that their reach is limited to smartphone users—which is where wearables come in. In Singapore, where many older adults who are vulnerable to COVID-19 don’t own smartphones, health authorities have broadened their contact tracing regimen to include specialized tokens. Each token exchanges Bluetooth signals with other tokens in the area, storing all interactions for 25 days. When a user tests positive for COVID-19, they must hand their token over to the authorities for contact tracing. Singapore’s approach of prioritizing the elderly should be a global one. Several studies show that older adults are more likely to develop either a severe or fatal case of COVID-19, and nursing homes have been especially dangerous due to the high
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transmissibility of the virus. One infected caregiver can potentially infect everyone else in the facility. Such challenges have inspired the creation of tools like iZhaohu, a Shanghai-based platform that uses artificial intelligence to personalize and optimize elder care services. To address the problem of viral transmission in nursing homes, iZhaohu created two digital systems: the Cheetah remote elderly care system, and the Dolphin automation system. When the Cheetah system is deployed with surveillance cameras, smart beds, sensors, and a single button alarm service, it becomes possible to detect the source of any infection. The Dolphin automation system, on the other hand, is designed for internal use by employees and clients. iZhaohu monitors the activity and needs of elderly, also making it ideal for those with chronic illnesses. Instead of trying to detect symptoms using wearable technology only, iZhaohu uses an integrated system made of many different elements. This is what made their work with COVID-19 successful. To replicate that success, elder care facilities must have professional ICT capabilities and strong emergency response capacities—features that, more often than not, are absent or lacking. Where wearables fail us While none of the studies on the technologies have published peer reviewed results, one thing has become clear: wearable technology alone is not enough to detect COVID-19 symptoms. Or at least, the ones we have now aren’t. More often than not, an app is already necessary when using such devices. The high infection rate of the virus poses an even greater challenge in tracing the source and limiting the number of cases. Add asymptomatic cases and the task becomes nearly impossible. It is thus crucial to use an integrated ICT system that gives users the big picture. Just because wearable devices don’t make accurate predictions of COVID-19 symptoms doesn’t mean they’re not useful healthcare tools. This is especially the case for people with chronic illnesses. Because all wearables measure heart rate, in April 2018 a man was saved by his Apple watch. The smartwatch detected a spike in his heart rate and warned him by setting off an alarm. The man, who 253
was feeling healthy, rushed to the hospital just in time to find out that two of his coronary arteries were fully blocked, and the third one was nearing 90 percent. In elder care facilities, this feature could be paired with an alarm system which also alerts caregivers or physicians. Such a feature could also prove useful in children who suffer from similar conditions. The biggest concern remains privacy. Some people are not willing to share their personal information, whether it is their medical history or their whereabouts. Such privacy concerns are the main reason many countries have not turned to wearable technology, even or contact tracing apps, for help in managing the outbreak. Another possible downside is the disparity in ownership of these devices within a population. Areas where the number of users is low will be neglected and outbreaks will be missed. While wearable technology is far from foolproof, that doesn’t mean we should disregard it, especially since artificial intelligence is on track to become a core part of healthcare. Even if wearable technology helps detect only a handful of cases, it shouldn’t be underestimated. This pandemic started with one person. To catch one infection early is to potentially save thousands of lives. This article originally appeared in Forbes and is available online here: Is Wearable Technology The Savior We’ve Been Waiting For?
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Is It Too Soon To Restart Sports? Forbes | July 10, 2020 | Article
After being stuck indoors for months due to COVID-19, many professional and amateur athletes are now returning to center field. But some are wondering if sports may be restarting too soon. The National Basketball Association just announced that 16 of its players have tested positive for COVID-19. To date, 40 Major League Baseball players are known to be infected. Major League Soccer, which has had 24 players already test positive, is thinking of resuming its season next week. And it’s not just the players—staff are falling ill as well. The problem with sports like football, baseball, soccer, and hockey is that their athletes are constantly too close for comfort. Every practice and every game, they’re face-to-face, sharing equipment, and almost always breathing heavily on each other. Social distancing is near impossible on the field, and equally challenging in locker rooms. In fact, the locker room is the definition of a COVID-19 hotspot: a damp, steamy indoor space in which contact with others is unavoidable. To protect players and staff, many teams and leagues are looking to corral them into a so-called “bubble”—a restricted environment intended to limit potential spread of the virus. The soccer players of the San Jose Earthquakes, for example, are staying at a Disney resort where they must keep to their rooms whenever they’re not out on the field or gathering for meals. This approach is patchy and problematic for many reasons. Restricting the mobility of a group of people isn’t enough to eliminate all risks—neither for the group, nor for the outsiders who brush up against them. One answer to this is to mandate testing for all players, but even that measure has its shortcomings, not least among them the threat of false negatives. There is also a chance that someone who recovers and tests negative might be able to spread the virus still.
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Another problem with the “bubble” idea to consider is that sports teams will be exposed to other teams when they play games. This introduces another variable: the new people the team will be in contact with. Not only must the safety of the visiting players be ensured, but that of visiting staff members and coaches. By allowing teams to play each other, the teams and leagues are completely going against the idea of what a bubble is supposed to be. The final, but not insignificant, issue that must be reckoned with is how to actually enforce the bubble in the first place. Asking a group of young athletes to remain indoors and out of contact with girlfriends, boyfriends, family, and friends is one thing. Ensuring they adhere to these demands is another entirely. Even in the midst of a global pandemic, sports haven’t lost their importance. Not only do they provide fans with a sense of normalcy, they also serve as a much-needed form of enjoyment and an escape from reality. But the fact remains that restarting sports too soon will open the door to numerous high risk transmission events—whether for players and staff, or for fans crowding the stands. Cody Lyster was a 21-year-old college baseball player who caught COVID-19 in April. Because Cody was a young athlete who had no existing health conditions, his family was sure he would make a successful recovery. However, within days of developing symptoms, he was put on a ventilator; on April 8, he passed away. Even young athletes are not immune to infection with COVID-19, and if they’re required to play on sports teams during the pandemic, it is likely that many more will contract the virus. While sports teams can attempt to reduce the spread of COVID19 among players and personnel by taking precautions—such as regular testing, reducing physical contact, maintaining six feet of distance between players, enforcing mask wearing, and constantly disinfecting equipment and locker rooms—sports are inherently high risk events. Our main priority should be keeping athletes, staff, and fans safe. To do so, we must slow down our approach and rethink when to restart sports altogether. This article originally appeared in Forbes and is available online here: Is It Too Soon To Restart Sports?
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Midsummer For The Season—But Not The Coronavirus: A Case In Poor Leadership, The U.S. Containment Strategy Has Lacked Clarity, Consistency, Credibility, And Compassion Think Global Health | July 10, 2020 | Article
COVID-19 stormed through our cities and towns but stayed in some locales much longer than others. It came to Asia in January and all but vanished with the winter. In Europe it stormed through countries in early spring and withered away by summer. Here in America, it struck New York and Chicago with deadly force in March and April but faded away in May—only to surge across other parts of the current, endless tidal wave across the American south, southwest country and west. As more cases continue to wash across the globe, but why, in midsummer 2020, is COVID-19 still raging across the US when it was so quick to leave other parts of the world? The answer is clear: the coronavirus succeeds where we fail. And by any metric, the government of the United States has failed. The pandemic exploits our greatest weaknesses as a nation. But it can still be foiled by our strengths. Absent effective drugs or vaccines, we still have the knowledge needed to stop COVID-19 though some may doubt whether we have the will to implement the measures we know are needed. In East Asia, New Zealand, and Australia countries were able to confront the challenge by accepting the magnitude of the problem and employing the public health tactics necessary to contain the outbreak. We failed to do the same because of weaknesses that, though profound, can be strengthened. Here I enumerate three: leadership, governance, and social solidarity. Leadership, Governance, and Social Solidarity
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In times of crisis, we first need leadership. Crises are chaotic by nature and we look to our leaders to guide us through the disarray. That guidance must be clear, credible, consistent, and compassionate. Clear, as crises often create confusion around real and imagined threats. Credible, as belief predicates action and requires trust. Consistent, as vacillation smacks of incompetence. Compassionate, as empathy is based on an understanding of our suffering. In Germany, a country with a leader who had previously been under fire over for her lack of strong leadership, Chancellor Angela Merkel took control early on in the crisis, defining the magnitude of the problem in a rare televised address and defining the steps that needed to be taken to avoid potential disaster. She rallied the support of leaders in all of the country’s states for a nationwide shutdown, which was based credible, science-backed approaches to pandemic. Even though Germany’s measures were strict—during the lockdown any gathering of more than two people from different households was banned entirely—consistent messaging and Merkel’s credible and compassionate approach convinced the great majority to adhere to the restrictions voluntarily. The same cannot be said about the United States, where President Donald J. Trump displayed poor leadership and is now suffering the consequences. COVID-19 cases are still on the rise, and there are no nationwide mandatory guidelines for people to follow to this day. In tandem with leadership, we also need good governance. A national crisis requires coordinated national action, and effective coordination depends on our ability to mobilize existing government agencies. They cannot be created on the spot. Responding agencies must be competent—each headed by an experienced leader, staffed by knowledgeable experts, and guided by the best knowledge available. The U.S. Centers for Disease Control and Prevention (CDC) and the National Institute of Allergy and Infectious Diseases (NIAID), normally play leading roles in providing the scientificallybacked guidance that national and state agencies use as the backbone of their efforts to respond to infectious disease outbreaks. But with COVID-19, the CDC was quickly sidelined and the advice of experts at the NIAID was repeatedly undermined by the president, who arguably played an outsize role in shaping public health 258
decisions about treatment options and approvals. Such a move created widespread disorganization and a lack of coordination on practically every element of our response, from testing to treatment and even the disbursement and availability of lifesaving medical equipment. Compare our response to that of our neighbors to the north. In Canada, the prime minister stepped back to allow the minister of health and head of the Public Health Agency of Canada—the country’s chief public health officer—to step in to offer advice to the prime minister on necessary measures. Those measures were then implemented at the provincial level through local public health officials and political leaders. Last but not least, we need social solidarity. Governments, no matter how competent, cannot manage a national disaster without their own citizens. Any collective response is the sum of individual actions. Some may argue that America, built on independence and personal freedom, is not suited to such solidarity. Yet, we have already proven that when faced with a real and deadly threat we are willing to forego some liberties to protect our nation. One need look no further than 9/11 for the proof. Grading Our Responses Taken together, leadership, governance, and solidarity give us a framework for understanding the successes and failures—both partial and total—in coping with COVID-19. After some initial vacillation, the leaders of Asian countries, as well as those of Australia and New Zealand, were clear, consistent, and credible. Some were compassionate, others not. Jacinda Ardern, New Zealand’s prime minister, was successful in implementing one of the world’s strictest lockdowns, but her actions were not without failing. She declared the country virus free too soon, which led to a second spike in infections. But when confronted with the tangible results of her health system’s failings she readily admitted the error and resolved to never let the same mistake happen again. The initial response of Western European leaders was slow— their early messaging, mixed. But as the magnitude of the disaster became apparent, each gave clear and consistent directives, warning of the danger and outlining a coherent response. They drew upon a 259
reservoir of credibility and compassion. Sweden proved to be the exception. Rather than leading, the government abdicated responsibility and the country continues to pay a heavy price. The United States government is a case in point for poor leadership. Its containment strategy has lacked clarity, consistency, credibility, and compassion. Right now, this seems to be a common failing for most leaders in the Americas. But in the United States, the wealthiest and most technologically advanced of all developed nations, this failing is particularly stark. This article originally appeared in Think Global Health and is available online here: Midsummer For The Season—But Not The Coronavirus: A Case In Poor Leadership, The U.S. Containment Strategy Has Lacked Clarity, Consistency, Credibility, And Compassion
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We're Wasting Time Talking About Herd Immunity CNN | July 13, 2020 | Article
Debate over whether herd immunity will be our salvation to the escalating COVID crisis was recently fueled by two new reports. The first was the release of a new nationwide study from Spain, a former COVID hotspot, which suggested that too many lives would be lost while waiting to achieve the approximate 60% infection rate needed for herd immunity, whereby so many people become immune to the disease that it is effectively stamped out. The second was a report from New York, which suggested that in some communities herd immunity may have already been achieved, with one health care clinic reporting that slightly more than 68% of COVID tests taken had come back positive. But we waste critical time with this pointless discussion, because the facts are already quite clear: herd immunity will likely never be achieved for COVID-19 or any other coronavirus. We know this thanks to new research on the development and decline of COVID antibodies and from a wealth of epidemiological evidence on coronaviruses as a whole. This article originally appeared on CNN. The full article is available here: We're Wasting Time Talking About Herd Immunity
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What Does Disappearing Immunity To COVID19 Mean For A Vaccine? Forbes | July 16, 2020 | Article
The first results of Moderna’s COVID-19 vaccine trials were officially published Tuesday and the news was good—patients injected with the mRNA-based vaccine produced antibodies that fight the COVID-19 virus. Just how good is this good news? That depends on whether or not you accept the fundamental assumption underlying this generation of COVID-19 vaccines as fact. To proclaim these trials a success is to take for granted that exposing people to viral proteins will trigger a vigorous, long-lasting immune response. But studies of the molecular biology of SARS-CoV-2, along with the natural history of the coronavirus family, may offer evidence to the contrary. Vaccines don’t act as shields, protecting you from a disease. Instead they act more as alarms. Just like a fire alarm won’t put out the fire, a vaccine won’t prevent you from infection. They’re just a means to alert your immune system early on that a danger exists. In the end, it’s your immune system—including those antibodies—that do all the work. Several recent studies have found that antibodies to SARS-CoV2 decline in strength and number in the weeks and months following infection. One study describes a decline in even neutralizing antibodies, which are thought to be protective against reinfection and disease. While this decline is not without precedent and is in fact typical of human coronavirus infections, the question is what it portends for the pandemic and for the success of COVID-19 vaccines. “Get it and forget it” SARS-CoV-2 is broadly similar to the four coronaviruses that cause about one third of all common colds. Each year, the same four viruses infect us the world over, sweeping the Northern Hemisphere from December to February; south of the Equator from May to July; and in the tropics, year-round. These waves of infection, which with 262
rare exceptions cause minor symptoms only, have repeated year in and year out since the discovery of the virus in the 1960s. The ability of this coronavirus quartet to persist absent alteration is highly unusual. Influenza infections occur annually, too, but the dominant strains differ each time to evade the population’s protective and persistent immune responses. In the 1970s two independent teams of medical researchers conducted experiments to determine whether or not the same coronavirus strain might reinfect and give a cold to the same person. Volunteers who were deliberately exposed to the virus contracted colds and recovered. A year later, they were again exposed to the same virus—and again were infected and developed cold symptoms. These experiments established that protective immunity to the coldcausing coronavirus is short-lived. I call this phenomenon "get it and forget it,” and it describes the interaction between these viruses and our immune systems that is so unique. Confronted with a cold-causing coronavirus, our bodies evidently forget that we were infected at all. For us, this leaves us susceptible to annual colds, which are generally harmless but a nuisance besides. For the viruses, this is a winning strategy, as it rids them of the need to change to survive. At present, we don’t understand coronaviruses in sufficient detail to know why our immunity to them so short-lived.* What we do know is that if SARS-CoV-2 behaves as its coronavirus cousins do, COVID-19 is sure to become a seasonally recurring pandemic. A vanishing act As I mentioned previously, it has already been confirmed that immunity to SARS-CoV-2 fades quickly after infection. When viral infection occurs, a type of antibody called IgM appears within one to two weeks. IgM antibodies mobilize against the virus, then begin to disappear in the weeks and months following infection. Two to three weeks after an infection has cleared, IgG antibodies appear. It is the case for many viruses, such as those that cause most childhood diseases, that reasonably high levels of IgG antibodies persist for many years. It is not the case for SARS-CoV-2. Studies show that the IgG antibodies we produce while recovering from COVID-19 decline rapidly. Not only that, but in blood samples from some convalescent COVID-19 patients, IgG antibodies and
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even IgM antibodies are altogether absent. (That these patients were, in fact, infected was confirmed by successive PCR tests.) How does SARS-CoV-2 engineer this disappearing trick, and what implications would the mechanism have for the development of vaccines? One possibility is that the coronavirus proteins have evolved to become weak immunostimulants. If this is so, it will be a problem for COVID-19 vaccine candidates that use natural variants of the virus proteins as antigens. To be successful, their makers will have to engineer proteins that differ from those in the virus itself— not an impossible task, but a difficult one that would take time. We won’t know the answer until we learn how well the vaccines protect against infection, and how long protection lasts. Manipulating immune memory Another possibility is that coronaviruses have developed the means to manipulate the human immune response to its own advance. Coronaviruses have carved out an interesting ecological niche for themselves. When a coronavirus enters the body, it downmodulates the immune system, reducing our immune response. In doing so, the virus gains a toehold allowing it to spread. Even if the immune system is able to eventually clear the virus, the damage has been done. By down-modulating our initial immune reaction, the coronavirus has ensured that our long-term response to the virus isn’t as powerful as it ought to be. Immunity fades and our bodies essentially forget that we were ever infected. In another, the virus could actively compromise the memory response upon re-infection. Remember that vaccines, once injected, don’t shield the body from infection. Instead, they equip the immune system with a sophisticated alarm system—one that will trigger a vigorous, rapid immune response whenever the invading virus sets off the alarm. Immune memory cells, trained by the vaccine to mobilize at the sound of the alarm, allow the body to mount a full-blown immune response in days rather than weeks. If SARSCoV-2 does have the ability to impede immune memory, that means it can effectively disconnect the alarm. A virus with the potential to compromise the memory response would pose a difficult vaccine challenge indeed. There are hints that coronaviruses, SARS-CoV-2 included, may employ several immune evasion techniques. We already know that SARS-CoV-2 does produce one or more proteins that actively 264
interfere with immune function. The orf-3b gene product specifically interferes with precisely those signals impotent for initiating the production of anti-viral antibodies and T-cells. The orf3b protein down-regulates the production of interferon-gamma and IL-2, both necessary for initiating the production of anti-viral antibodies and Tcells. The ability of orf3b to interfere with immune activation is very likely the tip of a very large iceberg when it comes to altering the immune response. At least 9 SARS virus proteins and 6 MERS virus proteins are known to interfere with the host immune response. It is very likely that SARS-CoV-2 also carries a full complement of similar genes that collectively may help explain three usual features of infection, antibody-negative convalescents, rapidly fading antibody levels, and re-infection. Immune reactions to SARS-CoV-2 infection and disease are complex, and we knew from the beginning that developing a vaccine that outwits the virus wouldn’t be easy. We would be very lucky to get it right on the first try. If we’re not blessed with such good fortune, we must buckle down and recognize that we’re in this for the long haul—and throw our support into the prolonged research effort necessary to ensure success. * One reason we don’t have the information we need is the startstop nature of coronavirus research funding. For 40 years postdiscovery, coronavirus research was a rare specialty. Research on many other viruses took precedence—mostly those that kill, such as HIV/AIDS, polio, smallpox, Ebola, and respiratory syncytial virus. It was not until the advent of SARS in 2003, followed by MERS, that research on these viruses was well-funded and scientists had the opportunity to begin to understand them in more detail. As SARS waned and the potential for MERS to cause pandemic disease disappeared, much of the funding for coronavirus vanished. We’re just now playing catch-up to understand some of the details of the interaction of SARS-CoV-2 with the human body at the level we understand HIV after more than 35 years of intense research. We’re filling in the gaps, but we have a long way to go. This article originally appeared in Forbes and is available online here: What Does Disappearing Immunity To COVID-19 Mean For A Vaccine?
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A Key To Understanding The Race For A COVID-19 Vaccine Forbes | July 20, 2020 | Article
Now is the time to prepare yourself for an incoming onslaught of COVID-19 vaccine news. With eight candidates already in human trials and almost 180 more in the wings, publications and press briefings touting progress will soon arrive wave after wave. In the face of so great an outpouring of information, how are we to understand what each new finding means for our children, our jobs, our economies, and a world in crisis? We can begin by listening for a moment to what Ken Frazier, CEO of Merck, had to say to a team from the Harvard Business School. He speaks on behalf of a company that has brought lifesaving vaccines to more people than all others combined. Here’s an excerpt: "…when people tell the public that there's going to be a vaccine by the end of 2020, for example, I think they do a grave disservice to the public. I think at the end of the day, we don't want to rush the vaccine before we've done rigorous science. We've seen in the past, for example, with the swine flu, that that vaccine did more harm than good. We don't have a great history of introducing vaccines quickly in the middle of a pandemic.” If speed can’t be a benchmark of success, then what is? Again, Frazier has the answer: “What we're hoping to be able to do with these different approaches is to create a vaccine that we can study quickly that can be both safe and effective and can be durable. Those are three different issues. No one knows for sure whether or not any of these vaccine programs will produce a vaccine like that. [emphasis added]” After saying in an earlier interview with CNBC that the Merck vaccine would not be ready for use by the end of 2020, Frazier added, "Our experience suggests those are very aggressive (12 to 18 months) compared to other timelines for getting a safe and effective vaccine...Speed is one factor, but in some ways we don’t really accept the concept of a race. We 266
understand the urgency, but our goal isn’t to be the frontrunner in the early stages — it’s to develop a vaccine that is safe and effective.” I would add that the goal is to develop a vaccine that can be given to billions of healthy people in countries rich and poor. Given the very large numbers of people destined to receive the vaccine, the fragility of the target older population, and the underlying health issues of the underserved populations who need protection direly, even rare side effects could wreak havoc. Contrast Frazier’s note of caution with the announcements from other leading pharmaceutical companies—like Pfizer, whose CEO told Time earlier this month that he believed their vaccine may receive FDA approval as early as October 2020. Or the many announcements from AstraZeneca that use similar rhetoric to hype up their Oxford vaccine. Other countries are also rushing into the fray. One of them is China, where an experimental vaccine has already been approved for military use. With this in mind, allow me to break down, piece by piece, the language surrounding the latest vaccine data from Moderna, an American biotechnology company. The preliminary report, published in the New England Journal of Medicine, describes the results of a safety trial of 45 volunteers for the company’s vaccine candidate. The vaccine was administered in two shots to the upper arm, given four weeks apart. Three groups of fifteen received low, medium, and high doses, respectively. The good news The vaccine elicited anti-SARS-CoV-2 antibodies in all who received the injection. What’s more, they all developed antibodies that had some level neutralizing activity, as well as antibodies that, at least in the laboratory, can inactivate the virus. Interpretation: This information, while good news indeed, does not help us predict whether the vaccine will actually prevent infection or disease. It only tells us that it might. The not so good news Two doses of the vaccine, spaced four weeks apart, are needed to develop these antibodies. While many vaccines require multiple doses, a single dose vaccine is the surest and swiftest way to vaccinate large underserved populations around the world. Experience has taught us that even if a second or third injection is mandated, many don’t show. 267
Interpretation: This vaccine is an unlikely candidate for global use. The worrying news The ratio of binding to neutralizing antibodies is about 1,000 – 2,000 to one. In other words, for every antibody that inactivates the virus, more than 1,000 do not. Such a ratio raises the possibility of antibody dependent-enhancement that Frazier mentions—meaning the vaccine may worsen disease, not prevent it. Most vaccines undergo rigorous testing in monkeys before human trials to limit the chances of this unfortunate outcome, but for this vaccine candidate that step appears to have been omitted. Interpretation: This observation introduces some uncertainty to the belief that this vaccine will be safe enough for widespread approval and use. The bad news The following sentence was included in the abstract of the publication: “Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250μg dose group reported one or more severe adverse events.” That means four of the 45 volunteers—including three who received a high dose—experienced “systemic” adverse effects” considered medically significant but not life-threatening. One of the volunteers described his experience for STAT News. Hours after receiving the second dose, he developed a fever 103, fainted, and sought medical attention at an urgent care center. After encountering such reactions at the highest dose, the company announced that it would proceed with the moderate dose only. But the conclusion to the abstract includes the following sentence: "The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants and no trial-limiting safety concerns were identified.” Interpretation: Were I the CEO of this company or a member of its FDA review committee, I would insist on collecting much more safety data before proceeding. I would ask for a much larger phase 1 trial in a likely target population that includes many older men and women—some with moderate underlying health conditions such as diabetes and obesity—before allowing further studies. 268
If such serious reactions occur at 2.5 times the trial dose in so few people, it is reasonable to expect the many severe and even lifethreatening reactions to occur at the middle dose when given to a large, diverse population. The first criterion of a successful vaccine is that it must be safe. Last takeaways Ken Frazier went on to make a final point in his interview with the Harvard Business School team. “When we do tell people that a vaccine’s coming right away,” he said, “we allow politicians to actually tell the public not to do the things that the public needs to do, like wear the…masks.” To this I would also add: Do not count on a drug or vaccine to save us from the pandemic. Evidence from other countries around the world and even in some states in the U.S. shows that collective behavior change can limit and eliminate the infection, even after it has spread widely. Ancient wisdom is sometimes the best. In our mad rush to a COVID-19 vaccine, recall the words of Ecclesiastes 9:11 (King James Version): “I returned, and saw under the sun, that the race is not to the swift, not the battle to the strong, neither yet bread to the wise, nor yet riches to men of understanding, nor yet favor to men of skill; but time and chance happeneth to them all.” This article originally appeared in Forbes and is available online here: A Key To Understanding The Race For A COVID-19 Vaccine
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COVID-19 Might Be Far More Widespread Than We Think. Here’s What We Can Do About It Forbes | July 22, 2020 | Article
Ever since COVID-19 first began to spread, the question of how many people are infected with the disease has remained difficult to answer. Official case counts, it is widely acknowledged, represent only the tip of the iceberg—a gap in our knowledge even more felt today, now that the virus is ten times as transmissible as earlier strains. Just how widespread is infection actually? In Spain, a broad survey of the country’s population found that about 5 percent—that is, 2.3 million people—were infected. Prevalence varied according to occupation (health workers, 10 percent) and age (children, 3 to 4 percent). The actual rate of infection, the study suggests, was about ten times the roughly 250,000 cases picked up by standard genome tests. Two JAMA articles, both published this month, report seroprevalence data that tells a similar story—only this time, the setting is 10 different locations in the United States. One article is a scientific-medical manuscript, the other a commentary. While the rate of infection varied widely from site to site, on average it was found to be about 10 percent. Since the population of the United States is about 330 million, a 10 percent infection rate would translate to a whopping 33 million infected people. As of today, the number of people who have tested positive in the United States is just shy of 4 million. This means that the actual rate of infection, as was the case in Spain, may be 10 times higher than originally reported. If that many more people are infected—and cable of infecting others—than previously thought, the implications are vast. One being that people who are infected but who don’t develop symptoms, no matter their age, are spreading the virus further and faster than we think.
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People of all ages who are asymptomatic, from young children to those 80 and older, are well capable of transmitting the virus to others, who may fall seriously ill or die. This observation reinforces the advice I often give to others: that you should assume everyone outside your personal “bubble” may be infected and act accordingly. Certainly it justifies the continuance of broad social distancing measures and restrictions on social and work activity. An infection rate of 10 percent would also present a challenge to those who are still holding out hope for so-called herd immunity, which requires prevalence of 60 to 70 percent to be achievable. As the authors of the JAMA commentary point out, the rates of 5 to 10 percent observed in Spain and the United States fall significantly short of this mark. The articles also tell us that infection rates vary not just between cities, but within cities as well. Perhaps unsurprisingly, given all the data we have on connections between social inequality and vulnerability to COVID-19, intra-city variation correlates with income and occupation. The lower the income level, the higher the infection rate. Those with lower incomes often have no choice but to continue working service jobs, exposing them to risks that those with higher incomes may avoid. As long as infection persists in any community, SARS-CoV-2 will continue to pose risks to the entire population. In Singapore, where case counts were so low for so long, disease outbreaks in neglected guest worker dorms did much to bring back the dangers of COVID-19 to all. To put a stop to this pandemic, we need to intensify our focus on reducing infections in marginalized and low-income populations. Whatever the number of undetected COVID-19 cases, these are the people the disease will hit hardest. This article originally appeared in Forbes and is available online here: COVID-19 Might Be Far More Widespread Than We Think. Here’s What We Can Do About It
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The Complex Pathogenesis Of COVID-19 Forbes | July 24, 2020 | Article
Our understanding of COVID-19 as a disease has evolved rapidly over the course of the pandemic. While many aspects of COVID19—from its symptoms to its duration to its short- and long-term aftereffects—remain difficult to pin down, we now have enough data to identify four broad stages of infection that can guide us going forward. To grasp the complete picture, it helps to look back on how each individual piece of the puzzle fell into place. The story began, like most mysteries, with an emerging problem and a complete lack of knowledge. In the first few weeks of the outbreak, COVID-19 appeared to be nothing more than a serious pneumonia. Symptomwise, it seemed similar enough to what some people experience when they contract a severe case of the flu. A month went by. Researchers in China, and soon enough elsewhere, began to realize that the lung damage associated with the disease was more complex than previously thought. This was due in large part to an overreaction of the immune system known as a cytokine storm. Not only was the pathology of autopsied lungs atypical for viral-induced pneumonia, but high levels of inflammatory chemokine and cytokines were present as well. About two months into the pandemic, physicians around the world began noticing hypercoagulation—rampant blood clots, in other words. Heart attacks, ischemic strokes, and lung emboli were noted, as well as the incidence of blood clot-related kidney disease. More recently, evidence has emerged that suggests the existence of a late hyperinflammatory phase. When COVID-19 patients enter this stage, the lining of the blood vessels—arteries and veins alike— becomes inflamed. Skin rashes, COVID toe, and other markers of hyperinflammation appear. What’s curious about the disease progression is that most of it occurs after the immune system begins to clear the replication-
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competent virus. What’s more, viral RNA has been found lingering in the body long after the infectious virus has disappeared. This raises the possibility that much of the late—and highly lethal, I might add—aspects of the disease don’t occur because the virus is continuing to propagate itself, but because replicationcompetent sub-genomic fragments persist that are partially sequestered from immune recognition. Such pathology would be unusual, but not unprecedented. The chart below, created by infectious disease specialist Dr. Daniel Griffin, represents our current knowledge of how COVID19 progresses, from the moment of infection to no certain end. The pathologies described above can be summed up in four phases: the viral phase, cytokine storm phase, coagulation phase, and late hyperinflammatory phase. Aspects of the infection not depicted in this chart include damage to insulin-producing islet cells, which leads to diabetes; damage to the splenium of the corpus callosum, which leads to neurological complications; and damage to cells of the liver and heart. More pathologies are to come, I’m sure, as the number of COVID-19 patients increases. That so many COVID-19 patients go on to develop such a diverse array of adverse health outcomes is troubling, to say the least. But the more we learn about this disease, the more capable we become of developing tools to mitigate it. My hope is that those come to fruition sooner rather than later. This article originally appeared in Forbes and is available online here: The Complex Pathogenesis Of COVID-19
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What If There’s No COVID Vaccine? Project Syndicate | July 24, 2020 | Article
Although the multi-decade struggle against HIV/AIDS featured a great deal of tragedy and despair, the upshot is that medical science prevailed: what was once a death sentence is now a chronic condition. In thinking about worstcase scenarios for COVID-19, this recent experience offers both lessons and hope. When it comes to ending the COVID-19 crisis, our experience beating back HIV/AIDS can teach us much. Above all, it was never clear during that earlier pandemic whether we could count on an eventual vaccine to be part of the solution. In our efforts to overcome today’s crisis, we would be remiss to forget this lesson. During the early years of the HIV/AIDS crisis, I ran a laboratory at Harvard University, where we were researching the virology of the disease. Early observations showed that an HIV infection elicits an unprecedentedly strong response from both arms of the immune system – the B cells and the T cells. The body detects the threat posed by the disease, and it fights back as hard as it can, but fails. How, I wondered, can we create a vaccine that outdoes the best our bodies can do? It has now been 35 years, and we still don’t have an answer. The quest for a COVID-19 vaccine isn’t this bleak, but nor is it particularly bright. Six decades of experience with coronaviruses – which cause the common cold as well as more serious diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) – offers reason for both optimism and caution. To read the full text of this article, please click here: What If There’s No COVID Vaccine?
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An Investigation Into The Basis For The Loss Of Smell As An Early Symptom Of COVID-19 Forbes | July 27, 2020 | Article
The loss of the sense of smell and taste has proven to be the most reliable indicator of early infection of the SARS-CoV-2 virus. Between 25% and 50% of people report anosmia and ageusia as the very first symptom of COVID-19. Studies of patient records around the world find that the loss of smell or taste is more than twenty times as likely to predict a SARS-CoV-2 positive PCR than a fever, cough, or a stuffy nose. That is very likely because fevers and coughs are associated with many illnesses other than COVID-19. The loss of smell and taste differs from that associated with most colds. A stuffy nose can, and often does, degrade the sense of smell but not usually that of taste. Moreover, the loss of smell for most colds is not absolute. In the case of most colds, inflamed and swollen tissue blocks odors from reaching the olfactory sensory neurons located high in the nasal cavity, just below the cribriform plate that separates the back of the nasal passage from the brain. In the cases where the virus-induced loss of smell is profound, recovery may take months. The presumed reason is the destruction of the sensory neurons themselves, which regenerate slowly. The acute loss of smell and taste following SARS-CoV-2 infection returns in weeks, not months, suggesting that the underlying pathology may differ. These observations prompted Harvard scientists to investigate the pathology responsible for the loss of smell following SARSCoV-2 infection. Their approach was indirect. Rather than tracking infection of the virus itself, they sought to determine what cells in the olfactory tissue harbored two genes used by SARS-CoV-2 to enter cells, the ACE2 surface protein that serves as a receptor, and the cellar protein TMPRSS2 that activates the spike protein of the virus before viral entry. The results were unexpected. The olfactory neurons that bind and detect the chemicals that produce the sensation of odor express neither ACE2 nor TMPRSS2. Therefore, it is unlikely that the 275
sensory neurons are themselves infected. However, cells that surround and support the olfactory sensory neurons do express both genes and are therefore likely targets of the virus. These are called the sustentacular cells. These cells wrap tightly around the receptor neurons. The authors speculate sustentacular cells are needed to provide an essential function for detecting odor. Virus infection and damage of these cells may account for the transient loss of smell. Presumably, the sustentacular cells regenerate more quickly than the olfactory neurons, accounting for the recovery of the sense of smell within weeks of the viral infection. These studies shed new light on the essential role of the sustentacular cells in odor perception. The authors also discuss studies that have examined tissues of the human brain for expression of the ACE2 and TRPMSS2 genes. These two proteins are not made by any central system neurons, including those in the olfactory bulbs that receive direct input from the olfactory neurons. They attribute the loss of the sense of smell to damage in the nasal cavity, not the brain. Both ACE2 and TRPMSS2 are expressed on the inner lining of blood vessels that supply the brain, an observation that may account for some of the central nervous system manifestations of COVID-19, including damage to the splenium of the corpus colosseum in adult and children with Multisystem Inflammatory Syndrome-Children (MISC). The conclusions of this report, while compelling, are based on indirect observations. Biopsies of infected tissue that show the virus does indeed infect and replicate in sustentacular cells would be more helpful. An observation of both the damage and recovery of the tissue would be even more compelling. Also left unexplained is what accounts for the loss of taste. Are the neurons of the taste receptor damaged or, as in the case of the odorant receptors, is the loss of the sense of taste also attributable to damage to the cells that support the taste sensory neurons? There is one cold causing coronavirus, HCoV-NL63, that also uses the ACE2 receptor. Do people who suffer from colds induced by HCov-NL63 also lose the sense of both smell and taste, or one but not the other? This report is sure to encourage further investigation, if not in humans, in sub-human primates.
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This article originally appeared in Forbes and is available online here: An Investigation Into The Basis For The Loss Of Smell As An Early Symptom Of COVID-19
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India Approves Antigen Test To Speed Detection And Management Of SARS-CoV-2 Infections Forbes | July 28, 2020 | Article
On July 23, India approved a rapid antigen test to detect SARSCoV-2 infections. The product is called the Pathocatch COVID-19 Antigen Rapid testing kit, developed and manufactured in India by Mylab Discovery Solutions. The test will be used as part of an integrated program to speed the detection and management of those infected by SARS-CoV-2. The targeted groups of people are the ones who are both capable of transmitting the disease to others and at risk of falling ill with mild to life-threatening symptoms of COVID-19. At present, more than 1.2 million people in India have tested positive for SARS-CoV-2, and the number is rising rapidly. On the day the new test was approved, 45,720 new cases of infection were reported. The antigen test will be used in conjunction with standard PCR tests. The SARS-CoV-2 viral particle is comprised of three types of substances: RNA (the virus genome), virus-specific proteins, and lipids. The PCR tests detect viral RNA and antigen tests detect viral proteins. These two types of tests have complementary advantages and disadvantages. PCR tests are very sensitive, capable of detecting only a few virus particles. PCR tests are also highly specific—a positive reading is a sure sign of infection. Under ideal conditions, PCR tests can detect greater than 98% of those with active virus replication. The actual detection rate varies, not so much because the test lacks sensitivity, but rather from difficulties in obtaining the sample from deep intranasal or throat swabs. PCR tests require relatively sophisticated equipment that is often available only in centrally located licensed facilities. Although analyzing the results of the tests requires only hours, sampling, transporting, and reading and reporting the results of the test may result in many days of delay, depending on how 278
efficient the complete testing and reporting cycle is. Point of diagnostic PCR tests exist, which are capable of much more rapid readout. However, these typically lack the accuracy obtained in reference laboratories. Some reports place the accuracy of rapid point of care PCR tests as low as 50%. PCR tests are often expensive. The actual cost to the testing facilities, whether public or private, is not easy to find. Consumers may pay between $120 to much more than $300 per test. It is worth noting that the cost of large scale PCR screening can be driven to as low as $5 per test. That is the cost of the PCR test used to screen over 4 million Egyptians as part of the 100 Million Healthy Lives Campaign. As previously mentioned, antigen tests detect the proteins of the virus. The tests make use of antibodies that recognize the virus proteins, triggering either a color change or an electrical signal. The advantage of antigen tests is that they are rapid, with the results appearing within five to thirty minutes, depending on the test. The sample may be obtained from a nasal swab or saliva. The technology behind antigen tests is much simpler. No complex equipment is needed. To the user, they resemble a pregnancy test. They can be packaged as a slide cassette for anyone to use and read. The unit cost to manufacture an antigen test can be less than fifty cents apiece. The disadvantage to antigen tests is sensitivity. Antigen tests can require significantly more virus particles as compared to the most sensitive PCR test. Practically, that means that antigen tests fail to detect many people who are actually infected. The recently approved Pathocatch test claims that it detects about half of those infected. Specificity, the ability to solely detect SARS-CoV-2 can also be an issue with antigen tests. Antibodies are inherently less specific than PCR. With care, the number of false positives can be reduced to a very low level. The antigen test that received FDA Emergency Use Authorization in the United States, as well as those in use in other countries, claim detection rates higher the 50%. However, none are as sensitive or as specific as PCR. Recognizing the advantages and disadvantages of both antigen and PCR tests, the Indian government devised a strategy that plays to the strengths of both. Everyone is first screened with the antigen test. Those who test positive are considered infected. That test is 279
completed on-site in less than thirty minutes. Those that test negative are considered still at risk of infection. They are then subject to a PCR test. The dual antigen-PCR strategy system has the advantage of quickly identifying about half of those infected. They can then be isolated and their contacts be traced without delay. Prescreening with a rapid inexpensive antigen test reduces the total number of people requiring PCR tests. The program has an added advantage, as the true capture ratio of those detected by the antigen versus the PCR tests will be quickly known. It is worth watching the India experiment closely. Reliable, rapid, and inexpensive antigen tests, even those that detect only half of those infected, will shorten the time to identification, isolation, and contact tracing. The impact of quickly identifying at least half of those infected on the course of the pandemic can be significant, depending on the follow-up procedures and protocols. I expect the sensitivity and specificity of the antigen tests to improve with time. I can imagine a time, sooner rather than later, when self-administered saliva-based antigen tests will be cheap and widely available, perhaps costing no more than fifty cents. These little slips of plastic may be a real game-changer for the pandemic in the United States and around the world. This article originally appeared in Forbes and is available online here: India Approves Antigen Test To Speed Detection And Management Of SARS-CoV-2 Infections
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New Evidence Suggests Young Children Spread COVID-19 More Efficiently Than Adults Forbes | July 31, 2020 | Article
Two new studies, though from different parts of the world, have arrived at the same conclusion: that young children not only transmit SARS-CoV-2 efficiently, but may be major drivers of the pandemic as well. The first, which was published in The Lancet yesterday, reports findings from a pediatric hospital in Chicago, Illinois. The second, a preprint manuscript awaiting peer review, was conducted in the mountainous province of Trento, Italy. The Chicago study examines the concentration of the SARSCoV-2 in the nasopharynx, or the upper region of the throat that connects to the nasal passages, of children and adults. According to the results, children 5 years and younger who develop mild to moderate COVID-19 symptoms have 10 to 100 times as much SARS-CoV-2 in the nasopharynx as older children and adults. Whenever these young children cough, sneeze, or shout, they expel virus-laden droplets from the nasopharynx into the air. If they have as much as one hundred times the amount of virus in their throat and nasal passages as adults, it only makes sense that they would spread the virus more efficiently. The study also shows that children from the ages of 5 to 17, also with mild to moderate COVID-19 symptoms, have the same amount of virus in the nasopharynx as adults age 18 and above. The authors conclude it is likely that young children, while not as prone to suffering from COVID-19 infection, still drive its spread—just as they do with several other respiratory diseases. The second manuscript reports the results of an extensive contact tracing study conducted in Trento, an autonomous region in Northern Italy. Despite a total lockdown that began in March with the closure of schools, universities, and all businesses except grocery stores, pharmacies, and newsstands, for more than a month the number of cases rose exponentially. 281
The researchers found that although young children had a somewhat lower risk of infection than adults and were less likely to become ill, children age 14 and younger transmit the virus more efficiently to other children and adults than adults themselves. Their risk of transmitting COVID-19 was 22.4 percent—more than twice that of adults aged 30 to 49, whose rate of contagiousness was about 11 percent. “Although childhood contacts were less likely to become cases,” they wrote, “children were more likely to infect household members.” The Trento study also found that its youngest participants were the most efficient transmitters of the disease, citing respiratory syncytial virus as an example of another infectious disease for which this has been the case. The younger the child, they noted, the higher the concentration of SARS-CoV-2 in their nasal passages—an observation consistent with the Chicago study. Both studies spell serious implications for countries contemplating whether or not to reopen schools in the face of lingering and out-of-control outbreaks, the United States included. Even if children are required to keep their hands to themselves, refrain from sharing toys and supplies, and wear masks at all times, we can’t realistically expect them to follow such rules without fail. So long as misbehavior is a possibility, so too is the rampant spread of infection. If children from ages 5 to 17 are as or possibly even more contagious than adults, then opening schools in areas where daily rates of infection remain moderate to high is extremely risky and unwise. The measures we deploy to contain the spread of COVID19 in our schools and our communities must take the entire population into account—children age 18 and below included. This article originally appeared in Forbes and is available online here: New Evidence Suggests Young Children Spread COVID-19 More Efficiently Than Adults
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August 2020
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The Flu Could Send Our Healthcare System Into Overdrive This Winter. This Drug Offers Some Hope. CNN | August 1, 2020 | Article
A study published in the July 23 issue of the New England Journal of Medicine found that the anti-influenza drug baloxavir marboxil significantly reduced transmission of influenza among people living in the same house The news comes just in time for the 2020-2021 flu season, which threatens to coincide with a new upswing of COVID-19 infections in countries this fall and winter. The confluence of these two viruses could overwhelm already strained medical resources and complicate testing procedures, particularly given that the illnesses they lead to have remarkably similar symptoms. A previous study, published in the Lancet in June, proved that a single dose of baloxavir was just as effective as Tamiflu (oseltamivir) at shortening the duration of the flu when administered twice daily for five days. But the newer July study is perhaps even more significant, as it shows the role that baloxavir plays in reducing the spread of illness among household members. This article originally appeared on CNN. The full article is available here: The Flu Could Send Our Healthcare System Into Overdrive This Winter. This Drug Offers Some Hope.
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Two-Step Testing Could Slow COVID-19 Transmission Dramatically Forbes | August 7, 2020 | Article
In the United States, testing for COVID-19 has become a persistent problem. For some without insurance, it is too costly. For others living in remote or underserved areas, too inaccessible. For us all, far too slow. While some tests take only a few minutes to complete, most tests take much longer to deliver results. If the person awaiting results isn’t cautious, the time needed to process samples in a lab— anywhere from a few days to a few weeks—becomes time enough for the virus to spread far and wide. The two-step method is not only a better way to test, but could potentially reduce transmission by 50 percent or more—and do so quickly. Key advances in our ability to detect SARS-CoV-2, the virus that causes COVID-19, make this new method possible. Tests were created early on that could measure the presence of viral RNA in any given sample using the polymerase chain reaction (PCR), which copies the sample a million times over to make traces of the virus easy to identify. Of all the different kinds of tests available for COVID-19, PCR tests have proven to be the most accurate. They’re also the most expensive and time-consuming. Since processing a PCR test requires special machinery that can only be found in labs and research centers, the wait for results tends to drag out, especially in places where case counts are surging and capacity strained. Another critical development was the creation of tests that detect SARS-CoV-2 by looking for viral proteins, or antigens, instead. Aptly called antigen tests, compared to the PCR tests these have the advantage of speed and convenience, in addition to being quick and easy to manufacture. A rapid antigen test authorized for use in India, the Pathocatch COVID-19 Antigen Rapid testing kit, reduces the wait time for results to as little as 30 minutes. 285
Like a pregnancy test, the rapid antigen test can potentially be used in the convenience and privacy of the home. But there is one major caveat to using antigen tests over PCR tests: they’re not nearly as accurate. Set loose in a sea of infections, the Pathocatch test, for instance, would only detect half. The two-step testing method combines antigen tests together with PCR tests such that the strengths of both are exploited. The first step? Conduct widespread antigen tests using existing testing facilities. Those who test positive are assumed to be infected and instructed to self-isolate at home, where they can be monitored by local health authorities. Within 24 hours a contact tracing team interviews them about recent contacts who may have been infected, all of whom are brought in for testing as well. Those who test negative proceed to the second step—the PCR test with a slower turnaround, but more accurate result. Until the PCR test results confirm or disprove their negative status, those who test negative the first time around must quarantine. Either way, the virus is stopped in its tracks. In India, this two-step takedown is already underway. In Egypt, it was successfully used to screen 68 million Egyptians for hepatitis C, though with antibody tests instead of antigen tests as a first step. It could be implemented just as easily here, where the U.S. Food and Drug Administration has already approved a rapid antigen test with a higher detection rate than the Pathocatch. Testing is nothing short of essential to our ability to monitor and mitigate COVID-19, and in the United States this component has so far been lacking. Studies conducted across Spain and the United States have shown that for every case of COVID-19 confirmed using PCR tests, as many as five to 10 more go undetected. Confirmed cases in the United States currently exceed 4.5 million, which means tens of millions of infections may be eluding our grasp. Even if the two-step testing method enables detection of just 50 percent of infected people, removing those 50 percent from circulation would slow the spread of COVID-19 dramatically. In other words, it is just the sort of sweeping intervention we need to make up for months of inefficiency and inaction. Why not start now? This article originally appeared in Forbes and is available online here: Two-Step Testing Could Slow COVID-19 Transmission Dramatically
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Will Reopening Gyms Improve Our Well-Being Or Put Us At Risk? Psychology Today | August 10, 2020 | Article
Is it better for our health to return to the gym or stay away? Since physical and mental health go hand-in-hand, taking care of both is of the utmost importance—especially during a global pandemic. For months, people have been deprived of a crucial outlet for relieving stress and improving wellness: their local gym. Now that lockdowns are lifting, and in some places, the disease receding, many are itching to ease back into their intense cardio and weightlifting routines. But with COVID-19 cases surging across the country, we must ask ourselves: Is it really safe to reopen gyms? Gyms typically house all types of bacteria. One study shows that free weights can have 362 times more bacteria than a toilet seat. This bacteria can not only make people sick, but it can also cause skin, ear, or eye infections. With COVID-19 potentially circulating in gyms, people could be even more at risk. Gyms: a place to get fit or get sick? According to a group of Korean researchers, the humid airflow containing people’s sweat, breath, and, therefore, their bacteria circulating in gyms will create an environment where minute respiratory droplets easily spread. These aerosols, which remain airborne for up to three hours, can spread COVID-19, which means virus transmission is more likely to occur in these confined training facilities than many other indoor settings. Gyms like Planet Fitness and O2 Fitness Clubs are taking several precautions to reduce this heightened risk of transmission. These include periodic equipment disinfection, mandated or recommended mask-wearing and handwashing, temperature checks for workers, and limits on the number of people in the facility at any given time.
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While certainly well-intentioned, these protocols in no way constitute a foolproof safeguard against the virus. As gymgoers take turns running on treadmills or using different weight machines, they’re bound to interact with the same bacteria and germs others have spread by touch, making the periodic equipment disinfection an inadequate protocol. Steam-filled locker rooms packed tightly with sweaty people present another problem and, in fact, could become more dangerous than the training facilities themselves, due to the confined space and limited airflow. As a result, social distancing becomes impossible and ineffective, while the risk of transmission becomes greater. Moving exercise out of the gym and into the home It wasn’t easy to maintain a fitness regimen during the lockdown, and even with lockdowns lifting, it isn’t easy now. That said, there are plenty of ways for people to take care of themselves physically and mentally without going to a gym, and as long as COVID-19 remains a threat, these alternatives are well worth considering. Light exercise is relatively easy. If the weather is nice, going for a walk in the neighborhood is a great way to get those steps in, as well as a breath of fresh air. Other options are buying a mat to do yoga in the backyard or doing ab exercises in the living room. There are options for more intense physical activity, too. For cardio, go on a run in a somewhat empty park trail, or if a hill is nearby, doing incline sprints is a great way to work up a sweat quickly. For bodyweight exercises, try combining squats, planks, crunches, lunges, burpees, and wall-sits in lieu of machines and free weights. By combining cardio workouts with bodyweight exercises, you create a high-intensity, serious workout that requires minimal equipment, eliminating the necessity to go to the gym as the virus continues to pose a threat. If weights are a must for your fitness routine, but you don’t have any at home and can’t purchase them online, figure out a creative alternative. For example, you can use household items as weights: filled milk or water gallon jugs, bags of sand or soil, large bottles of laundry detergent, a backpack filled with books, or even paint cans. If gymgoers need the motivation to exercise, they could set a virtual workout time with their friends and work out on FaceTime or other similar platforms together. Not only will this motivate them to work out during that time, but it will provide them with the 288
familiar gym environment of people working towards the same goal of staying in shape. Another option to motivate people to work out is watching YouTube videos of fitness gurus explaining and doing exercise circuits. In addition, they can enroll in one of the many online free fitness programs or apps currently available. Some of these programs create personalized workout plans and may also provide meal recipes to follow to stay healthy. With these effective options, it is easier to not only stay motivated and active but also stay safe in the comfort of one’s home. We should truly consider whether reopening gyms right now is in our best interest, especially with easy access to effective alternatives for working out at home. While gyms are a great place to blow off steam and stay fit, is it really the best idea to go in hopes of improving our mental well-being by putting our health on the line? This article originally appeared in Psychology Today and is available online here: Will Reopening Gyms Improve Our Well-Being Or Put Us At Risk?
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Back To School: A Tipping Point In US Politics Daily Clout | August 12, 2020 | Article
The debate over opening America’s schools may be the tipping point at which the unending politicization of the COVID-19 pandemic will finally end. Every night, at dinner tables around the country, parents are discussing the one topic that unifies our country—what is best for children. The answer will not be driven by partisan debates or political orientation, but by every parent’s desire to do right by the children in their care. Over the past few weeks, we have heard one politician after another make false claims about the health of American children. Some suggest that kids don’t catch COVID easily, others say they may become infected, but they won’t get ill if they do. Both assumptions are dangerously wrong. New research out of Italy shows that children, when infected, have as much—if not more—of the virus in their noses and throats as infected adults. Not only can children easily spread the disease to others, but they may be more infectious than any other group. After looking at nearly 1,500 confirmed COVID cases, researchers found the highest rate of contagiousness was among those 5 to 10 years old. It is thankfully true that the majority of children, once infected, show no symptoms or only mild ones. But that they rarely fall severely ill does not mean that it never happens. Just this week, a seven year old boy in Georgia, with no known chronic conditions, died from the disease. In others, infection triggers a multisystem inflammatory syndrome (MIS-C) that can lead to loss of speech, loss of coordination, and long term brain damage. The denial of the true and present danger COVID poses for students and their families is the latest in a series of politically motivated missteps that have only led us further and further along the brink of disaster. The failure of the current U.S. administration to recognize the scope of the pandemic and its impact on American families left us woefully underprepared for the level of testing needed to contain the outbreak in its earliest stages. In April, when infections 290
were surging in hotspots across the country, the actions of our leaders flew in the face of our nation’s best public health experts, as Americans were encouraged to plan for an Easter reopening complete with packed churches. Today, as the administration pushes for a full reopening of our nation’s schools, no matter the surge of infections in communities at large, they offer a new opening for this silent invader. If it weren’t for such erroneous blunders in governance and leadership, the virus would not be in such good stead as it is today. In the United States, a country of roughly 325 million, we had nearly 55,000 new infections and more than 1,300 deaths today. In China, a country more than five times our size, they had 37 cases and no reported deaths. Americans know that they are being led down a dangerous path. And parents know that politics is now putting their children at risk. Polls show that most parents, however burned out and overworked from their experiments with remote learning, disapprove of the U.S. administration’s handling of the issue and push to fully reopen schools. The decisions being made by this administration are not a remote abstraction. They are proximal and deeply personal. Do I trust this government enough to protect my children? Do I believe my President when he says my children are safe? Every parent and grandparent I know is desperate for someone to tell them what to do, but the voices they hear are not ones they are prepared to trust. With the start of a new school year fast approaching, we must finally ask ourselves how much we are willing to sacrifice. When it comes to the safety and schooling of our children, parents hold great power. The time has come to wield it and to hold this administration to account in the polls. This article originally appeared in the Daily Clout and is available online here: Back To School: A Tipping Point In US Politics
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What Restarting Sports And Reopening Schools Have In Common Forbes | August 14, 2020 | Article
On Saturday, the Mid-American Conference became the first Football Bowl Subdivision to postpone its upcoming season. The announcement comes amidst the most recent debate about schools doing the exact opposite—reopening and requiring students and faculty to return to campus. While many conferences, such as the Mid-American Conference, Mountain West Conference, and Atlantic 10 Conference, are delaying fall sports, some leagues have already brought players back to the field. Major League Soccer even hosted an MLS is Back Tournament with players, coaches, staff, referees, and other members of the delegation currently staying at a host hotel in Florida. What continues to happen with these attempts to restart sports is that even in the most tightly controlled settings—and with a multimillion dollar budget to boot—the virus still, somehow, finds a way in. I anticipated this outcome in a previous Forbes article on the topic, and regretfully my predictions have come true. These recent developments aren’t of interest to sports fans alone. Studying and learning from the successes and failures of so-called sports “bubbles” and other strategies of containment can help us think through the decisions we now face on whether to reopen schools—and if they do reopen, what we might expect. The fact of the matter is that no matter the protocols put in place, COVID-19 will still find its way into the classroom, resulting in unwanted surges in new cases. A soccer league’s attempt to keep the virus at bay In preparing for their comeback tournament, Major League Soccer teams took no shortage of precautions against the virus, including testing every other day before the trip to Florida; testing upon arrival and enforcing isolation for 12 hours until results come back; and testing every other day for the first two weeks. 292
At first, it appeared that the bubble was working. But with each team that arrives, even with so many rigorous safety measures in place, the League introduces more people into their bubble— making it all the more likely that the virus will also be brought in and spread among the athletes, coaches, and staff. Right before Toronto FC participated in the kickoff against D.C. United, both teams found out that each group had one positive COVID test, resulting in the league being thrown for a loop and having to postpone the match for a second time. What’s more, Toronto FC had not been in the bubble for seven days prior to their match. While Major League Soccer is continuing to conduct periodic testing and take extra precautions, we do not know what the future holds. The League, and anyone else who follows suit, treads dangerously close to the line of risk, as they open their bubble and make the spread of COVID-19 more likely. Sports stadiums, the White House—are schools next? As seen with Major League Soccer, even with strict protocols, it is still possible to have a positive COVID test among a group of people that have been living in a so-called bubble. Even the White House staff, despite adhering to guidelines such as conducting periodic testing and enforcing mask-wearing, has seen its own handful of positive cases, including National Security Advisor Robert O-Brien. Reopening schools is following a similar path to what sports teams and the White House are doing in order to safely bring people back to their usual routines—conducting daily temperature checks, enforcing mask-wearing, requiring social distancing, and so on. However, these measures do not guarantee that students, faculty, and staff will not bring the virus into the school and spread it. Schools in Israel, for example, slowly brought students back in May. However, after thinking they had beaten the virus and bringing the rest of the student body back, infections started to pop up in a high school in Jerusalem, which then spread to students’ homes, other schools, and neighborhoods. No matter the amount of money spent or number of precautions taken, forcing a premature “return to normal” as record-breaking COVID-19 outbreaks rage on is bound to backfire. If anything, rather than bringing sports back on schedule and school back in 293
session, we should follow the lead of the Mid-American Conference—postponing a false sense of normalcy in favor of our actual safety and wellbeing. This article originally appeared in Forbes and is available online here: What Restarting Sports And Reopening Schools Have In Common
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Cheap, Daily Home Tests Are The First Step To Containing The Pandemic Forbes | August 17, 2020 | Article
We don’t need drugs or vaccines to stop the COVID-19 pandemic. We can use something that is already available and at our disposal: rapid point-of-care and home diagnostics combined with contact tracing and isolation of possible transmitters. Backed by the right technology and strategy, testing can be used to detect the virus at its most contagious—and stop the people who carry it from spreading it to others. In the United States, this is currently far from the case. Barriers like the cost of a single test, which can range from $50 to $150, and uneven spread of testing sites, which for some demand long commutes, make testing a rarity reserved for worst case scenarios, rather than a safety measure accessible to all. The long waiting times render the results moot for many. Among the nearly 200 COVID-19 tests authorized for emergency use by the U.S. Food and Drug Administration are already several technologies that can make testing faster, cheaper, and more convenient. These new methods must become the basis of a nationwide testing regimen in which tens of millions of people are tested day in and day out. Part one: the technology PCR tests, named for the polymerase chain reaction used to magnify samples and detect viral RNA in labs or research centers, have so far been the gold standard and bedrock of most testing efforts. Though more accurate than most COVID-19 test types by a wide margin, the turnaround time for a PCR test result is typically a few days at best and a few weeks at worst. Such a delay impedes our ability to tally infections as they’re actually happening, meaning most national and even local case counts underestimate the rate at which disease is circulating in our communities at any given time. It 295
also means that people who might be at the very peak of their contagiousness leave the testing site ignorant, unknowingly continue to infect others, sometimes many others. Data collected in Spain, the United States, and several other countries using antibody tests, which pick up on the presence of COVID-19 specific antibodies in the blood, offers clues as to how great the gap between confirmed and active COVID-19 infections actually may be. SeroTracker, a Canadian analytics hub that aggregates this data, estimates the prevalence of COVID-19 antibodies in the U.S. population to be five percent on average— meaning the national confirmed case count that recently surpassed five million, a bit more than one percent of the country, likely represents only a fraction of infections currently active. While antibody tests are useful in shedding light on the true scope of an outbreak, they can only do so in hindsight, when infections have already happened. There’s also no knowing how many infections are left out because the carriers are unsuspectingly asymptomatic and therefore have no reason to seek out testing. To make testing a preventive, rather than reactive, form of disease control, we need speed and convenience. Such is the advantage of using antigen tests, which measure SARS-CoV-2 by way of viral proteins, or antigens, and don’t require the extra step of in-lab processing—hence a turnaround time as fast as 15 minutes. The tradeoff, as might be expected, is sensitivity, and an antigen test is indeed more likely to miss some who would test positive by PCR. But when it comes to controlling or preventing community spread, sensitivity isn’t necessarily the most significant factor. Data from preprint studies shows that the concentration of the COVID-19 virus in our nasal passages and throat is at its highest from the day before we develop symptoms to seven days after (see Figure 1). This is when we’re most likely to pass the infection on to others. From Day 7 onward the amount of virus in the body diminishes, as does our ability to transmit it—though most people remain PCR-positive for many days. Why this is so is a biologic mystery waiting to be solved, but the fact remains that if you give someone a rapid diagnostic early enough, their body will have so much virus a sensitive test won’t be necessary. Given these findings, the most useful tests for mass screenings are those that detect the amount of virus particles associated with 296
transmission, estimated to be about 100,000 or 105 per millimeter (see Figure 3). Fortunately antigen tests and other rapid diagnostics currently in development are up to the task (see Figure 2). One uses CRISPR technology to analyze nasal swabs or saliva samples for traces of viral genetic material. Another relies on the same paperbased laminar-/lateral-flow immunoassays as disposable pregnancy tests and could potentially give users the option to test themselves before school or work in the comfort of their own homes. While no rapid diagnostic yet has received regulatory approval for at-home or over-the-counter use, the FDA has recently amended its protocols to clear the path forward for such products. Once they’re brought to market, it will no longer be the case that the only people tested are those who act out of suspicion of exposure or infection. These tests will be for everyone—healthy and asymptomatic individuals included. Part two: the strategy I believe that each test should cost no more than fifty cents. That was the price of the Abbott rapid antibody tests that Egypt used to screen its entire population, ages 12 and older, for hepatitis C. Results should be available within 5 to 15 minutes. The low cost and speed should allow every schoolchild, every teacher and everybody working with others to know whether or not they are an asymptomatic, contagious carrier. It would allow public health authorities to identify and isolate those who are most contagious. The effect on the pandemic will be immediate and dramatic. With mass deployment of less sensitive, but rapid and easy-touse diagnostic tests that deliver results within minutes at the doctor’s office or at home, anyone infected will know almost immediately, before symptoms even begin to show, to stay at home and isolate— stopping the spread of the disease in its tracks and clearing the way for faster containment. Following up positive tests with contact tracing, a technique that was critical to mitigating COVID-19 in Singapore and South Korea, would ensure that recent contacts of the infected would do the same. This would be especially helpful in both removing so-called super-spreaders, or infected people with high viral loads, and freeing those who may test positive, but don’t have enough virus in their bodies to be infectious. 297
One way to mobilize this strategy is through the two-step testing method currently underway in India, where confirmed cases now exceed two million. The first step is to conduct widespread rapid tests at existing testing facilities and, once the technology is authorized and available, in our homes. Those who test positive with a viral load at or above 103 viral particles per millimeter are assumed to be infected and instructed to self-isolate at home, where they can be monitored by local health authorities. Within 24 hours a contact tracing team interviews them about recent contacts who may have been infected, all of whom are brought in for testing as well. Those who test positive but carry a viral load below 103 particles per millimeter are contact traced, but aren’t required to isolate, as they’re beyond the threshold of infectivity. Those who test negative, on the other hand, proceed to the second step: the PCR test with a slower turnaround, but more accurate result. They must also quarantine until the PCR test results confirm or disprove their negative status— unless they carry viral load below 103 particles per millimeter, in which case they must be contact traced but needn’t isolate. Insofar as antigen tests are also cheaper to manufacture and cheaper to purchase than PCR tests, they make an ideal tool for scaling up testing efforts at the community and national level. If mobilized through coordinated efforts like the recently announced interstate testing compact between seven state governments, test makers, and the Rockefeller Foundation, these speedy diagnostics could become truly accessible for a low price at a large scale. Taking such a strategy nationwide may seem ambitious, but meeting the challenges of the current crisis will require nothing less. The strategy of “test, trace, isolate” is nothing new. What’s different now is we have the technology to make it possible at a low cost and in a short amount of time. If we continue to underinvest in testing, we consign ourselves to repairing damage that has already been done—rather than preventing it in the first place. This article originally appeared in Forbes and is available online here: Cheap, Daily Home Tests Are The First Step To Containing The Pandemic
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The Moral Trauma of COVID-19: How the failures of our national leaders have torn the moral fabric of our lives Psychology Today | August 21, 2020 | Article
All of us, whether we have realized it by now or not, are being traumatized by the COVID-19 pandemic. Let’s begin with the darkening cloud apparent to many, the question I hear more than any other from my dismayed friends, "How can the richest, most technically advanced country in the world experience the worst effects of the pandemic?" With four percent of the world’s population, the United States accounts for almost one quarter of all recorded infections and death. COVID-19 is an immediate personal trauma for those who are ill, or who have family members hospitalized or die of the disease. Those who recover from the more serious consequences of infection may suffer ill health for years to come. COVID-19 is an immediate personal trauma for our children and grandchildren who ask, why is this happening, why is my life changed? The economic effects of the pandemic are broadly traumatic as well; we are experiencing the worst economic depression since the 1930s, with record unemployment, the destruction of countless small businesses, vanishing work opportunities for our young, and the dawning realization their lives will be forever changed. Social isolation, a consequence of efforts to control the pandemic, is in itself traumatic especially for the young. Social networks and relationships forged in our teenage and young adult lives remain amongst the most important throughout life. COVID-19 has shattered normal social life. These combined traumas deliver a heavy psychological blow. A study released in mid-August by the Centers for Disease Control and Prevention found that anxiety and depression, substance abuse, and thoughts of suicide were on the rise because of the COVID-19 pandemic. Forty percent of more than five thousand U.S. adults 299
participating in a late June survey said they had experienced one or more of those responses since April. Suicidal thoughts were notably higher among younger adults, aged 18 to 25, as well as Hispanics, Blacks, essential workers, and people who described themselves as unpaid caregivers for adults. Trauma related to COVID-19 first affected health care workers who were on the frontlines of our society’s response to the pandemic. These medical professionals and staff confronted extreme emotional distress. They were forced to deal daily with a lack of necessary equipment to save the lives of an overwhelming number of patients and to protect themselves and their families for lack of adequate supplies of personal protective equipment, all the time listening to leaders who minimized the problems. A dedicated ICU nurse commits suicide. An overwhelmed ER doctor commits suicide. Not long ago, a friend, overstressed by day to day workplace confrontation with COVID-19, leapt to his death onto a New York City sidewalk. Here I add another dimension to the traumas we all experience—what I will call moral trauma. I adapt the concept of moral trauma from the well studied military term moral injury that soldiers experience in wartime. The Wikipedia entry, citing several sources, defines moral injury and describes its causes and effects: “The term moral injury… was first coined by psychiatrist Jonathan Shay and colleagues based upon numerous narratives presented by military/veteran patients given their perception of injustice as a result of leadership malpractice. Shay's definition of moral injury had three components: “Moral injury is present when (i) there has been a betrayal of what is morally right, (ii) by someone who holds legitimate authority and (iii) in a high-stakes situation...” The term “moral injury” was modified by Brett Litz and colleagues as "perpetrating, failing to prevent, or bearing witness to acts that transgress deeply held moral beliefs and expectations may be deleterious in the long term, emotionally, psychologically, behaviorally, spiritually, and socially” Here I broaden the concepts underlying moral injury from the military to the civilian. I use the term moral trauma to distinguish the two. Until now moral injury has been used and studied almost exclusively in a military context. But isn’t moral trauma what we all experienced as we watched the video of the police officer staring 300
definitely at onlookers as he squeezed the life from a handcuffed and helpless George Floyd? Isn’t moral trauma what we experience as we witness politicians lead our country into the worst avoidable public health disaster in our history? Our moral fabric, however each of us may define this human quality, has been torn grievously on these two fronts—public health and civil rights—by failures of national political leaders. Six months and counting, our leaders continue to be overwhelmed and outmaneuvered by the COVID-19 virus, SARS-CoV-2. At the current rate, deaths in the United States from the pandemic will exceed within days, and in less than six months, more than three times the 58,000 Americans killed during eleven years of the Vietnam War. This is a shocking failure of our public health defenses. Those of us in public health, and I suspect many others, understand that almost all the COVID-19 related death, economic havoc, and disruption of personal lives was avoidable. China's experience with COVID-19 is a case in point. China has no medical tools to control COVID-19 that we lack. One can even argue that the US, a world leader in health research and cutting edge science, has the advantage. The numbers tell us how badly we are failing to make the most of our advantage. China, the country first affected by COVID-19, has four times the population in the United States, yet on a typical day in August when more than fifty-five thousand new infections were tallied in the US, only 31 new infections were reported in China. Since the epidemic began more than twice as many Americas have died of COVID as have been infected in China. I cite these figures not to praise China but rather to express a collective sense of bewilderment as to what has gone wrong with our response to the pandemic. Our moral trauma is witnessing death, contagion, and economic destruction around us, knowing full well it is unnecessary. Our country has been deeply morally traumatized—in my view, by the President through his denials, incompetence, and finger-pointing, and by his administration, his enablers in Congress, and compliant state governors. By contrast, our military leaders have long understood their responsibility to support troops they place in harm’s way. On 301
occasion, bad commanders issue orders that are repugnant even to seasoned hard-nosed veterans. The vast majority of soldiers despise killing other human beings. Medical professionals in the military recognize moral injury from treating veterans unable to quiet memories of witnessing, perpetrating, or failing to prevent violent deaths of enemy soldiers or civilians. This is beyond post-traumatic stress disorder. Emotional, physical, and spiritual harm persists in these men and women because those actions violated some deeply held moral beliefs or expectations of justice. The traumas we face now in civil life can and should be illuminated by our military’s rigorous analyses. As injuries and death inflicted by COVID-19 become more pronounced, more immediate in our lives, and those of family and friends, we suffer increasing moral trauma. For our mental health, we need to take time to reflect on our troubling thoughts and experiences, understand and analyze them, then take action to restore what is being damaged most: our self-respect. Our mental states suffer when the pain we experience is beyond our ability to control. We lose hope. We become overwhelmed. Family and friends find feelings and distressing events too painful to talk about. We find the feelings and distressing events too painful to talk about. We may retreat into our dark thoughts, feeling alone. But none of us should feel isolated or alone. Psychiatrists and psychologists often are trained to guide patients through four stages of awareness to understand, modify, and resolve disturbing behaviors or thoughts. The first is identifying the characteristics of these behaviors or thoughts; “See it.” The second step is crucially important: picking precise words or phrases to describe the problem; or, “Name it.” The name of our collective experience is moral trauma. Words or phrases become tools to help a patient or a society examine the problem they need to solve. In other words, “Analyze it.” The fourth step is to take stock of the analysis and then, take action. If you do not take action, a well-trained therapist will counsel, nothing will change. That is why the fourth step is, simply and emphatically: “Change it.” The COVID-19 pandemic has caused me to relive two personal traumas long past. The first was with HIV/AIDS. I was among a small group of virus experts pressing urgently to map HIV’s distinct 302
and deadly molecular biology in the early 1980s. I knew and tried to comfort dear friends, people I knew who struggled horribly then died from AIDS. We in medical science had no treatments for them. It was agonizing, deeply disturbing. At the time our national leaders refused to acknowledge the magnitude of the problem and to devote the public health and research funds needed to confront it. Those at the front lines of the fight against HIV/AIDS experienced what I now recognize as moral trauma. It took action, immediate action by a few, to change the nation’s indifference to AIDS. A campaign that summer led by Republican Senator Ted Stevens and Democratic Senator Ted Kennedy, actor Elizabeth Taylor, me, and others convinced a bipartisan coalition in Congress at the eleventh hour stand up to an indifferent Reagan White House and fund $320 million in 1986. That action resulted in discoveries by the early ‘90s that ended the AIDS death sentence, helping people infected to live nearly normal lives on a regimen of antiviral medications. We saw how our actions changed government policy. My other experience, shared with millions of others, was with the Vietnam War. Many felt the war was unnecessary and unjust. We were witness to hundreds of thousands of Vietnamese and tens of thousands of Americans dying for what appeared to be no valid reason. With the publication of the Pentagon Papers, we learned that our government under three presidents, Republican and Democratic, had been deceptive in describing the reasons for the war, the progress on the ground, the casualties inflicted on both sides, and the prospects for success. This while we mourned the deaths of many high school and college friends who had volunteered or been drafted into the war effort. Massive countrywide protests changed our national policy as much as defeat on the battlefield. We had no name for our collective trauma but we do now. The most important response we need to take as individuals and as a nation to heal is to recognize these deepening anxieties, restore our self-respect, and then do our utmost to help ourselves and others recover from these unprecedented and accumulating moral trauma of our time. We need collective action to return our government to a disciplined plan based on science to control the pandemic. We know with certainty it can be done with the tools at hand. No new miracle drug or vaccine is needed, only resolve, that of our 303
government to do what is right, and, if not, by we the people to make sure they do! This article originally appeared in Psychology Today and is available online here: The Moral Trauma of COVID-19: How the failures of our national leaders have torn the moral fabric of our lives
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Why Most Voters Oppose Schools Reopening Forbes | August 21, 2020 | Article
Even as test rates hover around six to seven percent and tens of thousands of new COVID-19 cases are being reported daily, school districts across the country will continue with plans to resume operations in the coming weeks. The latest survey data shows, however, that most Americans oppose reopening K-12 education in their states. Parents have reason to be concerned that sending their children to school could bring the virus into their homes, as well as spike positivity rates in their communities. From July 30th to August 13th, over 75,000 new child COVID-19 cases were reported, according to the American Academy of Pediatrics. The outcome would be disastrous were even one asymptomatic carrier to attend classes in the coming weeks. A recent survey conducted by the Financial Times-Peterson Foundation US Economic Monitor revealed that six in ten voters oppose reopening K-12 schools in their states, while as many as 81 percent urge the prioritization of health among students and faculty over the economy. Were children to get sick at school, not only would their health be endangered, but so would the health of their families. There would be no economy without healthy parents, which is why the vast majority of Americans urge the safety of American students over the state of the economy. One of the more prudent concerns about the resumption of K12 education is the social nature of a student’s daily life. School districts are assuring parents that they have put preventative measures in place, such as social distancing and classroom hybridization. But to assume students will have no interaction at all seems ludicrous. Children and teens have been out of the traditional school setting for over five months and they will be ready to interact with others. Despite the urge shared by parents and children alike to return to normal, the average voter realizes that the pandemic in the United States is far from over. Parents want their children to stay healthy for 305
many reasons—to ensure the physical health and wellbeing of the family, to ensure the economic livelihood of the family, and to avoid the unknown long term health risks associated with COVID-19. Around 65 percent of voters believe social distancing requirements and non essential business restrictions should be in place for at least another three months—a sacrifice many are willing to make for the sake of their families and children. Such statistics also show that people recognize there will be several more months of abnormality and want decision makers to take action accordingly, even if it means deprioritizing the economy. Families and individuals have been economically crippled by the pandemic and the US government’s lack of public assistance. The official unemployment rate still hovers around ten percent according to the Bureau of Labor Statistics. Low income families are struggling and eviction rates are sure to spike as rent moratoriums expire. These families have enough to worry about without the added pressure of sending their children back to school at this time. The reopening of K-12 school districts in the coming weeks presents medical and economic challenges for families in the pandemic era, especially those already disadvantaged or experiencing hardship. Societal immunity is a long way off; as thirty five percent of voters said they would not be likely to get a COVID-19 vaccine were one approved and available by the end of the year, meaning children of those thirty five percent would also be unlikely to get vaccinated. With the inability to ensure the health and safety of students and the unknown economic future to come, schools are better off staying online for the time being. This article originally appeared in Forbes and is available online here: Why Most Voters Oppose Schools Reopening
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Deregulating COVID-19 Treatment Sets Dangerous Precedent for Vaccine Approval Forbes | August 27, 2020 | Article
The current Administration in Washington is gambling on deregulation of the Food and Drug Administration. Regulations on COVID-19 testing meant to keep Americans safe are weakened by the Administration in a recent executive order. This change could result in unreliable tests being released, which only adds to the testing woes present in the United States. Unverified tests and fast-tracked treatments could lead to more, not less, spreading of the disease. The FDA expedited the approval of a COVID-19 treatment— convalescent plasma—against the advice of its internal experts and those at the National Institute of Health. Were the federal government to continue this theme, one could expect the approval of an underregulated COVID-19 vaccine in the coming months, regardless of definitive proof, safety, or efficacy, something both the governments of China and Russia appear to have done. Sunday’s emergency use authorization for convalescent plasma was issued as a therapy, which has been used to treat 70,000 COVID-19 patients. Its benefits are still unknown, as there has been no randomized controlled study on the effect of the treatment compared to a placebo. FDA Commissioner Stephan Hahn has even admitted to overstating the effectiveness of the treatment in a news conference by tenfold. To quote Hahn, “A 35% improvement in survival is a pretty substantial clinical benefit. What that means is — and if the data continue to pan out — 100 people who are sick with COVID-19, 35 would have been saved because of the administration of plasma.” The study in question suggests that closer to 3-5 people would be saved by convalescent plasma. Even that estimation is in question as the researchers did not compare plasma infusions to a control group. The result was pulled by comparing those who received a lot of antibodies early to those who received only a few later on.
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We have seen this type of behavior before in a failed emergency use authorization for hydroxychloroquine. Once touted as a “game changer”, the drug has now been noted to cause serious heart rhythm issues. The Infectious Diseases Society of America argues against the use of the drug in any setting as a treatment for COVID19. Despite these warnings, people continue to take hydroxychloroquine. They assume it is an effective treatment, while it is actually damaging to their health. This carries dangerous implications for potentially fast tracked vaccines. Were the federal government to fast track vaccines to market, what would be the damage? The most immediate and obvious answer is that vaccines would be untested, unproven, and potentially harmful, as previously seen by the damaging effects of hydroxychloroquine. The more complicated and storied answer is that of trust in the efficacy of vaccines. A recent survey found that if a COVID vaccine were to be approved and available by the end of the year, thirty five percent of voters would be unlikely to get it. People are already hesitant about being vaccinated for COVID-19 and an expedited, unregulated production would likely entrench their hesitation. These hesitations are not entirely unfounded, as in the African American community. From J Marion Sims operating on and mutilating unconsenting enslaved Black women to further his gynecological research to the Tuskegee Experiments, Black people have been the subject of abuse by medical professionals for decades and continue to be more poorly treated and cared for than their Caucasian counterparts. Paired with the distrust of medications and the professionals who administer them is another stumbling block: the close association between new vaccines and corporate profits. After receiving almost half a billion dollars from the US government, one company suggested it would not sell a developed vaccine for COVID-19 at cost of production. How can people be expected to trust the efficacy of a vaccine if they were fast-tracked through the approval process or regulatory processes for these vaccines were stripped based on politics and profits rather than sound public health advice? We have seen what happens to the infection when behavior changes: infections and death skyrocket, as has happened with the economic reopening. Approval of vaccines with unknown 308
effectiveness and safety could lead to even more infection and death. The damage to the FDA’s long term regulatory processes are massive. The sale of ineffective medicines, lack of confidence in medicines that do work, and political corruption of the medical field will lead to the further spreading of this disease. Were people to take vaccines they believe to be effective, they may return to society with the idea they are immune. Trust in the FDA is tainted when the public associates the agency with the politics of Washington. Vaccines are meant to be innovations by the scientific community, not devices of political gain. When FDA regulations are undermined by the current Administration for political gain, distrust in medical breakthroughs are sewn. The Administration’s attempt to find a vaccine for the disease before the election is a dangerous gamble. While finding a vaccine remains a top priority, throwing away the regulatory practices that ensure the efficacy of a vaccine is not a risk worth taking. We are moving back into the era of snake oil and patent medicine. We are opening the doors wide open to corruption. Where politicians for electoral, or personal gain, can approve or disapprove of medication. This is an extraordinarily dangerous situation. This article originally appeared in Forbes and is available online here: Deregulating COVID-19 Treatment Sets Dangerous Precedent for Vaccine Approval
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New CDC Guidelines Decrease Coronavirus Testing For Those Who Need It Most Forbes | August 31, 2020 | Article
The Center for Disease Control updated its COVID-19 testing guidelines to exclude those exposed to the virus who are asymptomatic. This is a sudden change of direction as the previous rendition encouraged everyone who came in contact with an infected person to seek testing. The revised guidelines are put in place as students return to school and businesses continue to reopen. Reduced testing puts these populations at risk as asymptomatic carriers are thought to be the most contagious spreaders of COVID19. It is unclear who made the final decision on the revisions as Brett P. Giroir, assistant Health and Human Services secretary and member of the White House Coronavirus Task Force, noted that the decision came after debate amongst the task force. Ultimately, Giroir claims the guideline revision was a “CDC action” and that the decision was made before it had even come across the President’s desk. CDC Director Robert Redfield was skeptical of the new guidelines, but seems to have yielded to the direction of Giroir. This is not the first time the Administration appears to have had a hand in CDC decision making. In May, the White House requested revisions for the CDC’s economic reopening guidelines, as they were too restrictive. Shortly after reopening, cases spiked from twenty thousand to fifty thousand per day and deaths increased from about three hundred and fifty to over a thousand per day. Similarly, plans to release guidelines for returning to schools this fall by the CDC were delayed after the President criticized the guidelines as impractical. This pattern of influence can be seen in the Food and Drug Administration as well, with the White House deregulating the approval processes for COVID-19 tests. Several Democratic governors have taken to social media expressing defiance and disdain for the new CDC guidelines. California Governor Gavin Newsom and Washington Governor Jay 310
Inslee stated that their states would continue to test people exposed to confirmed cases. New York Governor Andrew Cuomo went as far as to say “[he] consider[s] it political propaganda.” Testing is meant to identify those with the virus to prevent them from spreading it to others. Before the revision, those who came in contact with an infected person were encouraged to get tested to see if the virus had been transmitted. Catching those who were asymptomatic was crucial to stopping the spread. Now the CDC has revised its position, suggesting that those in contact with an infected person do not need to get tested if they do not exhibit symptoms. The figure below shows that in the early days of infection, virus particles in the body are much higher. This means that the infected person is most contagious before they show any symptoms. This makes the CDC revision even more dangerous, as those who are now less likely to get tested are those that pose the most danger to others. This new guideline does not slow the spread of the virus, but accelerates it. With the reopening of K12 schools and universities, this revised guideline may carry serious consequences. As seen with the economic reopening of the summer, as people venture back into society, the disease spreads. To counter the spread, schools are relying on robust testing and spread prevention. With relaxed testing guidelines for asymptomatic people, we could see a stark increase in cases with symptoms across the country. Rather than decrease testing, we must increase it. The way to beat the virus is to test every American frequently to find out who is contagious. To carry out this mission, there needs to be an affordable and accessible antigen test. One test of promise is an antigen test developed by Abbott Laboratories. This new antigen test, which received emergency use authorization from the Food and Drug Administration, offers diagnosis results in fifteen minutes. Antigen tests measure the body’s reaction to the virus, rather than the virus themselves. They detect those who are the most contagious, rather than specifically testing if one is sick. A healthcare worker takes a nasal swab from the patient and inserts it into a test card, which reads the results. The test is highly portable and is easy to administer. The tests are promising, but far from ideal. To eradicate this disease, tests need to be very cheap—roughly fifty cents—or even 311
free. They need to be widely available, saliva based and home based: not requiring a healthcare administrator. The New England Journal of Medicine recently found that there was “greater variation...in [nasal] swab specimens than in saliva specimens,” meaning saliva based tests may even result in more accurate testing. Abbott’s antigen test is a promising start, but there are still these improvements to strive for. Past the testing phase, we must have strong mitigation policies that mirror foreign COVID control, but have American Characteristics. The US must require mandatory reporting if positive. Political committees in California have been floating this as a policy proposal to decrease contact between the contagious and the healthy. The bill would require employers to notify employees, the California Department of Public Health, and the Occupational Safety and Health Division of any positive COVID test in the workplace. Failure to report could result in a misdemeanor and fine upwards of ten thousand dollars. The bill has passed the state legislators and moves to the Governor’s desk for approval. Further, there must be a greater emphasis and investment for assisted isolation. While contact tracing is important, enforcing compliance is expensive and unrealistic. If we can provide medical and social support to those who are contagious or infected, it will minimize the need for contact tracing. Assisted isolation could include isolating a whole family if one or more of the children are sick; they are provided food, medical assistance, financial support, and more in order to prioritize the isolation of the virus. If the infected person is living alone, there could be similar assistance. If they are with roommates, they can be taken to single isolation in the hospital. The success of this public venture would fall to the CDC. They would need to set up the infrastructure to aggregate data on an individual and family basis, then they use that data to coordinate the isolation process case by case. As it stands, the CDC and the White House seem to be more concerned with reducing the number of tests, returning people to the economy, and moving forward without worry about the consequences. This article originally appeared in Forbes and is available online here: New CDC Guidelines Decrease Coronavirus Testing For Those Who Need It Most 312
September 2020
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Containing COVID—American Style Daily Clout | September 2, 2020 | Article
In the span of last weekend alone, more than 80,000 new cases of COVID-19 were reported across the United States. Worse, the disease claims the lives of about 1,000 Americans daily. Meanwhile in China, the country where it all began, the number of cases from the past week didn’t even reach 200. The amount of deaths per day? On average, one to two. These numbers tell a tale of two countries in which initial response to the pandemic was as different as night and day—as was its impact on the lives of citizens. In China, crisis struck hard and fast, but gave way to rigorous measures of suppression and control that still hold steady. By contrast, the only stability to be found in the United States today lies in the steady increase of outbreaks, fatalities, and general chaos, all of which shows no sign of stopping. There is a strategy for containing COVID-19 that would bring an end to the pandemic in the United States without a vaccine or drug therapy. It is cost-effective, compatible with American values, and needs only two to three months to take effect. It uses the latest science to tailor one of the most effective components of China’s pandemic response—assisted isolation—to the sweeping scale of the U.S. outbreaks, and it deploys the latest testing technology to bring rapid diagnostics into the homes of hundreds of millions of Americans. While it will be some time before China is rid of COVID-19 completely, for a nation of nearly 1.4 billion people it has come incredibly close. Their pandemic response, which the World Health Organization (WHO) called “perhaps the most ambitious, agile, and aggressive disease containment effort in history,” continues to evolve in response to new challenges. In this article, I compare the containment strategies of China and the United States and explain how we can put an American spin to achieve the same degree of 314
success. Rather than mandatory isolation and contact tracing, we can use home testing and assisted isolation to put an end to this crisis. China’s containment strategy Most Americans, according to data collected by the Pew Research Center, believe China is in no small part to blame for the magnitude of the crisis and the devastation it has wrought. Some greet empirical and photographic evidence of China’s return to “normal” with deep and conspiratorial suspicion. As the Chair and President of an international think tank with offices in Shanghai and Beijing, I know such accusations couldn’t be further from the truth. My Chinese colleagues frequent movie theaters, public performances, and restaurants. They send their children to school and travel the country freely to visit relatives and friends. No longer do they live in fear. When early reports of a “mystery pneumonia-like illness” first surfaced in Wuhan in early December, local authorities made the fatal mistake of trying to obscure evidence and censor whistleblowers rather than notify the central government. But when national leadership in Beijing received word, they acted swiftly, alerting the WHO on December 31. China had made enormous strides in its public health and biomedical research capabilities since SARS, the first novel coronavirus pandemic that killed hundreds in 2002. While SARS ultimately didn’t reach nearly as many people as COVID-19, it did lead to considerable economic damage. From January 1 onwards, communication with international health agencies like the WHO became clear and consistent. Researchers mobilized and began investigating the disease with haste, identifying the virus on January 7 and releasing its entire genomic sequence to the world just three days later. Within two weeks, Wuhan and 15 surrounding cities in the Hubei province had entered lockdown—bringing the social and economic life of 60 million people to a screeching halt. Many hubs and modes of intercity transport were suspended, as were the crowd-drawing festivals that normally prompt huge shifts in population flow each spring. When the streets emptied out but local hospitals began to overflow, massive temporary shelter hospitals were constructed with the sole purpose of treating COVID-19 patients. 315
These large-scale directives, which came from the top down, ultimately served one common purpose: find the virus and drive it out at all costs. To detect cases as early and often as possible, temperature screenings and testing checkpoints were installed along streets, outside shops and markets, and around the exits and entrances of bus and train stations. Hotels were repurposed as quarantine facilities that hosted international travelers and others suspected of exposure—for free at first, but later at a cost to deter incoming visits. Anyone confirmed to have COVID-19 was rapidly contact traced and their close contacts quarantined, ideally within 24 to 48 hours. A high-tech Health Code system monitored the symptoms and movements of those identified, alerting local health authorities whenever someone infected or exposed broke isolation or quarantine. A green health code indicates good health; a yellow code, exposure; and a red code, infection. To this day, a green health code is still required to enter some establishments. After a month, towards the end of February, the number of COVID-19 cases in China began a steady decline. On April 8, the lockdown and travel restrictions in Wuhan lifted. All culminated in mid-May when China, for the first time since January, reported zero new cases of COVID-19. Since then, flare-ups or so-called “second waves” have been met with the blunt force of testing—an instrument of disease control that hasn’t received nearly as much attention as vaccines or drug treatments, but is perhaps the most effective means we have at our disposal for stopping the spread of COVID-19 in its tracks. United States containment strategy In terms of the leadership and actions of the national government, the United States and China couldn’t be more different. U.S. medical intelligence officials received word of a “cataclysmic” disease emerging in Wuhan as early as November 2019, and by January 20 the first case of COVID-19 on American shores was identified in Seattle, Washington. Despite this, the Trump administration didn’t declare the pandemic to be a national emergency, place bulk orders on medical supplies, or issue safety guidelines until mid-March. Even then the restrictions were merely recommended, not mandated—a stance so lenient and ineffectual 316
that several states didn’t enact limitations of any kind for months. California became the first to issue a stay-at-home order on March 19, followed swiftly by Nevada, Illinois, New Jersey, and Louisiana. A similar order took effect in New York on March 22—the same day New York City was declared a new global epicenter of the pandemic. In China, many neighborhoods and compounds in Wuhan and beyond banded together to carry out the orders given out by central leadership, appointing community representatives who could help local authorities monitor the health of residents. In the United States, inconsistent messaging from the White House on everything from drug treatments to mask-wearing appeared to have the opposite effect. When the federal “Guidelines for Opening Up American Again” were released on April 16, it fell on individual businesses, institutions, and above all citizens to reconcile conflicting sources of information and make decisions accordingly. State and local governments enforced and discarded COVID-19 protections in piecemeal fashion, such that even those who followed every possible precaution remained vulnerable to transmission. On April 28, COVID-19 cases in the United States topped one million. Today, four months later, that number is now over six million. With schools reopening and child infections on the rise, the demand for a robust, unifying, and evidence-based containment strategy is greater than ever—especially now that our fears around the possibility of COVID-19 reinfection seem to be coming true. We can either learn and adapt China’s success for our own purposes, or allow a mess of our own making to all but overwhelm us. Retooling our response In lieu of a nationwide shutdown that makes it easier to constrict mobility and subdue contagion, a combination of home testing and assisted isolation can give local and national authorities the information they need to understand and reduce the scope of an outbreak. If the key to containment in China was surveillance and constraint, the American counterpart might be convenience and affordability—using federal command and funding to pump 50 t0 100 million tests into the homes of Americans each or every other day. 317
An antigen test fast enough to make this vision a reality was authorized for emergency use by the U.S. Food and Drug Administration (FDA) on August 26. Created by Abbott Laboratories, the rapid antigen test has a price tag of just $5 a pop and can deliver results within 15 minutes. What we really need, however, is a saliva-based test, which unlike nasopharyngeal swabs requires no intervention from healthcare workers. This technology, which isn’t yet available but will be soon, would make COVID-19 tests as convenient and easy for families to use as pregnancy tests. If the overarching goal of China’s pandemic response was to isolate those exposed to the virus rather than those already infected, the criteria for isolation in the United States might be contagiousness instead. Data from preprint studies shows that the concentration of the COVID-19 virus in our nasal passages and throat is at its highest from before symptoms even appear to three or four days after they do (see Figure 1). That means the earliest phase of infection, when 10^6 to 10^9 viral particles are swarming our airways, is when we’re most likely to pass the virus on to others—as well as a critical juncture for testing and isolation. PCR tests, which detect viral DNA, are normally preferred to antigen tests like Abbott’s due to their heightened sensitivity to the virus. But when we test people early enough, the concentration of the virus in our bodies is so great that a sensitive test isn’t needed (see Figure 1). Isolating individuals when they’re at their most contagious also prevents them from exposing—and potentially infecting—the many people they may come into contact with. If rapid tests are made widely available for a low enough cost, the possibility of picking up on infection at this stage becomes more feasible. So does the objective of testing people every couple days or even daily. The next step is assisted isolation. Children who test positive for the disease would isolate with their families at home, where health authorities can monitor their disease progression and volunteers can deliver food and medical supplies. Adults 18 and older who don’t live alone would isolate in a hotel room or hospital, depending on their condition, where they could also be monitored and cared for. To ensure that data on their health status ends up in the right hands, lawmakers could create legislation—as political committees in California did back in August—that requires COVID-19 cases to be 318
reported within 24 hours of detection. While the California bill applied to employers only, with home tests mandatory reporting could be extended to the population at large. This would all but eliminate the need for contact tracing, which served a critical purpose in China but has so far been poorly organized in ineffective in most parts of the United States. The White House, after months of inaction, took the first major step towards advancing such a strategy in August when it put in a mass order of 150 million Abbott rapid antigen tests. Though the biggest investment the federal government has made in testing to date, it still isn’t nearly enough. We need many more hundreds of millions—billions, even—of tests to ensure equitable access to cheap and rapid home testing across the United States. Two years ago in Egypt, another rapid test made by Abbott Laboratories was used to screen the majority of adult Egyptians for hepatitis C for only 50 cents each. Back in May, China was able to test nine million people in Wuhan for COVID-19—keeping a second wave at bay as a result. If the United States is to contain its epidemic anytime soon, we must find a way to take what countries have successfully done before and retool it for our own purposes. Otherwise, we will continue to be exceptional only insofar as how staggeringly we have failed. This article originally appeared in the Daily Clout and is available online here: Containing COVID—American Style
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How We Can Contain COVID-19 Without A Vaccine CNN | September 4, 2020 | Article
While the world is waiting for a safe and effective COVID-19 vaccine, there is a strategy that can potentially bring an end to the pandemic in the United States without the development of pharmaceutical drugs. The strategy, which is cost-effective and compatible with American values like personal freedom, could feasibly bring the epidemic to a halt within two to three months. This strategy would revolve around the distribution of rapid, saliva-based tests that can be administered at home, so that those who are contagious can be quickly identified and isolated. This would also eliminate the need for contact tracing, which has become a nearly impossible task given the number of those potentially exposed in the US today. Advances in our technology, along with our knowledge of the coronavirus, enable this strategy. We now know, for example, that people with COVID-19 are at their most contagious shortly after infection (before symptoms even appear) and continue to be infectious for about 10 days thereafter. This article originally appeared on CNN. To read the full article, click here: How We Can Contain COVID-19 Without A Vaccine
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Herd Immunity: Reckless And Ineffective Strategy Daily Clout | September 8, 2020 | Article
A White House medical adviser is promoting a “herd immunity” strategy to battle COVID-19. This would involve allowing SarsCoV-2 to infect a majority of the population under a “benign neglect” strategy as the government would do little to stop it. This strategy would build immunity to a point where the virus could no longer move from host to host. The strategy would entail millions dead, millions more potentially left with unknown health complications, and no guarantee of success in the end. Herd immunity more accurately requires malign neglect. Were this strategy to be implemented in the US, the death toll would be catastrophic. Assuming seventy percent of the population must have antibodies to achieve herd immunity and a population of three hundred forty million in the US, that would require two hundred thirty eight million people infections, which could involve lifelong health complications for those who get seriously ill. Assuming a death rate of one percent to three percent, the herd immunity strategy would kill 2.4 to 7.1 million Americans and three times that at the current ratio of infected to deceased. Herd immunity has its origins in vaccines for diseases like polio and smallpox, but building immunity against a coronavirus is more difficult and there is every reason to believe a herd immunity strategy would not be successful. Coronaviruses are capable of reinfection in a short time frame. Coronaviruses like the common cold often seasonally reinfect and typically always are symptomatic. Scientists have recognized that reinfection from the same virus, but a different strain was possible for decades. There is a chance the coronavirus could return in another strain and reinfect the population. The herd immunity strategy hinges on the production of antibodies among the infected population. Ten percent or more of people infected with Sars-CoV-2 do not develop robust antibodies. They are immediately at risk of reinfection after getting healthy. For 321
those that do develop antibodies, they seem to fade over time which may account for reinfection by coronaviruses. This means they are immediately protected against reinfection, but only for a short time. Reinfections have already started to occur. In Hong Kong, a man in his mid thirties was infected a second time after about four months with his first infection. Analysis definitely showed that it was reinfection with a different strain of the virus from the one that caused the initial infection. The second case resulted after he took a trip to Europe and he picked up a different strain while abroad. He had developed no antibodies from his first infection after being mildly symptomatic. This different strain was confirmed by genome sequencing. The man had no symptoms the second time. Some have interpreted the Hong Kong patient not being sick the second time around as encouraging, however coronaviruses only cause disease in a small percentage of infections. There are cases in which the second infection causes greater illness. For example in Nevada, a man in his mid twenties was first diagnosed in April with symptoms and tested positive again five weeks later with intense symptoms. The second infection was caused by a different strain of virus. European reinfection cases follow a similar trend: Coronavirus reinfection is unpredictable and can cause similar or worse symptoms the second time around. The White House advisor is likely promoting a dangerous fantasy of something that is not possible. The herd immunity strategy allows millions of people to die as collateral damage, opens hundreds of millions of people to future health complications, endangers the healthcare system, and reaps untold socioeconomic costs to society. The floating of this strategy is reckless, and at best—inhumane. This article originally appeared in the Daily Clout and is available online here: Herd Immunity: Reckless And Ineffective Strategy
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The Case For Safer Emergency Use Authorizations Forbes | September 9, 2020 | Article
In emergency situations such as COVID-19, emergency use authorizations (EUA) are vital and necessary. There needs to be effective treatments and vaccines available to stop the spread of this virus. The failures like hydroxychloroquine show that the EUA process must be robust enough that the authorized products do not harm the public or entrench public distrust of medicine. There cannot be EUAs for products that do not work. The EUA for hydroxychloroquine and its eventual revocation show the shortfalls of the current EUA process. The treatment did not help COVID-19 patients and brought potential health risks to patients. Hydroxychloroquine should never have been authorized in the first place. The approval process must be revised for the safety of the population. The Food and Drug Administration (FDA) authorized hydroxychloroquine on March 28th after being the current Administration lauded its supposed effectiveness. The authorization letter did not describe evidence that suggested hydroxychloroquine was a successful therapeutic. It only alluded to a limited French study of thirty six participants. Within a few months, the scientific consensus was that hydroxychloroquine was ineffective in reducing the symptoms of COVID-19. The FDA revoked hydroxychloroquine’s EUA on June 15th. While “emergency use” implies haste, the quick process raises questions about the safety and effectiveness of a treatment. Understanding these treatments and their effects requires large studies over a significant amount of time. Pushing healthcare products without these studies is too much of a shot in the dark. The FDA is under strong political pressure as well. In addition to the Administration’s push for new treatments, public pressure to approve therapies may move the FDA towards authorization even faster. The ideal world is one where the FDA approves EUAs solely 323
on expert advice. Then the public sees the success of the expert backed EUA and continues to support the FDA. An understated consequence of an EUA failure is the further erosion of trust in the healthcare system and its governing bodies. Federal bodies approving and revoking authorization for treatments in rapid succession will be noticed by the public. Trust in the medical field is low, so this unregulated cycle will exacerbate public skepticism and lower confidence in future potential vaccine approvals. How can we improve the success rate of EUAs? First, authorization cannot move forward without examination and approval of an external advisory committee composed of independent experts, patients representatives, and other stakeholders. The advisory committee deliberations must be fully transparent, even live-streamed. Second, the FDA must insist on post-marketing phase four surveillance of the drug or vaccine for safety in a much larger group of patients for a much longer period than required for the initial authorization. A product that fails to meet the safety and effectiveness standards in a phase four trial is denied. Additionally, emphasizing the National Vaccine Injury Compensation Program to the public will ensure that those skeptical of a drug or vaccine's success will have the assurance of compensation in case something happens after a potential drug or vaccine is authorized. Third, the FDA must work diligently to inform the public and communicate the criteria for approval, the data supporting any recommendation, the advantages and risks of the product, and the provisional nature of EUA. There is no such thing as too much communication between federal agencies and the public during a pandemic. The FDA must be as open as possible in their authorization of treatments. These reforms would lead to an increased sense of transparency and accountability for the public, as well as a more robust approval process to ensure the safety and effectiveness of the authorized products. The consistent approval of successful EUA decisions would encourage the use of EUA treatments and that could potentially lead to an end to the pandemic sooner than otherwise. This article originally appeared in Forbes and is available online here: The Case For Safer Emergency Use Authorizations 324
Why Suspension Of The AstraZeneca Vaccine Trial Matters Forbes | September 9, 2020 | Article
The clinical hold placed on the AstraZeneca COVID-19 vaccine trial highlights serious issues with the rush to approve a new COVID vaccine, and the safety of vaccines already green lit for limited use in China and Russia. AstraZeneca’s vaccine, developed by a team at Oxford University, was considered one of the leading vaccine candidates, with reports of its safety and efficacy widely welcomed when early data was released in July. The United States administration has reportedly been trying to fast-track approval of the drug before the November presidential election and European leaders have already secured access to 400 million doses before the end of this year. The AstraZeneca vaccine, called AZD1222 or ChAdOx1 nCoV-19, is a recombinant viral vector vaccine which uses a weakened version of a common cold virus—an adenovirus—to build immunity to SARS-CoV-2 infection. The adenovirus vectors, such as the one used by the Oxford group, are the backbone of many COVID vaccine candidates, including those already approved for use in Russia and China. Pharmaceutical giant Johnson & Johnson, which is developing their vaccine candidate using the same method, calls their adenoviral vector platform a “proven” technology. But the news this week shows that this approach is far from proven. The details of the event that caused the clinical hold have not yet been fully disclosed. STAT News, which broke the story, received a statement from the drug maker claiming the hold was a routine action triggered by a standard review process that pauses clinical trials whenever a potentially unexplained illness arises. The rumors circulating today suggest that potentially unexplained illness was in fact a serious adverse reaction among one of the trial volunteers, meaning that a previously healthy individual, when given the shot, experienced a reaction that may have required hospitalization or be life-threatening. According to the STAT 325
report, the clinical hold on the AstraZeneca trial is affecting other AstraZeneca trials underway, as well as clinical trials being conducted by other vaccine manufacturers. While it is true that clinical holds are not uncommon, they can be a sign that something has gone very wrong with a potential new product. In this case, we have no real way of knowing the gravity and potential impact of the hold because, as has been the case far too often during this pandemic, the drug companies aren’t releasing enough data for us to know. This lack of immediate transparency is seemingly at odds with the recent declaration by AstraZeneca and eight other COVID vaccine developers to “stand with science” and ensure public confidence in the rigorous scientific and regulatory process by which COVID-19 vaccines are evaluated and potentially approved. The news of the hold is troubling in and of itself, but it highlights only one of the dangers of a rush to a vaccine, whether it be this AstraZeneca one or any of the others currently in development. In addition to the safety and efficacy of the vaccine itself, there are also serious matters regarding the quality and consistency of the manufacturing process that we need to be concerned about, as well as the distribution network for vaccines, the integrity of the cold chain—the system of transporting and storing vaccines at appropriate temperatures, and the safety of the needles and vials used to administer any drug. Allowing this hold to fly past us as a routine action downplays the potential severity of the news and prevents us from seeing this for what it is: a sign that any vaccine, rushed to approval, may prove dangerous to the healthy individuals who would be receiving the drug. This isn’t the first time we’ve seen adverse reactions to potential COVID vaccines and I am fairly certain it won’t be the last. Yes, we need a COVID-19 vaccine. But rushing the approval process, as we have seen this week, may lead to more harm than good. This article originally appeared in Forbes and is available online here: Why Suspension Of The AstraZeneca Vaccine Trial Matters
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A Defense of Self-Testing and Supported SelfIsolation Forbes | September 11, 2020 | Article
In a recent CNN article, I proposed a new way of containing COVID-19. The strategy would be a self test and supported self isolation approach, but some are skeptical. Rapid antigen testing at home for COVID-19 on a daily basis increases the chances of stopping the virus from spreading. Many claim the plan is impractical and that antigen tests are ineffective. Antigen testing catches the infection when it is at its most contagious. Having the public self test and financially assisting the quarantined will stop the spread of COVID-19 and control this pandemic. The strategy to defeat COVID-19 revolves around the free distribution of rapid, saliva based tests that are self administered at home. People are most contagious shortly after infection and before symptoms even appear, then slowly decrease in contagiousness over a ten day period. This is the period when testing and isolation is necessary. With regular at home testing, people can check themselves for the virus before symptoms occur. They can then isolate if they test positive, regardless of if they have symptoms. It would require roughly one hundred million tests per day to rest the US population every three days. These tests could cost as little as fifty cents. Administering one hundred million tests daily at fifty cents each for one hundred days would cost roughly five billion dollars, or less than one percent of the annual military budget. Critics claim this strategy is reliant on a type of testing that results in far too many false negatives. Antigen tests may miss between five and twenty percent of people who are RNA positive. However, people who test both antibody negative and PCR positive are only contagious about five percent of the time. No infectious virus is recoverable from people below the antibody test detection limit. In other words, no more than five percent of those actually contagious should slip through universal home testing for antigens. A ninety five
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percent success rate at detecting contagious infections would be a huge step in the right direction. PCR testing as done today misses up to ninety percent of all those contagious and actively spreading the disease. PCR testing has such a high miss rate for many reasons. First, PCR tests are not universally available. They are hard to access and are mostly reserved for the worried or the ill. Only about forty thousand people get tested every day. Second, most people who are contagious do not even know that they are infected. Many have no symptoms and do not have any reason to get tested. Third, the turnaround time for the results may stretch to a week or more during which people are contagious. The reason for testing is to stop the virus from spreading, not to understand who was sick last week. Skeptics will suggest that antigen tests cannot be home based for one reason or another. They cite the necessity of trained administration in a certified lab. These at home tests are comparable to another at home test with life altering implications: pregnancy testing. Partners have been testing themselves for pregnancy for decades. These tests are not one hundred percent accurate, but produce reliable enough results to be a mainstay of modern society. They are also simple to self administer, so why should a rapid antigen test be any different? The assumption in this strategy is that the entire public will comply with it, which critics point out as improbable. It is true that not all will use the test. Some who do use the test may conceal a positive result for themselves or their children. That is why workplaces and schools should have their own spot checks. The University of Illinois is requiring that all students and faculty get tested twice a week to avoid spreading the virus. This kind of community responsibility is encouraging, but we can do better. With some exceptions, most people would comply with testing procedures because they want to return to normal life. Americans have been ravaged by the pandemic for six months. Were an ambitious solution available to return them to normalcy, they would take it. To further incentivize compliance, assisted quarantine includes a daily cash stipend to compensate for lost wages and safe housing for those who do not have it, per day per household. The isolated would be assured food and medical supplies as well. There has to be help 328
for people that agree to quarantine. About one hundred thousand households would need assisted isolation a day for three months. Presuming about five hundred dollars per family per day for food, shelter, and income compensation, the cost of the three months would be about fifty billion dollars. Totaling fifty five billion dollars, the COVID-19 self test and supported self isolation approach would contain the spread of COVID-19 months faster than relying on a future vaccine. It would save the US trillions of dollars in lost productivity and spending. The skeptics question this strategy’s ambition, but ambition is necessary to control a global event like COVID-19. This article originally appeared in Forbes and is available online here: A Defense of Self-Testing and Supported Self-Isolation
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The University Of Illinois’s COVID-19 Control Shows That Mass Testing Is The Answer Forbes | September 15, 2020 | Article
The University of Illinois implemented an aggressive testing campaign to reign in the spread of COVID-19. The operation involves testing the entire student body and faculty twice per week—around fifteen thousand tests each day. Students tested positive are alerted and quarantined while the school grants building and facilities access to those who test negative. This testing regime illustrates how to conduct a nationwide testing campaign to overcome the COVID-19 pandemic. The saliva based tests used by the school were developed by a university research team. Tests are free and are available at 17 on campus testing centers. Students are typically alerted of their test results within five hours of administration. Tests are being processed 24 hours a day on weekdays and nearly all day on weekends. If a student or faculty member tests positive, they receive an alert immediately and must quarantine immediately. Additionally, the University allows students to enable bluetooth settings to track if they have been in close contact with a recently confirmed positive case. Those students are alerted and required to test immediately. A University app tied to student IDs moderates the whole process. This app also acts as a key to give negative students access to campus buildings and resources. How are these advances applicable to a nationwide project? It first shows that wide scale testing protocols are possible and effective. In a recent CNN article, I wrote about a testing plan to contain COVID-19. This plan includes testing the entire US population every three days, or about one hundred million tests per day. Simulations of this plan suggest eighty percent cuts in transmission. The University of Illinois is seeing similar results in its reduction of transmission. After students returned to campus, positivity rates peaked at 2.86 percent due to off campus parties and ignored isolation guidelines. After a week of testing and enforced isolation 330
guidelines, the University reduced the positivity rate to one percent and officials anticipate a rate of .5 percent in the coming weeks. That is a 65 to 85 percent reduction in positivity over a couple weeks. With a national testing regime, there could be a similar reduction seen. Second, these campus tests utilize saliva samples rather than nasal swabs. Citing a Yale study from April, campus researchers concluded that saliva samples are more sensitive and more quickly administered, without the help of a healthcare worker. Saliva based tests are essential to a national testing regime. Tests must be home based and self administered to ensure ease of use. Third, the University is able to deliver results on the same day. A nationwide testing protocol would hinge on rapid antigen testing and results in minutes. The slowdown at the University of Illinois is lab processing, which takes a few hours. Even with the hurdle of running tests through a lab, students and faculty still typically receive their results in about five hours. Breakthroughs in antigen testing by Abbott Laboratories and others are putting twenty minute tests into production at this moment. Same day results are encouraging, but same hour results are necessary. A lacking aspect of the University plan that is essential to a successful nationwide effort is assisted isolation. Individuals and families forced into quarantine due to a positive COVID-19 test do not stop having bills, stop having to pay rent, or stop buying food for their children. Isolation must be economically feasible for this strategy to succeed. The government would need to guarantee food, medical supplies, and shelter if necessary. The current positivity rate in the United States hovers around five percent. Reducing that by a simulated eighty percent would bring that down to one percent. That rate could optimistically go down to .5 percent if The University of Illinois is a valid preview of what could be. There must be aggressive action taken nationwide as we have seen at this university. The health of millions are at stake. This article originally appeared in Forbes and is available online here: The University Of Illinois’s COVID-19 Control Shows That Mass Testing Is The Answer
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Paused AstraZeneca Trials Emphasize Need For Vaccine Transparency Forbes | September 16, 2020 | Article
Astrazeneca, and all the other companies under Food and Drug Administration purview, are developing vaccines for COVID-19. In the midst of current trials across the globe, they paused operation when a participant in the United Kingdom developed symptoms of a spinal inflammatory disease. While this pause is an encouraging sign of ethical standards being upheld, why is there not more transparency in these trials and in vaccine approval in general? Details for the hold on trials by AstraZeneca have not been fully disclosed and internal discussions are not publicized. It is encouraging to see that they paused trials for the safety of a patient, yet the lack of transparency by the drug company is cause for caution. This vaccine is meant to save lives and return the world to normalcy, but the public is not allowed to know about the daily advancements of the drug? People ought to know more about the safety event in question. This is not to say reveal the identities of the participants. This is simply a request to know more about the trials, about the decision to stop the trials after the participant developed symptoms, about the decision to restart trials a week later in the UK and Brazil, but not in the United States, South Africa, or India, etc. National Institute of Health official Dr. Avindra Nath commented that AstraZeneca “need[s] to be more forthcoming with a potential complication of a vaccine which will eventually be given to millions of people...we would like to see how we can help, but the lack of information makes it difficult to do so." Dr. Jesse Goodman, a Georgetown University professor and former Chief Scientist at the FDA said that the FDA must consult with British vaccine regulators to understand why they resumed trials. He further commented that AstraZeneca must be required to update safety information provided to the participants.These trials
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must be more transparent in their development of a drug that will be administered to millions. Why stop at transparency in individual trials? The public deserves to know more about the vaccines being approved in the coming months. What are the vaccine requirements for emergency use authorization approval in the US? There is already evidence suggesting that the Food and Drug Administration has issued EUAs for therapies like hydroxychloroquine and convalescent serum without substantial research that they work. How many patients does a successful study need to have for an approved vaccine? Three hundred? Three thousand? Some experts recommend that the number be thirty thousand or more. That is only to get a vaccine approved. The FDA must require further controlled study once an EUA is granted. Phase four of typical clinical trials involves thousands of participants monitored in what is called a postmarketing surveillance trial. In short, drug companies monitor their released drugs to ensure they are working. Another transparency concern is the threshold of success a vaccine needs to have. The FDA has stated that a vaccine needs to prevent or reduce disease in a participant group by fifty percent. First, what happens to the other fifty percent? A successful vaccine should have a much higher hit rate. Second, what if a vaccine has a reduction rate of forty percent or even thirty percent? It is not too farfetched to suggest the FDA would take that number as a close enough figure. There are two related dangers with premature EUAs. First, a premature EUA granted to a vaccine may seriously compromise the integrity of future vaccine trials. Control groups are integral to the testing process. Though as we have seen with hydroxychloroquine and convalescent serum, participants may believe that it is their right to be given the actual vaccine in trials. Second, once a vaccine is granted authorization, many people will take that as a sign that the dangers of COVID-19 are over. This is far from the case, as it takes many months or even several years until we know the safety of a vaccine. Systems for administration have to be perfected. There is also a belief that once a vaccine is available, many will modify their behavior in a way that could seriously exacerbate the pandemic. Recent data suggests premature
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relaxation of habits can double or more infection rates, as we’ve seen in the US and abroad in recent months. Then there are the issues concerning long term protections and dangers. There have been cases of reinfection both in the US and abroad. Were reinfection to become a major issue as temperatures drop and people return indoors, the question of whether a new vaccine to cover reinfections for the future. There is also plenty of evidence of antibody dependent facilitation of reinfection, or reinfection with worse symptoms due to the presence of antibodies, such as with common cold causing viruses. This goes without mentioning the dangers of taking an undertested vaccine. Typically vaccines take years to ensure long term safety protections. It seems that a COVID-19 will be available by the end of the year, so any chance of understanding long term health risks will be out the window. The dangers to the public for taking an unproven and undertested vaccine are overwhelming. The opaque veil of vaccine approval must be lifted during this time of crisis. It is in the long term interest of the public to understand the process that has such a massive effect on their lives. This article originally appeared in Forbes and is available online here: Paused AstraZeneca Trials Emphasize Need For Vaccine Transparency
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Why We Can’t Rely On Natural Immunity To Protect Us From COVID-19 Forbes | September 18, 2020 | Article
There is a question that has crossed all our minds at some point, yet has no satisfactory answer: If I’m infected with SARS-CoV-2, the virus that causes COVID-19, how long am I immune? A more technical way of asking the same question is: How long do antiSARS-CoV-2 antibodies that bind to the spike protein persist? While a new study on anti-SARS-CoV-2 antibodies, published yesterday in JAMA, hasn’t much to offer in the way of definitive answers, it does provide some disturbing insight into our natural immunity—or lack thereof—to COVID-19. Compounded with recent reports of reinfection, this study and others like it give us much to think about when it comes to how we move forward in our pandemic response. When sampling healthcare personnel who work directly with COVID-19 patients at Vanderbilt University Medical Center in Nashville, Tennessee, researchers found that 58 percent of those who tested positive for anti-SARS-CoV-2 antibodies in April tested negative only two months later. Their antibody had levels dropped so precipitously, they were no longer detectable. Even the 42 percent of personnel whose antibody levels remained above threshold still experienced a significant decline (see Figure 1). The targets of the researchers’ assays—in other words, the specific antibodies they were measuring—were anti-SARS-CoV-2 antibodies developed against the viral spike protein. Previous research suggests that these antibodies are critical to the body’s ability to neutralize the virus in patients mildly or seriously ill. Whether their disappearance leaves the body wholly unprotected isn’t yet certain, but it does raise the question of which immune mechanisms do protect us if these antibodies cannot. We ask this question knowing, thanks to two scientific case studies released last month on COVID-19 patients in Hong Kong and the United States respectively, that it is possible to be reinfected 335
with COVID-19 mere months after having it the first time. While the United States case study, which focuses on a 25-year-old man in Nevada, is still undergoing peer review, it is in our collective interest to take these reports very seriously. Reinfection is something of a signature move for the coronavirus family, and documentation of this ability dates as far back as the late 1970s and 1980s. If SARS-CoV-2 is both more lethal and more transmissible than its seasonal cold-causing cousins, it would be naive to assume that it wouldn’t be more adept at weaponizing its oldest and dirtiest trick, too. A six-year study of the human coronavirus NL63 (HCoV-NL63), published in 2018, found that people who had contracted the virus in households and hospitals across coastal Kenya were sometimes infected not just once, or twice, but three times. The authors of the Kenya study speculate that antibodies may have potentiated infection, rather than preventing it, and remark that this was found to occur with SARS-CoV, the virus that caused the first lethal coronavirus pandemic. Such a possibility further complicates our understanding of the role of anti-SARS-CoV-2 antibodies and our immunity to coronaviruses more broadly. Even their tendency to be short-lived isn’t a given. A recent Icelandic study of population antibody levels discovered that about 91 percent of participants who tested positive for COVID-19 retained antiSARS-CoV-2 antibodies two months after their initial diagnosis. The reasons why such inconsistencies persist remain elusive, but their implications for how we control and contain COVID-19 are ultimately the same. We cannot rely on natural immunity to protect us from this virus. For as long as we don’t have a vaccine, we must use testing, assisted isolation, and other evidence-based public health measures to build up long-lasting and efficacious defenses. Too much is at stake for us to sit back and wait. This article originally appeared in Forbes and is available online here: Why We Can’t Rely On Natural Immunity To Protect Us From COVID-19
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Herd Immunity Is A Fantasy CNN | September 19, 2020 | Article
Despite what science or the failed coronavirus strategy in Sweden tell us, people continue to entertain herd immunity as a possible strategy for ending the COVID-19 pandemic. During ABC's town hall meeting with voters on Tuesday, President Donald Trump said the coronavirus would "go away," even without a vaccine. "You'll develop — you'll develop herd — like a herd mentality. It's going to be — it's going to be herddeveloped, and that's going to happen. That will all happen," he said. It seems Trump meant herd immunity, rather than "herd mentality," but no matter — the line of thinking he was apparently trying to invoke goes like this: if Americans let SARS-CoV-2, the virus that causes COVID-19, run amok, then eventually enough people will be immune (around 70 to 90%) that the virus will no longer pose a threat to the population. I've previously written about how reckless and ineffective this line of thinking is, and many experts have agreed. The strategy would cause a catastrophic number of deaths in the US. And Sweden, which took a lax approach to coronavirus restrictions, is still far from the herd immunity threshold. Thanks to researchers using genomic sequencing techniques, we now know that people can be reinfected with COVID-19 — a fact that should be the final nail in the coffin of any ill-conceived hopes for herd immunity. This article originally appeared on CNN. To read the full article, click here: Herd Immunity Is A Fantasy
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Lessons From AIDS For The COVID-19 Pandemic: We Can Learn From Parallels Between The Coronavirus And HIV Crises Scientific American | September 20, 2020 | Article
We are engaged in another deadly episode in the historic battle of man versus microbe. These battles have shaped the course of human evolution and of history. We have seen the face of our adversary, in this case a tiny virus.” I spoke these words in testimony before a U.S. Senate subcommittee on September 26, 1985. I was talking about HIV, but I could say the same thing today about the coronavirus we are facing. Like all viruses, coronaviruses are expert code crackers. SARSCoV-2 has certainly cracked ours. Think of this virus as an intelligent biological machine continuously running DNA experiments to adapt to the ecological niche it inhabits. This virus has caused a pandemic in large part because it acted on three of our most human vulnerabilities: our biological defenses, our clustering patterns of social behavior and our simmering political divides. How will the confrontation unfold in the next years and decades? What will be the human toll in deaths, ongoing disease, injuries and other impairments? How effective will new vaccines and treatments be in containing or even eradicating the virus? No one can say. But several lessons from the long battle with HIV, the human immunodeficiency virus that causes AIDS, suggest what may lie ahead. HIV/AIDS is one of the worst scourges humans have encountered. As a code cracker, HIV is an expert. By the end of 2019 the global death toll from this virus was roughly 33_ million people. In all, 76_ million people have been infected, and scientists estimate another 1.7 million people acquire the virus every year. Yet we must appreciate what our scientific defenses have accomplished. Of the nearly 38_million people currently living with HIV/AIDS, 25_million are receiving full antiretroviral treatments that prevent disease and suppress the virus so well they are unlikely 338
to pass it along. I would wager that another 25_million or more infections never happened, primarily in sub-Saharan Africa, because these treatments became available in most countries. From fighting this epic war against AIDS, doctors, virologists, epidemiologists and public health experts have learned crucial lessons that we can apply to the battle we are currently waging. For instance, we saw that vaccines are never a guarantee but that treatments can be our most important weapon. We discovered that human behavior plays a vital role in any disease-fighting effort and that we cannot overlook human nature. We have also seen how critical it is to build on knowledge and tools gained fighting earlier outbreaks—a strategy only possible if we continue funding research in between pandemics. VACCINE CHALLENGES Early observations of how HIV behaves in our bodies showed the road to a vaccine would be long and challenging. As the outbreak unfolded, we began tracking antibody levels and T cells (the white blood cells that wage war against invaders) in those infected. The high levels of both showed that patients were mounting incredibly active immune responses, more forceful than anything we had seen for any other disease. But even working at its highest capacity, the body’s immune system was never strong enough to clear out the virus completely. Unlike the hit-and-run polio virus, which evokes long-term immunity after an infection, HIV is a “catch it and keep it” virus— if you are infected, the pathogen stays in your body until it destroys the immune system, leaving you undefended against even mild infections. Moreover, HIV continually evolves—a shrewd opponent seeking ways to elude our immune responses. Although this does not mean a vaccine is impossible, it certainly meant developing one, especially when the virus hit in the 1980s, would not be easy. “Unfortunately, no one can predict with certainty that an AIDS vaccine can ever be made,” I testified in 1988 to the Presidential Commission on the HIV Epidemic. “That is not to say it is impossible to make such a vaccine only that we are not certain of success.” More that 30 years later there still is no effective vaccine to prevent HIV infection.
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From what we have seen of SARS-CoV-2, it interacts with our immune system in complex ways, resembling polio in some of its behavior and HIV in others. We know from nearly 60 years of observing coronaviruses that a body’s immune system can clear them. That seems to be generally the case for SARS-CoV-2 as well. But the cold causing coronaviruses, just like HIV, also have their tricks. Infection from one of them never seems to confer immunity to reinfection or symptoms by the same strain of virus—that is why the same cold viruses return each season. These coronaviruses are not a hit-and-run virus like polio or a catch-it-and-keep-it virus like HIV. I call them “get it and forget it” viruses—once cleared, your body tends to forget it ever fought this foe. Early studies with SARSCoV-2 suggest it might behave much like its cousins, raising transient immune protection. The path to a SARS-CoV-2 vaccine may be filled with obstacles. Whereas some people with COVID-19 make neutralizing antibodies that can clear the virus, not everybody does. Whether a vaccine will stimulate such antibodies in everyone is still unknown. Moreover, we do not know how long those antibodies can protect someone from infection. It may be two or three years before we will have the data to tell us and any confidence in the outcome. Another challenge is how this virus enters the body: through the nasal mucosal membranes. No COVID-19 vaccine currently in development has shown an ability to prevent infection through the nose. In nonhuman primates, some vaccines can prevent the disease from spreading efficiently to the lungs. But those studies do not tell us much about how the same drug will work in humans; the disease in our species is very different from what it is in monkeys, which do not become noticeably ill. We learned with HIV that attempts to prevent virus entry altogether do not work well—not for HIV and not for many other viruses, including influenza and even polio. Vaccines act more like fire alarms: rather than preventing fires from breaking out, they call the immune system for help once a fire has ignited. The hopes of the world rest on a COVID-19 vaccine. It seems likely that scientists will announce a “success” sometime this year, but success is not as simple as it sounds. As I write, officials in Russia have reported approving a COVID-19 vaccine. Will it work? Will it be safe? Will it be long lasting? No one will be able to provide 340
convincing answers to these questions for any forthcoming vaccine soon, perhaps not for at least several years. We have made remarkable improvements in our molecular biology tools since the 1980s, yet the lowest part of drug development remains human testing. That said, the infrastructure created for HIV/AIDS research is accelerating the testing process now. Thirty thousand volunteers around the world participate in networks built by the National Institutes of Health for studies of new HIV vaccine candidates, and these networks are being tapped for initial testing of COVID-19 vaccines, too. When doctors treat a patient who is likely to die, they are willing to risk that a drug might sicken the patient but still save their life. But doctors are less willing to do that to prevent disease; the chances of causing greater harm to the patient are too high. This is why for decades the quest for a vaccine to prevent HIV infection has lagged so far behind development of therapeutic drugs for HIV. FOCUS ON TREATMENTS These drugs now stand as an incredible success story. The first set of HIV drugs were nucleic acid inhibitors, known as chain terminator drugs. They inserted an additional “chain terminating” nucleotide as the virus copied its viral RNA into DNA, preventing the HIV chain of DNA from elongating. By the 1990s we had gotten better at using combinations of drugs to control HIV infections soon after patients were exposed. The first drug, AZT, found immediate application for health care workers who accidentally had a needlestick injury that infected them with contaminated blood. It was also used to reduce motherto-child transmission. For example, prenatal treatments for mothers with AIDS at that time reduced the number of babies born infected by as much as two thirds. Today combination chemotherapy reduces mother-to-child transmission to undetectable levels. The next set of drugs was protease inhibitors, one of which I helped to develop. The first was introduced in 1995 and was combined with other drugs in treating patients. These drugs inhibited the viral protease enzyme responsible for longer precursor proteins in the short active components of the virus. But there is a fundamental problem with these drugs, as well as those that inhibit 341
viral polymerases, which help to create virus DNA. Our bodies also use proteases for normal functioning, and we need polymerases to replicate our own nucleic acids. The same drugs that inhibit the viral proteins also inhibit our own cells. The difference between a concentration in which the drug inhibits the virus target and a concentration in which it hurts the human proteins is called the therapeutic index. The therapeutic index gives you the window in which the drug will be effective against the virus without causing undue side effects. That window is rather narrow for all polymerase and protease inhibitors. The gold standard for AIDS treatment now is called antiretroviral therapy—essentially patients take a cocktail of at least three different drugs that attack the HIV virus in different ways. The strategy is based on earlier success we had in fighting cancer. In the late 1970s I established a laboratory at Harvard University’s DanaFarber Cancer Institute to develop new drugs to treat cancer patients. Cancers developed resistance over time to single drugs, but combinations of drugs were effective in slowing, stopping or killing the cancers. We took that same lesson of combination chemotherapy to HIV. By the early 1990s the first combination AIDS treatments were saving the lives of people infected with HIV. Today an infection is far from the death sentence it used to be—patients can now live almost unaffected by HIV, with a relatively minimal impact on life expectancy. We already know resistance to single drugs will bedevil COVID19 treatments. We have seen resistance to single, anti-SARS-CoV2 drugs develop rapidly in early lab studies. Just as with AIDS and cancer, we need a combination of medicines to treat this disease. The goal of the biotechnology and pharmaceutical industries now is to develop an array of highly potent and specific drugs, each of which targets a different function of the virus. Decades of research on HIV has shown the way and gives us confidence in our eventual success. HUMAN BEHAVIOR In trying to understand and counter the AIDS epidemic, physician and virologist Robert Redfield (who is now head of the Centers for Disease Control and Prevention) and I became good 342
friends in the early 1980s. We quickly learned that while many politicians across the globe refused to recognize HIV as a threat to their populations, militaries were an exception. Nearly all countries considered AIDS a serious danger to troops and military readiness and a potentially huge drain on future military funds. Their view was, “Let’s not blind ourselves and pretend soldiers are saints. They are not. They are humans.” Redfield, then at Walter Reed Army Medical Center, helped to design and manage a program to test the entire U.S. uniformed forces for HIV infection (although the consequences of this test were controversial, and recruits who tested positive were barred from service). At the time there were no effective drugs; the disease killed more than 90 percent of those infected. When married couples were tested and one partner was infected and one not, doctors advised them in the strongest possible terms to use condoms. I was stunned to learn that fewer than a third complied with the advice. “If people don’t respond to the lethal danger of unprotected sex with their husband or wife, we are in real trouble,” I thought. Over the next five years more than three quarters of the uninfected partners contracted HIV. I have always used this experience as a guide to pit hope against reality. Human sexuality—the drive for sex and physical connection—is deeply embedded in our nature. I knew in the 1980s it was very unlikely people would change their sexual behavior in a major way. In the 19th century everyone knew how syphilis was contracted and that it was serious disease. Yet syphilis still infected at least 10 to 15 percent of American citizens at the beginning of the 20th century. It was not that people were ignorant of how to catch it; it is that they did not change their lifestyle accordingly. There is likewise a sexual dynamic to COVID-19 that often goes unmentioned. It is part of what is driving people out of their homes and into bars and parties. Anyone with a craving for a beer can quench their thirst in the safety of their own home, but gratification comes less easily for other desires, especially when one is young, single and living alone. Our public health strategies should not ignore this fact. The same lessons we learned in the midst of the HIV epidemic to help young people change their behaviors apply today to COVID-19: know your risk, know your partners and take necessary 343
precautions. Many young people operate under the false assumption that even if they become infected, they will not become severely ill. Not only is this belief untrue, but even people with asymptomatic infections can suffer serious, lasting damage. But the more people understand the risk—younger people especially—the greater likelihood they will take the steps necessary to protect themselves and others. We saw this happen with AIDS. FUNDING When I ask world experts what they know about the detailed molecular biology of SARS-CoV-2 or, for that matter, any other coronavirus, they do not have the kind of answers they should. Why? Because governments and industry pulled the plug on coronavirus research funding in 2006 after the first SARS (severe acute respiratory syndrome) pandemic faded away and again in the years immediately following the MERS (Middle East respiratory syndrome, also caused by a coronavirus) outbreak when it seemed to be controllable. Funding agencies everywhere, not just in the U.S. but in China, Japan, Singapore, Hong Kong and the Middle East— countries affected by SARS and MERS—underestimated the threat of coronaviruses. Despite clear, persistent, highly vocal warnings from many of those who battled SARS and MERS up close, funding dried up. The development of promising anti-SARS and MERS drugs, which might have been active against SARSCoV-2 as well, was left unfinished for lack of money. With 776,000 dead and 22 million infected globally as of midAugust, we have every motive to accelerate funding. The U.S. quickly opened the funding spigots last spring for research to hasten discoveries of vaccines and drugs. But will it be enough? We learned from the HIV crisis that it was important to have research pipelines already established. Cancer research in the 1950s, 1960s and 1970s built a foundation for HIV/AIDS studies. The government responded to public concerns, sharply increasing federal funding of cancer research during those decades. These efforts culminated in Congress’s approval of President Richard Nixon’s National Cancer Act in 1971. This $1.6-billion commitment for cancer research, equal to $10 billion in today’s money, built the
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science we needed to identify and understand HIV in the 1980s, although of course no one knew that payoff was coming. In the 1980s the Reagan administration did not want to talk about AIDS or commit much public funding to HIV research. The first time President Ronald Reagan gave a major speech on AIDS was in 1987. In his first administration, funding for HIV research was scarce; few scientists were willing to stake their careers on deciphering the molecular biology. Yet once the news broke that actor Rock Hudson was seriously ill with AIDS, Ted Stevens, the Senate Republican Whip, joined with Democratic Senator Ted Kennedy, actor Elizabeth Taylor, me and a few others in campaigning effectively to add $320 million in the fiscal 1986 budget for AIDS research. Barry Goldwater, Jesse Helms and John Warner, Republican leaders in the Senate, supported us. The money flowed, and outstanding scientists signed on. I helped to design this first congressionally funded AIDS research program with Anthony Fauci, the doctor now leading our nation’s fight against COVID-19. (And if there is one person in the world who has made the greatest contribution to the prevention and treatment of AIDS, that person is Fauci.) One difference between the 1980s and now is that Republican members of Congress were more willing to stand up to the president and White House staff when they failed to take the necessary steps to fight a global disease. For example, Stevens decided it was his job to protect the U.S. Army and other arms of the military and Secret Service as much as possible from HIV infection. He helped to move $55 million within the defense budget, designating it for screening recruits for HIV/AIDS. Our tool set for virus and pharmaceutical research has improved enormously in the past 36 years since HIV was discovered. This is one reason I am confident we will have effective antiviral drugs for treating COVID-19 infections by next year, if not sooner. What used to take us five or 10 years in the 1980s and 1990s in many cases now can be done in five or 10 months. We can rapidly identify and synthesize chemicals to predict which drugs will be effective. We can do cryoelectron microscopy to probe virus structures and simulate molecule-by-molecule interactions in a matter of weeks— something that used to take years. The lesson is to never let down our guard when it comes to funding antivirus research. We would 345
have no hope of beating COVID-19 if it were not for the molecular biology gains we made during earlier virus battles. What we learn this time around will help us out during the next pandemic, but we must keep the money coming. A LEAP INTO DARKNESS In November 2019 I spent several days in Wuhan, China, chairing a meeting of the U.S.-China Health Summit. Our group’s major concern, looming amid the U.S.-China trade war, was the threat of restrictions on sharing research discoveries. Otherwise, it was a delightful time in a beautiful city. Weeks later, back home in New York City, I could not shake a lingering cold virus infection I picked up on the Wuhan trip. (I later tested negative for COVID-19 antibodies, but that result is not definitive.) The head of my foundation in China called me one day with awful news. Three of his grandparents had died from some strange virus. “Everyone who gets this is really sick,” my colleague, in his mid-30s, said. “Everything is closed down. I can’t even go to my grandparents’ funerals.” A few weeks later I received a vivid firsthand account of how aggressively China was confronting the outbreak from another colleague who had just emerged from 14 days of isolation in a quarantine hotel. He explained that when one person in the back of his flight from Frankfurt, Germany, to Shanghai tested positive for the coronavirus, contact tracers called my friend days later and ordered him into isolation. His only human contact then was with hazmat-clad inspectors who came daily to disinfect his room and drop off meals. We are just beginning to glimpse what the long-term toll of COVID-19 might be. This is a new virus, so we will not have a clearer idea until after a few years, but we know it will be very high. We have barely scratched the surface of coronavirus molecular biology. What story will our children and grandchildren recount about our successes as scientists and as a society, and our failures, to contain this pandemic—the worst we have faced in 100 years? Science leaps into the darkness, the very edge of human knowledge. That is where we begin, as if deep in a cave, chipping away at a wall of hard stone. You do not know what you will find 346
on the other side. Some people chip away for a lifetime, only to accumulate a pile of flakes. We may be in for a protracted pandemic, or we may get lucky with effective treatments and vaccines soon. But we have been here before, facing an unknown viral enemy, and we can lean on lessons we have learned. This is not the first and will not be the last global epidemic. This article originally appeared on Scientific American. To read the full article, click here: Lessons From AIDS For The COVID-19 Pandemic: We Can Learn From Parallels Between The Coronavirus And HIV Crises
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Beware Of COVID-19 VaccineTrials Designed To Succeed From The Start Washington Post | September 22, 2020 | Article
In response to widespread demand for more transparency, pharmaceutical companies Moderna and Pfizer have released clinical study protocols for their COVID-19 vaccine trials. The goal is to reassure the public that the trials are being conducted responsibly and that any approved vaccine would be safe for all. But the protocols should heighten anxiety rather than alleviate it. A close reading suggests the clinical trials have been designed to ensure the greatest possible success for these candidates — and that could overstate their effectiveness. In both the Moderna and Pfizer trials, for example, the primary objective is to prevent any occurrence of COVID-19, not necessarily a severd nearly 1 million people worldwide and left many millions more with long-term damage. With the current protocols, it is conceivable that a vaccine might be considered effective — and eventually approved — based primarily on its ability to prevent mild cases alone. If we were developing a vaccine for a simple cold virus, perhaps this would indeed be enough. But COVID-19 is far from a common cold. People are not concerned about the tickle in their throat or a runny nose; they are concerned about put in the hospital. A COVID-19 vaccine should, first and foremost, protect us from severe instances of the disease. Equally troubling is the size of the group in which efficacy for each vaccine would be proved. Both Pfizer and Moderna have touted the large number of participants in their trials, at upwards of 30,000 participants slated for each. But while the full trial sizes might be large, the protocols suggest that efficacy can be proved in an initial test group of just 106 for the Moderna vaccine and in a group of 64 for Pfizer. But keep in mind only half of each group receives the vaccine; the other half receives a placebo.
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The protocols suggest that successful initial interim trials for the Moderna and Pfizer vaccines would show efficacy among 74 percent and 76.9 percent of participants, respectively. This means if 39 of those who receive the vaccine do not get sick, Moderna will consider the vaccine a success. For Pfizer, the number is 25. At this point, the Food and Drug Administration could grant emergency-use authorization. In other words, the two vaccines could hinge on the combined results of 64 people. Granted, proof of efficacy in such a small group doesn’t guarantee that a vaccine candidate will be approved for manufacturing and use worldwide. But the U.S. government has shown that it’s willing to rush new anti-COVID-19 drugs to market on promises of even less. Were these two vaccine-makers to come out with early results from an interim analysis of their trials and claim their candidates to be effective, there is little doubt the FDA would grant an emergency-use authorization. The public would likely take such a decision as a sign that the vaccine is completely effective, despite the fact that it would have been proved effective only in a small sampling of individuals and might not be useful at all in preventing severe cases of the disease. While both companies say they would continue their trials and continue to explore potential long-term health risks, it might not be possible to do so if participants receiving the placebo demand the real vaccine. As we saw with previous emergency authorizations — namely hydroxychloroquine, convalescent plasma and remdesivir — once they were granted, the trials ended. Are we really willing to conclude a drug is safe based on the health outcomes of so few? Recent trials by AstraZeneca were paused after a patient developed symptoms of an inflammatory spinal disease. Rushed Moderna and Pfizer trials could bring about similar short-term health consequences or, potentially far worse, lead to long-term health consequences that we won’t discover until months or years after the vaccine’s approval. At a time when an average of 40,000 cases and nearly a thousand deaths are reported every day in the United States — and far more globally — these protocols are outrageous. The fact that one would base the health of billions of humans on the outcomes of a few defies any definition of common sense.
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If — or perhaps when — positive early results from these trials are announced, keep my warnings in mind. These protocols seem designed to get a drug on the market sooner rather than later, on a timeline arguably based more on politics than public health. The lives of millions are at risk; we can and should demand better. This article originally appeared in the Washington Post and is available online here: Beware Of COVID-19 VaccineTrials Designed To Succeed From The Start
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What COVID-19 Reinfection Means For Vaccines Scientific American | September 23, 2020 | Article
We now know repeat infections are possible; understanding them will shape the fight against the pandemic The question of whether we can be reinfected with COVID-19 has been resolved. In August, genome sequencing confirmed that a 33-year-old man in Hong Kong had indeed been infected by the same virus a second time. So too was the case for a 25-year-old man in the United States, though the originating case study has yet to be peer reviewed. This strengthens earlier reports that have surfaced periodically throughout the pandemic. Most were in China and South Korea, and some in the U.S. None of these were ever verified in laboratory, leaving open the possibility that false positives or negatives had simply confounded test results. A new surge of similarly anecdotal reports is cropping up across Europe and India. If SARS-CoV-2, the virus that causes COVID-19, follows the precedent set by its coronavirus cousins, reinfection will soon become the rule, rather than the exception. The ability of commoncold-causing coronaviruses endemic to humans to infect the same person multiple times has been documented in studies going back decades and, more recently, in a detailed 2018 study conducted by researchers collaborating in the Netherlands and Kenya. This body of research, now that we know SARS-CoV-2 also possesses the ability to reinfect, can guide our attempts to answer the questions that remain—namely, how often we can expect to be reinfected, whether a second infection will induce symptoms more mild or severe than what came before, and what this all means for our ability to create a COVID-19 vaccine.
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Early evidence of reinfection dates back to series of experiments conducted in the late 1970s and 1980s. Healthy volunteers were exposed to a coronavirus one year, develop a cold, and recover. When exposed again a year later, the cycle repeated for the majority of participants—as many as two thirds, as was the case in a study published in 1990. Some of these are the same coronaviruses we battle year in and year out. The Kenya study, which incorporated gene sequencing methods, corroborates and elaborates on these findings. Carried out across rural hospitals and households in Kilifi County, Kenya, the study tracked the circulation of multiple coronaviruses throughout the community over a span of six years. Nearly 30 percent of those who caught one variant of the virus once experienced a second infection, while about 10 percent went on to contract it a third time—and at least one person was infected four times. Some were reinfected in as little as three months after their first diagnosis, and for a surprising number of those reinfections, viral load actually increased. If and when reinfections with COVID-19 become the norm, the majority of people will weather the virus as they would any other cold. You get it, and after a certain period of time your body forgets it, leaving you vulnerable to its return. The key difference is that seasonal cold-causing viruses rarely cause lethal disease, while COVID-19 does at rates of 1–5 percent, depending on the health status of those it affects. Why reinfection occurs so consistently across the coronavirus family, we don’t know. But what has become increasingly clear is that the defenses we mount against the virus during and after primary infection seem to fade relatively quickly—a disappearing act that doesn’t bode well for our prospects of achieving so-called herd immunity over a longer period of time. I’ve written before that, as a strategy, counting on herd immunity is reckless and ineffective. Immunity, we must remember, isn’t a switch the body can flip on and off at will. It consists of a complex series of reactions and interactions that are difficult to observe and detangle. One set of mechanisms is innate and at work constantly, irrespective of the threat at hand. Another is adaptive, chemically generated at the moment of encounter to attack a specific intruder in specific ways.
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A potential explanation of reinfection is that human coronaviruses are adept at tampering with our adaptive immunity, ensuring our long-term response to the virus isn’t as powerful or enduring as it is for many other viruses. Two defenses in particular, killer T cells and B cells (antibody-producing plasma cells), are responsible for sustaining this momentum. When viral infection occurs, a type of antibody called IgM appears within one to two weeks. IgM antibodies mobilize against the virus, then begin to disappear in the months that follow. Two to three weeks after an infection has cleared, IgG antibodies appear. It is the case for many viruses, including those that cause most childhood diseases, that reasonably high levels of IgG antibodies persist for many years. This is not the case for human coronaviruses. The 1990 study was among the first to monitor antibody levels in addition to reinfection. Although increases were detected within the three weeks following primary infection, within three months they declined sharply. Longer-term studies of recovered SARS and MERS patients also saw the antibody responses dwindled over a two- to three-year period. Thanks to months of intensive research, we now have a relatively clear picture of the antibody response triggered specifically by SARS-CoV-2. Those who are asymptomatic produce low— sometimes even undetectable—levels of antibodies, even when the virus has been cleared. For the most part, studies show that concentrations of these antibodies diminish rapidly, suggesting that asymptomatic individuals may be the most susceptible to reinfection. Those who fall ill, and particularly those who fall seriously ill, produce greater amounts of antibodies that persist for longer amounts of time—an outcome that would seem, upon first glance, to offer greater protection, too. The Kenya study on endemic human coronaviruses, however, offers evidence to the contrary that may turn out to be applicable to SARS-CoV-2. In some patients, it was found that high antibody levels actually potentiated infection rather than preventing or mitigating it—leaving open the possibility that no one, regardless of the nature of their primary infection, is totally safe from reinfection. There may also be differences from population to population. While the majority of studies have found that antibodies against SARSCoV-2 fade over time, one recent Icelandic study, published in the 353
New England Journal of Medicine early this month, found that more than 90 percent of the several thousands of people surveyed still had them four months after their initial diagnosis. Implication for Vaccines Vaccines, once injected, don’t shield the body from infection. Instead, they equip the immune system with a sophisticated alarm system—one that will trigger a vigorous and rapid response whenever the invading virus sets off the alarm. Immune memory cells, trained by the vaccine to mobilize as soon as the alarm sounds, allow the body to target and clear out the virus in a matter of days, rather than weeks. This process of short-circuiting an intruder’s life cycle is typical—and successful—for many of the vaccinations we receive as children, including measles, mumps and polio. These vaccines mimic a natural immune response, to the effect of developing long-term and in some cases lifelong immunity to reinfection. The natural immune response to coronaviruses, however, is far more complex. Since the virus does have a well-documented ability to reinfect us, we can infer with reasonable confidence that natural immunity won’t defend us against it in the long term. Based on what we know about our immunity against COVID-19 and coronaviruses at large, there are three questions that developers of COVID-19 vaccines—and those of us who will be queuing up to receive them— must contemplate if we’re to create one that is safe, effective and protective for a long duration. The first question is how long any immunity, whether natural or vaccine-mediated, will last. The second and more difficult question is whether a strong immune response can, in some, facilitate future infections, and if reinfection does occur, whether it might increase, rather than decrease, the amount of virus in the body. The third and final question concerns the mechanisms by which coronaviruses reestablish infection in a person who has already been infected once before. One possibility is that they inactivate our memory cells—the equivalent of disconnecting the alarm. This is what the measles virus does upon first infection: target and kill memory B cells specifically. For now, whether this is the case for coronaviruses is unknown.
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If SARS-CoV-2 doesn’t wipe out memory response upon reinfection, there is more or less a clear path forward for vaccine development. Over time, we may have to create new generations of vaccines because of antigenic drift, as we do with the flu. Aside from the fact that we may have to revaccinate people amid fading immunity, barring any other complications a vaccine will be able to protect us from reinfection. If SARS-CoV-2 it does tamper with our immune memory, however, we might be in trouble. There remains much we don’t know about COVID-19 specifically and human coronaviruses at large. What is clear at this moment is that reinfection and the mechanisms that drive it are a key piece of this puzzle—one we can’t leave out, and one that will bedevil our efforts for months and years to come as we struggle to put this genie back in its bottle. This article originally appeared in the Scientific American and is available online here: What COVID-19 Reinfection Means for Vaccines
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COVID-19 Vaccine Protocols Reveal That Trials Are Designed To Succeed Forbes | September 23, 2020 | Articles
Moderna, Pfizer, AstraZeneca, and Johnson & Johnson are leading candidates for the completion of a COVID-19 vaccine likely to be released in the coming months. These companies have published their vaccine trial protocols. This unusually transparent action during a major drug trial deserves praise, close inspection of the protocols raises surprising concerns. These trials seem designed to prove their vaccines work, even if the measured effects are minimal. What would a normal vaccine trial look like? Prevention of infection must be a critical endpoint. Any vaccine trial should include regular antigen testing every three days to test contagiousness to pick up early signs of infection and PCR testing once a week to confirm infection by SARS-CoV-2 test the ability of the vaccines to stave off infection. Prevention of infection is not a criterion for success for any of these vaccines. In fact, their endpoints all require confirmed infections and all those they will include in the analysis for success, the only difference being the severity of symptoms between the vaccinated and unvaccinated. Measuring differences amongst only those infected by SARS-CoV-2 underscores the implicit conclusion that the vaccines are not expected to prevent infection, only modify symptoms of those infected. We all expect an effective vaccine to prevent serious illness if infected. Three of the vaccine protocols—Moderna, Pfizer, and AstraZeneca—do not require that their vaccine prevent serious disease only that they prevent moderate symptoms which may be as mild as cough, or headache. The greatest fear people have is dying from this disease. A vaccine must significantly or entirely reduce deaths from COVID19. Over two hundred thousand people have died in the United States and nearly a million worldwide. None list mortality as a critical endpoint. 356
We recognize that the influenza vaccine does not prevent infection with that virus, but does have a measurable impact on hospitalization and death. The moderate protections from the influenza virus can potentially be replicated and improved on with COVID-19, but only with extensive trials that ensure the efficacy of a future vaccine. Vaccine efficacy is typically proved by large clinical trials over several years. The pharmaceutical companies intend to do trials ranging from thirty thousand to sixty thousand participants. This scale of study would be sufficient for testing vaccine efficacy. The first surprise found upon a closer reading of the protocols reveals that each study intends to complete interim and primary analyses that at most include 164 participants. These companies likely intend to apply for an emergency use authorization (EUA) from the Food and Drug Administration (FDA) with just their limited preliminary results. Interim analysis success requires a seventy percent efficacy. For Moderna, the interim analysis includes giving the vaccine to only 53 people. Their success margin is for 13 or less of those 53 to develop symptoms compared to 40 or more in their control group. For Johnson & Johnson, their interim analysis includes 77 vaccine recipients, with a success margin of 18 or less developing symptoms compared to 59 in the control group. For AstraZeneca, their interim analysis includes 50 vaccine recipients, with a success margin of 12 or less developing symptoms compared to 19 in the 25 person control group. Pfizer is even smaller in its success requirements. Their initial group includes 32 vaccine recipients, with a success margin of 7 or less developing symptoms compared to 25 in the control group. The primary analyses are a bit more expanded, but need to be less efficacious for success: about sixty percent. AstraZeneca, Moderna, Johnson & Johnson, and Pfizer have primary analyses that distribute the vaccine to only 100, 151, 154, and 164 participants respectively. These companies state that they do not “intend” to stop trials after the primary analyses, but there is every chance that they intend to pursue an EUA and focus on manufacturing the vaccine rather than further thorough testing. The second surprise from these protocols is how mild the requirements for contracted COVID-19 symptoms are. A careful 357
reading reveals that the minimum qualification for a case of COVID19 is a positive PCR test and one or two mild symptoms. These include headache, fever, cough, or mild nausea. This is far from adequate. These vaccine trials are testing to prevent common cold symptoms. These trials certainly do not give assurance that the vaccine will protect from the serious consequences of COVID-19. Johnson & Johnson is the only trial that requires the inclusion of severe COVID-19 cases, at least 5 for the 75 participant interim analysis. One of the more immediate questions a trial needs to answer is whether a vaccine prevents infection. If someone takes this vaccine, are they far less likely to become infected with the virus? These trials all clearly focus on eliminating symptoms of COVID-19, and not infections themselves. Asymptomatic infection is listed as a secondary objective in these trials when they should be of critical importance. It appears that all the pharmaceutical companies assume that the vaccine will never prevent infection. Their criteria for approval is the difference in symptoms between an infected control group and an infected vaccine group. They do not measure the difference between infection and noninfection as a primary motivation. A greater concern for the millions of older people and those with preexisting conditions is whether these trials test the vaccine's ability to prevent severe illness and death. Again we find that severe illness and death are only secondary objectives in these trials. None list the prevention of death and hospitalization as a critically important barrier. If total infections, hospitalizations, and death are going to be ignored in the preliminary trials of the vaccines, then there must be phase four testing to monitor their safety and efficacy. This would be long term massive scale monitoring of the vaccine. There must be an indication that the authorized vaccines are reducing infection, hospitalization, and death, or else they will not be able to stop this pandemic. These protocols do not emphasize the most important ramifications of COVID-19 that people are most interested in preventing: overall infection, hospitalization, and death. It boggles the mind and defies common sense that the National Institute of Health, the Center for Disease Control, the National Institute of Allergy and Infectious Disease, and the rest would consider the 358
approval of a vaccine that would be distributed to hundreds of millions on such slender threads of success. It appears that these trials are intended to pass the lowest possible barrier of success. As this is being written, the FDA is poised to announce tougher standards for a COVID-19 vaccine in the near future. It is my hope that these new standards for an EUA will at a minimum include requirements for protections from infection itself, protections from severe virus-related disease leading to hospitalization, and a significant improvement in COVID-19 related mortality. It is clear from these studies that the vaccines currently under trial will not be the silver bullet needed to end the pandemic. We must do all we can public health measures to control COVID-19 as China and other Asian countries have successfully done. This article originally appeared in the Forbes and is available online here:COVID-19 Vaccine Protocols Reveal That Trials Are Designed To Succeed
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To Contain COVID-19, Combine Mass Testing With Social And Economic Assistance Forbes | September 30, 2020 | Article
Several experts, myself included, have argued that cheap, widespread rapid testing is critical to containing the COVID-19 pandemic in the United States. An article published in Wired Magazine on Monday, while not disavowing the importance of diagnostics, did claim that a strategy too dependent on them cannot accommodate the “messiness of real life”—which is to say, the messiness of human behavior. In this respect, the author of the article is absolutely correct. All the rapid tests in the world, even if distributed plentifully amongst American households, won’t make the difference if we don’t act on their results. Some of us, the author also rightly points out, have neither the means nor the flexibility to drop everything and quarantine for 14 days straight. That is why, in addition to home tests, I make a case for assisted home isolation—a cushion of economic and social supports that will make the decision to stay home that much easier. If manufactured and deployed en masse, low-cost home tests would serve one primary function: to identify infections at their most contagious. Although it hasn’t been definitively proven that the peak of contagiousness coincides with that of viral load—the amount of active virus present in the body—enough evidence has accumulated behind this hypothesis for it to be actionable. Studies pinpoint this moment, when billions upon billions of viral particles are swarming and escaping our airways, as occurring early on in the disease course, when symptoms haven’t yet or have only just begun to appear. For no small number of us, they never will. Either way, no matter how many precautions we take, we risk spreading the virus to others. The problem, given that our current testing regime reaches few beyond the worried and already ill, is that many of those who contract the virus will be least aware of their own infectivity 360
precisely when it matters most. During this critical time window, rapid tests can not only pick up on infection quickly—in as little as 15 minutes—but reliably as well, with some manufacturers claiming upwards of 95 percent accuracy. As the amount of virus declines, so does the ability of a rapid test to detect it. There is only so much utility, however, in confirming infection when contagion is no longer a possibility, as the industry standard PCR tests do. While the Prevention Policy Modeling Lab at the Harvard T.H. Chan School of Public Health estimates that 41 million people in the United States have had COVID-19, the number of cases confirmed via PCR testing is only 7.4 million. Widespread rapid testing would allow us to intercept infections as they occur and apportion resources accordingly. Yes, false negatives and positives are bound to crop up, and yes, faulty equipment and human error will fudge a fraction of results, but better to miss five percent of cases than over 80 percent. The goal isn’t perfection, but to mount a response closer in size and scope to what Americans actually need—and what we’re actually capable of. The same goes for my proposal of assisted home isolation. Should anyone test positive for COVID-19 and need to self-isolate, they would receive a daily cash stipend to compensate for any wages lost and, if need be, accommodation in a hotel or hospital to keep other members of their household safe. Meals and medical supplies would be provided on request, as would additional assistance from health workers. Let’s say for three months, 100,000 new households applied for assisted isolation per day. If costs for food, shelter, and wage compensation amounted to $500 per family per day, the total cost of this program would amount to about $50 billion—far less than the many trillions of dollars we’ll rack up from national debt and lost economic opportunity if we allow this crisis to persist. Like home testing, this plan is ambitious, yet also the bare minimum of what should be done given the exceptional circumstances at hand. In a country of 350 million people, no nationwide public health intervention will ever go exactly according to plan. To account for those who cannot or will not report test results from home, we must shore up the diagnostic capabilities of our schools and workplaces as well. But one of the reasons why the individual behaviors and actions of Americans in response to the pandemic have varied so widely is because there has been next to no plan at all. We need to move 361
forward with a program as expansive as home testing and assisted home isolation, and we need to do it fast. It may be messy, but it will be worth it. This article originally appeared in the Forbes and is available online here: To Contain COVID-19, Combine Mass Testing With Social And Economic Assistance
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October 2020
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Eroding Faith In Public Health Leaders Think Global Health | October 1, 2020 | Article
I have spent my life in science, admiring and working alongside the doctors, researchers, and scientists who lead the United States’ most respected public health institutions—the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the Food and Drug Administration (FDA). Watching these celebrated individuals and institutions crumple and bow to political pressure and seeing their lives’ work and their reputations warped by Operation Warp Speed is one of the most distressing experiences of my life. The clinical trial protocols released by Moderna, Pfizer, AstraZeneca, and Johnson & Johnson suggest U.S. public health leaders are once again bending over backward to accommodate political considerations. The clinical trials, designed and approved by the NIH, are far removed from what most experts would consider rigorous testing. They are not designed to assess whether the vaccines will prevent infection, nor are they designed to prove that the drugs will save lives. They are not even chiefly focused on whether the vaccines will improve severe cases of the disease—the kinds of cases that have killed over a million people worldwide. Instead, the trials are designed to rapidly approve treatments based on whether they improve mild cases of COVID-19, which often resolve on their own without any medical intervention. This trial process is not a true test; it is equivalent to a rubber stamp of approval by the NIH regardless of a vaccine’s ability to affect the course of the pandemic. The relentless focus on a quick fix is inflicting serious damage on public health institutions and undermining public confidence in health-care leaders at a time when they are needed most. A recent Kaiser Family Foundation poll found that public trust in the CDC and the leaders of other public health institutions has dropped 10 percent since April of this year. And two-thirds of Americans worry 364
that political pressure from the Donald J. Trump administration will lead to approval of a vaccine that is not yet proven safe or effective— I do not blame those who feel this way. At the outset of the pandemic, the nation’s testing failures and supply shortages were a stark reminder that U.S. public health institutions were not prepared for an outbreak that many had predicted, in one form or another. Although some were quick to lay blame at the feet of the Trump administration, it soon became apparent that the chaos and dysfunction bled well beyond the White House walls. In late March, the FDA—the agency responsible for protecting Americans from unsafe and ineffective drugs—granted an emergency use authorization (EUA) for hydroxychloroquine as a treatment for COVID-19, despite a lack of proof that hydroxychloroquine was effective and knowing that the drug could be dangerous for some patients. Six weeks later, the FDA buckled under mounting evidence that the drug did not work and revoked the EUA. But the agency did not learn its lesson. It soon granted another emergency authorization for remdesivir, an investigational antiviral treatment—a move based on preliminary results from a clinical trial run by the NIH. The NIH claimed in a press release that the drug helped patients recover more quickly but refused to release the data for doctors to review for themselves. Three weeks later, the NIH published the full findings, which showed the treatment was not as it appeared—although the drug could have successfully reduced the time to release from hospital for people with milder cases of COVID-19, it was never clear whether the drug spared anyone from the long-term consequences of the disease. Moreover, the treatment was proven to have no effect on mortality. Still, the government claimed success, and Gilead, the manufacturer of remdesivir, reaped the rewards, selling their five-day course of treatment—which can only be administered in hospitals intravenously—to governments and insurers for thousands of dollars per patient. The FDA’s rollout of its most recent EUA for convalescent plasma—accompanied by misleading data about the benefits of the treatment—makes clear just how drastically America’s public health agencies have been manipulated for political purposes. With the NIH fast-tracking a vaccine toward approval on a timeline that seems more aligned with political convenience rather than public health, 365
the fear that a dangerous drug could be widely distributed is more immediate than ever. Let me be perfectly clear: Any suggestion of a vaccine or quickfix treatment by the end of this year is magical thinking, and magical thinking will not end the nation’s suffering. The way to end this pandemic quickly is through the forceful implementation of sound public health principles—principles that public health agencies should have been vigorously enforcing from the start. Two simple ideas could bring the pandemic to an end within three months: home testing and home isolation. Frequent, universal home testing using a saliva-based rapid test—akin to a home pregnancy test—would quickly identify who is infected and who is at risk. Home isolation could be implemented in a way that is recognizes the importance Americans place on , with financial support to make up for lost wages and cover medical supplies and other necessities given to families who test positive. The cost for this effort, which is estimated at $100 billion, is far less than the trillions being lost in joblessness, business closures, and health-care expenses today. It is not too late for public health leaders to reverse course and focus on the approaches that will save the most lives today. The leaders of America’s most valued public health agencies have a responsibility to stand up in the face of political pressure and bear down against those who would force them to follow a scientifically unsound path. This article originally appeared in Think Global Health and is available online here: Eroding Faith In Public Health Leaders
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The Encounter Was Inevitable. Trump Meets The Coronavirus. Forbes | October 1, 2020 | Article
President Trump is the most recent in a long line of country leaders to fall victim to infection by SARS-Cov-2. The most notable include the UK Prime Minister Boris Johnson who came with an angel's breath of dying in an intensive care ward, Brazil's President Jair Bolosonaro, Belarus strongman Alexander Lukashenko and a scattering of others around the world. Notably absent from this tally are President Xi Jiping of China and President Vladamir Putin of Russia. Both are infection-free and likely to remain so for very different reasons. President Xi and other Chinese high officials are unlikely to be infected as long as they remain China. Unique among the great nations China has virtually eliminated the virus its borders. Sporadic outbreaks involving no more than ten to twenty people still occur, mostly due to repatriated citizens. These outbreaks are quickly contained using the same methods used to halt the original epidemic. The Chinese leaders and the entire population of 1.4 billion people now live without fear of infection. China's example shows that humanity can defeat the virus by public health measures alone, without the benefit of effective vaccines or drugs. China has no magic bullet that other countries lack. The infections raging throughout most of the rest of the world are a consequence of failed policies, government inaction, and resistance of the populations to effective pandemic control measures. The world's collective blindness to China's accomplishments in eliminating COVID is close to incomprehensible. The reasons Vladimir Putin faces no danger from infection are radically different. Putin presides over a country with a raging infection much like that of President Trump. According to Russian sources, the pandemic in Russia reached an early peak in mid-May, decreased modestly over the summer, and is once again rampant, despite the "approval" of an anti-COVID vaccine in early August. 367
According to the best reporting available Putin remains in the world's most secluded bubble. He conducts all his business virtually, remaining isolated in a private Dacha outside of Moscow. He meets very few people personally and then only after that person has been in single isolation for fourteen days and has tested negative for infection. Putin's own protective measures belie his public statements that the average Russian citizen faces no danger from the coronavirus. Trump's America continues to lead the world in COVID-19 cases and deaths. To date, more than 7.3 million Americans have been infected and more than 206,000 have died. Daily COVID-19 cases reached an early peak of between twenty-five to 30,000 per day in April and never decreased much below twenty thousand per day in the late spring and early summer, only to rise sharply to a high of 75,000 in mid-August. After a modest decrease to about 45,000 thousand a day COVID-19infections are once again on the rise in the United States. Yesterday more than 53,000 Americans were reported as infected. COVID related deaths hover bout 1,000 per day and are on the rise once again. The pandemic in the United Staes is widespread. Despite the President's claims that the blue states fare worse than the red, the highest rates of daily infection, as measured in cases per 100,000, are in the Dakotas, 53 in North Dakota, 49 in South Dakota, and in Wisconsin (44), where Trump was planning a large rally, and Montana (31). For comparison, the average number of new cases per day in the United States is 13. Deaths per 100,000 closely mirror infection rates being highest in North and South Dakota and Wisconsin. The death rate along with the infection rate is increasing across the country. All of the above numbers are official and may substantially underrepresent the actual toll. How then could President Trump and his entourage avoid infection? Only by closely observing the protective measures recommended by his own administration, the Centers for Disease Control, the Department of Health and Human Services, and the President's own COVID Task Force. Despite these recommendations, the President and almost all others in the administration close to him refused to follow the recommended guidelines, including the obligatory wearing of masks, maintaining six feet distance for all others, limiting indoor gatherings to a few 368
people for short periods with attending all wearing masks, limiting the size of outdoor gatherings and insisting on masks and social distancing even outdoors. All these precautions were not observed and in fact, publicly defied. The President himself and members of his close circle mocked those who followed the recommended precautions including the protective actions of his rival for the Presidency. How could he and his team not have been infected while traveling thought the country, especially to those areas of the country with the highest know rates of infection? What has happened to Trump, his infection and illness were an obvious consequence of his own actions. As he is our President and a fellow human we must all hope for a speedy recovery. But we cannot offer such hope to the more than two hundred thousand Americans who have died and the hundreds of thousands more who may die before Trump's American pandemic draws to close. The tragedy is not in his infection but in his failure to act on what he knew the disease to be early on, that COVID-19 is a highly contagious airborne infection with lethal potential. Trump's life may be spared by heroic medical intervention, as was Boris Johnson's, but all of his fellow citizens must continue to live in fear. We must all face the personal and economic consequences of a pandemic that need not have happened. For decades and perhaps centuries people will ask if the Chinese with a vast population densely packed into megacities far larger than those of the United States could control the pandemic a drive it close to zero within a few months losing fewer than 5,000 lives, what went wrong in America? We as a people must now struggle to answer that question and act swiftly to bring COVID to a close using the tools that have been shown to work. If the President survives his inevitable meeting with a destiny of his own making, this must be his task and we must do all we can to help. If he does not the job is up to us. This article originally appeared in Forbes and is available online here: The Encounter Was Inevitable. Trump Meets The Coronavirus.
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Herd Immunity Will Not Defeat COVID-19 Project Syndicate | October 2, 2020 | Article
During a September 15 ABC News “town hall”-style event, US President Donald Trump told host George Stephanopoulos that without a vaccine, COVID-19 would still “go away.” Over time, Trump said, “You’ll develop herd – like a herd mentality. It’s going to be – it’s going to be herd-developed, and that’s going to happen.” What Trump was referring to, and misnamed, is herd immunity, which a population develops when so many of its members are infected by or vaccinated against a given contagion that a bulwark of resistance counters the contagion’s spread. But to base a pandemic-response strategy on the assumption that herd immunity is inevitable – vaccine or no vaccine – is to afford a virus a path of least resistance. That was the case in Sweden, where policymakers decided to forego lockdowns and business closures in favor of more lenient advisories on mask-wearing and social distancing. Unsurprisingly, Sweden’s subsequent COVID-19 infection and fatality rates were among the world’s highest. Moreover, the Swedish economy contracted by 8.6% in the second quarter of 2020 compared to the previous three months – an important outcome to note given the emphasis that many proponents of herd immunity place on reviving economic growth. One such supporter is Scott Atlas, a recently appointed pandemic adviser to Trump who has advocated for the so-called Swedish model on Fox News. “We like the fact that there’s a lot of cases,” Atlas said in one interview. “That’s exactly how we’re going to get herd immunity, population immunity.” Although Atlas has no epidemiological credentials or experience, he does seem to have the ear of the president – as evidenced by the latter’s remarks on “herd mentality.” On August 31, Trump made similarly pointed – yet evasive – comments to Fox News’s Laura Ingraham. “Once you get to a certain number, we use the word herd, right?” he said. “Once you get to a certain number, it’s going to go away.” 370
There’s just one problem: When it comes to coronaviruses, that “certain number” doesn’t exist. Research in recent decades has established time and time again that certain cold-causing coronaviruses can infect a person more than once – and even as many as three or four times, according to a six-year study conducted in Kenya. With SARS-CoV and MERS-CoV, the culprits of the last two lethal coronavirus epidemics, long-term research was too sparse and underfunded to verify their capacity for reinfection. But two scientific case studies – one on a patient in Hong Kong, and another (still undergoing peer review) on a patient in Nevada – have already confirmed that the SARS-CoV-2 virus that causes COVID-19 can reinfect an individual. These studies show that our immunity to coronaviruses is alarmingly short-lived and quick to fade – a disappearing act that makes building protection to SARS-CoV-2 difficult enough for an individual, much less an entire population. The day after Trump’s ABC News town hall, MSNBC’s Rachel Maddow ran the numbers on how herd immunity would play out in the United States, which has a population of roughly 330 million. If reaching herd immunity requires a minimum of 65% of people to be infected, as the World Health Organization’s chief scientist, Soumya Swaminathan, has said, that would mean 215 million cases of COVID-19 countrywide. If the US fatality rate remained what it is now – close to 3% – it would also mean 6,385,500 deaths. I have previously called herd immunity a “reckless and ineffective strategy.” Now that COVID-19 reinfections are not just a possibility, but a reality, I would add “lethal” to my description. “The White House is no longer even recommending that states do things to stop the spread of this virus – things that just weeks ago they were telling the states they needed to do,” Maddow said. “When it’s not just what [Trump] is saying, but what he’s doing, we have to recognize this as a huge deal.” Sign up for our weekly newsletter, PS on Sunday White House Press Secretary Kayleigh McEnany and Atlas himself have both categorically denied that the Trump administration has adopted herd immunity as a strategy. But the words and actions of their boss, who continued to eschew and mock 371
preventive measures as basic as wearing a face mask – and who tested positive for COVID-19 this week – tell a different story. Whether you call it herd immunity or “herd mentality,” the science remains the same. With coronaviruses, such an approach is not and never should be an option. This article originally appeared in Project Syndicate and is available online here: Herd Immunity Will Not Defeat COVID-19
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All The President’s Medicine Forbes | October 4, 2020 | Article
No one receives worse medicine, an old saying goes, than the poor and the powerful. The poor because they face so many barriers to medical care and supports, and the powerful because they face no barriers at all. The latest updates on President Trump’s COVID-19 treatment suggest he is very much of the latter ilk. The day after his positive diagnosis, he received two experimental therapies, the antiviral drug remdesivir and Regeneron’s anti-SARs-CoV-2 monoclonal antibodies, in combination with vitamin D, famotidine (pepcid), zinc, and melatonin. It was announced Sunday afternoon that dexamethasone, a steroid, was thrown into the mix on Saturday. Neither hydroxychloroquine nor convalescent sera, the two treatments touted by Trump so ardently and for so long, were included. This cocktail is not just highly unusual. The president is likely the first human being on the face of the earth to receive the triple whammy of remdesivir, monoclonal antibody drugs, and dexamethasone almost all at once. While the pronouncements of White House physician Sean Conley and his medical team would lead us to believe that the combination is a matter of necessity and sound clinical judgment, we cannot forget that this is no ordinary doctor-patient relationship. Trump is Conley’s ultimate superior, not to mention commander-in-chief to the doctors attending to him at Walter Reed National Military Medical Center. Reports from White House physician Sean Conley on Trump’s condition have been heavy on reassurances but light on clinical details, making it difficult to determine whether these therapies are intended to improve worsening symptoms or placate a panicked president. We may never know the true motivation, but we can at least use science to predict the outcome. Let’s begin with REGN-COV2, the monoclonal antibody drug developed by Regeneron Pharmaceuticals. Monoclonal antibody 373
drugs are engineered using a single cell that produces a single, highly neutralizing antibody, one that is replicated over and over again at a large scale. Hundreds of groups around the world, some of which I know well, are currently developing such antibodies against the SARS-CoV-2 spike protein, one of the key mechanisms the virus uses to replicate itself. The Regneron drug is what you might call an antibody cocktail—two neutralizing antibodies paired up to reduce the potential for immune escape. Trump was able to receive an 8-gram infusion of Regeneron’s monoclonal antibodies on Friday due to the FDA’s compassionate use program, which permits case-by-case use of as yet unapproved experimental therapies. The only data we have on the safety and efficacy of REGN-COV2 was released not even a week ago—in a company press release, rather than a peer-reviewed journal. While researchers conducting clinical trials for the drug claim it helped reduce viral load in COVID-19 patients with mild symptoms, it also appeared to have no effect on patients who had already developed anti-SARS-CoV-2 antibodies. Moreover, the study was unable to show any effect on prevention of serious disease or death. Two patients experienced adverse side effects, though the reasons why weren’t disclosed. The other experimental drug on the docket is remdesivir, an antiviral drug that has undergone more extensive evaluation than REGN-COV2. Though authorized in May by the FDA for emergency use, in clinical trials and patient population studies remdesivir has yielded only modest and rather disappointing results. The lack of notable therapeutic effects may be attributed to the fact that viral load peaks sooner rather than later in the progression of this disease, spiking shortly after symptom onset and dwindling within days. Antivirals can only provide so much relief when any active virus is already on the ebb—at that point, the damage is done and any treatment must palliate ensuing complications, rather than target the virus itself. Trump’s treatment course for remdesivir will take a total of five days and require several hospital-based infusions. Before today, there was still a decent possibility that Trump’s first infusion, also given on Friday, may have been administered just in time to help alleviate his symptoms. It has been speculated that Trump contracted the virus the day of or shortly after September 26, when an outdoor ceremony 374
celebrating his Supreme Court nominee, Judge Amy Coney Barrett, was held in the White House Garden. Seven attendees, the president included, have since tested positive for COVID-19. But now that Trump’s doctors have confirmed, a day after the fact, that he has in addition to REGN-COV2 and remdesivir received a dosage of dexamethasone, the alternative suddenly seems more likely: that the initial therapies failed to turn the tide on his illness and consequently desperate measures might be in order. Since steroids can harm, not help, the body’s innate immune response to COVID-19 if taken prematurely, they’re typically reserved for those in critical condition, deployed as a last resort to help mitigate the hyperinflammation seen in severe cases of the disease. According to a large study of the drug published in July, dexamethasone had the biggest and most beneficial impact on patients who had been critically ill and hospitalized for over a week. Given that Trump checked into Walter Reed just three days ago, the outlook—at least from the outside looking in—doesn’t seem particularly promising. If Trump is experiencing hyperinflammatory symptoms, he may be at risk for hypercoagulation, too, which in some COVID-19 patients causes heart attacks, lung emboli, and strokes major and minor. Prescribing anticoagulants (also known as blood thinners) to prevent clotting might help, but that would mean adding yet another medication to an already sizable list. Not for nothing must we note that large doses of dexamethasone can have potent, destabilizing effects on mood, temper, and reasoning, akin to mania. It is not advisable to entrust individuals being treated with the drug with making difficult judgment calls in a timely fashion, especially when they’re the leader of the United States. We may never know if the peculiar combination of remdesivir, REGN-COV2, and dexamethsome is what the doctor ordered or what Trump demanded. Either way, it will sadly fall to the American people to deal with what could be disastrous consequences. This article originally appeared in Forbes and is available online here: All The President’s Medicine
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The Difference Between COVID-19 And HIV/AIDS Forbes | October 5, 2020 | Article
For the October issue of Scientific American, I penned a piece on what we can learn from the parallels that exist between the coronavirus and HIV crises.* To this essay, called “Lessons from AIDS for the COVID-19 Pandemic,” I would add one more thought. A critical difference between AIDS and COVID-19 is that COVID-19 can be controlled by public health means. That continues to be much more difficult for HIV/AIDS. It is case identification, contact tracing and quarantine that has put the COVID-19 genie back in the bottle in China and several other East Asian countries. Except for sporadic outbreaks, quickly contained, China today is free from COVID-19 — back to work and back to school. It has never been possible to contain HIV/AIDS in any country at this remarkable level of effectiveness despite more than 35 years of strenuous public health measures and intense biomedical research. Strategies are different for containing COVID-19 and AIDS because their means of transmission and patterns of infection are different. HIV/AIDS primarily is transmitted sexually, secondarily by needle sharing. Public health approaches to modifying sexual practices, such as limiting the number of partners or promoting condom use, can be partially effective over time but have never been sufficient to tame the AIDS pandemic. Moreover, HIV infection is for life. Those infected are potentially contagious to others for a decade or more. COVID-19 on the other hand is airborne. Wearing masks, social distancing and short term isolation are sufficient to prevent infection. The SARS-CoV-2 virus quickly peaks within a few days of infection, then rapidly fades. Most people are contagious to others for no more than a week to ten days. These public health measures prevent transmission: testing to identify those infected, contact
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tracing to identify those exposed, then stringent isolation of those infected for a short period. Countries can and have controlled COVID-19 in the absence of a vaccine or effective drugs using public health measures alone, something not yet accomplished for HIV/AIDS. Would that this lesson be taken to heart by the regions of the world in which COVID-19 still roams almost freely. Many of those countries have been burdened by faulty governance in combating the pandemic, not by failures of public health techniques. I believe my proposal in a recent CNN op-ed, COVID-19 Control American Style, to use new technologies and public health measures in the absence of effective drugs and vaccines can bring the pandemic under control in a few short months. This article originally appeared in Forbes and is available online here: The Difference Between COVID-19 And HIV/AIDS
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COVID-19 Traumatic Stress Disorder: A Definition Of A New Disease: CVTSD. Psychology Today | October 6, 2020 | Article
Many of us are familiar with the once uncommon term PTSD— post-traumatic stress disorder—a mental health condition that develops after a person has experienced a traumatic, life-threatening event. People mostly associate PTSD with military personnel, as certain traumas such as combat and sexual assault make people more likely to develop the disorder. But the condition can actually affect anyone and its symptoms —depression, anxiety, domestic abuse, drug misuse, and suicide—can linger for years. Few have associated PTSD with COVID-19, but there is good evidence to suggest that COVID-19 can also be a cause of traumatic stress disorder. In this case, the symptoms would apply to individuals as well as to society as a whole. The way we look at this is not by focusing on the data for individual patients, but for societal trends. Depression is one of the most prevalent mental disorders in the U.S. During late June of this year, 31 percent of adults reported suffering from anxiety and depression symptoms. A recent study published on JAMA Network explores the factors that led to an increase in the prevalence of depression symptoms more than threefold since the beginning of the pandemic. A person’s likelihood of developing symptoms of depression depends on other stressors, such as job loss, death of loved ones, or increased financial responsibility; which are all direct consequences of COVID-19. There are, however, other factors that influence a person’s mental well-being. Humans are naturally social beings: they thrive on building relationships with one another. This is no longer as easy as it once was with the social distancing measures that are currently in place in many locations. These effects can be felt amongst all age groups; from kids not being able to make friends, young adults not being able to meet a partner, workplace relationships not being formed due to working from home, to not being able to see certain 378
family members. This puts a strain on people’s everyday lives, making them more likely to suffer from severe stress or anxiety. Hyperarousal, a very common symptom of PTSD, can lead to angry outbursts and can make the person abusive. Many have been feeling on edge ever since the pandemic began due to drastic changes in their lives. This can lead to them feeling anxious all the time or unable to relax, which can lead to angry outbursts. Living with someone who has abusive tendencies can also be traumatic. When lockdowns were announced in the U.S., an increase in demand for services of domestic-violence hotlines was expected. Yet some regions experienced a 50 percent drop in the number of calls. Victims could simply not connect to services safely, as their abusers were always home. The same applies to child abuse. When schools were still open, teachers and childcare providers could get a sense of what the child’s life was like at home but now, very few of the usual mandated reporters have enough opportunities to recognize signs of abuse. PTSD also comes with self-harming tendencies, such as drug abuse. A study conducted in Kentucky shows that the number of nonfatal opioid overdoses went up from 102 between March and June 2019 to 227 during the same timeline in 2020. Quarantine measures, unemployment, and economic recession, in addition to a pandemic, all affect drug use patterns. Past economic crises in the U.S. have been associated with an increase in cannabis and illicit drug consumption among adolescents. People who are struggling with addiction rely on social interactions even more. The economic and social stressors COVID-19 has created contribute to feelings of loneliness, which can cause people in recovery to relapse. Students and young adults are most at risk when it comes to developing an addiction, as they often live alone and need to form social bonds in order to move forward in both their private and professional lives. Uncertainty of the future is stressful under normal circumstances, and COVID-19 is making it worse. Another self-harming tendency which can be caused by PTSD is suicide. One person dies of suicide every 40 seconds. In the earlier stages of the pandemic, there was a surge in suicide rates among medical staff in New York, who could not take the pressure COVID-19 was putting on them. While it is too early to make a statement about overall COVID-related suicide trends, we can be 379
certain that the current health crisis will be followed by an economic recession which may very well cause rates to rise. What we do know is that suicidal thoughts are related to feelings of isolation—which the pandemic is aggravating. Another term that is also used in the military is moral trauma. A moral injury occurs when someone transgresses their moral conscience and values. In the military, this could be killing another person. For U.S. citizens and many others, it may be triggered by seeing our governments fail us. The U.S. government has mishandled the crisis from beginning to end, which can cause moral trauma as people watch the economic, social, and health-related damage the government has inflicted upon the nation. We likely could have avoided so much disruption had the government seen the virus for what it is. As U.S. citizens, many of us were taught to trust and believe in our leaders. Now, many feel as if we're watching them let us down over and over again, and sometimes even on purpose. We see the anti-mask movement and feel so powerless as we watch people enter stores in groups, claiming that they cannot breathe with a mask. The most basic of precautionary measures are not being respected, which is dividing the U.S. during a time when we should protect one another. COVID-19 has affected so many stressors that its effects will be felt long after we have diminished the virus itself. This composite data proves that symptoms often affecting military personnel are affecting us as a whole. Military personnel suffer psychologically after battle, and our society will suffer for many years because of COVID19. To highlight the severity of its effects, we should capture the latter under one name: COVID-19-related Traumatic Stress Disorder (CVTSD). This article originally appeared in Project Syndicate and is available online here: COVID-19 Traumatic Stress Disorder: A definition Of A New Disease: CVTSD.
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This Is Trump’s Last, Best Chance To Tell The Truth About The Virus Daily Beast | October 6, 2020 | Article
After months of downplaying the danger of COVID-19, President Trump and the First Lady tested positive and on Friday night the president was taken to the Walter Reed Medical Center “for the next few days” as “a precautionary measure.” On Saturday, a series of confusing and conflicting updates, on and off the record, about the president’s condition landed on top of the confusion spread by the president about the virus. He’s not the first national leader to be stricken with the virus and, when he recovers, the question may be which example he follows: that of Brazilian President Jair Bolsonaro or British Prime Minister Boris Johnson. Bolsonaro, who like Trump had been dismissive of the virus’ impact, was confirmed to have COVID-19 in July, made a relatively speedy recovery, and afterwards continued to dismiss the threat of the pandemic. Deaths from COVID-19 in Brazil, at nearly 150,000, are second in the world only to the United States. When Johnson, who’d also initially taken a lax approach to the threat, contracted the virus in March, he ended up in the intensive care unit and spent a solid month out of the limelight. Surveys show that government approval, rather than surging after his recovery, began a steady decline. Although British national leadership hasn’t gone to the lengths needed to contain further spread and Britain continues to lead the European continent in case numbers, Johnson’s rhetoric around the virus and public attitudes at large became much more cautious after his own experience with it. There is a chance that Trump could take that course and start taking the pandemic seriously, and commit to implementing public health measures we know will drive down infections. But if Trump recovers, like many patients, develops only mild symptoms (about 60 percent of people who catch COVID-19 go on to develop symptoms, but only around 20 percent are at risk of severe disease) 381
and recovers smoothly, his brush with COVID could easily bolster his denialism and become more grist for the mill—political fodder to restore voter confidence and support in the runup to election night. If he talks down the virus, and then loses office, many of his staunchest supporters would likely be that much less willing to heed the advice of scientists and doctors during a Biden administration. From the very beginning, Trump has denied the severity of this disease. His ignorance of the science and mockery of preventive safety measures has arguably left millions of Americans unnecessarily vulnerable to infection. Instead of enacting a robust testing regime and programs for social and economic assistance, Trump spread harmful misinformation about treatments and discouraged protections as basic as mask-wearing. Rather than holding himself and his government accountable, he has blamed his political opponents at every turn. This is his last best chance to change that dynamic. If Trump instead maintains this stance even after endangering himself, his family, and his inner circle, the ramifications would be deadly. In a best-case scenario, where mask-wearing is enforced universally across the country, the Institute for Health Metrics and Evaluation estimates we could limit the number of deaths to 273,000 by the end of this year. Still too high a number, but imagine what would happen if Trump recovered and used the momentum to ease the few restrictions we do have in place. According to the same projection, as many as half a million lives could be lost. There is no telling yet which way Trump’s illness will turn nor how he might spin the outcome for political purposes. No matter the direction of his disease or his judgement, there is one thing every American should be acutely aware of with the news today: this virus knows no bounds. The President and First Lady have entire teams of people to sweep every room before they enter and screen every person they meet. The bathrooms they use are meticulously scrubbed and sanitized to ward off disease. And, unlike the majority of Americans, they have immediate and unfettered access to COVID-19 tests. Yet still, their willingness to flout basic health protocols like wearing masks and social distancing may have landed them where they are today, as vulnerable as any among us.
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Until we acknowledge our own personal responsibility to stop spreading the virus — until we each do our part by wearing masks, accepting quarantines, and declining invitations to large gatherings — we will never contain COVID-19. Here’s hoping that the president will start communicating that message to the American people. This article originally appeared in Daily Beast and is available online here: This Is Trump’s Last, Best Chance To Tell The Truth About The Virus
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White House Continues To Choose Political Gain Over Public Health Forbes | October 6, 2020 | Article
The White House has made the decision to block a new slate of guidelines for COVID-19 vaccines, halting the latest attempt by the Food and Drug Administration to introduce some measure of regulatory rigor to a race that has escalated into a desperate rush to the finish line. In addition doubling down on safety and quality control, the guidance was drafted with the intention of assuring an increasingly wary public that all vaccine candidates will be held to the same standards. But it appears that the priorities of the current administration lay elsewhere. According to Politico, it was primarily “private-sector opposition,” rather than anything of concern to the average American, that led the White House to take issue with the FDA guidance. This alone should give us pause. Of course pharmaceutical companies will oppose that which interferes with their ability to make money and push product. To curb their avarice is why regulatory agencies exist in the first place. Another underlying motivation isn't explicitly acknowledged, but easy enough to read between the lines. One of the proposed FDA guidelines, the New York Times reports, is a follow-up to latestage trials at least a few months long that would allow researchers to continue monitoring volunteers for adverse and protective effects. Extending the timeline for vaccine approval to accommodate this would push the earliest possible end date well past November 3— denying President Trump and his campaign the opportunity to exploit any so-called success for reelection purposes. Days before the White House announced their decision, CNBC published a follow-up report of their own that details the side effects experienced by some of the participants in Pfizer and Moderna’s phase III trials. One volunteer described a 12-hour blitz of “full-on 384
COVID-like symptoms.” Others agreed that the vaccine’s aftereffects, which included high fever, pounding headaches, intense chills, and exhaustion, blew over relatively quickly, but were more debilitating than expected. These reports of adverse symptoms are far from the first. In May, a 29-year-old man who volunteered for Moderna’s phase I trials shared details about the “severe reaction” he had to the highest dosage of their vaccine with STAT News. The results of that 45person study, published months later in July, revealed that he was one of four to experience “grade 3” symptoms, classified as critical but not life-threatening. A life-threatening reaction in one person is grounds enough for suspension, as was suspected to be the case for the AstraZeneca vaccine studies put on hold last month. We must remember that to date, the adults who have participated in COVID-19 vaccine trials are healthy. If they exhibit adverse symptoms, it only makes sense that those of us more vulnerable to this disease, whether due to age or underlying conditions, will have it worse. About 15 percent of the older adults who volunteered for a Moderna phase I trial developed symptoms so severe as to require hospitalization. Granted, they received a higher dose than we would in a physician’s office, but what occurs at high doses for a few people is bound to occur at low doses for many people. The “many” in this case is millions—including children, another population we can’t discount. Distributing a vaccine nationwide without evaluating and validating its safety beyond a shadow of a doubt isn't a risk that any leadership invested in the wellbeing of its people should be willing to take. Ultimately, it will fall to an advisory committee to determine whether a COVID-19 vaccine might receive emergency use authorization (EUA) before Election Day. But if the EUA issued in August for convalescent plasma, a suspect and scientifically unsubstantiated treatment, is anything to go by, we cannot expect their decision to be impervious to political pressure. This article originally appeared in Forbes and is available online here: White House Continues To Choose Political Gain Over Public Health
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Federal Health Agencies Push Back Against Political Interference Forbes | October 8, 2020 | Article
Less than a month before the election and one week into President Trump’s own disease course, the White House is experiencing pushback from its foremost federal health agencies. On Tuesday, the Food and Drug Administration (FDA) released stricter guidelines for authorizing COVID-19 vaccines, despite the best efforts of the current administration to block them. The decision came shortly after the Centers for Disease Control and Prevention (CDC) revised its own safety guidelines to reaffirm the possibility of airborne transmission, resolving what has been a matter of contention for months. Both reversals are welcome developments for those of us who fear the White House has overstepped one too many boundaries to advance its own electoral agenda. Between slackening the criteria for emergency use authorizations and trumpeting promises of vaccines by Election Day, the potential for political interference to overdetermine a decision as consequential as approving a vaccine is alarming, to say the least. Why President Trump and his campaign would prefer more leniency in the criteria for vaccine approval isn’t difficult to see. One of the requirements included in the new FDA guidelines is a followup period to late-stage clinical trials that allows vaccine developers to continue monitoring volunteers for adverse side effects for at least two months—an addendum that all but prevents any of the current candidates from receiving clearance before November 3. As much as we all want a vaccine to arrive as soon as humanly possible, the stakes are simply too high for safety not to come first. Another requirement, for instance, is that at least five cases of serious illness must develop in the placebo group—the volunteers who aren’t receiving the vaccine—before an application for approval can be submitted. This benchmark helps developers gauge whether a vaccine can prevent severe symptoms as effectively as those mild and 386
moderate—a more than reasonable cause for delay, as it is for the most vulnerable among us that a vaccine arguably matters most. In addition to prioritizing safety over speed, the FDA vaccine guidance serves a broader purpose: creating a common standard all companies must adhere to, and in the process reassuring onlookers who suspect preferential treatment or foul play. Some states have so little trust in the current administration that they have pledged to conduct their own evaluations of any federally authorized vaccine. As for the general public, recent surveys show that the number of Americans age 18 and over who would “definitely or probably get a vaccine” for COVID-19 has dropped more than 20 percent since May. The new guidelines will reintroduce a measure of regulatory rigor that has thus far been minimized—and hopefully earn back some public trust. Similar questions of ultimate authority and accuracy have arisen with the CDC safety guidelines, which over the course of the pandemic became a trusted source of information for so many, from parents and educators to health providers and local health authorities. When the CDC modified its description of how the virus spreads to include airborne transmission last month—finally joining the consensus shared by hundreds of scientists around the world—only to delete it days later, confusion abounded. CDC representatives later claimed the update had been posted on accident, but the flipflop was too abrupt and confusing to be explained away so easily. The possibility that aerosols, or small respiratory particles, might be enough to transmit the virus from one person to another is a primary motivation for mask-wearing—one of the public health measures belittled by President Trump and disavowed by some of his supporters. In the grand scheme of things, the question of whether to include or exclude one piece of information may seem like small potatoes. But in lieu of vaccines, drug treatments, or a national action plan of any kind, our ability to protect ourselves from infection remains tied to our ability to learn as much as we can about COVID-19 and modify our everyday behaviors and routines accordingly. Our federal health agencies play a critical role in collating and disseminating this expertise, especially in times of crisis. As of Monday, the CDC has once again added language affirming the possibility that aerosols, or small respiratory particles, are one way 387
the virus can be transmitted. While their choice of words this time around is decidedly more evasive, acknowledging the virus is “sometimes be spread by airborne transmission” rather than outright calling it airborne, at least now the record reflects what we know based on scientific evidence. With faith in our national institutions on the decline, we need reassurance now more than ever that our health authorities are acting in the interest of the general public, rather than politicians or pharmaceutical companies. On October 22, an FDA advisory committee will meet to discuss and settle the legal requirements for authorizing a COVID-19 vaccine. Let us hope any judgment they reach can hold steady in the face of potential political backlash. This article originally appeared in Forbes and is available online here: Federal Health Agencies Push Back Against Political Interference
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What The Pause In The Johnson & Johnson And Eli Lilly COVID Drug Trials May Mean Forbes | October 14, 2020 | Article
For some time now I have been raising concerns regarding the safety and efficacy of the COVID vaccine and drug trials. Rushing toward approval—while understandable—can be dangerous. And the recent pause in the Johnson & Johnson and Eli Lilly trials should give all of us pause. Regarding vaccines: The COVID vaccines currently most advanced in the US are those of Pfizer and Moderna. People describe taking the vaccines as akin to being kicked by a horse—painful, in some cases dizzying, but transient discomfort. One can’t help but wonder if that will be the end of the story as the vaccine is rolled out to hundreds of millions of people, some of them already in fragile health. More cause for concern are the reports of at least two cases of transverse myelitis, which caused two pauses in the AstraZeneca vaccine trials. The most recent pause was reversed in some countries but not in the US. Now comes news of a pause of the Johnson & Johnson vaccine for at least one serious adverse event. It is unfortunate that the details in both cases are withheld, avowedly to protect the privacy of the affected person. It seems to me that autonomy can be preserved simply without revealing the identity of the person suffering the consequences of volunteering in the trials. We need to know what dangers may attend the use of these vaccines. It may be relevant that both the AstraZeneca and the Johnson & Johnson vaccine both use the same class of vector, a defanged adenovirus. The specific viral vectors differ slightly as do the components of the SARS-CoV-2 virus they carry. Adenoviruses are known for their ability to infect cells of the nervous system and are for that reason are a favored vector for gene therapy treatments of
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inherited nervous system disorders. Adverse events such as transverse myelitis may be due to the neurotropic nature of the vector. It is worth noting that COVID vaccines based on adenovirus vectors are already approved for use in Russia and in China. One of the two vectors used in the Russian vaccine is the same as that used by Johnson & Johnson. We have little to no information regarding the safety and efficacy of either the Chinese or Russian vaccines as they are currently deployed. An accurate accounting of observed adverse events of both vaccines would be very helpful as they are rumored in the press to been given to hundreds of thousands. Regarding anti-COVID drugs: The pause of the Eli Lilly monoclonal antibody therapy is especially troublesome as the President of the United States has called for immediate Emergency Use Authorization of the Lilly treatment along with that of Regeneron, well before the trials are complete. It is also concerning that an unproven treatment was given to the highest executive officer in the land, when it and other COVID monoclonal antibodies may have serious safety issues, issues deleterious enough that the FDA has presumably asked Lilly to pause the trial. The press releases and statements from the companies regarding the pause both emphasize they exercised “an abundance of caution”, and that serious adverse events are common in all large drug and vaccine trials. While this may be true, we deserve to know the details. The first tenant of medicine is do no harm. We expect and hope that this principle will be upheld despite the urgent need for treatments and vaccines. Author's Note: This article was not peer reviewed before publication. This article originally appeared in Forbes and is available online here: What The Pause In The Johnson & Johnson And Eli Lilly COVID Drug Trials May Mean
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How US Public Health Failed You And Me Forbes | October 14, 2020 | Article
This is the first of a three part series analyzing public health infrastructure in the United States. This introduction analyzes the governing bodies of US public health and why they are not getting the job done. COVID-19 exposed the failures of our government in the United States. The US government has not succeeded in protecting the health of its residents—its response to the epidemic has been disjointed, poorly coordinated and, in many regions of the country, largely ineffective. While the federal government has played a central and important role in research and in the development of COVID19 drugs and vaccines, messages coming from the White House and its supporters across government and from federal agencies like the Centers for Disease Control (CDC) and the National Institutes of Health often conflict. To be specific: There is no federal mask mandate. Thirty-three states issued statewide orders to wear masks, but these vary in detail and enforcement. There is no federal school reopening plan. Four states ordered school reopenings, Washington DC ordered schools remain closed, and nearly every other state left the decision to individual school districts. And there is no federal economic reopening plan. This map shows the fractured economic reopening of the country; many states are in flux as cases spike and jurisdictions panic. The consequence is that the US leads the world in the number of people known to be infected by SARS-CoV-2, the number of people per 100,000 population infected, and the total number of people who have died, more than 215,000 and counting. The estimated financial cost of our failures due to lost lives, lost productivity, and medical expenses alone is estimated to be more than $16 trillion and rising. Many fault the Trump administration for failing to perceive the magnitude and danger of the pandemic and for its unwillingness to use the power and resources of the federal government to address 391
the pandemic using standard public health measures. While this is undoubtedly the case, many of the issues plaguing the US response extend well beyond the current administration. I point the finger at both the governance and the structure of how we in the US address public health issues. Along with inept leadership, these issues lie deep in the heart of our dysfunction with regard to control of COVID19. The Nongoverning Governing Bodies The Department of Health and Human Services oversees public health in the United States and our Public Health Service (PHS), which includes the NIH, CDC, Food and Drug Administration (FDA), and five other public health divisions. The Public Health Service and its uniformed commissioned corps are ultimately responsible for the health of our nation. Under the 1944 Public Health Service Act, Congress granted the PHS the powers of public health regulation. The Federal Emergency Management Agency (FEMA) sits outside of the PHS but also has the power to coordinate a national response to a disaster, especially when states are overwhelmed or lack resources. Though FEMA and the PHS both have the constitutional and legislative right to lead our national response to COVID-19 and make good on their responsibilities to protect the health and security of our nation, neither has taken charge. Instead, the onus has been placed on states to manage the health response on their own, whether or not they have the resources or the skills to do so. In lieu of actively directing a national response, the CDC, the NIH and other federal agencies offer suggestions and guidance not mandates to “jurisdictions” that seem to have executive authority. A “jurisdiction” may be an entire state, county, city, or even township. The result of the dereliction of duty by PHS and FEMA is no more apparent than in the testing failures over the past eight months. The CDC offered some testing guidance for schools, businesses, and healthcare workers but no mandates were issued to states on how to expand access to tests. Congress approved twenty five billion dollars for state testing expansion but, without clear directives, most of that money now sits unused or is allocated elsewhere. A vast majority of states are far behind daily testing targets and the nation as a whole falls nearly five hundred thousand tests short per day. Underachieving state measures did not get the job done. What was 392
needed—and still is—is a comprehensive federal testing plan to standardize testing and hold states accountable for their failures. Takeaways from China’s COVID-19 Turnaround Countries that have taken a centralized, top-down approach to solving the problem of COVID-19 have fared much better than ours. The best example is China, the origin and initial epicenter of the pandemic. Though China has roughly four times the population of the US, they have kept their total case number to under one hundred thousand—less than two percent of the number of cases in the US. How is this possible? Early in the outbreak, once there was an overall sense that the virus was easily spread from person to person, China effectively banned more than seven hundred million residents from leaving their homes, with the exception of seeking food and medicine. The country instituted massive testing and contract tracing regimes and built hospitals in mere days to handle the surge in demand. Local districts were ordered to close schools and public venues, ban public gatherings, halt public transport, and isolate the infected. These top-down initiatives were not suggestions or tips, but mandatory rules. Critics assert that these directives were made possible because China’s government is totalitarian and that similar efforts in the US would never pass muster. But anyone who rejects China’s approach in the belief that they are rejecting totalitarianism is in fact rejecting the sound public health principles and practices that have been forged over hundreds of years. Endorsing the public health efforts of China is not an endorsement of the country’s governing ideology. The objective reality is that China handled the COVID-19 pandemic markedly better than the US. That is not to say we should weld iron bars to front doors forcing people to stay home, but the federal government must follow in China’s footsteps to drive a nationally mandated response to this public health crisis. Aggressive, top-down public health initiatives have worked elsewhere to control COVID-19 and have kept foreign nations healthier than ours for decades. Ignoring the public health success of others only reinforces our public health shortcomings. The next article in this series will explore the challenges of our current public health infrastructure and how choices we’ve made in the past have 393
made it more difficult for us to respond quickly and effectively to crises like the one we face today.
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Herd Immunity Is A Double Tragedy In The Making The Daily Clout | October 15, 2020 | Article
Yesterday we learned that two unnamed White House spokespeople confirmed that achieving “herd immunity” for COVID-19 is part of the President’s plan to control the pandemic. Achieving herd immunity means effectively letting the virus spread unchecked. The head of the World Health Organization, Tedros Adhanom Ghebreyesus, called the approach “scientifically and ethically problematic,” saying in a media briefing that “never in the history of public health has herd immunity been used as a strategy for responding to an outbreak.” But the WHO chief is pulling his punches. This policy is equivalent to mass murder because it anticipates between 2-6 million Americans die in the coming months from COVID-19. The math is simple and straightforward. Between 1 and 3% of those tested virus-positive die. The plan is to allow 250 million Americans to become infected. At 1% that is 2.5 million people—our friends, parents, and children included. A policy of “herd immunity” is a double tragedy in the making. There is no evidence that “herd immunity” exists for COVID-19. Quite the opposite. Naturally acquired immunity to well characterized human coronaviruses, and to SARS-CoV-2 in particular appears to be short-lasting, especially for the vast majority of those infected asymptomatically. The recent story in the New York Times, suggesting reinfection is rare, is misleading as reinfection with coronaviruses occurs yearly and would not be manifest for several months hence. Moreover, there has been no systematic effort to measure actual reinfection rates. We don’t see what we don’t measure.
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The hope that a vaccine will spare us seems ephemeral. At best as I can tell those developing COVID-19 vaccines are hoping that they will be as effective as the influenza vaccine, that is to say no more than 30 to 60% effective in reducing symptoms. We all know that flu vaccines do not prevent the annual reoccurrence of the flu, nor should we expect a COVID-19 vaccine to do better. In fact, flu vaccines do not even prevent those vaccinated from infection, and only partially protect us from serious disease. For the elderly, they do that poorly. In his broader comments about the herd immunity approach, Tedros reminds us that public health measures can control the pandemic—witness China—and that we need all the tools of public health and medicine if we are to be successful. We are in the early stages of a virulent second wave of disease sweeping Europe and an epidemic taking off to even greater heights in the US. This is no time to give up the fight! This article originally appeared in The Daily Clout and is available online here: Herd Immunity is a Double Tragedy in the Making
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Compromised Type I Interferon Response Common Among Severe COVID-19 Patients Clinical OMICs | October 19, 2020 | Article
Why COVID-19 makes some people so much sicker than others is a puzzle we’re continuously trying to crack. Thanks to two studies recently published in Science magazine, we now know of one very specific predisposing factor: a compromised type I interferon response. This discovery has implications for how we diagnose and treat COVID-19 that could not just reduce suffering, but potentially save lives. According to the new studies, which analyze data from hospitals around the world, about 14% of COVID-19 patients who go on to develop serious illness lack the ability to either make or mount interferons against invading pathogens. In one study, only 0.3% of the healthy control population had the same deficiencies. While each of the two papers examines a different reason for why this might be, they arrive at the same conclusion—that an absence or dysfunction of interferons might determine the severity of ensuing disease. Interferons, broadly speaking, are warning signals that alert the immune system whenever an intruder is on sight. Classified as type I, II, or III, these proteins serve a critical defense function in the early stages of infection, quite literally running interference so the host cells can slow viral replication. The first Science paper studies severely ill COVID-19 patients who have developed so-called “auto-antibodies” against their own type I interferons, reducing the number of interferons circulating in the blood to either extremely low or undetectable levels. These defective antibodies, which block interferons from signaling other cellular defenses into action, represent a certain type of autoimmunity—that is, immunity to substances made by your own body. It has been observed that autoantibodies are more prevalent in 397
older adults than younger, which might explain, at least in part, why COVID-19 is, too. The second paper focuses on patients who also had minimal to undetectable interferon levels, but whose interferon response was crippled by certain genetic mutations rather than autoantibodies. These mutations, which are also associated with severe influenza, were detected in the DNA of about 3.5 percent of critically ill COVID-19 patients. The control group, characterized by mild or asymptomatic infection, had none. The results echo the conclusions reached by a Dutch study of two sets of brothers who, despite being young and in good health, became critically ill from COVID-19. It was later found that they had inherited a genetic mutation that dampened their interferon response. It turns out that the SARS and MERS coronaviruses have a number of different non-essential proteins, and a handful of those are devoted to modulating the type I interferon response. For one of them, orf3b, it appears that type I interferons are the primary restraint. In other words, the virus expends much of its genetic energy trying to disable interferon function. These observations, along with the increased susceptibility to severe effects of infection demonstrated in the Science papers, suggest that type I interferons are one of the body’s most important defenses against SARS-CoV2. The clinical implications of these findings are threefold. First, we should be screening all identified COVID-19 patients for the autoantibodies and genetic mutations that might predispose them to severe illness. Healthcare workers and others who are regularly exposed to the virus should undergo the same testing regimen as well. Anyone found to have either deficiency would then know to take extra precautions and receive priority status for vaccinations. Second, if interferons are critical to our ability to fight SARSCoV-2 we must treat them as such. While interferon-based drug therapies will likely yield poor results if prescribed to patients with autoantibodies, such drugs could help other vulnerable populations avoid the worst this disease has to offer, including those whose 398
interferon response has been genetically compromised. There may even be a limited role, if given extremely early in cases of acute exposure, for limited interferon prophylaxis, or post-exposure prevention. The third and final implication relates to another experimental treatment—convalescent sera, or the blood plasma of recovered COVID-19 patients, authorized in the United States for emergency use. Potential plasma donors must not only be screened for autoantibodies against interferons, but also be removed from the donor pool if they test positive. Their plasma might otherwise unwittingly debilitate a recipient’s immune response. This applies as well to the donors selected to prepare hyperimmune globulins, or hyperimmune igG, a more purified and potent concentration of plasma. This article originally appeared in Clinical OMICs and is available online here: Compromised Type I Interferon Response Common Among Severe COVID-19 Patients
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Eli Lilly Plant Set To Manufacture COVID-19 Therapy Cited For Breaching FDA Regulations Forbes | October 20, 2020 | Article
An Eli Lilly pharmaceutical plant set to manufacture a COVID-19 treatment has been cited by the Food and Drug Administration (FDA) for quality control issues, according to Reuters. Sources close to the situation told Reuters that Eli Lilly had falsified records pertaining to FDA manufacturing standards. The COVID-19 treatment Eli Lilly is set to produce is an antibody therapy similar to a Regeneron therapy taken by the president during his infection. The President has called for the authorization of both treatments immediately. The discovery of falsified records stems from a November inspection of the Eli Lilly plant. Following the inspection, the FDA granted the plant an “Official Action Indicated” notice, which means that “the violations are serious enough and have a significant enough impact on the public health that something needs to be fixed” noted Patricia Zettler, a law professor at Ohio State University and former FDA official. This report confirms our concerns from the start with fasttracked COVID-19 therapies: beware of lower safety standards. Undue speed compromises manufacturing and distribution as well as efficacy and safety. Fast-tracked COVID-19 treatments already present health risks because nobody knows the long-term dangers of quickly approved and unstudied drugs and vaccines. Some health effects may occur over a period of many months to a year or more and cannot be evaluated in accelerated trials. The chance that undue speed may compromise safety is real, as the Lilly citation underscores. Under normal circumstances, the FDA requires several batches of drugs to be made, all meeting the same safety, consistency, stability, and potency standards using the same facilities used to eventually sell the drug. This safeguard was discarded in the rush to move drugs and vaccines to market, imperiling patients.
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We have seen EUAs for “miracle drugs” before after being highly touted by the administration. The EUA for hydroxychloroquine released in March was quickly revoked a few months later. The authorization letter cited only a limited French study of thirty-six participants. Despite only minimal evidence, the drug was allowed to proceed. After just three months, there was little evidence suggesting the drug effectively reduced COVID-19 symptoms, even provoking heart risks in some users, and was promptly revoked of its authorization status. The dangers of premature EUA are two-fold. The first is the health dangers of approving a drug that does not work. Fast-tracked drugs and vaccines are at risk of harming participants in drug trials in the short term or the greater population in the long term. There have already been pauses in vaccine and drug trials due to patient development of severe unknown illnesses. The second is the assurance that drugs will be safely and consistently produced. Production standards for drugs and vaccines are in place ultimately to protect the well-being of the nation. Someone hospitalized with severe COVID-19 symptoms is not concerned with the safety standards of some production plant. If their doctor tells them about an EUA approved drug, they will want it. It is the responsibility of the FDA to ensure that standards are being adhered to in order to protect those most at risk. The issues with drugs tested in the US raises the question of the potential safety and efficacy of vaccines approved in both China and Russia. Might they have similar undisclosed issues? Both of the vaccines on pause in the US are broadly similar to those approved in China and Russia. We know little to nothing of the quality and safety standards applied. There are reports that the Chinese vaccine has been given to “hundreds of thousands” and that the Russian vaccine is also widely administered. The recent clinical development pauses of two COVID-19 vaccines in the US are currently paused as is the trial of the Lilly monoclonal antibody therapy, data on the safety and efficacy of the Russian and Chinese trials are overdue. COVID-19 treatments have the potential to save thousands of lives as the United States approaches 220,000 deaths from the disease. To ensure a drug is successful, however, there must be regulations in place. The short-term protection from COVID-19 does not
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outweigh the long-term side effects of a defective drug. I hope that Eli Lilly is an aberration, not a trend. This article originally appeared in Forbes and is available online here:Eli Lilly Plant Set To Manufacture COVID-19 Therapy Cited For Breaching FDA Regulations
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Massive COVID-19 Drug Trial Underscores Importance Of Controlled Clinical Studies Forbes | October 20, 2020 | Article
The interim results of the World Health Organization’s massive Solidarity Therapeutics Trial are in — and they don’t bode well for remdesivir, the antiviral drug that for months was touted as a moderately effective treatment for COVID-19, and three other drugs. The study, which involved more than 11,300 people across 30 countries and is currently undergoing peer review, examined the efficacy of four repurposed antivirals — remdesivir, hydroxychloroquine, lopinavir-ritonavir, and interferon. Patients prescribed any of the four, the results show, weren’t any likelier to survive than those who weren’t. Neither were their hospital stays any shorter. We already knew this much, more or less, about hydroxychloroquine and lopinavir, in part due to the release of the results of the RECOVERY trial, a study similarly large but conducted only in the United Kingdom. Both treatments were dropped from the Solidarity trial roster shortly thereafter. But for remdesivir and interferon, the conclusion that neither drug reduces mortality carries more weight. When put to the test in smaller studies, remdesivir appeared to lead to earlier hospital discharges and an overall shorter disease course for some patients. It is notable that Gilead, the company behind remdesivir, cited this particularly promising outcome in justifying the treatment’s $3,120 price tag. As for interferon, a protein that alerts the immune system whenever an intruder is on sight, researchers had high hopes that interferon-based therapies might do more to help patients fend off severe and life-threatening symptoms. This hope was founded in part on earlier findings that the COVID-19 virus, SARS-CoV-2, actively dampens our interferon response as a means of weaseling into our cellular machinery. It so follows that a load of synthetic interferons 403
might shore up that critical yet compromised line of defense, though for this particular candidate that didn’t prove to be the case. While not many interferon-based therapies have made it very far down the research-to-market pipeline, the same can’t be said for remdesivir. Not only was it authorized for emergency use by the U.S. Food and Drug Administration in May and included in the treatment regimens of public figures as high-profile as the president of the United States himself, earlier this month a six-month supply of the drug was also sold to the European Commission for $1 billion. In a statement released shortly after the Solidarity trial results went live, Gilead expressed concern over “the limitations of the trial design,” which per their analysis “prioritized broad access” over methodological rigor. They fail to mention that one of their own studies on remdesivir — conducted in China and still heavily cited to this day — was prematurely terminated, ostensibly due to low patient enrollment. Many consider the randomized controlled trial to be an essential — if not inviolable — component of drug discovery and approval, even in times of crisis when stakes seem too high to deprive the selected control group of a potentially beneficial drug. Broad though the findings of the Solidarity trial may be, they give us the most accurate representation — so quickly as to nearly be in real time — yet of how these drugs are working around the world today, and how they would work if they were to be manufactured and distributed globally. The answer, unfortunately, is not so well, but that knowledge in and of itself is useful. It will be far more difficult to obtain for treatments like convalescent sera and monoclonal antibodies, which due to logistical complications are difficult to make, much less deploy, on a large scale. Not for nothing have both convalescent sera and monoclonal antibodies received emergency use authorizations (EUAs) in the United States, despite a lack of robust scientific evidence proving their efficacy. This doesn’t necessarily undermine the necessity of EUAs, but it does raise the question of whether their impact on the health and safety of actual patients nets positive or negative. Without large-scale clinical trials and strict regulatory standards, it becomes difficult to tell whether EUAs serve a purpose of clinical or political
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expediency — a boundary too dangerous to cross, especially when so many lives are on the line. It may be the case that using antivirals to treat late-stage COVID-19, which is associated with the hyperinflammatory symptoms that make the disease a matter of life or death for some, is something of a nonstarter. At that point, patients require interventions that address the onerous and occasionally lethal consequences of viral infection, rather than the virus itself. This may be the reason why treatments like anticoagulants and corticosteroids like dexamethasone are now more associated with survivability than their antiviral counterparts. In any case, the results of the WHO Solidarity trial form a valuable contribution to our ongoing search for COVID-19 treatments. They emphasize the importance of conducting largescale, randomized controlled drug trials even amidst a fastdeveloping global health crisis. This article originally appeared in Forbes and is available online here: Massive COVID-19 Drug Trial Underscores Importance Of Controlled Clinical Studies
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Underfunding Public Health Harms Americans Beyond COVID-19 Forbes | October 21, 2020 | Article
This is the second of a three-part series analyzing public health infrastructure in the United States. Part one can be found here. This midsection analyzes how the public health system is incapable of keeping people healthy even outside the pandemic. Public health is a federal responsibility. The acronymed agencies of the United States, the NIH, CDC, PHS, FDA, and others are tasked with ensuring the health and safety of the population were tested by the COVID-19 pandemic. With more than seven million infections and two hundred thousand deaths from COVID-19, the public health infrastructure of the US failed to maintain the people’s well-being. The current administration underestimated the scale and swiftness of COVID-19, but the US public health infrastructure would likely struggle under any party or administration. Public health is consistently underfunded and often viewed as less important than clinical medicine in the United States. The result is a population with a higher prevalence of chronic illnesses and shorter lives, especially among those in lower-income brackets. Under both Democratic and Republican leadership, the federal government took less responsibility for funding public health in the US. From the late 1960s to the 2010s, the federal share of total health expenditure for public health dropped from 45 percent to 15 percent. As a result, states were required to cover the gap in funding mostly on their own. However, states vary in economic strength and some fund public health more effectively than others. According to the Trust for America’s Health, almost $300 million was cut from the Public Health Emergency Preparedness Program between its inception in 2002 and 2017. The fund, which is the only federal program to support state and local health departments in health emergencies, was established by the CDC with a starting budget of $940 million, but was reduced to $667 406
million over the following fifteen years. When the program does receive an influx of funding, it is to respond to specific threats such as Ebola and Zika, and the money cannot be used to strengthen other aspects of the program. Recent research found that US public health departments are left about $4.5 billion short of what they need, according to public health expert Nason Maani and dean of Boston University’s public health school Sandro Galea. Reduced federal funding for public health has direct consequences for everyday citizens. As baby boomers age, there is a greater need for well-funded health services for the elderly. High opioid addiction levels require well-funded rehabilitation and assistance programs, which the US lacks. Our country has suicide rates ranking in the top ten of OECD countries, but there is not enough suicide prevention funding to lower them. The US has the highest chronic disease burden and an obesity rate at twice the OECD average. The US death rate from heart disease is the second highest amongst 17 similarly developed nations. The prevalence of lung disease, arthritis, diabetes, HIV, and more are higher than the OECD averages of these diseases. The US has an infant mortality rate of 5.9 deaths per one thousand live births and a maternal mortality rate of 14 deaths for every one hundred thousand live births, trailing nearly fifty countries. Kazakhstan, Bosnia and Herzegovina, and Bulgaria all have lower maternal mortality rates than the US. Among Black women, the maternal mortality rate in the US is over three times higher than it is among white women. Access to primary healthcare and public health services can improve the health of the population and decrease the risk of health threats such as epidemics. However, US residents go to the doctor less than residents of any other OECD country. A March 2020 survey of twenty-five hundred people found that nearly one in three families had not sought medical care within the previous twelve months due to prohibitively high out-of-pocket costs. Healthcare in this country is simply not as accessible as in other countries. According to the CDC, over fifty million American adults did not see a healthcare professional in 2018. This has serious implications in a pandemic where Americans may avoid seeking health services when in need of them due to high cost and, as a result, spread the infection to others. 407
Our per capita health spending is the highest in the world. Considering the health outcomes we have, where is that spending going? Researchers from Johns Hopkins School of Public Health came to a simple conclusion. It’s the prices. Higher healthcare spending is due to higher drug costs, higher doctor salaries, higher administrative costs, and higher-priced medical services, some of which could be avoided if we invested in a stronger public health system. The federal government must use its authority to address inflated costs and poor, unequitable health outcomes. There are examples of the federal government implementing public health programs to improve the health of the population. In 1998, the FDA required all enriched grains to be fortified with folic acid, which supports the neural tube development in utero, resulting in a 25% reduction in spina bifida and anencephaly, two major birth defects of a baby’s brain. However, our current public health infrastructure enables the declining health of our population. Other countries are paying less for better health outcomes. Throughout the COVID-19 response, the federal government has relied on the underfunded state and local health departments to implement testing and economic reopening with widely ranging levels of success, a practice that will likely continue during the eventual distribution of a vaccine. In anticipation of a possible COVID vaccine, the Centers for Disease Control and Prevention recently released what it described as a playbook that outlines how a vaccine should be distributed across the country. The CDC’s guidance, however, seems certain to be inefficient and likely to be ineffective. The playbook outlines a series of suggestions for what states and localities should do, rather than a full accounting of what they must do to ensure a vaccine is distributed equitably and efficiently. None of it is binding. The playbook parallels the damaging structural flaw of decisions generally being left to local authorities, even though the expertise often resides at the federal level, with the CDC. In the playbook, the federal government takes no responsibility in distributing eventual vaccines to US residents and suggests it will issue no federal mandates on how jurisdictions must handle distribution either. The decentralization of an effort so massive almost guarantees differences in vaccine access, storage standards, and racial or economic disparities. 408
The United States has the economic power to end health disparities but refuses to reinvent its public health capabilities. Investment in the current system is inadequate, akin to a new coat of paint on a broken-down car. There must be a revitalized, national public health system that effectively ensures the health of every resident of the United States. This article originally appeared in Forbes and is available online here: Underfunding Public Health Harms Americans Beyond COVID-19
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More Troubling Events In The Rush To Find COVID-19 Vaccine Forbes | October 22, 2020 | Article
Johnson & Johnson, one of four U.S. companies whose COVID-19 vaccine has advanced to the last phase of clinical trials, has hit pause on a study of 60,000 patients due to a case of “unexplained illness,” according to an official announcement released last week. Whether the illness was caused by the vaccine or a placebo remains unknown. The temporary pause, their statement goes on to clarify, differs from a clinical hold, which fellow vaccine developer AstraZeneca initiated after a participant in a U.K. trial developed serious neurological symptoms. Under normal (which is to say pre-COVID) circumstances, the interruption of the Johnson & Johnson trial would go unreported—so expected is it in a study that large. But it could be millions, not tens of thousands, who potentially receive this vaccine, and as such even the slightest hiccups warrant scrutiny. The same could be said for yesterday’s report that one of the participants in the AstraZeneca trial in Brazil has died, though the independent safety and monitoring committee that evaluated the case ultimately made the decision not to pause the trial. While their judgment gives us reason to believe that the death was unrelated to the vaccine or placebo that participant received, it still chalks up as yet another—and not likely the last—complication that AstraZeneca has noted but barreled past. Any vaccine, if efficacious, works furiously and potently to rev up the body’s immune system. Ideally, the effects are protective, stopping infection and preventing disease. The conditions that form a perfect storm in some, however, can unleash a cyclonic nightmare in others, triggering adverse reactions powerful enough to become illnesses in and of themselves, like Guillain-Barre syndrome. When pharmaceutical products of any kind, not just vaccines, are rushed to 410
market, these rare yet serious side effects are more likely to end up brushed under the rug. While desperate times call for desperate measures, ignoring the adverse outcomes of vaccine trials, however select the few, cannot be one of them. At least one patient in the AstraZeneca trial—later discovered to have multiple sclerosis, a condition undiagnosed prior to their participation—developed a rare disease known as transverse myelitis that involves inflammation of the spinal cord. The second patient to cause the AstraZeneca trial to pause due to illness, a source told the New York Times, was also ultimately confirmed to have transverse myelitis. I’ve spoken with a number of former FDA regulators who tell me this would typically be reason enough not just to put trials on hold, but also to terminate development of a particular vaccine altogether. The Johnson & Johnson vaccine, like the AstraZeneca vaccine, was created using an adenovirus—a common cold-causing virus— vector, specifically adenovirus serotype 26 (Ad26). Though the technology has been implemented in the creation of gene therapies and experimental Ebola vaccines, it has yet to yield a fully licensed vaccine and, tragically, has been associated with fatalities, like the death of Jesse Gelsinger. To be sure, the Johnson & Johnson adenovirus vector differs from that of AstraZeneca, but they do share the property of being neurotropic—that is, having the propensity to infect neural tissue of a variety of types. Somewhat worrying is that Ad26 is one of two adenovirus vectors used in the Russian COVID-19 vaccine, which the country’s Ministry of Health approved before a large-scale trial had even begun. The second of the two vectors, Ad5, was also used in one of four vaccines that hundreds of thousands are reportedly receiving in China, developed by CanSino Biologics. It would be beneficial to researchers and developers everywhere if data on the adverse side effects of these vaccines was made available to the general public, especially since other countries are buying them up by the millions. But such accounts, if they do exist, are currently shrouded in secrecy.
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If vaccines for COVID-19 aren’t held to the highest safety and efficacy standards we can muster, they could very well exacerbate, not mitigate, the pandemic. Across Europe, we’re seeing what happens when people let their guard down; in countries like Spain, Italy, and France, rates of infection and hospitalization now exceed those accumulated during the first wave. The public health risks that contribute to such resurgences, like congregating in large groups, and the risks of rushing out a vaccine tend to be treated as separate concerns. But if an only partially effective vaccine is authorized for mass use, whatever effectiveness there may be in reducing infection could be more than swamped by new infections that are the result of people letting down their guard. We all want this crisis to be over with—and for good. In our haste to recapture a sense of normalcy, however, we risk prolonging the pandemic by not just months, but potentially years. Safety, not a need for speed, must absolutely come first and foremost, and in the context of vaccine trials that means taking each pause or hold as seriously as needed. Proceeding with care and caution, contrary to what our basest instincts tell us, is what will dig us out of this mess. This article originally appeared in Forbes and is available online here: More Troubling Events In The Rush To Find COVID-19 Vaccine
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Vaccine Transporters Feel Unprepared For The Distributive Effort Ahead Forbes | October 22, 2020 | Article
As pharmaceutical companies conduct phase 3 vaccine trials, air cargo transporters are cautious about the logistics involved in the mass distribution of a COVID-19 vaccine. A recent survey found that less than 30% of air cargo companies felt prepared for the job ahead. Developing the vaccine is only the first step. Getting that vaccine to the population will prove as difficult. Vaccines are difficult to distribute in part because of their delicate structure. Most vaccines need to stay cool to maintain effectiveness. Moderna and Pfizer’s COVID-19 vaccine candidates need temperatures of -15 and -70 degrees Celsius. For reference, most flu vaccines are stored between 0 and -15 degrees Celsius. Shipping hundreds of millions of vaccines at -70 degrees Celsius would be an unprecedented distributive feat requiring thousands, if not millions of super cold transportation containers. Air cargo transporters concerned about transporting these vaccines note a lacking supply of these containers. Of the 181 companies surveyed by the International Air Cargo Association, less than half were capable of sub-zero temperature shipments at every company location. Even after shipping vaccines from the production facility to a jurisdiction, that shipment must be safely offloaded, ground-transported to a distribution center, and again stored in a freezer capable of such low temperatures. There seems to be an assumption that every healthcare center and pharmacy distributing these vaccines will have a sub-zero freezer on hand. Dry ice can keep the vaccines from thawing for a few days, but distributing thousands of vaccines in under a week to keep the vaccines potent seems to leave little room for error. The storage capabilities for keeping vaccines safe enough for long term storage and use are simply unavailable. Without federal support providing storage capabilities, it seems impossible to think rural or
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impoverished areas will have the vaccination success an urban area may have. Most vaccine candidates require two doses, which only amplifies distribution concerns. The Centers for Disease Control and Prevention released a vaccine distribution playbook that outlines how state and local jurisdictions should prepare their vaccine operations. The playbook notes that in addition to cold storage, vaccines come in two doses administered a certain number of days apart. Requiring two doses not only increases the load air cargo companies must transport, but it forces people to go get vaccinated twice. Going to a pharmacy twice in a month seems a small ask for those who own a car or live close to potential distribution centers, but two shots double the burden on the poor and rural communities. 8.7% of families were without a car in 2018. Low-income families may not have immediate access to a potential vaccine distribution site because of this. Parents in these families work long hours for low wages and may not have time to take the whole family via public transportation to a vaccine distribution site, not to mention twice. Rural Americans face similar concerns. As noted in the playbook, shipments of the vaccine will be sent to jurisdictions in packages of one thousand. This is manageable for urban areas with one thousand people living within a few blocks, but in rural areas, one thousand vaccines may disperse over hundreds of miles. Large vaccine shipments would need wide dispersal across a rural jurisdiction. Moving these vaccines may prove difficult in the coming months. Roads and weather will get treacherously icy in states like the Dakotas, Wyoming, Montana, etc. Rural midwestern states are current hot spots for COVID-19 infections, and those numbers will only worsen as temperatures continue to drop. Getting vaccines to rural Americans in these states is imperative, but damaging some vaccines in transit seems more of a likelihood than a possibility. Transportation is just one of the many issues with COVID-19 vaccine distribution, as a fast-tracked vaccine can provoke health risks in the short and long term. AstraZeneca, for instance, had to pause trials after a volunteer developed a rare spinal disease. It remains to be seen whether the vaccine caused the illness or not. Trials typically extend over years to monitor these instances, but 414
COVID-19 vaccine trials seem to be nearing the finish line already. Then the shot will be taken by hundreds of millions of Americans. It is impossible to know the long-term health risks of the fast-tracked vaccine. Hesitations by air cargo companies, vaccine storage concerns, and poor and rural inaccessibility express how unprepared for a pandemic we were. While the vaccine development process has been unquestionably quick, it seems that haste was not paralleled in the distribution preparation process. A vaccine may be ready soon, but whether that vaccine will make it to every American remains to be seen. This article originally appeared in Forbes and is available online here: Vaccine Transporters Feel Unprepared For The Distributive Effort Ahead
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Three Takeaways From Major FDA Advisory Meeting On COVID-19 Vaccines Forbes | October 23, 2020 | Article
Yesterday a panel of outside experts — formally known as the Vaccines and Related Biological Products Advisory Committee — and laypeople convened to advise the U.S. Food and Drug Administration (FDA) on how to make the approval process for COVID-19 vaccines safer, more robust, and deserving of public trust. One thing became clear over the course of the seven-hour meeting — that a hastily expedited vaccine might benefit some people, but fail those who need protection most. The primary objective of the ongoing late-stage vaccine trials, which have involved hundreds of thousands around the world, is to prevent the onset of COVID-19 symptoms in half of everyone vaccinated. What we really need from a vaccine, however, isn’t a broad reduction in mild cases, but mitigation of serious illness and death. The probing of the advisory committee, as well as presentations that featured insights and concerns from everyday folks, raised issues with the current regulatory framework that are threefold: efficacy, safety, and access. First and foremost is the issue of efficacy, or how well a vaccine candidate actually works when administered to the general public. The purpose of vaccinating against a disease as lethal as this one — a disease that has claimed more than a million lives since the beginning of the pandemic and brought harm and devastation to millions more — shouldn’t be to stop the majority of people from getting colds. It should be to protect the elderly and infirm, Blacks and Latinos, and other groups who are becoming critically ill and dying from COVID-19 at disproportionately higher rates. As of now, this isn’t the case. Earlier this month, the FDA published a set of stricter guidelines for clearing COVID-19 vaccines 416
— ostensibly against the wishes of their White House overseers, who held up their release for weeks. One of the new criteria is that some members of the control group — those participants receiving a placebo rather than the vaccine — need to develop severe symptoms. While intended to create some parameter for evaluating efficacy against serious disease where none existed beforehand, the magic number candidates must meet is startlingly low. Of the 30,000 people participating in a clinical trial, it only takes five cases of severe COVID-19 in the control group to tick this particular box. We cannot assume that a vaccine protective against mild illness will do the same for critical illness, and so long as we can’t assume it we must do better to prove it. The second issue discussed during yesterday’s meeting, not mutually exclusive from the first, is safety. Another criteria included in the updated FDA guidelines is a two-month monitoring period following the completion of phase III trials, notably pushing the potential timeline for any candidate well past Election Day. While the requirement of following up with participants to ensure the vaccine provides the protection it promises — not to mention doesn’t trigger any harmful side effects — is absolutely necessary, two months is hardly enough time to conduct a rigorous long-term evaluation. Human coronaviruses are some of the wilier threats we’ve faced from the microbial kingdom in decades, and studies show that they’re not just capable of reinfection, but potentially even linked to antibody-induced enhancement — meaning antibodies created against the virus enhance its capabilities upon reentry. If we don’t thrust the horizon of COVID-19 vaccine development beyond just a few months, we risk creating entirely preventable challenges that will play out over several years. This brings us to the third issue the panel raised — access, or who will receive a vaccine and when. It appears that emergency use authorizations (EUAs), as Helen Branswell of STAT News astutely observed, have perhaps fallen out favor with the FDA and the general public, who have seen treatments like hydroxychloroquine and convalescent plasma receive authorization based on preliminary 417
data, only to later be discredited by clinical and anecdotal reports of ineffectiveness or even harm. For the same fate to befall an emergency authorized vaccine — especially knowing that in the early days of rollout, doses will go to priority groups like healthcare workers and nursing home residents — would be nothing short of a humanitarian crisis. Instead, FDA representatives at the meeting floated the idea of distributing vaccines through a program of “expanded access” — a mechanism that, rather counterintuitively, would be more limiting in scope than an EUA and might potentially resolve an issue known as early unblinding. If a vaccine is approved through an EUA, members of control groups in ongoing clinical trials will naturally want the real deal rather than a placebo, all but eliminating the opportunity to obtain the long-term data on efficacy we need. While the alternative of “expanded access” raises the question of who, exactly, so limited a notion of access will privilege, once in effect it wouldn’t necessarily impede clinical trials. Recent surveys reveal that the number of Americans willing to get vaccinated as soon as they’re able has dropped significantly — more so for Black Americans than white. On the flip side, the fear that political interests will override scientific evidence as the primary criteria for vaccine approval is on the rise. The vaccine advisory committee meeting can serve as a catalyst for the FDA to reverse course, slow down, and introduce more regulatory rigor to a process that has largely gone off the rails. Now is not the time to take a gamble and try our luck on a shaky candidate. This article originally appeared in Forbes and is available online here: Three Takeaways From Major FDA Advisory Meeting On COVID-19 Vaccines
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Despite Conflicting Evidence, FDA Approves COVID-19 Drug Remdesivir Forbes | October 26, 2020 | Article
On Friday, the U.S. Food and Drug Administration (FDA) gave its first official stamp of approval to a COVID-19 drug — remdesivir. The repurposed antiviral, now also known by the generic name of Veklury, was granted emergency use authorization (EUA) in May and has been administered intravenously to hospitalized COVID-19 patients ever since. The conclusion of a study sponsored by the National Institutes of Health (NIH), which published its final report two weeks ago, appears to be the main reason regulators moved forward with approval. But like the preliminary research that paved the way for the drug’s EUA, the NIH study shows that remdesivir was at best only moderately effective in reducing the suffering and death of those who took it. Not too shabby, but not particularly heartening either. Just last week, newly published interim results from the largest clinical study of remdesivir (and three other drugs) to date, the World Health Organization’s (WHO) Solidarity trial, cast some doubt on even these modest benefits. Involving more than 11,300 people across 30 countries, the study found that COVID-19 patients prescribed remdesivir weren’t any likelier to survive than those who weren’t. Neither did they have a shorter or less painful hospital stay. Gilead, the pharmaceutical giant behind remdesivir, argued in a company statement that the findings of the WHO trial are too broad to be conclusive. By the same token, however, it could also be said that the other remdesivir studies are too small. While the NIH study — unlike the Solidarity trial — did involve a placebo group, it also only administered the drug to few more than 500 patients. It can hardly be assumed that the outcomes of this very specific patient population are more representative than those of several thousand people around the world.
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A safer and more reasonable conclusion, given the data at hand, is that remdesivir may be useful for some, but not all. In this respect the drug is hardly unique; rare is it that one therapeutic regimen fits all. But for a drug so patchy and uncertain in its efficacy, it sure is expensive. An average five-day treatment course costs $2,340 for patients covered by government health plans and $3,120 for those privately insured. What’s more, Royal Bank of Canada analysts predict that Gilead will make about $2.3 billion in revenue off remdesivir sales in 2020 alone — quite a pretty penny for a marginally effective product. Further investigation is needed to confirm the real extent of remdesivir’s positive effects. Let’s hope until then the next COVID19 drug the FDA approves has a less conflicting and more robust body of evidence behind it. Otherwise, we might end up with an assortment of treatments that do more financial harm to patients than clinical good. This article originally appeared in Forbes and is available online here: Despite Conflicting Evidence, FDA Approves COVID-19 Drug Remdesivir
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Restructuring The Federal Response To A Pandemic Forbes | October 26, 2020 | Article
This is the third of a three-part series analyzing public health infrastructure in the United States. Part one can be found here and part two can be found here. This finale analyzes the laws underlying why public health was left to the states and how public health preparedness can be structured moving forward. When COVID-19 began to spread in the United States, the federal government largely left the states to execute COVID-19 control plans individually. Where national mandates and regulations were needed, the federal government failed to deliver. States created their own plans for overcoming COVID-19 and returning to normal life, all of which resulted in inefficiency and case increases. This was not the sole option. The federal government has the legislative and constitutional authority to dictate how the US would control COVID-19. They instead allowed the fractured response that occurred. Federal bodies must levy their governing powers to stop COVID-19 and create a national public health system for the future. The key to a federal COVID-19 response is “state of emergency” legislation. The National Emergencies Act of 1976, the Public Health Service Act of 1944, and the Disaster Relief Act of 1988 allows the President the authority to declare public health national emergencies, in which time they can exercise emergency powers. In fact, President Trump declared a national emergency for COVID-19 back in March using this legislation. Historically, the power to regulate public health has been held by the states. Dr. Eric McDaniel, professor of government and health policy at the University of Texas, describes state and federal interaction “like education...it is the responsibility of the state to ensure the health of its citizens, much like the states are responsible for providing education. For the most part, the federal government is there in a support role.” 421
It seems that public health is one of the powers “not delegated to the [federal government]” and “reserved to the States” by the Tenth Amendment. McDaniel notes that the federal government “may issue guidelines and offer resources, but cannot force the states to abide by them.” However, this constitutional authority comes with a loophole in the form of the previously mentioned “state of emergency” laws. These laws suggest that the President may use the Public Health Service (PHS) to such an extent and manner that in their judgment promotes the public interest. The PHS includes federal bodies like the Food and Drug Administration, the National Institute of Health, the Centers for Disease Control, and others, as well as a uniformed corps of several thousand military personnel. The President essentially has the power to do whatever they need to in the face of a pandemic. If the President were so inclined, they could deploy the commissioned corps of the PHS across the country to run testing and vaccine distribution sites alongside public health officials. In a state of emergency, the President has the authority to override state public health authority. Were a President to use emergency powers effectively at the start of the pandemic, perhaps we would not be the worst-hit country in the world. We must contain future pandemics promptly and effectively. To do that, there are three pillars of public health that need an overhaul: leadership, governance, research, and social solidarity. Leadership The extent and intensity of COVID-19 took US federal leadership by surprise, to say the least. The fractured response to testing and economic downturn leads me to believe that nobody was prepared for the pandemic until it was too late. To address this, our leadership must be readily informed of new emerging diseases and pandemic awareness. The United States' death toll for COVID-19 is over 220,000. The cold months will force millions indoors and that count will certainly continue up. The American death count for World War 2 is around 415,000. It seems possible COVID-19 could reach a similar height. We must elevate public health policy to the importance of war threats. Trillions were spent on the War on
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Terror, yet a war against a deadly virus does not warrant the same importance? Every council, i.e. the National Security Council, National Economic Council, etc., should have a health staffer from the CDC. The Department of Homeland Security should be heavily advised so they could help the federal government prevent internal and international transmission of disease. In fact, the CDC should have staffers in every state government, major city government, and every embassy. The CDC must be ready to inform everyone of impending public health threats and assisting the formulation of effective, timely national policies. They are the intelligence agency to fight a war against disease. Governance The public health policymaking process begins with health agencies like the CDC, FDA, and NIH under the umbrella of the HHS. Though ultimately, public health policies are instituted and enforced by the President. Making sure the President is making informed decisions is imperative to successful health policy. Minimally, the Secretary of Health and Human Services must be added to the National Security Council to inform the president daily on ongoing disease threats and preventative measures. Though there needs to be an added layer of health governing. I suggest a new council dedicated to disease and pandemic prevention and response. In a similar vein to the National Security Council, the proposed National Disease Council can be organized between HHS agencies and meet regularly with the President to discuss impending public health threats. There is evidence suggesting the National Security Advisor was aware of COVID-19 as early as November 2019. Imagine the differing response to the pandemic if we had addressed it as a national security threat. This is all contingent on the willingness of the President to move forward with public health legislation. Some Presidents may take a more relaxed approach to pandemic preparedness. This must be mitigated by the nonpartisan quality of the National Disease Council. Appointments must extend past singular presidential terms. The leadership of the National Disease Council must overwhelm the President with information that would force them into action if necessary. Research 423
No less important than the political branch of policy development is the research aspect. All the agencies on the National Disease Council must work tirelessly to be on top of an emerging disease. Partnerships between public universities and private enterprises must continue to work on drug and vaccine developments. In 2003, President Bush enacted Project Bioshield: a funding program for the rapid development of medical countermeasures to biological, chemical, radiological, and nuclear weapons. The project directed significant funding to the Biomedical Advanced Research and Development Authority to oversee rapid medical device development. The project has been largely successful as eight medical countermeasures against anthrax, smallpox, etc. have been developed. Despite its success, any federal entity has a chance to be politically subordinated. One president may find the program irrelevant or that biological dangers are not a top priority. This cannot be allowed. Bioshield and BARDA funding must be a bipartisan guarantee. The NIH, FDA, FEMA, and BARDA are essential in overcoming a viral pandemic and cannot risk being politically undermined. After 9/11, Bioshield and BARDA were created. During and after this pandemic, these programs must be emboldened. Social Solidarity Finally, the lynchpin of defeating a pandemic is social solidarity. Public health education needs to be so much more than brushing teeth and eating healthy. What is a major reason one may quarantine? To ensure the people around them do not get sick. Public health education must emphasize responsibility to your family, neighbor, and society. If everyone approaches a pandemic situation with similar attitudes, implementing policy decisions will be much easier. Dr. Devi Sridhar, professor of global public health at the University of Edinburgh, emphasizes the need for public health policies to address problems, but to “implement them on an enormous scale that does not leave behind the poorest regions of the world.” This should be the call to action for the United States on a domestic scale. We have a duty to reinvent our public health system in order to protect our most vulnerable. The death and suffering 424
COVID-19 caused in the US should have been mitigated, but hopefully, the lessons we have learned will enable a brighter future for American public health. This article originally appeared in Forbes and is available online here: Restructuring The Federal Response To A Pandemic
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In Brazil, New Study Shows The Poor And Indigenous Suffer The Most From COVID-19 Forbes | October 27, 2020 | Article
The largest population level study of the prevalence of antibodies against the virus that causes COVID-19 was recently completed in Brazil. Population based information on COVID-19 is crucial to understand the impact of the virus on various segments of the population and to guide evidence-based policy decisions on control measures. The study estimated that in some cities only one in ten infections with the virus that causes COVID-19 were reported as COVID-19 cases. The low proportion of reported cases demonstrates the need for expanded testing in Brazil. The study also found disparities in individuals most affected by infection with the virus that causes COVID-19. These disparities highlight the importance of making policy decisions based on scientific evidence to protect all groups against the negative impacts of COVID-19. To determine the percentage of people with antibodies against the virus that causes COVID-19, researchers randomly tested residents of 132 cities in Brazil for these antibodies. If a person has antibodies against the virus that causes COVID-19, it suggests that the person was likely to have been infected with this virus previously. In each city, the goal was to test 250 individuals selected at random. However, the number of people who were in fact tested varied by each city. The study’s findings on antibody prevalence are likely to underestimate the true extent of previous infection because of how quickly antibody levels decrease and become undetectable by an antibody test, especially among the majority of cases who are asymptomatic. Researchers conducted two surveys two weeks apart, so they could measure the change in antibody prevalence over time. The first survey occurred at the end of May and included 25,025 participants. The second survey occurred at the beginning of June and included 31,165 participants. Randomly selected participants 426
provided two drops of blood that was tested for the presence of antibodies using the WONDFO SARS-CoV-2 point of care antibody test. Participants also completed a survey that asked questions about their demographics, socioeconomic status, and uptake of COVID-19 prevention behaviors. The demographic information included sex, ethnicity, age, and education level. The five groups recognized in the official Brazilian classification of ethnicity are: Branco (white), Pardo (Brown), Preto (Black), Amarelo (East Asian), and Indígena (Indigenous). There were large disparities in infection rates between the ethnic groups and income levels in Brazil. The prevalence of antibodies against COVID-19 in the second survey was 6.4 percent in Indigenous groups compared to 1.4 percent in the white population. Among the poorest twenty percent of participants, prevalence in the second survey was 3.7 percent compared to 1.7 percent among the wealthiest twenty percent of participants. Members of the Indigenous population were over four times more likely to have antibodies against COVID-19 in their blood compared to white people. This large difference is partially explained by region, number of household members, and wealth. Even after controlling for all these factors, Indigenous people were still over fifty percent more likely to have antibodies against COVID-19 in their blood than their white counterparts. Prevalence of antibodies against COVID-19 according to ethnicity and economic status Prevalence of antibodies against COVID-19 Ethnicity Survey 1 Survey 2 Branco (white) 0.7% 1.4% Pardo (Brown) 2.4% 3.6% Preto (Black) 1.2% 3.4% Amarelo (East Asian) 1.3% 2.1% Indígena (Indigenous) 4.2% 6.4% Wealth Quintiles Poorest 2.1% 2nd 1.8% 3rd 1.5% 4th 1.5%
3.7% 3.4% 2.5% 2.5% 427
Wealthiest
1.0% 1.7%
The Pardo population, those with mixed European, Black, and Indígena ancestry, had the second highest prevalence of COVID-19 antibodies at 2.4 percent in the first survey and 3.6 percent in the second. In both surveys, participants living with many household members were more likely to have antibodies against COVID-19 than those who lived with fewer people. The most surprising finding to researchers was the geographical concentration of cities with the highest antibody prevalence. Six of the cities with the highest antibody prevalence were found along one 2000 kilometer stretch of the Amazon river. COVID-19 first appeared in the north region of Brazil in the city of Manaus in March. The virus then spread along the main river-boat routes on the Amazon. River boat trips there are often long and overcrowded, providing an optimal vehicle for transmission of the virus. One study found that as the number of boats leaving Manaus to a given city increased, the number of days until the first case was reported in that same city decreased. Between the two studies, an increase in antibody prevalence occurred in most cities. In Boa Vista, a city in Northern Brazil, the prevalence increased from 4.7 percent in the first survey to 25.4 percent in the second. One city, Breves, was a notable exception and was the location of a decrease in antibody prevalence. The city had an antibody prevalence of 25.4 percent in the first survey and a prevalence of 12.2 percent in the second. This could be explained by rapidly decreasing antibody levels after infection with COVID19, especially among individuals who do not show symptoms. This study found that only one in ten infections were reported as COVID-19 cases in these 133 sentinel cities. This could even be an underestimate of the number of people previously infected with COVID-19 due to the quickly decreasing antibody levels that may not be detected by the test. Brazil’s response to COVID-19, much like the response in the United States, has been marked by a lack of leadership and a refusal to follow scientific evidence. The President of Brazil, Jair Bolsonaro, opposes social distancing measures and has promoted the use of hydroxychloroquine, despite no evidence that it is an effective treatment for COVID-19. Much like U.S. President Trump, 428
President Bolsonaro of Brazil did not change his handling of the pandemic even after he was infected with the virus in July. Upon testing positive, President Bolsonaro released a video showing him taking hydroxychloroquine. Testing in Brazil is restricted to the most severe cases of COVID-19. Even with over 150,000 deaths as of October 11, 2020, there is evidence that this is an undercount. Since the beginning of the pandemic, there has been a high rate of turnover of health ministers. Dr. Luiz Mandetta was fired in April due to a disagreement with President Bolsonaro over social distancing measures. Dr. Nelson Teich who replaced Dr. Mandetta quit in May following disagreements with the President over social distancing and the use of hydroxychloroquine. General Eduardo Pazuello, who has no training in public health, served as interim Health Minister from May to September. He became Minister of Health in the middle of October and has recently tested positive for coronavirus. Due to this lack of leadership from the President and at the Federal level, state governors and other local leaders have had to implement restrictions such as the closure of schools and nonessential businesses and have been the ones to recommend the use of face masks. To ensure that COVID-19 does not continue to impact marginalized groups and those with fewer resources disproportionately, the Federal Government in Brazil must follow scientific evidence and implement COVID-19 mitigation measures such as widespread testing, contact tracing, physical distancing, and the use of face masks. This article originally appeared in Forbes and is available online here: In Brazil, New Study Shows The Poor And Indigenous Suffer The Most From COVID-19
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Britain's Moral Bankruptcy Over COVID-19 Vaccines Think Global Health | October 27, 2020 | Article
The COVID vaccine challenge in the United Kingdom—where young, healthy individuals are deliberately infected with SARSCoV-2—is no gutsy gambit or bold step forward as some have described it. It is instead an act of cowardice and desperation by a government that has failed miserably to contain the spread of COVID-19. The human challenge study, announced last week in a press statement from Imperial College London, would recruit between thirty to fifty healthy volunteers age eighteen to thirty. Though the study design has yet to be finalized, the first phase of the trial will likely expose participants to increasingly large amounts of SARSCoV-2 to determine how much of the virus it takes to cause them to develop COVID-19. In subsequent phases, the pharmaceutical services company overseeing the trial, Open Orphan, says that it’s likely that several vaccines will be tested on volunteers and compared to a placebo. Volunteers who do become ill would be treated with antiviral drugs, like remdesivir, and potentially other drugs like dexamethasone. The trial, which some have lauded as a moral imperative, is actually a moral mistake. It's both unethical and unnecessary, and it's likely to prove uninformative as well. The Questionable Ethics of the Approach There is no evidence that remdesivir, nor any other treatment currently available, can stop a person who is ill from dying. Interim results from the World Health Organization’s (WHO) massive Solidarity Therapeutics Trial released earlier this month show that remdesivir and three other antiviral treatments have little impact on the course of the disease. Patients prescribed the drugs weren’t any likelier to survive than those who weren’t given access to the treatments, nor were their hospital stays any shorter. Dexamethasone
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may save a few people in late stages of the disease, but there is nothing to suggest that it can save everyone infected with the virus. Groups recruiting volunteers for the study have been underselling the risk to potential participants, claiming that “the risks are low and the potential benefits huge.” But we know in fact the opposite is true. The benefits in terms of knowledge gained may be inconsequential while the risk to volunteers is substantial. While young people infected with the virus may be more likely to avoid hospitalization than older adults, they often do become sick and symptomatic enough to be in bed for weeks and sometimes months. Follow-up exams have shown that many who recover are left with severe heart conditions, including inflammation and damage to the heart muscle itself. And death is an all-too-common outcome of COVID-19—even in the young. Without a real understanding of the risk involved and with a significant financial draw for volunteers during a time of widespread unemployment—participants may receive up to £4000 or the equivalent of almost a two-month salary in the United Kingdom— it is hard not to see the trial and the push to knowingly infect healthy individuals as immoral. This is especially true when one considers that the trial itself is entirely unnecessary. The number of new daily infections in the United Kingdom, in the United States, and in many other countries continues to rise sharply—the U.K. reached an all-time high of 26,000 new cases in a single day last week while the U.S. daily count peaked at 85,000 new infections. There is no need to deliberately infect the healthy in a laboratory setting when we are all at risk of infection out in the wild, where we live and work each day. The clinical vaccine trials currently underway take place in the real world, with volunteers who are exposed to infection through their routine daily behavior, as we each are exposed whenever we step outdoors. One seriously doubts that a trial of thirty to fifty healthy individuals will tell us anything that the larger and more carefully conducted clinical trials won't. My guess is we will learn very little. Challenge the Virus, Not the Volunteer The move to human challenges has more to do with political expediency than scientific necessity. It isn’t as if the world doesn’t know how to stop this disease. One need look no further than the success of Australia, New Zealand, China, and Taiwan to see that 431
basic public health measures—enforced mask-wearing, social distancing, and mandatory quarantine and isolation—could keep new infections and deaths close to zero. British citizens have paid a high price in morbidity and mortality, which are among the highest per capita in Europe. Desperate times like these may call for desperate measures—but not pointless ones. When I was a child and Britain was just emerging from the Second World War, I can remember how it was perceived by the rest of the world. Britain stood out for its persistence, stoicism, perseverance and bravery. The country’s reputation has now suffered because its government first proposed the murderous theory of herd immunity, and then, attempted to right its mistakes, relaxed its lockdown efforts far too soon. This challenge study is taking responsibility for his failures, Prime Minister Johnson is trying to accelerate the science with this Hail Mary pass in American football—a desperate if flashy fling that has little chance of success and only something you'd try when you've already lost. It will not solve the pandemic. It will only put more people at risk— deliberately and knowingly. The U.K. vaccine challenge isn’t the only one being considered. Belgium and the United States are both considering the same approach. But it is not too late to stop that from happening. The time is now to pressure our governments to take forceful action to keep all of us safe, not by treating us like human guinea pigs, but by implementing mandatory mask wearing and other public health measures no national leader in the United Kingdom or the United States have yet implemented. This article originally appeared in Think Global Health and is available online here: Britain's Moral Bankruptcy Over COVID-19 Vaccines
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Large Contact Tracing Study Reveals Efficient COVID Transmission Within All Age Groups From 5-10 Years On Up Forbes | October 27, 2020 | Article
The first ever large scale study using contact tracing data from two states in India provides critical new information about the virus that causes COVID-19 and how it spreads. Using data from over 85,000 confirmed COVID-19 cases and their 575,071 contacts, the study found that the virus spreads most often among people in the same age group and can cause illness and death even among young people. While previous studies have looked at how the virus spreads in nursing homes and in prisons, this is the first time that we have information about how it spreads among the general population. India and the United States are different settings, however, it is likely that there is a great deal of similarity in how the virus spreads within the two countries. The two states of Andhra Pradesh and Tamil Nadu in India implemented robust contact tracing systems in response to the pandemic. Strong contact tracing systems can be used to both decrease the spread of the virus and to provide valuable information about how it spreads. This information is crucial to inform evidencebased policy choices such as whether and how to safely open schools and to what extent businesses should be open. To identify positive cases of COVID-19, these two Indian states test anyone seeking medical care for severe acute respiratory illness or for flu like symptoms. After a person tests positive for COVID19 vis reverse-transcriptase polymerase chain reaction (RT-PCR), healthcare workers follow-up with their contacts everyday and test them five to fourteen days after contact with the index case, regardless of whether they have symptoms. Using this data from the two states in India on index cases and their contacts, researchers found that on average, traced contacts were 1.3 years younger than the index case and more likely to be 433
female. The probability of an index case transmitting the virus to a contact ranged from 4.7 percent in low risk encounters to 10.7 percent in high risk encounters, defined as close social contact or physical contact without any protective measures. The study also found that only 17.9 percent of deaths due to COVID-19 in the two states in India occurred in those ages 75 and above. In comparison, in the US 58.1 percent of deaths occurred in individuals 75 years and above. For the first time, we have conclusive evidence that the virus spreads most often among people in the same age range. There is no age group that is protected against getting infected by or being able to transmit the virus. Children spread the virus to other children, university students spread the virus to other university students, and working age adults spread the virus to other working age adults. This finding was especially strong in children ages zero to fourteen and in adults over the age of sixty-five. Children age zero to four infected twenty six percent of other children in that age group with whom they had contact. Similarly, children between the ages of five and seventeen infected eleven percent of their peers with whom they had contact. While the spread of the virus occurs most often within the same age groups, it is also possible for the virus to spread from younger people to older adults. Children age five to seventeen infected six percent of adults ages sixty-five to seventy-four with whom they had contact. While there is often an assumption that COVID-19 cases among children and young adults will be asymptomatic or mild, that is not necessarily true. Asthma, obesity, type II diabetes, and genetic susceptibility can all increase a person’s risk for severe COVID-19 illness. These conditions are found in all age groups of the population. Estimates suggest that up to thirty percent of Americans have underlying conditions that put them at higher risk for severe COVID-19 illness. This has important implications for the reopening policies of elementary schools, high schools, and universities and for whether parents will choose to send their children to in person school, if that option is available. In places where in person learning is taking place, the decision about whether to send children back to school is mostly up to parents. In person learning can cause a spike in COVID-19 cases. Just two weeks after opening, a single high school in Utah saw 90 434
cases of COVID-19. So how should parents choose whether to send their children back to school in person? To do this, families can start by considering three things: transmission in the area, the risk profile of your child and your family, and what kind of protective measures are being put in place. Although making decisions regarding keeping our families safe in the context of COVID-19 is new, we make decisions about keeping our families safe everyday. Thinking about the weather as an example can be helpful when gauging risk from COVID-19. If the risk of infection in your community is extremely high, think about what you would do if a hurricane were coming: stay home and stay safe. If the risk of infection in your community is high, think about what you would do in a thunderstorm: it is dangerous outside so you would go outside only when absolutely necessary. If the risk of infection in your community is moderate, think about what you would do in a heavy rainstorm: you probably wouldn’t go outside unless you are wearing a raincoat, rainboots, and brought an umbrella. The same goes for what you should do in the pandemic. Before going outside make sure you have a mask, gloves, and hand sanitizer. If there are near zero infections in your community, think of it as a bright sunny day: feel free to go out and enjoy. Even if COVID-19 risk in your community is extremely low right now, remember that just as the weather can change quickly so too can the risk of COVID-19 infection in your community. Brown University created a tool that uses zip code and activity type to assess the risk of different activities across the country. A report recently released by the US Centers for Disease Control (CDC) further challenges the notion that COVID-19 only impacts older adults. Between January 26 and October 3, 2020, the CDC estimates the US had 299,028 more deaths due to the pandemic than the typical number during the same period in previous years. Excess deaths are the deaths over and above what is expected in a certain time frame, using data from previous years as a baseline. Two-thirds of the excess deaths were attributed to COVID-19 while the other one-third were attributed to other causes. Excess deaths from the pandemic disproportionately affected people of color. The highest average increase in deaths over this period was found among Latinx people at 53.6 percent and among Black people at 32.9 percent. Most surprisingly, the largest percentage increases were among adults 435
aged twenty-five to forty-four. In this age group there was a 26.5 percent increase in deaths. The high rate of excess death among twenty-five to forty-four- year olds serves as a stark reminder that the pandemic is having a tremendous negative effect on younger adults as well. Until now, the extent to which children and younger adults can be infected with and spread the virus has been unclear. The new contact tracing study in India and data from the CDC confirms that children and young adults can be infected with and spread the virus. This additional knowledge can help both policymakers and individuals make choices to keep their families and communities safe. Making decisions based on evidence is the only way to avoid additional, unnecessary deaths from COVID-19. This article originally appeared in Forbes and is available online here: Large Contact Tracing Study Reveals Efficient COVID Transmission Within All Age Groups From 5-10 Years On Up
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Eli Lilly Stops Antibody Trial In Hospitalized COVID-19 Patients Forbes | October 28, 2020 | Article
How do we understand the decision of the National Institutes of Health (NIH) to halt the Eli Lilly antibody treatment trial? Is it a sign that monoclonal antibodies to SARS-CoV-2, the virus that causes COVID-19, are ineffective? The Lilly trial combined two drugs designed to interfere with SARS-CoV-2 infection: remdesivir, a drug that is intended to inhibit the viral RNA polymerase, and the Lilly drug, a monoclonal antibody that is meant to prevent the spread of the virus within an infected person. The trial participants were all hospitalized volunteers with serious complications from COVID-19. The intent of the trial was to speed up recovery and prevent further progression of the disease. I do not have information regarding the exact endpoints and whether or not they include prevention of progression, the need for intensive care, and death. Why two drugs? The presumptive benefits of remdesivir make it a drug of choice for most patients with COVID-19. A recent WHO study of remdesivir conducted in many countries found that remdesivir had no effect on hospitalized patients—neither with respect to progression nor more serious disease and death. This finding did not surprise me, as the effects of the drug even at their best are described as weak to marginal. Nonetheless, most volunteers in a study of a new drug would rather receive remdesivir along with the new drug. The NIH halted the trail because no effect on the hoped-for endpoints was observed. Patients on remdesivir fared as well (or as badly) as patients on the two-drug combination. In other words, the addition of the Lilly drug had no measurable effect. The preliminary report mentions no adverse events that occurred as a result of the two-drug combination. Is this the end for the Lilly drug? Not at all. Drugs designed to stop virus replication should work, if they work at all, during the 437
phase when the virus is most active. The figure above illustrates what we understand about SARS-CoV-2 growth in an infected person. There is a phase of a few days to a week following infection when virus growth is very slow. This is followed by a second phase when virus growth is rapid and the concentration of virus particles in nasal fluids, the lung, and the intestine is very high. That is followed by a third phase in which the growth of the virus is typically contained and reduced to nothing or near nothing. Antiviral drugs should work during the incubation phase and the phase of rapid growth, but not after the virus growth is controlled. Most people infected with SARS-CoV-2 do not experience symptoms until after the peak of virus replication. Even then the symptoms may be mild and not require hospitalization. It is only later, after the virus is no longer replicating, that the most serious symptoms appear—those that require hospitalization. Treating hospitalized COVID-19 patients with antiviral drugs designed to impede a virus that is no longer replicating is the equivalent of the proverbial closing the barn door after the horse is gone. When, then, should antiviral drugs be used? The answer is very early on in infection, or even before infection occurs. The obstacles that prevent us from using drugs early on in infection are related to how and who we test for infection. The people tested most frequently are those who have symptoms. By then the virus is already on the way out, and much of the damage the virus can do is already in progress. (There may be an exception for people who fail to make good interferon responses.) There is a potential solution: frequent universal testing, whereby most people are tested every two to three days using tests that yield answers in 5 to 10 minutes. Such a testing regime, which I believe to be the surest way forward for contagion control, will identify those in the earliest stage of infection. Identification of an infected person should be followed by immediate treatment. Then and only then might antiviral drugs work, be they chemicals like remdesivir or monoclonal antibodies. Antiviral drugs may also prevent infection, as is currently the case with HIV. Monoclonal antibodies are used to prevent respiratory syncytial virus (RSV) infection in infants. Antimalarial drugs are used to prevent malaria infections. The caveat is that such drugs must undergo rigorous evaluations for safety, for they are intended to be 438
used on healthy people who are not yet infected. The safety profiles of treatments for the healthy are much more stringent than those required to treat the ill. I suspect that Lilly will go on to test their drug in those reporting mild symptoms. The first issue of that trial design is that only some of those with mild symptoms will be detected early enough for the drug to have an effect. An even greater issue is that the great majority of those with early cold-like symptoms—perhaps 80 percent or more—will recover from the cold and not progress to serious disease whether given a drug or not. Therefore, any possible therapeutic benefit will be diluted by the great majority of those that will not progress in any event. Such is the life of a drug developer. The only way I see such trials as possible is the advent of very low cost, universally available rapid virus tests to identify those recently infected. Even then, the signal to noise ratio will be low. In conclusion, this is not the end of the line for the Lilly drug, but it is the beginning of a very long and rough road for not just their drug, but any other COVID-19 antiviral. This article originally appeared in Forbes and is available online here: Eli Lilly Stops Antibody Trial In Hospitalized COVID-19 Patients
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New Study Offers More Evidence That Immunity To COVID-19 Fades Quickly Forbes | October 28, 2020 | Article
This is the first article in a four-part series on fading immunity to COVID19 and the flu—the science behind it, and the implications it has for vaccine development and the pandemic at large. More evidence has emerged that immunity to COVID-19 is quick to fade—in people of all ages, but more so for the old than the young. A recently published British study, currently undergoing peer review, found that the prevalence of COVID-19 antibodies across England has dropped more than 26 percent in three months. The results come from 365,000 home tests that were sent to participants in three rounds, distributed randomly each time. Antibody testing, which measures the proteins your body produces to ward off a specific pathogen rather than live virus, has been used throughout the pandemic to pick up on infections that standard PCR tests miss. This is especially useful in detecting socalled silent spreaders—the asymptomatic carriers who don’t get tested because they don’t get sick, but may cause as many as 80 percent of infections. The most precipitous decline in antibodies observed in the British study, in fact, was in people who didn’t report a history of COVID-19 symptoms—in other words, asymptomatic participants. Antibody levels in this group dropped nearly two thirds between the first round of testing and the last, while those in the people who tested positive for the disease decreased by a bit more than 20 percent. Another notable drop was seen in a population that, if these antibodies are protective, need them most: participants 75 years of age and older. Their antibodies decreased by nearly 40 percent. In participants belonging to the youngest age group (18-24), the decline was much smaller at about 15 percent. Only in one group—
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health workers—did rates hold steady; this may be due to their increased exposure to the virus. The British study is the latest to join a growing body of research that arrives at the same conclusion—that the antibodies we produce against SARS-CoV-2, the virus that causes COVID-19, are shortlived. One study, published in Nature Medicine in June, measured antibody levels in a group of 37 COVID-19 patients three to four weeks after initial infection, then two months thereafter. Surprisingly, about 20 percent tested negative for antibodies altogether—indicating either total disappearance or levels so low as to be undetectable. These findings were echoed in another study published in JAMA last month on healthcare personnel who work directly with COVID-19 patients at Vanderbilt University Medical Center in Nashville, Tennessee. Nearly 60 percent of those who tested positive for anti-SARS-CoV-2 antibodies in April tested negative only two months later. Again, their antibody had levels dropped so sharply, they were no longer detectable. Since it is unknown whether these antibodies are even protective against the virus in the first place, it is difficult to say with certainty whether the swift dissipation of the antibody response leaves the body vulnerable to reinfection. But it would hardly be surprising if it did. Besides occasionally morphing to become highly transmissible and lethal threats to humankind, seasonal coronaviruses have another signature move—their ability to reinfect the same person not just once, but two or three times, as documented in research from the 1970s and 1980s and a much more recent 2018 study conducted in Kenya. There have been reports that the T cell response against coronavirus infections, including those caused by SARS-CoV-2, is longer lasting than the antibody response. T cells are a type of white blood cell that, like antibodies, are critical to our ability to prevent subsequent encounters with a harmful virus. In the case of seasonal cold-causing coronaviruses, however, T cell memory has little to no effect in preventing reinfection, which can occur yearly like clockwork. An absence of protective antibodies doesn’t augur well for T cell immunity, no matter how you spin it. A handful of COVID-19 reinfections have already been confirmed via genome sequencing in Hong Kong and the United 441
States and reported anecdotally in Europe, India, and South Korea. Now that a second wave of infections has overwhelmed Europe and a third is crashing over the United States, we’d be remiss to dismiss the possibility that subsequent waves of reinfection might exacerbate present and future outbreaks. Not only does this all but dispel the dangerous fantasy of herd immunity, it also complicates a near inevitability that actually looms large on the horizon—the coincidence of the ongoing COVID-19 pandemic with the arrival of seasonal flu. Antibodies against COVID-19, it turns out, aren’t the only ones to dwindle rapidly. Those produced by standard influenza vaccines, new studies show, disappear at a similar clip. I will explore the implications of this finding—both in the context of influenza research and the current health crisis—in the next part of this series. This article originally appeared in Forbes and is available online here: New Study Offers More Evidence That Immunity To COVID-19 Fades Quickly
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The FDA Will Not Inspect Vaccine Production Plants Forbes | October 29, 2020 | Article
Approval of a vaccine by the Food and Drug Administration (FDA) typically requires inspection of the vaccine’s manufacturing plants. In a COVID-19 world, this will not be the case. COVID-19 vaccine candidates will get a pass on FDA plant inspections, according to Bloomberg. As candidates reach the final phases of testing, emergency use authorization will be granted without pre-approval inspection, said FDA Director of Viral Products Jerry Weir. Beware of lower safety standards with fast-tracked COVID-19 treatments. Vaccines and therapies are being rushed through the testing and approval process without substantial evidence of success. Shorter test periods reduce the confidence that they will be safe and effective. I have described some of the uncertainties and potential hazards of rushed trails elsewhere. Under normal circumstances, the FDA requires several batches of vaccines and drugs to be made, all meeting the same safety, consistency, and potency standards using the same facilities as will be used to sell the drug or vaccines. These requirements prevent quality control issues on the side of the pharmaceutical company. Drug and vaccine manufacturing plant inspections are routine and any violation of protocols is cited. Just last year, an Eli Lilly pharmaceutical plant was cited by the Food and Drug Administration (FDA) for quality control issues, according to Reuters. Sources close to the situation told Reuters that Eli Lilly had falsified records pertaining to FDA manufacturing standards. That same Eli Lilly plant is set to manufacture a COVID-19 treatment used by the president during his infection. All biological drugs including vaccines, antibodies, and other proteins are subject to additional scrutiny because the preparations are likely to vary from batch to batch. Several of the leading vaccine candidates deploy entirely new technologies, technologies that have not been previously approved for human use. Verification that a 443
new manufacturing process yields the desired product is especially important. The rushed time frame also obligates the FDA to forgo stability tests of the new vaccines, if they are to be used before the end of this year or early2021. There simply is not time to do what is routine. Pushing COVID-19 vaccines and treatments through the approval process may have already contributed to health complications. Major vaccine trials like AstraZeneca and Johnson & Johnson paused testing due to severe illness in some participants. AstraZeneca has since restarted, but concerns about short and longterm health safety continue. The recent history of other pharmaceuticals pushed through the emergency use authorization process is instructive. Hydroxychloroquine was granted authorization back in March. The FDA’s authorization letter cited only a 36-person French study. Three months later, post-authorization monitoring found an increased risk of heart problems in hydroxychloroquine users, in addition to little evidence of reduced COVID-19 symptoms. The authorization was promptly revoked. Remdesivir was recently approved by the FDA. A recent WHO controlled trial found no benefit of remedesivir for hospitalized patients in a multi-country study. The dangers of unregulated COVID-19 drugs and vaccines are clear and present. Normal circumstances require years for a vaccine to be produced. I know pandemic fatigue is setting in for many. Many hope for a vaccine to stop the disease instantly. They will be sadly disappointed. Even if a vaccine is approved early next year, and even if it is safe and effective, the hoped-for relief will be months in coming. People may forgive the failure of a vaccine because of the intense difficulty of preventing COVID-19 infections. They will not forgive a vaccine that endangers their life because of manufacturing errors. People my age still remember the Cutter laboratory disaster with improperly inactivated polio vaccine preparations in the 1950s. FDA regulations are ultimately in place designed to protect us. They should not abrogate the essential duty for speed under any circumstance. This article originally appeared in Forbes and is available online here:The FDA Will Not Inspect Vaccine Production Plants
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New Research On Flu Vaccines Sheds Light On COVID-19 Vaccines Forbes | October 28, 2020 | Article
This is the second article in a four-part series on fading immunity to COVID-19 and the flu—the science behind it, and the implications it has for vaccine development and the pandemic at large. One of the reasons we get flu shots annually is because new strains of influenza emerge and circulate year in and year out. But another reason, a new study shows, is that vaccine-induced antibodies against influenza tend to fade relatively quickly, most within a year or less. For many of us, this likely comes as a surprise. If we’re vaccinated against a particular strain of influenza, we’d expect any protective immunity we gain to at least ward off the same strain the following year. Evidently, this isn’t the case—a discovery that gains all the more significance now that fast-fading immunity appears to be a defining, though still perplexing, feature of COVID-19. The study in question, published in Science magazine earlier this month, examined the activity of bone marrow plasma cells which play a critical role in sustaining the body’s long-term antibody response, in 53 volunteers who were vaccinated between the years 2009 and 2018. While the number of bone marrow plasma cells produced in patients as part of their natural immune response remained fairly consistent over time, those induced by vaccines declined to baseline levels after one year. Perhaps the most immediate implication of these findings, at least in the realm of influenza research and clinical practice, is that the optimal time for vaccinating against the flu might be later than previously thought. A 2018 study reached a similar conclusion, but by alternate means, focusing specifically on vaccine efficacy within the span of a single flu season. People vaccinated later in the season were less likely on average to eventually test positive for the flu—a correlation that runs contrary to the general assumption that when it comes to getting your flu shot, the earlier, the better. 445
The broader implications extend to the current pandemic and the ongoing race to develop COVID-19 vaccines. While SARSCoV-2, the virus that causes COVID-19, doesn’t mutate nearly as much as influenza viruses, recent research shows that the antibodies we produce to fight it can dwindle to undetectable levels in mere months. The challenge faced by any vaccine candidate, then, is to outperform the immune system in this regard. Yet even with flu vaccines, the Science study tells us, this has yet to be accomplished. Several of the COVID-19 vaccines either undergoing large-scale clinical trials around the world or being administered in China and Russia are manufactured using adenovirus vectors, a technology designed to trick the body into activating its defenses by slipping a sliver of genetic material from SARS-CoV-2 into a run-of-the-mill cold-causing virus. Until now, no such vaccine has been brought to market that prevents disease in humans. Even if one of these candidates becomes the first, it won’t have a particularly long shelf life; once the body begins making antibodies to the adenovirus vector itself, it can not be used as a booster the following year. Try as we might, we cannot continue to create goals and timelines for COVID-19 vaccine development—much less vaccine distribution—that gloss over the immunological complexities that make this virus, and our attempts to protect ourselves from it, so problematic. Thanks to scientific and medical progress we’ve made since SARS, the first coronavirus pandemic, we already know an impressive amount about SARS-CoV-2. Yet a sizable gulf remains between what we know and what we’re doing in response. In the next part of this series, I will discuss another phenomenon that will affect our ability to develop and deploy vaccines against COVID19—autoantibodies. This article originally appeared in Forbes and is available online here: New Research On Flu Vaccines Sheds Light On COVID-19 Vaccines
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November 2020
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New York City Limits The Chances For InPerson Learning For Students Forbes | November 2, 2020 | Article
Remote schooling has been a challenge for every parent during this pandemic. For a lucky few who have the luxury of not working or are able to work from home, school closures have been an added stress, but a manageable one. For others parents in need of the income but working for companies that reject the notion of working from home, remote schooling has been a near impossibility. Still, parents have made it work, mainly because they had no choice. In September, seventeen of the twenty biggest school districts in the US—Los Angeles, Chicago, Miami, Houston, Philadelphia, Baltimore, to name just a few—were only offering remote learning. But the largest district of them all, New York City, was an outlier. The district offered students hybrid, in-person schooling almost from the start, with a promise that parents who chose remote learning could opt back in to in-person learning every semester. The move to reopen school doors was largely born out of a desire to do right by all students, especially vulnerable children who use schools as sanctuaries from troubles at home and those who are unable to access classes online. But now New York City is changing its policy and parents are being forced to make an almost impossible choice: opt in to inperson learning before November 15— while new infections are skyrocketing and the pandemic surges across the country—or keep students at home for the next eight months, until the end of the school year in June. This is a cruel move for parents who hoped to keep their children home over the winter months—when COVID infections were widely expected to rise—but return them to school in spring when classroom windows could be opened, kids could play or study outdoors, and infection rates would hopefully dip again, as they did over this summer. 448
While few studies today show schools as a source of new outbreaks in the United States, that is likely due to the fact that most schools are operating remote-only or with a very limited number of students learning in-person. We do know, from a number of studies, that children are just as infectious—if not more infectious—than adults. Indeed, the first ever large scale study using contact tracing data shows us that no age group that is protected from becoming infected by SARS-CoV-2 or spreading the virus. Children spread the virus to other children, and students spread the virus to other students. Studies have also shown us the devastating impact of keeping kids at home and what another eight months of remote schooling may mean for the wellbeing of families. When parents can no longer send their children to school, problems otherwise unrelated to the disease arise, affecting everything from household income and employment to emotional and mental wellbeing. The majority of parents, many of whom had to quit their jobs or cut back on hours, are already burnt out from juggling competing demands of work, life, and remote learning. The harm to children is also widely recorded, especially the toll on mental health. A survey by the NYC Department of Education in the summer suggested that parents of at least half of the 1.1 million students in New York’s school system wanted to return for in-person learning in the fall. In the end, only around 238,000 students showed up. The lack of students isn’t a reflection of a lack of desire to return to school. Instead, I believe it has more to do with the fear many parents must have around the path the pandemic is now taking in the US, with new daily infections reaching all-time highs. The path of the pandemic will be nor more clear by November 15. Forcing parents into a final choice on in-person schooling by that arbitrary date is an irresponsible and potentially dangerous mistake. This article originally appeared in Forbes and is available online here:New York City Limits The Chances For In-Person Learning For Students
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Kushner Comments Suggest COVID-19 Decisions Are Politically Motivated Forbes | November 2, 2020 | Article
At the start of the summer, the federal government released guidelines to reopen the US economy, then left it to the states to figure out how the job would be done. The poorly organized reopening eventually resulted in a surge of new infections and thousands of COVID-19 related deaths. While there is a constitutional argument that public health is a state responsibility, recently released audio of Jared Kushner suggests deferring action on reopening to the governors was a political calculation — a successful reopening could be credited to the President, but any failure would be blamed on the governors instead. In an interview with journalist Bob Woodward, Kushner discusses the President’s political strategy regarding reopening. “The president...basically [says] no, no, no, no, I own the opening. Because again, the opening is going to be very popular,” Kushner says. “If it opens in the wrong way, the question will be, did the governors follow the guidelines we set out or not?” This raises questions as to whether all federal policies on COVID-19 were selected with Election Day in mind. On testing, for example, “the states have to own the testing. The federal government should not own the testing…it’s got to be up to the governors,” says Kushner in an apparent attempt to shift any blame for testing failures onto the states. With Election Day approaching, the Trump administration seems to be pinning its reelection odds to this COVID-19 blameshifting. The plan is simple: the federal government sets out guidelines for reopening and testing but provides little substantive support; if the states fail to control their outbreaks, they take the blame, and the federal government moves on. Even as Dr. Fauci and other public health experts were advising Americans to stay home, wear masks, and get tested to keep the outbreak under control, the Trump administration undermined their 450
efforts to get people back to work. “We’ve now put out rules to get back to work. Trump’s now back in charge. It’s not the doctors,” Kushner said. He continues, “The guidelines…[were] like Trump getting the country back from the doctors.” Getting people back to work was a last-ditch effort to revive the dying economy. Ironically, sending people back to work caused the pandemic to strike back with a vengeance. Compare Trump’s blame-shifting approach to COVID-19 to President Bush’s approach to pandemic preparedness. In the wake of the 9/11 terror attacks and deadly diseases like Avian Flu and SARS, Americans grew more cautious about biological warfare and pandemics. In response, Bush created a national pandemic preparedness strategy. This included a UN partnership on pandemic information transparency, launching a national biosurveillance initiative, stockpiling drugs and vaccines, increasing funding for pandemic preparedness, developing emergency plans for states and localities, and more. President Bush approached pandemics with federal responsibility. He integrated international cooperation, federal response, and local preparedness in his plan to beat the disease. Alternatively, Trump officials were aware of the virus as early as November 2019 and did not address pandemic preparedness. The federal response was limited to meager stimulus checks and policy guidelines, then states and localities were left to figure out the pandemic response on their own. With the election looming and the pandemic without an end in sight, it seems the fate of the country rests in the hands of the voters. Trump seems content to allow the virus to continue spreading as a vaccine works towards development. Recently, it seems the President is willing to ignore the threat entirely, pushing a narrative that COVID-19 is on the decline. We know where his approach has led us, with positive COVID-19 test rates higher than ever in the United States. If we want a different outcome than the one we have today, we must vote tomorrow with our health and our future in mind. This article originally appeared in Forbes and is available online here:Kushner Comments Suggest COVID-19 Decisions Are Politically Motivated
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What Are Autoantibodies? The Latest Risk Factor For Severe COVID-19 Forbes | November 3, 2020 | Article
This the third and final article in a three-part series on fading immunity to COVID-19 and the flu—the science behind it, and the implications it has for vaccine development and the pandemic at large. Read the first two articles here and here. We know that people who are older, obese, immunocompromised, pregnant, or diabetic are at greater risk of developing severe COVID-19. Now evidence has emerged that establishes another determinant of risk—something that isn’t inherited, but acquired over a lifetime. That is the inability to mount a robust interferon response. Interferons play a critical role in defending our bodies against invading pathogens like SARS-CoV-2, the coronavirus that causes COVID-19. They function as warning signals, alerting the immune system whenever an intruder is on sight. Some people, however, develop what are called autoantibodies against their own interferons—and research shows that they’re more susceptible than most to the more devastating effects of COVID-19, including death. If antibodies are the defenders our B cells produce to battle oncoming infection, autoantibodies are defectors that do precisely the opposite. Rather than detecting and debilitating viral genetic material, autoantibodies target us. A new study, made available on medRxiv but currently undergoing peer review, examined 52 patients with severe COVID-19 and found that nearly half had autoantibodies of some kind. In those most critically ill—specifically the top 50 percent—that number exceeds 70 percent. None of the patients who participated in the study reported a history of autoimmune disease, but it may be the case that survivors 452
continue to be prone to severe COVID-19 symptoms upon future encounters with the virus—potentially even worse than the first time around. The flipside is that they might benefit from drug therapies for conditions like lupus. Autoantibodies are more prevalent in older adults than younger, which might explain, at least in part, why COVID-19 is, too. If the results of this study aren’t momentous enough to impact how we treat COVID-19, at the very least they have bearing on how we diagnose and prevent it. First thing’s first, people who develop serious COVID-19 symptoms, whether they’re hospitalized or not, should be tested for autoantibodies against interferons and other relevant targets. Those who test positive, now that we know they’re more vulnerable to critical illness or death, must receive priority status for vaccinations and be cared for accordingly. More generally, people aged 65 and older should be routinely tested for anti-interferon antibodies as part of their annual checkup. Again, those who test positive will know to be especially cautious to protect themselves from infection. After all, regardless of whether the tide of the current pandemic is turned by widespread vaccination or any other deterrent, there’s no telling how long we’ll be dealing with COVID-19 in some form—particularly those most vulnerable. Any precautions we can take to prevent further spread, we should, and with haste. The last two articles in this series—on fading natural immunity to COVID-19 and fading vaccine-mediated immunity to influenza—feature research that puts into perspective the timeframe of infection, disease, and potential protection. For many, all of the above will tend towards the short-term, which has manifold implications for our methods of preventing and vaccinating against COVID-19. But in the months to come, more studies will be conducted that give us a clearer understanding of the long-term effects of this disease. These in turn will force us to reconsider our methods once more. The issue of autoantibodies is one to watch, as well as one we
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should act to address sooner rather than later. If you have autoantibodies against interferon, you may be in it for the long haul. This article originally appeared in Forbes and is available online here: What Are Autoantibodies? The Latest Risk Factor For Severe COVID-19
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Lancet Study Suggests U.S. Is Massively Undercounting COVID-19 Cases Forbes | November 4, 2020 | Article
While most Americans have their eyes focused squarely on the results of the Presidential election, there’s another number that we should be careful not to lose sight of: the skyrocketing number of new SARS-CoV-2 infections across the US. Over the past week, the country has seen record highs, with almost 100,000 new cases every single day. Those numbers are distressing enough, but the real number of new infections is likely much, much higher—far closer to a million newly infected each day than one hundred thousand. Most will never know they were infected, likely spreading the infection to family and friends as well as to strangers encountered while not wearing a mask. A recent Lancet study suggests we are grossly undercounting the number of Americans with COVID-19. Researchers examined data from 28,000 patients who received dialysis in July and were tested monthly for a variety of markers, including for SARS-CoV-2 antibodies. The routine testing gave the researchers a regular, unbiased assessment of SARS-CoV-2 seroprevalence in the random sampling of patients. What they found was that roughly ten percent of patients had antibodies to the virus, but only 9.2% of that group had been officially diagnosed. This confirms something that I have long thought true: multiply whatever number of new COVID-19 infections in your community by ten, because this is likely the true number of new infections. That means, in the United States today, we don’t have 92,000 new infections, we have 920,000. The finding highlights how important it is for each of us to take responsibility for our own health and wellbeing—avoiding large gatherings, especially indoors, maintaining a distance from others, and wearing a mask. It also underlines the critical need to immediately implement a universal testing system using rapid antigen tests and developing a support system to allow those who 455
test positive to isolate and avoid infecting others, without risking their jobs or livelihoods. Others have done this quite effectively, most notably in Asian countries like China, Singapore, South Korea, and Taiwan. But some European countries are now following suit. Over the weekend, Slovakia administered rapid antigen tests to two-thirds of its population. Nationally, one percent of the population was found to be infected but in some regions the number was as high as four percent. Everyone testing positive was required to remain in strict isolation for ten days, either in their home or in a state supported facility. Another round of nationwide testing will take place in one week. The Slovakia testing rollout was not without its critics but the hope is that the inconvenience of long testing lines last week will help the country avoid the far greater inconvenience of a nationwide lockdown in the weeks to come. Other European countries like Germany are now bulk buying rapid antigen tests as well, presumably in an effort to test more people, more frequently, to contain their outbreaks and avoid wider lockdowns. There is no reason why we in the United States don’t do the same. I have already calculated the cost of a COVID containment strategy which includes widespread testing and supportive isolation, where families are offered financial support and medical resources throughout the course of any mandatory isolation period. The total cost, while in the tens of billions, would still be far less than the many trillions of dollars of national debt we continue to rack up alongside lost economic opportunities. Whichever leader walks away with the Presidency of the United States for the next four years, would that he is willing to finally leverage the full power of the federal government to contain COVID-19 through widespread testing and isolation. This article originally appeared in Forbes and is available online here: Lancet Study Suggests U.S. Is Massively Undercounting COVID-19 Cases
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Lancet Study Concludes That Public Health Interventions Reduce Viral Transmission Forbes | November 5, 2020 | Article
On October 26th, the seven-day average for positive COVID-19 cases in the US was over seventy thousand—a new record. On October 29th, another record was set when over ninety thousand cases were reported in a single day. We are nowhere near the end of the pandemic. As the federal government banks on vaccine development, millions will be infected in the coming weeks and months. As demonstrated by China and others, public health initiatives like school closures, public event bans, and mask mandates beat COVID-19 swiftly and effectively. The Lancet’s Infectious Disease Journal released a study confirming China’s strategy. Researchers analyzed 131 countries at 790 different phases of policy implementation. They looked at public initiatives like school and workplace closures, public event bans, bans on gatherings larger than ten, public transportation closures, stay at home requirements, and internal and international movement limits. They monitored the R-value, or the number of secondary cases that a primary case may cause, of these countries. Whether the R-value is above or below one determines if a pandemic is on the rise or decline. The study confirms what public health experts have been suggesting for months: almost all of the public health initiatives studied reduced the viruses R-value. On October 26th, the seven-day average for positive COVID19 cases in the US was over seventy thousand—a new record. On October 29th, another record was set when over ninety thousand cases were reported in a single day. We are nowhere near the end of the pandemic. As the federal government banks on vaccine development, millions will be infected in the coming weeks and months. As demonstrated by China and others, public health initiatives like school closures, public event bans, and mask mandates beat COVID-19 swiftly and effectively. 457
The Lancet’s Infectious Disease Journal released a study confirming China’s strategy. Researchers analyzed 131 countries at 790 different phases of policy implementation. They looked at public initiatives like school and workplace closures, public event bans, bans on gatherings larger than ten, public transportation closures, stay at home requirements, and internal and international movement limits. They monitored the R-value, or the number of secondary cases that a primary case may cause, of these countries. Whether the R-value is above or below one determines if a pandemic is on the rise or decline. The study confirms what public health experts have been suggesting for months: almost all of the public health initiatives studied reduced the viruses R-value.
Graphs illustrating the effects of public health policies on viral transmission. THE LANCETThe figure above shows the range of R-values 28 days after an initiative is put in place and after it is lifted. Researchers found that six of the eight initiatives tested made a notable difference in R-value, two of which made significant differences. School closures and public events bans had significant sway over the R-value when enacted and revoked. Workplace closures, large gathering bans, stay at home orders, and internal movement limits also affected the R-value, but less significantly.
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International travel limits and public transport closures did not affect R in any statistically significant way. What are the implications of this study? As the graph above shows, six of the eight policies improve R-values for COVID-19 between three and 24 percent. That said, the effects of a policy being implemented appear at least a week or longer after the policy is put in place. In the case of large gathering bans, effects are not fully seen until three weeks following implementation. These policies work but on a delay. The federal government must consider a return to some of these six initiatives, then the American people must be patient with the results. Pairing them with significant mask use could counteract the unprecedented case numbers Americans face today. There have been two major resurgences of the virus since the pandemic began. After the economy reopened and after schools reopened. This study proves that reopening the economy and schools directly influenced the case resurgences. As the weather grows colder, the COVID-19 case rate will continue to climb. People will be forced inside at their workplaces, at restaurants, etc. The continued neglect to reimplement COVID19 controls by the federal and state governments is irresponsible. Over 700 people are dying per day on average and that rate is accelerating. China was able to control the spread of the virus with a stringent combination of the policies above. They have still not surpassed one hundred thousand cases in a country of over a billion people. The United States could realistically reach one hundred thousand cases per day by the end of the year. People are clearly succumbing to pandemic fatigue. They are tired of the isolation and want to return to normal life. Unfortunately, the time to return to normal life is not now, nor will that time come for a moment. COVID-19 is worse than ever in the United States. As the study shows, these policies take a few weeks to show an effect. Americans need to be patient. Stay home, wear a mask, and then we will all be able to return to a normal life together after the storm passes. This article originally appeared in Forbes and is available online here: Lancet Study Concludes That Public Health Interventions Reduce Viral Transmission 459
How Obesity Puts You At Risk For COVID-19 Forbes | November 6, 2020 | Article
A new study, released as a preprint in the Lancet, has found that obesity is one of the three greatest risk factors for suffering the most serious consequences of COVID-19, including age. The study give us insight into why COVID-19 has a more serious consequence for the obese and overweight. Fat cells express the receptor for SARSCoV-2, serving as a reservoir for virus infection. Those who are overweight and obese remain infected several days longer than their aged-matched leaner counterparts. Moreover, obesity creates an underlying inflammatory condition, one that very likely exacerbates the inflammation caused by SARS-C0V-2 infection, one of the leading causes of COVID-19 disease. This is particularly troubling news for those of us here in the United States, where 42% of Americans are obese and 32.5% are overweight. Obesity is not confined to adults. A total of 13.7 million American children and adolescents are obese—13.9% of children ages 2-5, 18.4% ages 6-11, and 20.6% ages 12-19. The American obesity epidemic coupled with the COVID-19 pandemic is a double disaster. More than two-thirds of adult Americans are at higher risk than average of falling ill when infected by SARS-CoV-2. Since January 2020, close to 900,000 children 0-17 are known to have been infected. Latin America has been hit with a twofold blow as well. The region has some of the highest COVID-19 death rates in the world and equally distressing levels of obesity and diabetes. In Mexico and Chile, more than 75% of the female population is overweight. Though research on the subject has been relatively limited, there are studies which suggest that obesity, combined with undernutrition, are closely tied to the large number of deaths and severe disease in the region. Those who favor letting the virus take its natural course in the young and the so-called "low-risk" groups fail to consider the millions of people who fall into a high-risk group simply because of 460
their weight. They often argue that letting the virus infect a low-risk group while protecting those at higher risk is a recipe for what they call "herd immunity". Not only is this flawed—the data suggest infection does not confer long-lasting immunity—but the low-risk group they point to comprises well less than one-third of the overall population in America and, in some populations and regions like Latin America, numbers that are far lower. Today we suffer the consequence of government policies at the federal and state level that mitigate our control of the virus. Mandating mask-wearing, limiting the size of crowds, recommending social distancing, and closing bars, all shown to be effective in the control of the disease. It is no wonder that we are witnessing an ever-increasing deluge of patients in our hospitals throughout the country and a rapidly rising death toll, a toll that may well exceed one million dead in the coming year unless we change course quickly. This article originally appeared in Forbes and is available online here: How Obesity Puts You At Risk For COVID-19
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A More Transparent And Trusted COVID Vaccine Forbes | November 6, 2020 | Article
I have long expressed concerns regarding the safety, efficacy, manufacturing quality, distribution, and administration of antiCOVID-19 vaccines. Many of these concerns have now been echoed by reporters at STAT, a publication that has become essential reading for all who follow diagnostic, vaccine, and drug development for COVID-19. The article highlights the loss of public trust in our public health institutions, with 62% of Americans worried the FDA will rush to approve vaccines because of political pressure, without adequate regard for safety and effectiveness. But in addition to highlighting the problem, the authors also point toward a solution: a Pew Research Center study which shows that open access to data and independent review inspires more trust in research findings— findings that in the case of a vaccine study need to be trusted for people to be willing to take the vaccine. While calling for broader access to information about the design, implementation, and results from the vaccine trials, the authors note that “vaccine manufacturers’ current legal obligations and voluntary commitments often fall short of full transparency.” I have enormous respect for their original reporting and unbiased, unvarnished journalism. This story of the need for increased transparency regarding vaccine development is case in point. The article is a must-read overview of some of what the public needs to know regarding vaccine development, what and information has been withheld. Proclamations by the companies that are developing vaccines ethically are an inadequate assurance. If read carefully, these assurances are as full of holes as Swiss cheese. It is only by shining the light on what is missing and by fully disclosing the data and problems encountered that we may achieve clarity and confidence that vaccines, if approved, are safe and gain a true measure of their potential effectiveness. 462
This article originally appeared in Forbes and is available online here: A More Transparent And Trusted COVID Vaccine
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Pregnant Women Are At Higher Risk For Severe COVID-19 And Death Forbes | November 9, 2020 | Article
A recent study, published by the Centers for Disease Control and Prevention (CDC), confirms that pregnant women are in fact at higher risk for severe COVID-19 and death compared to nonpregnant women in the same age range. Prior to this study, there was concern that pregnancy could increase the risk of severe outcomes from COVID-19, but not enough data to say for certain. Addressing a major gap in the research about the impact of COVID-19 on pregnant women, this large CDC study analyzed data from over 400,000 women between the ages of fifteen and forty-four, 23,434 of whom were pregnant. All of the women included had tested positive for the COVID-19 virus using a PCR test and were experiencing symptoms. After adjusting for age, race, ethnicity, and underlying conditions such as diabetes, cardiovascular disease, and chronic lung disease, pregnant women were three times more likely to be admitted to the intensive care unit (ICU), and 2.9 times more likely to receive mechanical ventilation compared to nonpregnant women in the same age group. While the absolute risk of death among pregnant women with COVID-19 remains low at 1.5 per 1,000 women, the risk is 70% higher in pregnant women compared to nonpregnant women. Physiological changes that women go through during pregnancy may account for this increased risk for severe COVID19. These changes include increased heart rate and oxygen consumption, decreased lung capacity, and decreased function of the immune system. Some of the most striking differences in outcomes between pregnant women and nonpregnant women came in women ages thirty-five to forty-four. In this age group, pregnant women were four times more likely to require mechanical ventilation and two times more likely to die compared to nonpregnant women of the same age group. 464
There are racial and ethnic disparities in pregnancy outcomes even in the absence of COVID-19. Unfortunately, these disparities are only amplified with the addition of COVID-19 infection. This study highlights the increased risk of severe outcomes among women of color who have COVID-19 during pregnancy. Asian women who were pregnant were 6.6 times more likely to be admitted to the ICU compared to nonpregnant Asian women. Native Hawaiian/Pacific Islander women had an increased risk of ICU admission of almost four times. The risk of death among Hispanic pregnant women was 2.4 times higher than the risk in nonpregnant Hispanic women. Black women in this study experienced a disproportionate number of deaths, irrespective of pregnancy status. Black women represented 14.1 percent of women in this study but accounted for 36.6 percent of the total deaths. Not only were women of color in this study at higher risk for more severe outcomes from COVID-19, but they were also at an increased risk of infection. Because of these disparities in infection rates and severity of outcome among women of color due to COVID-19, the CDC presents a call to action to address drivers of COVID-19 infection risk in these populations. In addition to decreasing COVID-19 infections among pregnant women, especially pregnant women of color, we must ensure that women have access to quality and affordable healthcare throughout their pregnancy and beyond, so that they can receive the care they need if they do become infected with COVID-19. The CDC also released a smaller study this week looking at the impact of COVID-19 in pregnancy on birth and infant outcomes. Of the almost 4,000 infants born to women with the COVID-19 virus infection in this study, 12.9 percent of them were born preterm (less than 37 weeks). In the general population, only about 10.2 percent of babies are born pre-term. Of the 610 infants who were tested for COVID-19 virus through the study, 2.6 percent tested positive for the virus, although it is unclear how transmission occurred. Most of these babies were born to mothers who had recently been infected with COVID-19. Maternal infections early in pregnancy often have a larger impact on an infant developmentally than infections that occur later on. Now that the virus has been with us for over nine months, there must be an increased focus on research to discover the impacts of 465
COVID-19 infection early in pregnancy on both pregnant women and infants. In the wake of these studies, the CDC recommends pregnant women continue going to prenatal care visits, stay up to date on their vaccinations, pay special attention to social distancing guidelines, wash their hands frequently, wear a mask in public, and avoid those who are not wearing masks. Pregnant women should avoid enclosed spaces and public transportation as much as possible. When absolutely necessary to be in an enclosed space, the time spent there should be limited. While in an enclosed space or a crowded place where others may not be wearing a mask, pregnant women should wear disposable gloves, an N95 or KN95 mask and a face shield. After taking off disposable gloves, mask, and face shield, pregnant women should wash their hands thoroughly. Face shields should not be used as a substitute for face masks, however, when worn in conjunction with a face mask, they can provide an extra level of protection from droplets that can enter through the eyes. In addition to these measures, we must all take responsibility and follow social distancing guidelines, wear masks in public, and wash our hands frequently to control the spread of COVID-19 in our entire population if we want to keep pregnant women and their children safe and healthy. This article originally appeared in Forbes and is available online here: Pregnant Women Are At Higher Risk For Severe COVID-19 And Death
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Are Frozen Foods A Risk For COVID-19 Infection? Possibly. Forbes | November 9, 2020 | Article
In the early days of the pandemic, when much about how SARSCoV-2 was spread was still very much unknown, consumers were warned to disinfect groceries before putting food onto their shelves or into their refrigerators. But over time, as the respiratory nature of the virus became more fully understood and our focus turned squarely to mask-wearing and social distancing, people eased up on these efforts. Even the World Health Organization and the US Centers for Disease Control reported that the risk of infection from handling packages of food was low. But it may not be as low as we think. In October, Chinese health authorities discovered live coronavirus on a package of frozen food in Qingdao—the first time active virus was detected on the outside of refrigerated goods. The finding was worrisome, especially when researchers realized the virus on the packaging may be linked to a cluster of new cases in the region. China is one of the only countries to conduct broad inspections of incoming food shipments. Since the inspections started, Chinese authorities have identified the virus on packages of frozen shrimp from Ecuador, squid from Russia, chicken wings from Brazil, and frozen seafood from Norway. As each new case was discovered, China doubled down on containment efforts, halting some imports, imposing new customs restrictions, and tightening inspections on all food entering the country, where new cases of COVID have been held to under 50 per day for months. Other countries, like New Zealand, have also become newly concerned about the potential risk. In August, after more than one hundred days without any new cases, authorities suspected that a new cluster of infections may have started at a food transport facility with an employee handling frozen foods A study out of the National University of Singapore confirms contaminated food and food packaging as a potential source of new 467
COVID-19 outbreaks and clusters of infection. The study notes the number of clusters in meat and seafood processing facilities across the world throughout the pandemic, with operations suspending poultry processing plants, tuna canneries, abattoirs, and slaughterhouses around the world. Dale Fisher, one of the authors of the study and the chair of the Global Outbreak Alert and Response Network says it’s possible that contaminated food imports can transfer the virus to workers as well as the environment and frozen food markets may be the first link on a new chain of transmission. “It’s hitching a ride on the food, infecting the first person that opens the box,” said Fisher in an interview. “It’s not to be confused with supermarket shelves getting infected. It’s really at the marketplace, before there’s been a lot of dilution.” This finding holds lessons for each of us at every stage of the food supply chain. At food processing and packaging plants, workers should be given every protection to keep themselves free from infection and to prevent it from spreading to the food—workers should be tested regularly, given financial support if they test positive so they can isolate at home, and have access to masks, glove, sanitizer and disinfectant in the workplace. Once the food arrives at stores, grocery store workers should be given the same protections to limit the risk of further transmission. And all consumers—whether in countries like the United States where the virus runs rampant, or in places like Taiwan where new infections are near zero—must continue to be vigilant. While many of us continue to close our doors to visitors, we still stock our cupboards with foods from all around the world. Contamination at major food distribution centers raises concerns for all of us around the world. If the virus can be found alive on the outside of frozen food packages, it’s possible that it could be found alive on the inside of those packages as well. It is only prudent then for each of us to approach food handling with caution—wash hands thoroughly after removing food from its package, handle any food carefully before it’s cooked, preferably with gloves, and make sure that all foods are cooked thoroughly, which is certain to inactivate the virus. This article originally appeared in Forbes and is available online here:Are Frozen Foods A Risk For COVID-19 Infection? Possibly.
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One Tenth Of Americans Infected By COVID-19 Are Children Forbes | November 9, 2020 | Article
Children aren’t as likely to become severely ill from COVID-19 as adults, and for this reason their ability to contract and transmit infection is often downplayed or unrecognized. But according to a new report from the American Academy of Pediatrics, more than 61,000 children in the United States—a record high—were diagnosed with COVID-19 in the span of one week alone, bringing the total number of pediatric cases confirmed this year to 853,635. In April, children accounted for only two percent of cases nationwide. Today, according to the Academy report, their share is more than five times as high—hovering around 11 percent. While the reason for the increase is unclear, it doesn’t seem probable that pediatric cases will dip back down in time for the holidays. Against the better judgment of health experts, large family gatherings and vacations are bound to occur, creating more opportunities for transmission across households that might spill over into the new year. In any case, it can be presumed that these numbers represent only a small fraction of the actual number of children who have active or past COVID-19 infections. Since the majority of children who catch the virus develop either mild symptoms or none at all, chances are many don’t get tested. Instead, they join the droves of so-called “silent shredders” who spread disease unawares and cause as many as 79 percent of infections. Some studies suggest that children spread the virus as well as adults—in which case they drive contagion more than we think, though more evidence is needed to prove this definitively. Thankfully, the rise in pediatric COVID-19 cases hasn’t been matched by a comparable rise in hospitalizations. Although 121 469
children have died from complications caused by the disease, children make up less than 3.5 percent of those hospitalized with it. Still, many of us aged 18 and over won’t be so lucky. With daily COVID-19 cases now exceeding 100,000 in the U.S., there is certainly reason enough for us to acknowledge that children aren’t exempt from this pandemic—especially when it comes to the part they may play in exacerbating existing outbreaks. Neither are children exempt from the potential long-term effects of COVID-19, both physical and mental. The longer the pandemic drags on, the more disruption children will face in their opportunities to learn and grow on many levels—from their social lives and behavior to their emotional intelligence and aptitude in school. Studies conducted across China, Bangladesh, Italy, and Spain have independently reached similar conclusions about depression and anxiety levels in children: that they’re increasing due to COVID-19. How long those trends persist remains to be seen, but like rates of infection, they’re unlikely to subside anytime soon. Winter is nearly upon us, and with it comes winter break—peak time for sickness in kids, pandemic or no pandemic. Remember that in March, an outbreak in a ski resort in the small Austrian town of Ischgl resulted in possibly the highest rate of infection in the world, with 42 percent of residents testing positive for antibodies and many nonresidents spreading the disease to other parts of the world. While the temptation to loosen up on restrictions, seek out adventure, and reunite with loved ones young and old will be strong, for the sake of our children and ourselves we must hold fast in our isolation. If not, we risk spending not just the upcoming holidays apart, but next year’s, too. This article originally appeared in Forbes and is available online here: One Tenth Of Americans Infected By COVID-19 Are Children
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This Nasal Spray Could Be The Breakthrough We Need To End COVID-19 Forbes | November 10, 2020 | Article
Researchers have discovered a new peptide, delivered in the form of a nasal spray, that has the potential to end the pandemic sooner than later. It appears to block transmission of the SARS-CoV-2 virus in ferrets, and if it proves effective in humans, a squirt or two up the nose would prevent contagion by even large amounts of virus. The only question is how long it will take to find out. In a small study published yesterday in bioRxiv and currently undergoing peer review, two ferrets were given the nasal spray and another two a placebo. Researchers stuck them in a cage with another ferret that had been infected the day before, and 24 hours later, out they came—two perfectly protected and two infected. Were the spray to protect humans as well as it does ferrets, it would be comparable with a successful vaccine in terms of its ability to prevent the spread of disease—not to mention better than many of the COVID-19 vaccines currently in phase 3 clinical trials that have proven only moderately effective. Rather than mitigating symptoms after the fact, the nasal spray would work prophylactically to stop infection altogether. Infection by SARS-C0V-2 involves the fusion of the membranes of the virus and of host cell proteins. In a series of previous studies by the authors of the current study, they showed that the peptides which inhibit the fusion process may inhibit the fusion of the measles virus, human parainfluenza virus type 3, and the Nipah virus. In this study, they show that a similar peptide acts as a potent inhibitor of fusion by SARS-CoV-2, both in cells and in ferrets. Beyond the novelty and promise of the approach, the study is notable for a number of reasons. First, the researchers took 471
considerable care to mimic the natural process of exposure and infection, cohousing the treated and untreated ferrets with ones that had been infected with SARS-CoV-2. While occasional tussling and biting might provide opportunities for transmission, it was just as likely that the ferrets would contract the virus simply by sharing the same air—much as we humans do. Second, manufacturing the nasal spray en masse would be relatively straightforward. Large quantities of the peptides that constitute the spray can be made quickly and easily. They can be delivered in a liquid formulation, freeze-dried, then reverted into liquid once more, entirely suitable for spraying into the human nose, according to the researchers. Because of the simplicity of the process and components involved, the spray would also be inexpensive to produce and ideally inexpensive to purchase. The study, like any other, comes with a few caveats. One is that it remains to be seen whether human mucosa—the mucous membranes that line our nose and other bodily cavities—behave like ferret mucosa. Another has to do with the ability of SARS-CoV-2 to mutate and potentially bypass attempted blockage. Although SARS-CoV-2 isn’t as quick to mutate as other viruses, it is possible that the efficacy of the spray might vary depending on the strain. Both the public and private sector—pharmaceutical companies, the National Institutes of Health, Operation Warp Speed—should put their full weight behind testing this nasal spray in humans as quickly and forcefully as they are with vaccines. If they do and the spray is found to be safe and effective in humans, it could be brought to market and available for use in as little as six months. This nasal spray may be the breakthrough we’ve been waiting for to end the pandemic. It will require a bold commitment from the federal government, but if anything deserves warp speed, in my opinion it’s this. This article originally appeared in Forbes and is available online here: This Nasal Spray Could Be The Breakthrough We Need To End COVID-19
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Long Lasting HIV Drugs Hold Lessons For Us All Forbes | November 10, 2020 | Article
The successful results from a clinical trial of a new, long-acting HIV prevention drug are not just a critical milestone for those working on HIV/AIDS, but also for researchers working on other deadly infectious diseases. The results prove that in the absence of a vaccine for a viral disease like HIV, we can develop the next best thing— long lasting drugs that are highly effective at preventing infection when taken prophylactically. The HIV drug, developed by ViiV Healthcare, is called cabotegravir and belongs to a class of drugs called integrase inhibitors. Integrase is an enzyme critical to viral replication. Block the integrase and you prevent the virus from replicating. It’s an approach that I and my Harvard research group identified nearly thirty years ago, now being applied to great effect. Results from a Phase III trial found that cabotegravir, when taken prophylactically, was 89% more effective in preventing HIV infection among women than Truvada, the current gold standard in HIV pre-exposure prophylaxis. Its long-lasting effectiveness in women is important because women bear such a disproportionate burden of this disease. In some parts of sub-Saharan Africa, 80% of new HIV infections among adolescents are young women. Truvada and other HIV prevention medications that need to be taken daily have been highly ineffective in reducing the burden of disease in this key population for a number of reasons, not the least of which is the lack of autonomy and independence given to many young girls when it comes to their sexual health and ability to access HIV services. This new drug, which can be taken once and provides protection for up two to three months, could free women from daily dosing and significantly reduce the number of new HIV infections globally. Another HIV drug, currently in development, has a similarly long-lasting effect, though it attacks a different part of the virus. GS473
6027, developed by Gilead, attacks capsid proteins which protect the virus but also play an important role in viral replication, facilitating virus entry and exit when infecting new cells. In July, Gilead demonstrated that their anti-capsid drug could potentially protect people for up to eight months with one single injection. Though GS-6027 and cabotegravir are very different drugs, they do have one important thing in common in addition to their longlasting effect: they have an enormous therapeutic index. A therapeutic index is essentially the ratio between how much a drug harms the patient and how much it harms the virus, tumor, or other agent that is causing the illness. Ideally, you want drugs that do a great deal of damage to the agent but leave the rest of the patient free from harm. These two drugs do just that, as they target functions that are specific to the virus and have no corresponding function in human biology. The success of these long-acting HIV drugs points to a strategy that may prove effective against COVID-19, influenza, and other infectious viral diseases. The early announcement by Pfizer of the potential effectiveness of their vaccine is promising, but there are still many unanswered questions. The Pfizer vaccine, like all the other COVID vaccines currently in development, does not prevent infection. It may prevent serious cases of COVID-19, but without any published data its still unclear how much a vaccine may limit the severity of disease. What we do know is that a vaccine that does not prevent infection is unlikely to reduce the size of the pandemic, on its own. This means we can’t shift our focus away from other approaches that we know work—like mask-wearing and social distancing—and that we think could have a very high potential of working, like drugs that target the integrase and capsid proteins which have shown such great success against HIV. It has been more than thirty-five years since we discovered the virus that causes AIDS and we still don’t have a vaccine. But now, for the first time, we may have not one, but two drugs—cabotegravir and GS-6027— that can effectively end the pandemic. If we pay attention to the lessons we have learned from that journey, I have hope that we will find a medical solution to COVID-19 far, far sooner.
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This article originally appeared in Forbes and is available online here: Long Lasting HIV Drugs Hold Lessons For Us All
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A Ray Of Hope For Treatment Of COVID-19 Forbes | November 13, 2020 | Article
New reports on the effectiveness of two different monoclonal antibody therapies have given us a ray of hope that we can prevent COVID-19 from turning deadly. In these preliminary reports both antibody drugs seem to reduce hospitalization for patients if the drugs are given early in the course of the disease. Other studies have shown that administering these same drugs after the disease progresses does little to no good. This finding points us towards two important steps we need to take to effectively contain the pandemic by as soon as next summer. The two therapies—one from Eli Lilly and the other from Regeneron—work directly on the virus to prevent it from replicating. For COVID-19, the virus acts in three distinct phases. The first phase takes place a few days to a week following infection. During this period, virus growth is slow. In the second phase, virus growth is rapid and the concentration of virus particles in nasal fluids, the lung, and the intestine is high. This is normally when patients begin to show symptoms, after the peak of virus replication. At this point, we enter the third phase. It is this phase that life-threatening symptoms unroll over a matter of two to three weeks and sometimes longer. Little to no infectious virus is present but the disease the virus started continues on. As might be expected, antiviral drugs such as the monoclonal antibodies seem to work only in the initial two phases, usually before a patient is hospitalized. This means that for the drugs to be administered early enough to be effective, those exposed to the virus must be tested regularly, whether or not they show symptoms of disease or not. An early positive result can lead to early treatment that might save a life. This is hopeful and promising news and is encouraging for the array of new chemically based antiviral drugs currently in early stages of clinical development. But the treatment isn’t without drawbacks. First, the treatment needs to be administered by infusion—it’s not a quick injection that 476
can be over and done in a few minutes at your regular walk-in clinic. Second, monoclonal antibodies are very expensive to manufacture. They are among the most expensive drugs on the market today. President Trump reportedly received an eight gram treatment of Regeneron’s investigational antibody cocktail, REGN-COV2— about two heaping teaspoons. The cost for that treatment—if we assume costs similar to those of other monoclonal antibody treatments like Keytruda, which is used for certain types of cancer— would be over four hundred thousand dollars. There was also a worrying finding from the Lilly trail. Even over the short course of treatment some patients developed resistant variants. As with many viruses such as HIV, combinations of antiviral drugs each directed to a different target may do the job. These drawbacks, combined, make monoclonal antibody treatments impractical for treating the large numbers of people in the United States infected today. Even if the cost of the drugs themselves wasn’t a challenge, manufacturing issues would be. There are only about 50,000 doses of REGN-COV2 available in the US today, which would cover just over half of the number of newly infected Americans yesterday. Still, there is hope. The Eli Lilly and Regeneron treatments have demonstrated proof of principle. Drugs that prevent replication of SARS-CoV-2 can prevent early SARS-CoV-2 from progression to serious disease if administered early on in the course of the disease. Now, we must do two things urgently. First, we must focus on developing chemically based antivirals that use a similar approach but are cheaper and easier to manufacture. These drugs exist and early prototypes have already been proven effective in lab settings against MERS, SARS, and SARS-CoV-2. Now we must accelerate efforts to safely move these treatments out of the labs and into clinical trial settings. Second, and perhaps more importantly, we must ensure we have a system in place to identify those newly infected as early as possible. This can only be done if we make rapid, five-minute antigen tests universally available, so every person potentially exposed can quickly assess whether they are infected or not. The only way to ensure these two critical steps are taken is through the power of the federal government. Through the course of this pandemic, the Trump administration has chosen not to use 477
the full weight of our national powers to propel the containment effort, instead leaving it to states to pull together a piecemeal approach. This should not stand. A massive, nationally coordinated testing strategy should be implemented immediately while federal resources are pulled together to help fast-track cheaper monoclonal antibody treatments. If we did these two things, we could end this pandemic by next summer. If not, let us prepare ourselves for COVID to control us not just next year but potentially for a few more years to come. This article originally appeared in Forbes and is available online here:A Ray Of Hope For Treatment Of COVID-19
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“COVID-19 Has Laid Bare The Inequities In Our Health System. What Are We Going To Do About It?” Daily Clout | November 13, 2020 | Article
Covid-19, which disproportionately affects people of color, continues to shine a light on the deep inequities ingrained in our society. Non-whites are more likely to be infected with the virus and suffer from severe illness than their white counterparts, according to data from the Centers for Disease Control and Prevention (CDC). Members of the American Indian and Alaska Native communities are 2.8 times more likely to be infected and 5.3 times more likely to be hospitalized than whites. Members of the Latinx community are 2.8 times more likely to be infected and 4.6 times more likely to be hospitalized compared to white people. Black people are 2.6 times more likely to be infected and 4.7 times more likely to be hospitalized. Inequitable policies in our health, criminal justice, education, housing and employment systems, have created the conditions for COVID-19 to harm communities of color disproportionately. Many of these unjust systems continue to implement racist policies. The harmful impacts of these policies on health equity have led many local and state leaders to declare racism a public health crisis. Black and Latinx people are over-represented in jobs deemed essential during the coronavirus pandemic, and cannot work remotely. These 479
jobs in transportation, local government, grocery stores, healthcare, and agriculture keep our society running, yet the workers are often poorly paid and not provided with adequate protective equipment. A study undertaken in Massachusetts of 104 grocery store workers, 61.5 percent of whom were non-white, found that twenty percent tested positive for the coronavirus. Many essential workers, and others not able to work from home during the pandemic, rely on public transportation, where risk of infection is increased, to get to work. Structural inequities entrenched in our health system have resulted in higher rates of chronic diseases among the Black and Latinx populations in the US. These chronic diseases including diabetes, obesity, and hypertension put individuals with these conditions at a higher risk of developing severe illness from coronavirus infection. Non-whites are also uninsured or underinsured at higher rates than white people in the US, and may have to wait until they are very sick to seek treatment because of uncertainty about how they are going to afford care. When seeking medical care, COVID-19 outcomes among people of color may be worse due to under resourced and over-crowded hospitals often accessed by those in communities of color. Centuries of racist housing, education, and economic policies have resulted in people of color in the United States disproportionately experiencing poverty. Living in crowded conditions, linked to low wages and unjust housing policies such as redlining, can facilitate the spread of the coronavirus and increase the risk of infection. In addition, environmental racism has resulted in higher levels of exposure to air pollution in Black and Latinx communities compared with white communities. A study conducted by researchers at Harvard found that individuals living in areas with high levels of air pollution before the pandemic were more likely to die from COVID-19. Over-policing, harsh drug laws, and strict non-discretionary sentencing guidelines, have led to Black people being highly overrepresented in the US prison population. Black people make up 13 percent of the US population, but represent over 38 percent of the prison population. Many COVID-19 outbreaks have been documented in correctional institutions, including the five largest known clusters of COVID-19. In addition, the death rate from 480
COVID-19 is higher in prison populations than it is in the general population. We must implement short term measures and work towards long term solutions to address the current racial health disparities that COVID-19 has exacerbated and to ensure that we address longstanding inequity starting now. In the short term, community testing needs to be expanded, especially in communities of color, and turnaround time for results must be drastically reduced. Those who test positive for the coronavirus must be compensated to stay home and those who cannot isolate safely at home should be provided with free accommodation to do so. Health education on the coronavirus should be readily available in languages other than English. Data on COVID-19 disaggregated by race and ethnicity at the Federal Level must be provided more often to inform our response and the equitable allocation of resources. In addition to these short-term measures, we must address the reality that the pandemic continues to highlight – that the US health system, and surrounding systemic structures, are deeply inequitable. In an article published in the New England Journal of Medicine, Dr. Michele K. Evans writes that “inequities in health, health care access, and quality of care are ingrained in the U.S. health care system. These inequities are not a sign of a broken system: in fact, in this sense, the system is operating just as it was built to operate.” We must reimagine and create a US health system that is well-funded, just, and equitable. A well-functioning health system must integrate with other sectors including education, housing, employment, and criminal justice if true health equity is to be achieved. We need to invest the necessary resources across sectors to improve health in the most marginalized communities. This article originally appeared in Daily Clout and is available online here:“COVID-19 has laid bare the inequities in our health system. What are we going to do about it?”
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A Note Of Caution On Moderna’s Promising COVID-19 Vaccine News Forbes | November 16, 2020 | Article
Early and favorable COVID-19 vaccine trial results announced this morning by Moderna are another sign that we may be moving ever closer to a medical solution to help us control the spread of this pandemic. But, even if the full data from the trial backs the early results issued in today’s press release, an approved vaccine will still not end the pandemic anytime soon. The Moderna results are from an interim analysis of the COVE study, which enrolled more than 30,000 volunteers to test Moderna’s mRNA-1273 vaccine candidate. Half of the participants received two doses of the vaccine, 28 days apart. The other half received placebos on the same schedule. Two weeks after the second vaccine dose, researchers found 95 cases of infection in the study participants—90 cases in the placebo group and 5 cases in the group that received the vaccine. Of those infected, 11 went on to develop a severe case of COVID-19. All those who developed severe illness were in the placebo group. The results suggest that Moderna’s vaccine may be able to limit both the number of people who develop COVID-19 and limit the severity of disease of those who fall ill. The results follow similarly favorable results from Pfizer and BioNTech last week, which issued their own press release claiming that their vaccine candidate was 90% effective in preventing disease. Neither Pfizer nor Moderna have yet published the full results from their interim analyses but it’s likely that even without published results both Moderna and Pfizer will submit their vaccines for an Emergency Use Authorization from the FDA and for authorization from other global regulatory agencies. While many view these developments as hopeful news, we should be cautious about putting too much faith in a quick end to the pandemic through a vaccine. First, because of the accelerated pace of the vaccine trials, we are only able to judge how the vaccine activates the body’s primary 482
immune response. This initial response may raise antibodies that can protect against infection, but that protection will fade and may fade rapidly, in as short a period as two months. Most vaccines rely on a long-term memory response instead. This long-term immune response is best tested six months to a year after vaccination which means, in the case of accelerated vaccine approval, we do not know if the vaccines generate long-term memory. Then there is the safety issue to consider. Moderna, like Pfizer, says their vaccine was generally well tolerated during the trials. In Moderna’s case, reported side effects from the vaccine included muscle aches, fatigue, and headaches shortly after vaccination. With our accelerated COVID vaccine timeline, no one can yet say what the long terms side effects of the vaccine may be. Vaccines are normally proven safe over the course of years, not months. The FDA is only requiring two months of safety data before potentially issuing emergency approval. What we can be sure of is that questions around the safety of a fast-tracked vaccine will likely stop many from agreeing to vaccination. A September Pew Research Center survey found that nearly half of all Americans would refuse a vaccine, due in large part to concerns about side effects and effectiveness. If the Pfizer and Moderna vaccines are approved and half of the population chooses to remain unvaccinated, the disease will continue to spread widely. The next issue to consider is distribution. Many have already highlighted issues with distributing Pfizer’s COVID-19 vaccine, especially its need to be stored at -94 degrees Fahrenheit (-70 degrees Celsius) or below. The Moderna vaccine can be kept at about 25 degrees Fahrenheit (-4 degrees Celsius), a temperature easily attained in a common refrigerator. But that doesn’t mean distribution won’t be without its challenges. Moderna estimates that it could have roughly 20 million doses available by end of year, at a cost of somewhere between $32 and $37 each. But those vaccines will likely be prioritized for frontline healthcare workers and those at the highest risk of becoming critically ill, such as those with multiple pre-existing conditions or the elderly. Broad distribution of a potential vaccine, even in the best case scenario, is still not likely to come until at least the second half of next year. Given that transmission of the disease is highest among those under the age of 44, this means that a vaccine 483
prioritized for the old and infirm will do little to stop the spread of the disease. This is no small matter. There are more than 150,000 new infections every day in America and there is still no treatment for the disease. Those who fall ill—young and old alike—risk long-term damage from this disease. I welcome the positive news to date on vaccines, but I fear our excitement around a medical solution may hamper our willingness to pursue the only course of action that we know with certainty can protect us today: mask-wearing, social distancing, and widespread testing and isolation. This article originally appeared in Forbes and is available online here:A Note Of Caution On Moderna’s Promising COVID-19 Vaccine News
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Build A Plan For COVID-19 Home Testing On Reason, Not Speculation Or Politics STAT News | November 16, 2020 | Article
John Maynard Keynes once famously observed that there’s nothing as disastrous as a rational investment policy in an irrational world. But when it comes to public health, rational policies make sense even in an irrational or chaotic time like the midst of a severe pandemic. When the government ignores rational health policy, and instead follows unsound ones, the effects can last longer than anyone expects. That’s what happened with the federal government’s unfounded resistance to home HIV testing, which cost millions of lives and trillions of dollars. We see similar resistance regarding home COVID-19 tests, which are being disparaged because they might not yield demographic data or might be misinterpreted. Putting up barriers to home testing would be disastrous. In the 1980s, home testing for HIV also made sense. But we were ridiculed for believing that HIV, a sexually transmitted virus with a decade long period between infection and the onset of outward symptoms, could be transmitted heterosexually and become a pandemic. In meetings, federal health officials laughed at our idea that empowering people to test in the privacy of their homes for a sexually transmitted virus could dramatically reduce new infections. Journalist Michael Fumento published a book, “The Myth of Heterosexual AIDS,” that attacked HIV researcher Robert Redfield (who now leads the Centers for Disease Control and Prevention) and one of us (W.H.) for suggesting that heterosexual individuals might be at risk for HIV/AIDS. A member of Congress attacked one of us (E.M.) as “unscrupulous and irresponsible” for proposing a home HIV test. Independently, we both developed home HIV tests and both began the process of seeking regulatory approval. After receiving an application from one of us (E.M.), the first premarket approval application for a home HIV test submitted to the FDA, the agency 485
in 1988 banned home HIV tests altogether. This was despite clinical trial data demonstrating that home HIV tests provided results identical to lab tests. It was also despite research that showed that one-third of people who wanted to test for HIV would only test with a home test, and two-thirds of Americans preferred the home test choice. Even when the CDC’s own survey revealed that 29% of Americans would get tested for HIV if a home HIV test was available versus just 9% who intended to test using existing alternatives, both the FDA and CDC opposed home tests. The public, trusting that the government was acting in their best interests, never caught on, and federal officials continued to insist that home tests were unsafe and unreliable. The data from clinical trials summarized in the 1987 submission for premarket approval of a home test unambiguously demonstrated safety and efficacy. But given the strong political pressure against home HIV testing — from labs, clinics, and initially from AIDS activists — instead of accepting the application for review, the FDA decided to ban even the consideration of home tests. In banning home HIV testing, the government rejected the clarity of science for the fog of politics. The blame goes to the same reasons that financial markets act irrationally: lack of discipline, a failure to undertake fundamental analysis, and greed, the biggest culprit. Some labs and testing clinics feared the financial competition of affordable home tests. They aggressively lobbied against them, preferring to maintain their stake in the status quo rather than support public health. Instead of standing up for what was scientifically and socially right, the FDA stacked the deck against home tests. When one of us (E.M.) challenged this ban in court in 1990, FDA settled, announcing an end to its ban and agreeing to hold an advisory committee meeting to review a home test kit application. But the government violated its agreement. At the outset of the advisory committee meeting, the FDA simply announced that its ban was still in place. While the chair of the advisory committee (who ran a clinical laboratory) complemented the “marvelous job of making a very articulate presentation” one of us (E.M.) made, he then called the idea of considering the approval of a home HIV test “an exercise in absurdity.” One FDA adviser saw the situation 486
clearly, stating, “It was almost as if this matter was brought before the FDA’s subcommittee on non-approvability. It did not occur to me that the agency was in the business of trying to protect existing suppliers from new products.” Sadly, that is exactly how the FDA saw its role. Another lawsuit was filed, the FDA once again settled, and once again the government violated its agreement. The ban on rapid home HIV tests, despite being irrational and scientifically unjustified, lasted until 2012, when the FDA approved the first such test in the U.S., 16 years after it had approved the first mail-in test. During that period, more than 1 million Americans became infected with HIV. Today, as COVID-19’s unrelenting assault on the U.S. continues, the FDA has expressed its openness to receiving applications for rapid home COVID-19 test kits. It’s reassuring that the FDA now recognizes the numerous benefits of allowing people to test without having to leave their homes. With a home test, people get results instantly, without having to risk exposing themselves or others at a testing site or wait days for lab results. If they’re positive, they can immediately seek medical guidance and take steps to prevent spreading infection. But the political winds are blowing ominously against home testing. Some of the same justifications that were used against home HIV testing are surfacing in the press about COVID-19 testing: concerns that laypeople will misinterpret results unless they learn them from a doctor, that home tests will hamper critical surveillance efforts, and that the potential for false positive and false negative results outweigh the benefits of testing. These worries ignore the central reality that no test, whether taken in the home or sent to a lab, is infallible. There is always a need to educate people about a test’s limitations. Some people will undoubtedly get false positive results and unnecessarily quarantine themselves. Others will get false negative results and may unknowingly spread the virus to others. Yet the benefits of testing far outweigh the risks. Making a home test for COVID-19 widely available — and encouraging Americans to test frequently — can save lives. With AIDS, the federal government brought its full force and power to fight the introduction of home HIV tests. With COVID, the government must instead mobilize its best and brightest — and 487
the power of its purse — to make affordable, easy to use home tests a part of daily life until the pandemic ends. History doesn’t repeat itself, but it often comes close. The lesson from the FDA’s unjustified 25-year ban on home HIV testing is one we should learn from, not repeat. Elliott J. Millenson is the CEO of Global Diagnostic Systems, a company developing a rapid home COVID-19 test. He was the CEO of Direct Access Diagnostics which developed the first FDA-approved home HIV test. William A. Haseltine is the chair of ACCESS Health International. This article originally appeared in Forbes and is available online here: Build A Plan For COVID-19 Home Testing On Reason, Not Speculation Or Politics
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Do Not Ignore COVID-19 Safety This Thanksgiving Forbes | November 17, 2020 | Article
After months of isolation and quarantine, many hoped that COVID19 would be under control by the holiday season so families could reunite. As Thanksgiving approaches, that hope feels like a distant memory as daily cases reach record highs in the United States. Caution must hold precedence over anything else as families question whether to gather in the coming weeks. We must set aside traditions for everyone’s safety. November of 2019 may seem like a lifetime ago, but examining the traditional thanksgiving dinner of yesteryear exposes the dangers such an event could hold in a pandemic. Events may range from ten to twenty or more family members. Caution lights should already be going off in your head. Avoiding large gatherings is one of the keys to fighting against the viral spread. Gathering a couple dozen family members in a single location exacerbates the danger of contraction for all in attendance. Of those couple dozen, odds are that many of them are from out-of-town. In 2019, 55.3 million Americans traveled for Thanksgiving. Midwestern states like Iowa, Wisconsin, Illinois, etc. are experiencing positive case rates of nearly one hundred per hundred thousand, or more than double the national average. A cousin from Iowa visiting a family in Vermont puts the Vermonters at enormous risk. Traveling by train, car, and bus can also expose the traveler to a risk of infection. Visitors from just the town over can be just as dangerous as the cousin traveling across the country. This helpful map demonstrates the risk of large gatherings by county. Avoid having visitors from counties in red, to be blunt. The greatest risk is the main indoor activity: eating and sharing the same indoor space. The virus spreads through droplets and aerosols in the air that we release when we cough, sneeze, talk, or even breathe. This is why masks are effective; they block these droplets from spreading. This is why restaurants and bars are 489
COVID-19 infection hotspots. People cannot wear masks when eating and drinking. Hosting a Thanksgiving get-together is akin to eating at a downtown restaurant, which several states and countries recommend against or even ban. Besides N95s, most masks do not even stop aerosols, which may hang in the air of poorly ventilated indoor spaces for hours. Masks also do not stop infection through the eyes via droplets or aerosols. The virus is also transmitted by touching surfaces on which droplets have landed and then touching the mouth, nose, or eyes before washing your hands. The risks of even a masked Thanksgiving event are still present and significant. A new national survey from the Ohio State University Wexner Medical Center finds that many are planning to recognize these risks and take necessary precautions in the coming weeks. Unfortunately, two in five Americans report they will attend a gathering of more than ten people and one in three will not ask guests to wear masks. This fraction of Thanksgiving celebrations will further COVID-19 transmission across the country. If someone in your household plans to attend one of these events, please convince them otherwise. Outside skipping the holiday this year altogether, public health experts recommend families keep it quaint this year. Limit attendance as much as possible; convince out-of-town folks to stay home; wear masks as much as possible; and remain outside. The CDC has released holiday guidelines for those keeping their gathering COVID-19 safe. Taking precautions does not mean be sad and lonely this holiday season. Spend time with those in your household; hold a virtual Thanksgiving with friends and family; reminisce on the time before COVID-19 and dream about the time after. The harsh reality of COVID-19 is that things are only going to get worse in the immediate future. A vaccine will not be available for months. Public health experts theorize that colder temperatures will force people inside closed spaces, where the virus spreads more effectively. Europe is headed back into lockdown to get their cases under control. The dangers are simply too high to be hosting large scale get-togethers centered around eating. Safety and caution this holiday season will help everyone return to normal for the next holiday season. Everyone is struggling to cope with isolation and loneliness. Despite the virus separating us, we are 490
all together in the fight to defeat it. For this Thanksgiving: stay home, stay safe, and next Thanksgiving will be all the better. This article originally appeared in Forbes and is available online here: Do Not Ignore COVID-19 Safety This Thanksgiving
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China Aims To Eliminate COVID-19 With New Testing Policy Forbes | November 18, 2020 | Article
On November 6, China debuted a new travel testing policy. Before, incoming airline passengers had to submit results for a conventional PCR test that proved the absence of COVID-19 and, upon landing, head to a predetermined location for a mandatory 14-day quarantine. Now, another item has joined the list: a negative IgM antibody test result. The policy is the first of its kind and has experts puzzled. One physician, in conversation with the New York Times, mused it might be “security theater.” Another called it a “huge inconvenience” for a measure of “minimal value.” But my best guess is that the Chinese government has information on the long-term consequences of infection that we don’t. The onus of pandemic control in China, we must keep in mind, is drastically different from the United States and Europe. With only 925 new cases and three deaths reported in the past month, China— a country of nearly 1.4 billion people—has come so close to containing COVID-19 that not one infection can be overlooked. A single new case can be enough to trigger a barrage of testing (by the millions), rippling economic losses and disruption, and citywide shutdowns. Now that most of China’s outbreaks originate outside national borders, either from shipments of frozen foods or travelers returning from overseas, shoring up points of entry is the obvious move. Another factor worth considering when analyzing the new policy is that China’s disease surveillance system is no longer oversaturated with ongoing outbreaks. Today, their health authorities have enough bandwidth and breathing room to connect the dots between rare yet scientifically proven clinical events. Longhaulers, long-term virus shedders, and COVID-19 patients with other mysterious symptoms or pathologies are now the primary
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targets of public health interventions—the outliers who typically slip through the cracks of more conventional control measures. Let’s backtrack to basics. A standard PCR test, or “nucleic acid test,” searches the body for viral genetic material. IgM, on the other hand, is the first in a series of antibodies the body produces to defend against invading pathogens. They fade relatively rapidly, on average within five to seven weeks. Because IgM antibodies are a marker of recent infection, and because their duration is weeks long, an IgM test is more likely to screen out rare individuals who exhibit longterm virus shedding. One woman, it was found in a recent case study, had infectious virus more than 70 days after her initial diagnosis. Whether or not the Chinese government has evidence that new focal areas of infection are a consequence of long-term virus shedding, we don’t know. But it may well be the case, which is why they introduced the IgM test. Another reason might be that travelers who initially tested negative by PCR later tested positive. If this is the case, the IgM test is again likely to screen out some, if not all, of those who test negative for viral RNA initially. The “re-positive” phenomenon was documented by Chinese researchers in a peer-reviewed Nature publication, as well as more recently in JAMA. Again, while examples of “re-positives” and long-term shedders are only available by the handful, it is precisely these outliers that a country as large and advanced in its pandemic control as China will have to prioritize to reach total elimination. It will likely be many months before countries as beset by COVID-19 as the United States and India can prune at the edges as China now can. Even so, it is in our collective best interest to pay attention to how China attempts to propel itself from a handful of cases to none. Once we do find ourselves in a comparable position, we can follow suit—rather than reverting back to disaster. This article originally appeared in Forbes and is available online here: China Aims To Eliminate COVID-19 With New Testing Policy
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We Finally Have Rapid At-Home COVID-19 Tests. What Happens Now? Forbes | November 19, 2020 | Article
The Food and Drug Administration has authorized the first rapid athome test for COVID-19. It is a critical step forward in our efforts to contain the spread of disease, though the journey is far from complete. The test, manufactured by Lucira Health, includes a nasal swab, sample vial, and a battery-operated testing device. Users swab each of their nostrils five times then stir the swab into the sample vial before pressing it into the testing unit. After 30 minutes, the testing device will shine green and indicate either a positive or negative test result. It is the first of its kind in the United States, and the only test that lets people swab themselves, analyze the sample, and receive results entirely from home. Public health leaders have long advocated for rapid at-home diagnostic kits to help stop the spread of COVID-19. If people suspect they’ve been infected and can quickly and easily confirm their suspicions, they can immediately self-isolate and warn those around them of their exposure, curtailing the ability of the virus to spread. Computer simulations have suggested that if Americans were tested every one to three days, transmission could be reduced by more than 80% — enough to conceivably put a rapid end to the epidemic. First, the test is only available with a prescription. This means people will still need to jump through a few hoops — speaking with their doctor, securing a prescription, and getting the kit from the pharmacy to their home — all before they can take the test. Not only does this take time, it also opens up new opportunities for spreading the virus if the person potentially infected has to leave home. The test is also not approved for at-home use for children under age 14, so a child exposed at school would still need to visit their doctor to find out if they’re infected.
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Second, the test doesn’t come cheap. According to Lucira, the test will cost around $50 US — a figure high enough to give most Americans pause and to prevent some from purchasing the test at all if payment is coming out of pocket. For rapid at-home tests to be useful at containing and potentially ending the pandemic they must be easily affordable for insured and uninsured alike, as well as widely available and regularly used. Some have called out the accuracy of the tests — or lack thereof — as a possible cause for concern. The reality is that even tests that deliver correct results 94 or 95% of the time, as the Lucira tests claim to, are accurate enough to get the job done. While some may give a false positive or negative, at this level of accuracy home tests will still catch not just the vast majority of those infected, but the vast majority of those with an elevated viral load who may be highly contagious (see Figure 1). If everyone is tested at least twice a week, whether at homes, schools or in the workplace, many false negative results will be corrected in a subsequent test. Those testing positive could test themselves again to ensure the accuracy of their results. To implement twice a week testing, ideally testing the entire US population every three to four days, we would need 100 million tests every day for at least six months to wrestle the pandemic under control. The tests should cost no more than 50 cents each, a price tag that some may consider unattainable but that recent history shows is possible. Abbott Laboratories, the American pharmaceutical company, recently supplied Egypt with enough 50 cent rapid hepatitis C tests to screen their entire population of about 60 million people, helping the country effectively eliminate the disease. Meanwhile in the United Kingdom, the Financial Times has reported that the Department of Health is purchasing one billion pounds worth of rapid tests to implement a mass testing program to control their national epidemic. The cost of each test hasn’t been publicly announced, but it’s rumored to be under $10 US per test. Not quite 50 cents but certainly much better than the fifty dollar price tag for Lucira’s device. Once issues around cost and widespread distribution are resolved, one critical step remains: encouraging those who test positive to isolate immediately. This can’t be done through public messaging alone. Americans who test positive should be encouraged to isolate for at least fourteen days following the time of their most 495
recent positive test. They should be able to do so without risk to their livelihoods and with additional financial support to cover any lost income or added costs for food, shelter, or medical supplies. By my calculations, this would come to about $500 per family per day. To receive funding, confirmation of infection from a healthcare provider would be required and monitoring to ensure compliance with self-isolation would be encouraged. If Americans knew that they had an easy and affordable way to test themselves for infection and knew they would be supported financially for choosing to stay home and self-isolate to avoid infecting others, I believe nearly every American would choose to do the right thing for themselves and those around them. Some may argue the costs of a program such as this would be too high. But compared to the trillions of dollars we risk losing with more widespread lockdowns, on top of the trillions we have lost to date, the cost is a relative drop in the bucket. This article originally appeared in Forbes and is available online here: We Finally Have Rapid At-Home COVID-19 Tests. What Happens Now?
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To Guarantee Safety Of COVID-19 Vaccines, Prioritize Long-Term Studies Forbes | November 19, 2020 | Article
In the past few weeks, COVID-19 vaccines created by Pfizer and Moderna have made headlines with their promising phase 3 trial results. Neck-in-neck in efficacy, both reported reductions in COVID-19 related disease higher than 90 percent. The Food and Drug Administration (FDA) could open the doors to widespread use of these vaccines, either through expanded access or emergency use authorization, as early as next month. Although the reviews leading up to a stamp of regulatory approval are proceeding full speed ahead, one last bend in the road awaits—phase 4 (see Figure 1). This stage is designed to catch any adverse effects that didn’t surface or register as significant over the course of clinical trials. It also involves monitoring the production of the vaccines themselves. Given the accelerated timeline, longterm followup will be of particular importance for any COVID-19 vaccine authorized for human use under any authority, and a new commentary in Science Magazine shows why. While vaccines may be one of the most successful scientific technologies ever invented, the authors acknowledge, throughout history several have failed us. Many of the vaccine regulations we have today were borne of lessons learned the hard way—a contaminated batch that went on to infect thousands, or a rare side effect far more prevalent than initially perceived. A vaccine that fails to serve its original purpose, the safe prevention of disease, doesn’t just damage human health. It also triggers a loss of public confidence and fuels the rejection of future vaccines. But these fatal mistakes, contrary to what proponents of the anti-vax movement believe, are entirely avoidable, so long as we take care not to repeat them. Sometimes the issue isn’t necessarily the vaccine technology itself, but a fundamental lack of quality control. Take, for instance, the so-called Cutter Incident of 1955. Cutter Laboratories was one of the pharmaceutical companies licensed to manufacture the Salk 497
polio vaccine, which successfully used inactivated virus to stimulate bodily defenses against a horrific disease. Two of their batches, however, were mistakenly loaded up with live virus—poised, in other words, to spread polio rather than stop it. Those two batches alone went on to infect about 40,000 people, paralyzing 51 and killing five. Another problem that can arise once a vaccine reaches the general public is vaccine-induced enhancement. When clinical studies fail to correctly determine the correlates of protection against disease, a vaccine can end up enhancing infection, rather than preventing it. Such was the case with an inactivated vaccine for respiratory syncytial virus (RSV) developed in the 1960s, approved because it generated a moderate antibody response in volunteers. The majority of children who received the vaccine ended up hospitalized. It was later found that the antibodies stimulated by the inactivated RSV vaccine weren’t neutralizing, and in fact appeared to contribute to disease enhancement. Last but not least is the question of adverse effects that don’t raise alarm in clinical trials, but go on to develop in a significant minority of people who receive the vaccine. For the first rotavirus vaccine, authorized in 1998, the side effect was intussusception, a rare but potentially fatal condition that involves obstruction of the intestines and all the food and fluids that flow through them. For an influenza vaccine tested and administered in 1976, it was Guillain-Barré syndrome, a deadly autoimmune disorder that targets and harms nerve cells. Five cases of intussusception were documented in the rotavirus vaccine phase 3 trial, followed by 15 more in its first year on the market—a prevalence high enough to warrant suspension. The 1976 influenza vaccine, determined to be safe after a 7,000patient trial, was terminated after causing about 450 cases of Guillain-Barré syndrome in a quarter of the U.S. population. The faulty rotavirus and influenza vaccines, like the Cutter Incident and 1960s RSV vaccine, show us how a single oversight or misstep in the development of a vaccine can have untold consequences for the people who ultimately receive it. Today, as part of phase 4, regulatory agencies are required to closely inspect designated manufacturing facilities, test fresh batches of vaccines for purity and strength, and track reports of severe side effects using the Vaccine Adverse Event Reporting System. The FDA can also 498
choose to implement phase 4 clinical trials that last years after a vaccine is licensed, a more active and scientifically rigorous approach to long-term follow-up. Another disaster not only can be prevented, but must be, especially if hundreds of millions are lining up for a dose of the first COVID-19 vaccine to hit the shelves. While the current FDA guidelines for COVID-19 vaccine authorizations allude to the continuation of clinical trials following approval, extra care must be taken to enforce and preserve the integrity and longevity of phase 4 safety and monitoring procedures. If we aren’t sufficiently cautious and methodical in our approach, we risk once again making history—and not the good kind. This article originally appeared in Forbes and is available online here: To Guarantee Safety Of COVID-19 Vaccines, Prioritize LongTerm Studies
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COVID-19 Reinfection Is Possible And Should Inform Pandemic Priorities Moving Forward Forbes | November 20, 2020 | Article
A year after discovering the SARS-CoV-2 virus, the pandemic’s end seems just beyond the horizon as more and more hold out hope that a highly effective vaccine may soon be widely available. Returning to a COVID-free reality is a yearning we all share, but there's reason to believe we may never be COVID-free again because of the genuine possibility that COVID-19 will become an endemic disease; people once infected may become reinfected. We still know little about COVID-19 reinfection incidence. There have been official cases across continents and undoubtedly many more that have gone unreported. A Lancet report confirmed that in mid-October, the virus reinfected a man in Nevada. His symptoms were more severe during the second infection, but he has since recovered. Whether symptoms are worse on the first or second infection seems to vary from case to case. That means reinfection occurs despite the body’s immune response with antibody or T-cell production. Common knowledge suggests that when I am sick, my body mounts an immune response against my specific disease to prevent sickness down the road. While this is technically correct, a vigorous immune response, including antiviral antibodies and T-cells, does not guarantee lasting protection from disease. While some antibodies last decades, such as measles, others may last six months or less. We do not know precisely how long our protective immune response to COVID-19 may last, but early indications seem to be leaning towards just a few months. This could explain why confirmed cases of reinfection are so rare, as well as why many more reinfections probably occur. If the first or second infection is asymptomatic, that infection may go undetected by the host. Of the fifty-five million global infections to date, it seems likely that COVID-19 reinfected more than just five people.
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Because of these uncertainties and the importance of reinfection, we call for a significant research effort to investigate this topic. This study would be constructed by first sequencing the virus of a large cohort of COVID-19 patients when they first present. Then we would follow them and regularly test with rapid antigen tests. These tests are the most efficient method of tracking those most contagious: asymptomatic and presymptomatic patients. Using rapid tests means the bulk of this study could include asymptomatic and presymptomatic patients, whose sequences could be used for later research. For every patient who tested negative and then later tested positive, we resequence to determine one of two possibilities. Either the virus persisted and reemerged, or it was a new infection. The true magnitude of reinfection may only be recognized after two or three years of such studies. Understanding reinfection is necessary to inform COVID-19 control strategy moving forward. Herd immunity strategists claim the potential to rapidly end the pandemic and save the economy (at the expense of millions dead). They believe a population exposed to the virus will trigger a widespread immune response and the development of antibodies and T-cells to a point where the virus no longer spreads. Though if our immune responses fail over time and reinfection can occur, herd immunity would fail along with them. Our understanding of SARS-CoV-2 reinfection will also have an impact on our vaccine strategy. Suppose a double dose of a COVID vaccine only protects for months instead of years. In that case, we will need to rethink the cost of manufacturing, distribution, vaccine acceptance for multiple doses, frequency of immunization, etc. Studies from the New England Journal of Medicine and Science have indicated that naturally produced antibodies may only last between two and five months. Vaccines may not be a silver bullet to stop the virus, but rather one of many tools to collectively take on the pandemic. All this research is preliminary, and we won’t know the full extent of vaccine-based immunity until an approved vaccine has been in circulation for a long while. Perhaps the vaccine will be effective enough to expel the virus almost entirely. We will have to wait and see, but we need to understand reinfection before we can understand what the best strategy is to contain COVID, whether a 501
vaccine or not. Be optimistic but cautious, for the pandemic is far from over. This article originally appeared in Forbes and is available online here: COVID-19 Reinfection Is Possible And Should Inform Pandemic Priorities Moving Forward
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How Is COVID-19 Impacting The Preparedness Of The US Military? Forbes | November 20, 2020 | Article
The outbreak of COVID-19 on the aircraft carrier the USS Theodore Roosevelt and the isolation of members of the Joint Chiefs of Staff in October highlight an often-overlooked consequence of this pandemic. Despite these clear indications that members of the armed forces are susceptible to COVID-19, there is a troubling lack of information on the virus’ impact on our military’s preparedness of forces at air, land, and sea. Transitions between Presidents already pose an increased risk to national security. With Donald Trump still actively trying to change the results of an election he lost, this transition is shaping up to be potentially the toughest transition of power in our nation’s history. This makes knowing whether the coronavirus has impacted our nation’s military’s ability to defend the country even more important. Yet, the only recent information that we have on the impact of COVID-19 on our armed forces is a laudatory photo-article about successful prevention measures implemented at the Marine Corps Recruit Depot in San Diego published by the New York Times. While it is true that at this one Marine Corps installation there are no known COVID-19 cases, the article paints far too rosy a picture of what is actually happening in our military. At another Marine Recruit Depot, in Parris Island, South Carolina, twenty-four recruits tested positive on day seven of a two-week supervised quarantine on a college campus, and eleven tested positive on day fourteen. Researchers found that spread had occurred within platoons, even though all training activities occurred outside. Why two recruit depots, within the same branch of the military, have had different levels of success with COVID-19 control is unclear. Outside of these two Marine recruit depots, the numbers of infections in our military suggests they are keeping the rate of infection within its ranks slightly lower than that of America as a 503
whole. As of November 23, there were 74,992 infections out of a total of 2,191,000 active and reserve military, or 2,387 cases per 100,000. Across the United States as a whole, there are 3,747 cases per 100,000 people. Some defense experts have noted that while the military has a lower infection rate than society overall, “the profile of military cases has nevertheless closely tracked the profile of cases in the U.S. population.” While they are doing better than the country at a large, perhaps a result of the military’s experience fighting infectious diseases for decades and its position as a leader in sanitation and infection control, they are still far from having the spread of disease under control. Much of the praise surrounding the military’s handling of the coronavirus has come from its low death rate. The death rate among the military is 0.14 per 1,000 people compared to 21.4 per 1,000 people in the general population, or 145 times lower. As of November 18th, 10 members of the armed forces have died of COVID-19. However, this is an unfair comparison given the young age distribution of those in the military and the fact that they are a much healthier group to begin with. The average age of an enlisted member is 27 years old and the average age of an officer is 35 years old. Also, members of the military have access to high quality healthcare that should be provided to all Americans but unfortunately is not. Back in March, the outbreak of coronavirus on the USS Theodore Roosevelt, provided some of the strongest evidence at the time that the virus can be spread by those without symptoms. On an aircraft carrier with 4,779 personnel, a total of 1,271 crew members became infected with the coronavirus. 43% of the individuals who were infected never had symptoms of COVID-19. Months later, in October, after being exposed to the vice Commandant of the Coast Guard who tested positive for COVID19, almost all the Joint Chiefs of Staff quarantined. This included General Mark A. Milley, the Chairman of the Joint Chiefs of Staff. After the announcement that the Joint Chiefs of Staff were quarantining, White House officials told the Department of Defense that they should not inform the public or the media about the status of coronavirus of Pentagon leaders. While the Department of Defense has questioned this direction, there is still far too much that
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we do not know about how COVID-19 is affecting our military’s readiness to defend the country. The only information that we have received about COVID-19 and the military has assured the public that they have the situation well in hand. Though they may be doing better than the country at large, they are far from containing COVID-19. Given the high infection rates and the fact that soldiers are vital to our national defense, it is reasonable to discuss publicly whether the military should be among the first to receive the vaccine that might be mere weeks away. As the coronavirus situation in the US has gone from bad to worse, with little hope of any semblance of a national strategy for at least another two months when President-elect Biden takes the oath of office, we must ask serious questions about what is happening in our military. We need the military to be more forthcoming about how it is controlling the coronavirus within its ranks. If there are problems, what can we do to address them? Especially during this tenuous time in our country’s democracy, the public needs assurances that the coronavirus has not hindered our military’s ability to protect us. This article originally appeared in Forbes and is available online here: How Is COVID-19 Impacting The Preparedness Of The US Military?
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Don’t Assume A 14-Day Quarantine Is Enough Forbes | November 23, 2020 | Article
One of the general assumptions we’ve formed about COVID-19 is that when someone is infected, they’re no longer contagious after two weeks—hence the recommended 14-day quarantine. But this isn’t necessarily the case. Following the first appearance of symptoms, the vast majority of people are unlikely to be infectious for more than two weeks. For people who develop severe symptoms, that period extends to 21 days. Now, the Chinese government has determined that as many as five percent of COVID-19 cases have an incubation period longer than two weeks, and is taking action accordingly. Their precedent may be one to follow. At NYU Shanghai, for example, local authorities recently issued a seven-day exclusion rule. Anyone returning to NYU Shanghai, a satellite campus of New York University, from overseas—even after a standard 14-day quarantine—cannot enter campus buildings for an additional seven days. While no specific study was cited in communications announcing the seven-day rule, the claim that some COVID-19 patients take longer than two weeks to develop symptoms isn’t without precedent. A study conducted by Chinese researchers early on in the pandemic and later published in New England Journal of Medicine pinpointed the incubation period between 0 to 24 days. For one man, government officials in Hubei Province reported in February, incubation took nearly four weeks. A preprint that analyzed more than 60 articles on the subject found the upper limit in some reports to be even higher—a maximum 34 days. That a small percentage of people might take longer than two weeks to get sick after being exposed to COVID-19 isn’t exactly surprising. From the long-haulers who experience mild but debilitating COVID-19 symptoms for months on end to the longterm virus shedders who remain contagious far longer than most, the general assumptions we use to shape our understanding of this 506
disease—as well as our defenses against it—are riddled with no shortage of outliers and exceptions. What is compelling about NYU Shanghai’s new policy is that it speaks to the sort of precautions we might have to take once the bulk of transmission has ceased—a horizon more distant for some of us than others, but hopefully inevitable for all. With only 913 new cases and three deaths reported in the past month, China has come so close to containing COVID-19 that not one infection can be overlooked. The Chinese government is well aware that the current pandemic started with the infection of one person, and to eliminate COVID-19 for good means eliminating every single case. The seven-day rule also targets faculty abroad for a reason. Most outbreaks in China now originate outside national borders, either from shipments of frozen foods or travelers returning from overseas. On November 6, another new policy went into effect—this one countrywide—that requires airline passengers flying into mainland China from other countries to not just quarantine for 14 days upon arrival and submit negative PCR test results beforehand, but include a negative IgM antibody test result as well. As was the case with the seven-day exclusion rule, the science behind the additional requirement isn’t specified, but can be inferred based on more marginal clinical presentations of the disease. Presumably, the IgM test functions as a second layer of security— screening out, perhaps, those who initially receive a negative PCR test result only to test positive later, a rare but not impossible occurrence according to studies in Nature and JAMA. At this point we can only speculate, and in the months to come we’ll be able to see if these strategies actually pan out. If they do, countries currently in the thick of the pandemic will know to follow suit once the worst is finally behind us. But for now, especially with winter holidays fast approaching, we can only continue to take extra precautions to keep ourselves and those around us safe. This article originally appeared in Forbes and is available online here: Don’t Assume A 14-Day Quarantine Is Enough
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One Man, One Plane, Seven Infections And Counting: A Cautionary Tale For All Those Planning Air Travel Forbes | November 23, 2020 | Article
In September, a man boarded a flight from Dubai to New Zealand. Not 48 hours before he had tested negative for COVID-19. Days after disembarking, while quarantining in compliance with national containment policy, he and six other passengers of the 86 on board were confirmed to be infected with the virus SARS-CoV-2. According to a preprint case study released by New Zealand health authorities, at least four of the infections occurred in-flight— all tracing back to one man who, at least by the time he stowed his belongings and took his seat, was presymptomatic but shedding active virus. The chain of transmission was confirmed afterwards via genomic analysis. Incoming travelers to New Zealand are required by law to quarantine for two weeks in designated hotels upon arrival, where they will be monitored and tested at least twice before being released. The samples of those who test positive are isolated, genomically sequenced, and compared to determine their exact origins. This was how health authorities were able to identify the four passengers who contracted the virus in-flight, as well as the man who gave it to them. While not the first piece of evidence to affirm the possibility of in-flight transmission—just last month another study traced nearly 60 COVID-19 cases back to a single flight—reports of the incident make for a cautionary tale, especially with Thanksgiving fast approaching in the United States. The first takeaway is that air travel is dangerous, even when everyone, including the crew, is instructed to wear masks and, as far as we can tell, observes those instructions. The second takeaway is that a negative test isn’t foolproof. Most likely, the man on the New Zealand flight was infected shortly
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before or after completing a test and didn’t develop symptoms until a day or two after arriving at his destination. Many Americans traveling by plane this Thanksgiving and for the winter holidays soon to follow will be heading straight from the airport into the arms of relatives and loved ones, rather than supervised quarantine facilities. Surveys show that in general, most recognize the risks this entails and will take necessary precautions. But they also show that two in five Americans plan on attending a gathering of more than ten people—and as for the hosts of these large gatherings, one in three won’t require guests to wear masks. Now New Zealand, unlike the United States, has come incredibly close to eliminating COVID-19. So has China. Perhaps in anticipation of the travel surges to come, the Chinese government has tightened restrictions on points of entry, now requiring all airline passengers entering mainland China to submit not just a negative PCR test, but a negative IgM antibody test. My interpretation of this is that health authorities picked up on enough “re-positives”— that is, people who initially test negative only to later test positive for SARS-CoV-2—to take action to prevent more. While confirmed cases of “re-positives,” just like those of inflight transmission, may be rare, many more likely elude detection and pose risks that cannot be ignored. Even if all guests at a given Thanksgiving dinner test negative prior to their commutes or the event itself, that doesn’t guarantee safety. Far from it. Between the frozen food that might be on the menu to the relative who flew in too late to quarantine, too many variables will be in play for those test results to be definitive. Anyone traveling by plane this Thanksgiving should gear up as if their lives—and their loved ones’—depended on it. That means an N95 mask, face shield, gloves (enough pairs to change after every handwashing), and preferably a hazmat suit. But the wiser and safer decision is to stay home. Painful though it may be to forego the creature comforts of gathering in person for a decidedly less cozy virtual affair, the protection will be well worth it. This article originally appeared in Forbes and is available online here: One Man, One Plane, Seven Infections And Counting: A Cautionary Tale For All Those Planning Air Travel
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The Mental Health Toll Of COVID-19 Psychology Today | November 24, 2020 | Article
In September, the American businessman Ted Leonsis tweeted about an “underreported pandemic: mental health”. His comment about friends he’d lost to suicide sparked a public discussion on the impact of the pandemic on our mental wellbeing and raised awareness of an issue many kept hidden in the shadows. But if the pandemic has taken a toll on a billionaire like Leonsis, with easy access to the best in mental health support, pity its impact on the rest of us. A slew of studies show just how damaging COVID-19 and its ensuing lockdowns have been on the mental health of specific communities in America. No group has been left untouched — no gender, ethnicity, age or income bracket — but some have suffered much more than others from what I have termed CVTSD, COVID19 Traumatic Stress Disorder. Age and mental wellbeing In the spring, when the pandemic surged in hotspots across the country, much was made of the impact of COVID-19 on the mental health of older Americans, who were being cautioned to stay home and isolate for their own safety. Isolation and loneliness among the elderly were a cause for concern before COVID and many feared that lockdowns would worsen isolation for older adults and, consequently, depression and anxiety. A recent Kaiser Family Foundation study suggests these fears were realized, with one in four adults ages 65 and older reporting anxiety or depression in the months between the start of the pandemic and August — a rate substantially higher than the one in 10 older adults who reported depression or anxiety in 2018. What surprised many experts though was the toll COVID is taking on the mental health of younger Americans. A CDC study shows that while 40 percent of Americans are now grappling with at least one mental health or drug-related problem following the pandemic, young adults have been hit harder than any other age 510
group, with 75 percent struggling. Even more alarming, was the finding that one in four young adults, age 18-24, had contemplated suicide over a 30 day period in the summer. While official figures are slow to roll in to confirm an increase in suicides among younger Americans, anecdotal reports from coroners and medical examiners suggest significant spikes in suicides across the country, in children as young as nine years old. Race, suicide, and mental health Trend lines also suggest that suicides are higher among some racial communities, suggesting that the mental toll on these communities is far greater than others. Cook County, Illinois, reported more suicides among African Americans in the first six months of 2020 than in all of 2019 combined. While SARS-CoV-2 is indiscriminate in terms of who it infects, the structure of American society has resulted in higher rates of infection, hospitalization and death among Black, Latinx, and Native American populations. These communities are two to five times more likely to be infected with the virus and suffer its consequences than their white communities. As a result, people within these communities are more likely to have directly suffered with the loss of a loved one, whether a family member or friend, and more likely to report anxiety and fear around becoming infected. These communities also face much greater challenges because of the economic downturn. Black and Latinx families have median net worths that are significantly lower than their white counterparts — around ten times lower — which means job losses and financial stresses have hit these communities more than most, increasing the risk of depression, anxiety, substance use, and suicide. Gender and coping with COVID Women have been disproportionately affected by COVID-19 in many of the same ways that Black, Latinx, and Native American communities have been disproportionately affected. Women make up the majority of the essential workforce in America, putting them more at risk of infection. They are also more likely to have experienced job loss due to the economic downturn, with more women employed in the hospitality and food service sectors that were among the hardest hit by the pandemic.
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These stressors — already significant —- were compounded by school and daycare closures which continue across much of the country today. Women have taken on more of the burden for caring for children throughout the pandemic, forcing some to give up jobs, juggle working hours, and adding to their overall stress, frustration, and anxiety. As a result, 83% of women compared to 36% of men are reporting significant increases in depression. A path forward There are no quick fixes to the mental health problems COVID19 has created among Americans overall and these key communities in particular. But there are a few things we can think about as we try to move forward. For example, as a vaccine becomes available, we should think about how we might prioritize distribution based not just on the physical risk of infection and serious disease, but also on the secondary risks to a person’s mental health and wellbeing. Similarly, as we think about how we might restructure our healthcare system to prepare ourselves for future pandemics, we should think about the systemic change needed across sectors to protect ourselves against future equivalents of CVTSD — the emotional fallout from a pandemic. Finally, and perhaps the step most simple for each of us to accomplish today, we should begin to talk much more openly about mental health, in homes, businesses, and schools alike. Research shows even modest interventions — such as asking people if they’re okay — can reduce suicides. Physical and mental health are intertwined, and we should speak as openly about the latter as we do of the former. This article originally appeared in Psychology Today and is available online here: The Mental Health Toll Of COVID-19
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Why The Biden Team Must Prioritize Cheap COVID-19 Rapid Test Production And Distribution Forbes | November 30, 2020 | Article
All of us hope that a COVID-19 vaccine will bring an end to our current suffering. But even in the best-case scenario, by the time a vaccine is widely available, hundreds of thousands more lives will be lost. We must use the tools at our disposal to control the virus. Rapid antigen tests could make a difference, but we need much more of them. Mass producing these tests and distributing them to all in need should be the first task of the Biden COVID-19 Task Force and eventual administration. Since the start of the pandemic, the United States has administered far fewer tests than necessary. A testing tracker developed by the Harvard Global Health Institute suggests that the United States is administering barely more than half the tests we need. Current testing regimes and test supplies are simply not good enough. Most of these early tests took days or even weeks to deliver results, possibly allowing the patient to spread the virus in that time if they were positive. Federal authorities left test administration to the states, leaving many states underfunded, unorganized, and outmatched by the virus’s raging spread. The FDA recently approved the first rapid antigen test for home use. These tests are the key to controlling the destructive spread of COVID-19 we experience today. We suggest a mass production project yielding 150 million tests per day, meaning every person in the United States is tested two or three times per week. These tests will be universal, as in accessible by everyone regardless of region, income, or health status; they will be self-administered, as in any adult could test themselves and their children at home without the aid of a healthcare worker, then receiving results within about fifteen minutes. They will be remarkably inexpensive, meaning ideally fifty cents per rapid test. 513
President-elect Biden should activate the Defense Production Act so these tests can be mass-produced. Earlier in the pandemic, the Defense Production Act was activated to increase the production of N-95 respirator masks and ventilators, so it seems Biden could quickly bolster rapid test production via the same method. We have the production facility capabilities; we have the technology available to produce these tests en masse; we just need a leader to coordinate this effort. When these tests are more widely available, there must be a coordinated national effort to control the virus and financially support the households with positive cases. COVID-19 is spreading rapidly: approaching two hundred thousand infections and two thousand deaths every day. Rapid tests will catch both contagious asymptomatic and symptomatic cases. Those with a positive test or a positive case in the household must stay home. Even if sick leave isn’t available in their jobs, the hope is that many people will do their best not to infect those they regularly see and love. Though ideally, sick leave of around $500 per person in an isolating household per day would be available. A positive COVID-19 test should not equate to a lost paycheck and no food on the table for a family. Without a coordinated effort, the virus will continue to spread. At the current rate, by the end of February, there will be an additional sixteen million cases and one hundred fifty thousand deaths. With all likelihood, infection and death rates will continue to rise due to holiday travelers, so those estimates are incredibly conservative. The pandemic is going to get worse before it gets better. A vaccine will be a great weapon against the virus, but we can’t wait until then. President-Elect Biden: It’s time to take charge and fix this. This article originally appeared in Psychology Today and is available online here: Why The Biden Team Must Prioritize Cheap COVID19 Rapid Test Production And Distribution
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Put An End To Publication By Proclamation For COVID Vaccines Forbes | November 30, 2020 | Article
Covid-19 has dealt a blow to many Americans, physically, mentally, and economically. But even the heaviest of hearts is likely to have been lifted by recent promises from COVID-19 drugmakers about the effectiveness and safety of their vaccines. As hopeful as these promises may be, we have still not seen the full data from any of the Phase III clinical trials. So if the FDA approves one of these vaccines in the coming weeks, we will soon have to decide whether we trust the drug manufacturers and agree to the vaccine or whether we hold off until we can examine the data. This dilemma becomes even more profound for our medical workers, who are likely to be first in line for any approved vaccine. Many are hesitating to commit to taking the vaccine until more data are released. A reasonable request in my opinion, but a sign of how difficult it may be to convince average Americans to accept the vaccine. If the doctors won’t take it, why would we, as patients? Generally, questions around the safety or efficacy of these vaccines has had less to do with any single concern about the drugs themselves and more to do with how data about the drugs has been released. Since the launch of Operation Warp Speed, data on vaccines has been released first by the drugmakers themselves, by proclamation or by press release. Only later, and sometimes after much criticism, is the full data published and able to be examined. Meanwhile, executives at these drug companies have made significant amounts of money off their early announcements of success. Since the launch of Operation Warp Speed, reports suggest that executives at five of the companies receiving COVID vaccine funding made stock transactions that increased the size of their personal pocketbooks by nearly $150 million US. That figure includes stock sales up until the end of August and excludes more recent sell-offs, like the one by Pfizer CEO Albert Bourla earlier this month. Pfizer announced that their COVID vaccine was 90% 515
effective on the very same day that the CEO was scheduled to sell 60% of his company stock. He earned $5.6 million from the sale that day. I am no lawyer, but as a vaccine maker and former CEO of a drug company myself, I can tell you that what these drug companies are doing is absolutely verboten. Had I done in the past what these drug companies are doing today, I would have had the U.S. Securities and Exchange Commission and the Board of my company on me immediately. But the SEC has remained largely silent on the moves made by drugmakers this year, despite calls by watchdog groups and some lawmakers for an investigation. Self-interest colors credibility. No drug company should be allowed to announce premature trial results without providing the full data to back up their claims. The move may have a positive effect on company stock prices, the wealth of drug company executives, and the value of the entire market. But our concern is not with the billions that businesses stand to make with each new announcement. It lies with the many millions of lives at stake if doubts about a vaccine prevent the vast majority from taking it. Recent polling suggests that forty-two percent of Americans would say no to a vaccine, if offered one today. With those numbers, even if a vaccine is approved and available to all, we would still not be able to end the pandemic. To build trust in a vaccine, we must end the trend of publication by proclamation. Drug companies should release the data so we can make an informed decision about what we each do next. This article originally appeared in Psychology Today and is available online here: Put An End To Publication By Proclamation For COVID Vaccines
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December 2020
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Why Most Countries Won't Benefit From Moderna And Pfizer’s Covid-19 Vaccines Forbes | December 2, 2020 | Article
That the Moderna and Pfizer Covid-19 vaccines demonstrated efficacy in more than 90 percent of phase 3 trial participants is cause for celebration. Developed at breakneck speed with heretofore unrealized mRNA technology, they have without a doubt made history, especially now that the British government has authorized the Pfizer vaccine for mass use. The problem—and regrettably, it is a big one—is that only a very small fraction of the global population will be able to reap the rewards of this achievement. To remain stable, the Pfizer vaccine must be stored in specialized freezers kept at an ultra-low temperature of negative 94 degrees Fahrenheit. Such storage units are manufactured at a select few “freezer farms” and priced at $10,000 to $15,000 apiece. While the Moderna vaccine doesn’t demand as deep a freeze—the requisite negative 4 degrees Fahrenheit is comparable to a standard home freezer—both must be administered in two doses a month apart, a logistical hurdle not uncommon but certainly not ideal in a quest for worldwide inoculation. Even hospitals in the United States and Europe, where governments have already bought up hundreds of millions of doses of the mRNA vaccines, will be hard-pressed to secure the equipment necessary for their safe storage and transport—especially those in small towns and rural areas where many residents, due to adverse socioeconomic and health conditions, are disproportionately vulnerable to Covid-19. The same is true of remote regions in Africa, Latin America, and Asia. Airlangga Hartarto, head of the Covid-19 task force in Indonesia, told Reuters that in his country, the Pfizer vaccine has already been ruled out as a viable option—so unlikely is it to survive distribution between 270 million people across 17,000-plus islands. In other words, Pfizer and Moderna have created a Lamborghini when what most countries really need is a Toyota—a vaccine that 518
can be manufactured, stored, and administered simply and cheaply, preferably via existing distribution channels. Luckily, such alternatives exist. One is the adenovirus vaccine being developed by companies like AstraZeneca and Johnson & Johnson, which uses a nonlethal cold-causing viral vector as its means of inoculation, rather than synthetic proteins as mRNA vaccines do. Adenovirus vaccines are, however, hampered by one deep and fundamental flaw. Recipients would risk developing immunity not just to Covid-19, but the vector itself, meaning after initial rounds of rollout, another candidate might have to be developed from scratch. The AstraZeneca vaccine and others of its ilk can be thought of as Mercedes—not as high-maintenance as a Lamborghini, but certainly not as practical as a Toyota. Chances are high that vaccination against Covid-19 won’t be a one-and-done affair, but an annual or even biannual reoccurrence like the seasonal flu shot. As such, the most efficacious vaccine will be one that can be deployed for years to come. Two types of vaccines fall into this category. The first is the subunit vaccine, which injects particular bits of the virus intramuscularly. This technology is behind the vaccine that has played a critical role in eliminating hepatitis B, a disease that causes liver damage and cancers when contracted at a young age. The second is the inactivated vaccine, whereby the virus is grown, killed, and remade into a form of bodily defense. The Salk polio vaccine—the best example by far—accomplished this in 1955 and has been the backbone of polio eradication efforts ever since. Three of the four Covid-19 vaccine candidates that have emerged as major contenders in China are of the inactivated variety. While data on the safety and efficacy of these vaccines has yet to be released, hundreds of thousands across China have reportedly already received one of the candidates. Additional phase 3 clinical trials are being held in numerous countries the world over, from Bahrain and the United Arab Emirates to Argentina and Peru. Inactivated vaccines aren’t without risks of their own, and several in the past have gone south due to insufficient safety evaluation and monitoring. But done right, they’re also the most tried-and-true approach we have. Alternatives to mRNA vaccines that are more logistically feasible and cost-effective for all won’t be available quite as immediately, but have a far greater chance of reaching more people in need when they 519
do hit the shelves. Two to three months is my best guess, at which point we’ll have a better idea of which populations the Pfizer and Moderna vaccines cannot penetrate. In a pandemic, no country is an island—a lesson China is learning on a weekly basis as new infections arrive in one form or another from overseas. A vaccine all but exclusive to urban, high-income countries won’t cut it. The more pragmatic solution is a vaccine viable and affordable to all. This article originally appeared in Forbes and is available online here: Why Most Countries Won't Benefit From Moderna And Pfizer’s Covid-19 Vaccines
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These Forms Of Covid-19 Transmission May Be Rare, But Can’t Be Ignored Forbes | December 3, 2020 | Article
Last month, China was struck with its worst outbreak of Covid-19 in months—183 infections across Xinjiang, a city in the western province of Kashgar. While the majority of cases traced back to a garment factory, we now know the true source: contaminated freight trucks. China is proving to be our canary in the coal mine when it comes to rare—yet consequential, as the Xinjiang outbreak shows— types of Covid-19 transmission. Two I’ve written about previously, cold supply chains and longer incubation periods. Contaminated freight makes a third. All three contradict guidance issued by the U.S. Centers for Disease Control and Prevention (CDC). All three are also largely undetectable in countries where disease surveillance is crippled by a constant influx of new cases. Patient zero of the Xinjiang outbreak is suspected to be a male loading worker who, at the time of contagion, was handling trucks of export goods, according to the China Center for Disease Control and Prevention. Genomic sequencing and analysis later uncovered traces of virus on the interior surfaces of multiple trucks. The agency’s chief epidemiologist, Wu Zunyou, noted that it is unclear whether the man contracted the virus from a contaminated surface or contaminated air. Either way, the evidence urges us to recognize a hazard heretofore largely dismissed—domestic and in particular international freight. Those of us currently in the thick of crisis have reason to pay attention to how China attends to its outbreaks’ more unusual suspects. First, it only takes one person to start—or in China’s case, given their near total elimination of the disease, restart—an epidemic, and as such even the most uncommon phenomena warrant scrutiny and caution. Second, China has gone to extreme lengths to contain Covid-19, as have its citizens. What occurs sporadically in China will likely be much more prevalent in countries 521
where the government and the people have a more relaxed approach towards containment, the United States among them. Since viruses fare far better at the lower temperatures winter brings than warmer climes, containers left cold and wet will naturally aid and abet their survival. While the shipments in the Kashgarbound trucks were neither frozen nor refrigerated, imports of frozen food have been linked to clusters of new Covid-19 cases along the eastern coast of China and, a hop and skip away, New Zealand. Chinese health authorities located virus on the packaging of frozen shrimp from Ecuador, squid from Russia, and chicken wings from Brazil, just to name a few. As recently as last week a handful of Covid-19 cases in Shanghai were linked to an air cargo container that held, once again, cold and frozen foods. While the U.S. CDC guidelines acknowledge that Covid-19 can spread from the surfaces of objects, they also say it is “unlikely to be spread from domestic or international mail, products or packaging.” Now we know this might not be the case. The same is true of another form of transmission that has provoked policy change in China, but virtually nowhere else—infection by a small fraction of people who take longer than two weeks to get sick after being exposed to Covid-19. The Chinese government has determined, according to local authorities in Shanghai, that as many as five percent of Covid-19 cases could fall into this category. Though lacking a specific citation, the claim isn’t without precedent. A study conducted by Chinese researchers early on in the pandemic and later published in New England Journal of Medicine pinpointed the incubation period between 0 to 24 days. For one man, government officials in Hubei Province reported in February, incubation took nearly four weeks. A preprint that analyzed more than 60 articles on the subject found the upper limit in some reports to be even higher—a maximum 34 days. A figure like five percent may seem too slight to be significant, but we must remember it doesn’t account for the many others those five percent could infect if they emerge from a two-week quarantine based on the false assumption they’re in the clear. In the United States, daily case counts are now toppling 200,000. Five percent of that figure alone is 10,000—a drop in the bucket in the grand scheme
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of things, perhaps, but plenty enough to drive up the spread of disease. Even contaminated freight, which so far has infected people by the tens and low hundreds, presents a risk that cannot be ignored, considering such outbreaks are bound to go forth and multiply into far greater proportions if not contained. (Not all countries are able to test 4.75 million residents in three days, as China did in the wake of the Xinjiang outbreak.) The practical consequence should be to sanitize our hands and surroundings far more frequently than we do now, especially after handling any packages or frozen foods delivered in these cold months. But more broadly speaking, we need to broaden the scope of our thinking around what causes and perpetuates the transmission of Covid-19 and revise our public health guidelines accordingly. Now that China has set an example, we won’t be able to claim we were caught unawares. This article originally appeared in Forbes and is available online here: These Forms Of Covid-19 Transmission May Be Rare, But Can’t Be Ignored
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America Needs a COVID-19 Reckoning The Atlantic | December 3, 2020 | Article
The coronavirus pandemic is a far greater economic and societal threat than anything the United States has faced in recent memory. The 9/11 attacks took nearly 3,000 lives. COVID-19 has taken a quarter million. The nation’s responses to these two threats—one a palpable and immediate terrorist attack; the other a virus that crossed our borders sight unseen—have been wildly divergent. About a year after 9/11, President George W. Bush signed legislation establishing a bipartisan commission to “prepare a full and complete account of the circumstances surrounding” the attacks. By figuring out what had gone wrong, the men and women on the panel would help prevent the same mistakes from recurring. A year has now passed since the first official reports of a new coronavirus in China. Our day of reckoning should be upon us, but Americans are too lost in our current tragedy and governmental obfuscation to protect ourselves from another catastrophe, be it another coronavirus, a deadly strain of the flu, or any other biological threat, including a bioterror attack that could dwarf the impact of COVID-19. This is a grave mistake. One of the first acts of President-elect Joe Biden’s new administration should be the creation of a COVID-19 commission to address the pandemic and prepare for future threats. His newly announced COVID-19 task force will rightly focus on helping the United States find a way out of our current morass. But the country also needs a separate, bipartisan inquiry that points to long-term structural solutions that would prevent a future disease from causing the levels of death, heartache, and economic disruption that the coronavirus has caused. If the new Democratic president and Republicans in Congress can agree on nothing else, surely they can agree on the need to learn from Americans’ current suffering. Formally known as the National Commission on Terrorist Attacks Upon the United States, the 9/11 Commission interviewed more than 1,000 people during a two-year investigation. It held 10 524
days of public hearings. In 2004, the bipartisan committee issued a 585-page report that identified “failures of imagination, policy, capabilities, and management” across the government. One key problem that members noted was a lack of coordination among government agencies, which left essential dots of intelligence unconnected. By overlooking crucial details—including false visa applications, fake passports, and suspect travel patterns—multiple agencies missed opportunities to thwart the men who ended up hijacking passenger jets and using them as weapons. The report showed the urgent need to restructure government operations to deal with the long-term, recurrent threat of terrorism. Congress had created the Department of Homeland Security in 2002, and the report established clear priorities for the fledgling agency. Today, DHS employs 240,000 people and oversees the country’s naturalization and immigration system, cybersecurity, and the TSA, which was also created in the aftermath of the attacks. The TSA is ever present in the lives of traveling Americans today, with its 47,000 officers performing all searches and screenings at airports. DHS’s duties also include ensuring an effective emergency response to major disasters, aiding recovery from disasters, building a comprehensive national incident-management system among federal, state, and local authorities, and developing comprehensive communication strategies for major disasters. The second significant institutional change was the creation of a Cabinet-level director of national intelligence in 2004. The DNI’s primary function is to oversee and coordinate among the NSA, the CIA, and other parts of the U.S. intelligence community, so that information that needs to be shared across the government doesn’t end up siloed within a single entity. These two changes transformed our government’s response to terrorist threats. Over time, federal surveillance powers were expanded, as was the scope of some criminal laws. After 9/11, Americans accepted more limits on their freedoms: increased security at airports, bag checks and camera surveillance at major public events. While perhaps not welcomed, these limitations were widely understood as necessary to protecting our nation against future attacks. The 9/11 Commission had focused the discussion, both in Congress and among the general public, on which
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adjustments and compromises Americans should contemplate in the name of safety. Like the 9/11 attacks, the coronavirus pandemic has revealed a dangerous lack of preparedness. In April, Representative Adam Schiff, the California Democrat who chairs the House Intelligence Committee, circulated a discussion draft of legislation to establish a bipartisan commission to provide a full accounting of the country’s response to the pandemic. The draft mimics the legislation that led to the establishment of the 9/11 Commission almost word for word, except that the nominating process for the new panel would be more overtly partisan than that for the 9/11 Commission. For a COVID19 commission to succeed, it needs bipartisan support from the beginning; its purpose must be to move beyond blame and seek long-range solutions to America’s vulnerability to disease. Throughout the course of this pandemic, politics has been an obstacle to public-health initiatives. A true accounting of what led us to our situation today—where the U.S. ranks among the 10 worst countries in the world on a deaths-per-capita and infections-percapita basis—requires an honest assessment of our failures, politics and party aside. A COVID-19 commission could interview officials from the U.S. military’s National Center for Medical Intelligence, which in November 2019 issued a report warning about the coronavirus then emerging in southern China. Panel members could also interview Robert Redfield, the director of the CDC, who was first notified about the new disease on January 3. They could speak with the White House national security adviser and his deputy, who warned the president of the threat on January 28. The list of people with potential insights also includes authorities at the local, state, and federal level; intelligence and law-enforcement officials; diplomats; border-control officials; pharmaceutical executives; and employees of global-health institutions. The COVID-19 commission should analyze resource-allocation blunders, potential failures of oversight by the White House and Congress, and the inability of the federal government to leverage its full weight to combat the disease. The questioning should sidestep the politics of the moment—as members of the 9/11 Commission tried to do—and focus firmly instead on what the nation could have done better. As with the 9/11 terror attacks, the coronavirus pandemic is not the result of a single 526
misstep. Our pandemic failures are the result of years of unpreparedness across administrations and months of downplaying the severity of the virus. The Trump administration dismantled the National Security Council’s pandemic-response unit in 2018, but America’s cycle of inattention to disease-related threats has roots that go back much further than that. The list of agencies with a role in the U.S. pandemic response includes DHS, FEMA, the CDC, the National Institutes of Health, and the Public Health Service. Yet they, like the agencies responsible for counterterrorism prior to 9/11, often act separately and without detailed knowledge of what others are doing. The establishment of DHS and the DNI as coordinating entities can act as a blueprint for post-coronavirus reforms. A COVID-19 commission might consider the creation of a new body, equivalent to the National Security Council or National Economic Council, but for disease. A National Disease Council could coordinate efforts to prepare for and defend ourselves against natural or man-made biological threats. Developing a Cabinet-level position, akin to the DNI, to lead this National Disease Council would allow for the implementation of a national pandemic-preparedness program. This article originally appeared in The Atlantic and is available online here: America Needs a COVID-19 Reckoning
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UK Vaccine Approval Sets Worrying Precedent For World Leaders Forbes | December 4, 2020 | Article
When the British government authorized Pfizer’s Covid-19 vaccine for mass use on Wednesday, it didn’t take long for backlash to arrive—first and foremost from the European Medicines Agency (EMA), the regulatory entity entrusted with vetting vaccines for the European Union (EU). Not a day after the announcement, Al Jazeera reported that an EU spokesperson criticized the decision and called the EMA’s own authorization procedures “the most effective regulatory mechanism to grant all EU citizens’ access to a safe and effective vaccine.” Several European legislators also made a point of expressing their disapproval, with one calling the move “problematic” and recommending neighboring countries to not follow suit. Pfizer and Moderna made history when they announced last month that their vaccine candidates—made using unprecedented mRNA technology—had demonstrated more than 90 percent efficacy in phase 3 clinical trials. The EMA has said previously that it will reach a decision regarding the Pfizer vaccine, which has yet to be cleared for emergency use in any country other than the United Kingdom, by December 29, while their verdict on the Moderna vaccine will likely arrive in early January. This stands in stark contrast to Britain’s ultra-expedient review, completed barely 10 days after Pfizer first publicized their results. As of Wednesday, England has also ended its second national lockdown, allowing restaurants and gyms to reopen and weddings and religious gatherings to resume. While the newly lifted restrictions had driven the country’s case count down by about 30 percent, tens of thousands of new cases continue to be reported weekly and will only increase in number, especially with the winter holidays fast approaching. At this rate, Britain can expect to see a dramatic surge in infections arising around Christmas and christening the new year. 528
The one-two punch of premature reopening and hasty vaccine authorization is ill-advised, if not suspect. In times of crisis, especially with millions of lives on the line, the temptation to prioritize speed over safety can be difficult to resist—that well-trodden path of eschewing appraisal for action no matter the consequences, rather than hunkering down to ensure maximum harm reduction. But even a cursory cost-benefit analysis shows that only one faction stands to benefit from these maneuvers: Prime Minister Boris Johnson and his Conservative Party. The prime minister has some of the best scientists and public health leaders in the world in his ear. He knows full well that a lockdown is still necessary, and that a vaccine approved now will take at least two months to have any discernible effect on the spread of disease. To make both moves in one fell swoop is to neglect the best interests of an unsuspecting public in favor of appeasing a zealous faction of conservative lawmakers. As the EU and EMA were so quick to point out, steamrolling regulatory protocols for a technology that has never been deployed at this scale could yield more risk than reward, especially with public confidence in vaccines so low. It also sets a worrying precedent for other world leaders—in particular President Donald Trump, whose administration has garnered a reputation for authorizing unproven or unreliable drug treatments for political clout. Before rushing authorization and mounting a full-fledged vaccination campaign, health authorities in the United States, Europe, and elsewhere must throw considerable weight behind not just a robust approval process, but repairing public acceptance and trust in vaccines. Former US presidents Barack Obama, Bill Clinton, and George W. Bush will be getting vaccinated on live television for this reason, but votes of confidence from figures outside the political establishment—scientists, celebrities, community leaders, and other thought leaders and influencers—are just as necessary. If governments don’t carefully consider and heed the concerns of their people when choosing how to proceed from here, they risk stripping one of our most tried and true instruments of pandemic control of its power. To do so would be at the peril of us all. This article originally appeared in Forbes and is available online here: UK Vaccine Approval Sets Worrying Precedent For World Leaders
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Modified CDC Guidelines Grant Covid-19 Patients Discretion To Leave Quarantine Early Forbes | December 4, 2020 | Article
In recent days, the CDC modified its quarantine guidelines such that infected individuals do not necessarily need to follow them. They still officially recommend fourteen days for Covid-19 isolation before returning to society, but quarantines may be reduced to only seven or ten days at the infected individual’s preference in certain cases. This change is a confusing approach to quarantine policy as the pandemic grows worse. Rather than affirmatively changing quarantine guidance, the CDC left quarantine decisions to the isolated individual’s preference, which will lead to unnecessary transmission and a longer pandemic. Covid-19 cases, hospitalizations, and deaths are peaking in the United States. Now would be the time to bolster public health standards to counter these trends, but instead, the CDC insists on softening measures meant to keep us safe. While the official CDC recommendation is fourteen days, the guidelines now state that quarantine can end after ten days if no symptoms exhibit throughout. Additionally, quarantine can end after day seven if the patient showed no symptoms and tested negative. Allowing individual discretion enables people to exit quarantine while still contagious. The CDC admits as much. The recommendation mentions that reducing quarantine lengths to seven to ten days comes with a 112% chance of post-quarantine transmission. Let’s do the math. On December 2nd, the United States reported about 200,000 positive cases. Assuming they all went into quarantine and stayed isolated for seven or ten days, 2,000 to 24,000 of those cases would go on to infect others. How is this acceptable? Why risk it? The shift seems based on CDC research that post-quarantine transmission risk drops after day five. Though, at their admittance, the transmission risk still exists. The risk of up to a 12% chance seems more than unnecessary. If a fourteen-day quarantine could cut that risk even only by 50%, that would equate to stopping potentially 530
12,000 cases from transmitting to others from the December 2nd group. It just does not seem worth the risk to shorten quarantines by a week or less. As we move in the direction of less caution, the Chinese government recently recommended the opposite. Studies have shown that around 5% of Covid-19 cases have incubation periods longer than fourteen days, and China is taking action accordingly by extending quarantines to 21 days. China has been at the forefront of Covid-19 public health policy throughout the pandemic. The country of nearly 1.4 billion people has had only 93,000 confirmed Covid-19 cases. Daily case reports have not surpassed 100 since midsummer. China is not the only country to stray from the fourteen-day quarantine. European countries like France and Belgium reduced their quarantine lengths to seven and ten days, respectively. Both countries experienced an explosion of Covid-19 cases in recent months after handling the start of the pandemic rather well. France reached a daily average of nearly 50,000 cases per day in early November, requiring a new lockdown to bring spread under control. Belgium experienced a similar trajectory of increased cases in the fall. Reduced quarantine limits may have contributed to the virus’s aggressive spread, which does not bode well for Americans who intend to follow the CDC’s seven to ten day options. Ultimately, a reduction of quarantine length will only extend the pandemic in the United States. People need to stay home if they are infected, whether symptomatic or not. There should not be a rush to get back into the world, especially if there is a chance to spread the virus to others. The CDC may suggest shorter quarantines are acceptable, but please err on the side of caution. Keep those you regularly see and care about safe. Stay home. This article originally appeared in Forbes and is available online here: Modified CDC Guidelines Grant Covid-19 Patients Discretion To Leave Quarantine Early
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New Study Shows Deep Impact Of Climate Change On Human Health Forbes | December 8, 2020 | Article
Our visual narratives of climate change have, historically, been replete with spectacular images of fire and flood. But the blood orange skies that loomed over San Francisco in early September— precipitated by a freak lightning storm that set regions surrounding the Bay Area ablaze—were what captured the popular imagination this year, at least in the United States. Photographs of the phenomenon, mundane otherwise, paint an ominous portrait of what awaits our warming world—more disaster, yes, but also warpings of everyday life as we know it. What’s at stake isn’t just the blueness of skies, but centuries of progress in human health that have allowed us to pursue longer, more active, and overall more fulfilling lives. To drive this home, a new report published by The Lancet Countdown, an interdisciplinary collaboration between 120 experts and 35 institutions, uses rigorous data collection and analysis to connect the dots between the well-being of our planet and ourselves. More than a compendium of stats, the report is a call to action for health professionals and policymakers the world over. If we want to retain the gains and livelihoods we’ve made as a species, it argues, we must recognize and mitigate the losses we’ve wrought on the natural world. From Siberia to California, wildfire scorched the earth in 2020. The number of people exposed to wildfire risks from 2016 to 2019, when compared with 2001 to 2004, has increased in 128 countries— in other words, most of the world. In California—no stranger to natural disaster but also known and revered for its temperate climes—this year was its worst for wildfires. Barely a day after the Countdown report was released, fire caught in the canyons of Orange County, fueled by wind gusts that exceeded 70 miles per hour. Over Labor Day weekend, the calamity was even worse— complete with far-reaching blackouts, incendiary bush fires, and 532
barrages of military helicopters dispatched to rescue whomever they could. Globally, for all ages, the number of heat-related deaths in 2018 was almost 300,000—a sad testament to the combined power of skyrocketing temperatures and intensifying heat waves that occur in the hundreds of millions each year. Extreme heat has been linked to everything from civil unrest and political instability to violence and suicide. In the past 20 years, according to the Countdown report, the number of people in the United States who have died due to heat-related causes has nearly doubled, reaching a record-high peak of 19,000 in 2018. To live past the age of 65, well into our 80s, 90s, and even 100s, was a hard-won milestone that some countries, as of 2015, have yet to reach. Today it is in jeopardy. According to another report released this year by the International Federation of Red Cross and Red Crescent Societies, extreme weather and natural disasters have killed more than 400,000 people worldwide since 2010. Notably excluded from that total are fatalities caused by infectious diseases like HIV, Ebola, Zika, and of course Covid-19, many of which make the leap to human hosts from other members of the animal kingdom. In less than a year Covid-19 has claimed more than 1.5 million lives around the world, while almost one million people die from HIV annually. Although infectious disease outbreaks aren’t classified as natural disasters per se, they’re inextricably bound up in climate and ecological dynamics— meaning that as environmental conditions become more volatile and landscapes more fragmented, the footholds available to pathogenic viruses increase in breadth and number. The Countdown report says that Covid-19 will contextualize our response to climate change for many years to come—as it should, given that disturbed habitats, deforestation, and wildlife markets are creating more ecological niches where novel disease-causing viruses and bacteria might thrive. Examples given in the report—to say nothing of unknown viruses, or what pandemic expert Dennis Carroll calls “viral dark matter”—include malaria, dengue, and Vibrio, a coast-dwelling bacteria that can cause water- and foodborne illnesses. In some parts of the Northeast, coastal waters have become 99 percent more suitable to Vibrio bacteria in just five years, permitting the propagation of a microorganism that can cause flesheating infections and even death in humans. 533
One European study estimates that nearly half the global population remains unaware of the connection between climate and disease—a gap in general knowledge that health professionals, scientists, and other thought leaders, using the current crisis as a catalyst, can begin to fill. From 2018 to 2019 alone, media coverage of the intersection of climate change and health at large increased 96 percent, while between 2007 and 2019 research on the same subject increased eight-fold. As was the case with tobacco restrictions and sanitation and hygiene practices more broadly, the science supporting the relationship between human and planetary health is there, and the devastating effects of Covid-19 are positioned to give it more prominence. What is needed now—what the Countdown report calls for—are economic, social, and environmental policies that codify this knowledge into a framework for sustained action. To this effect, the report recommends a slate of climate-mediated public health interventions specific to the United States that run the gamut of national infrastructure—among them divesting from fossil fuels, shifting to zero-carbon electricity, and reforming antiquated standards of agricultural production. It also advocates for an increase in public health spending that might begin to repair the growing damages of climate change. In the fiscal year 2018-19, barely $13 per person was spent on climate change adaptation in the health sector. We must not only increase that share substantially, but also communicate the urgency of such measures to the public. We only have one planet—and with Covid-19, one major opportunity to rally momentum around efforts to protect it. Let’s not allow either to go to waste. This article originally appeared in Forbes and is available online here: New Study Shows Deep Impact Of Climate Change On Human Health
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Cancer Rates Are On The Rise In Adolescents And Young Adults New Study Shows Forbes | December 8, 2020 | Article
While much of the health system and the world are, understandably, laser focused on the Covid-19 pandemic, it is all too easy to discount other health issues that must be addressed. In a recent study of cancer trends among adolescents and young adults in the US, researchers reported a stunning thirty percent increase in cancer diagnoses among individuals fifteen to thirty-nine years old between 1973 and 2015. Recently, there has been an increased awareness that adolescents and young adults are a distinct population when it comes to cancer. A cancer diagnosis at this pivotal stage in life where young peoples’ independence is increasing, careers are beginning, and new relationships are forming can be particularly destabilizing. In addition, adolescents and young adults are often less financially stable than older adults and have the lowest rates of health insurance coverage. There is also evidence that tumors in this age group are different on a molecular level from the tumors found in either children or older adults. While survival rates are higher among adolescents and young adults with cancer compared to older adults, cancer patients in younger age groups have a higher risk of developing long-term effects stemming from their cancer such as infertility, cardiovascular disease, sexual dysfunction, and cancer later in life. Because of young peoples’ unique experience with cancer, there has been more research trying to understand the rates and causes of cancers in this age group and to determine effective treatment options. This new study looking at trends in cancer diagnoses between 1973 and 2015 in adolescents and young adults provides important new insights on the long-term characteristics of cancers in this population. Researchers collected data on age at diagnosis, sex, race, type of cancer, and survival from almost 500,000 of the adolescents
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and young adults diagnosed with cancer between 1973 and 2015 from a National Cancer Institute database. Of the almost 500,000 individuals between the ages of fifteen and thirty-nine with invasive cancer included in this study, 80% were white. This surprising finding was unaddressed by the researchers and is another stark example of the disparities in access to healthcare between white and non-white populations. Diagnosis of cancer at a later stage, or not at all, contributes to the worse cancer outcomes among non-white individuals that too often occur. Overall, there was an increase in cancer incidence of almost 30% between 1973 and 2015. According to this research, colorectal, thyroid, and testicular cancers along with melanoma and nonHodgkin lymphoma are most responsible for this increase in cancers among adolescents and young adults. Researchers suggest that the increase is likely due to a combination of environmental and lifestyle factors, and changes in screening and diagnosis. Rates of obesity in adolescents and young adults have increased considerably in recent decades. For example, in 1998, 30.5 percent of young people were obese, compared to 42.4 percent in 2018. Given colorectal cancer’s strong link to obesity, the increasing obesity rates among adolescents and young adults likely also resulted in increased cancer rates as well. The increase in melanoma, which was greater among women than among men, may be due to increased sun and other sources of artificial UV exposure. Changes in diagnostic procedures may also play a role in this large increase in cancer incidence. For example, advances in detection practices and imaging for thyroid cancer have resulted in more people being diagnosed with the disease. This does not mean that more adolescents and young adults are developing the disease than they were before, but now we have better technology to find people with thyroid cancer so they can be treated. On the whole, cancer rates increased over the forty-two-year time period studied, but there were some exceptions. New cases of lung cancer and cervical cancer decreased over time, like due to a decrease in smoking rates and the discovery and availability of the vaccination for human papilloma virus (HPV) that protects against about 70% of cervical cancers. To see an increase in cancer rates of 30% over forty-two years, especially with rates of some cancers going down, is concerning. 536
While increases in obesity rates and improved detection methods of certain cancers explain some of the increase in cancer among adolescents and young adults, this large increase in cancer rates among a population group that is relatively healthy must be explored further. Cancer is the leading cause of disease-related deaths among young people. Advances in cancer prevention methods and treatment can have a huge, positive impact on the health of our nation’s adolescents and young adults so that they can be gaining independence and beginning their adult lives, not battling cancer. This article originally appeared in Forbes and is available online here: Cancer Rates Are On The Rise In Adolescents And Young Adults New Study Shows
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COVID-19: An Investment in Our Economy Think Global Health | December 10, 2020 | Article
The COVID-19 pandemic has already killed 1.5 million and sickened more than 68 million others — so it’s hard to fathom that its final death toll and health consequences will far exceed these numbers. The pandemic has affected all parts of the world and it has also disrupted every aspect of global health. Necessary precautions undertaken to slow the spread of the coronavirus are threatening to reverse decades of progress on infectious and chronic diseases that have improved the health of millions of people around the world. Vaccination coverage this year dropped to levels last seen in the 1990s, which will inevitably lead to new outbreaks of highly contagious diseases like measles and polio. Before the pandemic started, the growing toll of measles was a top concern for many public health officials. Now, 26 countries have had to pause their measles vaccination campaigns to focus instead on slowing the spread of SARS-CoV-2, leaving 94 million people at risk of missing these crucial vaccinations. Polio vaccination campaigns have been postponed in 28 countries, leading to new outbreaks— especially disappointing given how close a decades’ long effort had brought us to eradicating that disease worldwide. Health experts are equally concerned about a potential rise in cases of malaria, HIV, and tuberculosis — the big three of infectious diseases — as prevention and treatment efforts wane because of COVID-19-related restrictions. Some models predict that malaria deaths in sub-Saharan Africa could as much as double if prevention and treatment are severely hindered. The pandemic has similarly disrupted care for chronic diseases, reproductive health services for mothers and infants, and neglected tropical disease control programs, further heightening the stress on health systems globally. The last time an uncontrolled outbreak placed an equivalent amount of stress on global health systems was when HIV/AIDS loomed large. Indeed, the COVID-19 timeline, though vastly accelerated, mimics in many ways the early years of the HIV 538
pandemic: an unknown virus, a new disease, and a determined effort by public health experts to convince the general public of the scope of the danger. COVID-19 mimics AIDS in another important way: both diseases can and did quickly wreak havoc on our health systems and economies. AIDS’ impact on the economy was only slowly recognized — but substantial. The disease drove families into poverty when members fell ill and lost their jobs and when household budgets could no longer sustain the costs of medical treatment. Hospitals in hard-hit areas reported mounting fiscal strains and were unable to care for all patients in need. Countries lost hundreds of billions of dollars. Indirect costs of the first 10,000 cases of AIDS in the United States alone were estimated at $4.8 billion, and the year-to-year impact rose from $3.9 billion in 1985 to $7.0 billion in 1986 to $55.6 billion in 1991. Yet for 15 years, with limited funding and inadequate leadership, the world didn’t act — while more than 1.5 million people died and tens of millions were newly infected. COVID-19 presents us with an accelerated timeline, and we find ourselves in a similar spot just one year into this disease: tens of millions infected, more than 1.5 million deaths and a lack of leadership, action, and funding to blame. The year 2000 was a turning point on HIV/AIDS — we shifted how we thought about the disease and how we approached it as a global community. Instead of relegating it to the realms of public health alone, important leaders like then U.S. Ambassador to the United Nations Richard Holbrooke began talking about HIV as a matter of global security and economics. In January of that year, Holbrooke organized the first special session of the UN Security Council on HIV/AIDS. It was the first time the Council had ever addressed and debated a health issue. The next year, Holbrooke created the Global Business Coalition on HIV/AIDS, which mobilized business leaders in response to HIV and fostered unprecedented commitments from across the corporate sector. The message was clear: AIDS was not just a health issue. It affected the peace, security, and economic wellbeing of the world. Following this shift in thinking, funding and action on AIDS increased dramatically. Today, we need a similar shift in the narrative around COVID19. The economic impact of the pandemic is already well539
recognized, but too much of the debate pits health against the economy, as if they are two separate issues vying for our attention — do we save lives or save our livelihoods? What people fail to recognize is that the health of an economy depends on the health of its people. COVID-19 has demonstrated that our health systems are weak and easily fractured. Too many countries were unable to meet the surge in demand that this new virus created. Too many providers were unable to quickly shift to delivering routine telehealth services when hospitals shut down for all cases save those with the most acute needs. Too many patients were stranded in hospital beds and longterm care clinics instead of receiving care at home, where they could have been kept safe. As our health-care system collapsed, a critical diver of our economy fell with it: our workforce. Policymakers and business leaders must recognize that an investment in health is an investment in the economy, and an essential priority. The economic losses due to this pandemic are not solely the product of lockdowns. Employees have fallen ill or quit to take care of family, businesses have shuttered because of infections, and customers who fear hospitalization and lack health insurance are holding tight to their wallets. And the challenges will only be greater during future pandemics— the global population is aging, chronic illnesses are on the rise, and the potential for new and rapidly spreading pathogens is higher than ever. In the wake of COVID-19 we need a new message: economic growth is not just a function of our national productivity, regulatory frameworks, and trade policies, but a product of the performance of our health systems themselves. The UN helped highlight health and wellbeing as an essential component of sustainable development by enshrining it in its Sustainable Development Goals (SDG). Five years after the creation of the SDGs, COVID-19 is showing us just how poorly we have fulfilled the targets they laid out. The limited progress we have made is quickly disappearing, and our lack of preparedness for future pandemics could jeopardize future progress, too. This pandemic is an opportunity cloaked in tragedy. We have to improve disease surveillance to avoid future disasters. We need to improve our ability to respond to health emergencies. And we must invest in critical twenty-first century public services to improve our health systems and ensure their resilience in the face of any challenge. 540
This article originally appeared in Think Global Health and is available online here: COVID-19: An Investment in Our Economy
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How Will A Covid-19 Vaccine Impact Travel? Forbes | December 11, 2020 | Article
In the past decade, the world has seen a steady rise in travel and tourism that undoubtedly influenced the trajectory of the Covid-19 pandemic. People flew in and out of China six times as much on a daily basis in 2018 than in 2002—the year SARS, the first coronavirus to become lethal to humans, first appeared. Just as travel, and global mobility more broadly, has changed how fast and far infectious disease can spread, Covid-19 will no doubt impact how we travel. But what about a Covid-19 vaccine? Will the Pfizer vaccine on the verge of approval in the United States make travel safe again? At the moment, what we know about the Pfizer vaccine particularly is that it very likely protects against mild and, though this data is weaker, serious disease. What we don’t know—what prospective travelers must consider—is whether the vaccine prevents or at least reduces infection and transmission. We also don’t know how long vaccine-mediated protection lasts. It could be months, a year, or longer. Until enough time passes, we won’t be able to measure either variable. How we conduct ourselves in the meantime, then, is the question. Even if prevention measures and travel restrictions stay in place, once a safe and efficacious vaccine is available for mass use we can expect public attitudes and behaviors to shift accordingly. Once vaccinated, people who have holed up at home since the spring will be tempted to flee the coop and catch the next flight to their dream destination—whether that’s grandma’s house, Honolulu, or Honduras. You can’t blame them, either. Had public health interventions been enforced with adequate strategy and rigor early on in the pandemic, many more of us might be homeward bound for the holidays. So long as we don’t know whether vaccinated individuals can still catch and spread disease, however, we’ll need to exercise as much caution as ever. That means continuing to wear masks, wash 542
our hands, and yes, social distance. Vaccinated or not, we could very well still be vectors of disease. Until we know with certainty this isn’t the case, discarding the habits we’ve formed to protect ourselves and those around us won’t end well. Although some policies are necessarily here to stay, others will have to be redrawn to accommodate the realities of mass vaccination. One is the travel policy China debuted last month requiring, in addition to a negative PCR test result for Covid-19, a negative IgM antibody test result. The PCR test measures the amount of viral RNA in the nasopharynx, while the IgM test essentially detects whether or not the body has produced an initial antibody response against Covid-19. Those who receive a vaccine might test positive for Covid-19 specific antibodies despite being protected from sickness. Unless the rule changes, travel to China for the vaccinated will be difficult. There is another potential complication, though far less likely. Some of the RNA used to develop the Pfizer and Moderna vaccines—both of which were without precedent and created with the same technology—could have longer half lives than expected, making it detectable by the average PCR test. Tried and true methods that capitalize on other parts or forms of the virus, like the proteins used to develop subunit vaccines, would be easier to work around, but at least in the United States don’t have a horizon for rollout just yet. All in all, we must face the fact that a Covid-19 vaccine, no matter how successful, won’t be enough to pave over the bumpy road ahead, least of all when it comes to traveling. Rather than planning and preparing for a post-pandemic world, we should hunker down for a hazy limbo of sorts—knowing that if we continue to follow safety guidelines and take great care going forward, even after getting vaccinated, we’ll be that much closer to ending the current crisis for good. This article originally appeared in Forbes and is available online here: How Will A Covid-19 Vaccine Impact Travel?
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Even With A Vaccine, We Still Need Rapid Tests To End Covid-19 Forbes | December 11, 2020 | Article
Yesterday, an independent FDA advisory panel gave Pfizer’s Covid19 vaccine—already approved in Britain, Canada, and Saudi Arabia—its vote of confidence, setting it up to be authorized as early as this weekend for emergency use in the United States. Their recommendation extends to anyone age 16 and over, with health workers and long-term care residents first in line to get vaccinated. Sadly, the approval of a vaccine will not mark the beginning of the end of the pandemic in this country or any other—not if the public health measures we’ve mounted against the disease are left in their current state of dysfunction and disrepair. One intervention that is absolutely critical, yet in the US still severely lacking, is rapid testing. Beyond social distancing, mask wearing, and frequent handwashing—beyond the vaccine itself—rapid testing is what can give us the momentum we need to outmaneuver the virus that, up until now, has bested us at every turn. Imagine if, in households across the country, every parent could test themselves for Covid-19 before going to work, and every child before going to school. Imagine if schools could test every student and teacher, and if workplaces could do the same for their employees—within minutes, not days. State-sponsored rapid testing initiatives, whether they’re for schools in Tennessee or small businesses in Texas, are on the rise. But without the full force of federal policies and funds behind them, such programs simply cannot be as effective or far-reaching as they could and should. They also can’t provide households the economic support they need to isolate comfortably at home if one member tests positive. Rapid, self-administered Covid-19 tests should be available to anyone who asks for them. The tests themselves exist, some as easy to use as a pregnancy test and accurate enough to detect more than 95 percent of those contagious. The manufacturing capacity to produce more than 50 to 100 million tests per day also exists—and 544
the components required for assembly, cheap enough that they could be produced and potentially sold for less than 50 cents each, as demonstrated by the universal screening program that eradicated hepatitis C in Egypt. Rapid tests are so handy that one hospital in Latvia even has plans to install a vending machine that dispenses them, the first of 100 to be distributed all over the country. Beyond convenience and affordability, the benefits of rapid testing are well-documented. Widespread rapid testing, a recent UK study found, reduced the spread of Covid-19 in Slovakia by about 60 percent in just one week when combined with economic support for those who test positive and cannot work. Similarly steep declines in case counts have been observed in Liverpool following the launch of mass testing. In Austria, a successful new pilot program that dispatches mobile rapid testing teams to schools in at-risk areas will be expanding nationwide this month. And rapid testing at college campuses across the US has been so fruitful that some are partnering with local health authorities to broaden access to the wider community. The failure of the United States to provide these tests to all its citizens, many months into the pandemic, is multilayered. First and foremost was the failure at the highest levels of federal government to understand the power of rapid testing in curbing the spread of Covid-19. Even when the US administration buckled down and bought up hundreds of millions of rapid tests in August, they still failed to devise a national strategy for distributing the tests efficiently and intelligently. If the federal government issues an RFP (request for proposal) to build these tests, the industry would respond immediately. Next was the failure of our federal agencies and health authorities. The NIH and Operation Warp Speed failed to put the same weight behind the development of rapid tests as they did vaccines, while the FDA failed to devote sufficient capacity to reviewing and approving low-cost, self-administered models. The failure extends to other branches of the government as well. Congress failed to include provisions in emergency relief bills that would either cover or drive down the cost of rapid tests. Were tests priced at 50 cents a pop, the budget for administering around 150 million tests per day for three months would amount to $7.5
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billion—a small and necessary fraction of the trillions the pandemic is currently costing us. This is not a new call, and I am not alone. But the voices calling for such tests, mine just one among many, have been ignored—to the anguish of tens of millions of parents, children, and US citizens who now endure, if not infection from Covid-19 itself, long waits in the bitter cold for a single test and even longer turnaround times for their results. The difference between now and several months ago, when advocacy for rapid testing first began, is that our situation is considerably more desperate—a fact that isn’t likely to change once a vaccine has been rolled out. With adequate financing and a robust national strategy, rapid, self-administered testing could stem the ever-surging tide of disease and death. If only those who have the power to produce and supply this simple tool would wield it. Though it has taken far too long, it’s not too late. This article originally appeared in Forbes and is available online here: Even With A Vaccine, We Still Need Rapid Tests To End Covid19
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The Trouble With Herd Immunity And Covid19 Vaccines Forbes | December 11, 2020 | Article
Now that an independent advisory panel has voted in favor of approving Pfizer’s two-dose Covid-19 vaccine, it likely won’t be long before the US Food and Drug Administration (FDA) clears it for emergency use. Within 24 hours of their decision, millions of doses will be en route to health workers and long-term care residents across the country, beginning a mass vaccination campaign that many hope will end in herd immunity. A vaccine will make a critical addition to our defenses against Covid-19—this much is certain. But our ability to achieve vaccination-induced herd immunity is less so. While that shouldn’t stop us from trying, it also shouldn’t stop us from practicing and promoting safety guidelines that can actually contain the disease. If Covid-19 is a raging forest fire, and a vaccine the firefighter dispatched to quell it, tried-and-true prevention measures—social distancing, mask wearing, and rapid testing among them—are how we protect ourselves until the trucks come rolling in. The World Health Organization estimates that 65 to 70 percent of a given population must be vaccinated to halt the spread of disease. Once that threshold is crossed, the Covid-19 virus will have too few human hosts to choose from, driving down transmission rates dramatically. The process of getting there is simple enough in theory, but laborious and time-consuming in practice, involving many factors that can be enumerated endlessly but boiled down to four. The first factor involves properties intrinsic to both the vaccine and the virus. While the Pfizer vaccine has proven safe and effective at reducing disease in more than 95 percent of clinical trial participants, whether it prevents infection and transmission remains unknown. Likely it will, but until this is evident, we must continue to take great care in protecting ourselves and others from contracting disease, even post-vaccination.
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The second factor is the duration of protection—in other words, how long the protection conferred by a vaccine will last. Several studies, though not all, suggest that natural immunity to the Covid19 virus is quick to fade. Vaccine-induced immunity might do nature one better, but that isn’t always the case. The immune response precipitated by the influenza vaccine, for instance, dwindles in four to six months. Only time will tell whether our protection against Covid-19 is as short-lived. The third factor—social, rather than biological this time—is how many people take the vaccine. Due to a lack of data on how the Pfizer vaccine affects children and teens, Thursday’s FDA advisory panel deliberated its use in people 16 and over only. It may be that children below the age of 18, who make up about 23 percent of the population, aren’t cleared for vaccination for several months. Until then, the onus is on adults—some of whom have their own reasons for abstaining. Whether their skepticism is fueled by fearmongering from the anti-vax movement or, in the case of minority groups and in particular black Americans, a long history of malpractice in the name of medicine, the fact remains that 37 percent of adults in the United States would refuse to get vaccinated if the option were immediately available to them. Though trust, once lost, isn’t necessarily gone forever, it will take a concerted effort led by credible public figures and community leaders to undo damage that deep-seated. The fourth and final factor is that the pandemic won’t be over in the United States until it’s over everywhere. For the rest of the world, mass vaccination will likely proceed at a much slower pace. If national public health interventions and global vaccine equity initiatives don’t pick up the slack, we can expect an influx of infections to continue streaming in from overseas, whether on the backs of travelers or packaging of frozen foods. Try as they might— and for the most part succeed—at keeping the virus at bay, China has traced hundreds of new infections to contaminated freight and other imported goods. While China has the wherewithal to quash even the smallest, most localized outbreaks with a barrage of testing, in many countries that slow drip is enough to trigger a flood. Taking these factors into consideration, it becomes clear that vaccination-induced herd immunity isn’t a given. Whether it’s feasible, we probably won’t know for another couple of months. We 548
do know that containing Covid-19 without a vaccine is. Countries like Australia, New Zealand, Thailand, and Taiwan, where strict lockdowns and basic prevention measures were rigorously enforced, have barely a handful of new cases to report daily, if any at all. Vaccines are just one tool among many, and to end the pandemic by this time next year, we need to give it all we got. This article originally appeared in Forbes and is available online here: The Trouble With Herd Immunity And Covid-19 Vaccines
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The Covid-19 Pandemic Is Threatening Decades Of Progress In Global Health Forbes | December 14, 2020 | Article
With ever-present news of climbing case counts and deaths from Covid-19, and now the hopeful arrival of a vaccine, it can be easy to neglect the impact of the coronavirus on other health challenges around the world. The pandemic has caused sweeping disruptions to all aspects of our global health systems and has hindered individuals’ ability to access routine healthcare in all countries. Precautions that were necessary to slow the spread of the coronavirus such as pausing vaccination campaigns, are threatening to overturn decades of progress in addressing both infectious and chronic diseases that have improved the health of millions of people globally. Vaccination coverage this year has plummeted to levels last seen in the 1990s. For some vaccinations, a delay of a few months is not a huge problem and can simply be made up once immunization programs are up and running again. However, for highly contagious diseases like measles, even a short pause in vaccinations can lead to a spike in cases and death, mostly among children under five years old. Before the pandemic started, the measles crisis was a growing concern for many public health officials. In 2019, measles cases increased in all regions in the world, and the World Health Organization (WHO) reported 207,500 deaths from measles, the highest number in 23 years. This year, twenty-six countries have paused their measles vaccination campaigns to stop the spread of the coronavirus, leaving 94 million people at risk of missing these crucial vaccinations. The WHO and UNICEF predict that with measles vaccination campaigns on their current path, more child deaths will occur as a result of measles than as a result of Covid-19. In addition to suspending measles vaccinations, over sixty planned polio vaccination campaigns have been postponed in twenty-eight countries due to Covid-19. While pausing polio vaccination campaigns was important to keep both healthcare workers and communities safe, there are now growing polio 550
outbreaks. This is an especially heart-wrenching effect of the Covid19 pandemic, given how close we are to eradicating the disease from the world. There are now only two countries in the world – Afghanistan and Pakistan – in which polio is still endemic. Covid-19 is also harming children by decreasing access to nutrition around the world. Researchers estimate that acute malnutrition in children could rise by over fourteen percent if the issue is not addressed. Malnutrition in childhood can have lifelong consequences and can also decrease children’s ability to fight off infectious diseases. Researchers have estimated that malnutrition might even account for up to one-quarter of all childhood Covidrelated deaths. We know that children are unlikely to die from Covid-19 directly. However, the pandemic poses a threat to children indirectly by making it harder, and in some cases impossible, to receive routine, life-saving public health interventions such as vaccinations and access to essential nutrition. This pandemic is also threatening to undermine gains in controlling infectious diseases that impact both children and adults. Malaria, HIV, and tuberculosis (TB) are often known as the big three infectious diseases because of the large number of people these diseases infect each year. The impact of Covid-19 on malaria has been of special concern to public health officials. Some models predicted that malaria deaths in Sub-Saharan Africa could as much as double if prevention and treatment were severely hindered. Thankfully, this has not been the case, but there has been an increase in the number of malaria cases and deaths in the wake of Covid-19. HIV testing has significantly decreased during the pandemic. This could lead to more new infections of HIV as individuals may unwittingly spread the virus if they are unaware of their HIV-status. Similarly, the number of undiagnosed cases of TB is increasing due to Covid-19 as people may be unable to access healthcare facilities in the middle of the pandemic. This will also likely result in an increase in the number of new TB cases around the world, as those who do not know they are infected with TB may continue to spread the bacterium to others. The impact of COVID-19 on measles, polio, and the big three infectious diseases are a tremendous amount for any health system to handle. However, the pandemic has also interrupted routine care for chronic diseases such as diabetes and hypertension, reproductive 551
health services for mothers and their infants, and neglected tropical disease control programs such as trachoma and leishmaniasis, further heightening the stress on health systems globally. There is a recent example of the ripple effects of an epidemic causing more deaths than the epidemic itself. During the 2014-2016 Ebola outbreak, more people died from malaria in Guinea than died due to Ebola because of disruptions to malaria prevention activities caused by the outbreak. To prevent deaths both from Covid-19 itself and from other health challenges that the pandemic is exacerbating, we must implement innovative public health programs. We are already seeing this in some countries that are combining programs focused on deworming or the provision of vitamin A with vaccinations. In planning these public health activities, to keep healthcare workers and communities safe, countries must provide adequate personal protective equipment – masks, gloves, goggles, hand sanitizer, soap – and enforce social distancing guidelines. The Covid-19 pandemic has demonstrated how interconnected the world is and the enormous impact that one infectious disease can have on all other aspects of our health. Addressing Covid-19 means not only stopping the spread of the coronavirus, but also tackling the many indirect health consequences. In a world where outbreaks of emerging infectious diseases are at an unprecedented rate, we need to build strong health systems to address epidemics while continuing to provide vital, routine to all care as safely as possible. This article originally appeared in Forbes and is available online here: The Covid-19 Pandemic Is Threatening Decades Of Progress In Global Health
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Covid-19 Is Preventing Sustainable Investment In Developing Nations Forbes | December 16, 2020 | Article
Covid-19 has occupied most of our attention in 2020, and for good reason. We’ve had over 70 million infections, about 1.6 million deaths, and hundreds of thousands more contracting the disease every day. That said, yesteryear’s issues persist, such as our ongoing climate crisis and countries’ attempts at developing their economies to be more sustainable. Covid-19’s economic devastation stripped nations of their sustainable growth financing. The world’s economic powers must step in to fill the gaps. All countries, regardless of economic size, have struggled in the wake of the pandemic. As borders closed, workers stayed home, and social activity seized, the global economy experienced its worst downfall since the 1930s. Developing countries, however, faced a particularly severe crash. According to the United Nations Development Program, the average income lost for a developing country because of Covid-19 will exceed $200 billion. Many of these countries rely on tourism and international assistance to boost their economies, two items that are sorely lacking in the time of Covid-19. Understandably, many developing countries are focusing their efforts on rebuilding their crumbled economies. However, Covid-19 does not erase the existential threat of climate change, and many of these countries have goals revolving around sustainable development, such as the United Nations 2030 sustainable development goals. It seems these goals are set aside for the moment. According to the OECD’s Global Outlook on Financing for Sustainable Development, developing countries face a shortfall of $1.7 trillion for sustainable economic growth. OECD SecretaryGeneral Angel Gurria noted that “Covid-19 is erasing years of development progress and causing major setbacks...for developing countries under stress.” Of the $379 trillion in total global financial assets, the 122 developing countries only hold about 20% of those 553
assets. A large cut in sustainable-growth financing will only exacerbate this economic divide. Without financial support promoting sustainable growth, less sustainable industries will take root in their place. We have already seen practices like unregulated mass logging in South America cause vast devastation to regional wildlife and indigenous populations. Efforts to bolster sustainable logging and other sustainable practices will fall to the wayside if Covid-19 continues to drive economic havoc. The forthcoming vaccines may be a path to controlling Covid19, but it seems likely that we will be living with continued economic devastation for at least a few years. A Brookings Institute report estimates that Covid-19 financial ramifications will force over a hundred million people into extreme poverty, meaning household spending of less than $1.90 per day per person. Economic powers like the United States, China, and Europe have to help these people living in struggling countries. To financially assist these countries, perhaps economic recuperation from Covid-19 can work in tandem with sustainable development. For instance, international partnerships like the United Nations could establish national work programs, employing those facing extreme poverty. These work programs could focus on developing a sustainable industry while pulling a country’s residents from poverty. For example, perhaps the United Nations could send a few engineers and supplies to high poverty areas to help them build solar, wind, or water-powered generators for local communities. A program like this would have to be financed by industrialized economies, but that’s a necessary investment. Covid-19 is forcing aggregate wealth more into the hands of the already wealthy. Reversing that trend and returning wealth to developing countries would be no less than economic justice. Without help from advanced economies, developing nations will fall far behind their sustainable goals and revert to unsustainable development. For the health of the people living in developing countries, the plants and animals habiting developing nations, and the planet in general, we must counter Covid-19’s attack on sustainability. This article originally appeared in Forbes and is available online here: Covid-19 Is Preventing Sustainable Investment In Developing Nations 554
Why Covid-19 Is Overwhelming California Forbes | December 17, 2020 | Article
At this pivotal juncture in our nation’s history, California has become a microcosm of broader developments taking shape across the US. The country’s most populous state is also its most diverse, home to a wide range of cultures, ethnicities, and economies. To the north lie counties that voted red in the 2020 election and share more sensibilities with Dakotans than Los Angelenos. To the south, the US-Mexico border where millions of immigrants have passed through at rates comparable to Texas. And down the middle, the abundantly verdant, 450-mile Central Valley, where 40 billion pounds of milk, two thirds of the nation’s fruits and nuts, and a third of its vegetables are produced each year. All three regions are critical to Californian history and identity. All three are being hit hard by Covid-19. Statewide, case counts have increased by nearly 120 percent and deaths about 160 percent in just two weeks. Per California’s latest round of Covid-19 restrictions, a stay-at-home order kicks in wherever ICU capacity—namely, the share of unoccupied beds in intensive care units—dips below 15 percent, a milestone that Sacramento and Southern California have already reached. In San Joaquin County, a mostly rural region in the middle of Central Valley, zero ICU beds were available as of last Saturday. Even San Francisco is expected to run out by the end of December. As Dr. Eyad Almasri, a pulmonologist who works at UCSF Fresno, told the Los Angeles Times, “We’re saving lives. We just can’t save everyone at once.” While hospitalized Covid-19 patients are all shapes and ages, some populations carry a share of the disease burden disproportionate to their actual size. In California, the millions who labor in the state’s farms, meatpacking plants, and other food processing facilities—countless of them migrant workers of color— are exposed to Covid-19 at rates far higher than those who can either 555
work comfortably from home or, as Tesla CEO Elon Musk did days ago, comfortably relocate. In the fields and factories where social distancing, frequent handwashing, and other safety guidelines are difficult to enforce, and in the crowded households and dormitorystyle complexes where many migrant workers live, the virus has considerably more room to grow. And because this virus isn’t one to discriminate between viable human hosts, outbreaks that occur under poor working conditions will find a way to spread into the cities, suburbs, and beyond. In the rural north, the situation isn’t much better. Lassen County, where more Covid-19 cases per 100,000 have been confirmed in the past week than anywhere else in the state, is struggling to contain an ongoing outbreak at High Desert State Prison, where active cases currently outnumber those in local communities. About a fifth of the prison’s population has tested positive for Covid-19, as have 160 staff members. Given that Lassen County also has the designation of being the “Trumpiest county” in California, meaning residents voted for Trump by the widest margin in this year’s presidential election, public health measures like maskwearing likely aren’t so popular. Rural communities in general also have higher incidences of chronic illness, smoking, obesity, and other adverse health conditions that increase susceptibility to severe Covid-19, not to mention far less doctors and critical care facilities than urban areas. Now that the winter holidays are upon us—and with them, a precipitous increase in travel and indoor gatherings—the patchwork of public health protocols that kept case counts relatively low in the fall will only continue to prove insufficient. The 325,000 doses of Pfizer’s Covid-19 vaccine that California received this week may help, but the jury is still out on whether it prevents the spread of disease. Especially since California has fewer ICU beds per capita than most states, what the state needs as it awaits more vaccines are more robust, targeted, and comprehensive public health interventions that provide assistance to those who need it most. The idea isn’t to force people to comply with stay-at-home orders and other restrictions, but make the choice that much easier. This month, health officials in Santa Clara County launched a door-to-door testing program in the neighborhood of East San Jose, where more than half of residents are Latino. Bilingual volunteers 556
will distribute self-administered home tests to anyone who needs them, but with particular consideration Latino communities who may not have the means to get tested themselves. The California Department of Food and Agriculture is also expanding its Housing for Harvest program, an initiative to provide vulnerable agricultural and food processing workers with temporary housing options if they’re sick and need to self-isolate. In addition to securing a hotel room for the duration of their quarantine, participants also receive meals, wellness checks, and if needed economic assistance for family members at home. The program, introduced by Governor Gavin Newsom in July, now has footholds in San Joaquin, Fresno, and other Central Valley counties. Now more than ever, even with a vaccine on hand, Covid-19 is spiraling out of control in the US. To contain it, we need lockdowns as drastic as those imposed in France and across Europe. But we also need public health interventions that bring support to people who have difficulty accessing it on their own. They must be widespread and, for recipients, either low-cost or completely free. Some individuals will no doubt choose to defy public health guidelines willingly. As California Senator Richard Pan put it to the Los Angeles Times, “We can’t save people from themselves after a certain point.” But those we can help, we should. Simple as that. This article originally appeared in Forbes and is available online here: Why Covid-19 Is Overwhelming California
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Covid-19 Home Tests Should Be Much Cheaper Forbes | December 17, 2020 | Article
Great news: the US Food and Drug Administration (FDA) has approved its first over-the-counter, totally at-home test. Unlike previously authorized models, the Ellume COVID-19 Home Test requires neither a laboratory to process results, nor a health worker to facilitate, nor a prescription to purchase. Using an accompanying app that provides instructions and displays results, anyone can test themselves for Covid-19 and know their status in 15 to 20 minutes. In terms of convenience, the Ellume test is difficult to beat, similar functionally to a home pregnancy test. Technically, it is a rapid antigen laminar flow test—a mouthful of a term that means the kit comes with a swab, a dropper, and a tiny capsule of processing fluid. After swabbing their tonsils, the user is instructed to mix their sample into the fluid for 15 seconds. An analyzer with Bluetooth capability, also included in the kit, scans the sample and sends the results to the user’s phone and, if a country’s infrastructure allows it, relevant health authorities. The BinaxNOW COVID-19 Ag Card Home Test created by Abbott Laboratories, also FDA-approved quite recently, deploys a similar technology, but like the Lucira Health home testing kit—the very first of the bunch to receive emergency authorization—requires a prescription and supervision from a health provider. How accurate is the Ellume test? That depends. A study that compared the home test with a standard PCR test on about 200 people found it correctly identified 96 percent of the positive cases and 100 percent of the negative—but only in those with symptoms. In those without, the number of correctly identified positives fell to 91 percent. Like the vast majority of rapid tests, then, the Ellume home test isn’t as sensitive as its PCR counterpart. Epidemiologists like Michael Mina have argued, however, that from a public health perspective high sensitivity isn’t necessarily a dealbreaker. When containing disease at the population level, what matters significantly 558
more is frequency and volume—that more people can get tested more often. What I personally recommend to those who fear the ramifications of a false positive is, after testing positive initially, an immediate second test. This would, per a back-of-the-envelope calculation, reduce your chances almost a hundredfold, from 4 in 100 to 16 in 10,000. It follows that the bigger issue with the Ellume test and others like it isn’t convenience or sensitivity, but cost. The first kits, due to go out next month, will sell for about $30 a pop at your local pharmacy. The Abbott home tests, at $25 each, aren’t much better, and the $50 Lucira Health tests even worse. For many working families across the United States, especially those with children, these costs are nothing short of prohibitive. Ellume has said that it plans to pump out about 20 million of its Covid-19 home tests in the coming months. For Abbott, that number is 30 million. But it is difficult to imagine these tests making much of a difference if the people who need them most can’t afford them. The cost of a home pregnancy test Free On Board (FOB), which is to say the price point after factoring in manufacturing and shipping, is 79 cents, and less than 10 million pregnancy tests were used by women in the United States this year. Home Covid-19 tests, if made in batches of hundreds of millions, could potentially be priced at less than 50 cents—comparable to the cost of rapid hepatitis C tests in Egypt, which were used to screen more than 60 million people and, with follow-up treatment, effectively eliminate the disease. I would go so far as to urge state and federal governments to step up and provide Covid-19 home tests in mass quantities for free. In retrospect, one of the most serious mistakes made this year by world leaders everywhere was to relegate far too little attention and too few resources to testing. Done right, widespread and frequent testing could not only curb infection rates much faster than a vaccine, but also assist vaccination efforts in reducing the threshold for population immunity. The lower the prevalence of disease in a population, the lower the percentage needed to form a bulwark against transmission. Plus, if immunity conferred by Covid-19 vaccines ends up being short-lived, frequent testing would also mitigate the whiplash of subsequent outbreaks, allowing health authorities to isolate and contain them accordingly.
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With enough home tests available at a low enough price, parents could test themselves before going to work and their children before going to school. And if home tests were, with federal and state government support, made free to schools and businesses, employers and administrators could get ahead of pending outbreaks and save their staff a whole lot of pain. Frequent testing could even pave the way forward for Covid-19 drug treatments, many of which are more effective when given early on in the disease course—in other words, when someone tests early enough to know they need one. We have the technology to make the dream of widespread, frequent, and low-cost or even no-cost testing a reality—to flood US households with millions, even hundreds of millions, of home tests per day. What we need are the funds and political will to execute. If we secure both, it won’t be long before we have the momentum we need to wrench ourselves free of this crisis. But if we needlessly delay, we’ll remain down in the muck, too swamped by rising case counts to see the way out. This article originally appeared in Forbes and is available online here: Covid-19 Home Tests Should Be Much Cheaper
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The Mouse That Roared: What The US Can Learn From Andorra About Covid-19 Testing Forbes | December 17, 2020 | Article
One country is setting the global standard for Covid-19 testing, and it isn’t the United States. In anticipation of the winter holidays, the small European principality of Andorra has begun distributing rapid, selfadministered antigen tests for Covid-19 to all residents over the age of six. These home testing kits are free, government-provided, and available to pick up at designated locations. Though allocations are limited to one per resident, more free tests will be distributed after Christmas as well. Why is this significant? With a population of about 77,000, a landmass just 2.5 times the size of Washington DC, and both France and Spain as neighbors, at any point in the pandemic Andorra could very easily have been overwhelmed by an incoming tide of cases. While case counts did peak in October, when health authorities logged in a single month about 35 percent of their all-time 7,466 total, the surge paled in comparison to the explosive outbreaks occurring right outside their borders. Testing likely had a critical role to play in driving down the spread of disease among Andorrans. The Andorran government has been on top of the latest Covid-19 testing models since April, when it ordered enough antibody tests to test its entire population twice over. The home tests being distributed this month were purchased at about $5.30 USD each from South Korea and $4.50 USD each from Abbott Laboratories—a good deal for quantities much smaller than what larger countries are buying up. In addition to free holiday testing, Covid-19 screenings occur regularly in schools, long term care facilities, healthcare facilities, and many workplaces and local establishments, including restaurants and bars. In Andorra la Vella, the capital city that sits high in the Pyrenees, home tests are delivered to anyone older than 80 years of age. Those who would prefer not to test themselves can either seek 561
out a mobile StopLab or one of many point-of-care facilities. As of Wednesday, local pharmacies are also authorized to sell home tests, in addition to offering on-site rapid testing for about $18 to $25 USD. In making Covid-19 tests so widely available and encouraging residents to get tested at least once a month, the Andorran government was able to gain the upper hand over a disease that elsewhere in Europe wreaked havoc. And now that the latest tests are free, their advantage may very well carry over into the new year. Had the US government played a similarly supportive role in securing tests for its citizens, Americans might be heading into the holidays with rosier prospects. Sadly, this wasn’t and isn’t the case. Admiral Brett Giroir, Assistant Secretary for Health at the US Department of Health and Human Services and coordinator of national Covid-19 testing efforts, gave a talk this week in which he addressed, at least in part, the many failures that have hampered Covid-19 diagnostics across the country for most of the pandemic. In addition to admitting to an utter lack of preparedness—the supply chain a “wreck” at the outset of the crisis, not to mention “nothing in the stockpile”—Giroir affirmed the importance of rapid point-ofcare testing relative to PCR tests. On the subject of PCR testing, Giroir said, “I think it has served us all poorly to create the myth that it is a gold standard.” Echoing the arguments for rapid testing that epidemiologists like Michael Mina have made for months, he added that PCR tests can be “poor predictors of contagiousness” at the population level. Since May, the number of rapid antigen tests the US has on hand has grown from 1 million to 111 million. Yet due to concerns about their sensitivity and limited access to the general public, these tests remain greatly underutilized. The home test the Andorran government purchased from Abbott Laboratories, as a matter of fact, is probably the same one the FDA just cleared for use in the United States, along with another created by Ellume Health. Rather than being distributed among American households for free, however, they’ll be sold for about $25 to $30 USD. It’s not too late for the US government to reverse course and buy the home tests we need so direly in bulk. If Andorra shelled out just $5 a test for so small an order, the US could secure mass amounts for far less. 562
This article originally appeared in Forbes and is available online here: The Mouse That Roared: What The US Can Learn From Andorra About Covid-19 Testing
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When Implementing Or Easing Restrictions For Covid-19, Transparency Is Paramount Forbes | December 21, 2020 | Article
The coronavirus spread so far and so fast at the beginning of 2020 that most countries around the world were forced to resort to restricting citizens’ movement and shutting down all but the most essential businesses to control its spread. These so-called “lockdowns” were not intended as a permanent solution, but instead were implemented to ensure that hospitals were not overwhelmed and to buy governments time to mount a more sustainable response to the virus. A recent article published in the Lancet chronicles the experiences of nine high income countries – five in the Asia Pacific Region and four in Europe – as they implemented and eased lockdowns and other measures to stop the spread of the coronavirus. While all nine countries have instituted control measures to combat the coronavirus, there has been a lack of clarity surrounding how countries decide to institute and lift restrictions. To garner public trust in the response to Covid-19 and mitigate the negative impacts of this pandemic and future outbreaks, transparency, investment in health systems, widespread testing, and strong, compassionate leadership are crucial. Broadly speaking, countries have taken two approaches to decision-making when implementing and easing Covid-19 lockdowns. In some countries such as Singapore, Norway, and Spain, politicians –informed by public health experts – are responsible for discerning when to put in place and lift restrictions. In these countries, the criteria on which these decisions are based are not available to the public. In other countries like Japan, Germany, and South Korea, the government institutes and relaxes Covid-19 restrictions based on the number of cases in an area. The authors propose a framework of five requirements that countries should fulfill before lifting Covid-19 lockdowns: knowledge of infection status in the country, community
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engagement, sufficient public health capacity, sufficient healthsystem capacity, and implementation of border controls. Each of the nine countries studied went about calling for a lockdown and easing restrictions in a different way and experienced vastly different numbers of cases and deaths from Covid-19. Out of the countries studied, Spain had the highest number of cases per population – 373 cases per 10,000 people - while New Zealand had the lowest number of cases per population – just 4.3 cases per 10,000 people. The United Kingdom (UK) has had the highest number of deaths so far at 64,500 while there have been just 25 deaths due to Covid-19 in New Zealand. While each country’s experience handling the Covid-19 pandemic has been unique, comparing different approaches can help provide insight into the best way to institute and ease strict control measures for Covid-19 and future infectious disease outbreaks. The researchers argue that before reopening, at a bare minimum, countries must know the coronavirus infection status in their country. This means having an effective surveillance system to confirm that the number of Covid-19 cases has decreased during the lockdown and to monitor the number of new cases that emerge once restrictions are eased. Countries such as Hong Kong, Japan, Spain, Germany, and Norway have calculated the coronavirus’ reproduction number – or the number of people who one person with the coronavirus ultimately infects – at different points in time. A reproduction number of well below one can be used as a guideline that it is safe to begin reopening. While the driving factor around deciding whether to institute or ease a lockdown should be the number of cases in an area, governments must also be cognizant of the economic costs to citizens and provide the resources required so that people can stay in their homes and provide for themselves and their families. The researchers also highlight the importance of engaging communities before easing restrictions. Clear communication and involvement of citizens around long-term control measures such as physical distancing, mask wearing, working from home, and school policies are vital so that people are equipped with the information they need to keep themselves and their families safe. Messaging around physical distancing and mask wearing have been especially confusing during this pandemic. Physical distancing requirements 565
vary between countries with a range of one to two-meters (three to six-feet) of separation between people. Adoption of mask wearing occurred at different times throughout the pandemic. Countries in Asia adopted the use of face coverings much earlier than Europe, likely resulting in the lower numbers of cases per population in Asia compared to Europe. Lack of clarity and confusing messaging can decrease the public’s willingness to follow such restrictions. Time during severe restrictions on population movement should be used by governments to increase public health capacity and prepare to implement widespread testing, contact tracing, and isolation of those with confirmed infection. The two regions in this study have approached isolating confirmed cases differently. Asian countries isolate confirmed cases, regardless of whether or not they have symptoms, in hospitals or other institutions, whereas European countries isolate confirmed cases who are asymptomatic or have mild symptoms at home. Testing has changed dramatically throughout the outbreak as tests have become more widespread. Drive-through testing in South Korea and Germany and at-home testing in the UK and Hong Kong have improved access to testing and decreased the potential for people to become infected while getting a test at the hospital. South Korea, the golden standard for testing, mass tests all people who have visited public venues or been to events where anyone with Covid19 was present. This has resulted in one of the lowest infection rates per population in the world. Contact tracing has also improved throughout the pandemic as apps and other technologies are being used to assist individuals working for local health departments the world over. The largest reason presented for why lockdowns are put in place is so that health systems are not overwhelmed. To that end, the researchers describe the importance of ensuring that the health system has the capability to handle new Covid-19 cases that may occur once the lockdown is lifted. This means making sure there are enough staff, personal protective equipment (PPE), intensive-care unit (ICU) beds, and ventilators to treat Covid-19 patients with severe disease. Decisions made before the pandemic on health expenditure are now having a large impact on the set of options that a country has.
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Germany invested in its health system before Covid-19 and, even during the peak of its outbreak, always had plenty of ICU beds. Other European countries were forced to find other spaces within its hospitals and use other wards to treat all of those with severe Covid-19. Some countries have also struggled to provide healthcare workers with the proper PPE. This has had disastrous consequences in Spain where over ten percent of Covid-19 cases are healthcare workers. Countries in Asia such as South Korea, Singapore, and Hong Kong, however, stockpiled PPE before the pandemic and have had very few cases among healthcare workers. Lastly, before easing restrictions to decrease the spread of Covid19, countries must have a plan to decrease the risk of Covid-19 traveling across borders between countries. The five countries in the Asia Pacific region have much stricter border control measures compared to their European counterparts, which have been slow to require travelers to be tested routinely. New Zealand, which had no community transmission of Covid-19 for over 100 days, allows very few people to enter the country and requires any travelers coming from overseas to remain in a quarantine facility for two weeks. In contrast, Spain fully reopened its borders in July. These border policies likely played a role in the vast discrepancy between the number of cases and deaths in Spain and New Zealand – Spain has had 373 cases per 10,000 people and 48,013 deaths from Covid-19 while New Zealand has experienced only 4.29 cases per 10,000 people and 25 deaths from Covid-19 In many countries, Covid-19 has exacerbated existing inequities and had a disproportionate impact on already marginalized groups. This was especially true in the UK where Black people were diagnosed with Covid-19 at over 2.5 times the rate of white people. More data is needed from countries like Germany to understand and address the full scope of how Covid-19 disproportionately impacts people of color. During the periods of lockdown, the authors found that governments varied in the amount of support they provided to their citizens. In the Asia Pacific countries, governments provided onetime cash handouts to the public. European countries have been able to provide longer-term support. The UK paid the wages of furloughed workers until the end of October and Spain is providing a minimum monthly wage of around $500 for its poorest citizens. 567
The authors also noted that countries with female leaders have been the most successful at gaining public confidence and convincing citizens to follow both the lockdown requirements and the more sustainable public health measures necessary after the lockdown is lifted. New Zealand and South Korea – both of whom have female leaders – have the two lowest infection rates per population. As the vaccine rollout begins and the days of severe restrictions are hopefully coming to a close, some may ask – why focus on lessons learned from easing lockdowns now? The answer is that, with infectious disease outbreaks occurring with increased frequency, we need to heed the lessons of this outbreak to prevent future widespread epidemics. The authors of this study found that Asian countries were much more prepared for the coronavirus outbreak due to their past experiences with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). This is also a call to invest heavily in health and public health systems around the world. Austerity in Europe for the past ten-years has weakened health systems and decreased social protections. With the exception of Germany, all countries in Europe faced shortages of ICU beds and other necessities to fight this pandemic. Investments in our public health and health systems globally will enable countries to respond much more quickly to future outbreaks and increase the capacity of health systems so that they do not come so close to collapse. It is not nearly enough to hope that this is a once in a century pandemic, we need strong leadership, investments in health systems, and social protections that decrease inequity to ensure that we are all better prepared for the next outbreak. This article originally appeared in Forbes and is available online here: When Implementing Or Easing Restrictions For Covid-19, Transparency Is Paramount
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The Moderna Vaccine’s Antibodies May Not Last As Long As We Hoped Forbes | December 22, 2020 | Article
With the rollout of Covid-19 vaccines finally underway across the United States, data on the vaccines’ effectiveness is starting to become more available. But one key piece of information is still relatively unknown: how long the vaccines’ effectiveness will last. While only a preliminary analysis, a new study by the New England Journal of Medicine (NEJM) suggests that the long-term efficacy of Moderna’s mRNA-1273 vaccine, specifically the neutralizing antibody count, may be less than we were hoping for. Neutralizing antibodies bind to invading pathogens, like all antibodies do, but they bind in a manner that stops infection. That is why pharmaceutical companies stress neutralizing antibody counts as an essential measure for their vaccines’ success. The NEJM study followed a group of 34 patients who had taken both doses of mRNA-1273 and analyzed their antibody counts from the administration of the first dose for 119 days. Neutralizing antibodies were monitored in subgroups of 18-55 years of age, 5670, and 71+, as shown below.
Charts describing the duration of neutralizing antibodies from the Moderna vaccine. NEW ENGLAND JOURNAL OF MEDICINE A significant determinant of vaccines’ effectiveness in controlling a pandemic is antibody duration—how long the antibodies last in a person’s system. For those 18-55 years old, the majority only show a slight decrease in neutralizing antibodies in the three months 569
following their second vaccine dose. Two of the 34 patients in this age group saw a significant drop in neutralizing antibodies. Due to the limited number of participants in this study, we cannot draw conclusions from these outliers until further data becomes available. However, sustained antibody counts are not the case in the 5670 and 71+ age groups. In these subsets, the neutralizing antibody counts fall anywhere between 50 and 95 percent. This suggests that in these age groups, the duration of neutralizing antibodies from the Moderna vaccine will be relatively short, potentially less than a year. That is particularly troubling as these are the age groups most affected by severe Covid-19. It may well be that the levels of antibodies after three months, if maintained, are sufficient to protect these age groups, but it is unlikely they will continue to protect if levels fall still further. Moderna is simultaneously producing vaccines for avian influenzas H10N8 and H7N9. These two vaccine candidates show similar drops in neutralizing antibody counts to mRNA-1273 after three months. According to data from Science Direct, antibodies persisted up to six months after injection, but dropped as much as 90% in that time. Sustained protection from the virus requires sustained neutralizing antibodies, yet the patterns indicate that Covid-19 vaccines may be more than a one-time occurrence. In addition to Moderna’s bird flu vaccines presenting similar antibody trends to that of the Covid-19 vaccine, early trials required them to discontinue their 400 microgram dose due to patient side effects like injection site irritation and headaches. The mRNA-1273 vaccine will be two doses of 500 micrograms each, according to the CDC. While Moderna trials did note significant side effects from vaccine administration, some effects may arise in the general population. This is all not to say Moderna’s vaccine is not effective. Even at these low numbers, antibodies may still be fully or partially protective. That remains to be seen. Additionally, the NEJM study only analyzes 34 patients, most of whom are in the 18-55-year-old age group. Conclusions drawn from such small data sets must be taken with a pinch of salt, but we still need to take the results seriously—this data may be the first of many indicators that vaccines don’t last as long as we would hope.
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It is also vital to review similar data in the Pfizer and Biotech vaccines as it becomes available. The United States government and the governments of countries worldwide seem to be banking on the effectiveness of these vaccines. We urge pharmaceutical companies to be forthcoming on their continued monitoring of these early patients and those who have received the vaccine more recently. As more data like this is released, the clearer the picture of these next several months of the pandemic becomes. This article originally appeared in Forbes and is available online here: The Moderna Vaccine’s Antibodies May Not Last As Long As We Hoped
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Urban Flight Due To Covid-19 Is Temporary, Not Permanent Forbes | December 21, 2020 | Article
As Covid-19 ravages the United States, it seems some may have had enough of densely populated cities, electing to move to the openspace haven of suburbia. Covid-19 is forcing people to question whether they want to live near millions of others. Reports of widespread urban flight must be examined and analyzed. Is the pandemic causing people to leave urban environments for suburbia permanently, or is this a temporary solution to immediate health concerns many share? On its face, it does seem many Americans are choosing to leave cities in 2020. According to a paper out of the NYU Stern School of Business, as many as 15-20% of Manhattan residents had left the city by mid-summer 2020. Positive Covid-19 cases in New York peaked in mid-April but were brought under control by stringent lockdown regulations. These lockdowns may have encouraged some city-dwellers to find shelter elsewhere. If Manhattan experienced a 15-20% exodus in the early months of Covid-19, surely that means other American metropolitan areas have experienced something similar. San Francisco is another example with a similar high volume residential exodus. But interestingly, the list stops there. Most other cities are not experiencing urban flight nearly to the levels of Manhattan and San Francisco. These two urban pockets are amongst the most densely populated and expensive cities in the country. Young professionals in their twenties and thirties move there to “live their best life” and “experience new things.” With hefty Covid-19 guidelines preventing many from living out their urban dreams, those with the financial means are opting to leave for less-populated pastures. The NYU paper includes a breakdown of the flighters by demographic. Most of them seem to be wealthy, white, and young New Yorkers. They are moving to suburban areas close by. 572
Although, many of them are retaining their residence in the city, indicating they are only staying with friends or family temporarily. As for the San Franciscans, it looks as though they aren’t moving to escape the urban lifestyle. According to data from the moving service United Van Lines, the most popular destinations for those leaving San Francisco are other urban settings, specifically Seattle, Austin, Chicago, and New York. This data suggests that people who are moving, outside of the rich young folks who can stay with family for a while, are not moving because of Covid-19. If they were, they would move to less densely-populated settings rather than other major cities. If anything, people may be moving out of more expensive cities because of Covid-19 related job loss, rather than fear of the disease itself. A data set by Hire A Helper, another national moving company, indicates drops in moving percentage across nearly every state from March 11th to June 30th as compared to 2019. New York and California saw a 38% and 35% drop in moves, respectively. With a significant portion of these states’ populations concentrated in urban environments, the data contradicts the notion that city dwellers are running scared from the virus. At most, wealthy city residents are taking some time away from their expensive residences to spend Covid-19 with family or friends. Everyone else has hunkered down and in no rush to move anytime soon. For those retreating to rural areas, their efforts are already in vain. While infections were heavily concentrated in New York City and other urban areas at the start of the pandemic, rural areas have become increasingly susceptible to mass outbreaks. Due to a combination of limited access to medical equipment and Covid-19 therapies, looser Covid-19 restrictions at restaurants and social venues, and less general fear of the virus, rural states and populations were ravaged by Covid-19 in recent months. Regardless of our current state of disaster, people will return to cities. The trend of the past several decades tends towards further concentration of population in these areas. According to data from the United Nations World Urbanization Prospectus, over five times as many people lived in urban areas compared to rural areas in the United States in 2017. This is double the ratio from 1960, where only 2.5 times as many people were in urban areas. This trend is unlikely to be buckled by even a global pandemic. 573
Even work-from-home will not prevent the return to urban life that will follow the Covid-19 pandemic. While many white-collar employers may reduce office space and continue work-from-home into the future, tens of millions of people work in industries like retail, food service, public transportation, construction, and others that cannot be work from home. These industries are concentrated in high population areas. Therefore, as soon as businesses can, they will be back at full operation, requiring their full labor force. Just as we’ve seen other industries return with time, people will move again at typical rates. The end of the pandemic will usher a swift return to urban concentration. For now, the cries of urban flight may be more exaggerated than necessary. This article originally appeared in Forbes and is available online here: Urban Flight Due To Covid-19 Is Temporary, Not Permanent
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Here's what's worrying about the coronavirus variant CNN | December 23, 2020 | Article
The UK government has sounded the alarm about a variant strain of SARS-CoV-2 -- the virus that causes Covid-19 -- which appears to spread more easily than previous versions. While much is still unknown, what we do know about this new variant tells us important things about the virus: it can adapt to become more easily transmissible and may be able to become more difficult to neutralize and may possibly be able to outsmart the vaccine to a small extent. To date, SARS-CoV-2 has mutated at a fairly steady rate, with just one or two variations per month. Some variations have given scientists pause, at times mutating to become more transmissible and at other times mutating to become more effective at avoiding detection by our immune systems. But with this new variant, called B.1.1.7, the virus has acquired 17 mutations all at once that change the virus' proteins, according to the Centers for Disease Control and Prevention, which affect four different viral proteins: the spike protein, ORF1ab, Orf8 and the N protein, the major nucleocapsid. The full article is available on CNN here: Here's what's worrying about the coronavirus variant
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Why Most Countries Won't Benefit From Moderna and Pfizer’s Covid-19 Vaccines Le Monde | December 24, 2020 | Article
William Haseltine is president of ACCESS Health International. An infectious disease expert, Haseltine was formerly a Harvard Medical School professor and founder of the university’s cancer and HIV/AIDS research departments. His autobiography, My Lifelong Fight Against Disease, was published in October. That the Moderna and Pfizer Covid-19 vaccines demonstrated efficacy in more than 90 percent of phase 3 trial participants has been cause for celebration across the United States and Europe, so much so that the British government has even authorized the Pfizer vaccine for mass use. While no doubt groundbreaking, in the grander scheme of the global search for a vaccine their achievement falls short. Pfizer and Moderna have created a Lamborghini when what most countries really need is a Toyota—a vaccine that can be manufactured, stored, and administered simply and cheaply, preferably via existing distribution channels. To remain stable, the Pfizer vaccine must be stored in specialized freezers kept at an ultra-low temperature of negative 94 degrees Fahrenheit. Such storage units are manufactured at a select few “freezer farms” and priced at $10,000 to $15,000 apiece. While the Moderna vaccine doesn’t demand as deep a freeze—the requisite negative 4 degrees Fahrenheit is comparable to a standard home freezer—both must be administered in two doses a month apart, a logistical hurdle not uncommon but certainly not ideal in a quest for worldwide inoculation. Even hospitals in the United States and Europe, where governments have already bought up hundreds of millions of doses of the mRNA vaccines, will be hard-pressed to secure the equipment necessary for their safe storage and transport—especially those in small towns and rural areas where many residents, due to adverse socioeconomic and health conditions, are disproportionately 576
vulnerable to Covid-19. The same is true of remote regions in Africa, Latin America, and Asia. Airlangga Hartarto, head of the Covid-19 task force in Indonesia, told Reuters that in his country, the Pfizer vaccine has already been ruled out as a viable option—so unlikely is it to survive distribution between 270 million people across 17,000-plus islands. According to the World Health Organization, a lack of cold chain capacity is a primary reason why, globally, more than 50 percent of vaccines are wasted each year. Luckily, alternatives exist. One is the adenovirus vaccine being developed by companies like AstraZeneca and Johnson & Johnson, which uses a nonlethal cold-causing viral vector as its means of inoculation, rather than synthetic proteins as mRNA vaccines do. Adenovirus vaccines are, however, hampered by one deep and fundamental flaw. Recipients would risk developing immunity not just to Covid-19, but the vector itself, meaning after initial rounds of rollout, another candidate would have to be developed from scratch. The AstraZeneca vaccine and others of its ilk might be thought of as a Mercedes—not has high-maintenance as a Lamborhini, but certainly less practical than a Toyota. Chances are high that vaccination against Covid-19 won’t be a one-and-done affair, but an annual or even biannual reoccurrence like the seasonal flu shot. As such, the most efficacious vaccine will be one that can be deployed for years to come. Two types of vaccines fall into this category. The first is the subunit vaccine, which injects particular bits of the virus intramuscularly. This technology is behind the vaccine that has played a critical role in eliminating hepatitis B, a disease most prevalent in Africa and the Western Pacific that causes liver damage and cancers when contracted at a young age. The second is the inactivated vaccine, whereby the virus is grown, killed, and remade into a form of bodily defense. The Salk polio vaccine—the best example by far—accomplished this in 1955 and has been the backbone of polio eradication efforts ever since. It is one of the safest, most efficacious vaccines invented to date, preventing disease in 99 out of 100 children who receive the recommended dosage. While the oral polio vaccine is cheaper and used more widely, unlike the inactivated vaccine it can spread a weakened strain of poliovirus. Three of the four Covid-19 vaccine candidates that have emerged as major contenders in China are of the inactivated variety. 577
While data on the safety and efficacy of these vaccines has yet to be released, hundreds of thousands across China have reportedly already received one of the candidates. Additional phase 3 clinical trials are being held in numerous countries the world over, from Bahrain and the United Arab Emirates to Argentina and Peru. Inactivated vaccines aren’t without risks of their own, and several in the past have gone south due to insufficient safety evaluation and monitoring. But done right, they’re also the most tried-and-true approach we have. Alternatives to mRNA vaccines that are more logistically feasible and cost-effective for all won’t be available quite as immediately, but have a far greater chance of reaching more people in need when they do hit the shelves. Two to three months is my best guess, at which point we’ll have a better idea of which populations the Pfizer and Moderna vaccines cannot penetrate. In a pandemic, no country is an island—a lesson China is learning on a weekly basis as new infections arrive in one form or another from overseas. A vaccine all but exclusive to urban, high-income countries won’t cut it. The more pragmatic solution is a vaccine viable and affordable to all. This article originally appeared in LeMonde and is available online here: Why Most Countries Won't Benefit From Moderna and Pfizer’s Covid-19 Vaccines
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There Will Be No Quick COVID Fix Project Syndicate | December 29, 2020 | Article
Rather than waiting and hoping that scientists will deliver a fully effective vaccine or breakthrough treatment for COVID-19, the hardest-hit countries need to be fostering better leadership, governance, and social solidarity. Technology alone will not save us from the virus; we must save ourselves. CAMBRIDGE – COVID-19 stormed across the planet in 2020, striking first in Asia and then surging throughout Europe and the Americas in what seemed like an endless tidal wave of grief. With each passing milestone – the first 100 deaths in January, followed by the first 1,000 in February, 10,000 in March, 100,000 in April, and one million as of September – the question always has been when it will it end.PreviousNext Despite its virulence, many simply assume that the pandemic will end sometime in 2021. But such hopes are misplaced. Controlling an epidemic involves four fundamental components: leadership, governance, social solidarity, and a medical toolkit. Most countries today have failed on the first three, all but ensuring that COVID-19 will remain with us over the next year. Most likely, winter in the northern hemisphere will bring a sharp rise in infections and deaths. The losses will be particularly pronounced in Europe and North America, where daily infection rates were already spiking in mid-autumn. And just as the weather starts to warm in the north, South America will cool and another epidemic wave will crash over us. As for the fourth component of epidemic control, many assume that vaccination or a lifesaving treatment is imminent. True, the pandemic has brought out the very best in science and medicine. Researchers around the world have moved faster and collaborated more closely than ever before, identifying the virus, mapping its genetic makeup, and working toward potential vaccines and treatments. But even with these incredible successes, there is still only a slim chance that we will have a vaccine or treatment that is
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safe, universally available, and effective enough to stop the pandemic before the end of 2021. At the time of writing in late 2020, we are just beginning to see published results for the vaccines that gained regulatory approval in December. Based on what we know today, we should assume that none of the vaccines under development will prevent infection or provide lifelong, lasting immunity. At best, they will limit the symptoms of those infected and minimize the number of COVID19 cases that progress to severe illness. Moreover, the vaccines currently approved for use require multiple doses, with a delay of up to two months before the benefits kick in. Likewise, lifesaving treatments for those with COVID-19 will not come quickly. Treatments that initially met with great fanfare – remdesivir, convalescent plasma, and dexamethasone – have since proven to have little to no effect on overall morbidity or mortality. And treatments with greater therapeutic potential, like monoclonal antibodies, are still many months away, and may ultimately prove too costly to be made widely available. The absence of a medical quick fix will increase the need for leadership, governance, and social solidarity. Political leaders must accept full responsibility for the lives that are lost. Less than three weeks after scientists identified the virus, and after the first reported death in Wuhan, Chinese President Xi Jinping locked down 57 million Chinese citizens in Hubei province, preventing them from traveling to other regions or leaving their homes for anything other than necessities. China showed that new infections could be halved in just two weeks through standard measures such as enforced mask-wearing, social distancing, and mandatory quarantine and isolation. By contrast, in countries like Brazil, the United Kingdom, and the United States, national political leaders dismissed the threat and dithered in marshaling the appropriate response. Many commentators have attributed China’s success to totalitarianism, but a country’s system of government is not really the deciding factor. Far more important is whether political leaders are willing to trade short-term economic pain and quotidian conveniences for the safety of their citizens. In New Zealand and Australia – both vibrant democracies – bold leadership and strong governance brought new infections down almost to zero, and 580
political leaders like New Zealand Prime Minister Jacinda Ardern were rewarded accordingly at the ballot box. The first year of dealing with COVID-19 has taught us that piecemeal measures will only feed the pandemic. National and global crises call for national and global coordinated action. The US, the UK, Brazil, and other laggards have failed on both counts. Indeed, some countries are still pursuing the foolish notion of herd immunity, despite scientific evidence suggesting that no such protection exists for this disease. There are four common (though rarely remarked upon) coronaviruses that infect up to 15% of the world’s population each year, and that come back year after year, often re-infecting the same people. Assuming that SARS-CoV-2 is no exception, any country that places its hopes on a herd-immunity strategy will be endangering the rest of us year after year. Though the Chinese government made some critical misjudgments early on, one thing it did right was to warn the rest of the world that the virus was transmissible, airborne, and controllable only through drastic and immediate measures. The countries that ignored the warning have since suffered the most, both economically and in human terms. Meanwhile, the countries that demonstrated social solidarity in controlling their outbreaks have been able to reopen their economies, though not necessarily their borders. In the end, though, a collective response merely reflects the sum of individual actions. In too many countries, individuals fear that acceding to protective measures amounts to giving up one’s personal freedoms. Yet in times of war, when the dangers are apparent, people have shown time and again how much they are willing to sacrifice for their fellow citizens. Clearly, a change in messaging is in order. We are at war with a virus. Few doubt the importance of personal liberty, but this is a time when we all need to forego certain conveniences for the sake of those around us. Each new earthquake, tsunami, or emerging disease reminds us that nature is a dangerous force. If there was a reason why many Asian countries reacted more quickly and effectively to COVID-19, it was because they still harbored memories of SARS, H1N1, and the avian flu. Their experience in recent years shows that publichealth measures that are stringently applied through strong
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leadership, governance, and social solidarity can quickly bring a pandemic under control and limit the death toll. That is the biggest lesson of 2020. If it is not incorporated into national policies in 2021, the pandemic may well last not just through the next year but for many more years to come. This article originally appeared in Project Syndicate and is available online here: There Will Be No Quick COVID Fix
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It’s Time To Recalibrate: New Covid-19 Strains Will Only Make The Pandemic Worse Forbes | December 30, 2020 | Article
The new variant of SARS-CoV-2 emerging in the United Kingdom has made its way to the United States. As Covid-19 grows worse in the United States—around 180,000 cases and 2,000-4,000 deaths per day—this new, potentially more contagious variant of the virus will only accelerate the hardship of the coming months. It’s time to recalibrate. Measures to control Covid-19 in the US are not working and vaccine rollouts are slower than we hoped. Things will only get worse. We must rethink our strategies to manage Covid-19 to save the hundreds of thousands that will die in the coming months. The recipe for Covid-19 success requires quality ingredients. The first of these is to follow France’s lead: shut things down across the country. Asking people nicely to stay home, as we’ve done in the US, has unequivocally failed. As thousands lose their lives, nearly a million Americans flew on Christmas Eve. France experienced worse infections rates than us in recent months, but reduced rates by twenty times with strict lockdown enforcement. We’ve seen the effectiveness of stringent lockdown measures before. At the start of the pandemic, the US maintained adequate control over the spread before reopening the economy and unleashing the virus. In addition to France, European countries like the United Kingdom, Italy, and Spain similarly controlled Covid-19 to a high degree. Rates began to spiral, again, as economies reopened. Japan recently bar entry to all nonresident foreign nationals as a new Covid-19 precaution. A few weeks of lockdown could singlehandedly halt the rapid acceleration of cases we currently experience, and in tandem with other measures, can bring Covid19 completely under control. The next ingredient is to accelerate vaccine distribution throughout the country. The US vaccine rollout is already far behind schedule. Operation Warp Speed’s initial estimates were 20 million vaccinated by the New Year and 20-25 million more in January. 583
Only about 2 million have received the vaccine or 10% of the previously set goal. We have several high-quality US vaccines, but now there are two Chinese vaccines and the Oxford-Astrazeneca vaccine approved in other major nations. We should work to import those to bolster our vaccine distribution efforts at home. The Chinese vaccines are roughly comparable in effectiveness to the Moderna and Pfizer vaccines, but they are cheaper to produce and easier to transport. We need more data on the safety and effectiveness of all the vaccines, which will only be apparent in time, but having more vaccines available to more people would be significant progress. The third ingredient is the implementation of cheap, rapid, athome tests. These tests could cost as little as fifty cents, they deliver results within fifteen minutes, and they can be self-administered or administered by a parent for a child. The first at-home rapid test was granted emergency use authorization a few weeks ago. Abbott Laboratories, maker of a fifty-cent Hepatitis C test used in Egypt, is developing a cheap test of their own. Having everyone tested regularly could help us identify those infected, regardless of if they are symptomatic or asymptomatic. Those with a confirmed case would be quickly isolated and would receive financial assistance in the form of direct payments or commodities like food, shelter, medical needs, and so on. With all these ingredients, there must be a chef to prepare the recipe. The federal government has yet to take responsibility for major Covid-19 initiatives. Testing, treatment, and now vaccine regimes were left to the states to figure out. I suspect no level of US government—federal, state, or local—has the courage and the power to do what is needed in the face of likely citizen resistance. Americans don’t want to feel forced into home isolation, vaccinations, or mandatory testing, so American politicians are scared to implement such policies. The new strain is making all the above items all the more necessary. We don’t know much about the UK strain found in Colorado, but there are many causes for concern. It seems this is strain is highly infectious, more so than strains up to this point. It also opens the door to the possibility of other new strains of the virus. There are likely homegrown strains in the US that have yet to be identified. 584
With every new strain, there are new mutations to the structure of the virus. If there are too many mutations, the vaccines we are distributing may not provide protection. Scientists seem unconcerned that the UK variant will fall into this category, but variants may already exist that are too far gone for our current vaccine regime. We must act before this pandemic becomes any worse. A nationwide lockdown, improved vaccine distribution, and a rapid test regime could bring this pandemic under control in a matter of months. The recipe is written and the ingredients are available. At this point, the question is whether or not the chefs—our public leaders—decide to cook. This article originally appeared in Forbes and is available online here: It’s Time To Recalibrate: New Covid-19 Strains Will Only Make The Pandemic Worse
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How The US Military Is Handling Covid-19 And What We Can Learn From Their Experience Forbes | December 31, 2020 | Article
As vaccine news and Covid-19 case resurgence dominate the media’s attention, the military and its Covid-19 experience seem to be flying under the radar. While we at home isolate and reduce our societal interaction, military members continue to interact with hundreds if not thousands of other military personnel every day. How has Covid-19 impacted the United States’ armed forces, and will vaccines enable them to return to business as usual? While their media presence is limited, the military has dealt with more than their fair share of Covid-19. According to the Department of Defense (DoD), military personnel had over 104,000 cases since the start of the pandemic. While a small number in reference to the 180,000 cases the United States confirms every day, the military is comprised of only about 1.3 million active-duty personnel. Therefore, over 8% of military personnel have had a confirmed case of Covid-19, compared to about 15% of Americans. This is likely not more significant news because of the military’s lack of severe Covid-19 cases. Only 14 have died from the 104,000 cases, or a death rate about 130 times lower than the United States’ death rate. As severe Covid-19 tends to affect the elderly and those with pre-existing conditions more frequently, it makes sense that a group comprised of healthy, in-shape soldiers under forty were not inhibited much by Covid-19. The spread rate is still concerning as we don’t know the long-term effects of contracting the virus. It seems the close-quarter nature of military life allows the virus to flourish. On the USS Theodore Roosevelt, Covid-19 was able to spread rapidly among its crew of 4,779. Over a few weeks, 1,331 members of the crew tested positive or were suspected positive for Covid-19. A report by the New England Journal of Medicine suggested the tight living quarters of the ship and proximity to those infected enabled the virus to spread like wildfire. While only one of the crew died from Covid-19 related complications, who is to say 586
the unknown long-term complications those 1,331 may face later in life? The DoD is learning from its mistakes, like the USS Theodore Roosevelt, from the early pandemic. Efforts to quarantine sick personnel and standardize mask use have drastically improved in recent months. DoD officials are working with the Department of Health and Human Services to get the military vaccinated as a priority group. Personnel deployed abroad, such as in South Korea or Japan, have already begun vaccine administration. DoD officials may be pinning their hopes on the vaccine with the assumption that they can continue operating business as usual. Though, we still do not know much about the Covid-19 vaccine’s neutralizing antibodies. Preliminary data released by Moderna suggests that their vaccine’s neutralizing antibodies may deteriorate quicker than many were hoping for. The other vaccines have yet to release their antibody data, but that trend could be damaging to the thought that vaccines are a silver bullet for the pandemic. Additionally, these vaccines may not protect against infection and transmission, only symptoms. Preliminary data on whether the vaccines stop the SARS-CoV-2 virus from infecting a human host is still unavailable. That means that those in the military who are vaccinated may still transmit the virus to those who haven’t. Despite the unknowns regarding vaccines, the rest of society would do well to follow the military’s lead and their Covid-19 precautions. While their infection rate remains high, their attention to close-quarter Covid-19 protections on planes and ships could be a blueprint for the rest of us. Mandatory mask use, distancing as much as possible, regular rapid testing, and swift quarantine procedures are all policies that could save thousands of lives in the coming months if applied to the larger population. Any high-capacity military operation will yield positive Covid19 cases. While the not ideal due to the unknown long-term dangers of Covid-19, the military is implementing policies to protect their personnel, which should be noted by the larger population. Toplevel health officials have indicated January will be “the darkest time of the pandemic.” Tens of thousands will die in the coming weeks. We must follow the military’s lead and immediately implement
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common-sense Covid-19 policies as many other major nations already have. This article originally appeared in Forbes and is available online here: How The US Military Is Handling Covid-19 And What We Can Learn From Their Experience
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January 2021
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Vaccines Need To Be Cheap And Accessible Worldwide Forbes | January 5, 2021 | Article
Vaccine development typically takes years of research, design, and trial. For Covid-19 vaccines, pharmaceutical companies took only months to receive emergency use authorization from the Food and Drug Administration. This rapid development should be applauded, but the next steps are equally crucial. These vaccines need to be affordable and accessible, not just in the United States, but globally. As one of the world’s wealthiest countries, the US should do its part to ensure we achieve worldwide vaccination. Worldwide vaccination requires all countries receiving the vaccines they need. We need a sort of vaccine equity. Countries shouldn’t get more vaccines than they need, and all countries should receive what they require. Some countries like Canada and Germany are ordering as many as eight times more vaccines than people. This means poorer countries in Africa, South America, and Asia may not receive that surplus. Sharon Lerner of The Intercept calls this vaccine apartheid. “It’s already clear that the majority of countries will not have enough, while rich countries are hoarding vaccine supplies.” We cannot allow vaccine hoarding and unnecessary death in developing nations. As far as cost, Americans will not pay for the vaccine out of pocket, according to the Centers for Disease Control and Prevention. Typical employer-based or self-purchased health insurance is expected to cover any fees a vaccine provider may charge. Medicare and Medicaid will also cover these fees. A separate fund will reimburse medical providers for the vaccine costs for uninsured patients. While a promising development in the US, the vaccine will not be free for every person on the planet. The Moderna and Pfizer vaccines, which receive the bulk of media attention in the US, are priced between $20 and $37. While not extortionately expensive compared to other medical costs, as many as 650 million people 590
worldwide live in extreme poverty, or $1.90 per day or less. $37 could be two weeks of wages or more. These people deserve the vaccine too. Cheaper vaccine alternatives like the Oxford-Astrazeneca vaccine and the Chinese vaccines are priced around $4 or less. China is already fostering international partnerships to have their vaccine shipped to neighboring countries in the coming months. We should work with the Chinese and have these vaccines central to a UN-sponsored global vaccination effort. I have written that the Moderna and Pfizer vaccines are like Lamborghinis—high-end mRNA shots requiring super-cooling freezers and double doses. The world doesn’t need a Lamborghini; it needs a Toyota—a cheaply manufactured, stored, and administered vaccine accessible to all. The Chinese vaccines and other cheap alternatives are more like the Toyota, and they should be used to innoculate the world population. Transporting supercooling freezers to the Mojave desert or through the jungles of central Africa would be nearly impossible. Toyotas will always get the job done. But why should the average American care about the vaccination of Nigeria, Pakistan, or Brazil? The answer is simple: So long as there is an uncontrolled spread of the virus somewhere in the world, it could resurface in massive outbreaks. Take the new UK variant of SARS-CoV-2. There have already been reports of this new variant in the United States. It is also said to be much more infectious than the strains we’ve been working with, so it has likely spread to numerous other states and countries. Not to mention, there is a new variant in South Africa as well, suggesting that there may be emerging variants waiting to pop up all over the world. Some homegrown variants may even be hidden in the US. Covid-19 is dangerous; we all know that. The only way to permanently contain it is to ensure everyone in the world is vaccinated. The repercussions of another massive outbreak after the losses of 2020 are too great to bear. We all need to do our part. This article originally appeared in Forbes and is available online here:Vaccines Need To Be Cheap And Accessible Worldwide
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The Risks Of Delaying Or Diluting Covid-19 Vaccines Forbes | January 6, 2021 | Article
With a limited supply of Covid-19 vaccines, the question on many minds is whether to dilute the vaccines or delay the second dose to speed Covid-19 vaccination. My answer is neither—the greatest threat to population protection is virus resistance. Diluting the vaccine or delaying the second dose is a reckless wager, which may give SARS-CoV-2 an opportunity to mutate beyond the power and protection of our current set of vaccines. Yet, despite acknowledging the risk, countries like the UK still seem intent on pursuing the option, putting each and every one of us at risk. All the vaccines currently approved require two doses administered three to four weeks apart. The first shot starts building protection and the second shot helps elevate the levels of protection the vaccine has to offer. Data on protection from a single dose of the vaccine is sparse, but we know that the concentration of protective antibodies is low after one dose of the vaccine or after two doses of diluted vaccines. For the Pfizer vaccine, for example, a study published in the BMJ found that the vaccine was only 52% effective after the first dose. Only after the second dose did protective levels rise to 95%. There are reports that a single dose of the Moderna vaccine may be more protective, up to 80%, but the truth is that no one can say with certainty how protective a single dose may be and for how long. We do know, however, that most routine vaccinations require multiple doses over months and sometimes years to be fully protective. We should not assume that the Covid vaccine will be any different. Those suggesting that two diluted doses of a vaccine would provide the same protection as a two full doses are working off of even less solid evidence to back their claims. There is no data publicly available on how effective these diluted vaccines may be. Even executives at the pharmaceutical companies who have a dog in the fight have hesitated to sponsor the approach and the FDA has 592
called it “premature and not rooted solidly in the available evidence”. Despite the lack of data, we can say with near certainty that a diluted or delayed vaccine will lead to a large population with low antibody titers, which is the ideal condition for creating vaccine resistance. New strains of SARS-CoV-2 already exist that are more transmissible and lack at least two essential sites for virus neutralization. Contrary to many public statements, SARS-CoV-2 can and does mutate to evade immune pressure and can do so in a single individual. There is no telling what the implications may be of only partially vaccinating a large swath of the population against a virus as clever and wily as this one. Vaccine production is ramping up rapidly in the US, Europe, Russia, China, and India. Strategies intended to provide minimal protection to many place everyone, vaccinated or not, at needless risk from SARS-CoV-2 variants that no longer respond to extant vaccines. Rather than shortening the pandemic, delay and dilute strategies will most likely prolong the pandemic indefinitely. This article originally appeared in Forbes and is available online here:The Risks Of Delaying Or Diluting Covid-19 Vaccines
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New Covid-19 Variants In One Country Pose A Threat To All Countries Forbes | January 6, 2021 | Article
New variants of SARS-CoV-2 are an unexpected spanner in the works as countries around the world establish their vaccine distribution regimes. These new variants, which may be more contagious from early observations, pose new challenges in the global fight against Covid-19. SARS-CoV-2 variants cause problems for the afflicted countries and present dangers for all countries in the battle against Covid-19. The United Kingdom variant was first detected in October 2020 from a sample taken the month before. The variant gained notoriety in the international media as cases surged in the UK from October to December. By mid-December, it was estimated that nearly 60 percent of Covid-19 infections in London were caused by the new variant, which the UK viral advisory board concluded was more transmissible than other variants. Six thousand miles south, authorities in South Africa were discovering their own variant. On December 18, South African health officials announced a variant found the month before spreading through three provinces. The South African variant was also deemed more transmissible by health authorities in a similar light to the UK variant. As of January 5th, the UK variant has been discovered in over thirty other countries and the South African variant in four. The rapid spread should be disturbing to those anticipating an end to the pandemic in the coming months. These variants appear rapidly transmissible. After a holiday period where millions of people flew commercially in America alone, these cases stemming from the variants will only accelerate throughout January. Health authorities remain optimistic that the vaccines in distribution will still provide immunity for the UK variant, but we await proof that their optimism is justified. Vaccine distribution in the UK has already begun, and a resistant new variant would 594
complicate that venture. The South African variant has not been studied as closely or as long as the UK variant, and some are cautious that the vaccines may not cover its mutated structure. This is one of the dangers new variants prompts. Every transmission of the virus increases the chance of mutation, and with enough mutations, the virus may evade vaccines. If the UK and South Africa variants have mutated to become more transmissible, it seems equally possible that other variants could equally mutate their structure to avoid the vaccines that are currently being distributed worldwide. This is why a single country’s new variant affects all countries. With every mutation, the worldwide population faces the risk of ineffective vaccines. There’s also a sizable chance that the UK and South Africa variants are not alone. There have been over 80 million recorded Covid-19 cases and likely millions more. It almost seems more likely that variants are lurking, waiting to be discovered. There may be variants in the United States. The UK found its variant through genome sequencing, which the US has not been doing as much. There could be a vaccine-evading super spreader somewhere in New York, California, or Texas. We should try to find them before they cause significant damage. Ultimately, leaving any form of the virus in any country unaddressed could lead to serious outbreaks all over the world. Vaccines provide a chance to get most of the spread under control, but emerging variants make that plan a bit more difficult. If the UK, South African, or undiscovered variants of the virus become vaccine resistant, there need to be alternate plans in place. Research into these new variants should be held to the highest priority. We should also keep a close eye on new cases’ genomes to monitor for new emerging strains. We can beat this, but we need to keep working hard. This article originally appeared in Forbes and is available online here:New Covid-19 Variants In One Country Pose A Threat To All Countries
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How The Covid-19 Virus Changes Forbes | January 6, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the first in a series of articles on how the virus changes and what that means for humanity. In September 2020, a sample of the new coronavirus variant B.1.1.7, also known as the UK variant, was collected and identified for the first time. Within three months, B.1.1.7 would be, at least in Britain, the dominant strain of SARS-CoV-2. Today, its prevalence is estimated to be above 90 percent; its contagiousness, up to 75 percent greater than previous strains; and its viral load, higher too. B.1.1.7 wasn’t the first variant to successfully overthrow its predecessor, and now it can be found in more than 35 countries. Nor will it be the last, as the 501.v.2 variant, now the dominant strain circulating in South Africa, is already proving. But how do variants form in the first place? The answer goes back to the building blocks of life: the genome. More specifically, single-letter differentiations in viral RNA that may begin as mere errors, but when sufficiently multiplied increase a virus’s chances of survival. These are otherwise known as mutations. To replicate its genome and thus reproduce itself, SARS-CoV2 relies on an enzyme called the RNA-dependent RNA polymerase. As the polymerase does the mostly monotonous work of stringing together nucleotides—the organic, protein-coding molecules classified as either adenine (A), thymine (T), cytosine (C), or uracil (U)—a number of mistakes make their way into the mainframe. Many of these point mutations will ultimately be inconsequential. The ones that matter change proteins that impact how the virus functions, such as the spike protein.
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We can make sense of mutations using six distinct categories. The first and most common type is substitution. Where an A should go, for example, a G somehow ends up instead. Unlike most RNA viruses, human coronaviruses come equipped with corrective machinery that can normally fix substitutions. This so-called proofreading mechanism is why SARS-CoV-2 has thus far yielded a rate of error much lower than RNA viruses like HIV and influenza. But what this virus lacks in its capacity for variation, it makes up for in the large number of people it infects—meaning that when a variant does catch on, it can spread like wildfire. The second type is deletion. Deletions occur when the polymerase skips, leaving a gap in the genetic code. The nasty thing about deletions is that the virus cannot correct them retroactively. Though more likely to disrupt function than a substitution, and just as capable of killing the virus altogether, some deletions, both small and large, still allow the virus to grow. The mutations of this sort that are most advantageous to the virus—and of most concern to us—alter the virus in significant ways. Two kinds of deletions exist—in frame, and out of frame. So long as deletions appear in multiples of three, they remain in frame, unobtrusive to the protein as a whole. However, deletions that occur singly or doubly—out of frame—disrupt the entire protein, not unlike the misplaced letter in a run-on sentence that causes the reader to stop and stumble. The third type is insertion, a mutation that has been observed occasionally amongst the hundreds of thousands of genomic sequences stored in GISAID, an open-access sequence repository. Insertions describe the extra bits of genetic information, whether it’s one nucleotide or an entire segment, that end up in a given genome by chance. The fourth type is inversion, which happens when a segment of the genome is flipped on its head, reversing the order of its nucleotides. When the polymerase stutters and spits out the same bit of information over again, a duplicate is created—hence the fifth type, duplication. The sixth and final type is recombination. Literally, parts of two separate viruses become conjoined. When two different viral genomes find themselves in the same cell, their bits and pieces can 597
shuffle from one to the other, unwittingly settling into new forms in the process. The way SARS-CoV-2 produces its proteins encourages recombination. Even a region as crucial as the S protein could be up for grabs. The existing literature on coronaviruses already tells us they can recombine, at least in bats. In fact, this process is likely how SARSCoV-2 came to be born, possibly in the ant-eating mammals known as pangolins. There are unpublished reports that recombination among SARS-CoV-2 variants occurs. In a dense crowd, one person might be infected simultaneously by two different people, or reinfected when subgenomic remnants of their first infection still linger on in their system. SARS-CoV-2 can also infect animals that live closely with us, and as such recombination events combining SARS-CoV-2 with animal genes might also occur, changing the virus in unknown and possibly dangerous ways. Given the high prevalence of both SARS-CoV-2 and other cold-causing viruses at this time, I suspect all the events above have either already occurred or inevitably ill. At first glance, none of these mutations, taken in isolation, would appear capable of kickstarting a new variant of disease. Calculated and conceived at scale, however, a more swarming and certainly more startling impression begins to emerge. Take substitution. On average, in a viral genome 30,000 units long, substitution alters one unit of every 10,000. We can’t say for sure how many viruses are teeming at any moment within one person infected with Covid-19, but we do know that every milliliter of contagious nasal fluid contains something like 10^8 (one hundred million) to 10^9 (one billion) viral particles. One billion viruses, per our one per 10,000 average, means three billion substitutions—and that’s just in one drop of mucus. Multiply that by the actual volume of active virus in a single body, then the number of active Covid-19 infections in a given populace, and before long you’ll find yourself well into the quintillions. In other words, the mutations that give way to viral variation are happening all the time at rates nearly inconceivable. We now know the mechanisms by which viral variation arises. The reasons why are what I’ll cover in the next piece in this series. This article originally appeared in Forbes and is available online here: How The Covid-19 Virus Changes 598
How To Decipher The New Pfizer Study On Vaccines And Variants Forbes | January 8, 2021 | Article
One of the biggest and most pressing questions to arise about new SARS-CoV-2 variants like B.1.1.7, the so-called UK variant with 17 distinct mutations, and the so-called South African variant 501.V2 is whether they’ll impact the efficacy of Covid-19 vaccines. In an attempt to offer some reassurance and possibly some answers, Pfizer has released a new study suggesting that people who have been immunized with their vaccine have antibodies that remain potent against at least one of the more prominent mutations, N501Y. This mutation is one of many that alters the virus’s spike protein and increases its ability to bind to and infect our cells. But there is so much more to the story than just N501Y. The results of the Pfizer study, published yesterday and still undergoing peer review, are based on blood samples from 20 of the individuals who have already received the Pfizer vaccine. While it’s encouraging to know the Pfizer vaccine seems to be impervious to the effects of at least one significant variant, many more remain in the mix that we’re still unsure about. One such example is E484K, a mutation critical to the South African 501.V2 variant also located in the spike’s receptor-binding domain. Leaving out these key pieces of the puzzle risks oversimplifying what is actually an incredibly complex issue. Ever since NERVTAG, the British advisory committee tasked with surveilling emerging viral threats, established that the B.1.1.7 variant was up to 70 percent more transmissible than the previously dominant strain, experts have debated whether new variants will present challenges for containing the pandemic beyond increased contagiousness alone. Perhaps the most worrying possibility is that the B.1.1.7 variant, 501.V2 variant, and others like them have evolved to evade the full force of our natural immune responses—diminishing the ability of our antibodies to neutralize and clear out the virus.
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Were this true, the extent of the damage wouldn’t end with vaccines and their capacity to fully immunize and protect us. Two of the experimental treatments currently used on critically ill Covid19 patients, convalescent plasma and monoclonal antibody drugs, rely heavily on preparations of neutralization antibodies to work. Looking at the existing literature on how key SARS-CoV-2 mutations interact with these treatments, both designed to bolster the immunity of their recipients, can give us clues—if not concrete answers—as to how they might impact vaccine-mediated immunity. Another recently published research paper—also awaiting peer review—mapped how antibodies in several infusions of convalescent plasma were impacted by spike mutations. The spike, we must remember, is not just vital for SARS-CoV-2 and its goal to hijack our cells, but the primary target for both drug and vaccine development. While the main effect of mutation N501Y, an increased affinity for the virus’s favorite cellular receptor ACE-2, didn’t interfere with antibody binding, researchers found that mutations associated with E484, one of the sites left out of the Pfizer study, had the biggest impact on antibody neutralization. In some cases, E484-related mutations reduced the potency of convalescent plasma more than tenfold. One potential case of immune evasion is documented in more detail in a third preprint study of a man hospitalized with Covid-19 in May 2020 and administered not one, not two, but three rounds of convalescent plasma, among other drugs, over the course of 101 days. During his first hospital stay he appeared to recover, only to be readmitted about a month later due to breathing difficulties and a bad cough. Prior to contracting the virus, the man had already been diagnosed with lymphoma and treated with rituximab, an immunosuppressive therapy. It is possible that with each fresh infusion of antibodies, the virus—given next-to-free reign by a compromised immune system—was able to mutate, grow, and otherwise adapt more effectively than in other hosts. In other words, what SARS-CoV-2 is currently doing at the population level—navigating a checkerboard of partially immune and immunocompromised human hosts—it was doing in the body of an individual patient. In the time the patient described in the study spent at the hospital, researchers extracted and analyzed more than 20 different viral samples. They observed mutations like the H69600
V70 deletion, found in the N-terminal of the spike, that have also been detected in several new European strains. This mutation—like E484K, not included in the strain of virus Pfizer used to study antibodies in vaccinated patients—has also been associated with increased infectivity in the laboratory. The man eventually succumbed to the disease, leading to the likely conclusion that the virus evolved to escape the antibodies present in the convalescent plasma from three different patients. The new Pfizer study examines several variants that existed before B.1.1.7 and 501.V2 were discovered, with a promise of further research to come. But a much more thorough investigation into not just the E484K mutation and H69-V70 deletion but others, like those in the furin cleavage and others in the N-terminal sites, must be undertaken before we can rest assured that our vaccines, and our immune responses at large, guard us against emergent mutations and resultant strains. Until then, continued vigilance and adherence to public health measures remains of the utmost importance. Better safe, after all, than sorry. This article originally appeared in Forbes and is available online here: How To Decipher The New Pfizer Study On Vaccines And Variants
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Why The U.S. Needs To Step Up Covid-19 Genome Sequencing Forbes | January 8, 2021 | Articles
The United Kingdom and South Africa discovered new SARSCoV-2 variants in their domestic Covid-19 cases. The variants were found using genome sequencing techniques that analyze the structure of the virus and discern mutations. These genome sequencing techniques were regularly used worldwide at the start of the pandemic when we knew less about the virus, but they have since fallen by the wayside. The US and other countries should follow the UK and South Africa’s footsteps in terms of revamped genome sequencing regimes, as the next variant may be hiding in our backyard. Genome sequencing is essentially determining the order of chemical “bases” of a DNA molecule. Scientists use these sequences to identify genes, regulatory instructions, or in the case of Covid-19, mutations to a virus. Sequencing efforts early on in the pandemic helped scientists determine the structure of the virus, as well as early mutations that helped the virus be transmissible enough to cause a massive pandemic. More recently, genome sequencing was the key to identifying the more transmissible variant discovered in the UK. The Covid-19 Genomics Consortium has been tracking Covid-19’s genetic history for nearly a year, logging over 150,000 viral samples. Whereas most variants of the virus have one or two minor mutations from each other, the UK variant had 23 separate mutations. This discovery caused concern and further inspection by the Consortium, which determined the mutations led to an accelerated transmission process. The UK variant is thought to have fueled the massive influx of cases in the UK in recent weeks. South Africa’s new SARS-CoV-2 variant was discovered under the same technique. The new strain was found in late November and was announced a month later after further research and analysis. Like the one found in the UK, this new strain was determined to be 602
highly transmissible in comparison to the strains we have been working with for the majority of the pandemic. South Africa, which has weathered the Covid-19 storm relatively well, is now amid a surge in cases as the UK is. In the United States, our sequencing efforts have waned over time. At the start of the pandemic, the global community was trying to figure out what this virus was, and at that time, many samples were genome sequenced in that effort. Today, only .3% of samples have been sequenced in the United States, which ranks 43rd according to the GISAID Initiative, a global genome sequencing database project. Sequencing can aid in the fight against Covid-19 and the newly emerging variants. The UK and South Africa variants have already been detected in dozens of cases in the US. The transmissibility leads me to believe that cases involving these variants are already widespread, but our lack of genome sequencing allowed the variants to evade surveillance. In response to these new variants, the CDC announced a doubling of our sequencing effort. A robust sequencing regime may find more than just additional cases of the UK and South Africa variants. The virus can mutate every time it transmits to a new host, and with tens of millions of recorded cases worldwide, there are likely variants hidden waiting to be discovered. In the United States alone, some estimates suggest that 15-20% of Americans have had Covid-19, which would make a new variant stemming from a case in the US quite possible. If a homegrown variant is out there, that may have aided in the recent surge in Covid-19 cases observed over the holiday season. The prospect of a more contagious strain working its way through the US is scary enough, but there’s a chance that with enough mutations, a strain may be able to evade current vaccines. That is why efforts to find these strains must be bolstered. If a section of the population has a vaccine-resistant strain of Covid-19, national public health agencies must identify them and continue vaccine research from there. The hope is that these mutations haven’t occurred, but we don’t know for sure. The vaccine may cover the new strains in the UK and South Africa, vaccine distribution will continue as planned in the coming months, and life will return to normal in the latter half of 2021. The opposite is also possible. Genome sequencing in the US and 603
worldwide must be bolstered, and then new strains must be identified and isolated. Otherwise, we may be looking at a very long year. This article originally appeared in Forbes and is available online here: Why The U.S. Needs To Step Up Covid-19 Genome Sequencing
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Who Are The Vaccinated That Still Become Infected? Forbes | January 9, 2021 | Article
Vaccine development was one of the few shining lights during a dark past ten months. After a remarkably rapid design and trial period, pharmaceutical companies Moderna and Pfizer announced efficacy percentages in the high 90s. A tremendous achievement, but even an efficacy of 95% means five percent of vaccinated people are susceptible to Covid-19. Some vaccines, like the OxfordAstrazeneca and Chinese vaccines, have efficacy around 90 or even 80%. Assuming efficacy numbers hold true, many millions will still get infected after receiving a vaccine. Five percent of a global population approaching eight billion is upwards of 350 to 400 million people. Ten to twenty percent could be as many as 800 million to 1.6 billion people. For those people who were vaccinated that were later infected, what happened? Little data is available on those that are vaccinated, then infected. Most vaccine attention focuses on widespread distribution or lack thereof. As distribution settles down and the vaccine is available to more people, attention will likely shift to the vaccines’ success over time. Understanding those biological failures will enable scientists to improve vaccines prevent further viral spread. Once inside the body, many factors could increase or decrease the chance the vaccine will protect. As these vaccines require two doses three weeks apart, it’s possible that patients contracted Covid19 after their first dose when efficacy is much lower. Some experts suggest that those that have recently received a blood transfusion have impaired vaccine immune response. Some people’s immune systems may reject the vaccine antibodies altogether. There is still little known because we don’t have long term vaccination data yet. Everyone responds differently to the virus. No two Covid-19 patients have the exact same immune response to their infection. The same could be said for vaccines. Many of the vaccines in 605
distribution have neutralizing antibodies which help the body fend off the virus. In many cases—5 to 20% based on which vaccine is used—these antibodies may be rejected by the body’s natural immune response. This is data researchers need to be on the lookout for. If vaccines don’t cover everyone, we need to know why and how we can fix it. There should be some national vaccine data collection system in place to help researchers learn more. Such a system could be associated with social security numbers, simply indicating which people were vaccinated, which have yet to be, and who got sick after receiving their shots. This would allow researchers to investigate the cases where vaccines didn’t help, identify factors in the pre-inoculation process that may have gone wrong with that shot, or see if the patient had some reaction to the vaccine leading to it being ineffective. This system would also help state and federal health entities track vaccine distribution progress as they attempt to inoculate over 300 million people in the United States and nearly 8 billion worldwide. Vaccine distribution to this point has been an unmitigated disaster, with vaccination counts well below the estimations set in previous weeks. We need a change in administrative processes to catch those who fall through the vaccine safety-net. Additionally, the emerging Covid-19 variants render understanding vaccine efficacy all the more crucial. The mutations in the structure of the United Kingdom and South African variants created a more contagious virus. It’s possible that mutations could occur to make these variants or undiscovered variants resistant to current vaccines. Pfizer released a statement attempting to dissuade concern about variants being vaccine-resistant, but their studies did not test a full array of mutations to the virus, only one individual mutation. Their findings have also yet to be peer-reviewed. The reality is, we don’t know the dangers that lie in the viral variants. We need to learn more. If Moderna and Pfizer have access to information about those that may be less protected by their vaccines, that information needs to be released, studied, and tested. As millions are infected weekly, and thousands die every day, we need to protect those that vaccines cannot. Vaccines represent hope for many wanting an end to this pandemic. If they don’t end up working to
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the degree we hoped, there will be a widespread disappointment to pair with further Covid-19 devastation. This article originally appeared in Forbes and is available online here: Who Are The Vaccinated That Still Become Infected?
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Are We Creating Immune Resistant Variants Of SARS-CoV-2? Forbes | January 11, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the second in a series of articles on how the virus changes and what that means for humanity. Read the first piece here. In May 2020, a man was hospitalized and, soon after, diagnosed with Covid-19. Within weeks he recovered and went home, only to be readmitted the following month when his Covid-19 symptoms came back with a vengeance. This time he was administered, at distinct yet overlapping intervals, a plurality of treatments, including the steroid dexamethasone; two rounds of remdesivir, an experimental drug therapy; and convalescent plasma from not one, not two, but three different patients. The man, his body unable to mount the resistance it needed to clear out the virus, succumbed to the disease in late August. Over the course of the man’s hospitalization, researchers extracted, sequenced, and analyzed more than 20 different viral samples, a process they describe in a research paper currently undergoing peer review. They witnessed the virus evolving in real time, and over the course of 100-plus days noted the emergence of several mutations. One way to interpret this is that each time the man was given, via the blood plasma of previously recovered Covid19 patients, a new mix of anti-SARS-CoV-2 antibodies, the virus found new ways to resist neutralization. In other words, we might be looking at a classic case of immune evasion, a term that refers to the sum total of strategies a virus uses to evade or otherwise overcome the immune system. Immune evasion is a potential outcome of viral variation. I discussed the mechanisms by which viral variation occurs in the first 608
piece of this series—the substitutions, deletions, insertions, and other alterations to genetic code that, multiplied sufficiently in all the right places, can change how a virus functions significantly. Why this happens—the subject of this piece—is why most adaptations happen. When the coronavirus finds itself in an inhospitable environment, it must either adapt or die. What this means for us more broadly is that our attempts to counter the virus, whether at the individual and population level, push it down new evolutionary pathways. Though for most organisms this is a matter of course, that doesn’t mean it occurs without consequence. Notably, prior to his Covid-19 diagnosis the aforementioned patient was already living with lymphoma, a cancer of the blood that begins in the immune system, and receiving injections of rituximab, a treatment therapy that can have immunosuppressive effects. Over the course of several plasma fusions, his body became a sort of testing ground for new variants of virus—not unlike what is now happening to populations around the world. If a barrage of antibody treatments increased evolutionary pressure on the virus responsible for his infection, it can be said that the slow but steady amalgamation of vaccinated, recovered, and other partially immune individuals is doing the same for the virus out in the wild. What is remarkable is that some of the mutations observed in this one man, like the H69-V70 deletion, we’re now seeing in European variants of SARS-CoV-2 that have circulated among millions, including the so-called UK variant B.1.1.7. The H69-v70 deletion is found in the N-terminal domain of the spike protein, the primary target of many Covid-19 drugs and some vaccines. Another study, published last month but also awaiting review, mapped how other kinds of spike mutations impacted the potency of antibodies in preparations of convalescent plasma. Those researchers found that mutations associated with E484, one of many sites pinpointed on the spike, had the biggest and most detrimental impact, reducing the protective capabilities of some antibodies more than tenfold. One of the variants to develop the E484 mutation is none other than 501.V2, also known as the South African variant. Does this mean certain variants of SARS-CoV-2 will learn to evade our natural defenses against it, even in the majority of us who aren’t immunocompromised? Maybe, maybe not, but either way it remains a possibility we can’t afford to ignore. I already mentioned 609
in my last piece that B.1.1.7 is far more contagious than its predecessor, and charts showing skyrocketing case counts across Britain elucidate the dangers of increased transmissibility better than words ever could. The explosive spread of B.1.1.7 foretells what might happen in the United States if we don’t patch up and ramp up our Covid-19 control measures, vaccine distribution included, sooner than later. In my next piece I’ll discuss the implications viral variation has for vaccines—and what we’ll have to do to make sure current vaccination campaigns proceed uninterrupted. This article originally appeared in Forbes and is available online here: Are We Creating Immune Resistant Variants Of SARS-CoV-2?
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How The Vaccine Rollout Went Wrong And What To Do Next Forbes | January 12, 2021| Article
It’s been nearly a month since the Food and Drug Administration granted its first vaccine emergency use authorizations to Moderna and Pfizer. Since then, only about 7 million doses were administered, according to the Centers for Disease Control and Prevention (CDC). At current rates, it will take years to vaccinate everyone in the country. Why has the vaccine rollout fallen below expectations, and what can we do next to course-correct? It seems many of the issues with the vaccine rollout, as well as with testing and reopenings, stem from lacking federal planning. As early as October, the CDC released an interim playbook for vaccine distribution. The 75-page document outlined how vaccines would be distributed to you and me when authorized and available en masse. As I wrote for Forbes at the time, it was clear from this document that vaccine distribution would face difficulties. Like testing and reopening plans in the early pandemic, responsibility for vaccine distribution was shifted to states and localities. Federally led public health programs are uniform, organized, and typically more efficient. When spearheaded by states and localities, public health programs can be disorganized, overwhelmed, and unprepared. It seems the vaccine rollout would qualify as such. Complications with recruiting vaccine administrators, failing to reach week-by-week vaccination goals, and vaccine misinformation have troubled the rollout with slowdowns and confusion. When those interim vaccination plans were released in July, the Department of Health and Human Services (HHS) estimated 100 million doses would be available by the end of 2020. Enter 2021, and less than 7% of that amount was administered. With 2,000 to 4,000 people dying from Covid-19 in the US every day, we need to address the failed rollout and adjust our strategy moving forward. The first clear step is for the federal government, i.e., the entering Biden Administration, to take responsibility for vaccine 611
distribution. One of the most straightforward improvements a federally-led vaccine program would bring is clear goal-setting and standardized vaccine shipment plans. Federal authorities could prioritize vaccine shipments based on rates of Covid-19 infection and hospitalization, as well as population. Creating simple and standardized plans for distribution will help states efficiently prepare for vaccines and organize administration regimes. The incoming Biden Administration could additionally help with recruiting vaccine administrators. Some states are falling desperately short of staffers qualified for vaccine administration. A federal program for training health professionals or even volunteers to distribute a vaccine could alleviate those issues. The HHS also oversees the US Public Health Service Commissioned Corps, which are several thousand military personnel trained in healthcare and medical services. They should be fully utilized to manage vaccination efforts nationwide. The federal government finally needs to utilize its media reach to encourage everyone to seek the vaccine. It seems there has been a concerted effort to promote government officials receiving their vaccination online, but there remains significant potential for vaccine advertisement. Think of all the military ads you see on cable. According to the Center for Media Literacy, the military spends around $200 million annually on media marketing. A similar media effort should be made in support of the vaccination program. A transition of power in the coming weeks presents the opportunity to rapidly course-correct and administer tens of millions of vaccinations at a much faster rate. Democratic strategist Liza Acevedo assures that the Biden team “are going to utilize every resource possible” to achieve 100 million vaccinations in his first hundred days in office. Pfizer supported this rallying cry, releasing a statement claiming the company is “ready to release millions of doses each day.” The Biden team is also planning to distribute second doses efficiently and ethically. They do not plan on “withholding and not giving the second dose,” says Dr. Anthony Fauci. “They are completely committed to giving the second dose on time. They feel that the importance of getting as many people as possible is worth the risk.” Currently, all approved vaccines in the US come in two
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doses, but Johnson & Johnson is in the final stages of trial for a onedose vaccine, which would simplify distribution logistics immensely. It seems, based on statements in recent weeks, that PresidentElect Biden is willing to take on the vaccine task, but whether or not Congress will promote further Covid-19 spending remains to be seen. The federal government has a duty to protect its citizens. Let’s see if they uphold that duty in the coming months with vaccines. This article originally appeared in Forbes and is available online here: How The Vaccine Rollout Went Wrong And What To Do Next
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How New Covid-19 Variants Might Impact Vaccines Forbes | January 13, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the third part of a series of articles on how the virus changes and what that means for humanity. Read the first two parts here and here. Let’s recap what we’ve learned so far. Tiny, random alterations in viral RNA allow SARS-CoV-2 to change over time. Most of these mutations have next to no effect on the virus and some are even corrected using a special proofreading mechanism, slowing the speed of their natural selection. But a large population size—as in, the nearly 100 million people and counting who have caught Covid-19 worldwide—increases the odds that some mutations will end up giving the virus an evolutionary edge, one that benefits SARS-CoV-2 at great cost to us. I discussed in my last piece the risk that new variants of SARSCoV-2, whether already emergent or soon to come, might develop a propensity for immune escape. Now comes a question that has been top of mind for most since variants like B.1.1.7 and 501.V2 were first identified: what does this possibility mean for our efforts to vaccinate millions, if not billions, of people? A recently published preprint attempted to answer this question, at least for the lucky few who have received a dose of the vaccine created by Pfizer and BioNTech. Based on blood samples taken from 20 already inoculated individuals, the study suggests that antibodies generated by the Pfizer vaccine held strong against variants containing the mutation N501Y, an alteration to the spike protein that is also the defining feature of B.1.1.7. But these results, while reassuring, barely scratch the surface of what genomic databases like GISAID have proven to be a much deeper pool. 614
Though most mutations ultimately do little to increase the survival prospects of SARS-CoV-2, there are dozens that can. Some, like N501Y, help the virus become more transmissible by increasing its affinity for our cellular receptors, making it easier for it to latch on tight and force entry. Other mutations could increase viral load, pushing the number of infectious particles that overrun the body to explosive new heights. And others still—arguably the most dangerous of the bunch—might allow the virus to evade or overcome our immune defenses, even if they’re bolstered by vaccines. While it’s highly unlikely a variant will arise that renders current vaccines totally useless, mutations that encourage immune escape could make them less effective. One mutation experts fear will fall into this category is the substitution E484K, which like N501Y is located on the spike protein and has appeared in variants currently circulating in South Africa, Brazil, Japan, and several other countries. E484K appears to give SARS-CoV-2 an element of disguise, making it less recognizable to the antibodies a vaccine trains to eliminate it. Another preprint study found, after mapping the specific ways in which antibodies in several preparations of convalescent plasma were impacted by spike mutations, that E484—more than any other region—had the biggest and most adverse impact on antibody neutralization. In some participants, E484-related mutations reduced the potency of antibodies more than tenfold. And in Brazil, at least one woman who recovered from Covid-19 once before has not only been reinfected with a variant containing the E484K mutation, but also experienced worse symptoms the second time around. Other naturally occurring mutations have been found, either in laboratory experiments or clinical case studies, that have even more profound effects on escape from neutralization by convalescent plasma. The H69-V70 deletion, which I described in my last piece, might be one. Most of the research conducted so far has concentrated on the receptor binding domain, but clearly other viral proteins could assist in escape and thus deserve our attention. Immune escape isn’t the only development that could prove challenging for mass vaccination efforts. In the coming months and even years, so long as infections around the globe continue to rise or reoccur steadily, SARS-CoV-2 will become more efficient at the very task of evolving. Much as the virus has been mutating and 615
experimenting all this time, it has done so clumsily, through aimless and repetitious trial and error alone. Given its lack of sentience, as the virus evolves it will continue to be none the wiser. But that doesn’t mean it can’t get wilier, using each advantageous variation as a stepping stone to the fittest and fiercest version of itself. To avoid being crushed by the incoming tide, we’ll need to do two things. First, vaccinate as many people as possible—and fast. The snail’s crawl at which vaccine rollout is proceeding in the United States simply won’t cut it, especially now that researchers at Ohio State University have reported the discovery of a new SARS-CoV2 variant in Columbus, Ohio. People must be vaccinated not just to prevent them from getting sick, but to reduce the number of opportunities SARS-CoV-2 has to experiment, mutate, and evolve new means of surpassing our defenses. These new properties are ones we cannot anticipate—only observe and react to. Second, expand current efforts to sequence and survey new variants. We need to be prospecting the entirety of the genome, as well as the entirety of the biosphere, for alterations that encourage immune modulation. And we need to be prepared to adapt our vaccines to an adapting virus, as we do with seasonal flu. Over the course of the pandemic, not nearly enough emphasis has been placed on thinking longer term about the bigger picture. That has cost us dearly. We can’t afford to make the same mistake with these variants. Not when we know exactly what to do to protect ourselves against them. This article originally appeared in Forbes and is available online here: How New Covid-19 Variants Might Impact Vaccines
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New Covid-19 Variants Reshape Our Understanding Of Reinfection Forbes | January 14, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the fourth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, and part three. In the previous articles of this series, I explored how SARSCoV-2 changes, how those changes contribute to immune escape, and what this all means for global vaccination efforts. An aspect of SARS-CoV-2 particularly relevant to this discussion—one that remains under-examined more broadly—is its ability to reinfect the same host twice. While Covid-19 reinfections have been reported and confirmed previously, the case of one 45year-old woman in Brazil is the first to involve the mutation E484K, a defining feature of the South African variant 501.V2. It is also a mutation experts fear might evade even a robust immune response. The woman reinfected is a health executive who lives in the coastal city of Salvador, Bahia and kept an extensive record of her symptoms. According to the preprint study documenting her case, her first infection, which began mid-May 2020 and lasted about seven days, caused diarrhea, muscle pain, and fatigue. She took a corticosteroid called prednisone to treat it, and in three weeks was back to business as usual. The second time around, however, was much worse. It began nearly 150 days later in late October and involved severe symptoms on top of ones she had already experienced—among them a sore throat, belabored breathing, and exhaustion. Although the woman was able to recover from her first Covid19 infection just fine, that didn’t prevent her from developing a 617
severe case within months. This raises the worrying possibility that the natural immunity we develop to one variant of SARS-CoV-2 may not protect from another. This tracks with the findings of a preprint study that mapped the effects of different spike protein mutations on the potency of antibodies used in experimental Covid19 treatments, including monoclonal antibody drugs. Mutations at site E484, where E484K is located, prevented 9 of 11 different monoclonal antibodies from binding. (Another site on the spike protein, F456, prevented 11 of 11.) The Brazilian reinfection case confirms what we should’ve recognized long ago—that the recent surge in viral variation is only one piece of a much larger puzzle, one that will challenge our understanding of the crisis for many months to come. Our grasp of the immunology of SARS-CoV-2 remains tenuous at best. To truly make progress in our collective mission to lessen its toll on human life, we must accept the fact that this virus is not only here to stay, but in some respects just getting started. Which leads me to the subject of my next piece in this series—the first reports of viral variation in the United States. This article originally appeared in Forbes and is available online here: New Covid-19 Variants Reshape Our Understanding Of Reinfection
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Researchers Identify New Covid-19 Variant In Ohio Forbes | January 14, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the fourth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, and part four. Researchers have isolated two new variants of SARS-CoV-2 via genome sequencing in Columbus, Ohio, according to a preprint pending publication on bioRxiv. This is the first study to confirm our fear that variants have been evolving in the U.S. all along—we just haven’t been looking for them. But it won’t be the last. In fact, another preprint of a study conducted in Illinois was published just today. What follows is an analysis of the soon-to-be-published preprint, sent to me in advance by a colleague at the Wexner Medical Center. Previously I’ve discussed how the virus changes, through random alterations to its genetic code that accumulate with every passing host. The more viral transmission, the more variants of the virus lurking about. These variants may develop virus-enhancing properties, such as greater infectivity as we’ve seen with the UK and South African variants, or immune resistance, whether from naturally occurring antibodies or vaccines. The variants sequenced in the Ohio study are distinct from the UK and South Africa strains, B.1.1.7 and 501.V2 respectively, that have spread to most parts of the world. Analysis of their lineage revealed they were in fact native to the United States, evolving from a strain dominant in Columbus. The study, conducted by researchers at Ohio State University, examines the genomic sequences of two new variants of SARS619
CoV-2 selected from a set of 222 samples taken from April 2020 to January 2021. The first, observed in late December, has several mutations on the S, N, and M proteins. During the week of December 21st, these mutations were detected in 10 percent of samples sequenced. By the following week, the number had risen to 30 percent. The week after that, it was a staggering 60 percent—an increase steep enough to suggest the variant was highly contagious. A second potentially troubling variant, COH.20G/501Y, was also identified—this time possessing two mutations seen in the UK variant, N501Y and ORF8 R521. The N501Y spike protein mutation is thought to increase the transmissibility of the virus, though ORF8 R521 might also have a part to play. This variant is likely highly infectious. However, unlike the first variant, this was only isolated in one sample. While the sample size is so small the variation could be the consequence of a super-spreader event, the selection for advantageous mutations suggests a broader arc of evolution. More than anything, the Ohio study underscores the old adage that when you look, you will find. Now that we’re ramping up our ability to surveil the virus and follow our leads, we must also pivot from a place of complacency to one of heightened vigilance. The goal is to anticipate and prevent further circulation of new variants, rather than forever trailing behind. Though we can’t predict the precise mutations to come, we can look specifically for patterns that spell out certain dangers, such as increased contagiousness, virulence, or immune escape. Another lesson we can learn from the Ohio study is that the current focus on the envelope of the spike protein is much too narrow. Rather than tunnel in solely on the spike, we should expand our sights to include the entire genome. SARS-CoV-2 produces a number of proteins that go by the generic name open reading frame gene (orf), followed by a number and sometimes an additional letter to distinguish one from the other. Though we don’t know as much about them as the spike protein, for all we know orf genes like ORF8 could have a critical role in increasing the fitness of new variants. So could other structural proteins and non-structural proteins that have so far been excluded from the scope of investigation.
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These new Ohio variants and others that will likely be isolated in the near future may shed light on the aggressive rise in cases the US has faced in recent weeks. Sharing similar mutations to the UK variants, which have been confirmed to increase transmissibility and is the root cause of the UK’s current lockdown, suggests a similar rise in transmissibility is occurring in the US. As the number of people infected increased, and as the virus encountered mixed states of immunity full and partial, the virus has had ample opportunity to spread, mutate, and enhance its viral strength. Those opportunities will only continue to grow if not countered with rigorous public health measures and continuous vaccination. This article originally appeared in Forbes and is available online here: Researchers Identify New Covid-19 Variant In Ohio
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Why America Should Look To China To Contain Covid-19 Forbes| January 14, 2021 | Article
Since the earliest days of the Covid-19 pandemic, American news media has been rife with stories about how China handled – or according to many of the reports, mishandled – the initial outbreak. The most recent is a story in the New York Times, A Year After Wuhan, China Tells a Tale of Triumph (and No Mistakes). On the surface, it is the story of China’s "whitewashing" of the early days of the pandemic. But simmering just below is an unmistakable sentiment of anti-Chinese propaganda. There is some truth to the picture the Times story paints, as there is to other stories that point out missteps by the Chinese government in the early days. But beyond the grains of truth the story serves as an attack on how the Chinese handled the Covid-19 pandemic and avoids the ultimate reality: Despite experiencing the world’s first major epidemic, China has controlled Covid-19 since mid-spring better than almost any other country, snuffing out sporadic outbreaks that enter from a Covid-19 riddled world. I decry the stubborn resistance of most governments and people to acknowledge and to learn from China’s success. For most, their resistance is led by ignorance. China’s successes are not widely known and rarely covered by the US and international media. For others who are more well informed, it is willful disregard of an important public health achievement that we should all be learning from. When this negligence comes from our government representatives, it borders on dereliction of their public health duty. As one who frequently speaks to the national and international media about Covid-19, I try to shine the light on China’s success in hopes others can learn from it. Speaking to US, European, Middle Eastern, Indian outlets, a mention of China brings two immediate, knee-jerk, responses: You can’t believe their numbers, can you? And if the numbers are true, hasn’t it only been possible because of their
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totalitarian regime? Even my eight old grandson parrots this feeble defense. Yes, I do believe China's numbers, in part because of personal experience and the stories from my colleagues in China who describe their Covid-free daily lives. And no, China’s success in containing Covid-19 is not the consequence of totalitarianism. It is the consequence of a government that has learned to protect its people from pandemic tragedies. China is following a rulebook they first learned in large part at the Harvard School of Public Health following SARS. That China applied these lessons while we did not is a lasting embarrassment and tragedy for the nearly 400,000 lives lost, the one million-plus of our citizens who are scarred for life from their encounter with Covid-19, and for so many of us who have mourned the loss of family members and friends. This article originally appeared in Forbes and is available online here: Why America Should Look To China To Contain Covid-19
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When Society Returns To Normal PostPandemic, Common Viruses Will Return In Droves Forbes | January 14, 2021 | Article
Social distancing, wearing masks, and limiting group gatherings are all proven measures to control the spread of Covid-19. If more people follow those safety restrictions actively, the pandemic would be at a much better stage than it currently is. Though, Covid-19 policy measures brought unexpected side effects to the public health sphere. Transmission of other common viruses has hit record lows. Why has this happened, and what will the implications be when the pandemic comes to a close? As you may expect from a year when hand sanitizer was scarcely available, and face masks were a top-selling e-commerce item, common illness plummeted in 2020. As Covid-19 raged, annually recurring viruses like the flu, norovirus, respiratory syncytial virus, as well as common bacterial infections like whooping cough and pneumonia, were recorded far less than usual. It seems the vast reduction in human contact, eating around others, and general isolation caused the transmission of these ailments to occur rarely. Winter in the United States is typically plagued with rises in respiratory illness and flu infections. This chart by Biofire, a website designed to track trends in various infectious pathogens, demonstrates the abrupt fall in pathogenic detection following Covid-19 restrictions in mid-March. As states resumed their economies and schools reopened their doors, you can see a slight rise in infections, but nothing nearly as high as infections before the pandemic. Last year, the pathogens tracked in this chart were detected three times more than what is seen today. While an interesting side effect of our ongoing isolation, what are the ramifications of lowered viral detection for the months to come? We should expect a heavy-handed return of these diseases once Covid-19 restrictions are lifted. People will likely begin to 624
contract these diseases in droves once regular societal interaction resumes because any natural immunity to the viruses or bacteria may have been lost during the year in isolation. The old adage that being too clean may be a bad thing rings true in this scenario. When people return to everyday life, the viruses will have a wealth of new hosts that have lost any natural immunity they may have had before the pandemic. SARS-CoV-2 was so effective in its spread because it seems that very few if any humans had built-in immunity to the virus. The common viruses will experience aggressive spread by the same model. In the next couple of years, we will likely experience many more deaths relating to the flu, respiratory syncytial virus, and others than we are used to. Australia is in the midst of its post-pandemic viral re-emergence at this very moment. As the United States continues to have record Covid-19 cases, Australia controlled their Covid-19 outbreak with relative ease, as they never surpassed more than a few hundred cases per day. With Covid-19 cases on the floor, the country has spent the past several weeks rolling back public health restrictions. December, which is outside the typical flu season for the southern hemisphere nation, saw rates of flu six times higher than in the summer, when cases are typically at their peak. If other viruses and countries follow this trend, the year following Covid-19 may not be as relieving as we hoped. Ultimately, these viruses are endemic. They are always around us and infecting us. After Covid-19 restrictions hit, they went into a sort of dormant state, waiting for new hosts. New hosts will emerge with lowered pathogenic resistance when restrictions end, and these viruses will take advantage. This is likely what will happen with Covid-19 as well. It’s highly improbable that a virus that caused the magnitude of infection that Covid-19 did could be wiped from the planet. After vaccines and public health efforts eventually control the virus’s spread, there will be annual resurgences of Covid-19 around the world as we see with the flu. We will take new Covid-19 vaccines every year or two alongside our flu vaccines, some will die as with the flu, but life will go on. The trick is to limit these deaths and illnesses as much as possible and research new ways of controlling viruses so that future
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generations don’t have to deal with endemic diseases to the same degree. This article originally appeared in Forbes and is available online here: When Society Returns To Normal Post-Pandemic, Common Viruses Will Return In Droves
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Can SARS-CoV-2 Become Even More Troublesome Than The U.K. And South African Variants? Forbes | January 16, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the sixth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, and part five. We are rapidly learning how SARS-CoV-2 mutates to create variants with new characteristics. Some of these new variants, such as those found in the UK and South Africa, may affect our ability to control the pandemic, including contagion mitigation, diagnosis, and vaccination. Over the past few weeks, reports show that some variants of SARS-CoV-2 are more contagious than earlier strains. Sequence analysis of these variants reveals that their genome and proteins differ subtly from their less infectious origins. The viral protein studied in most detail is the spike protein. Multiple independent isolates harbor changes in the spike protein that account, at least partially, for their increased transmissibility. In a preprint published on January 11, scientists from the Weizmann Institute of Science describe an experiment in which they attempt to mimic what occurs naturally. They looked for laboratory-created variants that stick more tightly to a structure on the cell’s surface that the virus uses to gain entry into our bodies. They were successful. The absolute winner bound the cell surface receptor, the ACE2 protein, 600 times more tightly than the original virus.
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The shocking result was that their lab experiment reproduced almost exactly changes in naturally occurring strains in the UK and South Africa, and elsewhere. The lab-generated variants include precisely the same variants, specifically the changes designated S477N, E484K, and N501Y. The variants convey the same advantage in the test tube as they do in populations. The winning laboratory-created variant contains seven amino acid substitutions in the spike protein's receptor-binding domain. Studies of the structure of the protein reveal their function. Four of the seven stabilize the spike protein structure, and three tighten the intimate contacts the spike makes with the ACE receptor. These were not the only laboratory-created variants the researchers found. Some convey only a slight binding advantage. However, when combined with the ensemble of three winners, S477N, E484K, and N501Y, they create a spike protein that binds 600 times more tightly to the receptor than the original. This particular combination of variants has not yet been observed in nature. Given the rapid rate of change, it seems such a variant may appear soon. We may then be dealing with a more infectious virus than either the UK or South African strains. The public health implications of such an event are profound. Detailed analysis of the variants reveals how they improve the virus's ability to bind the ACE2 receptor. Four of the seven changes stabilize the spike protein structure, while three tighten the spike's intimate contacts with ACE2. In contemplating these observations' significance, consider that the scientists modified no more the 0.6% of the total genome and only about 12% of the spike protein. Analysis of many of the new variants that appear to be more infectious and seem to escape immune pressure reveals other spike locations and other viral proteins of interest. A similar study of the entire genome will likely reveal other tricks the virus deploys to increase infectivity and avoid immune detection. Last spring SARS-CoV-2 variant that contained the spike mutation D614G spread more rapidly. This strain was so successful it has now displaced all others. All of the newly discovered more infectious variants contain the D614G. In other words, these new mutations ratchet up virus infectivity still further. The laboratory
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experiments described here suggest that naturally occurring variants have not yet reached the peak of infectivity. It may be helpful to picture SARS-CoV-2 variants as a rapidly growing tree. At the base of the tree, a single strain of the virus provide the trunk. Ascending the tree branches appear, variants that contain all the earlier changes and still more of their own. Each is more fit to survive in its environment, the human population, than is its immediate ancestor. As we climb higher, the variants become more numerous, different from one another, even more fit to survive and flourish. What began as a few variants soon become many thousands, bedeviling our attempts to mitigate infection and disease. We must prune the tree. We need to reduce the number of branches, stunt the tree. How? With methods advocated all along. We must administer vaccines as quickly as possible; we need to reinforce public health measures — social distancing, mask-wearing, and social isolation. As needed appropriate, we must incentivize and, if necessary, enforce the isolation of those exposed and contagious. However dangerous we thought our foe, until a few weeks go we were confident we knew its form. We now realize that SARSCoV-2 is a shape changer. Like Proteus, it changes even as we hold it in our grasp. As Hercules prevailed, separating Anteus from his mother earth, we must clear the ever-growing forest of virus variants by reducing the numbers of people infected, not only in our country but everywhere it has taken root. This article originally appeared in Forbes and is available online here: Can SARS-CoV-2 Become Even More Troublesome Than The U.K. And South African Variants?
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The US Must Develop A National Vaccine Registry The Hill | January 18, 2021 | Article
Vaccine distribution in the United States to this point has been inefficient and ineffective. The incoming Biden administration offers hope that efforts can be turned around, but the concrete strategies to accomplish the turn-around are yet to be detailed. To simplify vaccine data systems, I propose a national vaccine registry that tracks vaccination records across the country. What would a national vaccine registry look like, and how would such a system help public health officials with their vaccine efforts? The most straightforward aspect of the national vaccine registry would be managing records for who has received the vaccine and who has not. If the U.S. government anticipates vaccinating all 300 million-plus Americans, there must be a standardized system to keep tabs on who has received their shots. A method for tracking vaccines nationwide exists in Operation Warp Speed’s Tiberius, but the path for data to reach this system is fragmented. After a patient has their vaccine administered, a physician inputs their data into their state’s immunization information systems, which takes several steps between the CDC, state health officials, commercial distribution centers, mass data storage centers and more before it reaches Tiberius. The process needs to be simplified and streamlined. Physicians must be able to upload vaccine data directly to a national registry and associate the patient’s social security number with a vaccine ID. This would produce an accurate and continuously updated track of who is vaccinated and who is not. The registry comes with secondary benefits. Associating patients with a vaccine ID means we could have national data on vaccine efficacy. Physicians could update vaccine ID profiles if a patient comes back with COVID-19 symptoms after being vaccinated. Then we could see which vaccine they took and oversee long-term efficacy by the vaccine manufacturer. This would also present the
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opportunity to track long-term antibody duration and analyze that data based on demographic information. The incoming Biden administration seems willing to adopt such a program. It ambitiously aims to administer 100 million vaccines in its first 100 days and, according to Democratic strategist Liza Acevedo, will “utilize every resource possible” to achieve that goal. The opportunity to right the ship with an incoming administration is promising and hopeful. To achieve such an efficient and complete national registry, we should look to other countries that have already accomplished the same. Australian health officials require providers to report vaccine administrations, including for the ongoing COVID-19 vaccines. Terry Slevin, chief executive of the Public Health Association of Australia, notes that “it is mandatory to have this kind of information to protect the population’s health.” Australia has done a phenomenal job of controlling the pandemic, with daily infection rates fewer than 1 in 100,000 people. Japan and South Korea are requiring similar registries for their COVID-19 vaccination efforts. Both countries had codified vaccination registries before the pandemic, requiring municipalities to maintain administration records for years after the visit. Both Japan and South Korea have controlled COVID-19 with a similar aptitude as Australia. Japan’s current daily infection rate is 5 in 100,000, and South Korea’s is as low as 1 in 100,000. These other nations, which inarguably have handled the pandemic far better than the current U.S. administration, are concluding that a national vaccine registry maintains quality and consistent records of vaccinations. Scientists estimate that at least 70 percent of a population needs to be immune to COVID-19 to achieve herd immunity. In the United States, that number is around 230 million vaccinations. If we are to achieve that, there should be a simplified and standardized way to track who has had their shot and who has not. It’s up to the incoming Biden administration to take the reins and implement such a system. This article originally appeared in The Hill and is available online here: The US Must Develop A National Vaccine Registry
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Billions In Low-Income Nations Will Not Receive Their Covid-19 Vaccine Anytime Soon Forbes | January 21, 2021 | Article
The urgency to develop and approve Covid-19 vaccines translated into a slow and arduous distribution process. According to the Bloomberg News Vaccine Tracker, a little over 50 million doses of vaccines have been distributed in 51 countries. That leaves only about 7.7 billion more people to go. Unless there’s a significant increase in production and distribution, billions will not receive the vaccine in 2021, most of which are located in low-income countries, which will result in hundreds of thousands, if not millions, of unnecessary deaths. A closer inspection of the vaccine tracker shows a stunning, yet unsurprising trend for vaccine administration. The vast majority of vaccines distributed have been in global economic powers like the United States, China, and Europe. Countries in the global south, which tend to be lower-income countries, distributed much fewer doses. Covid-19 is not absent in these countries, nor are their governments refusing to distribute vaccines. They are simply lower on the priority list in comparison to others. An early report in December by the People’s Vaccine Alliance noted that rich nations comprising only 14% of the world population had bought 53% of the vaccines to that point. This aligns with trends today as well. The United States, China, EU, UK, and Israel have administered about 45 million of the 50 million doses. Reports emerged that Canada was purchasing as many as five times the amount of vaccines as it has people. Vaccine hoarding endangers low-income countries and risks extending the pandemic. Some South African health officials have gone as far as labeling this health inequality as “vaccine apartheid.” Especially as South Africa is being ravaged by a new, more infectious SARS-CoV-2 variant, the need to accelerate vaccine distribution is at an all-time high. We know these variants mutate rapidly. Early indications suggest that the new South African variant may be able to reinfect 632
those who have previously had Covid-19, suggesting they may mutate to a point where they are immune-resistant to neutralizing antibodies and, potentially, vaccines. With the UK and South African variants spreading like wildfire and more new variants beginning to emerge, the global community needs to come together to get everyone vaccinated as quickly as possible. So long as there is a chance the current vaccines will protect against the virus, they should be distributed. If variants become resistant to vaccines, pharmaceutical companies will have to start working on the new strains, as they do with the influenza vaccines every year. Economic powerhouses like the US and EU should sponsor mass investment in vaccine distribution in low-income countries. These investments could strengthen health systems with vaccine distribution centers, rapid test production, and increasing health staffers. Not to mention, investments could be used to purchase and store vaccines until they are needed. The Moderna and Pfizer vaccines require super-cold storage to maintain efficacy, making them even more inaccessible for countries without many super-cold storage facilities. Investment in health systems could be extended past Covid-19 as well. Developing a vaccination distribution system could translate to non-Covid vaccine programs. Routine immunization is less common in low-income countries. With robust health systems and vaccine investment, more people could be vaccinated for communicable, vaccine-preventable diseases. Ideally, we could stop people from dying from Covid-19, but also diphtheria, tetanus, measles, and others. Vaccines, as they stand today, are inaccessible via shortages and vaccine hoarding. Preventing a long-term extension to the pandemic will require controlling Covid-19 in every country. So long as there are people infected, the virus may be able to mutate and spread. While we can, we should try to get these vaccines to every person possible. While there is no guarantee vaccines will put an end to Covid-19, there is a chance they can save thousands of lives, and that is a chance worth taking. This article originally appeared in Forbes and is available online here: Billions In Low-Income Nations Will Not Receive Their Covid-19 Vaccine Anytime Soon 633
Biden’s Covid-19 Plan Is A Welcome Relief — But It Needs To Go Further Forbes | January 21, 2021 | Articles
With great relief, we welcome President Biden's inauguration and his administration's robust and rational Covid-19 recovery and economic stimulus plan. The $1.9 trillion plan includes positive steps that public health experts have been calling for since the beginning of the pandemic. While it is painfully overdue, the significant investment signals a new era of competent and responsive leadership who will work with and not against vulnerable communities. Yet with the death toll surpassing 400,000 and new cases surging across the country, the plan needs to go further. Regular testing of all Americans is our best defense against Covid-19 Testing is our first and simplest line of defense against Covid-19. But throughout the pandemic, tests have not been readily available to all Americans. The $50 billion Biden has allocated in his plan to expanding testing infrastructure intends to solve this issue by increasing lab capacity and the availability of tests while developing consistent testing protocols for schools, long-term care facilities, and prisons. This is a welcome start, but Biden needs to invoke the Defense Production Act to ensure the production and distribution of 150 million inexpensive, at-home, rapid antigen tests per day that are freely distributed to the public. This would allow every American to self-administer a rapid test at home twice a week and catch a majority of asymptomatic infections before they spread into the community. If the Defense Production Act can be used to rapidly produce personal protective equipment, we can surely use it to produce tests. Treat vaccine rollout less like the flu and more like an act of bioterrorism Biden should be commended for injecting $20 billion in a national vaccination program that partners with states, localities, tribes, and territories. The sluggish start to vaccination cannot 634
continue if we want to swiftly reduce the death toll. Biden's commitment to launching community vaccination centers around the country and deploying mobile vaccination units to remote areas will help the vaccine reach underserved communities. In terms of escalating the rollout, the Biden administration should look towards how the federal government stockpiled and planned to rapidly administer medicines and vaccines in the aftermath of 9/11 in case of a bioterrorist attack involving anthrax or smallpox. Funding the creation of 100,000 public health jobs is also a creative solution to the simultaneous unemployment crisis. Senator Kirsten Gillibrand played a role in championing this legislation to train thousands of local community public health workers in vaccine outreach and contact tracing. These workers will relieve the burden on strained vaccination and testing sites and then transition into long-term community health roles that address the health disparities that have been exposed and amplified during the pandemic. Incentivized quarantine will help regain control over the virus Yet, with new highly contagious variants developing, vaccination alone will not eliminate the virus. Covid-19 will likely become an endemic human disease resembling the annual influenza. Biden's proposal to increase funding for sequencing and surveillance of the virus mutations will be essential to controlling the pandemic in the long term. Despite a robust approach towards medical control of the virus, Biden's plan neglects to include vital public health measures to control the pandemic. A national mask mandate is a good start, but we need to get serious about isolation protocols for those exposed or infected and replicate the successful public health practices of countries like China, Australia, and New Zealand who have achieved zero or near zero infection rates. The Biden Administration needs to go further and create a universal, incentivized home quarantine program in conjunction with self-administered testing at home. In such a program, those with verified infections would be paid to isolate at home for 14 days. Renewing the employer requirement to provide emergency paid sick leave allows some Americans the privilege of quarantine without financial burden. But some gig economy workers, such as delivery drivers who don't receive sick leave, are avoiding getting tested. They can't afford the loss of income if they test positive and 635
subsequently need to quarantine. Only with an incentivized quarantine program can we ensure that Americans don't have to choose between protecting their community and their paycheck. An incentivized quarantine program may seem extreme to some, but it has become devastatingly clear throughout the pandemic that there is no other option to regain control over the virus. With each reopening in the U.S., the UK, France, or Israel, cases have eventually come roaring back to terrifying levels. In contrast, China's mandatory 14-day quarantine policy for all who have been potentially exposed to the virus has meant the country, with a population of over 1.4 billion, has experienced just one Covidrelated death in the past eight months. With the above-mentioned substantial investment in rapid testing, we can be more efficient and focus resources on quarantining those infected. Some may argue that such a rigid approach would not work in the Western world. Yet, we have seen the Australian and New Zealand governments implement similar policies and have successfully returned to normal life without a vaccine. One of the great tragedies of the Covid-19 pandemic in the United States, Europe, and South America is that we have not learned from our neighbors and used the power of central government to enforce quarantines. Extend economic relief and legislate worker safety Biden's proposed eviction and foreclosure moratorium will also help with quarantine efforts and allow individuals and their families to safely shelter in place. The moratorium should continue for as long as needed based on the status of infection rates. Economic relief needs to be tied to the progression of the crisis and not an arbitrary date. Free hotel isolation programs like that of New York City should also be established in all states and be widely promoted. Nearly one year into the pandemic, employers have yet to receive regulations that would require them to protect their employees from Covid-19 exposure. Employers have been left to voluntarily develop their own Covid-19 safety protocols without public health experts' guidance. Predictably this has left frontline workers vulnerable. The responsibility of enforcing standards has again been left to the states, with only 14 states adopting comprehensive worker safety Covid-19 protections as of December 2020. 636
By authorizing the Occupational Safety and Health Administration to issue a Covid-19 Protection Standard that covers a broad set of workers, Biden will take the first step to ensure workers' safety. Additional funding for training and enforcement of OSHA standards will guarantee that businesses have the capacity, clarity and responsibility to carry out these protections. Cast a global focus to fighting the pandemic and address associated health issues Biden is also moving to restore U.S. leadership globally by joining the World Health Organization’s COVAX initiative and reinstituting humanitarian aid to address the pandemic's global impact on health, food security, and gender-based violence. This international focus is an important shift from the previous administration as the pandemic will never truly end until it is addressed globally. Finally, Biden's plan crucially addresses other health issues associated with the pandemic. Mental and behavioral health issues have been steadily rising throughout the pandemic and will likely persist long after it ends. Enabling the Substance Abuse and Mental Health Services Administration to expand access to mental health services is a worthwhile investment of $4 billion. Notably, Biden intends to fund studies of the long-term health impacts of Covid-19 and potential therapies. While the focus has been rightfully on the death toll, many Covid-19 'long haulers' are finding themselves unable to return to work or carry out personal responsibilities. Subsidizing COBRA coverage and lowering or eliminating health premiums through the Premium Tax Credit is another longoverdue policy. Debt and financial burden must not deter Americans from seeking care for Covid-19 infections or other health conditions. The dual pandemic and unemployment crises provide the perfect argument to move towards universal health coverage and away from predominantly employer-sponsored coverage. Biden's multifaceted and detailed plan instills hope for an evidence-based approach to fighting the pandemic in the future. Yet we must not risk complacency and go further by enhancing quarantine protocols and invoking appropriate legislation to increase the supply of tests and vaccines dramatically. We must not be so distracted in fighting the current pandemic's challenges that we
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neglect to plan and prepare for future epidemics and biological threats simultaneously. This article originally appeared in Forbes and is available online here: Biden’s Covid-19 Plan Is A Welcome Relief — But It Needs To Go Further
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For Insight On New Covid-19 Variants, Look To Natural History Of Coronaviruses Forbes | January 21, 2021 | Article
I’ve long been a believer in taking lessons from nature, not the laboratory, to understand biology, ecology, and human disease. That’s particularly true of natural infections. When I first learned that Covid-19 was caused by a coronavirus, I hit the books and went back to its natural history. The most recent episodes, SARS and MERS, came and went after being successfully contained. But as I looked deeper into coronaviruses in general, I realized their tendency wasn’t to come and go. Quite the contrary, if you look at the human coronaviruses that cause a third of the seasonal colds we catch like clockwork, the same strains come back again and again—suggesting that coronaviruses, like influenza, might be capable of slipping past immunity acquired from previous infections and returning year after year. The possibility that SARS-CoV-2, like these cold-causing coronaviruses, would come back to haunt us concerned me deeply, especially when it didn’t figure into early discussions about how to control the Covid-19 pandemic. Some even went so far as to argue that the only way out was through—allowing nature to take its course, even if it meant losing millions of lives in the process, in hopes that population immunity would develop and safeguard those who survived. Those who advanced this argument failed to recognize that such an outcome goes against the very nature of coronaviruses. If decades of research tell us that it is typical for one strain to come back, why would this one be any different? At first my thoughts, spurred by the discovery that the virus had the ability to alter the immune system, turned to the notion that the immunity we develop against SARS-CoV-2 might be short-lived— rendering the population immunity argument moot. Quite a bit of evidence suggests this, including the observation that the natural immune response to critical illness from Covid-19 is more robust than in asymptomatic and mild cases. 639
While insufficient time has passed between now and even the very first Covid-19 infections for us to know with certainty whether immunity truly persists, another fundamental assumption underpinned hopes for population immunity that begged scrutiny— that coronaviruses were intrinsically more stable than other RNA viruses just because they had an error proofing mechanism. The textbooks I consulted did indeed suggest that a low rate of mutation resulted in little variation between strains. The first hint, however, that this might not be the case was the D614G spike mutation that, when it emerged early on in the pandemic, increased the transmissibility of the virus by about tenfold—meaning transmission could happen with fewer particles and in less time. This observation, made later that spring, wasn’t taken seriously by many, who perhaps preferred alternative explanations. Now we know that D614G was a clear warning for what is occurring now—the widespread emergence of variants built on the same framework, but passed from one host to another with even greater ease, leading to transmission rates at least 20 times higher than those that came before. More researchers have begun sequencing viral samples from Covid-19 patients to identify new and emerging variants, and where they look, they find, first in Britain, then South Africa, and now everywhere from Brazil, Japan, and Germany to Ohio, Illinois, and California. They’re also taking a closer look at how coronaviruses come to vary in the first place—and the new findings are absolutely startling. Certain mutations, not just in the spike protein but across the entire viral genome, could assist the virus in achieving immune escape, allowing it to become more transmissible, virulent, or both. If SARS-CoV-2 were to gain the ability to mutate its way past our immune defenses, it wouldn’t be the first human coronavirus to do so. In December, a team of Seattle-based researchers published a preprint study (currently undergoing peer review) that set out to determine whether the antibodies of patients who were infected with the human coronavirus 229E one year could protect others from strains that emerged several years later. The antibodies were prepared and administered in the form of convalescent sera, an experimental treatment derived from the blood plasma of recovered patients. Sera for an “early” strain of 229E was tested for its potency against a “future” or later strain, and vice versa. 640
Though 229E isn’t nearly as hot a topic as SARS-CoV-2 these days, it is one of several coronaviruses that have been causing us colds for more than half a century. According to the study, sera from 2020 proved adept at neutralizing earlier coronaviruses—a good sign and likely testament to the strength of natural immunity. But sera from 1984, though plenty protective against a variant of 229E from that year, was ten times less effective against a variant from 1992. Similarly, sera collected in 1990 could neutralize the 1984 virus, but nothing more recent, while 1995 sera neutralized all viruses from the preceding decade, then nothing thereafter. Antibodies developed against “early” strains, these results show, faltered when confronted with “future” strains—suggesting that part of the problem lies not with our ability to develop immunity to coronaviruses, but their ability to adapt to us. The study, we must remember, is of the seasonal coronavirus 229E, not SARS-CoV-2. But just like SARS-CoV-2, the spike protein is how 229E binds to our cellular receptors, making the two ripe for comparison. When taking a closer look at the mutations that allowed 229E to evolve, the researchers did focus on the spike, but also parts of the N-terminal domain and receptor binding domain more broadly, finding significant variability in all three. Though we’ve known for some time that SARS-CoV-2 and coronaviruses in general don’t mutate as quickly as other RNA viruses like HIV, structure-wise they appear to be flexible enough to contort into uniquely advantageous shapes—excellent for their survivability, but not so much for ours. Beyond the actual fact of variation is the extent of variants that are possible—in other words, not just how many times a coronavirus like SARS-CoV-2 can change, but how much. In analyzing the spikes of five different variants of 229E that emerged from 1984 to 2016, the researchers found that across the entire amino acid sequence of each genome, they differed from one another by up to four percent. But in each spike’s receptor binding domain, the difference was vast—between the spike from 1984 and that from 2016, about 17 percent. This is a harbinger of the astonishing degree of variation of which the surface protein is capable. Far from thinking of these viruses as stable, we must consider them capable of extraordinary flexibility that could occur not just in the spike, but other proteins relevant to transmission and pathogenesis. 641
We already know, thanks to genomic databases like GISAID, that every single amino acid in SARS-CoV-2 is capable of mutating. We also know that several mutations—from small deletions to small insertions of other genes to small rearrangements of existing components—can occur simultaneously in a single variant, and that these mutations may preserve and even enhance the spike protein. At this rate, the SARS-CoV-2 we encounter a year from now, not to mention a decade down the road, could look very different from the virus we met over a year ago. Since we can't anticipate how different, or in what way, the best we can do is accept the possibility and give the virus less opportunities to experiment by reducing the overall disease burden. In many respects, SARS-CoV-2 is certainly a different beast than 229E—the global death toll of two million says as much. But the leap in lethality seen in SARS-CoV-2 and not other human coronaviruses is all the more reason to revisit what we’ve already learned about the entire family. The virus that causes Covid-19 isn’t a radical departure from its predecessors. It is a familiar foe that will dependably resort to the signature moves that helped it get ahead before, including the ability to change just enough to evade the immune system. We now have solid but not definitive evidence, published recently as a preprint, that people immunized with the PfizerBioNTech vaccine will be protected from new variants circulating in the UK and other countries. The data shows that antibodies in the blood of patients who have been vaccinated are capable of inactivating stomatitis virus carrying the B.1.1.7 lineage spike protein mutations. The question of whether other strains will meet the same fate, as well as whether other Covid-19 vaccines will be as successful, remains open. Might we need to continuously modify our vaccines for Covid19 like we do for the flu? Flu vaccines are adjusted each year to account for the major strains that arise, and a single flu vaccine often contains at least four different variants of influenza virus. Given what appears to be the rapid evolution of SARS-CoV-2 in disparate geographic regions, it seems possible, even likely, that future generations of Covid-19 vaccines will follow a similar pattern. In my next piece for this series I will go into further detail about the similarities between influenza and coronaviruses. 642
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the sixth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, and part six. This article originally appeared in Forbes and is available online here: For Insight On New Covid-19 Variants, Look To Natural History Of Coronaviruses
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Why Patterns In Covid-19 Variation Might Resemble Seasonal Flu Forbes | January 21, 2021 | Article
We’ve learned that some variants of SARS-CoV-2 are more transmissible. Equally troubling is the possibility that future variants — or ones currently circulating off our radar — will in some way compromise our natural immune response, complicating our ability to treat critically ill Covid-19 patients with the antibodies of those who recovered from the disease. In my previous story for this series, I discussed how the evolution of human coronaviruses more broadly gives us insight into what we might expect from SARS-CoV-2. The same is true of influenza viruses. Waves of influenza, like cold-causing coronaviruses, don’t come and go at random. They’re seasonal, recurring in patterns we can anticipate and plan interventions around after tracking them for many years. This we know. Why, though, do the dominant strains of influenza vary from one year to the next? Is there a linear evolutionary pathway to be traced from one strain to another, just as we’re attempting to do with SARS-CoV-2? A study published in 2017, coauthored by some of the same researchers behind the preprint on coronavirus evolution I analyzed previously, proposes a theory of influenza evolution that might just apply to Covid-19, too. According to this theory, the viruses that cause both diseases evolve across multiple scales — in individuals, between individuals, and around the globe. Most of us, when we catch either of these viruses, will develop a transient infection — meaning the duration of our sickness has a definite beginning and end. But a small fraction of people develop prolonged infections, either stretching on for weeks or months without pause or subsiding only to return with a vengeance. Chinese health authorities estimate that for Covid-19, this population of long-term shedders is as high as five percent. The reasons for persistence of infection vary, and in some cases elude us. One explanation consistent with both Covid-19 and the 644
flu is that some patients are immunocompromised, unable to generate an immune response vigorous enough to clear out the virus once and for all. It is also the case that either virus, if allowed an extended stay in a human host, has more time and space to alter itself in advantageous ways. Single mutations, as well as multiple cooccurring mutations, can change the face of the viral genome and, once replicated enough, become the norm, rather than the exception. In other words, an immunocompromised host gives the virus, which mutates constantly anyway, an opportunity to incubate a better version of itself — and by that I mean better for the virus, not necessarily us. We’ve already seen this process in action with SARS-CoV-2. Early on in this series, I described a case study of a man who was hospitalized twice with Covid-19, first in May then in August of 2020. Prior to contracting the virus, the man was already living with lymphoma and receiving treatment known to have immunosuppressive effects. He eventually succumbed to the disease, but before he did researchers sampled and sequenced the virus in his body more than 20 times. Remarkably, some of the mutations they observed in his viral RNA can now be found in the SARS-CoV-2 variants currently circulating around Europe, South America, and other parts of the world. One example is the H69-V70 deletion, a mutation of the N-terminal domain also seen in the so-called UK variant B.1.1.7. The 2017 study documents the same phenomenon, but with the influenza virus. Using samples from not one but four immunocompromised cancer patients, all who had prolonged flu infections, the researchers observed the same mutations arising frequently and independently in multiple hosts. For SARS-CoV-2, mutations that occur in and around the spike protein — which the virus uses to bind to and hijack our cells — have been the primary focus and worry. In the influenza genome, it was another surface protein known as hemagglutinin that researchers flagged as a hotspot for variation. In both cases, specific mutations occur in specific places in viral genomes found in specific patients — in addition to being identified in variants that occur globally. The researchers studying the flu called these “parallel mutations.” There are two possible explanations for why parallel mutations occur. One option is that new variants of SARS-CoV-2 and 645
influenza actually have their origins in immunocompromised patients. The other — less linear, more diffuse — option is simply that a virus’s drive and tendency towards change is as active and dynamic in the human body as it is in human populations. Either way, it begins to make more sense that the same infinitesimal changes to SARS-CoV-2, in some cases limited to a single amino acid, are popping up in different parts of the world. Expose the virus to similar selective pressures and challenges — namely, partial immunity — and it will adapt in similar ways. If I were to make a prediction based on what we’ve seen of SARS-CoV-2 and its capacity for variation so far, I’d say it is much more like influenza than any other virus we know of. To prepare ourselves accordingly, we must adjust our vaccine development pipelines and public health interventions more broadly to account for emergent and future variations. Otherwise we’ll be setting ourselves up to be blindsided yet again — against our best interests, and in favor of the virus’s. Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the sixth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, and part seven. This article originally appeared in Forbes and is available online here: Why Patterns In Covid-19 Variation Might Resemble Seasonal Flu
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This Devastating Covid-19 Outbreak In Brazil Is A Warning To The Rest Of The World Forbes | January 21, 2021 | Article
In March 2020, the Brazilian city of Manaus, the largest urban area in the Amazon, identified its first case of Covid-19. Prevalence of the disease went on to peak in early May, bringing untold devastation to local hospitals, economies, and community life. Researchers estimate that by October, as many as 76 percent of the city’s two million residents had been infected—a proportion that exceeds most theoretical thresholds for population immunity, the World Health Organization’s included. Were population immunity the glimmering light at the end of the tunnel some purport it to be, Manaus would be in the clear— and for a few short months, the virus did appear to recede. But recent weeks have seen a surge of fresh cases that is once again overwhelming the city, its health infrastructure, and its people. Cemeteries, already swamped the first time around, have traded individual plots for mass graves; many hospitals have run out of available beds and supplies of oxygen; and average deaths per day are up 22 percent from before. If three quarters of Manaus residents did develop some level of immunity as a result of last year’s outbreaks, it doesn’t appear to be doing much to deter the virus today. So what gives? Epidemiological factors, for one. In Brazil, not unlike the United States, the adoption of public health interventions like mask-wearing and social distancing has been uneven, unsteady, and far too slow, obstructed at least in part by a central government, led by President Jair Bolsonaro, that denied and spread misinformation about the disease instead of implementing measures to contain it. But viral variation could also have a part to play in promoting the survival and resurgence of Covid-19 in Manaus— though to what extent, we’re not yet sure. Here’s what we do know. Genomic sequencing, conducted retroactively on samples of viral RNA from Manaus residents dating back to late December, revealed that 42 percent belonged to a 647
previously unidentified lineage of SARS-CoV-2. This new variant, now known as P.1, is the very same that Japanese travelers contracted and brought back to Tokyo earlier this month. P.1. was also confirmed, quite notably, to have caused at least one case of reinfection in Manaus, a 29-year-old woman with no chronic health issues or history of immunosuppression or chronic illness yet had Covid-19 twice, once in March and again in December. How similar is P.1 to variants arising in other parts of the world? Quite similar, it turns out. P.1 has about 20 mutations, among them 17 unique amino acid alterations, three deletions, and an insertion. Two of these, which I’ve discussed at length in earlier stories, are N501Y and E484K—spike mutations that occur in the receptor binding domain and are associated with increased transmissibility. Along with an ORF1b deletion, P.1 has these mutations in common with B.1.1.7, the so-called UK variant, and 501.V2, the so-called South African variant. In all three, these mutations developed independently—a likely sign that they give the virus some kind of advantage, whether alone or in combination with other mutations, that increases its chances of survival. If P.1 is now the dominant SARS-CoV-2 variant circulating in Manaus, that suggests it has an evolutionary edge that runs counter to the city’s immune defenses, meaning reinfections like the young woman’s will become more commonplace if they haven’t already. Either P.1 has found a way to directly evade the immune system, or it is so ruthlessly transmissible that partial immunity is no longer sufficient protection. Marcus Venecia Lacerda, an infectious disease specialist and resident of the city, told NPR he believes reinfections might be driving continued transmission. “What is happening,” Lacerda said, “is that people who had some small exposure to the virus in the past are becoming infected now.” On the whole, Brazil has a population more youthful than most, which explains in part why Covid-19 has killed more Brazilians below the age of 60 than any other country. It could be the case that the youth of Manaus who developed asymptomatic or very mild infections last year had too weak an immune response to counter a more infectious virus. Regardless, the city’s second run-in with Covid-19 is a warning for anyone who still believes population immunity will take the edge of this disease. It also shows why remaining vigilant about safety measures, even with the arrival and 648
distribution of vaccines, is so important. Whether through biological or epidemiological means, SARS-CoV-2 will find a way to exploit our weaknesses—just as P.1 did with the unfortunate people of Manaus. Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the sixth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, and part eight. This article originally appeared in Forbes and is available online here: This Devastating Covid-19 Outbreak In Brazil Is A Warning To The Rest Of The World
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Opinion: “A Great Moment For Science” Daily Clout | January 25, 2021| Article
For the first time in history, a scientist now sits on the Cabinet of the United States. The move by the Biden administration to elevate the US Office of Science and Technology Policy to a Cabinet-level agency and to welcome its head of office, the Presidential Science Advisor, to the Cabinet table, signals an important shift — science will once more play a prominent role within the highest circles of government. This is a bold step in the right direction by the new administration. For the past 40 years, the role of science in creating government policy has steadily declined from its early heights during the Cold War years. The Presidential Science Advisor role was first established in 1941, at the very beginning of US involvement in the Second World War. Following the end of the war, as the tense standoff between the US and the Soviet Union ramped up, science reigned supreme. A leading edge in science and technology was considered a matter of life or death and of paramount importance to the nation’s survival. We were driven by science to create better weapons, faster missiles, and superior defenses — even to explore the outer reaches of space. The Science Advisor and the Science Advisory Committee (later renamed the Office of Science and Technology Policy) provided direct advice to the President, on issues as wide ranging as the economy, national security, and the design of the US census. Somewhere in the mid-1970s, science’s position of prominence began to decline. Part of this is no doubt due to complacency. We had won the war, proven ourselves to be leaders in science and technology, and held a strong belief that our scientific supremacy was enough to keep all threats — whether from man or nature — at bay. But ideological shifts were at play as well and could be seen in shifting public attitudes on global warming, sexuality, and even the origins of humankind. Over time, the role of science lost its standing. The Presidential Science Advisor position was briefly terminated in 650
1973. When it returned as a formal position in 1976, it had lost much of its influence. With President Biden’s elevation of the Science Advisor role to a Cabinet level position, the new administration is once again giving science a critical voice at center stage. The appointee, Eric Lander, does not come without controversy but he does come with strong scientific credentials. Lander is the president and founding director of the Broad Institute, which represents some of the smartest minds of both Harvard University and the Massachusetts Institute of Technology. He has a background in both the corporate world and governance, having served as co-chair of the President’s Council of Advisors on Science and Technology for eight years under former President Barack Obama. His appointment ensures a dispassionate voice at the table, bringing scientific analysis to the most important geopolitical, economic, and social decisions the government makes today. If I were forced to find fault in the new administration’s approach, it would only be in not going one step further and establishing a National Disease Council equivalent to the National Security Council or the Council of Economic Advisors. In a piece for the Atlantic, General John Allen, president of the Brookings Institution and former commander of the NATO International Security Assistance Force, and I called for the creation of this new entity to coordinate efforts to prepare for and defend ourselves against natural or man-made biological threats. The Council should support Science Advisor and new Cabinet member in his new position, providing high level input on policy across the whole spectrum of government. If there is one thing that 2020 has taught us, it is that science has a place in public life. It is vital to our nation’s security. It is vital to our ability to manage internal and external threats. And it will be the driving force behind solutions to some of our greatest challenges, like climate change, bioterrorism, and pandemics like the one we face today. President Biden’s endorsement of the importance of science in the highest councils of the US government sends a positive message of the importance of science, especially to younger generations today. When I was young, Presidents Eisenhower, Kennedy and Johnson set a similar example. It is in large part due to them that I pursued a life of science. I hope President Biden’s actions 651
inspire a new generation of young scientists — students who are today in elementary, secondary, and higher education — to enter careers in science and technology and help our country meet all the challenges that tomorrow may bring. This article originally appeared in Daily Clout and is available online here: Opinion: “A Great Moment For Science”
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A Tale Of Two Viruses
Forbes | January 25, 2021 | Article
As we enter the last week of January, much uncertainty remains around how new variants of the Covid-19 virus, SARS-CoV-2, will shape the year ahead of us. Reports from British officials that B.1.1.7, the so-called UK variant, isn’t just more transmissible than its predecessors but more lethal as well are raising equal parts alarm and skepticism, especially since the same variant has spread to at least 60 countries and is now dominant in a few. Meanwhile B.1.351—the so-called South Africa variant, formerly known as 501.V2—has become so widespread as to prompt the Biden administration to consider imposing a travel ban on non-US citizens hailing from South Africa. Researchers around the world are not just hustling to sequence these new variants (as of last week, in the US only 0.3 percent have been identified), but conduct studies and experiments that can help answer lingering questions about their impact on natural immunity, vaccines, and the duration of the current pandemic. Two recent publications, both still undergoing peer review, add some depth and nuance to our current understanding of B.1.1.7 and B.1.351— demonstrating that viral variation isn’t an inherently disastrous development, but could become one if we don’t adequately anticipate and address its consequences. The variant B.1.1.7: A match for vaccines? The first of the two studies, conducted by Pfizer and BioNTech employees in Germany and the US, investigated whether the B.1.1.7 variant could still be countered by vaccines, specifically the PfizerBioNTech vaccine used predominantly in the UK. The conclusion? The variant is likely to be neutralized, but further research and data is needed to be sure. The B.1.1.7 variant was first identified in September 2020 but only really entered the spotlight months later, when its prevalence in the UK and elsewhere rapidly increased. Genome sequencing indicates that B.1.1.7 has eight mutations that change the shape of 653
its spike (S), the protein that helps it bind to host cells. These mutations, specifically the N501Y mutation, allow the virus to bind even more tightly than usual, fueling worries that a vaccine built around the genomic architecture of the spike would lose its potency. In an attempt to quell these concerns, the researchers behind the study introduced different mutations exhibited by B.1.1.7 to pseudoviruses created in the laboratory that contained the SARSCoV-2 spike. They also drew antibodies from the blood of 16 people inoculated with the Pfizer-BioNTech vaccine. Fortunately, they found that these antibodies, administered in concentrations similar to those that neutralize older variants, could still deactivate the labmutated virus—excellent news that should calm the nerves of many preparing to receive the vaccine. It must be emphasized, however, that how non-replicating pseudoviruses react to antibodies in a controlled experiment might differ from how SARS-CoV-2 behaves in the real world. That’s why, in their concluding remarks, the researchers emphasize the need for further research. The variant B.1.351: Immune resistant? The second of the two studies focuses on B.1.351, rather than B.1.1.7. Conducted by a group of researchers working in South Africa, the country where the variant was first detected, the study tests whether immunity developed against previous strains of SARSCoV-2 would remain sufficiently protective against B.1.351. The results suggest, regrettably, that this might not be the case. In addition to increasing the binding abilities of the virus like N501Y, some mutations like K417N and E484K might have the added ability to cause or promote immune resistance or escape. Mutations associated with the E484 site in particular have, at least in one study, reduced the protective capabilities of some antibodies more than tenfold. To assess whether this was true of the B.1.351 variant as a whole, the South Africa-based researchers gathered viral samples from Covid-19 patients who were infected by the Wuhan strain during the summer, as well as from patients infected by the B.1.351 variant mid-November, and grew them in the laboratory. Then they gathered plasma samples that contained neutralizing antibodies from patients who were infected by, then recovered from, the older strain.
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As might be expected, the virus from the first wave was slowly and steadily neutralized as the dilution of plasma increased. But pitted against samples of the B.1.351 variant, the plasma didn’t appear to have the same neutralizing effect. As the concentration of antibodies increased, the virus remained intact. This lack of efficacy is painfully apparent in the charts and images of petri dishes below. Based on their observations, the researchers concluded that new strains mount significant resistance against older neutralizing antibodies. Their closing remarks raise caution that just because you’ve been infected with SARS-CoV-2 before does not mean you are immune to reinfection, specifically with this new strain. Additionally, the currently distributed vaccines that target the Sprotein of previous strains may not carry protection over to B.1.351. Viral variation: Piecing together the bigger picture At first glance, it might appear these studies are at odds, examining two distinct variants with two distinct methods. The first also directly involves a vaccine, while the second doesn’t. But both get at the same fundamental question—whether new variants of SARS-CoV-2 are adapting more rapidly to us than we are to them. They also have the same fundamental limitation, which is being confined to the laboratory. The first uses a pseudotype virus; the second, lab-cultured tissue. Excellent substitutes, in other words, but not the real thing. Until we have long-term clinical data on vaccine efficacy and reinfection—another indicator of the effectiveness of natural immunity—we won’t be able to answer this question with certainty. That the Pfizer-BioNTech vaccine appears to counter the mutations that constitute the B.1.1.7 variant is certainly a good sign. Moderna, the company behind the only other Covid-19 vaccine currently approved for use in the US, has also announced plans to accelerate development of a booster shot in light of a study they conducted that saw no change in their vaccine’s efficacy against B.1.1.7, but a five to tenfold reduction in its efficacy against B.1.351 pseudotyped viruses—results that must also be corroborated with infectious variant virions. This adds yet more complexity to the task of providing vaccine protection to people everywhere. Given the mixed results, what we can do is be safe, rather than sorry, and move full speed ahead with current efforts to stop and prevent disease in the general population. So long as the virus 655
continues to spread, it will continue to mutate, becoming potentially more infectious and immune resistant. The most effective way to try to defeat these variants, whether new or old, are measures we’ve been championing since nearly the beginning: wearing masks, social distancing, restricting large gatherings, and isolating the infected. Ramping up enforcement of these measures, as well as worldwide vaccine distribution, is the only way we might still get Covid-19 under control. This article originally appeared in Forbes and is available online here: A Tale Of Two Viruses
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Autoantibodies May Be A Driver Of Severe Covid-19 Reactions Forbes | January 26, 2021 | Article
While vaccine distribution and President Biden’s inauguration occupied most of the media’s attention, January marked the peaks of hospitalization and deaths among Covid-19 patients in the United States. Over 130,000 were in the hospital with severe Covid-19 symptoms in the past two weeks. Emerging evidence suggests one cause of severe Covid-19 reaction may be autoantibodies or antibodies that attack the body and not an invading pathogen. What do we know about autoantibodies, and how can our understanding of them inform Covid-19 research moving forward? A recent study out of NYU analyzed the sera of 86 hospitalized Covid-19 patients. Researchers were on the hunt for autoantibodies, self-attacking proteins mistakenly turn on the body in their attempt to root out pathogens. It is unknown how many people have these antibodies present in their immune systems, though ongoing research is looking into the matter. The NYU researchers hoped their presence could provide some clarity on why some patients get so sick from SARS-CoV-2 infection. They indeed found autoantibodies geared against the annexin A2 protein, which stabilizes cell membranes and blood vessels in the lungs. On average, hospitalized Covid-19 patients had a significantly higher level of these autoantibodies than non-severe patients, and their targetting of the lungs may be one of the causes for Covid-19 related respiratory issues. Autoantibodies targeting interferon responses are noted by several studies as a significant factor in severe Covid-19. The interferons are warning signals that alert the immune system whenever a pathogen invades, which I’ve written about here. A study out of Science showed autoantibodies reducing interferon circulation in the blood to extremely low levels, meaning the pathogen could easily spread throughout the body without having to worry about the substantial immune response. Autoantibodies also 657
seem more prevalent in older adults, which falls in line with who is more likely to have a severe Covid-19 reaction. A major question remains unresolved. Are annexin A2 and interferon autoantibodies activated by Covid-19 infection, preexisting in the patient, and therefore predisposing them to infection? Or are they actually induced by the infection itself? That is an interesting question for these specific autoantibodies, but also for autoantibodies in general found in patients ill with Covid-19. To this point, the existence of autoantibodies in patients prior to arriving at the hospital is unreported. Why do autoantibodies arise? Some are created when the immune system recognizes similar structures in the invading pathogens and human proteins. Some antibodies may be produced by a flood of cellular debris released upon pathogen destruction of cells. In the case of Covid-19, we don’t know the answer. A leading theory for autoantibody development in reference to Covid-19 relates to disfunction in the follicular node when a patient becomes infected. The follicular node is the B cell’s learning center; it is where an antibody learns to neutralize a pathogen. In hospitalized patients, this node is often damaged. This may lead to a B cell less equipped to create virus-fighting antibodies properly and may produce harmful autoantibodies that prompt severe symptoms. While research doesn’t seem to lean one way or the other on why we have autoantibodies waiting to pounce, studies are in the midst of production to find the answers. Rockefeller University in New York was one of the first to observe autoantibodies in Covid19 patients back in September and are currently screening as many as 40,000 patients to see how many had preexisting autoantibodies. If autoantibodies are found to be a significant driver of severe Covid-19 symptoms, pharmaceutical developers should be inclined to research further Covid-19 therapies geared towards them. Treatments that boost specific proteins in weakened immune systems may just be creating more targets for autoantibodies to attack. Testing for these autoantibodies could even be a strong indicator to identify at-risk people for severe Covid-19. Furthering our understanding of how Covid-19 works and why some experience severe Covid-19 symptoms may lead to more effective treatments for patients. Even if an autoantibody therapy or test could save a few lives, the research is worth doing. Ultimately, 658
autoantibody research may open doors for future understanding of this virus and how it affects us. This article originally appeared in Forbes and is available online here: Autoantibodies May Be A Driver Of Severe Covid-19 Reactions
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Israeli Study Shows A Majority Of Those Vaccinated Can Be Infected By SARS-CoV-2 After The First Shot Forbes | January 27 2021 | Article
As vaccine distribution is picking up with nearly 70 million doses administered worldwide, data regarding large-scale vaccination is becoming available. Last week, Israel released preliminary data on the effects of vaccination for infection. Early indications suggest that after vaccination, as many as 70% of people can still be infected by SARS-CoV-2 after the initial dose of the Pfizer vaccine. More data is needed to confirm the effects on transmissibility among the vaccinated. First and foremost, we need to draw a distinction between infection and disease. The Pfizer vaccine referenced in this study has efficacy of greater than 90% at preventing Covid-19 related symptoms. Vaccines do not, however, guarantee protection from infection, and a vaccinated person can still become infected. This study aims to answer how vaccination affects the infectivity of the virus for vaccinated people, not whether the vaccine is efficacious. Israel, which leads the world in vaccinations per capita at around 43 doses per 100 people, developed this study, available at the Clalit Research Institute website, to understand how the Pfizer-BioNTech vaccine affects viral infection. This study is not peer-reviewed and does not necessarily conclude the infectivity of the virus for vaccinated people. Previous studies show the vaccine is effective in preventing Covid-19 related mild and severe symptoms. While the Covid-19 vaccines are intended to protect a patient from symptoms, having your shots doesn’t necessarily mean you can’t still be infected by SARS-CoV-2 or spread it to others. The study contrasted a group of 200,000 vaccine recipients aged 60 and above with a group of 200,000 who hadn’t been vaccinated in the same age group. To quote the Clalit website:
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“The study showed that between the fifth day and the 12th day after receiving the first vaccine dose, there were no differences between the vaccinated group and the non-vaccinated group: the rate of positive tests for the SARSCoV-2 in the two groups was similar. In other words: no difference in infection rates was observed between those who were vaccinated and those who were not vaccinated.” The report continued “that 14 days after the injection of the first vaccine, there is a real decrease in the rate of infection in the SARS-CoV2.” 17 days after the initial dose of the vaccine, between 60 and 80% of people can still be infected. The release of this data is a positive development. For months, the impact of vaccines on the pandemic has been mostly speculative. Nobody knew how mass vaccination might affect infectability or transmissibility. This data is the first of many, and we await data from similar studies. While data remains limited on the transmissibility of the vaccinated, it may be the case that it is reduced among most. If neutralizing antibodies from the vaccines do their jobs, the viral load in a person infected with SARS-CoV-2 is much lower than in those who haven’t been vaccinated. A lower viral load may mean that they are less likely to infect others with the same efficiency that an unvaccinated person may. The vaccinated patient has less virus in them to spread around. Though we don’t know whether this is the case, more data is needed to know if those vaccinated and infected can transmit the virus to others. After the first dose, more than 50% of people remain at risk of infection. Vaccine protection from disease, but not infection, is observed for other respiratory viruses. The flu vaccine, for example, does not typically protect people from infection and further transmission, but only symptoms. Flu vaccines typically reduce risk by 40-60%, meaning receiving a flu shot won’t guarantee you protection from influenza infection. The question of transmissibility is more complicated. Some studies have been conducted on guinea pigs for influenza, showing a moderate reduction in influenza transmissibility from vaccinated hosts. Infection in those vaccinated may be a consequence of the short duration of the IgM and IgA antibodies active at mucosal surfaces, especially the nasal mucosa. Both IgM and IgA antibodies vanish after 4-5 weeks post-induction. The longer-acting IgG 661
antibodies are very likely key to reducing disease severity but are unlikely to prevent infection via the nasal mucosa or other mucosal surfaces. Emerging SARS-CoV-2 variants throw another spanner in the works. New variants have shown to be more aggressively transmissible. Some studies have even indicated that certain variants evade immune-responses from naturally occurring or even vaccine antibodies. If this is the case, a vaccinated community may be ravaged by a variant. Such variants have the potential to infect and sicken even those who have been vaccinated. A recent study from Chongqing China shows that sera from those infected by the original Wuhan strain in January and February of last year have little to no ability to protect against either the UK (B.1.1.7) the South African (B.1.351) strains. Ultimately, we need more data. This study is preliminary, and the results may not be completely indicative of global infectivity rates post-infection. As more countries continue to vaccinate in higher quantities, we will know important information like efficacy, transmissibility, infection among the vaccinated, and more. That information will roll in slowly but surely in the coming weeks. This article originally appeared in Forbes and is available online here: Israeli Study Shows A Majority Of Those Vaccinated Can Be Infected By SARS-CoV-2 After The First Shot
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SARS-CoV-2 Immunity: A Moving Target Forbes | January 28, 2021 | Article
The ability of newly discovered variants to reinfect those who have recovered from earlier Covid-19 infection or those immunized with Covid vaccines is a hot topic. The two strains receiving the most attention are the SARS-CoV-2 variants from the United Kingdom (B.1.1.7) and South Africa (B.1.351). There is mounting evidence that they may be resistant to neutralization by antibodies directed against earlier stains. Definitive proof of resistance can be accomplished by measuring the neutralizing activity of antibodies in the sera from patients infected in the early months of 2020 against both the original and the variant viruses. Scientists from Chongqing Medical University, China did just that in this study. They tested the activity of antibodies in the sera of twenty patients at two time points, in February and October. These patients were infected with SARS-CoV-2 in January and early February. First, they examined the sera’s ability to neutralize the Wuhan strain circulating in China at the time of the January and early February infections. Sera collected in February had high titers of neutralizing antibodies against the original virus. That was not the case for antibodies in the sera of the same patients harvested eight months later. The neutralizing titers of the October sera fell between two to tenfold when measured against the original strain. A fall in neutralizing titers over time has been reported previously in some, but not all studies. The February sera were significantly less effective in neutralizing both B.1.1.7 and B.1.351 than against the original virus strain. The average titer level for the original strain was 825, whereas it was 343 for B.1.1.7 and 148 for B.1.351. Some samples’ neutralization titers fell as much as ten times against the new variants, and six of 20 of the sample’s titers fell below the neutralization threshold against B.1.351.
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The decline in neutralizing activity for the October sera was even more dramatic. Eight of the 20 October sera failed to neutralize the B.1.1.7 variant at all. Only two of the 20 showed any measurable neutralizing activity against B.1.351. These results suggest early infection offers little or no lasting protection against either of the two variants. The results of the Chongqing study are congruent with a study of the ability of antibodies in the sera of patients in South Africa infected in the summer of 2020 to neutralize B.1.351. The titer of the South African sera decreased compared to the original strain by two to three times. Notably, the original infecting strain in China was unlikely to carry the D614G mutation in the spike protein, whereas those responsible for infections in South Africa in the summer of 2020 almost certainly did have D614G substitution. However, given the ubiquity of neutralization escape from these two variants, it’s unlikely that will make a significant difference in the outcome. Collectively, these studies provide a clear warning. First, neutralizing activity in the sera of those infected with SARS-CoV2 decreases over time, at least in some populations, potentially leaving them susceptible to new infections by the original virus. Secondly, SARS-CoV-2 has the potential to evade immune responses induced by either vaccination or natural infections. Immune evasion coupled with increased transmissibility, as is the case for both the B.1.1.7 and B.1.351 variants, poses daunting public health challenges. Not only must we increase public health mitigation measures, but we must also be prepared for a long battle against a moving target. This article originally appeared in Forbes and is available online here: SARS-CoV-2 Immunity: A Moving Target
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Eli Lilly’s Latest Combination Antibody Therapy Yields Strong Effectiveness Against Covid-19 Forbes | January 29, 2021 | Article
While Covid-19 infection rates have taken a downturn in recent days, hospitalizations and deaths are still at all-time highs. The need for effective therapies to treat severe Covid-19 symptoms has never been greater. Eli Lilly is one of the pharmaceutical companies taking on the task of developing these therapies, and a new antibody therapy trial released last week proved one combination therapy to be quite effective at reducing viral load in Covid-19 patients. The study aimed to determine the effect of bamlanivimab (BAM) as an antibody monotherapy and bamlanivimab paired with etesevimab (ETE) as an antibody combination therapy to reduce the viral load for severe SARS-CoV-2 patients. 613 patients were given BAM monotherapy, BAM and ETE combination therapy, or a placebo treatment. The BAM monotherapy yielded results only slightly better than the placebo group. The change in log viral load for the placebo group after 11 days was -3.80, whereas the change for a 700mg dose of BAM was -3.72 for 700 mg, -4.08 for 2800 mg, and -3.49 for 7000 mg. Across all dosages, it seems that the BAM monotherapy yielded around the same reduction in viral load as the placebo group did naturally over the time period. Researchers additionally tested BAM in conjunction with ETE to see if the combination therapy would yield a greater result. It did just that. After 11 days, while again the placebo reduction in viral load was -3.80, the combination therapy reduction was -4.37. According to the researchers, this was a statistically significant result, whereas the BAM monotherapy did not yield statistical significance. The secondary outcomes of this study also note that none of the therapies completely clear the virus from the patient. Neither the combination therapy nor the BAM monotherapy prompted two 665
consecutive PCR negative test results for SARS-CoV-2 within the 29 days of the start of the study. This means that none of the therapies completely cleared the virus from the patient. The remaining bits of the virus may not be enough to transmit to another host, but it’s noteworthy nonetheless. Another noteworthy piece of data from the secondary endpoints, and arguably a primary endpoint to many, is that all doses of the BAM monotherapy and the BAM/ETE combination reduced hospitalizations in patients with severe Covid-19. Among the placebo group, 5.8% of patients were hospitalized during the course of the trial. That percentage dropped to 1% for the 700 mg group, 1.9% for the 2800 mg group, 2% for the 7000 mg group, and .9% for the combination therapy. This is a positive result. It seems that some therapies in conjunction can yield greater results than monotherapies. This may speak to the strength of the virus to evade neutralizing antibodies or perhaps therapies in conjunction simply prompt a stronger immune response. As more data becomes available about the BAM/ETE combination therapy, greater confidence can be taken in distributing this therapy to those in overcrowded ICUs and hospitals across the country. Though a limiting hesitation remains. We don’t know the exact strain the patients involved in this study were infected with. Emerging data is indicating that mutant strains, like those originating in the UK and South Africa, may be immune resistant to neutralizing antibodies. Meaning the variants may resist antibodies from previous infection, antibodies delivered via vaccine, or even antibodies used in severe Covid-19 therapies. While we await new studies working to specifically target new variants with Covid-19 combination therapies, these results are encouraging. Bamlanivimab-etesevimab combination therapy could save countless lives that remain at risk. We eagerly await the results of its next stage of trial. This article originally appeared in Forbes and is available online here: SARS-CoV-2 Immunity: A Moving Target
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February 2021
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Will Population (Herd) Immunity To Covid-19 Be Permanent Or Seasonal? Forbes | February 1, 2021 | Article
In just three weeks, the number of Covid-19 cases in the United States has plummeted by 35 percent. Death rates have yet to follow suit, but they have leveled out, with hospitalization rates on the decline, too. Given that the vaccine rollout is still proceeding slowly, the ebb is the glimmer of hope we need as we start to emerge from a long, dark winter. But is this really the light at the end of the tunnel, or just a period of calm before yet another storm? There are two possible expirations for the sudden decrease. Americans, whether chastened by the holiday surges or influenced by the new administration, may be embracing safety measures like mask-wearing and social distancing. But it could be that population immunity, also known as herd immunity, is on the horizon. While confirmed case counts hover around 26 million, a study recently published in JAMA suggests the actual number is likely four times as high, around 100 million. Between the 100 million Americans who have contracted the virus and the 24 million vaccinated so far, we may be in the early phase of a steady decline. Similarly, India reached peak infection in mid-September 2020, a time when an estimated one third of the population has been infected. Since then new cases have been on a steady decline from a high of 100,000 per day to roughly 12,000.
Chart of new Covid-19 cases in India. Each day shows new cases reported since the previous day. JHU CSSE COVID-19 DATA HTTPS://GITHUB.COM/CSSEGISANDDATA/COVID-19
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Chart of new Covid-19 cases in US. Each day shows new cases reported since the previous day. JHU CSSE COVID-19 DATA HTTPS://GITHUB.COM/CSSEGISANDDATA/COVID-19
By many estimates population immunity requires the majority of a population, around 60 to 70 percent, to have some level of immunity to the virus, offsetting its ability to move freely amongst naive hosts. Last summer, there was discussion that herd immunity— achieved not with vaccines, but through rampant, unchecked infection—might be a potential strategy for ending the pandemic. In the writings I published in response, I argued that this was not just a fallacy, but a recipe for further carnage and tragedy. With deaths in the US alone projected to surpass half a million by the end of February, this is regrettably now our reality. But now that case counts are down and mass vaccinations underway, population immunity has re-entered the realm of possibility cast in a much different light. In today’s discussions, population immunity isn’t a strategy in and of itself, but a byproduct of unevenly implemented public health interventions and a year’s worth of transmission. Some now argue that infection of only third of the population is enough to spark a downward trend. How might the pandemic play out over the next 11 months of 2021? Will the rate of infection drop and remain low, or will we face yet another wave of increased infections and deaths come late fall and early winter? In other words, are we entering a period of prolonged or of seasonal population immunity? In considering these two possibilities, I look to three factors: the immune response to infection, the history of coronaviruses that cause colds each winter, and the emergent shape-changing proclivities of SARS-CoV-2, the virus that calls SARS-CoV-2. Our collective experience with both 669
cold viruses and influenza acquaints us all with the concept of immunity that lasts but a season.
Left: Seasonal variation of human coronaviruses in Stockholm, Sweden. Test results between 2010 and ... [+] (1) POTENTIAL IMPACT OF SEASONAL FORCING ON A SARS-COV-2 PANDEMIC DOI: HTTPS://DOI.ORG/10.4414/SMW.2020.20224 PUBLICATION DATE: 16.03.2020 (2) CDC 2007-08 U.S. INFLUENZA SEASON SUMMARY HTTPS://WWW.CDC.GOV/FLU/WEEKLY/WEEKLYARCHIVES20072008/07-08SUMMARY.HTM
Infection by SARS-CoV-2 triggers the production of IgM, IgA, and IgG antibodies that recognize the virus. IgM and IgA antibodies protect us against infection at our mucosal surfaces, but they are effervescent, lasting no more than a few weeks. IgG antibodies are thus the longest-acting of the three and carry the greatest potential for preventing infection, though reports of just how long neutralizing antibodies last in people infected by SARS-CoV-2 have so far been mixed. In some studies, including a recent one from China, neutralizing activity decreased as much as tenfold between February and October 2020. Overall both the magnitude and duration antibody response may depend upon the severity of the disease. We all know influenza has the propensity to return to plague us each winter in a new guise, one that slips by our natural and vaccineinduced defenses. That is why we receive annual vaccines— to protect us from the latest influenza variants. The capacity of influenza to change seems unlimited. For as long as I can remember, each new winter is heralded by a new flu variant. Until very recently the annual return of cold-causing coronaviruses was more mysterious, as these viruses were thought to be stable, with no significant variations reported. As it happens that 670
is because no one looked until now. Surprise! Influenza now has a changing cousin. The one cold-causing coronavirus strain studied, known as 229E, not only changes, but evolves over time to evade the prevailing immune responses to its predecessors. The seasonal influenza's winter peaks and those of the cold causing coronaviruses appear to be due to the same two factors, waning protective immunity and immune evasion. It is this context that makes the recent discovery of new SARSCoV-2 coronavirus variants so troubling. The variants share several features of concern. They are more easily transmitted than their predecessors, more resistant to neutralization by the antibodies in the blood of patients infected with early strains of the virus (and in some cases to the antibodies in those immunized with anti-Covid-19 vaccines), and are found in more abundance in nasal secretions of those infected. Specifically, one recent study found that whereas most of the sera collected in October from 20 people infected in January was able to neutralize the original, so-called Wuhan strain, only two of the 20 inactivated B.1.351, the so-called South Africa strain. Meanwhile another study conducted in South Africa found definitive evidence that B.1.351 infects those who’ve recovered from prior infection by the original infecting variant. The South Africa variant is also far more resistant to the Novavax vaccine, evading both natural and vaccine induced immunity. My conclusion is that we may very well face a renewed winter wave of Covid-19 this year, driven both by aging immunity and virus variation. We must heed the lessons of influenza, as well as those of other coronaviruses. What we may be entering now may be only a respite, best described as seasonal immunity. We are not helpless. First and foremost, we must do all we can to eradicate Covid-19 as quickly and as thoroughly as possible within our respective borders. Today the US accounts for almost one quarter of all infections. We should beware not only imported variants but homegrown ones as well, some of which, like the California and Ohio strains, may have been spotted already. The current vaccines will speed us on our way. New vaccines adapted to the variants as they arise will also help. But I am not alone in warning that vaccines alone are not the entire solution. We must also do what is needed to prevent transmission by following the guidance of our public health experts. Others have 671
kept their countries free of Covid-19, save for intermittent imported outbreaks. Identification of those infected, followed by isolation of those infected and exposed, is critical. Today the US has fallen far short of this goal. Vaccines will make the job of eliminating Covid19 easier, but cannot do it alone. Failing Covid-19 eradication, I fear we are in for another dark winter—perhaps not as dark as today, but one we all must do our best to avoid. This article originally appeared in Forbes and is available online here: Will Population (Herd) Immunity To Covid-19 Be Permanent Or Seasonal?
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Travel Bans Won’t Stop The Spread Of New Variants — Travel Restrictions Might Forbes | February 3, 2021 | Article
Alot has been made of the Biden administration’s move to ban nonUS travelers from South Africa to the United States and to extend the ban on travelers from Brazil and twenty-eight countries in Europe. The move is an attempt to limit the spread of new, fastmoving variants of SARS-CoV-2, which are much more contagious and may be more deadly than the most dominant variant in the US today. But these efforts do little to solve our problem and are likely to prove as ineffective as our initial ban on travelers from China in stopping the early spread of Covid-19. Many have expressed worry over the South African variant in particular, which is estimated to be up to 50% more contagious than current variants and more effective at resisting neutralizing antibodies generated by vaccines or previous infection. A ban on travelers from South Africa does little to stop the virus from arriving on our shores. The variant has already been found in more than 20 countries, including our closest neighbor to the North where it has been circulating for nearly a month. What we need instead are restrictions on all travelers, no matter their citizenship or country of origin. Every person arriving in the US should be required to test negative twice for Covid-19 at maximum 36 hours before their travel begins. The first test should be a PCR test, which can show whether a person has an active infection. The second should be an IgM antibody test, which can show whether a person was recently infected and may still be contagious. Some travelers who were recently vaccinated may have a negative PCR test result but a positive antibody test due to the vaccine and not a recent infection. In these cases, an additional antibody test directed at proteins not targeted by the current vaccines would be required. Upon arrival in the US, all travelers should be tested again with a rapid antigen test or PCR test. We know already that these tests 673
miss cases anywhere from 20% to 100% of the time, depending on when during the course of an infection they’re administered. This means that even if a traveler tests negative before travel and upon arrival, they should still be required to isolate themselves for a minimum of two weeks in a controlled facility. We’re not talking about vague promises to head directly home and stay there, we’re talking about supervised isolation where temperatures are monitored, tests are administered, and those who fall ill are treated and cared for without risking the further spread of disease. I know these restrictions may seem severe and they place yet another burden on a nation already carrying a heavy weight that only grows larger with every new death, every job lost, and every day we are confined to our homes, alone. But these restrictions are necessary if we are to prevent things from becoming much, much worse. Other countries — Australia, China, New Zealand and Taiwan to name just a few — have followed this approach and have proven themselves successful against the spread of disease and the new variants. Indeed, some places have even more stringent restrictions. Hong Kong, for example, requires three weeks of quarantine in a controlled facility with follow up tests. Mainland China requires the same three week quarantine period, though the last week can, for now, be served at home. While these restrictions haven’t prevented travelers from carrying the variants into the country, they have prevented the variants from spreading and becoming the new dominant strain. We should not only impose these restrictions on travelers to our country, we should hope that all countries impose these same restrictions on American travelers heading abroad. The US is home to the largest Covid-19 outbreak in the world. We are almost certainly generating our own variants, that may be more contagious and more deadly than any that have been identified to date. Worse, we aren’t doing the necessary sequencing to identify these variants or warn others of their spread. This means that we are as much of a threat, if not more, than any other country today. With these new variants, the virus has shown us that it can adapt to escape some of our best defenses. Now we must adapt in turn. No more compromise, no half measures, just strong and decisive action to avert what looks to be a growing disaster.
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This article originally appeared in Forbes and is available online here: Travel Bans Won’t Stop The Spread Of New Variants — Travel Restrictions Might
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Concerns Grow Over The Newly Discovered Southern California Covid-19 Variant Forbes | February 3, 2021 | Article
The rate at which new variants have appeared over the past few months is alarming. In the past few weeks alone, along with the insurgence of the United Kingdom (B.1.1.7) and South African (B.1.351) variants, more have been identified in Brazil, Ohio, and now California. The increased rates of infection and deaths in Manaus, Brazil, despite prior infections affecting 76% of the population, serve as a warning that a new variant may reinfect a population infected with an earlier strain. A similar situation may be occurring in Southern California. Here we examine their situation in more detail. One of the few vigorous SARS-CoV-2 genome sequencing efforts in the US comes from Cedars Sinai Hospital in Los Angeles. Analyzing countless samples on the lookout for the dangerous emerging variants, researchers found a strain all its own as far back as July. Only a single sample at the time, not much was thought of it. Fast forward to January and the California variant (CAL.20C) accounts for half of the analyzed isolates. CAL.20C has three unique amino acid substitutions in its spike protein. The spike protein is the part of the virus that interacts and locks into proteins from the human host cell, essentially the key to open the host to the virus. Among these are S13I and W152C in the N-terminal domain, and L452R in the receptor-binding domain. It is possible that S13I increases the efficiency of cleavage on the 12 amino-peptide terminal, which may increase the volume of Sprotein on the host cell. This would lead to a more infectious virus. Additionally, W152C may boost immune-resistance or N-terminal domain efficiency, or something else. We need more data on these two placements before we can draw definitive conclusions from these two substitutions. The L452R substitution provides a bit clearer insight. The L452R substitutes a hydrophobic amino acid leucine for arginine. 676
Not only is the side chain of the amino acid longer, but it is also positively charged. To understand the relationship between the receptor-binding domain and the ACE2 receptor, think of magnetic puzzle pieces. Not only must the shape be an exact match for the two pieces to fit, but the magnetic poles must be aligned as well. Variation in shape or polarity may affect the fit of the pieces. L452R may improve the fit and charge complementarity of the two pieces. According to preliminary data from the Fred Hutchinson Cancer Research Center, which isolated mutation placements to test for immune escape, a mutation to the 452 placement escaped slightly more than a mutation to the 501 placement. N501Y is commonly attributed to the immune-resistance of B.1.1.7. If this preliminary data is any indicator, CAL.20C may be able to escape neutralizing antibodies about as well as B.1.1.7. Again, more data is needed to draw any conclusions about this emerging variant, but the sooner we know the better. We now know what we’ve long speculated: homegrown SARSCoV-2 variants are mutating right under our noses. This is a logical development, as the US has more infections than any other country in the world, by far. We now know the existence of this and the Ohio variants. The likelihood that more remain undetected is high. Labs around the country should follow the lead of Cedar Sinai and genome sequence as many samples as they can. Identifying emerging variants is the first step to understanding and controlling their spread. Unfortunately, as more variants arise, the chances that the indistribution vaccines cover every variant dwindles. Ample data is available to suggest that B.1.351 is up to ten-fold immune-resistant to several vaccines, and could likely reinfect those previously infected. As P.1 carries many of the same mutations, there is a strong chance it is as well. In all likelihood, Covid-19 vaccines will need to be adapted annually, as we do with the flu. Manufacturers will need to guess, as they do for flu, which SARS-CoV-2 variants will arise in which region at which time. Most of all, we must reinforce and tighten infection control measures in the United States, despite the apparent waning in infection rates. If these variants grow out of control, we will face another large wave of infections, hospitalizations, and deaths. We are likely to be living with Covid-19 for a long time. The question is, can we figure out a way to manage Covid-19 spread 677
without the significant loss of life we’ve all experienced this past year? This article originally appeared in Forbes and is available online here:Concerns Grow Over The Newly Discovered Southern California Covid-19 Variant
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COVID Control American Style ClinicalOMICS | February 8, 2021 | Article
The United States is spiraling. Seven-day averages for positive COVID-19 cases have exceeded 250,000 per day, having risen sharply after the Thanksgiving holiday and rising again after end-ofyear celebrations. While many wait on distribution of a vaccine, at press time more than 4,000 Americans are dying on some days— unnecessary and preventable deaths in my view. We could bring this pandemic under control quickly, and well before the vaccines are widely available later this year. The way to do it is something I call COVID Control American Style: a plan to test every U.S. resident using at-home, inexpensive, rapid tests. The testing dilemma The U.S. federal government has a responsibility to supply and distribute COVID-19 tests to everyone in the country, so people can know if they’re infected and infectious, and can isolate appropriately. But current testing regimes are insufficient and uncoordinated. Receiving a test in the early months of the pandemic and even today requires sitting in lines for hours and waiting days for results. During that time, an infected person may spread the virus to dozens of others, particularly if they were asymptomatic and unaware of their contagiousness. The limited supplies and testing waits were centered, for the most part, around PCR testing. This type of testing detects the virus’s genetic material and requires lab analysis. A cheaper and faster alternative is the rapid test. This test would likely be an antigen test, which detects specific proteins on the virus’s surface and can deliver results in as little as 15 minutes. However, another rapid test option is CRISPR, which detects specific DNA sequences. These tests would only be viable if they could be as inexpensive and widelyavailable as antigen tests. COVID Control American Style builds on these types of rapid tests. While most rapid tests today are administered at a lab by a 679
healthcare worker, some are optimized for at-home, selfadministered use. The FDA granted the first emergency use authorization to an at-home test in mid-November. These tests are the key to controlling the pandemic, but they must be more than just self-administered. They need to be universally accessible and inexpensive. Cheaper tests and assisted isolation Ideally, the President would activate the Defense Production Act to produce the at-home tests. The nation’s manufacturing capabilities could make hundreds of millions of tests per week, which could be as small and simple as a pregnancy test. This would create a supply that would guarantee access to all American residents. Additionally, it could drive the price well below $5 per test. Our estimates suggest a cost of 50 cents per test is achievable, as demonstrated by Egypt’s eradication of Hepatitis C with similarly priced, widely available tests. Assuming tests cost 50 cents each, the cost to administer around 150 million tests per day over 100 days would be about $7.5 billion. For context, the Congressional Budget Office estimated the pandemic’s economic fallout would cost the United States around $8 trillion in the next ten years. That is ‘trillion’ with a ‘t.’ Considering the financial ramifications of doing nothing and letting COVID-19 continue to ravage the country, spending a measly $7.5 billion seems more than reasonable. Once we’ve identified those that have tested positive, the federal government would help the contagious make it economically and physically possible to remain in isolation for their infection’s duration. Assisted isolation would require social support, including food, medical supplies, and shelter as necessary. This would no doubt be more costly than the tests themselves, but it still pales in comparison to the economic fallout estimates. Assuming around 100,000 households require assisted isolation per day over 100 days, providing those households with a $500 per day payment for two weeks would amount to roughly $70 billion. Meaning the total cost of COVID Control American Style is approximately $77.5 billion. While not inexpensive, this total is remarkably less than the COVID packages that have already been implemented by Congress. 680
The potential for success A mass testing pilot program for COVID-19 began in England at the end of 2020 and showed initial promising results, despite some concerns about test accuracy. The government ordered two billion antigen tests and launched an initial testing program in Liverpool. This identified nearly one thousand asymptomatic carriers in the first few weeks, each of whom then isolated themselves. Positive cases in Liverpool declined steeply after the testing was introduced and only began to increase again as the new wave of the virus hit most areas of the country at the end of December. Liverpool’s testing program used healthcare workers to administer the tests. Imagine the widespread use and success that inexpensive at-home testing would entail. The U.K.’s mass testing program provides further evidence for the success COVID Control American Style would bring. Challenges to consider There are a few immediate concerns that must be overcome for COVID Control American Style to work. First, rapid tests are less sensitive and have slightly lower specificity than PCR lab testing. Sensitivity is the ability to accurately identify those with the disease, and specificity is the ability to accurately identify those without the disease. For instance, Abbott Laboratory’s rapid antigen test has around 97 to 99% specificity and sensitivity in clinical study. In other words, between one and three of every 100 people may receive a false positive or false negative. Inflating that rate to 300 million people, 3 to 9 million may receive false results, which is problematic. That said, accuracy is improving as the tests become more refined, and CRISPR tests are already nearly as accurate as PCR tests. The solution to overcome false positives is to retake the test. If someone receives a positive result, test again to be sure as the test is not cost-prohibitive. The rate factors itself, meaning if the 3 to 9 million that receive a false result test again, only 30,000 to 270,000 will receive a false result again. To be more sure, a third test would take those results down lower: 300 to 8,100. False negatives are a bit trickier. Yes, there will be some. With PCR testing, there are still some false negatives because people may get tested too early to have their virus detectable. There will always be false negatives, but detecting 98% of people infected is far better 681
than current rates. Ten or even twenty percent of those getting PCR tests do so too early and receive a negative result. The second immediate concern is people not using the tests. With financial aid and inexpensive, convenient tests, it still seems likely that many Americans will not take part in the program. Even as COVID-19 rages throughout the nation, millions traveled for Thanksgiving, and countless people continue to eat out at restaurants, go to bars, and generally ignore COVID-19 guidelines. To counteract this, making the test widely available to schools and workplaces would force many of those who refuse to take them at home to get tested. Despite these shortcomings, COVID Control American Style could be a powerful tool in the arsenal to strike down COVID-19. This program is not in competition with forthcoming vaccine candidates. The vaccines by Moderna, Pfizer, and others will help to fend off COVID-19, but their long-term effectiveness remains unknown, and they will not be widely available for several months. COVID Control American Style could begin production and distribution of tests immediately, and pairing this program with a federal vaccine distribution program would ideally bring the pandemic to an end even faster. COVID-19 can be stopped, but not without action. Vaccines are making their way to the public, but it will be months before most can get in line for one. COVID Control American Style uses the tools currently available to control the virus’s spread at relatively little cost rapidly. Ultimately, stopping the pandemic is everyone’s foremost priority. Our plan could bring about that reality sooner rather than later. This article originally appeared in ClinicalOMICS and is available online here:COVID Control American Style
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Covid-19 Could End Up Like The Flu—Or Worse Forbes | February 11, 2021 | Article
The more we learn about emergent variants of SARS-CoV-2, the virus that causes Covid-19, the more obvious it becomes that we underestimated their potential impact on our lives. Between growing evidence of increased transmissibility, immune evasion, and possibly even lethality, I can now say with certainty what I could only speculate before. Right now these new variants are a serious cause for concern, and they could continue to be for many years to come. The question, then, is no longer if SARS-CoV-2 will vary, but how—and in this respect it bears resemblance to another notoriously harmful virus, influenza. One theory, based on years of intensive research done by evolutionary biologist Jesse Bloom and his collaborators, is that these viruses can evolve within and across multiple scales of time and space. Though evolution, at least in the popular imagination, is generally thought to be a large-scale endeavor occurring at the population level, the common prerogative of viruses to alter themselves endlessly is as present and feasible in an individual body as it is across their host species. Per this logic, the variations that arise over the course of someone’s infection can be the same as those seen in the pandemic at large, achieving a striking degree of spatiotemporal coherence. How can scientists possibly observe such a phenomenon? Though influenza and SARS-CoV-2 can mutate no matter the health or background of their host, immunocompromised individuals tend to develop longer-lasting infections that are easier to study. For them, what a healthy immune system can neutralize in a matter of days can take weeks or even months, giving the virus more breathing room to experiment with the very slight alterations—sometimes as miniscule as a single amino acid—that might improve its fitness. When researchers cross-referenced these changes with those in variants either already dominant or on the 683
verge of it, they found a remarkable amount of overlap—hence the term “parallel mutations,” a phrase that captures the fact that the same mutations developed independently of one another. One such study, published in 2017, examined four immunosuppressed cancer patients who developed very persistent and severe cases of the flu from 2006 to 2007 (Figure 1). For several months researchers obtained weekly samples of influenza virus that they sequenced, analyzed for mutations, and compared to one another. Notably, besides having a common foe in cancer and influenza, the patients were quite different — diverging in age, gender, pre-existing health conditions, and duration of infection. Patient W, for instance, was a woman in the 25 to 44 age group who was being treated for Hodgkin’s Disease, a type of lymphoma, prior to catching the flu and died 80 days after her first sample. Meanwhile Patient Y, a man in the 45 to 65 age group with leukemia, tested positive for cytomegalovirus and cold-causing coronavirus over the course of his infection but eventually recovered.
Figure 1. Overview of patient influenza infections and treatments. Periods of oseltamivir (Tamiflu) ... [+] “PARALLEL EVOLUTION OF INFLUENZA ACROSS MULTIPLE SPATIOTEMPORAL SCALES” HTTPS://ELIFESCIENCES.ORG/ARTICLES/26875
Two major findings came of this study. First, the researchers were able to identify several mutations that developed in two or more patients in parallel (Figure 2). While these mutations appeared across nine different sites in the influenza genome, five of those sites were located on hemagglutinin, a surface protein critical to the virus for both binding and fusion purposes (Figure 3). Second, variation in four of these five hemagglutinin sites was also prevalent in influenza strains circulating globally, with two mutations in
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particular—V223I and N225D—reaching high frequency in the decade after the study participants were first infected.
Figure 2. (A) Number of nonsynonymous (orange) and synonymous (green) variants in each influenza ... [+] SOURCE: “PARALLEL EVOLUTION OF INFLUENZA ACROSS MULTIPLE SPATIOTEMPORAL SCALES” HTTPS://ELIFESCIENCES.ORG/ARTICLES/26875
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Figure 3. Sites of (A) nonsynonymous and (B) synonymous within-host mutations are shown on an HA ... [+] SOURCE: “PARALLEL EVOLUTION OF INFLUENZA ACROSS MULTIPLE SPATIOTEMPORAL SCALES” HTTPS://ELIFESCIENCES.ORG/ARTICLES/26875
Today we see the same parallels arising between immunocompromised Covid-19 patients and the new SARS-CoV2 variants. In May 2020, a man living in London—I’ll refer to him as the London patient—was hospitalized and diagnosed with Covid19. He recovered and went home, only to be readmitted the following month when his symptoms came back with a vengeance. This time he was administered, at distinct yet overlapping intervals, a plurality of treatments, including the steroid dexamethasone; two rounds of remdesivir, an experimental drug therapy; and convalescent plasma, a highly potent preparation of anti-SARSCoV-2 antibodies, from not one, not two, but three different patients. Like half of the influenza study participants, he was being treated for lymphoma prior to his diagnosis. 686
Figure 4. Clinical timeline of events with longitudinal respiratory sample CT (cycle time) values. SOURCE: “NEUTRALISING ANTIBODIES IN SPIKE MEDIATED SARS-COV-2 ADAPTATION” HTTPS://WWW.MEDRXIV.ORG/CONTENT/10.1101/2020.12.05.20241 927V3
Over the course of the London patient’s second hospitalization, which lasted more than 100 days, researchers extracted, sequenced, and analyzed more than 20 different viral samples, a process they describe in a research paper currently undergoing peer review (Figure 4). They were able to observe the evolution of the virus in real time, watching as some amino acid changes came about in competition with others, then became fixed. One example is the H69-70 deletion in the N-terminal domain of the spike—a surface protein comparable to hemagglutinin in function and significance— which went on to become a defining feature of the B.1.1.7, or UK, variant.
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Figure 5. Variants detected in the London patient from days 1-81. SOURCE: “NEUTRALISING ANTIBODIES IN SPIKE MEDIATED SARS-COV-2 ADAPTATION” HTTPS://WWW.MEDRXIV.ORG/CONTENT/10.1101/2020.12.05.20241 927V3
The London patient is not the only evidence of parallel mutations in SARS-CoV-2. Another example is a 45-year-old, immunocompromised man in Boston who had Covid-19 for nearly five months. A case study of his infection, published mid-November in the New England Journal of Medicine, revealed that the E484K mutation, the very same to appear in the B.1.351 variant originating in South Africa and the P.1 variant circulating in Brazil, was detected in his viral samples. So was N501Y, yet another substitution in the spike protein most prominent for its likely role in increasing the transmissibility of the UK variant. A research paper published in Science early this month added a third precedent to the list, a cancer patient in Pittsburgh who had Covid-19 for at least 74 days before passing away. They, too, were immunocompromised—and they, too, had SARS-CoV-2 replicating inside them that sported mutations found in the UK and South Africa variants. Recall that researchers began following the case of the London patient when he was readmitted to the hospital in June of last year. The world didn’t catch wind of the UK and South Africa variants until a full six months later—meaning that the surface protein 688
mutations researchers identified in this single patient anticipated those to come globally. Sound familiar? That’s because the same sentence could be used to describe the outcomes of the 2017 influenza study. The similarities don’t end there, either. The variation mapping technique that first established the E484K mutation could reduce the neutralizing power of convalescent sera up to tenfold was also used on hemagglutinin back in 2019. That data pointed to a related but more general conclusion. Anti-flu antibodies recognize a portion of the surface protein so tiny, a single amino acid change is all it takes for the virus to evade the defensive attacks mounted by convalescent sera. Is it the case that mutations don’t just arise in parallel within immunocompromised hosts and across global populations, but that the former originate the latter? We can’t be sure. What is almost certain, however, is that the evolutionary pathways traversed by SARS-CoV-2 are too close to influenza for comfort. We know that nonlethal human coronaviruses occur seasonally like the flu, each time in a new guise. Partially immunized populations, it seems, buffer these viruses much in the same way that a weakened immune system bolstered by sera does— the flipside of introducing new measures against contagion or disease being an increase in pressure on the virus to surmount those same defenses. We may think we have a grasp on the direction SARS-CoV-2 is headed in—predicting it will become less lethal or capable of causing serious disease, akin to a common cold—but allowing optimism to cloud our judgment only sets us up to be blindsided by more unpleasant surprises further down the line. At this point this virus has proven itself so flexible and wily, to think it might cease to change and conveniently fade into the background isn’t just optimistic, but naive. Influenza has caused five pandemics in the past 100 years and continues to kill tens of thousands of people annually—and it isn’t nearly as lethal as Covid-19. If we don’t strengthen our efforts to contain this disease considerably, taking a line of attack aimed at not just eliminating the virus, but averting its evolution into more dangerous forms, we can expect it to mirror influenza in this respect, too—continuing year after year to add to the toll on human life that is already too great to bear. Analysis of persistent infections in immunocompromised patients gives us valuable insights we can use to improve our drugs, diagnostics, and vaccines, which is why my 689
next article in this series will take a closer look at the patients from Boston and Pittsburgh. Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the eleventh part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, and part ten. This article originally appeared in Forbes and is available online here: Covid-19 Could End Up Like The Flu—Or Worse
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Weighing Biden's First Executive Orders to Address COVID-19 Think Global Health | February 11, 2021 | Article
Within days of his inauguration, President Joe Biden followed through on his promise to get straight to work fighting COVID-19, swiftly signing numerous executive orders aimed at mitigating the pandemic. These directives include everything from enforcing mask-wearing to enhancing worker safety, increasing testing to reopening schools safely, and reducing racial and ethnic disparities. Yet a close look at them reveals there is still much to be done. Over a year into the pandemic, much of the population is worn out, tired perhaps from trying to adhere to a confusing set of mixed messages from federal, state, and local officials. Biden's orders provide clearer direction. For example, he signed an executive order requiring masks to be worn on federal property, at airports, and on interstate transit, though he lacked the legal authority to enforce a nationwide mandate for other locales. But his actions to date are not nearly enough. Here are five ways the new administration can build on Biden's early executive orders to fight the pandemic: 1. Mass Produce Rapid, Self-Administered Tests and Enforce Quarantine Measures To date, Biden's COVID-19 strategy seems to be focused on two fronts: deploying a medical solution such as vaccines, and enforcing a limited set of public health measures such as maskwearing and increased use of personal protective equipment (PPE). But these efforts leave out a critical tool that other countries like Australia, China, and Singapore have used to bring community transmission of COVID-19 down to nearly zero: widespread testing and mandatory isolation and quarantine of those at risk of spreading disease. By establishing a COVID-19 Pandemic Testing Board via executive order, Biden demonstrated a commitment to rapidly expanding testing and boosting the supply chain, something the 691
previous administration miserably failed to accomplish. But the administration must place a greater focus on mass producing selfadministered, rapid antigen tests, something I have advocated for repeatedly and which would drive down prices to less than $0.50 per test. A recent deal the United States struck with Australian rapid test manufacturer Ellume is the wrong approach. Shipping the tests across the globe wastes precious time, the tests themselves are far too expensive, and fall 2021 is far too long to wait for domestic mass production. The FDA needs to move quickly to grant emergency authorization for cheaper, rapid paper-strip tests. Beyond widespread testing, the focus should be on what happens when people test positive or have been in close contact with someone who has. Currently, people are asked to quarantine but little is done to ensure they can adequately adhere to the request. For single-income households or low-wage earners such as delivery drivers, isolation and quarantine are more than an inconvenience, they are a path toward poverty, bankruptcy, or worse. We need to pay those with verified infections to isolate at home for fourteen days and provide more support to others asked to quarantine. Calling on Congress to renew the requirement for emergency employer paid sick leave is a good start, but the new administration should do more. If every American had inexpensive tests to assess themselves twice a week and the ability to quarantine, without financial burden, should they prove infected, we could significantly reduce the rate of community transmission. This would also help fulfill Biden's goals of safely reopening schools, childcare facilities, and local businesses. 2. Give Local Government and Communities Consistent Guidelines The CDC's policy encouraging Americans to physically distance and avoid large gatherings is too vague and open to misinterpretation. The new administration needs to work with state and local governments to set consistent caps on gatherings, to define essential and non-essential activities, and to put restrictions on travelers arriving from abroad or from a neighboring state. These policies should be adjusted predictably as infection levels change, so the public is assured that these restrictions are not permanent. Biden has usefully described using a "dimmer switch" to 692
"dial" up and down restrictions according to infection rates, which may resonate with members of the public who are increasingly scarred by the indefinite and abstract term "lockdown." Australia has regularly adjusted local restrictions on indoor and outdoor gatherings and household visitors based on infection rates in each state and communicated the changes to the media and public in daily press conferences. The United States may struggle to emulate this approach because Americans became accustomed to a complete lack of restrictions under the Trump Administration, but it's still critical to provide all Americans clear guidance on what they can and can't do based on the rate of infection in their community. Likewise, U.S. states need consistent guidelines on when to trigger local lockdowns, based on mortality and positivity rates and hospital capacity. Consider the case of New York: as cases escalated there in the fall, Governor Andrew Cuomo pledged to lock down neighborhoods where positivity rates exceeded 4 percent. Yet when cases began to surge, Cuomo scrapped the plan and allowed schools, restaurants, and bars to remain open, which confused parents, school administrators, and business owners alike. Consistent lockdown guidelines will encourage adherence and provide a clear pathway to reopening. 3. Accelerate the Development of Therapies Another executive order signed by Biden aims to accelerate the development of novel therapies to treat COVID-19. The administration should be commended for advocating for the inclusion of populations who have been historically underrepresented in clinical trials to ensure a more equitable drug development process. While a welcome change from the Trump administration, whose delay in developing treatments was inexcusable, the order is light on details about how research will be accelerated. The global battle against HIV has shown that antivirals can successfully control an epidemic, and now we need to develop direct, powerful, fast-acting antiviral drugs that can be given to patients in the early stages of COVID-19 infection before the virus causes them severe illness. As early as May 2020, I wrote about a study by a group of physicians in Hong Kong that reported COVID19 responded to a cocktail of antiviral drugs, reducing recovery time for patients with mild to moderate symptoms from twelve to seven 693
days. The drugs work on SARS-CoV-2 itself, targeting the functions of the virus and preventing it from replicating in the body. But the Trump administration touted Remdesivir instead, without sufficient data to back that claim. 4. Remove Barriers to Vaccination As the United States broadens criteria for vaccination to include healthy people as young as 65, we have witnessed how woefully unprepared each state is to efficiently and equitably distribute vaccines. Online booking portals are frequently crashing and hotlines are overloaded. In many cases, only the tech-savvy, with the luxury of unrestricted computer and internet access and unlimited time, can secure an appointment. Biden's plan to create a public health workforce may rectify some of these inequities. Every state should roll out or expand a vaccine booking assistance hotline. Every neighborhood should have a mobile outdoor appointment booth, staffed by helpful assistants. Programs that already serve vulnerable communities such as Meals on Wheels, food pantries, religious organizations, and homeless shelters are natural partners for ensuring that no one is left behind in vaccine distribution. Biden has acknowledged these vast health disparities by appointing a health disparities advisor and creating a COVID-19 Health Equity Task Force, commendable and historic actions, but we have yet to see how these initiatives will play out in practice. 5. Ensure Worker Safety Biden called upon the federal government to issue long overdue science-based guidance for reducing workers' risk of COVID-19 exposure, and allocated funds in his COVID-19 budget to enforce those health and safety requirements. Previously, only fourteen states have adopted comprehensive worker safety protections, the adoption of national requirements will have a profound impact on workplace transmission. Biden also requested the Department of Labor consider clarifying that workers who refuse unsafe working conditions can still receive unemployment insurance. This order is a positive step towards ensuring that Americans don't have to choose between their safety and a paycheck. But these regulations, along with the emergency sick leave requirement, need to apply to all workers, including gig workers such as delivery and ride-share drivers 694
By enacting these COVID-19-related executive orders, in just a few days Biden has already instilled more confidence in his administration's ability to fight the pandemic than the Trump administration did in an entire year. But inheriting a crisis of this magnitude will require unprecedented and ambitious policy changes beyond what the current executive orders propose. Mass rapid testing needs to be swiftly and cheaply rolled out in order to curb transmission and safely reopen schools and businesses. Public health measures such as consistent quarantine and lockdown protocols cannot be ignored. Vaccines need to be easily accessible to all and new therapies to treat COVID-19 patients need to be accelerated. Implementing these strategies in tandem with the executive orders will allow the Biden administration to begin controlling the pandemic. This article originally appeared in Think Global Health and is available online here: Weighing Biden's First Executive Orders to Address COVID-19
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Persistently Infected Covid-19 Patients: A Potential Source For New Variants Forbes | February 16, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the twelfth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, and part eleven. Previously I described the evolution of a viral variant in an immunosuppressed patient in London who was persistently infected with SARS-CoV-2. I also went into detail about the specific changes in the genomes of viruses isolated from the London patient that were identical to those identified in the variants of concern in South Africa and Brazil. Some of the same mutations are found in laboratory experiments that purposefully generate and select for virus strains resistant to antibodies in the blood of patients who have recovered from Covid-19. These observations raise two interesting possibilities. Can it be that persistently infected, immunosuppressed Covid-19 patients are the actual source of variants? Or are the pathways to increased transmission, virulence, and immune evasion in populations independent but parallel to those occurring in immunosuppressed patients and laboratory experiments? Either way, taking a look at the viral variants that arise in infected, immunosuppressed patients can provide us a valuable window into what the future may hold. Here I describe observations of another immunosuppressed, persistently infected patient in Boston. In November 2020, the New England Journal of Medicine published a case study of a 45-year-old man who at some point last year checked into the hospital with a bad fever and some other 696
minor Covid-19 symptoms—henceforth known as the Boston patient. At the time, the Boston patient was undergoing treatment for severe antiphospholipid syndrome, an autoimmune disorder that causes the body to turn against its own cells. He ended up staying in the hospital for a total of 154 days, from the day he first tested positive for Covid-19 up until the day he passed away (Figure 1). The doctors treating the Boston patient gave him several experimental therapies over the course of his hospitalization, from the antiviral remdesivir to the Regeneron antibody cocktail, which contains two SARS-CoV-2 monoclonal antibodies. As was the case with the London patient, rather than causing the virus to subsist, these treatments evidently put more pressure on it to evolve. Also like the London patient, the man’s immune system was already weakened by a preexisting health condition, creating an ideal environment for the virus to continuously experiment with newer, better versions of itself—the result being the development of multiple mutations, as many as 24, along the spike protein (Figure 2, Figure 3). You may recall that the spike is what SARS-CoV-2 uses to latch onto our cells’ ACE2 receptors. In the Boston patient, almost all of the mutations that appear in this part of the virus were located in two main subregions, the N-terminal domain and the receptor binding domain. In the N-terminal domain, deletions occurred from sites 142 through 144 (Figure 4). While not much is known about the functionality or broader significance of these particular amino acids, it does appear that SARS-CoV-2 can sustain multiple deletions in the N-terminal domain and still maintain full infectivity. The London patient also had a mutation in this area—the H69-70 deletion that later appeared in the B.1.1.7, or UK, variant. The deletions in the N-terminal domain are most likely to delete neutralizing antibody epitopes, while maintaining the function of the entire S1 protein. On the other hand, all the mutations in the receptor binding domain are point mutations, or substitutions, which may affect immunogenicity and affinity but leave existing functions intact. This region seems to be intolerant of deletions. D614G, a mutation that became dominant last spring and forewarned the current explosion in variation, is one example. On the whole, the mutations in the receptor binding domain are more
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striking, if only because more parallels exist between them and the new variants threatening populations the world over. Two of these substitutions, E484K and N501Y, are known to play a critical role in allowing variants that originated in the UK, South Africa, and Brazil to spread faster and further from host to host. The N501Y mutation, which substitutes one positively charged amino acid for one even more highly charged, increases the affinity of the spike for our receptors and was also seen in the London patient. The E484K mutation, on the other hand, is thought to decrease the potency of experimental therapies that rely on the antibodies of recovered Covid-19 patients to neutralize the virus, such as convalescent sera and monoclonal antibodies. E484K, in other words, probably assists SARS-CoV-2 in slipping past our immune systems, leaving us more vulnerable to disease. Another substitution identified in the Boston patient, Q493K, was also found in another immunocompromised Covid-19 patient I’ll call the Italian patient, whose case I’ll discuss in a forthcoming piece. It appears that Q493K may facilitate escape from neutralization and increase binding affinities. The last two mutations in the receptor binding domain of note, T478K and S494P, have yet to arise in any of the variants currently circulating around the globe, but did appear in separate laboratory experiments conducted by scientists Jesse Bloom and Gideon Schreiber and could in future variants. Bloom’s study analyzed potential mutations for their ability to resist convalescent sera, while Schreiber’s looked at ones that increased binding affinity to the ACE2 receptor. Their work, along with the findings from the London and Boston patients, sheds light on the variations of SARS-CoV-2 that may blindside us further down the road. Outside the N-terminal and receptor binding domains in the virus sequenced from the Boston patient are a couple more mutations worth mentioning, even though their purpose remains largely unknown. One substitution, I870V, falls between the fusion peptide and heptad repeat 1 regions of the spike. It is worth noting there are more changes in the viral genome, like ORF1a and ORF1b, where a deletion and three point mutations are located. In the next installment of this series, I will discuss the Pittsburgh patient, yet another individual case of Covid-19 that might have
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implications for variants that may contribute to recurrent seasonal infections. This article originally appeared in Forbes and is available online here: Persistently Infected Covid-19 Patients: A Potential Source For New Variants
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Rapid Spread Of Variants Across Europe Is A Dire Warning For The U.S. Forbes | February 17, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the thirteenth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, and part thirteen. Cases of Covid-19 are now found across all continents, but the global rollout of vaccines and declining case rates in several countries have brought hope to many. Globally, four vaccines have been approved for full use and six have been granted emergency authorization for limited use. As of mid-February 2021, more than 181 million doses have been administered across 79 countries. However, declining case rates in some areas do not tell the full story and as we are now witnessing the rapid spread of new variants. The efficacy of the current vaccines against these variants has not yet been confirmed and it is possible we are entering a new stage of the pandemic. The highly transmissible SARS-CoV-2 variants have now become the dominant strains in the UK (B.1.1.7), South Africa (B.1351) and South America (P.1). The B.1.1.7 UK variant accounts for approximately 96% percent of all new COVID-19 infections recorded in the United Kingdom. Worse still, a new study from the UK Government shows that the B.1.1.7 variant is more transmissible and linked to increased hospitalizations and deaths when compared to other forms of the virus. This gives us a disturbing preview of what is to occur in the U.S. in the following weeks and months if we do not implement vigilant public health protocols and rapidly expand genomic surveillance. 700
The UK variant accounted for a third of all viral samples examined at three major laboratories in England in December 2020, just over two months later the variant now accounts for 96% of all viral samples in the UK. In France, the UK variant is responsible for 15% of positive PCR tests cases nationwide (as of February 11, 2021) and over 37% of positive tests in the Île-de-France region. Biogroup performs 25% of the RT-PCR tests carried out in France and developed the graphic below to demonstrate the UK variant’s prevalence across France from February 1 - 7, 2021 based on their testing. Seven variants of U.S. origin have been discovered and CDC director Dr. Rochelle Walensky has projected that the UK variant could become the dominant virus by March. We have already seen evidence of how quickly the California variant B.1.429 and the collection of viruses with the 677 mutation expands through the population. In mid-December 2020, the B.1.429 variant accounted for almost one-third of all cases in Southern California. By late January 2021, the B.1.429 accounted for more than 50% of all isolates tested as measured by Cedars Sinai Hospital. The emergence of the B.1.429 variant coincides with a sharp increase in infections as well Covid-19 related hospitalizations and deaths in Southern California.A preprint study shows that between December 2020 and January 2021, the collection of viruses with the Q677H mutation represented 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. More recently it was reported in the mainstream press that two variants of concern B.1.1.7 UK variant and the California B.1.429 variant may have combined their genomes to form a heavily mutated hybrid version of the virus, with properties yet to be determined. With more variants and mutations than any other country, the U.S. will soon be facing similar or even more dire challenges than Europe if swift action is not taken to stop the spread of variants. We risk losing the progress we have made in declining case rates and unleashing a new epidemic. The U.S. currently sequences less than 1 percent of all coronavirus test samples. It is likely that the variants are spreading faster than the limited data we are recording. This is simply unacceptable when we have the capacity for far greater surveillance. We need a Federal strategy that coordinates and standardizes the reporting process from different labs. Failing to 701
invest in a national strategy for genomic surveillance would echo the failure to establish a national testing infrastructure in the pandemic’s early days. A costly mistake we cannot afford to repeat. Not only do variants need to be identified through genomic sequencing but they also need to need to be characterized so we can develop appropriate defensive strategies whether they be public health measures or medical developments. Until we know how each variant evades or reacts to natural or acquired antibodies, those who have been vaccinated need to remain cautious and follow public health guidelines. Now is not the time to be loosening Covid-19 restrictions as many U.S. states are. Danish public health officials, who have one of the most robust surveillance systems, warn other countries not to ignore genomic sequencing of variants. They emphasize if it were not for their extensive monitoring, they would be feeling a false sense of confidence and would risk exposing their population to dangerous variants by rolling back restrictions. There is a growing consensus amongst the scientific community that this pandemic will eventually evolve into an endemic. This means we will continue to deal with variants as they arise. As we develop systems to gather more data and learn more about how the virus mutates and how that impacts our immunity, this process will get easier. But until then, we cannot begin to roll back restrictions until we have a clear picture of how the rapidly spreading variants will affect us. This article originally appeared in Forbes and is available online here: Rapid Spread Of Variants Across Europe Is A Dire Warning For The U.S.
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This Region Of The Covid-19 Virus Is One We Can’t Ignore Forbes | February 17, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the thirteenth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, and part twelve. In my last two articles, I went over the case studies of the London and Boston patients. Both were immunocompromised and persistently infected with Covid-19. Both also had, in the samples of SARS-CoV-2 taken from their bodies by researchers, mutations that arose independently, but were identical to those seen in new variants of the virus—a phenomenon previously documented by Jesse Bloom and his colleagues in influenza viruses. These cases and many similar to theirs, I argued, open up a window into what this virus has in store for us. Which brings me to my next subject, one I’ll call the Pittsburgh patient, whose story was documented in a study published in Science magazine earlier this month. Prior to their positive Covid-19 diagnosis, this patient was being treated for cancer and, the authors of the study note, already immunocompromised. The Pittsburgh patient endured severe Covid-19 for about two and a half months before succumbing to the disease. Like the London and Boston patients, while hospitalized the Pittsburgh patient received a multiplicity of experimental therapies, including the steroid dexamethasone, the antiviral drug remdesivir, and two rounds of convalescent serum, or preparations of highly neutralizing antibodies collected from recovered Covid-19 patients (Figure 1). These treatments put pressure on the virus to evolve— 703
and evolve it did, though in ways that diverge from the cases of other persistently infected patients. What remained consistent across all three, however, is that these mutations evidently gave SARS-CoV2 some sort of advantage, or it wouldn’t have persisted so long. Most of the mutations of note in the London and Boston patients occurred in the spike protein’s receptor binding domain, the target for many drugs and vaccines, as well as the furin cleavage site. Almost all were also point mutations, changes that affected only one amino acid at a time, with the exception of a few deletions. This wasn’t so for the Pittsburgh patient, who had far more deletions in their viral genomes than any other kind of mutation. Additionally, the vast majority were clustered in the N-terminal domain: Δ69-70, Δ141144, Δ144-145, Δ146, Δ210, and Δ243-244 (Figures 2, 3, 4). If there were mutations in other regions of the virus, they weren’t explicitly stated in the study. The absence of mutations in the receptor binding domain makes the Pittsburgh patient an outlier. Yet the end result is ultimately the same—the virus persists far longer than normal. Most of the adverse outcomes we’ve attributed to the new SARS-CoV-2 variants— increased transmissibility, immune evasion, and so on—we trace back to point mutations located in the receptor binding domain. But these variants also have mutations in the N-terminal domain that we’d be remiss to neglect. The data on the Pittsburgh patient does indeed suggest that we should pay far more attention to deletions and the N-terminal domain more broadly as potential effectors of change, particularly when it comes to how the virus interacts with the immune system and vice versa. A number of laboratory experiments show that a variety of mutations in the N-terminal domain create resistance to the effects of convalescent sera. The overall function of this globular region of SARS-CoV-2 may be unknown, but I’ve speculated, based on its distinct shape, that in the new variants it could either be increasing affinity as a second receptor or deleting antigenic sites where monoclonal antibodies bind. Some of the deletions in the Pittsburgh patient we’ve seen before, both at the individual and population level. Δ69-70, for instance, is present in the UK variant, B.1.1.7, while Δ243-244 is a feature of the South Africa variant B.1.153. Not to mention Δ141146 are nearly the same as deletions found in the Boston patient. 704
When Kevin McCarthy, the lead researcher behind the Pittsburgh patient study, cross-referenced this data with that of GISAID, a genome sequencing database for SARS-CoV-2 and influenza, he found that of all the viruses with deletions in the S protein, 90 percent of those deletions occurred in one of four sites in the Nterminal domain. This means the deletions in McCarthy’s study were prevalent in genomes sequenced all around the world. The case of the Pittsburgh patient makes one thing clear. If we don’t pay attention to mutations occurring across the entire breadth of the SARS-CoV-2 genome, we risk missing a piece of the puzzle that could prove to be significant for the variants to come. My next piece in this series will be on another persistently infected Covid-19 patient whose mutations might anticipate the ones we see in nature: the Italian patient. This article originally appeared in Forbes and is available online here: This Region Of The Covid-19 Virus Is One We Can’t Ignore
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How One Covid-19 Patient’s Infection Foreshadowed The Rise Of New Variants Forbes | February 18, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the fifteenth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, and part fourteen. Let’s recap my last few articles on parallel evolution, the term researchers have conceived to describe the ability some viruses have—namely, coronaviruses and influenza—to evolve independently of one another across multiple scales of time and space. Last week I discussed the origins of this theory in influenza research, the recent studies that apply it to SARS-CoV-2, and the London patient, the first of many immunocompromised and persistently infected Covid-19 patients with documented evidence of parallel mutations. Next in line was the Boston patient, followed shortly thereafter by the Pittsburgh patient. Through the lens of these case studies I examined the myriad aspects and potential consequences of viral variation—where it occurs, why it occurs, and what it means for the future of the pandemic. Today I’ll turn my focus to yet another case study involving parallel mutations, that of the Italian patient, which was published in The Lancet last month. Unlike the examples we’ve discussed thus far, the research paper doesn’t disclose whether or not this patient, a 59-year-old man, had underlying health conditions prior to his Covid-19 diagnosis. He did, however, experience a similarly persistent infection that evidently lasted a few months. Though the details regarding when the Italian patient’s disease course began and ended, as well as the treatments he received, if any, also aren’t 706
elaborated, researchers were able to extract and sequence viral samples at least twice, first in August and again in September. They then compared these samples with isolates of SARS-CoV-2 strains that were circulating in Italy either concurrently or earlier on in the pandemic. One of the more striking implications of the theory of parallel evolution is that some of the mutations that develop in persistently infected Covid-19 patients either appear in or foreshadow new variants that emerge and become dominant in the wider population. Excluding D614G, the mutation that reached near universal prevalence among active strains last spring, the viral sample taken from the Italian patient in August had a total of nine mutations that distinguished it from early strains (Table 1). Three were located in the ORF1a region of the virus (D1639N, P4715L, and A6914V), two in the receptor binding domain of the spike protein (Q493K and N501T), two in the N-terminal domain of the spike protein (K182N and L242 del), and two in the N protein (R203K and G204R). Of these nine, the easiest to make inferences about are in the receptor binding domain, a key target for Covid-19 drugs and vaccines (Figure 1). The most recognizable is N501T, an amino acid change that occurred in the same position as N501Y, one of the defining characteristics of the B.1.1.7 (UK), B.1.351 (South Africa), and P.1 (Brazil) variants. It also appeared independently in the viral genomes of the Boston and London patients. Thanks to laboratory experiments, we now know that N501Y—shorthand for the substitution of the polar, uncharged asparagine with tyrosine, a larger nonpolar molecule—increases the affinity of the virus, though most likely with only minor changes to immunogenicity. N501T, which sees asparagine swapped for threonine, is far less dramatic, but still notable for its symmetry. While another spike protein mutation, Q493K, has yet to make an appearance in a globally prevalent variant, it marks another point of convergence between the Italian and Boston patients—a parallel that warrants further investigation. Not for nothing, the same in-lab studies that confirmed the increased affinity of N501Y found that another mutation at the 493 site, Q493H, had a comparable effect. In my story on the Pittsburgh patient, I argued that the Nterminal domain is one to watch due to the significant effect 707
mutations in the region have on the ability of SARS-CoV-2 to evade our immune defenses, whether naturally produced or mediated by preventive medicine. The N-terminal domain mutations of the Italian patient (K182N and L242 del), though not identical to any we’ve seen thus far, do fall within close range of the deletions at the 183 and 242 sites that occurred in the Pittsburgh patient, as well as a Q183H substitution noted in the Boston patient. The B.1.351 (South Africa) variant also has a deletion in the 242 position. Moving on, the second sample collected from the Italian patient in November had three new mutations in addition to the original nine, two of which were located in the ORF1a region (R5661C and V6207I) and one in ORF3a (L108F). Though the significance of mutations in these areas isn’t widely understood, like the Nterminal domain the ORFs may have a role to play in modulating the efficacy of SARS-CoV-2 that will become either more discernible or more deleterious down the line.* All the more reason to keep a close eye on both. While the case study of the Italian patient doesn’t substantiate the theory of parallel evolution as neatly as, say, the London or Boston patients, the parallels become clearer when we take into account local transmission in his country of origin (Figure 3). Italian researchers estimate that by the time they analyzed the first sample from the patient in August, variants with alterations to the 501 site were already circulating in northern Italy. A lack of genomic surveillance, not just in Italy but worldwide, helped these variants remain under the radar—until September, that is, when reports of the B.1.1.7 variant and its signature N501Y mutation first emerged. If their predictions are true, this means the Italian patient did in fact foreshadow the arrival of more infectious strains. To say so may be too little too late, but not if we learn from this lesson going forward. It is not only possible, but highly likely that Covid-19 will become a seasonal phenomenon, just like influenza and its coldcausing coronavirus cousins. In light of this, it becomes the task of scientists everywhere, myself included, to analyze the clinical and epidemiological data we currently have in our possession and make interpretations that will guide us in the future. The evidence that SARS-CoV-2 is a wily, capable, and ruthlessly adaptable adversary is piling up steadily. My next contribution to this body of evidence, 708
and this series, will be an examination of the 677 mutations that are appearing in Covid-19 variants across the United States. This article originally appeared in Forbes and is available online here: How One Covid-19 Patient’s Infection Foreshadowed The Rise Of New Variants
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How will the Coronavirus Evolve? Scientific American | February 19, 2021 | Article
With declining rates of new infections and the rollout of vaccines, some are beginning to speak of an end to COVID-19. But that rhetoric, in my opinion, is ill-considered and premature. Based on what we know now of SARS-CoV-2, it may no longer be a question of months before an end to the pandemic but a question of years, if not decades. We should plan for it. Viruses exist to thrive. Those that infect humans are faced with an impressive array of defensive weaponry, not just our natural adaptive immunity but also our intelligently designed defenses— vaccines, drugs and social controls. For a virus to survive, it must be adapted to its chosen ecological niche—in this case, us—and capable of further intricate adaptation to overcome our best efforts at prevention and treatment. Initially, many assumed that coronaviruses in general and SARSCoV-2 in particular were more stable and less prone to adaptation than other RNA viruses because of their error-proofing mechanisms. But we have since been proven wrong. Last summer, a researcher in Texas noticed that a mutated SARS-CoV-2 virus with a substitution in the spike protein had overtaken previous forms to become the dominant strain. Since then, multiple new variants have emerged with mutations that can make the virus more transmissible, more lethal and more able to evade our immune defenses. These variants have seemingly been forged in fires of our own making. In Boston, a middle-aged man struggled with a COVID-19 infection for five months before succumbing to the disease. He was undergoing treatment with immunosuppressive drugs when he fell ill, and, during his illness, he received multiple rounds of additional treatment, with remdesivir nonimmune gamma globulin, and with monoclonal antibodies. Under this intense immune pressure, key mutations in the virus emerged. The doctors and scientists who witnessed their birth called it “accelerated viral evolution.” 710
Other viruses, like influenza, have shown themselves similarly capable of rapid evolution when faced with our best defenses. Indeed, based on what we’ve seen of SARS-CoV-2 and its capacity for variation, I’d say this virus is much more like influenza than any other virus known to date. Which means influenza’s evolutionary pathway may hold important clues about the road COVID-19 will follow. Influenza, as we know, comes and goes in seasonal waves in the Northern and Southern Hemispheres. In the tropics it occurs throughout the year, with only shallow peaks. This pattern mimics what we know of cold-causing coronaviruses, which, ever since their discovery in the 1960s, have returned annually to infect us. For the flu, antigenic drift—the accumulation of small genetic changes in the virus—has been the primary explanation for recurrent seasonal epidemics. Dominant flu strains evolve from year to year, and the immunity we develop in response to a previous strain has only a muted effect on the new strain. We’ve learned more recently that immunity to influenza also fades, often disappearing within a year, which also makes us susceptible to reinfection. We used to believe that the cold-causing coronaviruses were stable—meaning no antigenic drift—but returned yearly because of faded immune protection. But over the past year, our understanding of coronaviruses has improved and we now know that at least one of the cold-causing coronaviruses, designated 229E, undergoes antigenic drift similar to that of influenza. SARS-CoV-2, like 229E, has already shown that it can drift. But, like influenza, it has also shown itself capable of much more abrupt and substantial changes. One way these major changes happen occurs when a virus jumps to a new population, for example from animals to humans or back again. When a virus makes this jump, big things—and often bad things—materialize. Both influenza and SARS-CoV-2 have huge animal reservoirs. Coronaviruses have infected every type of vertebrate, from whales and bats to salamanders and snakes. Influenza is similar. This means they both have the potential to evolve to become much more damaging to our population. The two previous coronavirus outbreaks both started when coronaviruses jumped from animals to humans, from civet cats in 2003 with SARS and from camels with MERS in 2012. The 1918 influenza pandemic likely started with a jump from animals too. 711
If we’re lucky, SARS-CoV-2 will evolve, like the 1918 virus dubbed the “Spanish flu,” to become less lethal. After infecting an estimated 500 million worldwide and killing at least 50 million, the 1918 flu virus receded. But hope that this coronavirus will attenuate over time is no guarantee that it will. We already know that coronaviruses can become much more lethal; we need look no further than SARS-CoV-1, which killed 50 percent of those aged 65 and older, and MERS, which killed one out of three infected. First, we must accept the harsh truth told by this virus and its variants. We can expect it to come back—potentially for years to come—and we need to prepare ourselves for the possibility that when it does, it may be more lethal and even more transmissible than the variants that exist today. We must adjust our vaccine development pipelines and public health interventions to account for emergent and future variations. Much like what has been proposed with influenza, we must develop COVID risk assessment tools that can identify the viral properties of dominant strains—how transmissible they may be or how resistant they are to current drugs or vaccines—to help us align our public health response with the level of risk. Otherwise, we’ll be setting ourselves up for failure once more. I have often likened SARS-CoV-2 to the mythical Proteus in Homer’s Odyssey. Like Proteus, SARS-CoV-2 is the quintessential shape-shifter, able to alter its form whenever grasped. It is only through sheer persistence that Menelaus, the great hero, is able to wrestle Proteus to a standstill. By claiming victory too soon, we risk losing our battle with this shape-shifting virus, a tragedy that would unfold this time not in words but in many more millions of lives lost.
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What Are The 677 Mutations? New Covid-19 Variants Found In The US Forbes | February 19, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the sixteenth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, and part fifteen. This winter, new variants of SARS-CoV-2 have taken the world by storm. They have emerged in corners of the globe as disparate as Brazil and the United Kingdom; exhibited an array of new and worrisome properties, ranging from increased transmissibility to immunogenicity; and complicated our best efforts to collectively mitigate the spread of Covid-19 through public health measures and vaccines. Earlier this week I wrote a piece detailing why this trend is so concerning for the United States, where variants of concern have been identified in states like Ohio and California but otherwise remain relatively under the radar, circulating unbeknownst to most Americans. In today’s installment, I want to focus on the recent appearance of what researchers are calling the 677 variants, a crop of lineages that at least for now seems confined to the US alone. A hallmark of viral variation is that the tiny alterations distinguishing one variant from the next can arise in separate locations at the same time, developing independently of one another. One example is the N501Y spike protein mutation that is known to increase the affinity of the virus for our ACE2 receptors. N501Y was first spotted in the genome of the B.1.1.7 (UK) variant, but it didn’t take long for scientists to discover its presence in the B.1.351 (South Africa) and P.1 (Brazil) variants as well. Another spike protein mutation linked to immune escape, E484K, has also 713
acquired high global frequency, appearing first in B.1.351 and more recently in B.1.525, the latest variant to wash up on British shores. The 677 variants, according to a preprint study published last week, are similar in that they were first detected in October by genomic surveillance programs nearly a thousand miles apart. They’re named for their one commonality—mutations at the 677 amino acid site. In Louisiana, where one of the programs to successfully trace them is located, researchers found that the proportion of SARS-CoV-2 viruses in local circulation carrying a Q677P mutation rose from nil to nearly a third (28 percent) between early December 2020 and late January 2021. Within the same timeframe, the mutation’s prevalence in New Mexico, where the other program is based, shot up to just over 11 percent. The researchers were so intrigued by the convergence around the 677 site that they decided to seek out other 677 point mutations by conducting phylogenetic analysis on available genomic data (Figure 1). One mutation, Q77H, appeared in six distinct lineages from August to November 2020. Though four of the six were confirmed in only about 100 Covid-19 cases or fewer, the remaining two popped up with considerably more frequency—one with nearly 300 cases and the other close to 800. Slight as these figures may seem compared to the 28 million cases reported in the US so far, given the relative paucity of US genomic sequencing efforts they do indicate a potential for further spread. I’ve written previously about a variant spreading rapidly in Columbus, Ohio that has the Q77H mutation, though in that particular state the UK B.1.1.7 variant is reportedly disposed to become the dominant stain by March or April, according to Dr. Bruce Vanderhoff, their chief medical officer. The emergent B.1.525 variant, which has been identified in Nigeria, Denmark, the UK, and several other countries, also carries the Q77H mutation, making it the only international variant to do so. But beyond that, mutations on the 677 site are conspicuously absent from all the variants that have become dominant around the world thus far, appearing almost exclusively in nascent lineages in the US. Though mutations at the 677 site haven’t been observed in most of the new variants spreading around Europe, South America, and elsewhere, others have that are also located in the gray area between the receptor-binding and fusion peptide domains. The B.1.1.7 (UK) 714
variant, for instance, has a P681H mutation just a few amino acids away, while a mink variant making the rounds in Denmark has an I692V mutation in similarly close range (Figure 2). The 677 site is also not far from the furin cleavage site, located between the S1 and S2 proteins at amino acids 685 to 686. I’ve speculated in my new book Variants! that an additional furin cleavage site, which decorates the surface of the virus with spikes that are primed and ready to go, is one of the reasons SARS-CoV-2 is so infectious. It may be the case that the 677 mutations enhance this mechanism—akin to adding a hair trigger to a cocked pistol—but much more research is needed before we can say this with certainty. In my next piece, I’ll go over why the new variants represent an opportunity for the US to reevaluate and upgrade its public health protocols. More than just preventing the worst, these measures will be a move towards the level of pandemic preparedness that will protect us from future outbreaks of Covid-19 and any other diseases to come, no matter how various they may become. This article originally appeared in Forbes and is available online here: What Are The 677 Mutations? New Covid-19 Variants Found In The US
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UK Approves Human Challenge Trials For Covid-19, But At What Cost? Forbes | February 19, 2021 | Article
When the UK’s Covid Vaccine Challenge was initially announced — a study set to deliberately infect healthy people with SARS-CoV2 — I and many of my colleagues in science and public health condemned the approach. Human challenge trials can be useful, but they come at a risk to healthy volunteers. Only when we are absolutely certain that the benefits outweigh the risks should we proceed. This week, the UK government confirmed the trial would go forward as planned, but we are nowhere near the threshold that would warrant such a dangerous endeavor. The risk to the 90 healthy volunteers who will be recruited for this trial is very real. The press release announcing the challenge claims that “the safety of volunteers is paramount” and highlights how only healthy young adults will be chosen. Yet it ignores the mounting evidence that even a mild case of Covid in a healthy young adult can lead to long term lung damage and other potentially serious lifelong symptoms. To make it worthwhile to put 90 healthy young people at risk for lifelong illness, the benefits have to be very real. But the reality is that this trial is likely to prove relatively meaningless. Since the issue of human challenge trials for Covid-19 was first introduced last year, our understanding of the virus has evolved dramatically. We now know that the virus can change, and it can change quickly. One of the primary purposes of this vaccine challenge, at least according to the release, is to establish “the smallest amount of virus needed to cause infection, which will give doctors greater understanding of Covid-19 and help support the pandemic response by aiding vaccine and treatment development.” Yet given what we know of SARS-CoV-2 today, it is highly likely that the virus used in the challenge expected to begin in just a few weeks will be markedly different than the virus that the world will be dealing with when the results are released. 716
Take the UK variant of the virus, otherwise known as B.1.1.7. That virus is known to be up to 75% more transmissible than any previously known strain. We know, from another study in a lab setting, that SARS-CoV-2 can mutate beyond that level of transmissibility to become up to 600 times more transmissible than any of the variants seen to date. So whatever data we discover from this trial may become moot within days, weeks, or months, when the world is faced with a newer, more transmissible variant, able to infect with far fewer particles. Beyond that basic fact, there is no need to actively infect healthy individuals when we are going to have real comparison data to work with from the millions of people already vaccinated and the hundreds of millions more who will be vaccinated in the near future. What could possibly be the reason behind actively infecting healthy people while the same data could be garnered through other, less risky means? I can’t help but wonder if the answer doesn’t have more to do with national or economic gain rather than public health. A vaccine challenge would allow the UK to test its own national vaccine champion, the Oxford vaccine, against the virus, perhaps putting it an advantage at the risk of human lives. I sincerely hope this is not the case. But I have yet to read or hear another rationale that makes more sense. Yes, we need to develop new and second generation vaccines. Yes, we need the data to support their development. But risking the lives of ninety healthy volunteers isn’t the way to do it, when we have so many other options at hand. This article originally appeared in Forbes and is available online here: UK Approves Human Challenge Trials For Covid-19, But At What Cost?
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NBA Study Reveals The UK Variant May Last Longer In Human Hosts Forbes | February 19, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the seventeenth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, part fifteen, and part sixteen. As variants account for a more significant proportion of global Covid-19 day-by-day, we have to adjust our public health policy accordingly. SARS-CoV-2 variants possess a well-documented bag of tricks. Some are immune-evading, like the South African and Brazilian variants, and others are far more transmissible, like the United Kingdom variant (B.1.1.7). A recent study from the Harvard University School of Public Health suggests that B.1.1.7 may even remain in human hosts nearly twice as long as non-B.1.1.7 SARSCoV-2, extending the potential contagious period from about eight days to thirteen days. The study was conducted in conjunction with the National Basketball Association (NBA). In Summer 2020, the NBA restarted their season after it was paused by the start of the Covid-19 pandemic. The players involved were isolated at Disneyworld resort and were administered daily Covid-19 testing. That practice expanded to the recently begun 2020-2021 season, and Harvard University took the opportunity to genome sequence the basketball players’ samples for research purposes. The Harvard researchers identified seven samples infected with B.1.1.7 among a cohort of 65 individuals infected with SARS-CoV2. “For individuals infected with B.1.1.7, the mean duration of the 718
proliferation phase was 5.3 days, the mean duration of the clearance phase was 8.0 days, and the mean overall duration of infection was 13.3 days. These compare to a mean proliferation phase of 2.0 days, a mean clearance phase of 6.2 days, and a mean duration of infection of 8.2 days for non-B.1.1.7 virus.” Additionally, peak viral concentrations for B.1.1.7 were slightly higher than non-B.1.1.7 patients, 8.5 log10 RNA copies/ml for B.1.1.7 and 8.2 log10 RNA copies/ml for others on average. In other words, the B.1.1.7 patients experienced extended infections with more viral particles, as displayed by the graph above. The overall viral burden for those with B.1.1.7 was higher than their non-B.1.1.7 counterparts on average for a greater period of time. The extended duration of B.1.1.7 is likely associated with its increased transmissibility. The Centers for Disease Controls and Prevention (CDC) state that B.1.1.7 transmits at 50% the rate that non-B.1.1.7 SARS-CoV-2 is capable. The virus is adjusting to our immune responses, and now, we see the B.1.1.7 capable of withstanding the human immune response over 60% longer than previous viruses. Respiratory viruses typically have shorter lifespans and must jump from host to host quickly to survive and spread, but this virus sticks around for a while. Longer infections mean the virus has the opportunity to spread to more people, increasing infections, which leads to greater spread, and the positive feedback loop continues. This is deeply concerning. As I’ve written about for Forbes, the CDC recommends that infected people remain in quarantine for 14 days but only require seven or ten days of quarantine based on the patient’s individual circumstances. If the B.1.1.7 variant infects someone and they only quarantine for seven to ten days, they may go on to infect others thinking they are free of the virus. In response to the growing concerns of rapidly spreading SARSCoV-2 variants, the Chinese government increased their required isolation period to three weeks in the past few months. This more than encompasses the 13.3-day duration the Harvard researchers observed from the B.1.1.7 variant. While the authors of this research focus on transmissibility, it may also go a long way to understand virulence. Those that are infected with B.1.1.7 have a higher probability of dying from the infection. Spike protein mutations like those found in B.1.1.7 719
increase transmissibility by increasing affinity to the human ACE2 receptor. That may not be the whole story. During the extended period of time B.1.1.7 survives within the host, it must fend off the immune system. SARS-CoV-2 specifies immune modulators like ORF3a, ORF8, and others. These may be altered during the virus’s extended stay, resulting in greater virulence and chance of death. If we are to control these variants before they become out of hand, we need to adjust public health policy accordingly. As the Chinese have done, we should extend quarantine requirements to three weeks. Of course, people cannot be out of work for three weeks without pay. As I have been championing for months upon months, the federal government must assist those in isolation, financially, as well as with medical supplies and shelter if necessary. We must also further understand how B.1.1.7 and other variants pull off these dangerous tricks of immune-evasion, increased transmissibility, and virulotion. This data adds to the growing narrative around B.1.1.7 and SARS-CoV-2 variants in general. They are dangerous and adaptive, growing more accustomed to the human immune response with every infection. We must similarly adapt our public health approach to fight back and control these viral variants before we see a resurgence of the virus in the near future. This article originally appeared in Forbes and is available online here: NBA Study Reveals The UK Variant May Last Longer In Human Hosts
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Variants Could Cause A Rapid Rise In Covid-19 Cases In The U.S. Unless We Implement These Public Health Measures Forbes | February 19, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the eighteenth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, part fifteen, part sixteen and part seventeen. In a prior column for Forbes, I detailed how the rapid spread of variants across Europe should serve as a warning for the US. I explained how data from the UK, Denmark, Belgium and Switzerland collectively demonstrate that the UK B.1.1.7 variant predictably overtakes previously dominating strains progressing from 20% to 80% of the circulating viruses in just 4 weeks. The below model (Figure 1) shows that those countries could be facing new waves of epidemics as early as mid-March. The CDC has now issued a similar warning in the form of two new reports, suggesting that variants could cause a rapid rise in Covid-19 cases in the US, based on international and local examples. In one report, the CDC has used the international example of the country of Zambia in East Africa as a warning. After 3 months of relatively low case counts, Covid-19 cases began rapidly rising throughout Zambia in mid-December 2020. Among the 23 positive Covid-19 specimens collected during December 16–23, 2020 by the University of Zambia and PATH, 22 (96%) were classified as the B.1.351 variant demonstrating a clear link to increased transmissibility by the B.1.351 variant. The below chart (Figure 2) 721
tracks the evolution of Covid-19 cases in Zambia throughout the pandemic. The second CDC report, details an investigation into the spread of the first identified cases of the B.1.1.7 UK variant in Minnesota and urges the public to engage in “mitigation measures such as mask use, physical distancing, avoiding crowds and poorly ventilated indoor spaces, isolation of persons with diagnosed COVID-19, quarantine of close contacts of persons with COVID-19, and adherence to CDC travel guidance.” A recent preprint study gives a more thorough picture of the spread of the B.1.1.7 UK variant throughout the U.S. The study used the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K. as a proxy for B.1.1.7 detection. Through this method, they found detection of the B.1.1.7 UK variant in the U.S. from December 2020 to January 2021 increased at a logarithmic rate similar to what has been observed overseas with a doubling rate of a little over a week and an increased transmission rate of 35-45%. The study shows that community transmission enabled the B.1.1.7 UK variant first detected in late November 2020, to spread to at least 30 states as of January 2021. More recent CDC data shows the B.1.1.7 UK variant has been detected in 41 states and Washington, DC. The below chart (Figure 3) shows the rapid spread of the B.1.1.7 UK variant in different U.S. states and the U.S. overall. In addition to studies on the UK B.1.1.7 variant, we have already seen evidence of how quickly the California variant B.1.429 and the collection of viruses with the mutation 677 spreads through the population. It is clear from these domestic and international examples that the U.S. needs to act fast to stop a potential rapid rise in Covid-19 cases stemming from new variants. Americans are becoming complacent as cases decline, but now is not the time to be rolling back restrictions as some states are. As seen in Figure 3, Florida has one of the highest concentrations of the UK B.1.1.7 variant, yet Governor Ron DeSantis has recently rolled back Covid-19 restrictions entirely and has not enforced a mask mandate. A mistake which could have dire consequences. The UK B.1.1.7 and South African B.1.351 variants have shown evidence of increased viral load which is associated with increased disease severity and mortality.
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Below I outline the public health measures that need to be taken to protect ourselves against the new variants based on what we currently know: Behavioral protocols The UK B.1.1.7 and South African B.1.351 variants have proven to be more transmissible which means fewer virus particles are needed to transmit the virus. When asked, I recommend the use of N95 masks with face shields to protect yourself and others. Cloth masks may no longer be sufficient as it is difficult to maintain the tight seal needed, especially in children. Everyone needs to accept a vaccine when available to them, but a vaccine is not a get out-of-covid free card. Currently, we know that Pfizer-BioNTech Covid-19 vaccine loses some potency against the South African B.1.351 variant. Until we have comprehensive data on the efficacy of all approved vaccines against the new variants, those who are vaccinated should still take precautions such as maskwearing, physical distancing, and avoiding indoor activities where possible. Travel restrictions and incentivized quarantining Six of the first eight people first identified with the UK variant B.1.1.7 in the CDC Minnesota investigation reported recent travel (three international and three domestic, none had traveled to the UK) further emphasizing that it is absolutely critical to avoid travel. Unfortunately, US Airports have seen some of their busiest days since the holidays. The TSA reported it screened more than 967,000 people at airports on Monday and a further 738,000 people on Tuesday. There needs to be better communication about the serious risks of traveling while these highly transmissible variants are developing. For those who cannot avoid travel, the CDC needs to stipulate mandatory testing for both domestic and international traveling, as currently it only requires the latter. I have repeatedly advocated for incentivized isolation, in which those who have or been exposed to or infected with Covid-19 are paid to quarantine at home, removing the potential burden of lost income. Those who cannot isolate safely at home should be offered a free hotel room, like the program run in NYC. With the highly transmissible nature of some variants, this has never been more critical.
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The length of quarantine should be based on the latest data available on the period of contagion for different variants. A small, not yet peer reviewed study was recently released by Harvard which analysed the daily PCR tests of 65 NBA players all infected with SARS-CoV2, seven of them infected with the UK B.1.1.7 variant. The mean duration of overall infection for the players infected with the variant was 13.3 days compared to the players infected with SARS-CoV2 who had a mean duration of infection of 8 days. While a relatively small sample, we should proceed with caution and extend our quarantine period to three weeks like China has done, until we have more comprehensive data. A comprehensive genomic surveillance system Biden’s investment of $200 million in virus genome sequencing is a welcome start, but it does not go far enough. Genome sequencing is one of our most important tools to track the developing variants and emerging threats, make timely public health decisions and update vaccines. We should also be tying genome sequencing to information such as robust contact tracing to more fully understand how the variants are spreading. We should be aiming to replicate the approach of the COG-UK Consortium and sequence at least 5-10% of all virus samples. The Biden Administration estimates that the $200 million investment will increase the sequencing capacity of the CDC from about 7,000 samples per week to approximately 25,000. If case rates remain consistent (which is unlikely) this number barely puts us at sequencing 5% of virus samples. A paper in Cell, encourages strong coordination between the entities performing diagnostic SARS-CoV-2 testing, the labs with the expertise, capacity, and resources to conduct relatively large-scale sequencing and computational groups who can process and analyze the large genomic datasets for an optimal genomic surveillance system. Due to the global nature of Covid-19 variants, the paper also suggests that the international community should also provide financial and technical support to bolster genomic surveillance in areas that are less resourced. By following these public health measures, such as avoiding travel, incentivized isolation, wearing N95 masks and face shields, physical distancing, avoiding indoor activities, and implementing a 724
comprehensive and coordinated genomic surveillance system we can avoid a potential rapid rise in cases stemming from the variants. This article originally appeared in Forbes and is available online here: Variants Could Cause A Rapid Rise In Covid-19 Cases In The U.S. Unless We Implement These Public Health Measures
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Beware The Next Wave: What To Expect From Covid-19 Forbes | February 22, 2021 | Article
Last week, the US hit its lowest number of daily new Covid cases since last fall, dropping to 53,800 from its high of 300,000 at the beginning of this year. After twelve months of watching cases steadily rise — twelve months that left many of us damaged, weary, and generally overwhelmed — many now cling to this new and encouraging trend as a sign of hope that the end of the pandemic could finally be near. Unfortunately, in my opinion, we are nowhere close to the end. But we may be approaching a welcome reprieve from our current tragedies and an opportunity to prepare for a much longer battle ahead. Based on what we know of the virus that causes Covid-19, I believe we can expect the disease to return in waves each year. Longlasting population or herd immunity like what we have for polio or the measles is not, in my opinion, a possibility for Covid-19, even with a vaccine. What we can expect instead is seasonal population immunity, with patterns of infection and reinfection that mirrors what we see with the flu. Influenza viruses and coronaviruses have many similar characteristics which should lead us to expect similar patterns of infection. Both viruses have proven able to evolve to escape our best defenses, be they vaccines, drugs or our own natural immune protection. This ability to shift shape is partly why influenza comes back each fall and winter in the Northern and Southern hemispheres to reinfect us. The dominant flu strain from one year is different from the flu strains that dominate in subsequent years, having accumulated small genetic changes as the virus passes through individuals, within communities, and in and out of other populations, like animals. Any immunity generated in response to a previous strain has only a limited effect, if any, in preventing infection from the new strain.
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Based on what we know of SARS-CoV-2 and the cold-causing coronaviruses which have long circulated in our communities, coronaviruses can do the same. The first time we noticed SARSCoV-2’s ability to evolve was last summer, when a virus with a mutation in its spike protein became the dominant strain. Since then, multiple new variants have emerged, often appearing in people who had been fighting the infection over a period of months, giving the virus time and opportunity to adapt to and evade the patient’s natural immune response and medical treatments. The virus can shift, like the flu, within a single patient, as it circulates between people, and even as it jumps from humans to other populations. Early in the pandemic, we suspected that reinfection by SARSCoV-2 was possible, but now we know it to be true. The latest case of reinfection is a man in France, initially infected in September and reinfected in January with the South African variant of the virus. Perhaps the most troubling part of the story is that though his first infection came and went with relative ease, whatever immunity he developed has done little to protect him against severe disease this second time around — he is now hospitalized and critically ill from the second infection. This real world reinfection adds emphasis to the results that scientists in China had already generated in their labs — SARS-CoV-2 can mutate to reinfect those who have already generated immunity to a previous strain of the virus. The likelihood of reinfection is exacerbated by the fact that immunity to SARS-CoV-2 fades over time, again like the flu. With influenza, recent studies have shown that immunity often disappears within a year, potentially allowing the same strain of the virus to reinfect the same person after their immunity fades. With SARSCoV-2, the timeline may differ but the end result is the same. From what we know today, naturally induced immunity from neutralizing antibodies can begin to decline as early as three months after infection. While we suspect that even a declining level of neutralizing antibodies can still afford someone protection against reinfection by the same strain of the virus, it’s unclear how long that protection might last. What we know with certainty is that eventually those antibodies disappear. Protection afforded to us through vaccination may last longer, but it is still unclear for how long.
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With all the similarities between influenza and coronaviruses and how our bodies respond to infections from each, we should look at the decline in infections today in the same way we look at the decline in new flu infections which has also been dropping since the start of this year. Enough people may have been infected with the current dominant strain that we are now achieving some degree of seasonal immunity. But the curve of new infections will tilt upwards again once immunity fades or a new strain of the virus takes hold and begins to reinfect widely. This means we must act now. We likely have only a short window of time before infections begin to rise again. If we double down on current public health efforts — mask-wearing and social distancing — and reinforce them with additional tools, such as widespread testing, contract tracing and mandatory isolation, we may be able to bring new infections down to near zero. This would be an enormous achievement and, maintained over time, would allow us to track and trace new infections, preventing a new outbreak the size of what we saw this past year from ever occurring again. But there are two outlying conditions that could throw us for a loop. First, the variants. The ones we know of — the UK variant, the South African variant, the Brazil variant, and our own homegrown variants — are already proving far more transmissible than previous strains. Some are also more lethal, some more effectively evade our immune responses, and some are proving resistant to some of our vaccines. Recent reports suggest that some of these variants have even recombined, forming a newer heavily mutated virus. This, in itself, is bad news. But the news could get much, much worse. Lab studies suggest the virus could become up to 640 times more transmissible than current strains. If a highly transmissible variant took hold in the US, all bets on bringing infections down to near zero would be off. If that variant was also more lethal — remember SARS-CoV-1 killed 50% of those aged 65 and older and MERS killed one out of three infected — the results would be catastrophic. The second outlier is, oddly enough, ourselves. To date, Americans have not proven willing to make the sacrifices required to come close to near zero infections. We’ve refused to wear masks, refused to quarantine, and generally questioned any attempt to restrict individual liberty in the name of public health. I appreciate 728
the debate, but every delay in our willingness to act comes at the expense of American lives. There is no time to lose — we tried last April to flatten the curve, and we failed. We tried again in July when new cases surged again, and we failed again. This may be our last chance. This article originally appeared in Forbes and is available online here: Beware The Next Wave: What To Expect From Covid-19
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Questions The FDA Must Ask Drug Makers As It Considers Full COVID-19 Vaccine Approval The Hill | February 22, 2021 | Article
With attention firmly focused on the COVID-19 vaccine rollout in the United States, a key point in the process has been largely overlooked: full approval of the vaccines themselves. The vaccines currently being distributed and administered across the U.S. are still approved only under the U.S. Food and Drug Administration’s (FDA) Emergency Use Authorization. Full vaccine approval normally takes five to ten years. But rumor has it that FDA approval for COVID vaccines may come as early as this year. The approval process gives the FDA an opportunity to ensure we have the long-term data needed to make use of the vaccines as a tool to stem the pandemic. While some hold out hope that mass vaccination alone will bring an end to the pandemic, from what we know today about the virus and its ability to mutate and evolve, there’s no guarantee it will. With the approval process, the FDA can move us closer to that goal. There are some pieces of data that we will definitely have access to through the FDA approval process. We now have roughly eight months of clinical trial data on some of the vaccines, including realworld data since distribution began. The approval process will likely give us access to the data showing, over the course of the full eight months, whether the vaccines provide robust protection from infection or from serious or severe disease. We’ll also receive more definitive evidence about the safety of the vaccines which, at least so far, do not seem to be causing major, widespread concerns. But the FDA can go much further as they consider full approval for the vaccines, and ask the vaccine makers to provide more information about other aspects of how the vaccines are performing. First, we need to dig into the details of vaccine efficacy and the durability of the protection it affords us. The antibodies to even the best of the vaccines will no doubt fade over time, but to what extent? Do the levels of neutralizing antibodies generated in response to the 730
vaccines drop quickly or slowly and at what point does it fade away entirely? And what of the T cell response and how it may change over a period of one, two or five years? Will we need booster shots or to be revaccinated every year? A more technical question that the FDA can help us answer is whether adenovirus vector vaccines, if proven effective against initial infection, can be used as boosters or for revaccination if needed. Possibly the biggest question that the FDA could help us answer is around the effectiveness of vaccines against variants of the virus. We already know that variants can be more transmissible and that some are also more lethal and better able to evade our immune protections. We can also assume that as our immune protection from a vaccine fades over time, we may be more susceptible to infection by the variants. In addition to asking companies to provide data on known variants, the FDA can ask them to collect and share data on the vaccine’s efficacy against new variants, as they appear. The final question the FDA can ask the companies to answer is whether the vaccines can stop the pandemic by inhibiting both infection and transmission. While it’s tempting to believe that an effective vaccine automatically prevents further transmission of a virus, the truth is that not all vaccines can manage both sides of the equation. For example, the inactivated polio vaccine developed by Jonas Salk does an excellent job of triggering an immune response that can prevent illness, but it doesn’t stop people from transmitting the virus to those around them. It wasn’t until the oral polio vaccine was developed that we had a vaccine that could do both. This article originally appeared in The Hill and is available online here: Questions The FDA Must Ask Drug Makers As It Considers Full COVID-19 Vaccine Approval
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New SARS-CoV-2 Variant Discovered In Japan Nearly Identical To Dangerous Brazilian Variant Forbes | February 22, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the nineteenth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, part fifteen, part sixteen, part seventeen, and part eighteen. As the scientific community becomes keenly aware of the dangers SARS-CoV-2 variants present, increased sequencing efforts seek to uncover new mutants before they begin to spread widely in the population. Among the new variants discovered in recent weeks is the Japanese variant (B.1.1.248) identified both through spread in the community and in their Covid-19 isolation facility. This viral mutant is nearly identical to the Brazilian (P.1) variant and carries similar mutations to the infamous United Kingdom (B.1.1.7) and South Africa (B.1.351), but also has one mutation unique to its structure, further complicating the Covid-19 puzzle for Japan and the world. In early January, The National Institue of Infectious Diseases in Japan detected a new variant of SARS-CoV-2 in travelers arriving from Brazil a few days earlier. The new variant carried identical mutations to the spike protein as P.1, aside from one additional point mutation—V1176F. Notably, B.1.1.248 carries the N501Y mutation, which is documented to increase the virus’s transmissibility, and E484K, which increases the virus’s resistance to
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neutralizing antibodies. Mutations to other proteins were not included in the published literature. P.1 is a particularly nasty variant of SARS-CoV-2. It has reinfected people in Manaus, making them sick once again after infection earlier in the pandemic. It is also highly transmissible and reportedly resistant to antibodies from both vaccines and monoclonal antibody therapies. The unique point mutation V1176F is located in the second heptad repeat of the virus. The heptad repeats form a helix structure centrally-located on the virus. These helical bundles are essential for the viral fusion of the virus to the human cell. A mutation to this region may increase the transmissibility of the virus by optimizing viral fusion, but further investigation is necessary to confirm this hypothesis. Japan’s Covid-19 timeline mirrors that of the United States. In April and July, there were spikes in infections. Late October through mid-January saw an explosion in cases, peaking around January 9th. Recent weeks have brought about much lower infection rates as the third wave has seemingly passed, but a new, more transmissible and antibody-resistant variant could complicate progression. The new variant has been detected in 93 cases throughout the country, according to Chief Cabinet Secretary Katsunobu Kato, but that number is likely higher due to unreported cases. Ideally, these cases would be isolated to prevent further spread, but only time will tell if B.1.1.248 creates more significant inroads in the country. B.1.1.248 is but a short entry in a more extensive Covid-19 anthology. As we continue vaccination efforts worldwide, variants potentially resistant to vaccines are appearing in tandem, including the Japanese variant. B.1.351 has even recently been detected in the United States. Not to mention, there may be other point mutations that have similar or greater effects on antibody resistance yet to emerge. In the past month, many countries have seen a deep decline in Covid-19 cases, like the United States and the United Kingdom, but elsewhere cases have plateaued or even slightly risen, like in India, likely due to these new variants. Whether a repercussion of vaccinations, increased natural immunity, luck, or a combination of these, we mustn’t falter in our Covid-19 prevention efforts. These variants present a great risk. 733
As the influenza virus returns every year with a different strain, the same could be said for SARS-CoV-2. Antibodies developed from natural infection or administered via vaccine will not last forever. As they decay, the virus will find ways around our immune defenses. The front line of defense has to remain public health measures. Social distancing, contact tracing, and isolation must continue as the stalwart protections against a potential new wave. This article originally appeared in Forbes and is available online here: New SARS-CoV-2 Variant Discovered In Japan Nearly Identical To Dangerous Brazilian Variant
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The Spread Of New Variants Calls For Extending Quarantine Guidelines Forbes | February 22, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the twentieth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, part fifteen, part sixteen, part seventeen, part eighteen, and part nineteen. With variants spreading rapidly across the globe, we are entering a new stage of the pandemic and should proceed with caution to save lives. The U.K. B.1.1.7 and South African B.1.351 variants have demonstrated increased transmissibility and shown evidence of increased viral load, which is associated with increased disease severity and mortality. As we gather more data on the variants, we are learning that they act very differently from the original SARSCoV-2 Wuhan strain, and we need to adjust public health protocols accordingly to prevent another rapid rise in cases. Two recent studies indicated that the infection incubation period for the variants is longer than the SARS-CoV-2 strain. Therefore we need to adjust the quarantine period to three weeks as China has done. The first study was conducted in Alachua County, Florida, when schools reopened in Fall 2020. Researchers investigated SARSCoV-2 positivity rates among student contacts of positive cases on or after 9 days of quarantine. For 257 confirmed cases of SARSCoV-2 infection, 2189 contacts were quarantined. 134 students (6.1%) were tested on day 3, and 839 (38.3%) were tested on days 9 to 14. Of the 134 student contacts tested on day 3, 14 (10.4%) were positive for SARS-CoV-2 infection. Of the 839 student contacts
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tested on days 9 to 14, 40 (4.8%) were positive for SARS-CoV-2 infection. Amid 799 student contacts of confirmed SARS-CoV-cases with a negative test result on days 9 to 14, one became symptomatic after returning to high school and had a positive test result on day 14 after their initial negative test result on day 9. After sequencing that virus, scientists found out that it was genetically different from the virus, which was initially isolated for the study. I have discussed the second (not yet peer-reviewed) study from the Harvard University School of Public Health in detail for a previous Forbes column. The study analyzed the daily PCR tests of 65 NBA players, all infected with SARS-CoV2, seven of them infected with the U.K. B.1.1.7 variant. The mean duration of overall infection for the players infected with the variant was 13.3 days compared to the players infected with SARS-CoV2, who had a mean duration of infection of 8 days. Current CDC guidelines endorse a 14-day quarantine period as the gold standard or a seven-day quarantine period with a negative result on day five or later, or a 10-day quarantine without a negative test as an option to reduce quarantine. Both studies demonstrate the increased incubation period of the variants and the need to swiftly extend these quarantine guidelines. Due to the rapidly changing nature of the variants and a lack of comprehensive data, I am urging the CDC to err on the side of caution and extend the quarantine period to three weeks as China has done. I understand that a three-week quarantine is a far greater burden than 14 or 10 days. This is why I have repeatedly advocated for the federal government to assist those in isolation, financially, as well as with medical supplies and shelter if necessary. If we do not immediately implement this public health measure, well-meaning members of the public could be unknowingly infecting their community after only completing a 10 or 14-day quarantine. It is the duty of the CDC to keep the public informed of best practices to fight the spread of variants as they come to light. We cannot afford to be complacent due to declining case rates. After months of declining case rates, India is now experiencing a sudden spike in cases across five different states where an Indian variant N440K has been identified. I have also written about how the variants are linked to a spike in cases across Europe. We must 736
learn from these examples and take them as a warning for what could occur in the U.S. if we do not move quickly to implement new public health measures. This article originally appeared in Forbes and is available online here: The Spread Of New Variants Calls For Extending Quarantine Guidelines
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What To Make Of Covid-19 Infections In French Daycare Centers Forbes | February 22, 2021 | Article
Arecent study carried out in France dove into the contribution of very young children to the transmission of SARS-CoV-2. The study included 22 daycare centers that remained open for essential workers’ children during a nationwide lockdown between March 15 and May 9 of last year, prior to the arrival of variants. 327 children between the ages of 5 months and 4.4 years, 197 daycare center staff, and 164 adults who are not occupationally in contact with infected patients were enrolled to estimate SARSCoV-2 seroprevalence. 3.7% of children and 6.8% of daycare center staff tested positive for the virus. The comparator group came close with a seroprevalence of 5%. This indicates that infected children were most likely exposed to the virus at home. While these results seem to suggest that intrafamily transmission is more likely than transmission in daycare centers, they are part of an exploratory hypothesis and further research is necessary. Many saw this study as positive news that might lead to schools re-opening, but it is too early to make such claims. The study was not carried out in the right setting, and it does not take new, more dangerous variants into consideration. The environment the study was carried out in was too controlled to accurately represent day-to-day life. The centers operated at limited capacity, taking in fewer children, respecting social distancing rules among adults, wearing face masks, and regularly disinfecting surfaces. Parents were also instructed to remain outside the centers, and to screen their children for symptoms prior to sending them in. We do not know how the new variants of SARS-CoV-2 affect young children yet. What we do know is that the new strains have a higher affinity for ACE2 receptors, making them more likely to infect the cell. Initially, children were at a lower risk of infection as they have less ACE2 receptors, but this is no longer true. 738
Prematurely opening schools could lead to a surge in SARS-CoV-2 cases in children. Another rising threat to children is Multisystem Inflammatory Syndrome in Children, or MIS-C. The condition is associated to SARS-CoV-2, with most patients either testing positive for antibodies or for active infection. The syndrome can afflict infants and children up to 20 years of age, but it is uncertain what exactly predisposes children to the condition. While MIS-C remains rare, an increasing percentage of patients are becoming critically ill. Whether or not the new variants have a role to play in increasing the fatality of MIS-C, governments should acknowledge the severity of the condition and reconsider re-opening public schools. More studies on the different strains and in different environments must be carried out before we can use the findings of the French study as a reason to ease restrictions. France has also not been exemplary in fighting the virus. Averaging at around 18,000 cases daily, it is the country with the second most cases in Europe. The study is more of a cautionary tale for country leaders not to act too quickly in the name of science. We must monitor the rising number of Covid-19 infections and MIS-C cases in children ages 1 to 10 carefully, and be prepared to adjust policies governing daycare centers and school re-openings and based on emerging data lest the sharply rising numbers of Covid-19 variants hit us where it will hurt the most, our precious children and grandchildren. This article originally appeared in Forbes and is available online here: What To Make Of Covid-19 Infections In French Daycare Centers
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Opinion: “How To Redesign Covid-19 Vaccines So They Protect Against Variants” The Daily Clout | February 23, 2021 | Article
Given that the SARS-CoV-2 variants can evidently evade immunity produced by vaccines or previous infections, scientists are exploring the idea of redesigning the vaccines currently being rolled out worldwide. While researchers are still debating whether the new variants have an effect on the first generation Covid-19 vaccines, some vaccine developers are charging forward with plans to update their shots so that they more effectively target emerging variants. These lineages carry mutations that seem to dampen the effects of antibodies crucial to fending off infection. Researchers are considering following the strategy used by influenza vaccines, meaning that they would update Covid-19 vaccines periodically and readminister them to the public. According to Mani Foroohar, a biotechnology analyst at the investment bank SVB Leerink in Boston, the best strategy to combat the threat of emerging variants is to “vaccinate as many people as possible with current shots”. This is only a strategy to use until the future vaccines become effective against these variants. Will we need updated Covid-19 vaccines? According to some virologists, updating Covid-19 vaccines will be necessary. Labs are working around the clock to understand how effective the vaccines are against the new variants. Up until recently, the million-dollar question, according to Kanta Subbarao, a virologist at the Peter Doherty Institute for Infection and Immunity, is whether these changes are enough to lower the effectiveness of the vaccines, because we don’t know how much antibody is required. As of the 28th of January, Biotech firm Novavax released data from clinical trials which showed their experimental vaccine being around 60% effective against the 501Y.V2 (South African) variant. Two COVID-19 vaccines from Chinese companies including Sinopharm also had weaker effects when it triggered immunity 740
against a highly transmissible coronavirus B.1.1.7 variant, shown in this study conducted. “I think it’s inevitable for the vaccines to maintain tip-top efficacy, they will need to be updated. The only question is how often and when,” says Paul Bieniasz, a virologist at the Rockefeller University in New York City who co-led one of the neutralizingantibody studies. How should we decide when to update vaccines? Scientists are only now learning how different mutations are altering vaccine response. By following models of other vaccines, it can create a potential blueprint in our fight against Covid-19. According to Subbarao, “One model that COVID vaccine updates could follow is that of seasonal flu vaccines”. Subbarao also directs the World Health Organization Collaborating Centre for Reference and Research on Influenza in Melbourne. One of her objectives is to monitor emerging flu changes that may have influential characteristics on the vaccines’ effectiveness but to act upon changes “ only when a vaccine-evading strain is widespread”. This comes from the fact that it would not be viable to change a vaccine if the vaccine-evading strain is concentrated to a region or a country. “We can’t be chasing every variant that emerges,” says Subbarao. How will the vaccines be updated? There are three potential approaches that are being considered. Given that fact that the variants including 501Y.V2 carry spike mutations that alter regions targeted by neutralizing antibodies. So, one approach is to just swap the vaccines’ old versions of the spike protein with an updated version that has the specific amino-acid changes that hinder antibody responses. As simple as it sounds, researchers are still to determine if any changes may lead to other effects which may alter the immune response to the vaccine. A second approach is to look at a multivalent vaccine, which includes both new and old forms of spike protein. Just like the first approach, “It’s not going to be as simple as [altering] an amino acid site and saying, ‘okay we got it’”, says Subbarao. Studies will need to be conducted on animals and humans before any update is made to the vaccines. The third and final approach could be using T-cells (‘Killer Cells’). Being a group of immune cells that can target and destroy virus-infected cells, T-cells have the potential of replacing antibodies 741
in regards to long term immunity. “It makes sense biologically. We don’t have the data, but we can hope” says Daina Graybosch, a biotechnology analyst at investment bank SVB Leerink in New York City. According to Annika Karlsson, an immunologist at the Karolinska Institute in Stockholm, T cells can help mitigate the severity of the infection. “T-cells could mean the difference between a mild infection and a severe one that requires hospital treatment,” she says. Since antibodies only detect proteins that are outside the cell, this approach is different than the first two as the T-cells can target viral proteins expressed inside infected cells, and some of those proteins are very stable, she says. Given that many viruses target the spike protein (found on the surface of the cell), it may succumb to mutation and may increase the risk of emerging variants as spike protein tend to be variable. Researchers have discovered similarities and differences between the features of all beta coronaviruses that cause human disease, which allude to the idea that T-Cells may be the way to go. Approvals and trials for the new vaccine With the first-generation vaccines already being distributed worldwide, testing updated vaccines is going to be slow and difficult. Looking at the seasonal flu vaccines, they do not tend to require fresh trials. But we must keep in mind that in contrast to the seasonal flu, we do not have the substantial clinical data (from years of experience) Covid-19 to follow the same suit. By focusing on markers such as ‘correlates of protection’ (measurable features of an immune response), researchers can reduce the timeline in our benefit. By measuring the immune response after each doses, researchers will save on time as they will not have to wait for the trial participants to be infected with the coronavirus to know if the vaccine is effective or not. This article originally appeared in The Daily Clout and is available online here: Opinion: “How To Redesign Covid-19 Vaccines So They Protect Against Variants”
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Pfizer/BioNtech And Moderna MRNA Covid-19 Vaccines Closely Mimic The Immune Response Of Natural SARS-CoV-2 Infections Forbes | February 24, 2021 | Article
As more and more variants of SARS-CoV-2 either emerge or make landfall in the United States, the question of whether they’ll be able to bypass the immune defenses we’ve acquired against Covid-19 becomes increasingly pressing. The official record states that nearly 30 million people across the United States have had Covid-19 at some point in the past year— resulting in, at least in theory, a certain degree of natural immunity— while about 44 million and counting have received at least one dose of a vaccine. Though the immunology of Covid-19 is complex and only partially understood, a recent study comparing the characteristics of naturally occurring and mRNA-induced antibodies against the new variants offers some much-needed insight into the difficulties we can expect to encounter in our attempts to protect ourselves going forward. The study, published in Nature earlier this month, examines the immune responses of 20 participants vaccinated against Covid-19, comparing them to people who were naturally infected. Of the 20, 14 received the Moderna vaccine and 6 received the PfizerBioNTech vaccine. Researchers measured levels of both antibodies and memory B cells, as well as their duration over time. Antibodies and memory B cells Two months after volunteers received the second of two injections required for full immunization, the researchers found that their IgG antibodies persisted longer than their IgM and IgA counterparts, typical of most immune responses to both infection and vaccination. They also found that the IgG and IgM levels noted in vaccinees surpassed those of the naturally infected patients, whose samples were obtained 1.3 months after initial infection, then a second time five months later, consistent with previous reports. 743
The researchers also measured memory B cells, which like IgG antibodies play a critical role in sustaining immunity. Almost immediately following immunization, the antibody response naturally decreases, with the half life of antibodies lasting anywhere from six weeks to three months. Within a year, protection from disease is guaranteed only by memory cells. In this study, the amount of memory B cells specific to the receptor-binding domain recorded in convalescents 1.3 months following infection was higher than that of vaccinees, but about the same after six months. Other studies have found, however, that memory B cells from natural infection increase over time. Variants vs. vaccines Though further confirmation that the Moderna and PfizerBioNTech vaccines generate a robust immune response is always welcome, when new variants are thrown into the mix the results are less promising. Researchers investigated this particular piece of the puzzle by pitting antibody-loaded plasma from the vaccinees against lab-generated SARS-CoV-2 spike proteins containing some of the defining mutations of emergent variants, including N501Y, K417N, and E484K (Figure 1). All three of these mutations appear either singularly or simultaneously in the B.1.1.7 (UK), B.1.351 (South Africa), and P.1 (Brazil) variants, and all three are either suspected or known to play a role in increasing chances of immune evasion and person-to-person transmission. Once again, the results of vaccines and convalescents from natural infection proved similar—though not as encouraging. According to the paper, vaccinee sera about three times less effective against viruses carrying a combination N501Y, K417N, and E484K, while convalescent sera fared even worse. For convalescent sera obtained about a month after infection, the average decrease in potency was 2.9. For six-month-old sera, it was 4.3. The antibodies’ lackluster performance against mutated spike proteins is a cause for concern. Though memory B cells can usually be depended upon to produce protective antibodies against proteins recognized earlier, the response takes several days to be effective. Memory responses do not typically prevent reinfection for the original or variant strains. The memory response often protects those reinfected from serious disease. The question of whether or not the
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immune memory will be sufficient to protect against disease upon reinfection by a variant strain is an open question. Variants are reported to cause serious disease upon reinfection of those previously infected. The similarity of the natural and vaccine immune response is cause for concern, not reassurance in this circumstance. Likewise vaccines that raise effective immune responses to the original spike protein are not always effective protecting against infection by a variant strain. These observations raise profound questions regarding Covid-19 control strategies. Variants vs. monoclonal antibodies In another portion of the study, the researchers selected the most potent of the monoclonal antibodies, sorted them into provisional classes based on neutralizing activity, and tested them individually or in combination against the SARS-CoV-2 variants. The vast majority of the antibodies were less effective against viruses containing the E484K mutation by a factor of at least tenfold—a finding that echoes those of previous research, in particular another preprint study led by Washington-based researchers that came out in early January. An equivalent reduction in efficacy was seen in some of the antibodies matched against Kr17N and N501Y mutations as well. The researchers examined the nature of mutations that allowed the spike protein to evade neutralization by a set of monoclonal antibodies. They found that three of antibodies selected for mutations at the 501 site (including N501Y), six selected for mutations at the 417 site (including K417N), and five selected for E484K specifically. These observations recall the theory of parallel evolution that I’ve discussed in previous writings—the notion that the same mutations, facing comparable selection pressures, can arise independently but concurrently in individual patients, in vitro laboratory experiments, and global populations. Summary What this study confirms is that antibodies, whether generated by vaccines or by primary infection or reinfection, fade over time and cannot be expected to protect us from primary infection. We’ll have to rely on the strength and speed of immune memory, which in itself contains a large number of unknowns, including whether or not it will be effective against variants that have evolved to evade the secondary immune response.
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The implications all point to one broader conclusion: that current and future variants of SARS-CoV-2 demand a certain level of adaptability from the drugs and vaccines we’re relying on to prevent Covid-19. If we want to save ourselves from another catastrophic winter, we need to be able to beat the virus at its own game—or, at the very least, keep pace with its maneuvers, just as we do with influenza. Otherwise, we risk leaving ourselves vulnerable once again, despite knowing full well what we’re in for. This article originally appeared in Forbes and is available online here: Pfizer/BioNtech And Moderna MRNA Covid-19 Vaccines Closely Mimic The Immune Response Of Natural SARS-CoV-2 Infections
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If I Had Covid-19, Should I Still Get Vaccinated? Absolutely Forbes | February 24, 2021 | Article
The number of people who have received at least one dose of a Covid-19 vaccine is growing steadily greater by the day. While most of those vaccinated thus far belong to high-priority, high-risk groups—older adults, health workers, educators, and so on—in due time a much broader swathe of the population will gain eligibility, including the many millions of us who have caught and recovered from the disease at least once since the pandemic began. Though at least some level of natural immunity likely persists among those who had Covid-19 before, the emergence of SARSCoV-2 variants that are not only more transmissible but probably also more challenging for the immune system to overcome has put a damper on mass vaccination efforts that depend almost entirely on technologies created using the original Wuhan strain. Just as there exists a large possibility that vaccines will have to be modified to keep pace with viral variation, previously infected individuals may be more susceptible to reinfection by the new variants—bad news for everyone, certainly, but especially for those who had a long or life-threatening battle with the disease the first time around. At least one preprint study can provide some clarification on the subject—not to mention some encouraging findings. According to the study, which was uploaded to the preprint server medRxiv in early February, the neutralizing antibody response of individuals who had Covid-19 previously strengthened considerably—by 1000fold, to be precise—following their first injection of a Pfizer or Moderna mRNA vaccine. Their antibodies not only neutralized both the Wuhan and South Africa (B.1.351) strains, but in some cases SARS-CoV-1 as well. To understand the wider implications of these findings, we must unpack them piece by piece. The study enlisted ten previously infected men and women in the Seattle area, the majority in their 40’s or 50’s. Seven received a shot of the Pfizer-BioNTech vaccine, 747
while the remaining three received the Moderna vaccine. On average, about 200 days had lapsed between the day the participants first reported Covid-19 symptoms and their first clinical pre-vaccine visit. Pre-vaccination data was collected a couple weeks before their first shot, followed by post-vaccination data around two weeks after. In terms of their laboratory studies, the researchers began with some baseline antibody neutralization experiments that compared the effectiveness of monoclonal antibodies against the original Wuhan spike protein, on the one hand, and a South Africa (B.1.351) spike on the other, which included the increasingly prevalent and problematic mutations E484K, N501Y, and K417N. The mutated spike was more resistant to neutralization than the original, with the potency of the monoclonal antibodies pitted against it decreasing as much as tenfold. This finding is consistent with previous reports, though it bears mentioning that mutations occurring in other parts of the virus, such as the N-terminal domain and accessory genes, weren’t mentioned in the research paper and may have been left out of this study. The next step for the researchers was to test whether blood plasma collected from the study’s participants pre- and postvaccination would fare just as poorly against the South Africa variant. They focused on the binding responses of IgG, IgM, and IgA antibodies specific to the receptor-binding domain, as well as any changes in antibody concentration. (Binding, it must be noted, is a mechanism related to but separate from neutralization, which will be discussed shortly.) The convalescent sera—that is, the prevaccination antibody response—responded variably and rather unpredictably to both the original and mutated strains, the immune response of one donor so slight as to be undetectable. Following immunization, antibody binding signals increased 50-fold across the board, but in the case of the South Africa spike they were much lower. The difference in binding strength pre- and post-vaccination, as well as from one spike to the next, was large enough to beg the question of whether measurements of neutralization would proceed in a similar fashion. While pre-vaccination samples of convalescent sera from nine of the 10 participants were able to neutralize the Wuhan spike, only five could sufficiently neutralize the South Africa spike. Fewer still—two out of those five—reached 80 percent 748
neutralization or higher. But in the weeks following vaccination, concentrations of neutralizing antibodies against both strains leapt 1000-fold. They were even effective against lab-generated SARSCoV-1. Thanks to this study, three different levels of immunity against Covid-19 now have precedent—natural immunity, vaccinemediated immunity, and a combination of both facilitated by a single vaccine dose. The last of these three appears to be most potent by a wide margin. Though further investigation is needed to know whether that potency is sustained over a period of several months, the fact that it only took half the standard two-dose vaccination regimen to elicit such a large jump in neutralizing capability is extremely promising. If corroborated by more data, this finding could change the way we allocate vaccines. The study also has potential implications for drugmakers, particularly those developing monoclonal antibody drugs. I recommend them to take a closer look at the antibodies that were cross-reactive against not just the Wuhan and South Africa strains, but SARS-CoV-1, too. More than anything, what will allow us to continue protecting ourselves against Covid-19 in the face of dangerous new variants is our ability to use studies like this one to make smarter and more informed decisions, both in our individual lives and our national policies. This article originally appeared in Forbes and is available online here: If I Had Covid-19, Should I Still Get Vaccinated? Absolutely
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A New Covid-19 Variant From Nigeria Raises Increased Concerns For Containment And Vaccination Forbes | February 24, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes but changes in ways that are significant. This is the twenty-first part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, part fifteen, part sixteen, part seventeen, part eighteen, part nineteen, and part twenty. The near-simultaneous detection of SARS-CoV-2 variants from the four corners of the globe deepens our uncertainty regarding the pandemic's future and our ability to control Covid-19. How serious the problem will be will depend on how many different variants there are, how they differ from one another, how capable they are of reinfecting people, and resisting current and future vaccines. In this context, here we describe the newfound Nigerian variant (B.1.525). The Nigerian isolates carry mutations mirroring those seen in previous variants and some unique to their structure. B.1.525 was first detected by genome sequence in midDecember in Nigeria but was also quickly found in cases in the United Kingdom, France, and elsewhere. After only two months, B.1.525 represented over 20% of genomes sequenced in Nigeria. It has been detected in more than 200 cases globally. The mutation of B.1.525 may increase transmissibility, virulence, and immune escape. The amino acid substitutions Q52R and A67V are located in the spike protein's N-terminal domain, as are the deletions at positions 69-70 and 144. (See figure). The two point mutations are unique to the B.1.525. Both deletions are 750
characteristics of the UK variant B.1.1.7. The deletion of 69-70 is also found in several naturally occurring variants. No specific function is as yet assigned to the N-terminal domain. Many mutations (and even multiple deletions) in this region are not deleterious to either the transmission, replication, or virulence. The N-terminal domain is highly antigenic. The primary effect of mutations in this region is likely neutralization escape. The amino acid substitution at position 888 is in the membraneproximal stem region of the spike protein, nearby a similar change at position 870 found in a neutralization escape variant isolated from a person with persistent SARS-CoV-2 infection. Among the point mutations and deletions in the spike protein, B.1.525 carries several ubiquitous in SARS-CoV-2 variants today. D614G confers increased transmissibility and is present in nearly all SARS-CoV-2 variants at this stage. The mutation E484K is also present in the South African and Brazilian strains. Amino acid 484 is located in the receptor-binding motif. The E484K change confers approximately three-fold resistance to several Covid vaccines and tenfold resistance to most convalescent antibodies. The amino acid substitution at position 677 ( Q677H) is identical to that found in variants recently described in the United States. These mutations occur in the S1 portion of the spike protein found far from the receptor-binding domain. Like the D614G mutation (also present in the Nigerian variant), the change at position 677 may increase the stability of the S1-S2 association and thereby increase transmissibility. The 677 mutations may also favor the open rather than closed conjugation of the receptor-binding domain. The Nigerian variant NB.1.525 is also rich in mutations in the genome regions that specify proteins other than the spike (Figure 2.) Three of these occur in the genes that comprise the massive replication complex, including three in Orf1a NSP3: (T1189I), NSP6: (a three amino acid deletion 106- 108), and one in Orf1b NSP12:(P323F)- the major RNA dependent RNA polymerase. Four other mutations occur in the genes specifying viral structural proteins E: (l21F), M:(I82 F), and N:(A12G) and (T208I). It is noteworthy most of these mutations occur in transmembrane proteins NSP6, E, M, and that the N protein is highly antigenic in people infected by SARS-CoV-2. All these mutations may assist
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neutralization escape. The remaining variants in orf1a may increase replication efficiency, immune escape, or both. This variant maintains the trend we have seen in the past few months. As genome sequencing efforts increased, more new variants are discovered. With each new variant comes more nuanced mutations to its structure that aid its proliferation. Some of the mutations and variants spreading at this very moment confer vaccine-resistance. I fear a relaxation of public health measures in reaction to vaccine distribution and recent declination in Covid-19 cases. Understandably, the ordinary person thinks themself safe after receiving their vaccine. Antibodies, however, do not last forever, and if new variants are immune-resistant, they may not even be fully effective. With each new variant, we gain increased insight into the multiple ways SARS-CoV-2 is adapting to us, its host. These include: Increasing the avidity of the virus for the receptor; Increasing transmissibility; Evasion of both novel and existing immune defenses; Increase replication competence; Increase in the duration of productive viremia. B.1.525 now joins the growing array of variants of concern. The protean ability of SARS-CoV-2 to circumvent social and medical containment strategies raises serious questions we must now adapt to this new reality. This article originally appeared in Forbes and is available online here: A New Covid-19 Variant From Nigeria Raises Increased Concerns For Containment And Vaccination
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Identification of a Novel Covid-19 Variant Cluster Isolated from a Sick Newborn in US Capital Forbes | February 25, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes but changes in ways that are significant. This is the twenty-second part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, part fifteen, part sixteen, part seventeen, part eighteen, part nineteen, part twenty, and part twentyone. The variants have caused us to reevaluate our strategies of control for the Covid-19 pandemic. Variants have now popped up from many parts of the world. They confer new and dangerous properties including increased transmission, the ability to evade the immune response elicited from previous infection or vaccination, and increased virulence and infection, especially in children. It is in this context that we describe a Washington DC variant (B.1.189) first identified from an outbreak in pediatric patients. B.1.189 differs from many other variants in that it carries a single, rather than multiple, mutation in the spike protein. Nonetheless, this single mutation appears to alter the virus properties in significant ways Variant B.1.189, detailed in a study by the Children’s National Hospital in Washington DC, was first identified in mid-October in an infected newborn displaying more aggressive symptoms than most other infected children. Not only was the newborn feverish, but when the doctors measured the viral load, it was over 50,000 times the median of other pediatric patients. This realization prompted
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greater genome sequencing of young patients in Children’s National Hospital, leading to several more cases of the variant identified. The variant’s mutational makeup is far simpler than most emerging SARS-CoV-2 strains. Aside from D614G, which is included in nearly all circulated viruses today, B.1.189 only carries one additional mutation to the spike protein at position 679— N679S. This mutation has not been previously identified in variants of concern, however, the GISAID database contains several hundred instances of N679K. Mutations are point 679 are found in two distinct clades. In tracing back the origin, it seems the first appearance of this mutation in the US occurred in Texas, but most recently in the DC area in pediatric cases. The importance of 679 in providing an advantage to the virus is also attested to by detection of the same mutation in an independent lineage in East Asia as well. The N679S mutation is located in a critical area for determining the infectivity of the virus particle. For SARS-CoV-2 to affect the cell, two cleavage events are required. One at the furin cleavage site and the other just before the fusion peptide. These cleavage events are the final steps of activation prior to the merger of the virus and the cell. The researchers speculate that N679S is close to a cleavage site around amino acid 681. The infectivity is increased by these cleavage sites. We propose that the mutation increases the infectivity of the virus by further facilitating the effect. Increasing the rate of cleavage may benefit the virus in two ways: increasing its ability to be transmitted and increasing the efficiency of replication once the infection has been initiated. N679K may also increase infectivity in other variants around the world. We also note that the B.1.1.7 variant now circulating widely around the world, which is known to have a substantial increase in transmission, infectivity, and disease potential, is located in the same region and is postulated to have similar activity. It is also notable that B.1.1.7 is recorded to infect and sicken children at a higher rate than strains without these mutations. Additionally, B.1.189 carries mutations to several points in ORF1ab and ORF3a. These mutations are commonplace in variants of concern and further enhance replication and virulence. Among these are P1200L in non-structural protein (NSP) 3, which is a 754
transmembrane protein, and a mutation to this mechanism could increase immune escape. Other mutations to transmembrane proteins that could increase immune escape are A231V in NSP4 and P96S in NSP6. S26F in NSP7 and P323L in NSP12 both are involved in transcription and could increase replication competency. Variant B.1.189’s discovery in children mirrors a rise in SARSCoV-2 cases among children in other areas of the world. Recent data shows a surge in both Italy and Israel youth cases, the latter experiencing more positive cases for children and teens than in any other month of the pandemic. The researchers conclude by championing recent genome sequencing efforts. With the rise of the United Kingdom and South Africa variants, the scientific community and political bodies are becoming keenly aware of the threat that new variants represent. While cases have been on a recent decline, in many countries, over the past few weeks those declinations are plateauing. In some cases, such as in the United States, we have seen a slight uptick. Whether that is due to the increased spread of the variants or relaxation in mitigation measures, time will tell. This article originally appeared in Forbes and is available online here: Identification of a Novel Covid-19 Variant Cluster Isolated from a Sick Newborn in US Capital
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New York Finds Its Own Covid Variants. The News Is Not Good Forbes | February 26, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes but changes in ways that are significant. This is the twenty-third part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, part fifteen, part sixteen, part seventeen, part eighteen, part nineteen, part twenty, part twenty-one, and part twenty-two. In a hostile takeover of sorts, SARS-CoV-2 variants have emerged the world over, threatening progress made towards ending the Covid-19 pandemic. Certain mutations confer some variants the ability to evade vaccines, whereas others make the virus far more transmissible and more deadly. Here, we analyze the genetic makeup of another one of these shifty variants identified in New York (B.1.526). This strain, in particular, carries several well know mutations known to be troublesome and some of its very own. The variant was first identified in late November by researchers at the California Institute of Technology Biology and Biological Engineering Division grew to account for nearly 30% of genomes sequenced from New York through mid-February 2021, as shown in the table below. Let’s take a brief tour of what we find in the New York variant, actually two variants sharing a common designation. The first of these, a mutation at amino acid 614 (D614G), was first noticed in March 2020 in Europe as a minor variant. The change in a single amino acid conferred such an advantage in transmission over earlier stains, such as that found initially in Wuhan, China. Today, it is ubiquitous and is found in almost every SARS-CoV-2 isolate in the 756
world. This single amino acid change improves the stability of the spike protein on the surface of the virus. It allows the virus to bind to the ACE2 receptor surface more readily to begin the process of infection. That small change allowed the viruses that carried it to outcompete all others. Today, we face many similar changes, each of which confers some advantage, large or small, that allows one virus to adapt better to an ever-changing environment as we, its target, seek to moderate its ravages through behavior change and medicine. Some of the B.1.526 variants carry a mutation at position 484 (E484K). This is one of the most significant mutations, as we know some of what it allows the virus to do. The same change is present in several other troublesome variants, including those first isolated in South Africa and Brazil. Viruses which carry the E484K (sometimes called the EEEK! mutation) are less sensitive to protective antibodies made in response to natural infection or vaccination. In practical terms, that means that these viruses can reinfect those already infected. It also means that the current generation of vaccines is less effective in protecting people who encounter the virus. The B.1.526 variants that lack the E484K change have another at position 477 (S477N). This mutation also occurs in the region of the virus that binds the ACE2 receptor. We have some inkling of how it may help the virus spread rapidly. Laboratory experiments show that this change dramatically increases how tightly the virus can bind to the receptor, a feature we know from the success of the D614G variant that gives the virus a competitive advantage. For us, this means that variants of B1.526 that carry this change are more contagious. Both of the B.1.526 variants contain another mutation at position 701 (A701V). Before the virus can begin infection, the membranes surrounding the virus and cell must fuse. Fusion requires that the region of the spike protein buried deep in the structure be free. The mutation at 701 allows that to happen more easily, once again improving the ease with which the virus can enter a target cell. That is yet another way for this virus to become more contagious. The New York variant has independently evolved two of the tricks used by the South African variant B.1.351 as it too carries identical mutations at positions 484 and 701.
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We know something more about one of the other mutations common to the B.1.526 variants. The change at position 253 (D253G) is in a region of the spike protein called the N-Terminal Domain (NTD). This region is highly antigenic, meaning that is the target of many antibodies is partially protective. The D253G change shields the virus from protective antibodies, assisting immune evasion. When combined, these changes present a formable challenge both to the prevention of infection by standard public health measures and the current generation of vaccines. The figure here depicts the location of the B.1.526 mutations along the length of the spike protein. The spike protein folds into a complex structure. The location of each amino acid change is also shown in the assembled spike. The RBD indicates the region of the spike that binds to the receptor. Both the 484 and 477 variants clearly reside in the receptor-binding domain. The 701 mutation is located in the spike stem adjacent to the region necessary for membrane fusion. The New York variants also share other mutations scattered throughout the genome, as pictured below, as is the case for several rapidly spreading variants. Much more research is required before we understand how or if these mutations affect transmission, immune evasion, and virulence. It is striking how rapidly the B.1.526 variants have emerged as dominant strains in the New York area in the late weeks of February. They have a competitive advantage over others in the spread from person to person. The identity of mutations in these variants with that known pose increased risks contagion, immune resistance, and virulence should put us all on guard. The news comes as a cruel blow to this of us who were hoping to be able to relax mitigation measures and revel in our newfound vaccine-induced protection. This article originally appeared in Forbes and is available online here: New York Finds Its Own Covid Variants. The News Is Not Good
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Covid-19 Cases Are Rising Again Globally Forbes | February 26, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes but changes in ways that are significant. This is the twenty-third part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, part fifteen, part sixteen, part seventeen, part eighteen, part nineteen, part twenty, part twenty-one, part twenty-two, and part twenty three. After a period of decline, we are now seeing a rise in Covid-19 cases globally and in the U.S. According to WHO, there was a daily increase of 84,383 cases globally as of February 25, 2021, bringing the total number of current global confirmed cases to 421,406. (Figure 1). John Hopkins is reporting 77,804 new cases in the US as of February 25, 2021. This demonstrates a steady increase from the 55,195 new cases reported in the U.S. on February 21, 2021, as seen in the chart below (Figure 2). A disturbing trend that should caution us against the complacency that some governors are showing by rolling back state Covid-19 restrictions. As I have written in prior columns for Forbes, the increase in cases is likely due to the spread of the highly transmissible UK B.1.1.7, South African B.1.351, and Brazil P.1 variants. These dangerous variants have shown evidence of increased viral load which is associated with increased disease severity and mortality. We simply need to look at the U.K. to see how these variants can quickly become a dominant strain and lead to a surge in cases. The B.1.1.7 UK variant now accounts for approximately 96% percent of all new COVID-19 infections recorded in the U.K. We are now seeing similar patterns play out around the world, as the rapidly mutating variants signal a new stage of the pandemic. 759
After months of plummeting case rates and a swift vaccination rollout, India is now experiencing a sudden spike in cases. The spike has been most pronounced in the western state of Maharashtra, where an Indian variant N440K has been identified and nearly 7,000 cases were detected earlier this week. That accounts for a significant portion of India’s overall confirmed 16,577 cases (Figure 3) as of February 25, 2021. With the UK B.1.1.7, South African B.1.351, and Brazil P.1 variants and our own home-grown variants the CAL.20C, the 677 mutations, and now the New York B.1.526 variant all active in the U.S. we cannot afford to be complacent. These new developments remind us that the pandemic is far from over and the variants could lead to a new surge in cases. In a prior column for Forbes, I detailed the public health measures that need to be put into place if we are to prevent the spread of the variants. I will summarize them again here. Increasing vaccinations is a critical step but until we have comprehensive data on the efficacy of all approved vaccines against the variants, those who are vaccinated must continue to wear masks, sanitize, physically distance, and avoid indoor activities. The federal government needs to incentivize quarantining both financially, as well as with medical supplies and shelter if necessary. Non-essential travel must be avoided at all costs and testing must be a requirement of domestic and international travel. Finally, the Biden administration needs to continue to scale up the genomic surveillance system and link that information with robust contact tracing, so we may have a greater understanding of how the variants are spreading. By swiftly implementing and following these measures, we can help avoid a rapid rise in Covid-19 cases stemming from the variants, as we have seen play out overseas. This article originally appeared in Forbes and is available online here:Covid-19 Cases Are Rising Again Globally
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Self-Testing: A Route To School Re-Opening – The Austrian Example Forbes | February 26, 2021 | Article
Austria is seeking something different to reopen its schools. After months of battling SARS-CoV-2, the government is asking students to test themselves twice a week before they can attend class. The country could become an example for the U.S., where many schools remain closed. Last week, the U.S. Centers for Disease Control and Prevention encouraged elementary and secondary schools to reopen in the wake of a debate about how they could function amid the pandemic. School reopenings have also been prioritized by European governments, but the continent's slow introduction of vaccines and the spread of highly infectious coronavirus variants mean that there are major risks. Austria is taking this a step further, where testing numbers have been reaching an all-time high after recent PCR and antigen tests were expected to book a hair appointment. According to Die Presse, 1,522,739 antigen and PCR tests were carried out last Sunday. To allow people to access services, the government aims to meet a goal of up to 3.5 million tests per week with a combination of PCR and antigen tests. From March 1, up to five "living-room" antigen tests will be assigned to each person, which only require a shallow swab of the nasal cavity and can be performed at home. There will also be increased testing at schools and businesses. So far, 787 pharmacies and 730 companies are taking part in the free test campaign. Schools have reopened this month after almost three months of distance learning. Initially, the reopening schedule will require all students to test once a week on Monday. This will later be raised to twice a week. Children will be able to collect their sample by turning a swab in their noses before inserting it into a cartridge, dropping a few drops of liquid on it and waiting for the result for 15 minutes. It is supposed to be “as easy as picking your nose”. To date, the Austrian government has ordered 24 million tests of this type from 761
a Chinese manufacturer for what is equivalent to $2.90 each. Children in primary schools will be able to take the test home so that a parent can administer it. Older students will perform the test at school. Children with parents who refuse to participate in the mass-testing will have to continue remote learning. It is projected that a record of about 2.2 million tests will be administered in schools every week. In European schools, safety initiatives have varied widely, similar to the U.S., including increased hand-washing, staggered arrival and recess times, separate classes and compulsory mask-wearing, often only in hallways, sometimes everywhere. Austria has implemented a 'triple safety net' composed of three steps to cut infection risks in order to mitigate infections. This entails wearing N95 masks for children from the age of 14, performing routine testing and organizing classes and lessons in two shifts, where half of the students going to school on Monday and half of the students coming to school on Tuesday. Compared to laboratory PCR tests, which are highly accurate but require more time to generate a result, antigen tests have often been criticized for their lower sensitivity. Yet, researchers say there is increasing evidence that repeated antigen testing can help distinguish the most contagious cases within large groups and help contain contamination. Last week, 364 children and 172 teachers were positive out of 1.3 million tests across Austria. The low rate may be because the children were coming out of a months-long lockdown, but some scientists suggested the possibility that children were not correctly collecting samples. Nonetheless, parents and students should not be fooled into a false sense of safety by negative tests. they only offer a snapshot of the infectiousness of a person on a given day. Other safety measures, such as mask-wearing and self-distancing, should continue to be mandatory. This article originally appeared in Forbes and is available online here:Self-Testing: A Route To School Re-Opening – The Austrian Example
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Should Anticoagulants Be Used Early Or Late In Patients Hospitalized With Covid-19: Two Conflicting Answers Forbes | February 26, 2021 | Article
Doctors treating patients with a new disease face uncertainties. Will the treatment benefit or harm the patient or make no measurable difference. The results of controlled clinical trials and the difference between treatment and placebo, provide the guideposts for decisions. What must doctors do when the results of early clinical trials are ambiguous or contradictory as they often are for a new disease such as Covid-19. Here I describe just such an example. Should patients hospitalized for Covid-19 be treated with anticoagulants as early as possible, or should treatment be delayed until clinical signs indicate that hyper-coagulation is likely? This is just one of the many judgments caregivers must make in facing a new complex disease such as Covid-19. Hyper-coagulation (excessive blood-clotting) is a cause of death and disability facing patients hospitalized for severe Covid-19. Anticoagulants (blood thinners) have been reported to reduce inhospital deaths. The question then becomes how early should anticoagulation therapy begin upon hospitalization. Here I review two studies that reach different conclusions. The use of Heparin-based anticoagulants (blood-thinners) as a therapy for COVID-19 was initially put forward by a study of 449 patients with COVID-19 from Wuhan, China. The results concluded that no difference in 28‐day mortality was found between heparin users and nonusers. But patient subgroups at-risk of sepsis and coagulation dysfunction who had received low-dose prophylactic doses of heparin had approximately 20% lower mortality than patients who had not. This study has some limitations as it did not control for medical or symptom history. The study was also conducted from January 1 763
to February 13, 2020 when there were still insufficient medical resources in Wuhan, China and the influence of other therapies on these patients has not been evaluated. However, the study still used a large patient population and due to the lack of treatment options for Covid-19 at the time, all patients received relatively similar supportive care. A different US-based study demonstrates a link between the early initiation of preventative (prophylactic) anticoagulation in newly admitted COVID-19 patients lowers coronavirus disease mortality, compared with no treatment. The study examined 4297 patients (median age, 68 years; 93% men) who were admitted to Department of Veterans Affairs hospitals from March 1 to July 31, 2020 with laboratory-confirmed COVID-19 infection, and no history of anticoagulation. Those who received anticoagulation in the first 24 hours after hospital admission had a 27% lower risk for 30-day mortality than patients who received no anticoagulation therapy. The early onset of prophylactic anticoagulation was also not associated with an increased risk of transfusion-related bleeding. In contrast to these two studies, a study from Northwestern University showed that patients who were newly started on therapeutic anticoagulation in the hospital had worse clinical outcomes. The study looked at 1716 adults hospitalized with COVID-19 of whom 372 were on therapeutic anticoagulation during their admission. After adjusting for controlled variables, there was no difference in death, critical illness or mechanical ventilation among patients who continued on therapeutic anticoagulation prescribed prior to admission when compared to patients who received preventative (prophylactic) anticoagulation. Patients who were newly started on therapeutic anticoagulation for COVID-19 infection, in the hospital had worse clinical outcomes; there was an increased risk of overall death, critical illness, mechanical ventilation, and death in critical illness. However, it is worth noting that 85.9% of these subjects who newly received therapeutic anticoagulation for COVID-19 infection had a critical illness status. The study concluded that they did not find any benefit of therapeutic anticoagulation in patients with COVID-19. Based on these studies, it is currently too soon to broadly recommend the early use of low-dose anticoagulants to reduce Covid-19 related mortality rates. More research is needed to 764
determine whether the apparent benefit of heparins could be related to their anti-inflammatory and antiviral effects, not just to their anticoagulant effect. We also need further research to investigate how the disease stage impacts the use of anticoagulants and what other subgroups would benefit most from this treatment. For now please sympathize with the doctors who must make this and other life and death decisions based on insufficient data several times a day as the pandemic rolls on. This article originally appeared in Forbes and is available online here:Should Anticoagulants Be Used Early Or Late In Patients Hospitalized With Covid-19: Two Conflicting Answers
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The California Variant Is More Transmissible, Evokes Worse Symptoms, And May Resist Vaccines Forbes | February 27, 2021 | Article
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes but changes in ways that are significant. This is the twenty-fourth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, part fifteen, part sixteen, part seventeen, part eighteen, part nineteen, part twenty, part twenty-one, part twenty-two, and part twenty-three. As SARS-CoV-2 variants develop mutations, they enhance their ability to spread, sicken, and resist antibodies, which results in more and harsher Covid-19 cases. Earlier this month, I detailed one of such variants beginning to circulate in Southern California (B.1.427/429). In the weeks since, the virus has predictably grown in prevalence, and recent data describing its structure and spread echoes the dangers I feared it could impart on the people of California, the United States, and the world at large. To refresh, the viral strain was first described by genome sequencing efforts from Cedars Sinai Hospital in Los Angeles. From their variant surveillance efforts, they tracked a dangerous strain of SARS-CoV-2 dating back to July 2020. In the months since, B.1.427/429 has spread among the population to account for over half the analyzed isolates in California by late January. We postulated that its distinct mutations—S13I, W152C, and L452R—would confer higher transmissibility and increased antibody resistance, akin to the United Kingdom, South African, and Brazilian strains. These and other mutations are depicted in the figure below. I speak in 766
greater detail about the individual mutations and their functions here. It seems our fears were realized. New data announced by Dr. Charles Chiu of the University of California San Francisco demonstrates B.1.427/429’s destructive capabilities in detail. The study, according to Chiu, will be published in the coming days. Samples collected from a number of California counties suggest the variant is 19 to 24% more transmissible. One elder-care facility saw transmission increase nearly six times that of prior viruses. Additionally, it seems viral load is increasing among patients as well. In comparison to infected individuals with non-B.1.427/429 versions of the virus, those infected with the California variant measured viral loads about twice as high. A greater viral load has several unnerving implications. First, the infected person is much more likely to have severe symptoms or symptoms in general. Second, they may have a longer duration of infection, which was shown in a study on a group of NBA basketball players. Third, they have a much greater chance of infecting others, as every sneeze, cough, and breath carries greater proportions of viral particles. As predicted as well, the mutations in B.1.427/429 confer a significant level of antibody resistance, both for naturally occurring antibodies from a previous infection, as well as those administered via vaccination. Much of this can be attributed to the L452R mutation alone, which is located in the receptor-binding domain: the mechanism which connects to the human cell ACE2 receptor. One version of the virus called CAL.20A which had solely this mutation witnessed an infectivity rate that was 40% higher than the general B.1.427/429 strain and 200% higher than the initial wildtype virus in a group of gorillas at the San Diego zoo. Further research from the San Fransisco study indicates increased virulence as well. Aligning with the observation of increased viral load, researchers found a 21% increase in ICU admissions and an eleven times increase in death among those contracting B.1.427/429. The spike protein, however, may not be the only source of these mortifying data. A variety of mutations external to the spike protein could be cause for increased immune escape, transmissibility, and virulence as well. Among these mutations are point mutations T114I and S385T in non-structural protein 4, which is a transmembrane 767
protein. A change to this mechanism could enhance immune escape, which this strain demonstrates. Mutation P323L to non-structural protein 12, which is notably present in many strains such as the UK, South Africa, Brazil, and many in the US, is involved in transcription. A mutation to this mechanism likely increases viral load and thus transmissibility and virulence. The full range of mutations external to the spike protein is depicted in the figure below. These numbers are shocking. They illustrate the full power of variants. Within a matter of months, B.1.427/429 grew from a single isolate to over half the cases in the state. Without a doubt, the variant has spread along the pacific coast and into the continental United States. We find ourselves in a battle against a swarm of emerging strains, all equipped with state-of-the-art weaponry: immune escape, increased virulence, and greater transmission. We must step up our tools as well with stronger public health efforts, variant surveillance, and perhaps adaptive vaccines if we are to win this war. This article originally appeared in Forbes and is available online here:The California Variant Is More Transmissible, Evokes Worse Symptoms, And May Resist Vaccines
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Schools Must Reconsider Accelerating Plans To Reopen In Light Of Dangerous New Covid-19 Variants Forbes | February 28, 2021 | Article
Nearly a year has passed since schools across the country began shuttering their doors to protect students, educators, and their families from Covid-19. Since then, many parents juggling work and schooling duties have incurred more stress while making less money; a high percentage of kids are suffering psychologically and losing their motivation to learn; and nearly a third of teachers across the US are contemplating leaving the profession altogether, so exhausted are they from the combined toll of continuous safety concerns, longer hours, and inadequate administrative support. Given all this, it is understandable that most of the country’s 3,000-plus school districts see the current drop in new Covid-19 cases, as well as recent reports from CDC officials that affirm the success of safety protocols in reducing transmission in schools, as an opportunity to not only resume limited in-person learning but also accelerate plans to expand it come the 2021-22 school year. But if they want to keep schools safe, they’ll have to include a new factor in their calculations—the emergence of new variants of SARSCoV-2, the virus that causes Covid-19. Researchers estimate that the first variant to enter the spotlight, B.1.1.7, initially surfaced in September 2020. By December it became the dominant strain, and as of this writing it has been detected in nearly 80 countries. Many others have emerged since, each more transmissible, more immune-evasive, and in some cases more deadly than its predecessors. Most of the discussion on variants to date has revolved around their potential to impact the efficacy of Covid-19 vaccines, many of which were developed using technologies specific to the first strain of the virus that originated in Wuhan, China. While vaccine developers are already reconfiguring their pipelines to allow for the possibility of more viral variation, 769
other public health interventions we’ve relied on to contain the pandemic thus far remain to be recalculated—especially those we implement in schools. Until now, parents and educators took great comfort in the fact that children are less likely to catch and get sick from Covid-19 than adults. But in Italy and Israel, where the UK variant made landfall last year, health authorities are witnessing an uptick in spread among children and teens far greater than any recorded in their first or second waves. According to a study published earlier this month in BMJ, more than 50,000 school-age Israelis were confirmed to have Covid-19 in January alone. Meanwhile in Italy, the northern village of Corzano, population 1,400, has recently experienced an outbreak that infected at least 10 percent of residents. More than half—60 percent—of these cases were children who went on to infect other members of their household. Not for nothing, the number of Covid-19 cases recorded at colleges and universities across the US has gone up 31 percent since last year, with more than 120,000 confirmed since January 1. As is the case with primary and secondary schools, these universities have been in a state of complete or partial closure since March of last year. The spike in infections makes it clear that attempts to move forward with a more robust reopening have been complicated by the new variants, which arrived just in time for the spring semester. The concern isn’t just that kids who catch a more evolved and contagious form of the virus will spread it to their teachers and family members. The more children get infected with Covid-19, the more they’ll develop a rare condition known as Multisystem Inflammatory Syndrome in Children, or MIS-C. This mysterious inflammatory syndrome, which has appeared in more than 2,000 pediatric Covid19 cases in the US so far, can start out causing fever, red eyes, and digestive problems but lead to heart dysfunction and even death. In the first two weeks of February, the number of MIS-C cases documented in Los Angeles County shot up 35 percent. Though we can only speculate why, the increase may have something to do with B.1.427/B.1.429, a highly contagious variant that began circulating in Southern California in November and is now present in at least 45 states. If the new SARS-CoV-2 variants are as capable of spreading amongst school-age children as the BMJ report suggests, any return 770
to in-person learning cannot be accompanied by slackened safety measures. On the contrary, vigilance will have to be at an all-time high—a difficult thing to ask, given the level of pandemic fatigue that has set in for most, but a necessity if we want to protect our children from a condition that has already taken 30 young lives. Vaccinating teachers isn’t enough. Upon reopening, schools must ramp up safety measures and keep them at full tilt, especially in places where community spread has yet to be contained. In addition to mandating masks and, if possible, face shields, temperature checks, frequent handwashing, and continuous social distancing must be rigorously enforced. To proactively detect and prevent contagion, a testing program comparable to the one being piloted in Austria, which provides free home tests to families, should be implemented. Hybrid learning options that combine remote and in-person education, allowing parents maximum flexibility and plenty of leeway to self-isolate if they suspect their kids have been exposed to Covid-19, should also be maintained, as well as longer quarantine periods for students and educators who test positive just to be safe. And parents, if you’re lucky enough have the luxury of being able to keep your children at home at little cost to them or yourselves, think long and hard about whether sending them back to school is the right thing to do. For some students, in-person learning is a matter of preference. But for others, it is a matter of survival. This article originally appeared in Forbes and is available online here: Schools Must Reconsider Accelerating Plans To Reopen In Light Of Dangerous New Covid-19 Variants
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Italian Scientists Create Live SARS-CoV-2 Neutralization Escape Variant Forbes | March 1, 2021 | Articles
Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes but changes in ways that are significant. This is the twenty-fifth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, part fifteen, part sixteen, part seventeen, part eighteen, part nineteen, part twenty, part twenty-one, part twenty-two, part twenty-three, and part twenty-four. Variants spread rapidly through populations and become the dominant strains, at least locally. There has been an enormous effort to understand the extent, function, and epidemiological consequences of these variants. In the past few months, genome sequencing efforts isolated many SARS-CoV-2 variants throughout the world. Other variants were isolated in laboratories using monoclonal antibodies or pseudotyped viruses, which are virus particles whose envelope proteins can be dictated by researchers to measure antiviral compounds and antibody responses. Rino Rappuoli and his team of Italian researchers took this one step further. The study, conducted by the Monoclonal Antibody Discovery Lab, among others, aimed to investigate the evolution of SARS-CoV-2 in the immune population. As opposed to many in vitro studies where mutations are artificially created, Rappuoli and his team co-incubated live virus with a highly neutralizing plasma from a patient infected with the wild-type. After 45 days of exposure, the virus sample developed a deletion to position 140 of the spike protein in the N-terminal domain (NTD). After 73 days, the substitution E484K to the receptor bind 773
domain (RBD) developed, notably observed in the South African, Brazilian, Nigerian, and New York variants. After 80 days, an insertion to the NTD containing rendered the virus entirely resistant for the convalescent plasma sample. The mutations were remarkably evasive in their own right. The deletion at F140 decreased neutralization titers by four times. The mutation E484K additionally reduced titers four-fold. The insertion in the NTD was able to finish the job, taking neutralization titers from roughly 60 to zero in a matter of days. These mutations developed naturally in conjunction meaning similar mutations could happen in the real world in long-haul Covid-19 infections. The researchers speculated that the F140 deletion alters the loops in the NTD, depicted in the figure below, which decreases the region’s stability. This, paired with the insertion that remodels part of the region, helps the NTD evade antibodies targeting that specific section of the spike protein. Additionally, E484K swaps the charge at that position and alters antibody binding in the RBD. These three alterations enabled the complete prevention of any antibody neutralization, also shown below. An unanswered question from this paper is if there were mutations in other protein and non-protein areas of the genome, as there are for naturally occurring variants. Convalescent sera may neutralize through recognition of the envelope, nucleocapsid, or membrane proteins, as well as some of the proteins in the replication complex or elsewhere. There is a word of caution for this paper. The Italian lab created an immunological escape variant virus capable of infection and transmission. We can only hope that the containment conditions of that laboratory are sufficient so that such a creation never escapes that facility. How do these results then affect the larger population? A virus aims to survive and spread. It is capable of changing its structure to accomplish this goal. As shown in several long-term immunocompromised Covid-19 patients, such as the Boston, Pittsburgh, and London patients, extended exposure of SARS-CoV2 to neutralizing antibodies may yield mutations that create a resistant virus.
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These variants are going to continue to pose a challenge to the control of the pandemic through both public health measures and vaccination. This article originally appeared in Forbes and is available online here: Italian Scientists Create Live SARS-CoV-2 Neutralization Escape Variant
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New York Covid-19 Variants Are Causing Concern Forbes | March 2, 2021 | Article
The news of coronavirus variants now circulating in New York comes at an unfortunate time, with many New Yorkers eyeing more relaxed precautions now that relief from the vaccines was finally in sight. But the alarming rise in the number infected by one variant, dubbed B.1.526, should give us all pause. B.1.526 first appeared in late November and now accounts for about 25% of all coronavirus genomes sequenced in New York. Its ability to spread so rapidly is likely due to a set of mutations in the spike protein that increase viral infectivity, allow the virus to replicate more quickly, and keep the virus circulating in the body for longer. While that alone is concerning, it could become much worse. Some of the mutations — like E484K and D253G — have been seen in other variants and are known to give the virus a leg up against our immune system. The well-studied E484K mutation alone has been shown to diminish our body’s ability to neutralize the virus, even among those recently vaccinated. Mutations that allow the virus to evade our immune response, give the virus a greater chance of surviving inside our bodies. Combine that with a mutation that allows the virus to replicate more quickly and the virus now poses a very real and immediate threat. A higher viral load is associated with more severe illness and a greater chance of death. This means this new New York variant may not just be more transmissible and more capable of evading our immune defenses, it may also prove to be more deadly. I, like every other New Yorker, was hopeful that the recent decline in new cases and the accelerated rollout of Covid vaccines was a sign that soon we could return to a greater sense of normalcy. But having studied this variant’s mutations and as a long time investigator of infectious diseases, I am no longer so hopeful. To
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keep this variant from spreading even further, all of us must double down on our efforts to contain its spread. First, we should all be more careful when leaving our homes than we’ve ever been before. It’s not enough now to mask up with our usual one or two cloth masks. Now’s the time to pull out the harder core PPE: N95 or KF94 masks and our face shields. Wearing a quality mask and face shield have been proven highly effective at preventing transmission even in indoor hospital settings. Second, those eligible for vaccination should get their shots as soon as they can. Even though this variant may be better able to evade our immune responses, studies of variants with similar mutations have shown that while the vaccines may not be as effective compared to the wild type virus, they can still provide some protection. Those who can should take every bit of help available to them. Third, if you’ve been sending your children into school but you have the luxury of keeping them home, now’s the time to reconsider that option. The mutations in this variant give the virus greater affinity, meaning they can latch on more effectively to our ACE2 receptors. Many experts believe that one of the reasons why Covid19 may not have been as prevalent in children was because they have fewer ACE2 receptors. Now, with a variant with higher affinity, this may no longer matter as much and our children may become much more susceptible to infection, transmission, and the risk of more serious disease. Finally, if you do unfortunately fall ill, isolate yourself immediately from those you love and make sure that you and those around you who were exposed quarantine for at least 14 days and ideally three weeks, not the seven to ten days that many schools and businesses require. We know from other studies that these variants can linger in the body for longer and you may transmit the variant unknowingly if you or those exposed break quarantine too soon. These New York variants have been circulating for a while now and if you’ve escaped them so far, consider yourself lucky. We also know that other variants — some known like the South African one and others still unidentified and potentially even more transmissible — are circulating as well. We have a rare opportunity today, with new cases still on the decline, to contain the spread of these new variants and prevent another major outbreak. It won’t be easy. But 777
remember all we fought for a year ago next month, when we were thrown into the throes of alarm and despair when the city first locked down. If we don’t take the right steps now, we may all be condemned to repeat it. This article originally appeared in Forbes and is available online here:New York Covid-19 Variants Are Causing Concern
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How COVID-19 Could Make Us Healthier The Hill | March 2, 2021 | Article
COVID-19 has exposed countless weaknesses and inequities in our health care systems, with long-term effects that will be felt for generations to come. Yet it has also given us an important opportunity to improve where we have failed. Public health is now deeply embedded in our consciousness as a top priority. The pandemic has already helped facilitate long-overdue improvements in our health care system, such as the rapid expansion in virtual care and greater awareness of racial health disparities. But further progress will not be inevitable without more comprehensive reforms. Some positive changes will come in the form of how we adapt our behavior to protect ourselves and others. After almost a year of vigilant hand washing, sanitizing and mask-wearing, many of us are recoiling at how unsanitary our pre-pandemic actions were. The idea of powering through a cold or illness at the office is no longer to be celebrated. Instead, we are left with much greater respect for employees who choose to work remotely when ill and employers who are willing to offer the flexibility or the sick leave to let staff stay home. Even mask-wearing – a hotly debated topic across the U.S. – may become the norm whenever anyone feels ill, much like in Asia, where it has long been encouraged. With a historical decline in influenza cases this season, we are already seeing the benefits of the approach. If we persist with better personal hygiene beyond the pandemic, the trend could continue, potentially saving tens of thousands of lives every year. The pandemic has also played an important role in destigmatizing mental health issues, turning a spotlight on the need for more integrated care, where attention is paid to the physical, mental and social needs of every patient. By talking more, as we are now, about issues like anxiety, depression, alcoholism and domestic violence, we have made it easier for people to ask for care. Now we need to build the infrastructure to accommodate the demand and ensure that patients can access and afford mental health care, either 779
by incentivizing providers to accept insurance or through legislating better coverage for mental health care. One critical improvement over the past year has been our ability to deliver care wherever patients need it most, often in their homes. Thanks to emergency measures to eliminate regulatory and insurance barriers, virtual care became standard for patients. Providers also explored other ways of delivering care outside the traditional hospital setting, like in ambulatory care centers. Now, we need to make these emergency authorizations permanent and ensure that health care providers have the training and technology to deliver optimal levels of care. But training and technology for providers will get us only so far. To fully realize the potential of telemedicine, we need to ensure equitable internet access for all Americans, which opens up a whole new set of issues that have yet to be solved. The rapid spread of COVID-19 demonstrated that stronger health systems that address health inequities benefit us all. COVID19 cannot be controlled unless it is controlled across the entire population. This means every American, no matter their age, income or background, should be able to access affordable care. Health care costs have long been a deterrent in the U.S., leading us to worse outcomes and underperforming at a world standard. Stories of surprise bills costing thousands of dollars associated with COVID19 tests acted as a deterrent to low-income earners from seeking out tests. The benefits of universal health care were never clearer than when a global health crisis coincided with millions losing their jobs and health insurance. The COVID-19 pandemic gives us a clear mandate to invest in a long-term strategy to strengthen our health systems and improve public health, which has been chronically underfunded for many years. We need to seize this moment to build respect for the work of public health professionals and use the power of government agencies such as FEMA and the Department of Homeland Security to roll out public health initiatives. Not just so we can respond proactively to health emergencies, but also so we can address some of the rampant co-morbidities like diabetes and obesity that made our population more vulnerable to COVID-19. Even with all that must be improved within our own borders, we cannot neglect what lies beyond. Assisting more vulnerable 780
countries to strengthen their health systems to fight this pandemic and emerging threats will, in the end, help us as well. The U.S. should reclaim its position as a global health leader and foster greater collaboration and data sharing among all nations to build a robust surveillance system for chronic and infectious diseases. The 1918 flu pandemic and the HIV epidemic have both revolutionized the way we approach health and deliver care, and so should this pandemic. America has a wealth of knowledge from universities, researchers and think tanks on best practices in health. The challenge lies in the funding and implementation, and COVID19 provides the ideal momentum. This article originally appeared in The Hill and is available online here: How COVID-19 Could Make Us Healthier
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Variants: Forewarned Is Forearmed— For Those Who Listen Forbes | March 3, 2021 | Article
We now know the adaptive power of SARS-CoV-2 variants. Newly described Covid-19 variants isolated in the United Kingdom, South African, Brazil, the United States, and Nigeria appear to be more transmissible, resist neutralization. and may be more virulent. Now turn back the wheels of time. Were we to know about this variant future, perhaps we could have been prepared. As it turns out, one scientist, Dr. Li Lanjuan, and her colleagues at Zhejiang University provided that early warning. In a set of two papers released in March and April 2020, Dr. Li revealed what today is common knowledge. After deep sequencing patients from Hangzhou, Li identified a series of mutations in the genome and specifically in the spike protein. Her studies spelled out the potential dangers of rapidly mutating virus, one that not only could change, but a change in critical regions that could affect how well the virus might be transmitted and its potential to cause severe disease. Perhaps Li Lanjuan's studies did not draw international attention as she speculated that as the virus adapted, it would like become less rather than more virulent. Nonetheless, the studies had an essential part of the story right. SARS-CoV-2 is a shape-shifting virus on par with influenza. Remarkably, the virus's ability to change and to change rapidly was reported in mid-March and April 2020 at a time most dramatically underestimated the potential for change. So often wrong in science, conventional wisdom held that because coronaviruses change slowly because they have an error-correcting mechanism. At the time, no one could offer a convincing explanation of why cold-causing coronaviruses return year after year like influenza, often to infect the same person. We now know that cold-causing coronaviruses and SARS-CoV-2 change rapidly to avoid immunity. Will Rodgers is reported to have said, "It isn't what
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we don't know that is the problem. It's that so much of what we know ain't so!" Li commented on the high volume emergence of one specific mutation to several European samples' spike protein. This mutation conferred greater viral load to those that the virus-infected. The mutation is D614G. Over the next few months, D614G came to dominate every strain and infection of SARS-CoV-2 and is likely a driving force behind the spring and summer 2020 surges of Covid19. Dr. Li was the first to identify the implications of the D614G variant. In the April 2020 paper, she wrote. "...specifically, we note the following A23403G (D614G in S) found a group 192 of 231 viral sequences, most of which were isolated in Europe." The first notice of the potential importance of the D614G mutation outside of China was reported by Bette Korber in early May 2020, to widespread skepticism regarding its relevance. In the figure below, Li displays the widespread appearance of variants across continents, including D614G in Europe. Among the other mutations in Dr. Li's papers of note are several the S or spike protein. The spike protein mutation at position 215 ( D215H) is also present in the highly infectious and immune-resistant South African variant. The S protein mutation at position 682 (R682Q) escapes neutralization by a therapeutic monoclonal antibody. Another mutation at position 247 (S247R) in the Nterminal domain of the S protein, observed in these early isolates, falls with the N-terminal domain of the S protein. Mutations external to the S protein are not without their effects on the virus. For instance, South Africa, Brazil, New York, and others, and this exact mutation in the Japanese variant. All of these mutations found in other variants are noted in the figure below along with unique mutations Li noted. Another of Li Lanjuan’s prescient insights is the importance of mutants adjacent to the S protein's two cleavage sites, the furin cleavage site between that S1 and S2 proteins, and the cleavage at the site proximal to the fusion peptide. Her speculation that these mutants confer increase infectivity by enhancing cleavage is recapitulated in the current literature regarding similar variants. The early studies note the "looped out structures" of the regions, rendering them especially vulnerable to proteases.
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Dr. Li's research, coupled with her observation of the rapidly growing number of mutations in the GISAID database as early as one year ago, were red flags that went unremarked for too long. Had we heeded this warning, we would not now be playing a desperate game of catchup by ramping up genomic sequencing efforts in the US and worldwide. Forewarned is forearmed... if anyone is paying attention. This article originally appeared in Forbes and is available online here:Variants: Forewarned Is Forearmed— For Those Who Listen
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More Cause For Concern Around Covid-19 And Schools Forbes | March 5, 2021 | Article
Earlier this week I wrote a column which raised an alarm around whether it was worth sending our children into school when we know that more transmissible and possibly more lethal SARS-CoV2 variants are circulating. Now, new reports from Italy of a spike in cases among the very young have those alarm bells ringing even louder. The B.1.1.7 variant — first identified in the UK late last year — was reported to be circulating in Italy in early February. By February 18, the variant accounted for more than half of all infections in the European country. This week, Italy’s health minister confirmed the alarming uptick in new cases but shared even more worrisome news: the new infections were especially pervasive “among the youngest age group”. In response, Italy has tightened restrictions around schools, forcing elementary and daycares closed in red zones across the country, where infections are peaking. There are a few lessons that the rest of the world should absorb from Italy’s current crisis. Covid-19 has long been thought to be a worry for the old, not for the young among us, especially not elementary and nursery school age children. But Italy’s experience is proving us all wrong — the incidence of new cases among young people has now eclipsed cases among the old. Since the start of the pandemic, scientists have wondered why children have accounted for such a small percentage of identified cases. Over time, studies have suggested that part of the reason why children may be less susceptible to infection is that they have fewer ACE2 receptors than adults, which is the critical entry point into our bodies for Covid-19. But many of the emerging variants, including the B.1.1.7 variant, have mutations that increase the virus’ ability to bind to our ACE2 receptors — tighter receptor binding means that even with fewer ACE2 receptors, children now have a higher likelihood of becoming infected when they encounter the virus. 785
Compounding the problem is the fact that children are a relatively naive population — not in terms of education or intelligence, but in terms of immunity. Having no widespread immunity conferred from previous infections, our youngest generations are more susceptible to infection today. This is why we must all take special note of the warnings from Italy. In the United States, the relatively low rate of severe illness and death among children has been used as the rationale for reopening schools and has fed into the current CDC school guidelines. Those guidelines note that children are less susceptible to infection than adults and suggest they may be less infectious, even though other studies have shown that Americans living with a child attending school in-person are at an increased risk of Covid-19, especially when schools don’t employ comprehensive mitigation measures. It was nearly a year ago that Europe unwillingly became the epicenter of the epidemic, before passing that title on to those of us in the United States. Now, once more, their unfortunate experience risks being passed on to those of us here if we don’t heed the alarm and pay greater attention to the possibility of widespread infections in our schools. Already, we are seeing tragic ripple effects of the pandemic on the health of our youngest, on their mental health, routine vaccinations, and even on their ability to access lifesaving services like cancer care. We cannot stand by and watch another tragedy unfold. Decisions on school reopening should be based on data — what is the prevalence in all school populations, children, adults, students, teachers and support staff? When new data emerges, like the data coming out of Italy, we must keep a close eye on it. The situation can change quickly, particularly with the variants. We must act on real, transparent, actionable data to protect our youngest, not on our perceptions. With this disease, the past is not prologue. This article originally appeared in Forbes and is available online here:More Cause For Concern Around Covid-19 And Schools
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Opinion: “Covid-19 Variants and the Safety of Students” Daily Clout | March 5, 2021 | Article
This month one year ago, schools and universities across the United States closed down to assure the safety of students, faculty members, and their families from SARS-CoV-2. Since then, more dangerous, infectious variants have emerged that should have us redoubling efforts to make schools and universities safe. The first variant to make the news, B.1.1.7, is thought to have surfaced in September 2020. It became the dominant strain by December, and it has been found in nearly 80 countries as of today. Since its discovery, plenty of new variants have emerged, with mutations that could make some more transmissible, immuneevasive, and more lethal. To date, the majority of the discussion on variants has focused on their ability to affect the effectiveness of SARS-CoV-2 vaccines, many of which were produced using technologies unique to the virus’s first strain, which originated in Wuhan, China. Although vaccine developers are now reconfiguring their pipelines to allow for more viral variety, there is still a need to recalculate other public health strategies that we have relied on to contain the pandemic—especially those implemented in schools. Until now, parents and educators took solace in the fact that children are less likely than adults to contract SARS-CoV-2 and become sick as a result of it. Conversely, in Italy and Israel, where the UK variant appeared last year, health officials are reporting a much greater rate of spread among children and teenagers than in the first or second waves. In January alone, more than 50,000 schoolage Israelis were confirmed to have SARS-CoV-2, according to a report published earlier this month in BMJ. Meanwhile, in Italy, the northern village of Corzano, which has a population of 1,400 people, has recently experienced an epidemic that has infected at least 10% of the population. More than half of these cases—60%— involved children who then infected other family members.
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University campuses are a breeding ground for SARS-CoV-2, with greek life and college sports posing serious risks to the health of students and faculty members. As of December of last year, college sports reported at least 6,629 cases of SARS-CoV-2. The true number is much higher. Universities have also found it particularly difficult to control fraternities and sororities. Despite the fact that they dominate social life on many campuses, the homes that house them are often not owned or controlled by the institutions, and have been the central hotspots for social events. According to some researchers, the same lack of oversight is given to the containment of the virus. As of now, even though campuses are offering online lectures, people are still living in some fraternity and sorority houses. Given the unpredictable nature of the variants, the potential surge of cases by reopening schools and universities may trigger a deadly fourth wave. According to a recent publication by the University of Michigan, three individuals have tested positive for the SARS-CoV-2 variant, B.1.1.7. University health authorities are collaborating with state and local public health officials and continue to recommend that both undergraduate and graduate students in the Ann Arbor area be tested regularly, even though they are attending all of their classes online. For people who come to campus, weekly testing is mandatory. As part of its “Covid-19 sampling and tracking program”, the University of Michigan is testing asymptomatic undergraduate, graduate, and professional students for free. Averaging at over 21,000 tests weekly, it is taking the right steps towards what could eventually be a safe reopening. The next step would be to make self-administered rapid tests widely available for free, as Austria has done with its school children who are required to test themselves twice a week in order to return to school. The fear isn’t just that students infected with a more evolved and infectious strain of the virus will pass it on to others. The more students who are infected with SARS-CoV-2, the more will experience MIS-C, or Multisystem Inflammatory Syndrome in Children. This rare inflammatory condition affects children as young as 4 months to as old as 20 years and can cause fever, swollen eyes, and intestinal issues, as well as heart failure and death. The number of MIS-C cases reported in Los Angeles County increased by 35% in the first two weeks of February. According to the CDC, 15-20 year olds make up 15% of all MIS-C cases, which encompasses a 788
large proportion of undergraduate students which stands at 18.1 million. With further research required on MIS-C, we still do not know what role variants have to play, so we must enforce stronger public measures to prevent a surge in SARS-CoV-2 cases. With obvious implications on the physical well-being of students, SARS-CoV-2 has also taken a huge mental toll on them. In a recent study “almost 75% of respondents reported their mental health has worsened, worsened somewhat, or worsened significantly since the beginning of the pandemic”. Slightly more than 87% of students reported stress or anxiety, and 60.7% reported depression have all escalated since the outbreak of the pandemic. With a total of 22.4 million graduate and undergraduate students currently enrolled in schools in the US, that means 16.8 million students reported worsened mental health. These statistics are the reason why we should do everything in our power to avoid a fourth wave. According to Dr. Rochelle Walensky, head of the CDC, and the Covid-19 Response Team, the new variants are a threat not to ignore. “Please hear me clearly,” she added. “At this level of cases, with variants spreading, we stand to completely lose the hard-earned ground we have gained. These variants are a very real threat to our people and our progress. Now is not the time to relax the critical safeguards that we know can stop the spread of Covid-19 in our communities, not when we are so close. We have the ability to stop a potential fourth surge of cases in this country. Please stay strong in your conviction. Continue wearing your well-fitted mask and taking the other public health prevention actions that we know work.” While some might argue that reopening schools now will help mitigate the psychological effects of the pandemic on young adults, now is not the time to give in. The pandemic seems to be winding down and vaccines are more widely available, giving some a false sense of security. With their stronger nature, variants pose dangers of reinfection and illness more fatal than ever before. This article originally appeared in Daily Clout and is available online here: Opinion: “Covid-19 Variants and the Safety of Students”
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Lessons From The Past And Present For Controlling Covid-19: Polio Forbes | March 8, 2021 | Article
This article is the first in an ongoing series about what we can learn from successful efforts to vaccinate against other diseases and apply to interventions against Covid-19. Though we’ve cycled through many kinds of public health interventions in our struggle to stop Covid-19 from spreading, mass vaccination is now the primary means through which we’re aiming to end the pandemic for good. Given this, more than ever we need to be studying mass vaccination campaigns that proved successful. The most astounding of these by far was polio—an eradication effort more than 70 years in the making that, thanks to a new vaccine model, may finally come to an end. In this article I’ll explore the research behind this vaccine in greater detail, not just to elaborate on why it is so impressive, but to delve deeper into its lessons for the current crisis. Of all the diseases to cause global pandemics in the past century, the only we’ve eradicated so far is polio. Thanks to vaccines, polio prevalence has been reduced to a small sliver of what it once was— at its worst in the late 1940s, infecting hundreds of thousands and paralyzing more than 35,000 people a year. Unlike SARS-CoV-2, the virus that causes Covid-19, the poliovirus exists only in humans, meaning it can’t come at us sideways from an animal reservoir. Even so, parallels exist between the two that are worth considering as our conversations begin to shift from short-term to long-term immunity. One lesson from polio we must take into account is the importance of distinguishing between a vaccine that prevents disease and a vaccine that prevents transmission. The struggle to eradicate polio drove home the fact that different vaccines elicit different types of immunity, each with its own set of implications for public health. The current generation of Covid-19 vaccines, created by the likes of Moderna and Pfizer, prevents serious illness and death, as
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evidenced by their enormous success in clinical trials. But whether they will stop transmission is currently unknown. The distinction is an important one, in some cases a matter of life or death. The inactivated polio vaccine created by Jonas Salk in 1953 is able to prevent disease—that is, the onset of debilitating symptoms like paralysis—and trigger a long-lasting antibody response that can remain in effect for many, many years. But it doesn’t prevent infection or transmission through the nose, mouth, or gut, which is why it wasn’t effective at wiping out the poliovirus altogether. People vaccinated with it could still shed infectious virus. It was ultimately the live-attenuated oral polio vaccine, an invention of Albert Sabin’s used for the first time in 1961, that made the largest contribution to global eradication, not just because it was cheaper and easier to administer, but also by virtue of its ability to prevent the holy trinity of infection, transmission, and disease. How it elicits such powerful immunity remains somewhat a mystery, but its efficacy cannot be denied. Another important distinction exists between SARS-CoV-2 and poliovirus that is equally instructive. For both viruses the roots of transmission are similar but different. For polio, it’s mostly gut-based but also nasopharyngeal; for Covid-19, it’s the opposite, mostly through the nose and mouth but occasionally the gut, characteristic of respiratory viruses in general. That we still need an annual flu shot is proof of how difficult it has been to develop vaccines capable of engendering long-lasting immunity against respiratory viruses. One reason why is we simply don’t know enough about their immunology more broadly—a gap in our knowledge we’ve had opportunities to fill, but whether for lack of interest, funds, or infrastructure never did. Intimate knowledge of viral mechanisms of transmission doesn't come easy or cheap. Our near-global eradication of polio, as well as our deep understanding of how the poliovirus works, is the product of many decades of research dedicated not just to polio specifically but molecular biology, gene manipulation, and advancing biomedicine at large. Funding was in abundance, and the collective will to push the frontiers of what we knew was strong. Over a span of decades scientists around the world studied the virus rigorously, discovering that the main obstacle to permanent eradication was its ability to occasionally regain virulence despite vaccination—hence 791
the handful of cases each year. Every so often, they discovered, the attenuated virus—that is, a non-virulent version—used to create the vaccine reverts to its original disease-causing and potentially paralyzing form. Infections caused by these viruses, which are estimated to occur at a rate of 4.7 per million births, are referred to as vaccine associated paralytic poliomyelitis. For decades, vaccine associated paralytic poliomyelitis was considered a necessary risk. But as we’re now well aware, thanks to our struggle to contain Covid-19, so long as one person is infected, no one is totally safe from harm. The good news is that advances in genetic technology are helping us tackle the challenge of viral evolution with greater precision—which is exactly what a group of scientists working under the auspices of the New Oral Poliovirus Vaccine Consortium has done, according to a study published last year in Cell Host & Microbe. By identifying the exact mutations that allow an attenuated poliovirus to become dangerous once again and engineering a version that averts them, this research brings us one step closer to a vaccine that could eradicate polio once and for all. Perhaps the main reason why the oral polio vaccine is so effective at preventing infection and transmission is its ability to engender immunity in both the mouth, nose, and gut. As I mentioned before, excretions from both these bodily points of entry and exit are the most efficient routes a poliovirus can take—aided and abetted by poor sanitary conditions—to get from one host to another. By introducing an attenuated virus at the intestinal level, the oral vaccine eliminates these modes of contagion, and by extension its ability to circulate freely in the wild. One of the biggest determinants of attenuation is a point mutation, 481A, in a noncoding region of the poliovirus known as domain V, or domV, that destabilizes the virus’s translation mechanism, in essence keeping it from expressing more lethal forms of itself. It is in the best interest of the virus, however, to mutate and select for structural stability. And when the difference between the two is only a matter of a single nucleotide, it should come as no surprise that in the few VAPP outbreaks that have occurred in recent years, a 481 A-to-G mutation appeared with high frequency. The goal of the researchers, then, was to engineer a virus that greatly reduced the likelihood of mutation and recombination 792
events—in other words, curtail its capacity to adapt even further— without compromising the process of viral replication that is so essential to building gut immunity. How they did this came down to a total of five modifications, divided up between three areas of focus. First was domV, which they not only stabilized but locked into a tight configuration, so as to occlude any possibility of reversion. Second, they altered the error-prone polymerase, an enzyme key to viral evolution and genetic diversity more generally. Last but not least, they relocated a cis-acting replication element (cre) closer to and upstream of domV. That way if the virus does attempt recombination, it won’t be able to swap out the stabilized bits so readily. These alterations, deduced based on evidence from cell culture and animal models, work against reversion in tandem, but are at their core functionally independent, coming together to form a “multilayer safety-net.” Even if mutations still developed in all three of these targeted areas—a highly unlikely occurrence, but minutely possible nonetheless—that strain would still be at least 250 times as attenuated as a reverted version of the current oral vaccine. The next step was to test the safety and efficacy of the engineered virus through a phase I vaccination trial. To work, the new vaccine, which the researchers called nOPV2, had to be just as antigenic and immunogenic as before, but without the near omnipresence of reversion-enabling mutations in the shed virus of trial participants. Strikingly, trial participants who received a dose of the nOPV2 vaccine had no mutations, including at the 481 site, in the domV region, confirming that the modifications had successfully impeded viral evolution without affecting replication. What these researchers were able to achieve by using new technology to rigorously analyze the poliovirus, its enabling mechanisms, and countermeasures against it is nothing short of remarkable. Therein lies the final and arguably most important lesson that polio research has for those of us trying to unravel the current crisis. To create effective, long-lasting countermeasures like vaccines that will grant us immunity from Covid-19 not just this year, but the next and the many thereafter, we need to understand the virus SARS-CoV-2 in much greater detail, pouring as much funding and resources into coronavirus research as we did for polio back in the 1940’s and 50’s. Such an effort would come with the added bonus 793
of shedding light on other respiratory viruses—primarily influenza— that have mystified us for so long. In my next piece for this series, I will delve further into how the battle against polio was won, focusing specifically on a factor that isn’t altogether missing from efforts to stop the current pandemic, but could certainly be improved: global cooperation. This article originally appeared in Forbes and is available online here: Lessons From The Past And Present For Controlling Covid-19: Polio
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T-Cell Responses Hold Up Against SARS-CoV-2 Variants, Study Finds Forbes | March 8, 2021 | Article
There is remarkable news regarding the immune response to SARSCoV-2. It is clear now that the virus mutates to evade the neutralizing antibody responses. There are new results that suggest that is not the whole story. When it comes to another arm of immunity, T-cell immunity, high response to one form of the virus means high response to them all. Here we will review what that might mean for the future of Covid-19. In the months since SARS-CoV-2 variants came to the forefront of Covid-19 discussion, the average person is left with a number of questions. Will the vaccine my grandmother just received protect her from emerging strains? What about my previous infection during the summer? How long might that protection last? Vaccines and prior infections confer antibodies, which are proteins produced by B-cells to counteract a specific antigen. Picture a custom couture tailored to you. The fabric aligns perfectly with every inch of your torso. An antibody is like a tailor-made protein that fits a specific pathogen, in this case, SARS-CoV-2. However, ample research indicates that these antibodies fade rather quickly over time, and may not protect as well against some variants. Though as it turns out, B-cells and antibodies are only half the adaptive immunity puzzle. The other piece is the T-cell. These are types of white blood cells in the immune system which act as the front-line soldiers against disease. Their purpose is to eliminate invading pathogens and clean up dead cellular debris. They do this by remembering past infections, waiting to encounter short amino acid sequences of the virus called peptides, then killing the virus when it reappears. Whereas antibodies are tailor-made proteins for a specific virus, T-cells attack a range of different pathogens, like a suit purchased off the rack. It may not quite fit exactly, but close enough will do and it will fit many others as well. 795
The T-cell is another tool in the arsenal against Covid-19, but the questions above must be translated in reference to this secondary weapon. Will T-cells protect against rapidly emerging variants of the virus that show signs of resistance to antibodies? Research from the La Jolla Institute of Immunology, led by Dr. Alessandro Sette and Dr. Shane Crotty, sought to illuminate these unknowns. Their findings were encouraging. When exposing human Tcells from a wide range of hosts previously infected with Covid-19 to a number of SARS-CoV-2 variants, the T-cell response held up well. Responses decreased at most 30% relative to that cell’s response to the SARS-CoV-2 wild type. In some cases, such as the South Africa variant, T-cells produced a nearly equal response to the variant as the unmutated virus. The same can be said for samples pulled from people vaccinated against Covid-19. Their T-cells responded in an equal or slightly decreased volume in comparison to the wild type. This is a major victory, confirming that T-cells have some effect in slowing mutated variants down, but to what extent? There are strengths and weaknesses to the T-cell response. The strength, as shown by these researchers, is the blanket coverage they have over the variants. The virus is adaptive and mutative—changing over time. When we introduce antibodies specific to the virus, it has shown an ability to develop mutations to the receptor-binding domain, n-terminal domain, or elsewhere, that renders the antibody less effective. With T-cells, because everyone has their own unique hereditary set rather than one specific developed antibody from a vaccine or previous infection, the virus cannot adapt. The weakness, however, is that T-cell responses to SARS-CoV2 are limited. T-cells are not designed to prevent infection, only to kill the cells once they are in the body. The researchers confirm this by concluding that “while it is not anticipated that circulating memory T cells would be effective in preventing SARS-CoV-2 infection, it is plausible that they can reduce Covid-19 severity.” Given all this, it may be the case that SARS-CoV-2 is allowing a certain level of T-cell response. Variants evolved while T-cells were present, prompting the idea that viruses are modulating the Tcell response to low enough levels for them to continue to spread. While mostly speculative, it seems possible that the virus could have regulatory influence on the T-cell. 796
Regardless, T-cell reactivity in the face of variant forms of SARS-CoV-2 is an unmitigated positive. The implication is that those vaccinated or previously infected will have at least some form of defense against newly circulating variants, even if they are capable of evading antibodies. This is much needed positive news in the face of the growing variant threat. This article originally appeared in Forbes and is available online here: T-Cell Responses Hold Up Against SARS-CoV-2 Variants, Study Finds
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The Covid Syndemic: The Mental Health Crisis Of Mental Health Workers Forbes | March 8, 2021 | Article
Asyndemic refers to multiple interrelated epidemics happening at the same time. Covid-19 has unleashed and amplified a number of simultaneous personal, social, medical, political, and economic crises. This is the first in a series of articles exploring the impact of the Covid-19 syndemic. When we think of frontline health workers battling the pandemic, we often think only of the physicians working on-site in hospital settings. But while most mental health professionals aren't physically serving on the frontlines of this pandemic, they have been hearing about it in excruciating detail from their patients for almost a year. As the pandemic continues, so does the demand for mental health services. According to the Kaiser Family Foundation, 4 in 10 adults in the U.S. have reported symptoms of anxiety or depressive disorder during the pandemic. This figure has risen dramatically from one in ten adults who reported these symptoms from January to June 2019. Research from prior economic downturns shows that job loss is associated with increased depression, anxiety, distress, and low selfesteem. Even those who have not been impacted financially or have experienced the loss of a loved one have still had their lives disrupted and live with the daily uncertainty that the pandemic brings. In a CDC survey of 5,412 Americans during June 2020, 40.9% of respondents reported at least one adverse mental or behavioral health condition, including symptoms of anxiety disorder or depressive disorder (30.9%), symptoms of trauma, and stress-related disorder arising from the pandemic (26.3%). Healthcare workers are putting their physical health at risk by caring for Covid-19 patients and their mental health as they endure unprecedented death tolls. Mental health professionals are finding themselves charged with the heavy responsibility of guiding others through this time of loss and uncertainty, without most of their usual coping mechanisms. Many are taking on larger caseloads and working longer hours as the 798
demand far exceeds the number of therapists available, leaving little time for respite. According to an American Psychological Association (APA) poll of nearly 1,800 psychologists published in November, 74 percent said they were seeing more patients with anxiety disorders compared with before the pandemic, and 60 percent said they were seeing more patients with depressive disorders. Psychiatrists have written about the challenges of regulating their own reactions during sessions as they learn how to provide therapy during a pandemic. In an APA poll, 4 in 10 psychologists (41%) said that they felt burned out and 30% said that they have not been able to meet the demand for treatment from their patients. When their patients are experiencing the same stress and expressing the same anxieties it becomes increasingly difficult for therapists to compartmentalize. An article from the American Psychological Association warns of the risk of psychologists developing "compassion fatigue" during the pandemic. Charles R. Figley, PhD founder of the Traumatology Institute at Tulane University, defines a phenomenon he calls "compassion fatigue" as psychologists or others taking on the suffering of patients who have experienced extreme stress or trauma. "It's like a dark cloud that hangs over your head, goes wherever you go and invades your thoughts," he says. Compassion fatigue manifests as a lack of empathy for patients, physical and emotional exhaustion, and feelings of numbness, anxiety, and depression. All these conditions inhibit therapists from providing care to patients and wreak havoc on their mental health. The American Psychological Association suggests several strategies to build resilience against compassion fatigue. The most important step is recognizing the signs of compassion fatigue. The Professional Quality of Life measure developed by psychologist Beth Hudnall Stamm, PhD can be used as an objective tool to determine symptoms such as loss of productivity, depression, intrusive thoughts, and compassion satisfaction. Introducing self-care strategies such as adequate sleep, healthy nutrition, physical activity, relaxation and safe socializing as part of a consistent routine is also important. Practicing self-compassion by acknowledging the difficulty of your situation and taking days off without feeling guilty is also encouraged. Finally, therapists should create community by 799
reaching out to their professional networks for support and understanding. Encouraging mental health professionals to practice these strategies is one step towards preventing burnout. But in addition to caring for our current mental health professionals, we need to encourage more people to enter the profession in order to meet the overwhelming demand. This article originally appeared in Forbes and is available online here: The Covid Syndemic: The Mental Health Crisis Of Mental Health Workers
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Covid-19 Reinfections Are Real And Serious— All The More Reason To Be Vaccinated Forbes | March 10, 2021 | Article
Emerging news from Brazil on Covid-19 reinfection is a potential warning for all of us on the danger SARS-CoV-2 variants pose, both to those who have already been infected and, very likely, to those who have been vaccinated. This new data on the antibody-resistant Brazilian variant (P.1) can begin to shed light on a number of questions people may have. Can you get reinfected if you had a past infection and if you are reinfected, will you get sick? Lead researchers on the Brazilian strain, including Dr. Nuno Faria of the Imperial College of London, first released their discovery and analysis of the variant on January 12th, 2021. The sample arose in Brazil in December 2020 but rocketed to 87% of samples by early January and over 99% of samples by February. For such a drastic acceleration of variant integration, there must have been reinfections. As it turns out, it may have been the driving force. Dr. Faria noted the likelihood that most of the cases observed in P.1’s spread the past few months were reinfections. This likelihood is derived from antibody effectiveness six times weaker against P.1 in comparison to previous SARS-CoV-2 strains. Another study found that when the P.1 spike protein is implanted in another virus, antibodies neutralized it at lower levels than the wild-type virus, but not quite as low as the full P.1 pseudotype. This means that mutation to other parts of the genome, specifically ORF1ab, ORF3a, ORF8, and the nucleocapsid protein, likely have a hand in immune evasion as well. Using data from Manaus and other areas of Brazil, Faria estimates that P.1 was between 1.4 and 2.2 times more transmissible than previous SARS-CoV-2 strains and that between 25 and 61% of previously infected patients were susceptible to P.1 reinfection. Natural infections do not seem to protect against reinfection, yet vaccines remain to be seen. While Faria found that antibodies derived from the CoronaVac vaccine in Brazil were less effective at 801
stopping the P.1 variant, little data is yet available on reinfections after vaccine administration. We know that antibodies fade over time and data suggests that you lose tremendous antibody potency six to eight months after natural infections. It is possible that vaccine protection wanes six months to a year after administration, but that data will not be available for many months. In brief, the notion that antibodies are completely protective is tainted. P.1 prompts reduced protection against natural antibodies and could potentially do the same for vaccines down the road. This strain presents a dangerous potential for spread even after mass vaccination. Reinfection en masse is a significant possibility. The figure below shows the decline of immunity for the Brazilian variant in red, as opposed to the wild-type or UK variant. While rare as of yet, reinfection cases seem to have more intense symptoms on average. A recent report from the Centers for Disease Control and Prevention (CDC) details reinfection in a Kentucky elderly facility. In the summer of 2020, this nursing home reported 25 positive cases of Covid-19. Several months later, from October to December, the same facility reported over 100 cases, with five testing positive for the second time. While only three of the five experienced moderate to severe symptoms of the first infection, all five did the second time around. One reinfected resident was hospitalized and succumbed to their illness. All five residents tested negative for the virus at least four times between infections, confirming reinfection and not simply a prolonged infection. The study notes the possibility that mild or asymptomatic cases of Covid-19 during the first infection may indicate a less than sufficient immune response to prevent reinfection. If this is the case, and second infections are more severe, then many millions of previously asymptomatic Covid-19 cases face the danger of aggressive reinfection. We also have examples of reinfection from other parts of the world, namely South Africa. During the Novavax vaccine trials in South Africa, the study found an overall primary efficacy of 49.4% in 4,400 participants, meaning about half of the patients vaccinated and later infected did not experience symptoms. Genomic analyses revealed that about a third of the 4,400 were previously positive for infection, meaning the South African variant was then and is now
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capable of reinfection, evading neutralizing antibodies in a similar capacity to the Brazilian variant. I emphatically agree with all those who encourage everyone to be vaccinated as soon as possible. The current generation of vaccines will protect you, at the very least, in the short run. How long that protection may last, we cannot say. We hope when data becomes available, indications point to protection for at least a year from the wild-type and emerging variants of the virus. Until we have answers to these long-term questions, we must remain hopeful, but cautious. This article originally appeared in Forbes and is available online here: Covid-19 Reinfections Are Real And Serious—All The More Reason To Be Vaccinated
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New Study Using Live Virus Explores Whether Pfizer-BioNTech Vaccine Protects Against Variants Forbes | March 11, 2021 | Article
When new variants of SARS-CoV-2, the virus that causes Covid19, were discovered to be circulating around the world, the first question for many was whether they would present a serious problem for nascent vaccination programs against Covid-19. While the answer still eludes us, study by study researchers are firming up their notions of what the future, now that it involves a virus that evolves far more rapidly than previously understood, will hold. This early on, the general consensus is mixed. Many are optimistic that the technologies at our disposal—the same that did, after all, miraculously produce safe and efficacious vaccines in less than a year—can adapt and ultimately prevail over the new variants, which have been found to be more transmissible, immune-evasive, and in some cases more virulent than their predecessors. But several experts are also expressing caution insofar as the current generation of vaccines are concerned, in part due to recent reports that antibodies, whether collected from recovered Covid-19 patients or people recently immunized, are less effective at neutralizing artificially mutated versions of SARS-CoV-2. Moving forward, the trick will be striking a balance between these two observations: acknowledging and celebrating the good news that comes our way, but remaining vigilant and ready to take action should viral variation have longer-term consequences on our ability to contain the pandemic this year and for years to come. A correspondence published this week in the New England Journal of Medicine gives us another reason to be of both minds. It details a study of 20 samples of serum that were taken from 15 participants who received two doses of the Pfizer-BioNTech vaccine, then exposed to five viruses carrying mutations seen in the B.1.1.7, B.1.351, and P.1 lineages of the virus—variants that 804
originated in Britain, South Africa, and Brazil, respectively. That they used live viruses is significant, since previous research relied instead on pseudotyped viruses created in-lab by decorating the envelope of other viruses with SARS-CoV-2 spike proteins. The serum, collected two to four weeks after the second immunization, was able to neutralize all five, though the virus carrying a more complete subset of mutations from the B.1.351 variant proved more resistant than the rest, a finding consistent with previous studies of its potential for immune evasion (figure 1). Many media reports have interpreted this as confirmation that two doses of the Pfizer-BioNTech vaccine is adequate protection against the new variants. While the data is certainly encouraging, a number of caveats that weren’t fully addressed in the publication are worth mentioning. First, infection in a test tube is not the same as infection in a person. The researchers who conducted the study acknowledged this, citing a need for “real-world evidence” to further corroborate their findings, but don’t elaborate beyond that. The plaque reduction assay they used in their experiments may not necessarily mimic the full potential and limitations of the antibody response in a person undergoing infection. For a bigger, more accurate picture, cell cultures, primate models, and other methods must be used. Second, the scope of the study doesn’t go beyond mutations that are part of the spike protein, even though this region comprises only 10 percent of the entire viral genome (see difference between Figure 2, a linear representation of the mutations used in one virus looked at in this study, compared to Figure 3, a linear representation of the P.1 genome vs. the P.1 spike). The mutations that weren’t included, which appear in regions like the virus’s non-structural and accessory proteins, may play a pivotal role in affecting antigenicity and immunogenicity that we’ve simply yet to understand. Why these mutations have been neglected so consistently is questionable; if nature is sending us a message, we’d do best to listen in. Future studies must aim to be more comprehensive or risk creating blind spots in the development of variant-specific drugs and vaccines. Third, the serum samples were collected from vaccinees when neutralizing activity was at its theoretical peak. Several studies, including a far more extensive one published in Nature last month and included six recipients of the Pfizer-BioNTech vaccine as well as 14 who were administered the Moderna vaccine instead, show 805
that the potency of sera, whether it belongs to a recovered patient or vaccinee, drops considerably over time (Figure 4). This is true of samples exposed to the original SARS-CoV-2 strain that originated in Wuhan, but even more so of those exposed to new variants. A clinical study conducted by Pfizer and BioNtech is already underway that will test the efficacy of a recently developed booster shot against the new variants. Ideally this study and others like it will involve the full breadth of the viral genomes being analyzed, rather than a narrower selection, in addition to a longer timeline that accounts for the potential reduction in neutralizing antibodies. For now, let’s remain hopeful that more promising evidence awaits us, but keep in mind that SARS-CoV-2 is a force of nature to be reckoned with—one that has surprised us several times over, and may do so again if we’re not sufficiently careful. This article originally appeared in Forbes and is available online here: New Study Using Live Virus Explores Whether Pfizer-BioNTech Vaccine Protects Against Variants
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New Hope For A Covid-19 Vaccine That Protects Against All Variants Forbes | March 11, 2021 | Article
The first generation of Covid-19 vaccines has proven to be remarkably effective. But now that new variants of SARS-CoV-2 are on the rise, the durability and true extent of the protection they offer is being called into question. While we certainly hope that their makers will be able to adapt, there is now evidence that a vaccine capable of immunizing against coronaviruses more broadly—not just SARS-CoV-2 and its new variants—could be on the horizon. Were this pancoronavirus vaccine to come to fruition, revising existing Covid-19 vaccines year in and year out wouldn’t be necessary. The first hint that more potent forms of immunization are possible was a preprint study that analyzed, among other things, the immune responses of recovered Covid-19 patients who had also received a dose of either the Moderna or Pfizer-BioNTech mRNA vaccines. Antibody titers from participants who had prior infections and at least one dose of a vaccine were so high, and packed a punch so powerful, they even demonstrated cross-protective capabilities against SARS-CoV-1. Two new research papers reinforce this concept. Though their methods differ, both use animal models to test whether nanoparticle immunization technology, which combines fragments of different viruses into a single particle and loads it up into a vaccine, is effective at protecting against a large spectrum of coronaviruses. Both also obtained promising results—which, if expanded upon in further studies and eventually clinical trials, could pave the way for a more potent and more broadly protective second generation of vaccines. Not only that, but nanoparticle vaccines are reportedly more costeffective and easier to develop and store—qualities that will become all the more crucial when the frontlines of immunization campaigns shift to more rural and remote parts of the country. The first study, conducted by researchers at Duke University and currently undergoing peer view, developed its nanoparticle vaccine 807
using a “cage” made of ferritin, an iron-rich blood protein. The ferritin cage served as a base for constructing a multimeric nanoparticle, aggregating bits of spike protein from different viruses to reach an optimal level of compatibility with the immune system. The average antibody titer elicited by the resulting vaccine was nearly 50,000—a remarkably robust response comparable to that of recovered Covid-19 patients who have also been vaccinated. It also eclipsed the response generated by an mRNA vaccine the researchers made that was functionally similar to those created by Moderna, Pfizer, and BioNTech—the implication being a correlation between high antibody titers and robust immunization. The second study, which used mice models, was conducted by researchers from Caltech and published in Science this past January. Their nanoparticles were of the “mosaic” variety, consisting of 60 spike protein fragments that were identical in appearance and function, but in actuality taken from up to eight different coronaviruses. Tested against a homotypic nanoparticle—a uniform structure with SARS-CoV-2 fragments only—the mosaic nanoparticles were proven to have more potent binding and neutralizing capabilities. Not only that, but they remained effective against SARS-like coronaviruses found in Chinese, Buglarian, and Kenyan bats, the animal reservoir suspected to be the origins of Covid-19. Even a mosaic that didn’t include a fragment of SARSCoV-2 was nevertheless able to neutralize the virus, while the mosaic with fragments from eight distinct viruses performed exceptionally well, much better than homotypic SARS-CoV-2. If the first study established the significance of high antibody titers to a strong immune response, this one emphasized that cross-protection can be just as important. Do nanoparticle vaccines work in animals other than mice? According to the first study, which gave injections to macaque monkeys, the answer is yes. The monkeys received a total of three booster shots and were exposed to not just SARS-CoV-2 and bat coronaviruses, but the B.1.1.7 (UK) variant, SARS-CoV-1, and MERS-CoV as well. While the nanoparticle vaccine performed best against SARS-CoV-2, consistent with the first study its antibodies were cross-protective, effective at neutralizing B.1.1.7, SARS-CoV1, and bat coronaviruses. Notably, it failed to neutralize seasonal cold-causing coronaviruses and MERS-CoV, a deficiency that can 808
be attributed to differences in their receptor-binding domains. This isn’t a dealbreaker, however, as it can be improved upon in future iterations. While the longer-term effects of new SARS-CoV-2 variants remain to be seen, by now we should know that any chance we have to outmaneuver this virus and prevent further carnage must be seized with haste. SARS-CoV-2 is unlikely to be the last coronavirus to make the leap from animals to humans, just as Covid-19 won’t be the last lethal pandemic to shift the course of modern life. We must pour resources, funds, and brainpower into further lab and clinical studies that explore our potential to create a pancoronavirus vaccine. If we don’t, the consequences will be far greater than a missed opportunity. This article originally appeared in Forbes and is available online here: New Hope For A Covid-19 Vaccine That Protects Against All Variants
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Clearer COVID-19 Guidelines Cause Less Stress for Us All Psychology Today | March 12, 2021 | Article
For almost a year, many of us have watched in anger and frustration as we see others flout public health guidelines. A crisis that could have built social solidarity has pushed us further apart. In a year that has brought countless sources of stress and anxiety, the experience of seeing a friend post about a large indoor gathering on social media, a stranger without a mask, or a celebrity take a lavish international vacation is maddening. Those who are flouting guidelines form a broad spectrum, from those confused by conflicting advice or suffering from “pandemic fatigue” to extreme cases that deny the existence of COVID-19 or reject expert consensus safety measures like mask-wearing despite mounting death tolls. We cannot blame those who are confused by conflicting advice from authorities. The Trump Administration could have introduced centrally coordinated tracing and testing strategies and data-based federal guidelines to uniformly inform local restrictions at the beginning of the pandemic. Instead, states were left to design and enforce their own conflicting public health guidelines. Trump created further chaos by encouraging people to violate emergency orders and “liberate” their states from the most basic safety protocols such as mask-wearing. Residents of some states, like New York, that lived through the trauma of a massive outbreak early in the pandemic have watched in horror as others, like those in Florida, went on about their regular routines, having never been subject to strict public health measures or state mask mandates. Not only are restrictions conflicting between states but also within the states. In November 2020, Rhode Island residents were prohibited from gathering indoors or outdoors with a single individual from outside their household, but restaurants were allowed to operate indoor dining with 66% capacity, and indoor gyms were operating with limited capacity.
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Across the country, people were encouraged not to gather together for Thanksgiving and Christmas meals while watching large groups gather to dine indoors at restaurants or frequent bars. While many understood the motivation to reopen restaurants was to restart the economy, the disconnect between what was done publicly and what was asked of us privately created a discrepancy that was hard to understand. Had the Trump administration provided greater economic security during the pandemic, businesses, individuals and local governments may not have been forced to make such dangerous decisions to preserve their economies and incomes. The inconsistent reasoning behind restrictions erodes public trust and confuses people already exhausted from a year of risk assessment. Many believe that if businesses like restaurants or gyms are allowed to open, it must mean that they are safe, and this confusion over what is safe and what isn’t can lead to clashes with family members or friends over their concerns about the increased risk of infection in these spaces. Arguments over what is considered “safe” or “acceptable” behavior during the pandemic are causing divisive social fractures in the same way polarising political beliefs have in the last few years but with potentially higher stakes. A UK study noted that 56% of 2237 participants reported having had arguments, felt angry, or had fallen out with others because of COVID-19, 22% of participants reported that they had confronted or reported someone. Adult children are exasperated at their high-risk parents for taking unnecessary risks during the pandemic. Those who formed a “bubble” with close friends and family are shocked to find that they can’t agree on what constitutes high-risk behavior or that the size of their bubble has rapidly expanded without their consent. People who have cautiously spent much of the year isolated at home are enraged to regularly see their friends indoor dining, frequenting bars, or jetting across the country and bragging about it on social media. Many friends and family members in your immediate orbit may have initially agreed to vigilantly comply with all guidelines, but as we reach the one-year mark, they are letting down their guard. Healthcare workers have felt much of this anger, having risked their lives and endured unimaginable trauma to care for COVID-19 patients without sufficient PPE. In return for their service, they have watched members of the public carelessly violate public health 811
guidelines, and a President ignore science and mock others for protecting themselves while wearing masks. They have then tangibly experienced the impact as hospitals fill up with COVID-19 patients which will undoubtedly contribute to their PTSD. All these experiences contribute to a feeling of helplessness and despair in the face of the pandemic. Many feel as if they have pointlessly suffered through isolating restrictions when they see stories of unmasked underground parties. The rise of mutual aid networks during the pandemic has restored some faith in humanity, but witnessing the repeated violation of COVID-19 public health guidelines that puts others at risk contributes to a degradation of social solidarity. Many have ended friendships, relationships, and cut themselves off from family members over disagreements about COVID-19 safety precautions. With social distancing in place, it is difficult to replace those friendships and social networks in a meaningful way. The long-term effect is that many will emerge from this pandemic with reduced social support networks which we know are essential to maintaining optimal psychological and physical health. With 4 in 10 adults in the U.S. experiencing symptoms of anxiety or depressive disorder during the pandemic, this is yet another stressor that will contribute to the mental health syndemic evolving from COVID-19. We need to learn from this experience and change how we communicate public health guidelines and information. The fundamental principles are simple enough; you need to be consistent, accurate, and not withhold vital information or set unrealistic expectations. It’s in the execution that the challenge lies. Finding the appropriate messenger for the right audience is key; they need to be well informed to build trust, and most importantly, they need to demonstrate empathy. We have learned during the pandemic that negative messaging or shaming does not encourage behavior change, so we need to take a different approach. We need to understand why some Americans are still opposed to mask-wearing and find a different, more optimistic way to persuade them. Many non-masks wearers still dispute facts about COVID-19 transmission, but something no one can deny is the existence of is flu season. Cases of the flu have seen a historic global decline this season, with only one pediatric death reported in the US. This is a direct result of safety precautions like 812
mask-wearing and social distancing and a big incentive for those who haven’t to start adopting those behaviors. By having clearer, consistent guidelines communicated empathetically from the onset of a public health crisis, not only do we reduce transmission but we also reduce the stress associated with following those guidelines. This article originally appeared in Psychology Today and is available online here: Clearer COVID-19 Guidelines Cause Less Stress for Us All
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Novavax Covid-19 Vaccine Performs Well In Clinical Trials, But Variants Remain A Threat Forbes | March 16, 2021 | Article
More than 330 million vaccinations have been administered in the fight against Covid-19, and a new vaccine candidate is now ready to enter the ring. Novavax recently completed its final analyses and will seek FDA and international approval in the coming weeks. The new candidate uses a mechanism to prompt immune responses that is different from vaccines already in circulation, but remains effective against non-variant forms of the virus. Here I discuss the results and implications of the Novavax trials and the vaccine’s performance against surging variants of SARS-CoV-2. The press release details a United Kingdom trial of 15,000 participants. Against the wild-type strain of the virus, the two-dose vaccine posted 96.4% efficacy. Notably, the vaccine was also 100% effective in preventing severe disease, which included symptoms like tachypnea, high resting heart rate, required ventilation, hospitalization, among others. Included in those 15,000 participants were also infections via the highly transmissible UK variant of the virus. The vaccine still posted an impressive 86.3% efficacy against the variant, which comes to an overall vaccine efficacy of 89.7% among the 15,000 participant study. Additionally, of non-placebo participants in the trial, only one case of Covid-19 was reported among those 65 and older, a demographic heavily hit by the pandemic. Novavax also wanted to see how its vaccine would fare against the antibody-resistant South African variant of the virus. Among a participant group of 2,905 adults, the vaccine demonstrated an overall efficacy of only 48.6% against the predominant B.1.351 variant. While no severe Covid-19 was noted in the vaccine group, these numbers are less encouraging than the UK group. Among HIV-negative adults, the efficacy rises to 55.4%, which is still well below par. This is a consistent theme across the vaccine landscape. The South African variant, along with its genetically similar 814
counterparts like those in Brazil, Japan, and elsewhere are significantly resistant to vaccine-induced and naturally formed antibodies. The Novavax vaccine works by combining a purified spike protein with an adjuvant, or a substance designed to enhance a given immune response. In 1984, I used essentially the same formula — adjuvant, envelope, and the equivalent of a spike — to create a vaccine that prevents cats from contracting leukemia. It is an old technology, but arguably the most direct line of attack we can mount against a virus. Other FDA-approved Covid-19 vaccines employ methods that are certainly innovative and still effective, but on the whole more roundabout approaches to hitting the same target. These include the messenger RNA in the Moderna and PfizerBioNTech vaccines, which instruct human cells to make spike proteins, and the adenovirus vectors in the Johnson & Johnson and AstraZeneca vaccines, which carry instructions for creating antiSARS-CoV-2 antibodies. That the clinical trials for the Novavax vaccine have yielded such promising results is a great sign, especially given the rise of new variants. Many pharmaceutical companies have already announced that they are developing second-generation vaccines tailored directly for these new variants. The only hesitations to note are which ones are they tailoring towards, and what if new ones arise in the time it takes to develop, test, and distribute? The illustration below shows some of the many variants that have branched off from the wild-type of SARS-CoV-2. Regardless, these hesitations should not take away from the positive news regarding this story. A new vaccine will soon be available that posts high efficacy towards the wild-type and one of the most prolific variants. Here’s hoping this vaccine will help reign in case numbers as new vaccines are developed in the coming months. This article originally appeared in Forbes and is available online here: Novavax Covid-19 Vaccine Performs Well In Clinical Trials, But Variants Remain A Threat
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Molnupiravir: A New Hope For Prevention And Treatment Of Covid-19 And Other Dangerous Viruses Forbes | March 16, 2021 | Article
A new Covid-19 therapy has completed its phase two human trial and the results are promising. Molnupiravir, developed by Ridgeback Biotherapeutics LP and Merck & Co., reached its endpoint objective of reducing the length of Covid-19 infections, according to a Merck press release. This endpoint, among others, will be examined in greater depth upon the full data release from the trial. Respiratory viruses like influenza, respiratory syncytial virus, and now Covid-19 are uniquely challenging to treat once symptoms arise. Because infections and symptoms for respiratory viruses are typically short-lived, the immune system quickly engages in viral replication suppression. Common form antivirals like Tamiflu and Xofluza for the flu, and now Remdesivir and monoclonal antibodies for Covid-19 must be administered within the first few days of infection to reduce symptom severity and infection duration. For respiratory antivirals, their ideal use is for those recently exposed to viruses from family members or workplaces. Following known exposure, Influenza A antiviral Xofluza reduced transmission by 80% in a close-quarter family context. For Covid-19, monoclonal antibodies have been shown to achieve similar close-quarter transmission effectiveness, but they have a catch. Unlike Xofluza, monoclonal antibodies require infusion outside the home. Xofluza and antivirals like it are pill-based, capable of home-use, and can be ingested quickly after exposure. This new drug, Molnupiravir, may be a Xofluza-like alternative for Covid-19, which could be a powerful addition to our armamentarium, in addition to vaccines, especially for variants that seem to escape vaccines. Molnupiravir was first developed as preventative medicine and treatment for SARS-CoV and MERS in the early 2000s. The drug 816
has been previously shown to work against many viruses that employ an RNA-dependent RNA polymerase, which SARS-CoV-2 also has. The polymerase is the enzyme that copies the genetic material of the virus into new genetic material and produces the messenger RNAs that direct the production of all the viral proteins. Molnupiravir is a shape-shifter, called a tautomer. It assumes two forms, one which closely resembles uracil and the other cytosine. Because it appears in these two different forms, once it is recopied, the replicating polymerase develops transition mutations, where a U nucleotide is converted to a C and a C to U. Copying RNA that contains Molnupiravir results in fatal flaws in the sequence, stopping replication, shortening infection, and limiting transmission. The figure below shows the replication process, and the red box indicates the polymerase mechanism with which Molnupiravir incorporates. The difference between the structure of an authentic nucleotide and Molnupiravir is apparently too subtle to trigger removal by the exonuclease repair function of the viral polymerase, a function that has bedeviled these of many other nucleoside inhibitors. Early studies on Molnupiravir on SARS-CoV-2 in vitro indicated a logarithmic drop in virus production dependent on the dose of Molnupiravir introduced. This was possible because the RdRp of SARS-CoV-2 and SARS-CoV, which the drug was initially intended to treat, have 99.1% nucleotide similarity. Whole-genome deep-sequencing showed dose-dependent accumulation of random low-frequency mutations. Repeat exposure of virus populations to the drug was rapidly sterilizing, confirming that none of the random mutations mediate resistance to the drug. In the figures below, titer levels and genome production of SARS-CoV-2 decrease as the drug is introduced in higher volumes. At the time of the early study, mouse models and human testing were not yet available for Molnupiravir, but human trials began in June 2020. As detailed in a press release by Merck & Co, the preliminary results of these trials are promising. The trial was comprised of nonhospitalized adults who had symptoms of Covid-19 within seven days and confirmed SARS-CoV-2 infection. The released details indicate that Molnupiravir in its full dosage prompts a reduction in days to negativity for the virus in nasopharyngeal swabs taken from participants with symptomatic 817
SARS-CoV-2 infections. Five days after dose administration, 0% of those who received the dose were positive for the virus (0/47) compared with 24% of the placebo group (6/25). While details and study size is limited, a measurable drop in infection length is significant, as shorter infections may yield a smaller chance of transmission or severe symptoms. The Merck press release follows a detailed study of this polymerase inhibitor in ferrets, given that ferrets and related members of the weasel genus can transmit viruses asymptomatically, resembling the human spread of viruses. Researchers found that this drug not only prevents close-quarter animal groupings from becoming as sick but the drug also reduces transmission of the virus. The figure below demonstrates the ferret study duration and test grouping. These results may very well be replicated in human trials when that data is released in the coming weeks. The positive results of Molnupiravir represent an emerging hope for more Covid-19 therapies to come. Its oral administration indicates a potential drug that could come before hospitalization and perhaps even prevent severe symptoms. Were a pill-based treatment for Covid-19 available, many lives would be easily saved and many hospital beds could be opened for those who need them. In addition to its reduction of Covid-19 transmission, Molnupiravir is likely to be useful against influenza, ebola, and a large swath of other viruses as well. Its development appears to be a major advancement in virus control and should be active against Covid-19 variants and variants of other viruses. However, we caution Molnupiravir should be administered in conjunction with other therapies to avoid viruses rapidly developing resistance, which all these viruses are well-equipped to do. Though, as these results are preliminary, we eagerly await the full release of the phase two data and the drug’s eventual full trial outcomes. This could be a real winner. This article originally appeared in Forbes and is available online here: Molnupiravir: A New Hope For Prevention And Treatment Of Covid-19 And Other Dangerous Viruses
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COVID-19 Survivors At Risk Of Depression And Other Disorders Psychology Today | March 16, 2021 | Article
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One study revealed that 52% of people who recovered from COVID-19 met criteria for major depressive disorder.
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Another study showed that twice as many COVID-19 patients received a psychiatric diagnosis after recovery compared to those who had influenza.
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Support for COVID-19 patients needs to include psychiatric screenings and pathways to treatment and care.
Two studies have given insight into how COVID-19 symptoms are associated with the probability of subsequent depressive symptoms or psychiatric disorders. The first study by researchers at Massachusetts General Hospital in Boston has found that some COVID-19 patients who suffer from prolonged symptoms after recovery, including anxiety, mood disorders, sleep problems, and fatigue, are also at a greater risk for depression. The study looked at more than 3,900 Americans with prior COVID-19 illness surveyed through online questionnaires between May 2020 and January 2021. Participants were asked to indicate the presence or absence of specific symptoms and self-report the overall severity of COVID-19 infection. The participants then completed a screen for symptoms of depression with those scoring higher than 10 considered to be suffering from depressive symptoms. The average length of time since initial COVID-19 symptoms was four months. A total of 2046 participants (52.4%) met the criteria for symptoms of major depressive disorder. The results of the study demonstrated that depressive symptoms were more prevalent in
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younger patients, men, and those who self-reported their COVID19 infections to be more severe. However the study’s authors acknowledge that they did not control participants for prior history of depressive episodes, so they cannot attribute these symptoms to new onset of depression or determine whether those with preexisting depressive symptoms could have a greater risk of contracting COVID-19. The second study from the University of Oxford which looks more broadly at the development of psychiatric disorders including anxiety and depression post-COVID-19 diagnosis sheds some light on these questions. The study analyses the electronic health records of 69 million Americans, 62,354 of whom had a diagnosis of COVID-19. Nearly 6 percent of individuals diagnosed with COVID-19 developed a psychiatric disorder for the first time ever within 90 days, compared to 3.4 percent of patients who didn’t have COVID-19. Psychiatric diagnoses after recovering from COVID19 were two times higher than being diagnosed with a psychiatric condition after recovering from influenza. These numbers demonstrate the significant neuropsychiatric consequences of COVID-19 infection in some patients compared to other health events. In addition to this study, a report in the mainstream press from STAT cites that experts predict 1 in 3 patients recovering from COVID-19 could experience neurological or psychological after-effects of their infections. Finally, patients with pre-existing psychiatric disorders were 65 percent more likely to be diagnosed with COVID-19. While this is just one study, the sample size is significant and highlights how psychiatric disorders like other chronic diseases such as obesity and diabetes can leave our population especially vulnerable to future epidemics and pandemics like COVID-19. Both studies contribute to a growing body of evidence that implores us to consider the potential neuropsychiatric consequences of COVID-19 infection. Efforts should be made to establish a primary care doctor for patients who are diagnosed with COVID19 who can guide them through all elements of the recovery process. Follow-up care for post-COVID-19 patients should include psychiatric screenings and pathways to treatment and care if patients develop symptoms of depression or another psychiatric disorder. The overall numbers in the second study could be higher due to the 820
barriers in accessing care and treatment. We need to begin to build the mental health treatment infrastructure that will serve all the influx of patients who have developed one or more mental illnesses as a direct or indirect consequence of COVID-19. This article originally appeared in Psychology Today and is available online here: COVID-19 Survivors At Risk Of Depression And Other Disorders
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The Covid Pandemic Is Not Over: The Past May Be Prologue Forbes | March 16, 2021 | Article
Public health officials have told us that we are in a race between Covid-19 vaccines and the virus. But in order for us to win, we need a much longer track. With a slight decline in new infections—likely the result of a combination of the vaccine rollout and seasonal population immunity— and the advent of spring, there is a natural desire to return to regular business and social life after a brutal and desperate winter. But our public health officials are telling us differently. Theirs is a united message, "This is no time to relax!" What do the experts see that we miss? We need only look at our recent past to remind ourselves of the danger that lurks in our midst, ever ready to emerge and cause havoc. Look, as I do, each morning at the number of new Covid cases diagnosed the day before. You will see three waves of the pandemic, each touching more lives and killing more. After each peak, we reach a new plateau, first 20,000 new cases a day, then at 35,000 per day, and now what looks like our new plateau, 55,000. Each time we rise to a new plateau, we develop a numbness to the new numbers, seemingly comfortable with our new and deadly status quo. We relax, jet off for fun in the sun, or celebrate our holidays. The rates begin to climb steeply, reaching ever new heights—not surprising given the high starting point. Each time we are reassured by the words "herd immunity," which always seems just beyond our grasp—beyond our grasp because, as I have argued before, the concept will never apply to Covid no matter how many are vaccinated or infected. If we are lucky, our vaccines will give us seasonal "herd" immunity, a temporary reprieve from a spate of new infections but a reprieve that will need to be renewed each year via vaccination and vigilance. Last winter and spring, we saw our future in Italy. Let's look to that unfortunate country again to see a glimpse of what may await us. This time last year, Italy experienced its first Covid wave, peaking 822
at 6,200 new cases in one day. Based on population size, the US equivalent of that level of infection would be 34,000 new cases a day. Italy’s path was an important foreshadowing of our future. Less than three weeks after Italy hit its peak in the first wave, we hit ours with 33,473 new cases in a single day on April 10, 2020. Through the spring and summer, infections dropped in Italy, not to zero but to around 300 new cases per day, an equivalent of around 1,640 cases in the US. But we were never able to get our numbers down that low. Instead, we averaged 20,000 during the same period. Come fall, Covid cases in Italy spiked again to a high of 40,000 cases per day, or the equivalent of around 215,0000 cases in the US. But because we had never managed to control our outbreak our second wave was much worse than it should have been—we reached a peak of more than 300,000 new case in early January. That is what happens when we don’t control our pandemic. In January, as we reached our peak, Italy went into partial lockdown. In January and February, daily cases plateaued around 12,000, which is equivalent to around what our current plateau is today at 55,000 daily cases. When Italy reached its plateau it started lifting restrictions. Did Italy’s numbers stay level? Not in the least. As I write, Italy is headed back into lockdown, with cases having peaked again at just over 26,000, an equivalent of roughly 146,000 cases per day in the US. Italy is no anomaly. A third wave is sweeping across Europe, even among countries who had managed to control their outbreaks better than we did throughout the warmer months of 2020. Look at the new peaks these countries are reaching and what they say about the numbers we here in the US could reach – are we really ready for 463,000 new infections per day, which is the US equivalent of the spike in cases in the Czech Republic? There is another path though. Consider Australia, a country which reached a peak of 715 cases in August (equivalent to 9,135 cases in the US) but brought those numbers down to near zero and kept it there, through constant vigilance and exhaustive testing, tracing and quarantine measures. Today, the country is inching ever closer to pre-pandemic life, with small weddings allowed, bigger sporting events, and even dancing in clubs.
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Number of new Covid cases per day, Australia JHU SSE COVID-19 DATA, AS COMPILED BY GOOGLE
Which will be our future?
Number of new Covid cases per day, USA, with potential future path indicated by arrows. ACCESS HEALTH INTERNATIONAL
If we want the parties and the dancing, Spring Break is not the time to do it. We need to hold the line, maintain our vigilance, and continue to drive down new infections. There will be time for a party, but that time is not now. First let’s take advantage of the warmer weather to reinforce mask wearing, social distancing and outdoor gatherings only to bring down new infections closer to zero—at least under a couple thousand. Then, and only then, can we start thinking about the plan needed to restart the party: widespread testing through rapid inexpensive home tests, comprehensive contact tracing, and assisted mandatory isolation where everyone known to be exposed to Covid-19 is monitored through quarantine and given support so they do not risk their jobs, their income, or their ability to look after the children in their care. 824
Past is prologue. If we don’t act now, expect a new peak, higher than our last. This article originally appeared in Forbes and is available online here: The Covid Pandemic Is Not Over: The Past May Be Prologue
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AstraZeneca Vaccine Fails To Protect Against The South African Variant Forbes | March 17, 2021 | Article
Two doses of the AstraZeneca Covid-19 vaccine were found to have only a 10.4% efficacy against mild-to-moderate infections caused by the B.1.351 South Africa variant, according to a phase 1b-2 clinical trial published on Tuesday in the New England Journal of Medicine. This is a cause for grave concern as the South African variants share similar mutations to the other variants leaving those vaccinated with the AstraZeneca vaccine potentially exposed to multiple variants. This new finding should force a rapid acceleration of secondgeneration vaccines and encourage further research into the possibility of a pancoronavirus vaccine. The trial evaluated the safety and the efficacy of the AstraZeneca vaccine in HIV-negative adults aged between 18 to 64 years old with a median age of 30 years old. The trial was conducted between June 24 and November 9, 2020 in South Africa using a multisite, doubleblind, randomized, placebo-controlled approach. Out of the trial’s 750 vaccine recipients, 19 (2.5%) developed mild to moderate COVID-19 more than 14 days after the second dose, compared with 23 of 717 placebo recipients (3.2%). Of the 42 total cases of Covid19, 39 (93%) were caused by the B.1.351 South Africa variant. These results demonstrated that the AstraZeneca vaccine was only 10.4% effective against the B.1.351 South Africa variant. It is important to note that there were still no cases of hospitalization for severe Covid-19 or deaths observed in the study. Yet the authors did caution that the relatively young median age of participants (30 years) likely influenced the lack of severe Covid-19 cases. The South African B.1.351 shares similar mutations with several other variants. Mutations to positions 417 (K417N), 484 (E484K), and 501 (N501Y) are all located in the receptor-binding domain. This structure is the part of the spike protein that attaches to the ACE2 receptor of the human cell. The K417N and E484K 826
mutations have been seen in the Brazilian and Japanese variants, and N501Y has additionally been seen in the UK variant. External to the spike protein, there are a set of three deletions in non-structural protein six which also appear in the Brazilian, Japanese, UK, Nigerian, and New York variants. NSP6 is a structural transmembrane protein and these deletions additionally may assist in neutralization escape. NSP2 also carries a common mutation: T85I. This mutation appears in the California variant, the New York variant, and a number of other US variants. While NSP2 has no known function, the pervasiveness of the mutation is notable at the very least. In NSP12, mutation P323L is pervasive in nearly every variant. This protein is the polymerase, which controls viral replication. While it may not aid immune-escape, this mutation certainly aids increased transmissibility of the South African variant and others. Suffice to say, despite these variants carrying unique sets of mutations, individual changes are shared across lineages that may aid to the neutralization escape the South African variant demonstrates. As these variants threaten to become the dominant source of coronavirus cases globally, we urgently need second generation vaccines that provide greater protection against the variants if we are going to prevent another wave of infections and return to a level of normalcy. The UK B.1.351 variant and NYC variant B.1.5.26 are now responsible for over 51% of New York Covid-19 cases. Updates to the AstraZeneca and other Covid-19 vaccines that target the B.1351 variant and others are currently underway. President Biden needs to invoke the power of Operation Warp Speed to rapidly accelerate the development of these vaccines and the logistics involved for rollout within the year. Other countries who are relying on the AstraZeneca vaccine to vaccine the bulk of their population need to do the same, as we have painfully learned no one will be completely protected from Covid-19 until we all are. While we await these updated vaccines, those who have the opportunity should still accept the current AstraZeneca vaccine in order to protect themselves against the risk of hospitalization and death. In a prior column for Forbes, I wrote about promising research into a pancoronavirus vaccine that protects all variants. This is the long-term goal we should be working towards, if such a vaccine 827
were to come to fruition would no longer need to revise the Covid19 vaccines each year. This article originally appeared in Forbes and is available online here: The Covid Pandemic Is Not Over: The Past May Be Prologue
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A New Variant In The Philippines Forbes| March 18, 2021 | Article
Covid-19 has reached extraordinarily high levels in the Philippines. In early January, the country reported around 1,500 cases per day. Today, that rate is over 10,000, as seen below in figure 1. This resurgence of SARS-CoV-2 is coincident with the observation of a new Philippine variant: B.1.1.28.3. First identified in the Central Visayas region of the island nation, the variant is derived from the Brazilian B.1.1.28 strain and shares many mutations with the P.1 variant identified in Manaus in early January. However, this variant also has many characteristics unique to the Philippines. Here, we will analyze these unique and shared mutations and discuss their potential impact on the virus.
Seven-day rolling average of confirmed Covid-19 cases in the Philippines. GOOGLE / JHU CSSE
The B.1.1.28.3 variant contains the aspartic acid to glycine at position 614 (D614G) in the spike protein. This mutation was first 829
spotted in the opening months of 2020 and later came to dominate nearly all strains of the virus in circulation today. The B.1.1.28.3 variant also contains spike mutations of glutamic acid to lysine at position 484 (E484K) and asparagine to tyrosine at position 501 (N501Y). The N501Y mutation is notable for its appearance in the widespread UK B.1.1.7 variant and the E484K mutation is similarly notable for its presence in the South African B.1.351 variant. Vaccine-elicited antibodies have been found to have reduced neutralization of pseudovirus containing these mutations. In addition, the Philippine variant contains a number of other genome changes of note. Using the GISAID database, we will examine how many sequenced viruses share mutations with those found in the B.1.1.28.3 variant. Two sets of deletions from positions 141 to 143 and 243 to 244 in the N-terminal domain are found in only 72 of over 990,000 viruses sequenced on GISAID, most of which are concentrated in the Philippines. The deletions from positions 243 to 244 are notably present in a several months-long Covid-19 patient from Pittsburgh, indicating that these deletions may play a role in immune evasion as mutant viruses in long-Covid patients must adapt and evade the immune system to survive. There are also two unique point mutations in the latter end of the spike sequence. Glutamic acid to lysine at position 1092 (E1092K) and histidine to tyrosine at position 1101 (H1101Y) are found in only 102 sequenced viruses. These two mutations are found predominantly in SARS-CoV-2 isolates from the Philippines. A study on SARS-CoV found this region susceptible to a series of neutralizing antibodies. Because much of the structure between SARS-CoV and SARS-CoV-2 is shared, it is possible that mutations to this site could additionally increase immune evasion, but further study on SARS-CoV-2 would be needed to confirm that hypothesis. Despite what seems likely to derived from the B.1.1.28 lineage, the Philippine B.1.1.28.3 variant and the Brazilian P.1 variant differ substantially within the S protein and protein-coding regions of the virus, specifically ORF1a and several of the accessory proteins. The effect of each of the mutations outside of the spike protein deserved to be analyzed for the effect in cell culture and in animal models, alone and in combination, to assess their effects on the ability of the virus to replicate, transmit, and induce disease. The figure below displays the full set of spike mutations. 830
We also note that although many focus on the mutations in the spike protein, there should be an emphasis on the mutations in other proteins as determinants of transmission, virulence, and immune escape as well. While the spike protein is the mechanism controlling receptor binding and viral fusion with the host cell, the other proteins are significantly involved in pathogenesis, viral replication, and evasion from the immune system. Some of the more notable mutations external to the spike protein include a change from arginine to lysine at position 203 (R203K) and glycine to arginine and position 204 (G204R) both in the nucleocapsid protein (N). The same mutations in N are present in other variants of concern including P.1, the UK B.1.1.7, the Danish B.1.1.298, and a cluster of 677 variants in the United States. The N protein is multifunctional. It stabilizes the virus particle, inhibits the interferon response to infection, and binds to genomic RNA. All three functions may contribute to infectivity and pathogenesis. Three unique mutations of note are serine to glycine at position 80 (S80G), leucine to phenylalanine at position 280 (L280F), and alanine to valine at position 368 (A368V) in the nonstructural protein thirteen (NSP13) of ORF1a. NSP13 is an RNA helicase, critical to virus replication. The contribution, if any, to the efficiency of virus replication is worthy of further investigation. The figure below displays the full set of mutations external to the spike protein.
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The B.1.1.28.3 variant is in the Philippines but is one of many unique variants popping up around the world. Each testifies to the ability of SARS-CoV-2 to adapt to new conditions of mitigation, prior immunity, and treatment. Continued vigilance coupled with government-mandated mitigation efforts coupled to rapid vaccination of entire populations may be the most effective means to blunt the potentially devastating impact of the onslaught of the variants. We thank Dr. Maria Rosario S. Vergeire and the Philippine Department of Health for their insights in preparation of this updated report. This article originally appeared in Forbes and is available online here: A New Variant In The Philippines
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Can America Beat COVID-19?
Project Syndicate | March 18, 2021 | Article
Now that the United States has finally started to reduce its coronavirus infection rate, some political leaders have rushed to ease safety restrictions. But without a three-pronged strategy of testing, contact tracing, and mandatory assisted quarantine, the virus is likely to keep re-emerging, with or without mass vaccination. CAMBRIDGE – After a year of steadily increasing COVID-19 case counts, the United States may finally be at an inflection point. The recent overall decline in the number of new infections represents an opportunity finally to eliminate the virus within US borders, and to begin to eradicate it globally. But this window may not be open for long, given the emergence of new, more transmissible variants and a resurgence of cases in some parts of the Midwest. PreviousNext The recent declines are likely a result of seasonal population immunity (coronaviruses, in general, are seasonal contagions), vaccination, and a renewed commitment to safety measures such as face masks and social distancing. If the US can maintain these practices and contain new variants, it can quickly bring new daily infections down to around 3,000, at which point local transmission could be eliminated through widespread rapid testing, contact tracing, and assisted mandatory isolation. Many will see this as a daunting task. But Australia, Bhutan, China, New Zealand, Singapore, Taiwan, and others have used precisely this approach to keep case counts near zero and stamp out the spread of new strains. If the US could adopt the same threepronged strategy and then help other countries do the same, a COVID-free world would be within striking distance. The US is currently processing around 1.5 million tests per day, which is a far cry from what is needed to contain the epidemic (though it is better than recent past performance). To make up for the shortfall, self-administered rapid tests should be made widely 833
available free of charge at every school, workplace, and public institution. The goal should be for every American to be tested at least twice per week. Simple, inexpensive paper strip tests already exist, but have yet to be broadly commissioned by the federal government, owing perhaps to their relative insensitivity compared to the premium tests available today. But even if the tests deliver more false positives or false negatives than others, their low cost and widespread availability would allow for people to test themselves again at home. Beyond testing, the US must finally take on the task of contact tracing and assisted mandatory isolation. Right now, an American who walks into her local grocery store has no way of knowing whether she has come into contact with an infected person. By contrast, the countries that have nearly eliminated the virus have deployed armies of contact tracers who can notify people of potential exposure through digital apps. But contact tracing alone isn’t enough. The US also needs to confront the politically difficult issue of quarantining the infected, without which there is almost no way to eliminate the virus completely. Of course, mandated quarantines should be made as painless as possible. Quarantining should never come with the risk of losing employment or income, or at the expense of caring for children or other family members in need. In the countries where the virus has been largely contained, governments either provide food and lodging for monitored quarantines, or allow for home quarantines with remote monitoring and enforced check-ins. Many also provide medical kits (including thermometers and masks) and financial aid for those at risk of losing their jobs or income. There is no good reason why a country as rich as the US cannot deploy the same strategy that a much poorer country like Bhutan has successfully implemented. The costs of doing so (according to my own estimate and those of other public-health experts) might seem high, but they pale in comparison to the alternative: a lingering epidemic that causes trillions of dollars in lost output. The Biden administration has committed to creating an army of 100,000 contact tracers, community health workers, and publichealth nurses to track exposures, encourage quarantines, and expand testing. But still more is needed. According to George Washington 834
University’s “Contact Tracing Workforce Estimator,” America would need a minimum of 353,000 contact tracers to keep up with the 14-day case count as of mid-March. Even then, contact tracing must be accompanied by an effective quarantine protocol (mandating two weeks of isolation, if not more). This is a critical moment. With cases declining, the cost of contact tracing and assisted isolation will be high but manageable. But if any of the new highly transmissible variants take hold, infections could spiral out of control, and the current window of opportunity will slam shut. Already, the vaccine-resistant P.1 variant, which first appeared in Brazil, has been detected in the Philippines. Far from being a reason to ease up on containment measures, the reduction in new infections demands even more urgent action. Without widespread testing, tracing, and mandatory assisted isolation, the US will not be free of the coronavirus. And once we have eliminated local transmission here, we must help other countries do the same. Otherwise, the virus will keep coming back, each time stronger than the last. This article originally appeared in Project Syndicate and is available online here: Can America Beat COVID-19?
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Science will save us in our battle against COVID-19 The Hill | March 19, 2021 | Article
In the history of mankind’s battles against deadly disease, our first line of defense has always been public health. Quarantines, border controls, sanitation, disinfection — these have been the tools used over hundreds of years to ward off death. As our knowledge evolved, so too did our methods. The importance of testing, contact tracing and isolation rose to the fore. But even as our technique improved, the approach remained the same: Public health has always manned the frontlines. In the United States, we were late to send our soldiers into battle. Our testing program was non-existent, no army of contact tracers was deployed and far too many of us refused to volunteer, shrugging off requests to wear masks or avoid large groups. By the time our attitude shifted and troops arrived, any chance of holding the line was long gone. We’ve paid the price in more than a half million dead and hundreds of thousands more wounded. Today, our second line of defense – vaccines – has moved to the front and is on the attack. But as hopeful as we once were of their success, the virus may have already mutated its way around us. The Moderna and Pfizer/BioNTech vaccines are more than 90 percent effective against the original type of coronavirus. But some of the new variants (the B.1.135 South African variant in particular) have shown an ability to neutralize the power of the vaccines by nearly two-thirds. Some of the other vaccines in the pipeline have also fared poorly against the variant. The efficacy of the Johnson & Johnson vaccines was just 57 percent in South Africa, and the Novavax vaccine was less than 50 percent effective in preventing disease. Given how quickly SARS-CoV-2 can adapt and the potential variations it has yet to unleash, the possibility that our second line of defense will someday be overrun is strong. What then is left to save us?
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Thankfully, science. Recently there has been a spate of new scientific discoveries that hold real promise for a second generation of vaccines and treatments. First, are two studies (one in mice and one in monkeys) that show that vaccines using nanoparticle technology may be effective against SARS-CoV-2, its variants and perhaps more broadly against other coronaviruses. These vaccines essentially combine bits and pieces of several different coronaviruses into a single mix, one that helps the vaccine reach an optimal level of compatibility with our immune system. Taken together, the studies show that this type of vaccine can produce a robust immune response that rivals current vaccines. More importantly, they can produce a response that could protect us from not just the original SARS-CoV-2 virus, but also its variants and new and emerging coronaviruses. Scientists have also made real progress on new antiviral drugs to treat COVID-19. In a recent joint press release, two pharmaceutical companies released results from a Phase 2a trial for a new oral antiviral drug, molnupiravir. The study was done in a group of 182 people who had tested positive for COVID-19 in the past week. Of those who received the drug, not a single one tested positive for the virus after five days. In those who didn’t receive the drug and received a placebo instead, 25 percent tested positive after five days. These preliminary results are not without caveat — the drugmakers have yet to prove it can prevent severe illness or the long-term effects seen in many of those who had asymptomatic infections. Additionally, with a virus like this one, we need to be careful about the virus’s ability to find a way to overrun us again by developing resistance. Still, the findings give us hope of a treatment that can work better than Tamiflu — something more like Xofluza, which protects both those infected and those around them. Since the beginning of the pandemic, the virus has had us on the run. But Operation Warp Speed brought the best of science to battle. What started as isolated labs working on a scientific solution to COVID-19 has become an unprecedented and almost unimaginable global collaboration. If people aren’t willing to take the steps necessary to protect themselves and all those around them, then science is our last and only hope. Thankfully, the scientific community has committed itself to saving us, and their efforts are finally beginning to pay off. 837
The tragedy, of course, is in the hundreds of thousands of casualties we suffer in the meantime, nearly all of which could have been avoided had we acted more prudently from the beginning. This article originally appeared in The Hill and is available online here: Science will save us in our battle against COVID-19
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Preventing Fecal-Oral And Fecal-Aerosol Transmission Of Covid-19 Forbes| March 22, 2021 | Article
Last year, I conducted an interview with a friend who traveled to Shanghai and was forced to quarantine in a hotel for 11 days under the supervision of local health authorities. He was brought hot meals, subjected to temperature checks twice daily, and charged not a cent for his stay—standard protocol in China and other countries that, prior to the widespread imposition of travel bans, isolated and accommodated visitors from abroad early on in the Covid-19 pandemic. One detail, however, struck me as rather curious, if not startling. When my friend checked in, a woman handed them a blue bucket and a little bottle of disinfectant tablets. “For toilet,” she told him, then laughed when she saw the look of shock and horror on his face. “No, no, no, no. Not for that. Dissolve the tablets in water in the bucket, then dump the mixture into the toilet before you flush.” It didn’t matter whether it was number one or number two, my friend told me. He had to treat his waste as if it was potentially infectious and carrying the virus that causes Covid-19, SARS-CoV-2—using half a bucket of water and six tablets for urine, or a whole bucket and twelve tablets for feces. Disinfecting toilets isn’t the only safety measure that addresses the possibility that SARS-CoV-2 can be transmitted through human waste. More recently, China has been heavily criticized, particularly by the Japanese government, for using anal swabs to test incoming travelers for Covid-19 either instead of or in addition to the traditional naseopharngeal swabs. These interventions, like most China has implemented to contain further spread, may be extreme, but the rationale behind them isn’t. Evidence not just from the past year, but the original SARS pandemic, shows that SARS-CoV-2 infects the intestines and colon and from there spreads to others, traveling from the toilet to the sewer to the water we use and the air
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we breathe—one reason why sewage surveillance across cities and within neighborhoods has become so commonplace. Pathogenesis and severity: SARS-CoV-2 in the gut While it’s true that respiratory symptoms are far and away the most ubiquitous sign of Covid-19, the prevalence of gastrointestinal symptoms is often underestimated. Diarrhea, which occurs in 20 to 25 percent of Covid-19 patients, is the most common, but nausea, vomiting, and abdominal pain are reported with relative frequency as well. More serious symptoms, like acid reflux, gastrointestinal bleeding, constipation, and hematochezia (also known as blood in stool), are a rarity, but not so rare as to be total outliers. Other respiratory viruses, like influenza and even SARS-CoV, also cause their share of gastrointestinal symptoms, though why exactly this is the case isn’t certain. Diarrhea, for example, is a symptom shared by SARS, MERS, and Covid-19. Early studies of SARS-CoV-2 speculated that the virus could infect organs beyond the lungs, a theory corroborated by experiments involving organoids that showed how it could spread to the bloodstream and the kidneys. Using gut organoids, one such experiment found SARS-CoV-2 to be capable of replicating in the intestines, supporting the notion that the virus not only reaches our gut tissues, but damages them as well—hence the gastrointestinal discomfort many Covid-19 patients experience. But organoid experiments are ultimately limited in their ability to simulate virus-host interactions, offering insight into only one system at a time, rather than the complex whole. A more recent study, published in Nature last month, looked across the existing literature on gastrointestinal symptoms and attempted to extrapolate their causal mechanism, though this proved to be difficult. For diarrhea alone the possible explanations ranged widely. It could be osmotic diarrhea caused by an inflammatory immune response that extends to the gut. It could also be more indirect than that, caused by changes to the gut biome—more specifically, its bacterial composition—that trace back to inflammation of the lungs, rather than the gut itself. One question that has beleaguered scientists and doctors almost since the pandemic began is why the virus persists so long in some Covid-19 patients and not others. I speculate that infection and damage to the gut might have a part to play in such cases of persistence, in which case
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a symptom like diarrhea or gastrointestinal bleeding would represent only the tip of the iceberg of more extensive damage. Were researchers to conduct studies that deepen our understanding of the gastrointestinal symptoms triggered by Covid19, doctors would be better able to treat them in clinical settings. This raises another question—whether or not manifestation of these symptoms can be linked to the severity of disease. At least one study, published in December 2020, has concluded based on multivariate analysis that this might be the case, though other studies found no statistically significant correlation. A more explicit yet less obvious link may exist, however, between critical cases of Coivid-19 and interleukin 18 (IL-18), an inflammatory cytokine that appears primarily in intestinal cells and plays a critical role in lung diseases like asthma chronic obstructive pulmonary disease. When an overreaction of the immune system known as a cytokine storm occurs in someone sick with Covid-19, it can lead to the onset of severe pneumonia or death. Studies show that the fecal samples of people who test positive for Covid-19 have higher IL-18 levels than those who don’t. Based on this data, the authors of the February Nature study propose that elevated levels IL18 might not just indicate gut infection by SARS-CoV-2, but hint at the possibility of an incoming cytokine storm, too. If their conjecture is correct, drugs that block IL-18 might be of use to doctors treating critically ill Covid-19 patients. In any case, the information we currently have on hand isn’t enough to act on. More research remains to be done on the gastrointestinal tract if we’re to unravel its pathogenic implications in their entirety—not just for Covid-19 patients with severe symptoms, but pediatric patients as well. Some children who have contracted the virus and have also developed a rare inflammatory condition known as MIS-C that, in some cases, inflames the gut. Fecal-oral and fecal-aerosol transmission of Covid-19 Filling the gaps in our knowledge around gastrointestinal symptoms and the severity of potential Covid-19 gut infections, as I’ve discussed, can do more than improve how we treat our ill. Recall the story of my friend with the bucket and disinfectant tablets in Shanghai. If SARS-CoV-2 does indeed replicate in the intestines, it may be able to exit the body intact, contaminating our waste— meaning we’d have to shift our public health strategies accordingly. 841
Though the main way Covid-19 spreads will always be from person to person, exposure to infectious waste and sewage has a part to play in starting outbreaks, especially in apartment buildings or schools where many people share close quarters at regular intervals of the day. In theory, the virus can travel from one person’s waste to another’s lungs through one of two routes. The first is fecal-oral route, which involves either direct ingestion of contaminated water through the mouth or indirect exposure through the eyes or nose. The second is what I call the fecal-aerosol route, whereby the virus enters the body via sewer gas or even smaller, yet still virus-laden particles known as aerosols. The ability of the virus to successfully traverse either depends on whether it can remain infectious and replicate at sufficient concentrations as it slogs through the digestive juices of the human gut. There is some virological evidence that SARS-CoV-2 can, in fact, replicate in the gut and shed through feces. One study, conducted in Zhejiang, China, discovered viral RNA in the stool of 59 percent of Covid-19 patients tested, remaining at detectable levels for three weeks on average. Another study found that the virus persisted longer in fecal samples than even respiratory samples. Though the presence of viral RNA doesn’t necessarily indicate the presence of live, actively replicating virus, the latter has been isolated and cultured from fecal samples in the laboratory. No coincidence is it that the expression of ACE-2, the receptor SARS-CoV-2 uses to attach to human cells, is at its highest in the small intestine’s enterocytes, or the cells that line its inner surface. On a separate but related note, ACE-2 is also amply expressed in the vagina and uterus, alluding to the potential for sexual transmission— which may go without saying, but must be accounted for nevertheless. Fecal-aerosol transmission, according to a research paper published in Annals of Internal Medicine in December 2020, was suspected to be the cause of a Covid-19 outbreak in a high-rise apartment building in Guangzhou, China that infected at least nine people across three separate households. Prior to the outbreak, one of the families had traveled to Wuhan, the original epicenter of the pandemic. The other two had not, nor did they have any close contact with the first family in the weeks leading up to symptom 842
onset. In addition to swabbing the infected residents, researchers who investigated the case collected environmental and air samples from their private residences and common areas, including elevators and ventilation outlets on the roof. Almost all of the environmental samples that came back positive were from the master bathrooms, giving the researchers reason to believe that the drainage pipes connecting the three units were to blame. If fecal-aerosol transmission was the source of the Guangzhou outbreak, it wouldn’t be without precedent. In 2003, a much larger outbreak of SARS, the first human coronavirus pandemic, infected more than 300 people living in Amoy Gardens, a large apartment complex of about 15,000 residents in Hong Kong. The team of experts dispatched to contain the spread, which happened virtually overnight and ultimately killed 42 people, traced it back to two causal factors. The first was the index patient, or “patient zero,” a 33-year-old man who actually lived in Shenzhen but frequented his brother’s Amoy Gardens apartment and, once he got sick with SARS, had explosive diarrhea. The second was the complex’s defective drainage system, which dried up the toilets of many residents—most of them in Block E, the building that ultimately had the most deaths—forcing them to resort to bucket flushing. Exhaust fans installed in the bathrooms for ventilation purposes may have unwittingly contributed to the spread of viral particles as well. Looking over this wide-ranging body of evidence, it becomes clear that our lack of understanding of how SARS-CoV-2 interacts with the human gut and transmits itself through human waste isn’t due to their unimportance. Much as we all want this pandemic to be behind us, expanding and deepening our knowledge of the virus that caused it is the only way we can prevent it from happening again. That means moving beyond the general assumptions that have guided us up until this point and making those less obvious connections that can firm up any protection we’ve managed to acquire. It’s time for public health officials to mount a more comprehensive response to potential fecal-oral and fecal-aerosol transmission of Covid-19. Official guidance should be issued that recommends anyone infected with Covid-19 to to disinfect their feces, with extra emphasis on implementation in congregate living situations like prisons, long-term care centers, and military 843
installations. The same set of guidelines should advise people living in apartment buildings or complexes to notify their landlords or local authorities if they smell sewer gas—the most common point of entry being dried-out drain traps in the sink, bath, or shower. Finally, if any of us smell sewer gas while walking down the street, we should take it upon ourselves to notify local authorities who can take remedial action and nip the problem in the bud. We can’t make the mistake of allowing our public health responses to grow stagnant as the virus continues to evolve. After all, what is the point of acquiring more knowledge on SARS-CoV-2 if we can’t use it to protect ourselves and others? This article originally appeared in Forbes and is available online here: Preventing Fecal-Oral And Fecal-Aerosol Transmission Of Covid19
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Controversy Over OSHA Proposals To Create A Covid-19 Safe Workplace Forbes | March 22, 2021 | Article
President Biden announced that OSHA had decided to issue a temporary binding standard to set new infection prevention requirements for employers. Much like other Biden Administration safety measures, the OSHA Covid-19 standard will, unfortunately, face implementation challenges due to the late stage in the pandemic in which it is occurring. While the Biden Administration has made incredible progress in under two months implementing life-saving and long-overdue reforms. The standard will likely meet resistance from frustrated business owners who are desperately trying to preserve their livelihoods, one year into the pandemic. It is critical that the Biden Administration finds a way to work with business owners to prevent another wave of infections amongst the largely unvaccinated labor force. The exact details of the rule have not yet been released, passing by the initial March 15 deadline set for OSHA by the executive order issued in January. However, current guidance issued by OSHA on January 29 advises; mask-wearing, regular testing, physical distancing, and better ventilation, routine cleaning and disinfecting, hazard assessment, and minimizing the burden on employees who need to quarantine through remote work or paid leave amongst other strategies. These guidelines are currently optional but likely to inform the binding standard which would give OSHA more power to levy fines against employers who don’t follow the CDC’s safety precautions. Workers' rights groups have been crying out for these kinds of national advisories or standards throughout the pandemic. Thousands of lives could have been saved with the early adoption of Covid-19 workplace safety protocols. From the workers themselves to the family and friends they cohabitate with. OSHA never issued any binding safety rules for Covid-19, under the Trump 845
Administration. Instead, they simply recommended workplaces follow the CDC guidelines which were open to interpretation. Again the responsibility was left to the states, with only 14 states adopting comprehensive worker safety protections. Mandatory paid leave for employees who need to quarantine due to infection or exposure also needs to form part of the standard. The American Rescue Plan does not require employers to provide paid leave but has expanded the prior tax credit period for emergency leave from March 31, 2021, to Sept. 30, 2021, and the qualifying reasons. Employers can currently voluntarily provide this leave and be reimbursed for qualifying wages. This does not go far enough. We saw what happened at meatpacking plants last spring when workers were forced to choose between their livelihood and potentially exposing others to the virus. As of March 2021, 46,000 Covid-19 cases have been tied to meat and poultry processing facilities across the nation. Many of those meat packing plants still do not provide any form of paid leave to their employees and threaten to fire those who take unpaid leave. While workers' rights groups will be relieved to see a standard enforced, states such as Texas and Mississippi who have recently rolled back mask mandates may rile against being forced to adopt masks in the workplace, despite their obvious life-saving benefits. There are 16 other states that currently have no mask mandates in a place where OSHA will face similar challenges. Asking business owners to bear the cost of updated ventilation at this late stage in the pandemic when many are financially strained will also cause some objections. Yet both of these requirements will be crucial to preventing the spread of infections in the workplace. While OSHA may have the threat of fines to dangle in front of businesses, the reality is that OSHA is a relatively small agency whose power was rolled back under the Trump Administration. OSHA has not yet inspected 26 out of the 65 meatpacking plants, where workers died of COVID-19. President Biden needs to work with OSHA to find a way to incentivize workplaces to adopt the standard when it is enforced. Even as we make progress with vaccinations, we know they have a reduced efficiency against the variants that are spreading quickly across the country. Therefore we must remain vigilant to protect those who are vulnerable to infection and prevent another wave like we are seeing in Europe. 846
This article originally appeared in Forbes and is available online here: Controversy Over OSHA Proposals To Create A Covid-19 Safe Workplace
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What Can We Learn From Australia’s Covid-19 Response? Forbes | March 24, 2021 | Article
Australia’s Covid-19 response has been the envy of many countries with Dr. Fauci recently praising the country for being a world leader on “containment and management of emerging variants”. Aside from a few brief snap lockdowns in certain states, most Australians have been enjoying a relatively normal life with the Broadway production of Hamilton recently opening in Sydney to full capacity theaters. As of March 23, 2020, Australia has just five new cases of Covid19. The majority of these new cases are not from community transmission but from the hotel quarantine system that houses Australian citizens returning from overseas. Even after experiencing a second surge of cases last year, Australia swiftly learned from its mistakes and cases never rose over 1,000 for a population of 25.36 million. All of this has been achieved without vaccinations. Australia only began its vaccination program on Feb 21, 2021, yet as you can see in the chart below (Figure 1) cases have remained low for almost six months. While Australia does have considerable advantages in terms of geographic isolation and population density there is still much we can learn from their response. Australia’s success proves that a strong public health response enforced by a democratic government focused on vigilant testing, tracing and quarantine is the key to fighting a pandemic. Below I’ve outlined some of the key lessons from Australia’s response that can be applied globally. 1) Act quickly and decisively based on incoming data When Covid-19 first became a real threat to Australia in March last year, the Federal government responded quickly closing international borders and implementing a mandatory home isolation program for returning Australian citizens. Police were dispatched to homes to check that returned travelers were adhering to quarantine requirements and when breaches were discovered, Australia quickly moved to a mandatory hotel quarantine system in which hotel rooms 848
were often guarded by police or military. The states and territories also temporarily shut their borders down for the first time since 1919 during the Spanish flu pandemic. These early border closures stopped the rapid spread of the virus and allowed for Australia to build a testing and tracing system that was not immediately overwhelmed and therefore very effective at controlling the spread of the virus. Closing state borders also meant that states like New South Wales and Western Australia were able to reopen their local economies after just two months of lockdown. The progress of individual states did not affect the entire country. State and territory borders have now reopened but international borders have remained closed due to the threat of the variants. Australia has also implemented a cap on incoming international flights carrying returned citizens in order to ensure the quarantine system isn’t overwhelmed. While this has been an effective policy it has not been without controversy. Approximately 40,000 Australians are currently stranded overseas, desperate for a place on those limited flights which has been considered a human rights violation by some. Australia’s lockdown restrictions and behavioral safety protocols were also enacted swiftly. While restrictions varied between the states and rural and urban populations, they were clearly communicated through daily televised press conferences, public signage and advertising and further media outreach. Non-essential businesses were immediately closed, everyone was given a limited radius that they could not leave unless it was for essential work, medical appointments or caretaking, and households were not allowed to mix with some exceptions. Anyone found to be violating those restrictions faced a hefty fine. The easing of these restrictions and eventually restrictions on indoor and outdoor gatherings were tied to declining infection rates. This gave Australians a clear, logical path forward to reopening and encouraged compliance. These swift, decisive actions have allowed Australia to reach zero cases at certain stages of the pandemic. When there is a small rise in cases (usually from workers at quarantine hotels) they have the systems in place to trace exposures and lockdown certain regions for a few days. With case numbers so low, the media is able to publish the exposure locations that the infected person visited in addition to traditional contact tracing. While there are a few complaints, the
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public is happy to comply with these brief lockdowns as they know that they will shortly return to the luxury of normal life. 2) Bipartisan unity is essential to an emergency response Australia’s two major political parties are definitely still closer to the center than Republicans and Democrats but have grown increasingly combative in the last 10 years, with legislation often gridlocked in the two Houses of Parliament. However, when Covid-19 struck, they put aside their differences to work on a unified pandemic response. While Australia’s current conservative government normally clashes with the trade union movement, they recognized that union cooperation would be essential in implementing their emergency measures and gave them a role in shaping policy. Early in the pandemic, the federal government introduced a $130 billion dollar economic bailout which included a six-month wage subsidy scheme. The legislation was rushed through Parliament in just one sitting day in order to get relief to Australians who needed it most. State leaders met in March 2020 to coordinate their responses and form a National Cabinet which would share data and strategies. Conservative Prime Minister Scott Morrison also preached a message of unity, saying “There are no blue or red teams. There are no unions or bosses. There are just Australians now”. The political truce between the parties did not outlast the crisis stage of the pandemic but it was essential in the early days. 3) Social capital builds trust amongst the public While Australians will always find plenty to criticize about their government, including their poor record on climate change, immigration policy, and reconciliation with the Indigenous populations, but there is always a baseline level of trust in the government due to the fundamental social support all citizens receive. Australians would never think twice about the price tag associated with a Covid-19 test or avoid the emergency room due to fear of bankruptcy. This is all thanks to Australia’s universal health care known as Medicare. Australia became an early leader in Covid-19 testing when the Peter Doherty Institute in Melbourne was the first laboratory outside China to successfully grow the coronavirus from a patient sample. This provided international laboratories with crucial information to help combat the virus. Australia was among the first countries to 850
implement drive-through COVID-19 testing clinics in March 2020. This meant that Australians could confidently access a Covid-19 test whenever needed through a health system that they trusted. Even when case rates began to lower or hit zero, Australia maintained its vigilance towards testing, nearly 15 million Covid-19 tests have been conducted, equivalent to more than half the country’s population. However countries cannot rely on an accessible health system alone to fight the pandemic. Countries like France have universal healthcare systems and have been unsuccessful in controlling several waves of infection as seen in the chart (Figure 2) below. Accessible healthcare needs to be paired with vigilant public health measures and social support. In addition to a strong health system, businesses and employees were provided with swift economic relief. The Jobkeeper program paid the biweekly wages (up to $1500.00) of employees such as hospitality workers who were not able to work during lockdown periods, so they could seamlessly resume work upon the economy reopening. The Jobseeker program provided unemployment benefits. These social supports paired with consistent, clear communication built confidence in the government response and consequently compliance in the public. Australians are known for having a rebellious nature, often describing themselves as “larrikins”. Yet very few Australians protested mask-wearing and restrictions and approval ratings swelled for leaders (even those who were previously unpopular) during even the toughest lockdowns. 4) Meaningfully engage with different communities to find out what they need. Indigenous Australians have worse health outcomes than other Australians, with a life expectancy of 8 years fewer than nonIndigenous Australians. When Covid-19 struck, they insisted they run their own response and the government listened for once and provided resources. The incredible result was Indigenous Australians were six times less likely to contract Covid-19 and there were zero deaths. Only 148 contracted the disease, and just 15 percent of these people were hospitalized. Remote communities were closed to outsiders, food was supplied to limit travel, and information campaigns were full of Indigenous humor and values. The passion for protecting their elders was a central part of the response.
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Hopefully, Australia will use the success of this program as a springboard for addressing other Indigenous health outcomes. Australia’s worst outbreak in the state of Victoria, was partially because migrant communities living in public housing could not access public health information or signage in their own languages. A critical mistake that could have been avoided with better community engagement by the government or local health authorities. This pandemic has taught us all the benefits of engaging with different communities to better understand their needs and or why they aren’t responding to certain policies or initiatives. It’s a lesson we can use not only in the face of a pandemic but in addressing other health disparities as well. This article originally appeared in Forbes and is available online here: What Can We Learn From Australia’s Covid-19 Response?
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New Study Predicts Immune Protection May Vary For Different Covid-19 Vaccines Forbes | March 25, 2021 | Article
After more than a year of lockdowns, isolation, and great loss of human life, the slow but steady rollout of Covid-19 vaccines has given us all a much-needed glimmer of hope. As of March 22, the total number of doses administered worldwide is nearing 500 million, with millions more to come as the eligibility pool expands from high priority groups to the broader population. But for all the progress being made, much remains unknown about how protected people really are—and how long that protection will last—once they’re vaccinated, especially now that more infectious and immunologically challenging variants of SARSCoV-2 are on the loose. Though it will be some time before we have long-term clinical data on vaccinees that can answer these questions definitively, a new preprint study has taken the first step by using predictive modeling techniques to estimate the strength and length of immune protection conferred by seven different vaccines over time. The results suggest that the more protective a vaccine is immediately following immunization, the longer protection will last. More than that, however, they imply we’ll have to retool our vaccine strategies so they better address the issue of waning immunity against Covid-19. To predict the trajectory of immune protection for each vaccine, the researchers premised their model on the fundamental assumption that high levels of neutralizing antibodies correlate with immune protection—an observation that has come up numerous times in previous research on reinfection in recovered Covid-19 patients and vaccine safety and efficacy. Using data on Pfizer-BioNTech, Moderna, Sputnik-V, Bharat Biotech, Johnson & Johnson, AstraZeneca, and SinoPharm vaccines, they were able to plot how the neutralizing antibodies generated by each one fell over a theoretical timeline of 250 days. The researchers then compared these trajectories to those of recovered Covid-19 patients who had 853
natural immunity vis-a-vis data on convalescent sera, in addition to modeling how lower antibody titers might fare against new SARSCoV-2 variants. They also used convalescent sera as a baseline for normalizing the vaccine data, which in its original state came from a diverse array of assays and was difficult to collate as a result. Ultimately, the researchers’ hope is that the evidence-based modeling study, in their words, “will assist in developing vaccine strategies to control the future trajectory of the pandemic.” One consideration such strategies will have to take into account is that protection from disease isn’t the same as protection from infection. When the researchers cross-analyzed the neutralization titers produced by each vaccine and plugged the numbers into their model, they found that protection from severe Covid-19 held steady, but protection from infection by SARS-CoV-2 declined significantly. By how much, according to their model, depended on the initial strength of the neutralizing antibody response. The second consideration, which I’ve already written about at length in my viral variation series for Forbes, is that the new SARSCoV-2 variants are proving to be more difficult to neutralize than the original wild-type virus that emerged out of Wuhan, China. Several studies have already documented how the efficacy of the first generation of Covid-19 vaccines—even at their most potent, in the days following immunization—falters against the B.1.351 variant in particular, remaining protective but not as much as before. The predictive model echoed this, showing that the variants pose a greater threat to vaccines with a lower initial efficacy against the wild-type virus. If the initial efficacy of a vaccine is around 70 percent, for example, and the neutralizing titers of the vaccine are reduced five-fold due to a new variant, the researchers predict efficacy will fall to just 25 percent. This brings up a third and final consideration—that not all vaccines are created equal. While the correlation between initial efficacy and duration of protection is consistent across all the vaccines, their individual neutralizing antibody titers varied widely. The Pfizer and Moderna mRNA vaccines performed the strongest, with an initial efficacy of 95 percent that didn’t drop to 50 percent until around day 200. By contrast, the Johnson & Johnson and AstraZeneca adenovirus vaccines, which had an initial efficacy of 67 and 62 percent respectively, reached the 50 percent mark around 854
day 50. At the far end of the spectrum was the Sinopharm vaccine, which had an initial efficacy of 50 percent in the first place and, within the same amount of time, offered next to no protection at all. If this predictive model is indeed an accurate reflection of reality, that means those who receive the Sinopharm vaccine will have the same level of protection immediately after immunization as those who received a Pfizer or Moderna vaccine 200 days prior. The Pfizer and Moderna vaccines also had immunization trajectories similar to those of recovered Covid-19 patients, while the Johnson & Johnson, AstraZeneca, and Sinopharm vaccines fared worse. This isn’t to say that any of the above vaccines should be ruled out as ineffective—quite the contrary. Nor does it necessarily contradict current public health messaging, which dictates that if we’re given the opportunity to get vaccinated against Covid-19, we should take it, no matter the type. Ultimately, the researchers acknowledge, this study is predictive, not prescriptive, and it comes inbuilt with many caveats, among them the lack of standardization across neutralization assays and the potential role of T cells in providing immune protection. The biggest caveat by far is that these calculations aren’t based on real measurements, but hypothetical averages taken from available data on convalescent sera. In actuality, as a recent study on Singapore Covid-19 patients makes clear, the duration of the neutralizing antibody response varies from individual to individual, with a very small fraction experiencing very long persistence and another fraction, no antibodies at all. But the modeling study still serves as a dire warning—to vaccine developers, policymakers, and anyone who thinks this initial wave of vaccinations will be enough to protect us from the virus for the remainder of 2021. If we don’t reconfigure our vaccine strategies to address the discrepancies between vaccines and their reduced potency over time and against the variants—especially that of the adenovirus vaccines—we risk leaving some vaccinees more vulnerable than others for no reason other than negligence and complacency. For as hopeful as it is that many of us will be vaccinated by the end of this year, if we don’t look to the future, we risk ending up back where we started: isolated, unprotected, and wondering why our public health leaders didn’t act sooner.
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This article originally appeared in Forbes and is available online here: New Study Predicts Immune Protection May Vary For Different Covid-19 Vaccines
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Spring Break Could Trigger A National Surge In Cases Fueled By Variants Forbes | March 25, 2021 | Article
Spring break is upon us as and despite the CDC’s non-essential travel warning, thousands of students and families are still traveling across the country. More than a million passengers have traveled through US airports daily for at least 11 days in a row, according to data from the TSA, breaking a record for travel during the pandemic. Many have flocked to Florida, with the state's complete lack of Covid-19 restrictions a tempting respite for some. As spring break travelers return home to different corners of the U.S. they could accelerate the spread of the variants, prompting a potential national surge unless states cease relaxing Covid-19 restrictions Let's begin by looking at last year, Florida Governor Ron Desantis famously minimized the impact of spring break parties, neglecting the fact that as spring break travelers returned home they seeded the virus across the country. As infections eventually spread nationwide, Florida experienced its own surge in the summer and over winter (Figure 1). As public health officials have repeatedly cautioned throughout the pandemic, none of our population is safe from infection until the entire population is safe. If you look at the case rates in the table below (Figure 2) you will see how national cases rose dramatically after Spring break last year. This year the infectious conditions for Spring break are even more potent with the introduction of several highly transmissible variants. Daily US case rates are sitting at approximately 55,000 compared to the few hundreds from last year. The B.1.1.7 variant now represents more than half of Florida’s cases and could be even higher since fewer than 1% of Covid-19 cases are tested in Florida to detect the mutations. The chances of exposure at the Spring break parties are high with zero Covid-19 mitigation measures in place and Police officers finding that they have no avenue to enforce safe behavior with the rollback of mandates. Returning travelers will also
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be seeding these variants in states that have relaxed restrictions, leaving them even more vulnerable. To see what can happen in the U.S. let's look at the current wave of infections engulfing Europe fueled by the more contagious variants. The B.1.1.7 variant is rapidly spreading across 27 European countries and is now dominant in Denmark, Italy, Ireland, Germany, France, the Netherlands, Spain, and Portugal. New daily cases in Italy have surged from a weekly average of just over 12,000 in January to more than 22,000 this week as a result of new variants. In Germany, 7,485 new infections and 250 deaths were reported over a 24-hour period this week. Even without the impact of Spring break, cases in some states such as Michigan and Connecticut have begun to rise and cases in other states like New York have plateaued at a disturbing high level. Approximately 15 states have more cases than they did two weeks ago, and about 19 states have higher test positivity rates than two weeks ago, which points to higher rates of infection. Michigan recorded nearly 17,000 new cases last week, resulting in a 300% increase from the same week last month (Figure 3). The state’s positivity rate recently hit 9%, the highest increase since midJanuary. In Connecticut, there has been an average of 944 cases per day for the last week, an increase of 32 percent from the average two weeks earlier (Figure 4). It is still too early to rely on vaccinations alone to protect us from this potential surge. Only 13.7% of the total U.S. population has been fully vaccinated and these will take two weeks to take effect. The UK’s success in dramatically reducing cases has been a combination of mass vaccinations and stringent public measures including travel bans and strict lockdowns. Israel’s relative success in reopening after a strong vaccination campaign is also due to a strong contract tracing system and the use of QR codes to keep track of those who are vaccinated. But Israel is still threatened by the very high infection in neighboring countries Jordan (Figure 5) and Lebanon. The efficacy of the current vaccines against the variants and the complete duration of immune protection is still largely uncharted territory and we must as always err on the side of caution. A recent preprint study used predictive modeling techniques to estimate the strength and length of immune protection conferred by seven 858
different vaccines over time. The results suggest that the more protective a vaccine is immediately following immunization, the longer protection will last. This means the Pfizer vaccine, for example, would only take about six months for the vaccine to drop to a level of only 50% protection and the J&J vaccine would take just two months to drop to such low levels. If this prediction is correct we will need to retool our vaccine strategies so they better address the issue of waning immunity against Covid-19 and do not leave vaccines vulnerable. This should not deter anyone from accepting any vaccine when available, all vaccines still protect recipients from death and hospitalization caused by Covid-19. It is simply a reminder that despite the glimmer of hope vaccines provide, we are far from the end of the pandemic and with the rapidly spreading variants now is the time to be doubling down on restrictions not relaxing them. This article originally appeared in Forbes and is available online here: Spring Break Could Trigger A National Surge In Cases Fueled By Variants
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From Cats And Dogs To Minks And Mice, Covid-19 Variants Are Infecting The Ecosystem Forbes | March 26, 2021 | Article
To witness a dog come down with Covid-19 is a curious thing. Though mine have been spared, I have a friend whose two dogs got sick in addition to the rest of their family. In videos my friend sent me, I could see the dogs were lethargic, sneezy, and seemingly suffering. While most of the domestic pets that tested positive for the disease last year didn’t exhibit symptoms like theirs, those that did mirrored the mild infections we experience as humans, tiring easily and developing colds. The good news is that my friend’s dogs made a smooth recovery. (So did their family members.) The not-so-good news is that new variants of SARS-CoV-2, which we now know are more infectious and more dangerous than the original strain, might have adapted to animals as well as they’ve adapted to us—our favorite household pets included. While the original strain was already capable of infecting enough animal species to fill Noah’s ark—among them minks, ferrets, weasels, dogs, lions, tigers, and cats, oh my—the new variants are even more adventurous, finding a home in an even larger range of animal hosts. According to new studies, the animals that were vulnerable to the original strain may also be at greater risk of getting sick from the new variants. The first variant to garner global attention was B.1.1.7, also known as the UK variant. At least 50 percent more transmissible than the previously dominant SARS-CoV-2 strain, B.1.1.7 likely contributed to the surge in new Covid-19 cases that swept through Britain in late December and early January and is now wreaking havoc across Europe and expanding rapidly in the United States. No coincidence is it, then, that the location of the first study I’ll discuss, a preprint still undergoing peer review but available to read on bioRxiv, was a veterinary center outside London. From December to February—precisely the same timeframe that B.1.1.7 had its catastrophic rise and fall—the Ralph Veterinary 860
Referral Centre noticed a significant uptick in the number of pets, in particular cats and dogs, admitted to its cardiology unit with myocarditis, an inflammatory condition of the heart that at its worst can lead to heart failure. In just two months, incidence of myocarditis increased ninefold, from 1.4 to 12.8 percent. The study focuses on eight cats and three dogs who were treated for myocarditis at the center. Their owners reported similar symptoms—acute lethargy, loss of appetite, fainting. Further cardiac testing revealed that the pets had excess fluid in their lungs and arrhythmic heartbeats. All 11 had one thing in common: they were exhibiting telltale signs of Covid-19. Prior to taking their pets to the vet, five of the pet owners had already been diagnosed with Covid-19. Ultimately six of the 11 pets—four cats and two dogs—tested positive, either through PCR or antibody diagnostics, for SARS-CoV-2. The three diagnosed via PCR had the B.1.1.7 variant—the first pets on record to be infected with the ultra-contagious strain. They wouldn't be the last. In midMarch, researchers across the pond at Texas A&M University announced that a dog and cat from the same home in Brazos County, Texas tested positive for the B.1.1.7 variant. Though all of the pets, with the exception of one cat that relapsed and was later euthanized, are now in good health, it isn’t a good sign that B.1.1.7 seemed to take a greater toll on the pets it infected than what was observed with the original strain. More severe symptoms isn’t the only cause for concern, however. There is also the issue of a more expansive host range— meaning the new variants might be spreading among animal populations it couldn’t reach before. Common breeds of laboratory mice were once included in this out-of-range species pool, due to the fact that the original SARS-CoV-2 strain couldn’t bind as well to the mouse ACE-2 receptors as it could to those in humans. But according to another recent preprint, this is no longer the case. The French researchers who conducted the study injected 8week-old mice with either the original strain or one of the most common new variants—B.1.1.7, B.1.351, or P.1. The original strain, as expected, was unable to take hold and start replicating in the mice inoculated with it. The new variants, by contrast, not only replicated quite efficiently in mice airways, but reached high titers as well, with B.1.351 and P.1 yielding the highest. This finding is 861
consistent with previous studies in humans, which establish a consistent link between the mutations exhibited by B.1.351 and P.1 and a greater potential for infectivity and immune escape. Though none of the mice developed symptoms, whether or not more mice are getting sick isn’t exactly the worst of our problems. Far more concerning is the possibility that this virus is circulating among mice and evolving fitter, more virulent versions of itself. Rodents, the French researchers pointed out, “have been hypothesized as the ancestral host of some betacoronaviruses.” And who doesn’t have mousetraps in their apartment or basement? Were mice to become yet another animal reservoir for SARS-CoV-2 to incubate in, the potential for cross-species transmission would be alarmingly high. Such patterns in viral variation and transmission have already been noted and studied in Danish mink farms, where virus originated with farmhands, ripped through the closely packed minks, and jumped back full circle, slightly varied, into human handlers. Even if public health measures and medical interventions succeed in eliminating Covid-19 from humans, there is still the entire living ecosystem to consider. This disease has reached 125 million humans so far, and that’s only the cases we’ve officially confirmed. It would be naive to assume that the ripple effects of numbers this large haven’t penetrated deep into the rest of the biosphere, especially when we consider that many animals, like mice and like us, have ACE-2 receptors ripe for the taking. Across 130 species of mammals, 75 species of birds, 67 species of bone fish, and several more, a group of scientists has identified 80 ACE-2 proteins that could potentially facilitate binding to SARS-CoV-2. But identification is only the first step of many we must take to prevent another lethal leap from an animal reservoir to humans. More animal reservoirs means more opportunities for SARSCoV-2 and other coronaviruses to hide in plain sight, where they can comfortably evolve and become more dangerous without human interference. We need a comprehensive, integrated, and adaptive surveillance framework that can rapidly detect any emergent coronaviruses in suspect populations. Just as important is the development of pipelines for altering coronavirus vaccines and drugs that their makers can turn to if their previous technologies fail to neutralize a new variant. The next animal to bring a deadly virus 862
to our doorstep needn't be an exotic bat. It could be a cat, a dog, or the lowly field mouse that makes its nest in your home every winter. This article originally appeared in Forbes and is available online here: From Cats And Dogs To Minks And Mice, Covid-19 Variants Are Infecting The Ecosystem
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Covid-19 Has Exacerbated Child Poverty, Forcing A Long Overdue Policy Focus Forbes | March 27, 2021 | Article
Before Covid-19, the poverty rate in America had been on a slow decline, but the pandemic has stalled—if not reversed—that progress. Among the hardest hit are children from low-income families, where school closures and the high cost of childcare forced previously employed parents to give up their jobs and income to care for their kids. This vicious cycle of poverty among parents and children is becoming an important part of the policy debate in the US and President Biden's $1.9 trillion economic stimulus plan. According to the United Nations Educational, Scientific, and Cultural Organization, 138 nations have closed schools nationally, with many others implementing regional or local closures. Around the world, 80 percent of children's schooling is impacted by school closures. While closing schools may prevent virus transmission, there is no denying that extended school closures can have a detrimental impact on young children living in poverty and may be intensifying existing disparities. In the U.S. almost one in every five children lives in poverty, a percentage that is significantly higher than that of adults. African American, Hispanic, and American Indian/Alaska Native children are disproportionately affected by poverty. Childhood poverty is linked to a higher incidence of accidents, chronic disease, and mental health issues, with effects that last not just throughout childhood but also throughout one's life and well into adulthood. To begin with, school closures will exacerbate food insecurity. For many low-income families, school is not only a place to learn but also a place to eat. Research shows school lunch is linked to improved academic performance, while food insecurity (including irregular or unhealthy diets) is linked to lower educational achievement and significant risks to children's physical and mental health. In the U.S. estimates indicate that 14 percent of households
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with children suffered from food insecurity in 2018; that number is likely even greater today. Despite the fact that learning is expected to continue, the closures are likely to deepen the learning gap between children from lower-income and higher-income families. Children from lowincome families face challenges when it comes to homeschooling as they may lack access to a computer, or even stable housing. In the U.S. approximately 2.5 percent of students do not live in a stable residence. One in ten students in New York City was homeless or had serious housing instability during the previous school year. While children from higher-income families may be able to continue their education without interruption, children from lowerincome families are more likely to struggle with homework and online courses due to their insecure housing circumstances. We know that chronic absenteeism, such as missing 10% or more of a school year, has an effect on academic results such as reading levels, grade retention, graduation rates, and high school dropout rates. Children from low-income households are already disproportionately impacted by chronic absenteeism. Missing months of school due to unstable housing or technology will have a far more serious impact. As a result of Covid-19, families are losing their sources of revenue, and the world economy is in a slump, more households are going into monetary poverty. Previous recessions have worsened child poverty levels, with long-term repercussions for children's health, well-being, and educational outcomes. According to forecasts as of November 2020, the worldwide socio-economic crisis triggered by the pandemic will push 142 million more children into monetary poor households in developed countries by the end of the year. In the absence of any mitigation policies, the worldwide number of children living in poor families will reach just over 725 million. Because children experience poverty differently than adults, it's crucial to evaluate their material needs and potential deprivations, as well as to measure their poverty in more than just financial terms. The United Kingdom launched an ambitious strategy to tackle child poverty twenty-two years ago. More than a fifth of British children were poor at the time. Government payments to families with
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children were at the center of the initiative. In the eight years following the initiative, the child poverty rate had decreased by half. Today, the pandemic should be thought of as a systemic shock to the determinants of child health, affecting family functioning and income, as well as access to healthcare and education. If child health is not prioritized in policy debates, it will suffer terribly. The child tax benefit, which has been overshadowed by other aspects of President Biden's $1.9 trillion stimulus package has the makings of a policy revolution. Despite the fact that it is framed in technocratic terms as an extension of an existing tax credit, it is actually a guaranteed income for families with children, similar to the children's allowances that are common in other advanced economies. For 2021, the law will also increase the child and dependent care tax credit, as well as the earned-income tax credit for jobs without children for this year. It will exclude student loan forgiveness from income taxes until 2025. The bill also includes around $130 billion for schools and $350 billion for states, local governments, territories, and tribal governments. It provides funds for colleges and universities, public transportation, housing assistance, child care, and food assistance. According to predictions from Columbia University's Center on Poverty and Social Policy, the benefit would reduce child poverty to around 6 percent this year from around 14 percent last year. Black and Hispanic children will experience the greatest declines. Figures released by the Biden Administration that the monthly transfers — up to $300 for small children and $250 for those over the age of five — will reduce child poverty by 45 percent, and by more than 50 percent among Black families. That said, the jury is still out on how much impact it might actually have. According to a group of US experts who reviewed the study for the National Academy of Sciences, a universal child benefit would have a "negligible" effect on employment. Still, a newfound focus on this growing problem is a welcome development. Policymakers, school administrators, and other local officials and lawmakers must be prepared for the significant problems that will arise once the pandemic has passed. To begin to close the learning gap, an appropriate response must include targeted education and material support for children from low-income households. Biden’s stimulus package is a big step in the right 866
direction, but it should, but should be extended to support lowincome families beyond the pandemic and well into its recovery period. This article originally appeared in Forbes and is available online here: Covid-19 Has Exacerbated Child Poverty, Forcing A Long Overdue Policy Focus
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Persistence Of Covid-19 Antibodies Varies Widely From Person To Person Forbes | March 30, 2021 | Article
One of the greatest unsolved mysteries of Covid-19 is why the neutralizing antibodies our bodies generate in response to the virus tend to dwindle in number so quickly. A small minority of studies, including one completed in Iceland last summer, have observed lengthier periods of persistence in their participants, but the vast majority—spanning a wide breadth of people and places, from specialized Covid-19 hospitals in China to healthcare workers in Tennessee—concluded that anti-Covid-19 antibodies were fast to fade, so much so that some patients didn’t even appear to develop any, at least not at levels that could be detected by researchers. Another way of interpreting this array of data, however, is that antibody persistence varies from person to person—meaning people with longer-lasting antibodies wouldn’t be outliers, but just one clause of a general rule. This is the argument made by a new study published in The Lancet last week, which sorted participants into five different categories based on the titer and duration of their neutralizing antibody response. While distribution between them was by no means equal, it ranged enough to beg the question of whether current conceptions of immunity from Covid-19, which influence everything from nationwide vaccine strategies to our individual choices and behaviors, require revision. The subjects of the study were 164 Covid-19 patients living in Singapore. Researchers collected data on these patients using both neutralizing and binding assays over a period of 180 days, then plugged that data into an algorithmic model to predict how long their antibodies would last in the years and even decades following initial infection. Based on the longevity of their antibody responses, patients were sorted into one of five groups: the negative group, or patients whose antibodies never reached detectable levels; the rapid waning group, or patients whose antibody levels were detectable within 20 days of infection, but dropped in less than 180 days; the 868
slow waning group, or patients who still tested antibody-positive 180 days after infection; the persistent group, or patients whose antibody levels, over many months, showed little to no signs of decay; and the delayed response group, or patients who, against all odds, had a late surge in antibody levels later in their recovery as opposed to after infection. Earlier immunological research on Covid-19 placed most patients in one of the first two categories—negative or rapid waning. But this study (see Figure 1 & Table 1) found that the spread between the rapid waning, slow waning, and persistent groups was as close to even as it gets, with about 29.8 percent of participants falling in the rapid waning group, 29 percent in the slow waning group, and 31.7 percent in the persistent group. Just below 12 percent landed in the negative group, with a small sliver—just 1.8 percent—rounding out the curve in the delayed response group. What sort of factors determined which patients had more persistent neutralizing antibody responses than others? Though the correlates for protection weren’t exactly cut and dry, a handful stood out as potentially significant. Most salient among these was disease severity, meaning the price of admission to the persistent group was poorer health outcomes overall. The more robust a patient’s antibody response, the greater the chance they previously developed pneumonia, needed supplemental oxygen, spent time in the intensive care unit, and so on. A more technical determinant was the avidity, or binding strength, between SARS-CoV-2 and IgG antibodies, which typically help form the basis of a longer-term immune protection. Members of the persistent group also developed highly avid IgG antibodies earlier on in their infections. Yet another factor that draws from the correlation with disease severity, consistent with new research on vaccine-mediated immunity, is titer, or the concentration of antibodies. Being sicker, it seems, triggers antibody production at higher titers, which may contribute to the longevity of the immune response overall. These predictors of persistence were what the researchers used to create their prediction model, which took months’ worth of data and stretched it over longer spells of time. According to this model, patients who currently have persistent levels of anti-Covid-19 antibodies could potentially retain them for several years. However, as might be expected, those whose antibodies are quicker to fade in 869
the months following initial infection will be as vulnerable to reinfection in subsequent years as those who never caught the virus in the first place. It can be helpful to think of the duration of the antibody response in terms of half life. Using the tables included in the study for reference (Figure 1), we can deduce that the neutralizing antibodies of patients in the rapid waning group fall to 50 percent after about 90 days, or three months. For the slow waning group it takes 125 days, or a bit more than four months. Gauging this for the persistent group is more difficult, as its members have the greatest variance in antibody levels between them. The predicted duration of their antibodies was 326 days minimum but 14,881 days maximum. This isn’t to ignore the role of protective T cells, which beyond neutralizing antibodies likely have a part to play in building natural immunity, too. But the dynamics of the neutralizing antibody response and their correlation with disease severity are too striking to dismiss—especially since, as the researchers later found, they bear a certain resemblance to those of SAS-CoV, the first coronavirus to become lethal to humans. Recruiting 20 SARS patients who recovered from the disease 17 years prior, the researchers tested whether the long-term persistence they predicted for a subset of Covid-19 patients was evident in SARS patients as well. Remarkably, about 90 percent of the former SARS patients had antibody levels high enough to pass a virus neutralization test. One group I’ve yet to discuss is the least populous of the five— the delayed response group. They’re visualized as a gray area for a reason, not least because the sample size is only three and thus difficult to analyze for meaningful trends. While we can only speculate as to why some Covid-19 patients don’t develop neutralizing antibodies until much later in their disease course, one of the more startling explanations is persistent infection—the flipside of which is the ability to shed infectious, replicative virus for months at a time. This may have something to do with the presence of SARS-CoV-2 in the gut, but further investigation is needed to confirm why. We’ve known practically since the pandemic’s outset that the pathogenesis of SARS-CoV-2 is highly variable. In most of the people the virus infects it manifests as symptoms that are totally inapparent, but it can also cause death, chronic illness, and 870
everything in between. Not only do the immune responses of humans vary widely in their ability to fend off the virus due to preexisting characteristics and conditions—among them age, medical history, genetics, and current or recent medical treatments— but the virus itself also has potent tools at its disposal for interfering with various immune functions and robbing them of their power. What we don’t know is whether individual variations in antibody persistence also occur following vaccination against Covid19. Some scientists have already created models and conducted studies showing that when it comes to antibody duration and titer, not all vaccines are created equal. From a public health perspective, the biggest questions that remain—the ones the general public wants and deserves to know for their own safety—is how long and how well they’re protected from new variants of the virus, both the ones currently in circulation and the ones we’ve yet to encounter out in the wild. What happens if protection only lasts a number of months? Or if pre-existing conditions affect the duration of protection? Or if naturally occurring antibodies are less equipped to neutralize a new variant than the original strain? We need answers to all these questions and more if we’re to prevent as much needless sickness and death as possible. My first recommendation is to the physicians and healthcare workers at the frontlines. Were it standard practice for doctors to educate Covid-19 patients on the significance of their neutralizing antibody levels and their correlation to immune protection, they’d be able to make more informed decisions about their recovery and routines going forward. Doctors should have easy access to nationally standardized assays they can use to measure neutralizing antibody levels at their convenience. My second recommendation is to vaccine developers and policymakers. So far, the current generation of vaccines has been an astounding success. But without ongoing data collection and transparency from developers, we won’t have the knowledge we need to make informed decisions for ourselves or in our policies. The data can’t just be from the laboratory; we need ongoing disease surveillance on the ground. If we use research and public health measures to monitor this virus to the best of our ability, any national vaccination strategy will be outfitted to anticipate and accommodate individual differences in protection. If we don’t, we risk leaving 871
some people more vulnerable than others—creating blindspots where the virus can continue to replicate, evolve, and get past our defenses once more. This article originally appeared in Forbes and is available online here: Persistence Of Covid-19 Antibodies Varies Widely From Person To Person
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Moderna And Pfizer Vaccines Prevent Infection As Well As Disease: Key Questions Remain Forbes | March 30, 2021 | Article
Ever since the US vaccine rollout officially commenced in December, a question that has been top of mind is whether the messenger RNA (mRNA) vaccines created by Moderna and Pfizer/BioNTech would perform as well under real-world conditions as they did in the laboratory. Though the clinical trials of mRNA vaccines proved they were largely effective at preventing disease, their ability to prevent infection remained unknown. Thanks to a study published yesterday by the US Centers for Disease Control and Prevention, we now have our answer. According to the study, which was conducted on nearly 4,000 healthcare workers, first responders, and other essential workers at the frontlines in eight locations across the country, the mRNA vaccines are 90 percent effective at preventing infection. That means in addition to stopping the development of Covid-19 symptoms, they can stop the disease from spreading from one person to another, too. In December 2020, the study’s participants, who lived everywhere from Phoenix, Arizona to Portland, Oregon, began receiving doses of the Moderna or Pfizer-BioNTech vaccines. Almost three quarters had at least one dose by March 2021. To cast a wide net that could catch both symptomatic and asymptomatic infections, researchers required their subjects to test themselves for Covid-19 week in and week out using standard nasal swabs. In the group of unvaccinated workers, 161 ended up developing infections. By contrast, in the group of vaccinated workers, only 16 who received one dose caught the virus before they could get their second, while just three received both but caught it in the two-week period following the second dose. It was those three infections that brought the efficacy of the full two-dose regimen of the mRNA vaccines down to 90 percent. The mRNA vaccines aren’t foolproof,
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in other words, but given the circumstances they’re performing remarkably well. The results of this study, of course, are only preliminary, with investigations of greater depth and breadth to come. And though we hope the Covid-19 vaccines that use other platforms, like the adenovirus vaccines created by Johnson & Johnson and AstraZeneca, prove to be just as successful, they fall outside the bounds of this particular report. That said, two issues worth noting remain for all vaccines that the mRNA vaccine study didn’t address but forthcoming research might. The first is how long protection from disease and infection lasts. One recently published preprint study used a predictive model to answer this question in theory, calculating the duration of vaccine-mediated antibody responses—their indicator of immune protection of choice—based on already available data. Their best guess is that duration of protection correlates with a vaccine’s initial efficacy, but without real-world data we can’t be sure. The second issue is whether the protection will hold up against new variants of SARS-CoV-2. While the report never explicitly states that the participants contracted the original strain, if the question of viral variation wasn’t broached we can only assume it wasn’t relevant at the time. Various laboratory studies have found that the antibody-rich plasma of people who receive the mRNA vaccines loses its potency when pitted against new variants of the virus, particularly B.1.351 and P.1, which contain mutations now associated with a greater potential for immune escape. Overall, the news that the mRNA vaccines prevent infection in addition to disease is excellent. What it isn’t is a reason to let down our guard. As vaccine developers collect more data on how their products operate in real-world contexts, they must continue to release it in a timely fashion. They must also address the key questions that people who are pinning so many hopes on their vaccines continue to have. Important though it may be to celebrate every milestone, so long as this disease continues to spread among us and take lives, we must tackle every unresolved mystery with great haste and rigor. Nobody wants to be left in the dark—least of all when the light at the end of the tunnel seems increasingly near.
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This article originally appeared in Forbes and is available online here: Moderna And Pfizer Vaccines Prevent Infection As Well As Disease: Key Questions Remain
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Why Was CDC Director Rochelle Walensky Fighting Back Tears? Forbes | March 31, 2021 | Article
All public health officials agree, the United States is at a critical stage if we want to control the pandemic. All of them express deep fears that ignoring the Covid-19 pandemic at this stage is foolhardy. Especially dispensing with masks, social distancing, and other mitigations. President Biden has urged states to put aside politics and reinstate mask mandates. CDC director Rochelle Walensky was fighting back tears during an address where she went off script and pleaded with Americans to "hold on a little longer". Their fears are well-founded, as infections are ticking up across the United States and abroad, as the global disaster of Covid-19 is unfolding once again. The seven-day average of new virus cases in the U.S. is currently over 65,000, a level comparable with late October’s average. As seen in the chart below (Figure 1), cases are rising again worldwide, with just a few exceptions. Brazil is recording the world's highest daily death tolls, which far exceed anything seen earlier in the pandemic and German officials have warned that this third wave could be far worse than the previous two. These cases demonstrate that evidently, Covid-19 is a disease for all seasons, regardless of where in the world you might be. The U.S. was not spared the last time around. Indeed our infection rates soared to over 250,000 cases a day. Why does it appear that many of my fellow countrymen believe that they will be spared today? Scaling up vaccination campaigns will help, but with only 15.8% of the total population currently fully vaccinated, it is not enough to ward off this impending disaster. We are not dealing with the same virus we were in previous waves. Our failure to fully control the pandemic in the early days has led to the proliferation of the variants. The variants are far more contagious than the original SARS-CoV-2 strain and make up an increasing number of cases across the country. Florida has seen cases 876
of the B.1.1.7 variant double from 1,075 to 2,330 and Brazil variant P.1 almost double from 19 to 42 cases in just the last week. With the relaxation of Covid-19 restrictions in many states and the highest rates of travel during the pandemic, our population is even more vulnerable to infection. Last week, I wrote about how careless spring break parties will contribute to a surge in cases. Seeing behaviors like these that could leave hundreds or thousands of more Americans dead is more than enough reason to cry. We cannot let "pandemic fatigue" get in the way of saving lives, if we don't immediately implement precautions, any deaths that will come in the next few months will be needless with vaccinations so close. This article originally appeared in Forbes and is available online here: Why Was CDC Director Rochelle Walensky Fighting Back Tears?
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New Belgian Variant Illustrates The Versatility Of SARS-CoV-2 In Escaping Immune Suppression Forbes | March 31, 2021 | Article
There is now a new mutant to add to the global SARS-CoV-2 variant collection, this one in Belgium. This new Belgian variant (B.1.214), first detected in January by researchers at the University of Liege, although it is only a relatively small percentage of cases domestically and abroad, it appears to have the potential to become quite pervasive. It has mutations, not only in the spike protein as many others have, but also in other parts of the genome, all of which may contribute to increased transmission, virulence, and immune evasion. Beginning within the spike protein, the B.1.214 variant carries six total mutations. The function of the spike protein is to seek out and bind to ACE2 receptors of human host cells in the nasopharynx, intestines, and other parts of the body. It allows the virus to bind and open an entry port to the cell to infect and spread within the host. This is a frequent site of mutations for past variants, some of which may cause increased virulence and infectivity. Although the B.1.214 variant lacks some of the most common mutations, such as E484K, N501Y, and others, it has unique mutations of concern. Of these mutations, we believe the following is the most potentially troubling. An asparagine to lysine change at position 450 (N450K) lies in the receptor-binding domain, which binds directly to the ACE2. In other variants, this type of mutation may have a dual effect. First, a mutation to this mechanism could increase the affinity of the spike protein, leading to greater infectivity of the virus. Second, these types of mutations could abrogate the ability of neutralizing antibodies to bind, leading to a more immune-evasive virus. There are additional mutations in the spike protein that could be of similar
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concern. Shown below in figure one is the full wealth of mutations in the spike protein. Replication of the SARS-CoV-2 virus is complex. It involves the creation of specialized compartments to shield the virus from immune surveillance, as well as a unique and elaborate method of producing replicated viral proteins unique to this family of viruses. That requires the cooperation of at least sixteen proteins, the nonstructural proteins (NSP), many of which are multifunctional. Changes to the NSPs numbered one through sixteen can increase the ability of the virus to grow to rather high titers. A common characteristic among variants is a large number of mutations to this complex. These variants are also often noted to produce in high titers, likely leading to increased severity of disease. We note that the B.1.214 variant has eleven mutations, many of these in critical areas for facilitating virus replication. Immune Modulators The SARS-CoV-2 genome contains a set of proteins, as many as fourteen, which alter both the innate and the adaptive immune responses to its own advantage. Many pervasive SARS-CoV-2 variants, including the widespread United Kingdom (B.1.1.7) variant, have a number of mutations to these proteins as well. We note that the B.1.214 variant contains significant changes to the immune modulators, and the following are some of great concern. In the nucleocapsid protein, the aspartic acid to leucine mutation at position 3 (D3L) lies in the signal peptide, which drives the protein through the membrane. The nucleocapsid protein provides stability to the virus, antagonizes viral RNA and interferon responses, and inhibits genome replication in the host cell, thus a mutation to this region could enhance these critical processes. In the open-reading frame three (ORF3a) protein, there are a set of nine amino acid deletions from positions 20 to 28. ORF3a is additionally involved in antagonizing interferon responses and is a common site for mutations across SARS-CoV-2 variants. The B.1.214 variant is unusual in that ORF8, which is often heavily mutated or even eliminated in some variants, is fully intact. Shown below in figure 2 is the full wealth of mutations in B.1.214 external to the spike protein. Notably, both the deletions in ORF3a and the D3L mutation in the nucleocapsid protein, among others, are also observed in the 879
widespread B.1.1.7 variant. There are two possible explanations for this. Either they were derived entirely independently, or that they derive from a precursor variant. Given the significant number of mutations that these, and only these variants share, we speculate that both come from common stock. The lineage is shown in figure three below. The B.1.214 variant shows a concerning combination of common mutations that have caused trouble with previous widespread variants, as well as unique mutations which may only add to the dangerous recipe. We suggest it receive continued monitoring and research as it could be a driver of new surges in cases yet to come. One current speculation is that SARS-CoV-2 has a limited set of mutations, which it may have exhausted. If this is true, it would be far more susceptible to second and third-generation vaccines. We find this conclusion unlikely. As you can see from the B.1.214 variants and others we have previously discussed, there is a wide array of variants that spread widely, despite lacking the popular N501Y and E484K mutations, such as the California and Washington DC variants. Additionally, the cold-causing coronaviruses recur annually and studies show the spike protein can vary 4% between cold seasons and the receptor-binding domain specifically can vary up to 17%. We estimate this is a lower limit on the mutative capabilities of SARSCoV-2, in other words, we have not begun to see the virtuosity of this virus in its wealth of mutation and immune evasiveness. This article originally appeared in Forbes and is available online here:New Belgian Variant Illustrates The Versatility Of SARS-CoV2 In Escaping Immune Suppression
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April 2021
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Despite Progress, Protecting The Population Against Covid-19 Variants Remains Complex Forbes | April 1, 2021 | Article
More positive news comes from Pfizer and BioNTech this week as the latest results from their clinical trial data suggest that their vaccine protects against the more contagious B.1.351 variant initially detected in South Africa. The vaccine showed 100 percent efficacy in South Africa, where B.1351 is prevalent. Nine people in the study contracted Covid-19, all of whom were in the placebo group. However, these findings are limited as only 800 participants were enrolled in South Africa. Nonetheless, this is a very positive result and very different from the response of the AstraZeneca vaccine to the B.1.351 variant which recent studies showed only 10.4% efficacy against mild-to-moderate infections. The difference could be related to the amount of antibody titers produced by both vaccines, as although they are both reacting to the same antigen, the concentration of neutralizing antibodies is generally much higher in the Pfizer and Moderna vaccines than it is for the adenovirus vaccines. However, the challenges in protecting the population against the ever-evolving variants remain complex, especially with regards to the unknown duration of protection. A study published this month takes a different approach to protection, asking the question do antibodies generated by infection with a variant protect against other strains. The study used plasma collected from adults hospitalized with Covid-19 who were infected with two South African infection waves, with the second wave dominated by the B.1.351 variant. Sequencing demonstrated that infections in first wave plasma donors did not have any of the B.1.351 defining mutations, except for one with the E484K mutation in the receptor-binding domain.
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The B.1.351 virus was effectively neutralized by plasma from second wave infections and the first wave virus (SARS-CoV-2) was effectively neutralized by first wave plasma. However, in crossneutralization, the B.1.351 virus was poorly neutralized by first wave plasma, with a 15.1-fold drop relative to B.1.351 neutralization by second wave plasma across participants. In contrast, second wave plasma cross-neutralization of the first wave virus was more effective, showing only a 2.3-fold decline relative to first wave plasma neutralization of first wave virus. These results would seem to suggest that yes, antibodies generated by infection with a variant do protect against other strains and the second-generation vaccines that are being developed based on the B.1.351 should provide greater protection. However, the duration of that protection and protection against future evolving variants is still uncertain. Unlike the speculations made by other virologists, I do not believe Covid-19 will “run out of tricks” and eventually cease to significantly mutate. To reach this conclusion, we only need to look at the continual evolution of the Influenza virus and the work of evolutionary biologist Jesse Bloom, Ph.D., and his collaborators, who I have written about in past Forbes columns. Bloom has studied coldcausing coronaviruses over a 25 year period and found that although the later serum neutralizes the early virus that doesn’t mean there weren’t further mutations. Covid-19 is likely to become endemic. The best model we have for protecting ourselves against evolving mutations of the original SARS- CoV-2 strain is how we protect ourselves against Influenza, which will likely mean annual vaccinations along with drug treatments and other public health measures. This article originally appeared in Forbes and is available online here:Despite Progress, Protecting The Population Against Covid-19 Variants Remains Complex
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Pfizer’s New Oral Protease Inhibitor Could Possibly Treat And Prevent Covid-19 Forbes | April 5, 2021 | Article
Currently, we are pinning all our hopes on vaccines for return to normalcy, which in the case of new data from Moderna and Pfizer have been found not just to protect against severe disease and death but also infection. This is a positive development and the secondgeneration vaccines currently being developed will likely bring greater efficacy. Yet the question remains will vaccination alone be enough to contain the Covid-19 pandemic. Vaccines still pose a myriad of challenges in terms of vaccine hesitancy, the unknown length, and duration of protection, and their efficacy against the ever-mutating variants. Therefore, it is clear that only a multifaceted approach utilizing vaccines, drug treatments, and public health measures will prevent infections from spreading. The good news is that Remdesivir and other cocktails of monoclonal antibodies have shown that prevention and early treatment with antiviral drugs do work to reduce disease. However, these drugs are currently administered via infusion and require hospitalization, which makes delivery challenging and inaccessible to mass populations. This is why Pfizer’s announcement that they are developing an oral antiviral drug that could be used at the first sign of infection or exposure is such promising news. The drug is part of a class of medicines called protease inhibitors and works by inhibiting an enzyme that the virus needs to replicate in human cells. Protease inhibitors are used to treat other viral pathogens such as HIV and hepatitis C. A virus takes over our cell’s RNA in order to produce viral proteins to make more copies of itself. Initially, the infected cell forms a single viral protein chain like a long string that is mostly nonfunctional. The protease enzyme cuts the protein chain in specific areas to produce fully-functional working subunits that are critical for the virus to replicate. Protease inhibitors are a class of antiviral 884
drugs that shut down this protein-cutting process and stops a virus from multiplying. Respiratory viruses like influenza, respiratory syncytial virus, and now Covid-19 are uniquely challenging to treat once symptoms arise. Because infections and symptoms for respiratory viruses are typically short-lived, the immune system quickly engages in viral replication suppression. This is why these protease inhibitor drugs are ideally used in congregate living situations such as long-term care facilities, workplaces, schools, prisons, and family homes. Once an infection is detected in those communities, everyone exposed can immediately start prophylactic (preventative) treatment by taking a pill while isolating, preventing the viral replication and the spread of infection in the greater community. An antiviral used for Influenza, Xofluza demonstrates the success of this approach, with the drug reducing transmission by 80% in a close-quarter family context. By attacking the virus before it has a chance to replicate we have the opportunity to prevent the spread of infections and mutation of future variants. Of course, for this strategy to be completely successful, it needs to be combined with a mass rapid antigen testing program to detect infections in their earliest stages. Many public health officials, including myself, have been calling for a program like this to stop the spread of infections since the early days of the pandemic, I have detailed what such a plan would look like in an earlier piece on containing Covid-19 within the U.S. If successful, the Pfizer drug could also be used for those experiencing long Covid-19 in order to prevent long-term shedding of the virus and potential transmission to others. In a prior column for Forbes, I wrote about research demonstrating the fecal transmission of Covid-19. One study, conducted in Zhejiang, China, discovered viral RNA in the stool of 59 percent of Covid19 patients tested, remaining at detectable levels for three weeks on average. Another study found that the virus persisted longer in fecal samples than even respiratory samples. Though the presence of viral RNA doesn’t necessarily indicate the presence of live, actively replicating virus, the latter has been isolated and cultured from fecal samples in the laboratory. Protease inhibitors have a long history of use, a good safety profile, and are generally well-tolerated so they
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could even be given to asymptomatic Covid-19 patients to eliminate this longer-term shedding and risk of potential transmission. Egypt’s 100 Million Healthy Lives initiative provides an example of how we could accomplish this. Egypt previously had one of the highest rates of Hepatitis C in the world. In 2018, Egypt launched the 100 Million Healthy Lives program. The goal was to screen all Egyptians over the age of 12 for active hepatitis C virus replication along with other chronic conditions. Those who tested positive were treated with the antiviral medication Sovaldi (sofosbuvir) a nucleotide analogue that inhibits the polymerase enzyme of hepatitis C and blocks its replication. This program means that Egypt may soon be the first country to eliminate hepatitis C. The research for this current Pfizer drug comes from a revived compound identified in 2003 as a potential treatment for the Severe Acute Respiratory Syndrome (SARS) epidemic in China. The Pfizer compound was developed to inhibit an enzyme called a protease. The revived compound is specific to the proteases produced by coronaviruses, which are responsible for causing SARS in 2003 and COVID-19 today. It is a tragedy that the development of this drug and others like it were abandoned until recently. Had we seen this research to completion after SARS and MERS, governments could have stockpiled the drugs years in advance of this latest outbreak and administered one-day delivery to all locations where the virus has been detected or suspected. All patients, hospital workers and any other persons suspected of contact would have been treated to stop the epidemic in its tracks. We need to learn from this mistake and invest in producing multiple antiviral drugs to prevent and treat Covid-19 the same way we have for HIV/AIDS, as well as long acting prevention drugs. A study from China has also shown success in designing 32 new protease inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro in a mouse model. This shows the potential for how many antiviral drugs could be developed. For the strongest possible defence against Covid-19 and mutations of the virus we should look at the approach used for treating AIDS known as combination therapy. The gold standard for AIDS treatment now is called antiretroviral therapy. This is when 886
patients take a cocktail of at least three different drugs that attack the HIV virus in different ways. The strategy is based on earlier success we had in fighting cancer. In the late 1970s, I established a laboratory at Harvard University's Dana-Farber Cancer Institute to develop new drugs to treat cancer patients. Cancers developed resistance over time to single drugs, but combinations of drugs were effective in slowing, stopping or killing the cancers. We took that same lesson of combination chemotherapy to HIV. By the early 1990s, the first combination AIDS treatments were saving the lives of people infected with HIV. Today an infection is far from the death sentence it used to be, patients can now live almost unaffected by HIV, with a relatively minimal impact on life expectancy. If trials of the Pfizer drug are successful, we need to apply this same approach and combine the Pfizer drug with other antivirals like Molnupiravir to outsmart the shape-shifting Covid-19 virus. Developing a drug to treat Covid-19 is actually easier than with HIV/AIDS as the drug only needs to be tolerated for a short period of time, as opposed to HIV/AIDS drugs which need to be taken for a lifetime. Antiviral drugs will form an important part of our armamentarium, alongside vaccines and public health measures as we continue our fight against the Covid-19 pandemic. This article originally appeared in Forbes and is available online here:Pfizer’s New Oral Protease Inhibitor Could Possibly Treat And Prevent Covid-19
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HBO Doc ‘The Last Cruise’ Gives Insight Into Nightmarish Covid-19 Outbreak Forbes | April 6, 2021 | Article
In the first few minutes of The Last Cruise, a new HBO documentary directed by Hannah Olson, the skies are clear, the waters blue, and aboard the Diamond Princess, aerobics classes involving hundreds are in full swing. The date is January 20, 2020, and the cruise ship has just set sail on a tour of Southeast Asia that will allow its 2,500+ passengers to explore cities like Hong Kong, Keelung, and Okinawa against the resplendent backdrop of the Lunar Year. Media reports of a mysterious virus circulating in China bleed in occasionally, but not enough to disrupt the ongoing festivities or dampen the enthusiasm shared by passengers and crew alike. The ebullient atmosphere of the film takes a sharp turn when the Diamond Princess returns to Yokohama Port the evening of February 3. Though passengers are scheduled to disembark the following morning, preliminary medical screenings reveal that Covid-19—at the time still without an official name—has been detected on the ship, effectively forcing everyone aboard into a 14day quarantine. Using cellphone footage captured by the guests and crew members themselves as its primary source material, the film invites viewers to witness the downward spiral of the Diamond Princess into mayhem through their eyes, turning a disaster of nearmythic proportions into an intimate account of survival, tragedy, and inequality. After the Japanese Ministry of Health announces that numerous passengers have contracted the virus, we follow Dede Samsul Fuad, an Indonesian dishwasher, as he wanders the empty halls of the ship’s restaurant corridor, where he usually works. Similarly but separately, pastry chef Maruja Daya takes in the eerie silence of the high-end shops that have been abandoned in the virus’s wake—a moment of calm before the storm. The film immediately cuts to a shot of where all the action is taking place: the cramped kitchens in the hull. Virus 888
or no virus, it falls on the crew to keep the ship running and the guests happy, a tall order that includes doing laundry, cleaning common areas, and preparing 3,000 meals three times a day. Meanwhile above deck, a guest confined to a comparatively spacious cabin films herself limply poking at a dessert with her spoon, complaining about its consistency. The juxtaposition between the toiling crew and the inconvenienced passenger is one of many made throughout the film. Though neither population is monolithic, broad divisions based on class and nationality emerge early on that harden as the crisis intensifies. By February 7, 61 people aboard the ship had tested positive for Covid-19, but actual information on the virus—how it was transmitted, who was most at risk—remained scarce. Though the Diamond Princess passengers and crew are encouraged to stay calm, sounds of helicopters whirring above and sightings of hazmatsuited health workers milling about the port hint that the situation is more dire than it seems. Two days and nine additional confirmed infections later, we see guests Kent and Rebecca Frasure watching a video in which the chief medical officer of Princess Cruises explains the basic mechanics of the virus, stating that no evidence for airborne transmission currently exists. Minutes after the video finishes, Kent hears someone rummaging outside their room. When he peers into the hallway to check for the source of the commotion, he notices a sheet of paper has been taped onto the vent at the bottom of the door—clearly implying that airborne transmission, however uncertain, was still a threat. Though the Frasures are lucky enough to be staying in a penthouse suite, Rebecca is immunocompromised due to her multiple sclerosis and unsure how her body might react to the virus. Like the service workers down below, she and her husband must find ways to cope with the anxiety and dread that weighs heavier with each passing day. But unlike the Frasures, the crew has virtually no means of preventing their exposure to the virus when they’re healthy or isolating themselves when they’re sick, packed as they are into dorm-style accommodations with no windows, bunk beds, and only curtains for privacy. When Sonali Thakkar, a member of the ship’s security personnel, learned her shipmate had tested positive but couldn’t get tested herself for four whole days, she made the risky decision to break her contract and take their plight to the 889
media. “We need help,” she said in a televised interview with Times Now. “Each and every crew member needs to also be tested and be separated. We are happy to do whatever we have to do to help others, but we don’t feel safe.” The nightmare ends for most of the ship’s American passengers on February 17 when they board two government-charted military planes bound for the United States. (Since Rebecca Frasure eventually tested positive for Covid-19 and had to be hospitalized, she and her husband were among the holdouts.) Italy, Canada, Australia, and other high-income countries dispatch their own rescue planes shortly thereafter. Unsurprisingly, we find out that the last passengers to leave the ship—nearly a week and half after American guests—are members of the crew, most of whom hail from Indonesia, India, and the Philippines. Come March 1, all passengers evacuate the Diamond Princess for good, with the Indonesian passengers being the last to leave. But until they were finally off the ship, the concern that they’d been left for dead— “being killed slowly,” as one crew member put it—remained horrifyingly real. In just two weeks, the Diamond Princess had become the site of the largest outbreak of Covid-19 outside mainland China, with 712 confirmed infections and 14 deaths. Watching the film, I couldn’t help but wish we had more clarity on the exact steps Princess Cruises and the Japanese government were taking to protect the lives of those on board. Too much of the 40-minute runtime is devoted to the antics of the more privileged passengers and too little to making connections between the events surrounding the outbreak and the Covid-19 pandemic at large. In restricting our knowledge to the perspectives of the passengers and crew, however, the filmmakers succeeded in creating a first-person narrative that likely resonates for all viewers in one way or another. Likely for many of us the isolation, fear, and confusion that descended upon the Diamond Princess still hits too close to home. We can only hope that the next time a pandemic of this magnitude befalls us, we’ll be able to act confidently and knowledgeably to help ourselves and each other, rather than stay scrambling in the dark. This article originally appeared in Forbes and is available online here: HBO Doc ‘The Last Cruise’ Gives Insight Into Nightmarish Covid19 Outbreak 890
Rapid Home Testing: If The UK Can Do It, Why Can’t We? Forbes | April 8, 2021 | Article
News outlets in the US have been blanketed with feel-good stories about the unprecedented vaccine rollout and the potential of a postpandemic world. While some articles express concern over how the new variants come into play, few if any of the articles are focused on what we actually need to return to our pre-pandemic ways: testing. The countries that have successfully reopened—countries like Australia, China, New Zealand, Taiwan—have done it through a combination of vaccines, testing, tracing, and mandatory quarantine. Even these countries have had subsequent outbreaks, but when the outbreaks have happened they have been able to wrestle them under control. That is in stark contrast to countries like our own, who have failed from the beginning to build an adequate testing infrastructure. We’ve paid for this failing in the hundreds of thousands who have died unnecessarily. That’s right—these were avoidable deaths, had we been willing to test and trace at the level required. The United States is currently hovering around 1.5 million Covid tests per day, give or take a few hundred thousand. But it is a far cray from what is needed to contain the epidemic. Selfadministered rapid tests should be widely available for free at every school, business and public institution in the country so every American can be tested at least twice a week. This means we should not be talking about millions of tests per day but rather tens of millions of tests. Previous simulations of such a testing program suggest that a high level of testing, combined with contract tracing and quarantine could lead to an eighty percent cut in transmissions. On a small, this approach has worked well. Last September, the University of Illinois implemented an aggressive testing campaign to reign in the spread of COVID-19 and launched an online dashboard with real time reporting of new cases. Students tested positive are alerted and quarantined while the school grants building and facilities access to 891
those who test negative. The approach has helped keep the school open safely for students—while the test positivity rate across the state hovers at a two month high of 3.8%, the university has kept its rate below 0.18% over the same time period. Some argue that this approach is impossible to replicate on a national scale, for a country like ours that has let it’s outbreak spiral out of control. But what’s happening in the United Kingdom today suggests that such a view is far from reality. The UK also struggled with implementing a comprehensive testing regime, from the very beginning of the pandemic. And they too have let their outbreak spiral out of control, reaching an all time high of new cases per day at he beginning of this year. And yet, as of this week, everyone in England will be able to access free, rapid coronavirus tests for themselves and their entire families so they can test themselves regularly, at least twice a week. The move paves the way for businesses and society to reopen. Given that one in three people with Covid-19 do not experience any symptoms, people are frequently contributing to the spread of the virus without knowing they are even infected in the first place. With this initiative, rapid testing will be offered to everyone—they can have the tests delivered to their home, they’ll have access to on-site workplace testing and testing at community sites, in pharmacies and in some other public venues. What it means is that everyone in the country will be able to know their Covid status and will be able to decide whether they can safely head to work, to school or to see friends at bars and restaurants or if they need to stay home instead, protecting those they love from potential illness. As the UK government notes, the testing program, in addition to the vaccine rollout, is an important step that needs to be taken in order to ease restrictions and help suppress the spread of variants. Rapid testing was previously available to frontline health workers and other essential workers in public-facing roles. Those tests detected over 120,000 positive cases that would not have been discovered otherwise. More cases would be detected as a result of making rapid testing available to all, breaking transmission chains and saving lives. If England can roll out a rapid testing campaign in tandem with their vaccines, why can't we? In March, the FDA authorized several over-the-counter tests in an effort to get more tests for screening 892
asymptomatic individuals on the market. That’s a step in the right direction, but the government has done little to help cover the costs of the test, which run anywhere from $25 to $50—far more than what most families could afford on a regular basis. Our next step should follow the UK’s, ensuring that these tests are available to everyone, whether insured and earning an income or not. No matter the cost, it will no doubt be far less than the trillions of dollars in lost productivity and spending with an ongoing outbreak. This article originally appeared in Forbes and is available online here: Rapid Home Testing: If The UK Can Do It, Why Can’t We?
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An Indian SARS-CoV-2 Variant Lands In California. More Danger Ahead? Forbes | April 12, 2021 | Article
On April 9th, 145,384 India reported 145,382 new infections, a tenfold increase over the 11,012 new infections reported on February 9, just two months ago. The Indian variant designated B.1.617 is likely, at least in part, to be driving the current wave. The new strain has been detected in at least 5 Indian states, including Maharashtra, Delhi, and Punjab, which have all contributed to the surge of cases in the country, in addition to the B.1.1.7 (UK), B.1.351 (South Africa), and P.1 (Brazil) variants which are also circulating India. It is unknown the extent to which this strain has spread, but of the 2,844 sequences submitted to the GISAID database from India since March 1, 162 sequences have been classified as B.1.617, or about 6%. This percentage is likely to grow. This is all the more reason for concern now that this variant has arrived here in the United States. Detailed analysis of the genome and proteins of B.1.617 reveal it arose independently in India. It differs substantially from the B.1.1.7, P.1, B.1.351, B.1.427/9 (California), and B.1.526 (New York) variants currently circulating in the United States. All of the 15 amino acid changes of B.1.617 differ from those of all other variants of concern when compared to the globally dominant D614G strain designated B.1 with two notable exceptions. The exceptions are in a region of the spike protein, the receptorbinding domain (RBD), that is critical both for binding to the ACE2 receptor and antibody neutralization. The first of these is a leucine to arginine substitution at amino acid 452 (L452R). This is the same change found in the California variant (B.1.427/429). Laboratory experiments demonstrate that this change both increases the affinity of the spike for the receptor and decreases antibody recognition, including recognition by antibodies present in convalescent serum and as well as some clinically important neutralizing monoclonal antibodies. 894
The second mutation of interest occurs at amino acid 484. Many of the variants of concern, including the B.1.351, P.1, and B.1.526 variants, substitute glutamic acid for lysine (E484K), which is a substitution of a negatively charged for a positively charged amino acid. This change reduces neutralization by convalescent antisera and binding of some monoclonal antibodies and increases the affinity for ACE2. The Indian variant B.1.617 is also mutated at position 484. However, the 484 mutation is different. The glutamic acid is substituted by the polar uncharged amino acid glutamine (E484Q). Laboratory experiments confirm that this change also confers increased ACE2 binding and immune evasion properties. The combination of the two, sometimes called the double mutant, goes a long way toward explaining the increased transmission of the India variant in its home country, and highlights the danger now that it is established here in the United States. Two of the five remaining mutations in the spike protein are located in the N-terminal domain of the S1 protein, a region that is extensively mutated in other variants of concern. These two mutations are unique to the Indian variant. The third mutant in S1, the substitution of proline for arginine (P681R), is located near the cleavage site between S1 and S2. This change may increase the infectivity of the virus particles by facilitating cleavage of the S precursor protein to the active S1/S2 configuration. The contribution of the two remaining amino acid substitutions in the S2 portions is also unique to the Indian variant. The full extent of spike mutations in the B.1.617 variant can be found in the figure below. Most of the variants of concern also contain an extensive set of mutations in the structural proteins, the replication enzymes, and the accessory proteins. B.1.617 is no exception. B.1.617 carries one mutation in each of the replication enzymes, NSP3, NSP6, NSP13, NSP15, NSP16 as well as one mutation in the accessory proteins orf3a, orf6, and orf7a. As before, these changes are unique to the Indian variant. All these mutations are illustrated in the following figure. It is still early days in understanding the importance of the arrival of the Indian variant in the United States. The B.1.617 variant has all the hallmarks of a very dangerous virus. If indeed it is this variant 895
that is driving the unprecedented exponential increase in infections in India, the potential for trouble here in the United States is real and immediate. We must do all that is possible to identify its spread and to contain it. We thank Dr. Benjamin Pinsky and Dr. Malaya Kumar Sahoo for their insights in preparation for this report. April 16th Update: Seventy-seven new cases of the B.1.617 variant have been discovered in the United Kingdom, according to a report by the Financial Times. The virus is rapidly spreading in India and “confirmed cases [in the UK] are growing at a similar rate to B.1.1.7 at the same stage of its emergence.” This variant must continue to be monitored as it appears to have rapid-spread capabilities like many variants of concern. A number of people have minimized the variants in terms of their potential to spread, reinfect, and avoid vaccination. As I look around the world, I find variants are increasing their cause for concern in all respects. This discovery only reinforces the urgency to dramatically increase domestic and international surveillance of disease to prepare us for what appears to be a continuous onslaught of SARS-CoV-2 variants. This article originally appeared in Forbes and is available online here: An Indian SARS-CoV-2 Variant Lands In California. More Danger Ahead?
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Covid-19 Increases Stress And Traumatic Stress Disorders Including Drug Abuse And Fatal Overdoses Forbes | April 13, 2021 | Article
A syndemic refers to multiple interrelated epidemics happening at the same time. Covid-19 has unleashed and amplified a number of simultaneous personal, social, medical, political, and economic crises. This article is part two of a series of articles exploring the impact of the Covid-19 syndemic. Read part one here. Post-traumatic stress disorder (PTSD) is an anxiety disorder that is caused by a traumatic experience in a person’s life, such as military combat, sexual abuse, violence, disasters, or acts of terrorism. Symptoms often include flashbacks, nightmares, severe anxiety and depression as well as uncontrollable and intrusive thoughts surrounding the events that caused the PTSD. Covid-19 has created so many stressors from strained finances to grieving the death of loved ones to the moral trauma of global leaders mishandling or ignoring the crisis. It is likely that an unprecedented amount of people have and will experience PTSD related to the effects of Covid-19. A recent study demonstrated the prevalence of PTSD in 30.2% of patients after acute Covid-19 infection This alone is a grave concern as our health systems are not currently equipped to care for and treat such an influx of patients and even access to mental health care remains a convoluted issue. Amplifying the crisis is that PTSD and substance abuse disorders are commonly linked as co-occurring disorders. Research consistently demonstrates that individuals who suffer from trauma or PTSD are more likely to have problems with substance dependence. The U.S. National Comorbidity Survey revealed that 34.5% of men and 26.9% of women who had PTSD at some point in their lifetime also had a problem with drug abuse or dependence. Based on this knowledge, substance abuse and addiction could even be seen as manifesting as a symptom of PTSD. 897
According to the CDC, as of June 2020, 13% of Americans reported starting or increasing substance use as a way of coping with stress or emotions related to COVID-19. As the pandemic has continued, the crisis has only worsened. In Colorado, overdose deaths were up 20% through the end of last year, and those involving fentanyl doubled. 2020 proved to be the deadliest year of the opioid epidemic on record for Maine with 502 fatal drug overdoses reported. The latest national data from the CDC shows there were more than 88,000 overdose deaths in the year through August 2020, up from nearly 70,000 in the same time period of 2019. According to a report from the Commonwealth Fund, the final 2020 total in the United States could exceed 90,000 overdose deaths, compared to 70,630 in 2019. That would not only be the highest annual number on record but the largest single-year percentage increase in the past 20 years. There are many reasons that may explain why the pandemic has facilitated this steep rise in addiction, relapse, and overdoses. Americans have fewer coping and resilience-building strategies available to them in the pandemic, they can’t exercise at a gym or fitness center and they can’t socialize or see family regularly. Isolation makes it easier to hide the effects of addiction from family and friends who might otherwise intervene. People are also more likely to die when they are using drugs alone because there’s no one there to call emergency services or administer naloxone, an opioid-reversal agent. The impact of PTSD related to Covid-19 can also not be underestimated. During the early stages of the pandemic and even currently, addiction treatment centers have shut down or reduced their inperson services. While clinics and services have shifted to telehealth services, many patients lack access to stable housing and/or the technology to access these services. Some patients feel the intimacy and impact of a group meeting are lost in a virtual setting and stop attending. That’s not to say telehealth can’t be effective in providing greater access to care, particularly in rural areas. But the choice to use telehealth in addiction treatment needs to be voluntary, not inflicted by a pandemic. Despite the clear and desperate need, many states are cutting addiction programs due to the financial toll of the pandemic. The 898
National Council on Behavioral Health conducted an online survey of 880 behavioral health organizations across the country in April 2020. 61.8% of organizations closed at least one program. Nearly all of the organizations (92.6%) have reduced their operations. 46.7% of behavioral health organizations have had to, or plan to, lay off or furlough employees as a result of Covid-19. One option to address this disparity in care is Medicaid expansion, which has been associated with positive insurance coverage, treatment access, and mortality outcomes for substanceuse patients. With the federal government funding 90 percent of the cost, Medicaid expansion can be a key source of external funding for states to sustain substance abuse care providers and facilitate better access for patients. Florida, South Carolina, and Tennessee, which have high overdose rates, have yet to expand Medicaid. Utilizing Medicaid also decreases the reliance on annual discretionary funding to support siloed treatment programs. On April 1st, 2021, the Biden administration announced its drug policy priorities for the first year. These priorities included expanding access to quality treatment, enhancing harm reduction services to engage and build trust with people who use drugs, and working to reduce the lethal supply of illegal substances in the U.S, advancing recovery-ready workplaces, expanding the addiction workforce, and increasing access to recovery support services such as safe and stable housing. While these are critical and long-overdue reforms, there also needs to be a greater focus on preventive mental health screenings and care due to their link with substance abuse disorders. Childhood trauma is also linked with future substance use disorders and will likely be exacerbated by the increase in child poverty during the pandemic. Creating integrated healthcare systems that treat the physical, mental and social health of patients will be critical in fighting the syndemics such as PTSD and addiction that accompany the Covid-19 pandemic. This article originally appeared in Forbes and is available online here: Covid-19 Increases Stress And Traumatic Stress Disorders Including Drug Abuse And Fatal Overdoses
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A Dangerous New Covid-19 Variant Detected In Oregon Forbes | April 13, 2021 | Article
The SARS-CoV-2 variant B.1.1.7 virus, first detected in the UK in late October 2020, has become the dominant strain in the UK, throughout most of Europe and India, and is now the most frequent virus isolated in the United States. The B.1.1.7 variant is more infectious than the SARS-CoV-2 strains that circulated earlier in the pandemic, is almost twice as deadly, and infects younger people and even children at a higher rate. Many speculate that the current surge of infections throughout Europe, the United States, and possibly India can be attributed, at least in part, to the increased efficiency of transmission of the B.1.1.7 virus. The hope is that the current generation of Covid-19 vaccines, all of which are based on the spike protein of the original Wuhan strain, will be effective against the B.1.1.7 strain. This hope is based on the observation that antibodies from plasma of those who receive the vaccine recognize and neutralize the B.1.1.7 virus only slightly less well than they do the original Wuhan strain. Now comes a troubling report of the discovery of a new variant from Oregon. As of yet, there are only two confirmed isolates in Oregon with this sequence, but the number of undetected cases is likely larger. The variant does not yet have an official designation. I will call it B.1.1.7-O as the variant carries all of the mutations of B.1.1.7 plus an additional six mutations of its own, one in the spike protein, three on the replication complex (ORF1ab), one in the structural protein N, and one in the accessory protein ORF8. This variant arises on the west coast as the B.1.427/9 variants have surged through California, making up over 50% of the cases sequenced. Of these, the single change in the spike protein, a substitution of the negatively charged amino acid glutamic acid (E) for the positively charged lysine at position 484 (E484K), nicknamed the “EEK!” variant, is of special concern particularly when coupled with the N501Y mutation (asparagine (N) to tyrosine (Y) at amino acid 501). 900
The combination of these two mutations in the receptor-binding domain of the spike protein is the principal cause of vaccine resistance of the Brazilian isolate B.1.1.28.1 and the South African variant B.1.351. Together these two mutations are associated with an increased transmission and vaccine resistance. For example, the Astra-Zeneca adenovirus-based vaccine is only 10% effective against the B.1.351 South African variant. The potency of the Moderna and Pfizer vaccines is reduced almost tenfold when tested against the B.1.351 and B.1.1.28.1 variants. The B.1.1.7-O variant is likely to be similarly resistant to the current vaccines. The figure below depicts the full range of B.1.1.7-O’s spike mutations. The single additional mutation in the accessory gene ORF8 may also contribute to increased infectivity and/or immune evasion. The mutation at position 68 of ORF8 introduces a stop codon preventing the expression of the protein altogether. This is in addition to a stop codon at position 27 and two amino acid changes at positions 52 and 71 of B.1.1.7. ORF8 is highly antigenic and the stop codon introduces two non-exclusive possibilities. First, ORF8 is eliminated as a key immunogenic epitope, allowing increased immune evasion in the variant. Second, its elimination may remove a factor that attenuates virulence. Premature termination in ORF8 in SARS-CoV-2 is relatively rare, but other mutations to the accessory protein occur in the B.1.1.28.1, Californian B.1.427/9, New York B.1.526, and Philippine B.1.1.28.3 variants. The selection pressure against the expression of ORF8 seems to be exceptionally powerful. The ORF8 protein is expressed upon infection with the original Wuhan strain and the D614G variant B.1 as evidenced by antibodies to the ORF8 with convalescent sera. Is it possible that ORF8 attenuates the virulence of SARS-CoV-2 and that the premature termination increases symptoms in infected hosts? The four additional mutations that distinguish B.1.1.7-O from B.1.1.7 include one change of a single amino acid in each of the nonstructural proteins, NSP2, the polymerase NSP12, and exonuclease NSP14, and in the structural protein, N. The NSP2 and N mutations are rare, showing up in only a few hundred isolates of B.1.1.7 of the over 300,000 in the GISAID database. The NSP12 and NSP14 mutations, however, are a bit more common, but not lineage-defining. The NSP12 mutation appears in around 28,000 901
isolates and the NSP14 mutation in around 6,000 isolates, with both below 10% of sequenced B.1.1.7 isolates. The figure below depicts the full range of B.1.1.7-O’s genomic mutations outside of the spike protein. The detection B.1.1.7-O is troubling for several reasons. The variant may spread rapidly in the United States and may be vaccineresistant. The variant also may be able to re-infect those infected earlier in the pandemic as is the case for both B.1.351 and B.1.1.28.1 that carry the E484K and N501Y mutations. The appearance of B.1.1.7-O serves as a warning of the continuing evolution of SARS-CoV-2 from older variants, like B.1.1.7, towards increased transmissibility, virulence, and immune evasion in the United States and elsewhere. Effective public health mitigation measures, surveillance, and rapid deployment of secondgeneration vaccines seem the only way to contain this ever more dangerous virus. This article originally appeared in Forbes and is available online here: A Dangerous New Covid-19 Variant Detected In Oregon
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Young People Hit Hardest By Loneliness And Depression During Covid-19 Forbes | April 13, 2021 | Article
A syndemic refers to multiple interrelated epidemics happening at the same time. Covid-19 has unleashed and amplified a number of simultaneous personal, social, medical, political, and economic crises. This article is part three of a series of articles exploring the impact of the Covid-19 syndemic, read part one and part two. Loneliness can be a risk factor in a range of health issues, including depression, anxiety, substance abuse, and domestic abuse. All problems that are unsurprisingly increasing as we continue to remain isolated during the pandemic. However it would appear that one demographic is feeling the effects of isolation more than others. A CDC online survey indicates that young people between the ages of 18-24 are more likely to suffer mental health problems during the pandemic than any age group. According to this survey, 63% of young people are suffering significant symptoms of anxiety or depression. Nearly a quarter of respondents reported that they had started or increased their abuse of substances, including alcohol, marijuana and prescription drugs, to cope with their emotions.Their experiences during the pandemic put them at risk of developing Covid-19 related PTSD. This is a general problem developing throughout society but felt acutely by young adults. This data quantifies an alarming trend that we have seen emerge anecdotally, that the pandemic will have a long lasting impact on the mental health of young people. One of the authors of the study, Mark Czeisler is hoping to conduct further research into why this particular demographic is so affected. He is currently looking into the extent in which people can tolerate uncertainty, or “the ability to accept the unknown, because now there are so many questions, especially for young people, about relative risk, duration of the pandemic and what their futures will look like.”
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For young people who are navigating choices about higher education, their careers, building relationships or deciding when to start a family, the uncertainty of the pandemic can add pressure to already stressful decisions. They may feel like their options are restricted or like their lives are on an endless pause during a critical developmental stage. Teenage and young adult brains are wired for new experiences and that developmental need is not being met. These stressors are in addition to the anxiety we all feel about our health and the health of our loved ones. Richard Weissbourd, a psychologist and senior lecturer at the Harvard Graduate School of Education helped lead a study conducted last October by researchers at Making Care Common which further reinforced the results of the CDC survey. The study highlighted the rising trend in loneliness among young adults compared to the elderly. As discussed, loneliness is at the root of many mental health Issues. In a national survey, of approximately 950 Americans, 36 percent reported feeling lonely “frequently” or “almost all the time” in the past four weeks. Sixty-one percent of the respondents aged 18 to 25 reported high levels of loneliness. Weissbourd suggests that young adults’ loneliness may be caused by the transition between “inherited families [and] chosen families”— friends who share a strong emotional bond may be unavailable to young adults when they are locked down with their family members at home. A 2016 report published in the journal Pediatric Clinics of North America cited research that found onethird of gay, lesbian and bisexual youth experienced parental rejection due to their sexual orientation. For this and other reasons, many people in LGBTQ community form “chosen families”. Since chosen families often don’t live together, many have been unable to see each other during the pandemic. Like others they may have lost close ones to Covid-19 and they aren’t able to access the in person support of their communities to grieve. Even those who have not been outright rejected by their “inherited families” may feel a disconnect between their families personal beliefs and their own and are therefore less likely to reach out to them for emotional support. Students in college may struggle with anxiety and lack social support if they are unable to return home to their families and may struggle to make new connections during the pandemic like they might normally do in classes at school. Meaningful relationships act 904
as critical guardrails against loneliness and the more lonely young adults feel, the greater the toll on their mental wellbeing. We cannot underestimate the impact of peer support on mental health during this time. The Making Care Common study highlighted how emotions like loneliness are further intensified when questions about the reliability of relationships surface. The survey showed that those who reported higher feelings of loneliness, felt that they reached out and listened to people more often, and such efforts were not reciprocated from the other end – causing them to feel as if no one “genuinely cared” about them. Friendships have also been strained and fractured over differing opinions about what is considered “safe” during the pandemic. This could result in reduced social support networks even after the pandemic is over. With the long stretches of time spent away from friends and family, young adults tend to use social media as an outlet and form of connectivity with the world around them. Connections on social media can sometimes create solidarity and help build a support system. Yet as we are well aware, dialogues on social media can quickly turn toxic and trigger negative emotions Weissbourd and his team argue that tackling loneliness and associated mental health issues would require a “robust social infrastructure” and suggests that key social and cultural institutions including workplaces, schools and colleges, and religious and secular community organizations, can be far more intentional and systematic about connecting us to each other through events and initiatives. These institutions can also encourage and support the behaviors and skills needed in caring for those who are lonely. Outside of these systems, we can also look to our health systems to address these issues. Doctors can incorporate questions about loneliness in annual physical checkups, and later help connect those struggling to treatment, resources, and support groups. Often loneliness is stigmatized which undermines its severity. Public education campaigns can have a huge impact on removing and alleviating the stigma of loneliness. An Australian suicide prevention organization runs a national annual “R U OK? Day” with the goal of encouraging Australians to meaningfully connect with the people around them and start a conversation with anyone who may be struggling with life. Participants who were exposed to 905
the R U OK? Day campaign were up to six times more likely to reach out to someone who might be experiencing personal difficulties compared to those not exposed to the campaign. A similar program could be adopted in the U.S. for loneliness and other mental health issues. Weissbourd and his team suggest a similar approach encouraging everyone to reach out and check in on the young people around them—a simple hello can have a major impact on how young adults feel during these unpredictable times. This article originally appeared in Forbes and is available online here: Young People Hit Hardest By Loneliness And Depression During Covid-19
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New Tanzanian Variant Detected In Angola From An Entirely New Branch Of SARS-CoV-2 Forbes | April 15, 2021 | Article
The versatility of SARS-CoV-2 to evolve new variants that increase transmissibility, virulence, and immune evasion is a new troubling feature of the Covid-19 pandemic. The recent discovery of a novel variant emerging from Tanzania adds a new chapter to this disturbing story. Up until the discovery of the new variant, all other variants of interest or concern derive from a common ancestral virus, the B.1 strain that first made its appearance in early 2020. This is not so for the newly described variant. It evolved from an entirely different source, the A lineage, a finding that substantially expands our understanding of the repertoire of mutants we must be prepared to contend with in the months and years ahead. The difference between the A and B lineages are three mutations that have come to define the B lineage that has displaced almost all others around the world. The common understanding is that a single amino acid change in the spike protein, the D614G mutation, increases both the ability of the virus to bind to the ACE2 receptor and, at the same time, stabilizes the interaction between the S1 and S2 protein of the spike, conferring an increase in transmissibility. I and others have suggested that the D614G substitution may not be all to the story of success for the B.1 variant. The B.1 linage viruses carry two additional mutations: the P323L mutation in the RNAdependent RNA polymerase (NSP12), which is the key to virus replication and the production of viral mRNA and another mutation in the 5 prime untranslated region of the genome. Although hardly studied, both of these mutations may contribute, along with D614G, to the replication competence and transmissibility in the spike protein. The Tanzanian variant (which is how I will denote it as it lacks official designation) teaches us that variants of interest and concern may lack all three defining mutations of the B.1 strain. Nonetheless, the new variant is of interest and of possible concern as it carries a 907
number of mutations in the spike protein characteristic of other bonafide variants of concern from the B.1 lineage. Of the 13 mutations that distinguish the spike protein of the Tanzanian variant from the original Wuhan strain, eight are found in the B.1 family of variants. This is a remarkable illustration of convergent evolution. No one B.1 variant carries all these mutations, but each must confer some selective advantage to the A lineage variant. It is worth noting the five spike mutations unique to the Tanzanian virus, as they are likely to appear sooner or later in B.1 linage variants as well. The observation of greatest concern is that the Tanzanian virus posses the E484K mutation found in many of the B.1 variants of concern. This mutation confers resistance to neutralizing antibodies of convalescent and vaccine plasma and also reduces the activity of some neutralizing monoclonal antibodies. This observation suggests that like other variants, this Tanzanian virus may heed resistant, at least partially, to the current generation of Covid-19 vaccines. The E484K mutation also increases the affinity of the spike protein for the ACE2 receptor, raising the possibility of increased transmissibility. Another mutation of note in the spike protein is P681H. This change occurs near the cleavage site between the S1 and S2 spike subproteins. We and others speculate that this mutation increases transmissibility by increasing the efficiency of the spike precursor S protein, a requirement for infectivity. All of the variants of concern carry a number of mutants in the N-terminal domain of the spike protein. Again, in an example of convergent evolution, four of these mutations are present in B.1 lineage variants, but not all together in any other single variant. The N-terminal domain contains a super antigenic site, the target of many neutralizing antibodies. Many of the N-terminal domain mutants of the Tanzanian virus map to this site. As no specific function is attributed as yet to the N-terminal domain, this set of mutations is thought to increase the ability of the virus to escape immune detection. I suspect that is not all there is to the story. We can ask the question: Why are there such convergence-specific mutations in the superantigenic and other sites? Investigations of the functions of the N-terminal domain deserve further study.
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An additional 18 amino acid changes occur in proteins outside the spike protein. These include 14 in the orf1ab proteins that specify the replication complex. Extensive mutations in the replication complex are a common feature of B.1 linage variants. I and others speculate that these mutations confer enhanced replication competence, contributing to an increase in viral load virulence and transmission. Not all of the selective advantage of variants is readily attributed to mutations in the spike proteins alone. Of the remaining four amino acid changes outside of the spike protein, there are two in the structural proteins, one each in the envelope (E) protein and nucleocapsid (N) protein. Antibodies targeting both are present in convalescent plasma raising the possibility that these changes contribute to immune evasion. The remaining two mutants both change the coding sequence of the accessory orf8 protein. One of these is identical to a mutation in a B.1 linage variant of concern. I note that orf8 is amongst the most frequently mutated viral proteins common to all variants of concern. The orf8 protein is one of the most antigenic of the SARS-CoV-2 proteins, raising the reasonable hypothesis that these are escape mutants. Elsewhere, some have suggested that orf8 may slow viral replication and that mutations that truncate the orf8 protein otherwise reduce its function may increase the viral load in infected patients. So why is this new variant relevant? This is another variant we have to be especially vigilant towards. It may be as infectious and immune evasive as the widespread B.1.1.7 and B.1.351 variants, in addition to potential reinfection capabilities, as they carry similar mutations. It also represents why we need more comprehensive variant surveillance around the world. Were this not detected in the Angolan airport, it may have caused havoc in the country and elsewhere. We do not yet know exactly how dangerous the Tanzanian variant may be. That is partly due to the new total blackout of information during the pandemic from that country. Official data would have that no infections have occurred in Tanzania since May 2020, which is clearly not the case. The appearance of a new variant of interest and possibly of concern detected in travelers from that country highlights the need for transparency, both for the control of
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Covid-19 within the country and for the dangers viruses emanating from Tanzania may pose for the rest of the world. This article originally appeared in Forbes and is available online here: New Tanzanian Variant Detected In Angola From An Entirely New Branch Of SARS-CoV-2
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How Covid-19 Impacts The Digestive System Forbes | April 23, 2021 | Article
In late January 2020—when Covid-19, then known as 2019-nCoV, had yet to penetrate most national borders—a research paper was published in The Lancet medical journal detailing the symptoms of a cohort of 41 patients hospitalized in Wuhan, China. The study, though tiny in scale, went on to become the year’s most widely cited, and more importantly it established fever, cough, and fatigue as telltale signs of Covid-19. But it also mischaracterized one symptom as rare that we now know, in retrospect, to be common: diarrhea. According to the study, only three percent of patients—that is, just one of the 41—reported diarrhea, while 98 percent reported fever. Personal safety guidelines released by the CDC and other public health agencies early on in the pandemic reflected back this pecking order, as did their testing policies. If someone suspected they had Covid-19 but, for example, had only diarrhea and no fever, they were refused a test. Thankfully these protocols have since been revised; as of June 2020, diarrhea, nausea, and vomiting— collectively referred to as gastrointestinal symptoms—were upgraded to the CDC’s official list of primary symptoms. In the popular imagination, however, Covid-19 is still thought of as a respiratory disease first and foremost, if not exclusively, while the pathology of the gut remains overlooked. Understanding the full extent of how Covid-19 manifests in the human body is critical to understanding how to treat it, particularly in so-called long haulers who harbor the virus for months. Infection of the gut also has serious implications for transmission—a factor that demands consideration if we’re intent on controlling and eventually eliminating this disease once and for all. By no strange coincidence does SARS-CoV-2, the virus that causes Covid-19, have an affinity for our ACE2 receptors. Tissues rich with ACE2 are dispersed across several of our bodily organs, from the epithelial cells lining our bronchial tubes and alveoli to the 911
endothelial cells in our arteries and veins. Surprisingly, it isn’t in the lungs and nasopharynx where ACE2 is found in greatest abundance, but in the gut—our liver, kidneys, gallbladder, pancreas, and gastrointestinal (GI) tract. Your skin isn’t the only part of the body exposed to the outside world. SARS-CoV-2 isn’t just breathable, but swallowable. Think of the GI tract as an elongated donut with two exterior points of entry, the mouth and anus. Stretching between them are the esophagus, stomach, and intestines. If the virus manages to get inside your mouth, it can then infect your saliva—which, like mucus and breath, SARS-CoV-2 will commandeer as a new mode of transportation, allowing it to travel deep inside the gut. With its expansive surface area and plethora of ACE2 receptors, the gut makes an ideal breeding ground not just for the virus, but other microbially inclined diseases, like inflammatory bowel disease and pneumonia. Gut infection gives the virus more room to go forth, multiply, and shed itself through our feces. And since the early Wuhan study, many papers on gastrointestinal Covid-19 symptoms have been published that suggest as much. Two surveys released in April 2020—the first conducted in California, the second in Massachusetts—found that 32 percent and 61 percent of subjects, respectively, reported digestive symptoms. An even more reliable indicator of gut infection than presence of digestive symptoms— prevalence of viral RNA in stool—has also been observed in multiple studies. A meta-analysis of data collected around the world reported that nearly 50 percent of fecal samples taken from patients contained traces of SARS-CoV-2. For patients with severe Covid19, the rate was nearly 70 percent. Adding to the pile of supportive evidence is a study that unleashed the virus upon intestinal organoids—experimental models of our digestive organs grown from stem cells—and found it able to colonize the epithelial tissues quite rapidly. It might also be the case that gut infection prolongs the length of time SARS-CoV-2 remains in the body. According to one study involving about 200 Covid-19 patients with either digestive symptoms, respiratory symptoms, or a combination of the two, those who experienced gastrointestinal complications took seven to nine days longer to reach viral clearance than those who didn’t. Another 912
study shows that in general, fecal samples taken from Covid-19 patients continue to test PCR-positive even after nasopharyngeal samples start testing negative, which is why China implemented an anal swab testing policy for incoming travelers. If the virus that lingers on in patient stool is live and infectious, that opens up fecaloral or fecal-aerosol routes of transmission. As I’ve already discussed in a previous Forbes article, epidemiological evidence of this exists not just for SARS-CoV-2 but SARS-CoV as well, the most prominent case being an outbreak of more than 300 cases in a Hong Kong apartment complex that health officials traced back to one man’s infectious diarrhea and a defective drainage system. More research on Covid-19 gut infection is needed to understand the full extent of its impact on the body and the pandemic at large. If we leave lesser known manifestations of this virus unaccounted for in the drugs we develop to treat it, patients will continue to slip through the cracks—just as they did in the early days of the pandemic when digestive symptoms weren’t given their due. Much as we’ve learned about SARS-CoV-2 since then, our knowledge is still nowhere near complete. The sooner we can fill these gaps in our collective understanding of the virus, the better. This article originally appeared in Forbes and is available online here: How Covid-19 Impacts The Digestive System
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The Recent Rise of Indian Covid-19 Cases Display The Dangers Of SARS-CoV-2 Variants Forbes | April 23, 2021 | Article
In mere weeks, the second wave of Covid-19 to hit India has gone from bad to worse. At the beginning of March, seven-day averages in India were around 15,000 cases per day. By late April, the rate reached almost 300,000. Today, infection numbers are spiraling out of control. The new B.1.617 variant, while not the only contributing factor, is likely the driving force behind the surge, displaying for all to see the dangers of the mutant SARS-CoV-2 variants circulating in India and around the world. After a modest increase in cases last summer, infection rates dropped and remained low, raising hopes that India might escape the disastrous fate of similarly populous countries like the United States and Brazil. It was widely believed that the higher temperatures of the spring months, which hover around 90 degrees Fahrenheit in major metropolitan areas, would slow the virus and keep people safely outdoors. But despite the heat, case numbers climbed to heights never before seen. This suggests not only that the summer won’t offer a reprieve, but also that the new variants are likely far more contagious than previous strains. In addition to the B.1.617, which I described in detail in a previous article, a number of strains with additional mutations are also circulating that are currently less prevalent, but still cause for concern. These mutations, which are heavily concentrated in the Nterminal and receptor-binding domains of the spike protein, likely make their respective variants more resistant to convalescent sera and vaccine-administered antibodies. Among these mutations is W152L, located in the N-terminal domain, which is thought to be a neutralizing antibody binding site due to its high antigenicity. Mutations to this area could reduce neutralization capability and make the virus more resistant to convalescent sera and vaccines. Another mutation, V382L, is also located in the receptor-binding domain. The variants we’ve seen so 914
far don’t usually have many mutations in this region, which is a target site of potential antibody therapies. This mutation may work against that prospect, making the virus less susceptible to neutralizing antibodies. Further mutations found in India include N450K, which is also found in the Belgian B.1.214 variant; S477N, which is also seen in the New York B.1.526 variant; and a series of others, all heavily concentrated in the receptor-binding domain. Mutations to this region affect both binding to human ACE2 receptors and potential resistance to neutralization. All these mutations, in addition to the rise of the B.1.617 variant, display the swift capability of variants growing out of control, possibly foreshadowing what’s to come in other countries. Take the United States for example. The B.1.1.7 variant is circulating widely throughout the United States, as is the South African B.1.351 variant. In addition, there is an infectious New York B.1.526 variant and a Californian B.1.427/9 variant. All the while in Oregon, a strain of B.1.1.7 has been detected that has a new addition of E484K, or EEK!, which confers greater immune resistance to the virus. How many variants can the United States reasonably deal with before our Covid-19 case counts are as out of control as those in India? One recent article claimed that first-generation Covid-19 vaccines protect against the New York variant. But a deeper analysis into the referenced study reveals that protection may last only as long as neutralizing titers do. The study found that B.1.526 virus is neutralized four to five times less for vaccinees in comparison to older strains. In other words, vaccines may cover the New York variant at first, but protection may fade much more quickly than against the wild-type virus. This may well be the case for many of the variants circulating in the United States. As we have seen with the B.1.617 variant in India and the mutated B.1.1.7 variant in Oregon, SARS-CoV-2 will only continue to mutate. For the general population, this means being vaccinated is not necessarily a reason to go out and live as normal again. Though any protection against the variants is better than none, it is no time to relax. We must remain vigilant in our Covid-19 mitigation efforts if we are to avoid the fate India currently faces.
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This article originally appeared in Forbes and is available online here: The Recent Rise of Indian Covid-19 Cases Display The Dangers Of SARS-CoV-2 Variants
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Opinion: “The Common Good Of Gun Control And Covid Control” Daily Clout | April 25, 2021 | Article
After more than a year of unspeakable tragedy, we continue to be traumatized by new reports of shootings and gun violence. As we grieve those lost in recent shootings, thousands more around the country will be receiving the heart-wrenching news that a loved one has passed away from Covid-19. Each life lost — whether by gun or by virus — is a life lost unnecessarily. Each could have been saved by simple interventions, nothing more than minor inconveniences but with a profound impact on saving lives. Gun control measures and mask-wearing are both topics that are unnecessarily politicized, weaponized by those they intended to protect. Experts agree that mass shooters often purchase their guns at thelast minute shortly before their attack. The gunman in the Atlanta-area spa shootings purchased a 9mm semi-automatic pistol mere hours before he used it to kill eight people on March 16. A mandatory waiting period or licensing requirement could have possibly prevented the needless death — extra steps that are a small price to pay for gun owners when weighed against the cost to human life. But while gun control measures are debated endlessly in Congress, there is an immediate action we can all take to save lives. Wear a mask around those outside your household. I know by this late stage in the pandemic, the message feels tired. Yet according to a study by USC, half of U.S. adults still don’t wear masks when in close contact with non-household members, so clearly the message isn’t getting through. One thing that we can all agree on, is that no one particularly enjoys wearing a mask. In the same way, some don’t enjoy a wearing bike helmet or a seatbelt. Yet we have all agreed as a society that these interventions are a minor inconvenience and worth the lifesaving benefits.
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Why is it that we can’t apply the same logical rationale to wearing face masks that dramatically reduce the transmission of a rapidly mutating, deathly virus? How has a piece of cloth turned into such a polarizing issue? The tired arguments of infringements on our freedom and liberty simply don’t hold up. How can you claim that we are free if we are all just one unmasked cough from away from contracting a deadly virus? Like many Americans, I am desperate for my freedom. The freedom to reunite with close friends and family members without the fear of infecting them. But with an average of 75,000 new cases of Covid-19 a day in the US, aided by the rapidly spreading variants this will remain out of reach until more Americans commit to wearing masks. By implementing public health measures like gun control or mask mandates, public officials are not trying to take anything away from Americans. By contrast, they are giving us the gift of life. The countries that have been so successful in eliminating in Covid-19, like Australia and New Zealand have done so by presenting a united front. Politicians from both sides of the aisle buried the hatchet to present a singular public health message focused on preventing transmission of the disease at all costs. It is time for Americans to embody the same values of unity and mask up to prevent needless deaths This article originally appeared in Daily Clout and is available online here: Opinion: “The Common Good Of Gun Control And Covid Control”
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New Antibody Therapy And Prophylactic Shows Promise In Defending Against SARSCoV-2 Variants Of Concern Forbes | April 26, 2021 | Article
As SARS-CoV-2 variants grow in type and frequency, Covid-19 researchers are on the hunt for parts of the virus that remain consistent across variants in order to create Covid-19 treatments that work for multiple strains of the virus. This is the first in a series discussing these potential Achilles’ heels for Covid-19. In a search for an Achilles’ heel for the virus, the scientific world is monitoring potential targets for virus neutralization. One of these targets is a highly conserved region of the receptor-binding domain in the spike protein and two new monoclonal antibodies targeting this region are rapidly advancing in development and trial. The first of Vir Biotechnology and GSK’s two experimental antibodies, VIR 7831, aims to be used as a monotherapy for the early treatment of Covid-19 in adults at high risk of hospitalization. Early trial returns showed an 85% reduction in hospitalization or death, indicating the potential success of the antibody. The second, VIR 7832, is still in the preliminary stages of study as a dual-action prophylactic that potentially blocks viral entry to healthy cells and enhances clearance of infected cells. These antibodies are highly engineered and merit deeper analyses, as they could have wide-ranging therapeutic and prophylactic success against Covid-19, including SARS-CoV-2 variants, in the near future. Work began on these antibodies as early as April and May 2020 as researchers searched for neutralizing monoclonal antibodies for SARS-CoV that may carry over effectiveness to SARS-CoV-2. One SARS-CoV antibody extracted from B-cells in a SARS-CoV patient, S309, potently neutralized both SARS-CoV and SARSCoV-2, prompting a deeper study of the antibody and the epitope to which it binds.
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The S309 antibody recognizes a proteoglycan epitope on the receptor-binding domain of SARS-CoV-2. The antibody is composed of 6 complementarity-determining regions (CDR) loops which come in contact with amino acids 337-344, 356-361, and 440-444 in the spike protein. Two of these CDRs, CDRH3 and CDRL2 sandwich the glycan of the SARS-CoV-2 spike protein at position N343, making it a significant point of contact for the antibody. The reason S309 carries over its neutralizing effects from SARSCoV is the significant conservation of contact amino acids between viruses. Of the 22 residues involved in antibody binding, 17 are strictly conserved, four are conservatively conserved, ad one is semiconserved between viruses. This research concludes by noting the potential of S309 as a Covid-19 countermeasure and that variants of S309 that may have boosted half-lives and effector functions have already entered accelerated development. Early in 2021, GSK and Vir Biotechnology began work on the S309 antibody to optimize it for SARS-CoV-2 prevention and treatment, resulting in VIR-7831 and VIR-7832. Both antibodies were mutated to contain an “LS” mutation in the Fc region to prolong antibody half-life and potentially enhance distribution to the respiratory mucosa. This would block viral entry to greater effect and would provide protection against infection for longer. The VIR-7832 antibody additionally contains an Fc GAALIE mutation shown to boost T-cell immunity. GAALIE is an acronym for the amino acid mutations in the Fc region, specifically G236A, A330L, and I332E. These mutations would enable antibodydependent complement-mediated cytotoxicity without inducing antibody-dependent enhancement. In other words, it would neutralize the virus and clear out infected cells faster. Early trials indicate that these antibodies effectively neutralized wild-type SARS-CoV-2 at highly effective levels. Additionally, and perhaps more notably, both antibodies additionally neutralize the United Kingdom B.1.1.7, South Africa B.1.351, and Brazilian B.1.1.28.1 variants at high levels. The Brazilian and South African variants are neutralized as well as the wild-type and the United Kingdom variant neutralized about 25% less effectively for both VIR-7831 and VIR-7832, as displayed in the figure below.
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As a word of caution, there are now variants with mutations in the highly conserved target region that these antibodies attack. While B.1.1.7, B.1.351, and B.1.1.28.1 are all mostly conserved in the regions 337-344, 356-361, and 440-444, there are a number of sequenced viruses in the GISAID database which carry mutations at some of these locations. The most frequent of these are at position 440 where there are 1,689 mutants, position 357 where there are 699 mutants, and position 344 where there are 307 mutants. While these numbers are relatively low in comparison to the 1.2 million sequences in GISAID and the millions of infections worldwide, India has taught us that a strong and resistant virus can spread rapidly. Some of these mutations may have a large effect on antibody resistance, for instance, some mutations to P337 and E340 reduce the neutralizing capability of the antibodies up to 200-fold, showing that this potential Achilles’ heel may have an Achilles’ heel of its own. These antibodies are ultimately a promising step towards furthering Covid-19 therapeutics ad prophylactics. They show strong neutralization of the wild-type virus and some of the major variants of concern. However, there are mutants out there that may be resistant to VIR-7831 and VIR-7832. We suggest more research on these antibodies could clear up concerns about mutations in the conserved region. While this targeted region is not the ultimate Achilles’ heel, it may turn out to be a good starting point as we explore more possibilities in future additions to this series. This article originally appeared in Forbes and is available online here: New Antibody Therapy And Prophylactic Shows Promise In Defending Against SARS-CoV-2 Variants Of Concern
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Written From The Frontlines Of The Pandemic, Rachel Clarke’s Memoir ‘Breathtaking’ Is A Must Read Forbes | April 26, 2021 | Article
Breathtaking: Inside the NHS in a Time of Pandemic by Rachel Clarke ISBN-13: 978-1408713785 Little, Brown and Company Weeks before the first wave of Covid-19 overwhelmed Britain last spring, palliative care doctor Rachel Clarke came down with symptoms that, any other year, would be a dead ringer for the common cold. But one in particular gave her pause: an usual degree of breathlessness. Her husband, a pilot, had recently flown back and forth from Lombardy, where the first major European outbreak was in progress. She suspected he might have exposed her and wanted to get tested for Covid-19, but didn’t meet the criteria. “This isn’t for me,” she urged the call center worker who picked up when she called the hotline. “It’s to make sure I don’t walk back into my hospice as patient zero and infect all the patients I’m trying to look after. Can I be tested to make sure that doesn’t happen?” The answer was no. The loss of breath is a recurring theme in Clarke’s latest book, Breathtaking: Inside the NHS in a Time of Pandemic, an intimate and impassioned account of her experience on the frontlines of Covid-19 from January to April 2020. In that time, the virus spread from China to Italy to London to Oxfordshire, the location of the hospice where Clarke usually works and the NHS hospital where she eventually volunteers. But as designated wards overflow with intubated patients and the death toll climbs ever higher, another refrain emerges—the loss of trust between frontline medics and their national government. As a doctor who specializes in treating patients with chronic or late-stage illness—many nearing the end of their lives—Clarke 922
knows firsthand that “care is inescapably visceral.” Hers is a line of work that demands compassion, empathy, and constant emphasis on the whole of the human, not just the integrity of the body. The nuance and tenderness this calls for, however, are difficult to muster when patients are lying nearly shoulder-to-shoulder in makeshift ICUs and care providers are buried under several layers of personal protective equipment (PPE)—even more so when their protective getup is cobbled together from DIY shops and trash bags, as was the case when government-supplied kits were at their most meager. According to Clarke, what was hardest to bear wasn’t the insufficient equipment or even the long, exhausting hours. “What hurts staff most about the pit is not its physical demands,” she writes, referring to the heart of the Covid-19 wards, “but the psychological assault of seeing patients so entirely cut off from their loved ones.” These passages of the book—where a patient is on the brink of death but, for fear of exposure, can bid only a virtual or otherwise distanced goodbye to their family members—are among the hardest to get through, not least because Clarke renders them so vividly. Prime Minister Boris Johnson, meanwhile, gave press conference after press conference in which either mixed messages or false reassurances—such as his promise to “turn the tide” in 12 weeks— ring hollow, far and away from the brutal realities faced by the NHS system he praised so fervently. “Moral injury” is the term Clarke invokes to sum up the psychological effects of bearing witness to so much horror and iniquity. As Downing Street engaged in “numbers theatre” to improve the optics of their pandemic response—superficially inflating quantities of supplies rather than actually increasing them— Clarke and her colleagues fell back on each other to endure the unbearable. Though in April the government finally issued a directive placing due emphasis on PPE, Britain’s 30,000+ long-term care centers—among them, Clarke’s hospice—were given only two days’ worth of masks. By the narrowest of margins, Clarke was able to procure adequate gear and save the hospice from closure. But not all were so lucky; within a month, more than 20,000 British care home residents would lose their lives to Covid-19. What frontline healthcare workers needed from their government wasn’t unreasonable—not by a longshot. “My needs were more prosaic,” Clarke writes. “Really, I just wanted honesty 923
from those who rule us, sufficient Covid testing and fit-for-purpose PPE.” Instead they were exposed to disease at unnecessarily high rates, left little choice but to make incredible sacrifices—one doctor, for instance, took to sleeping on a mattress in his garage to protect his family—and on top of everything else, had virtually no space to breathe, let alone repair from the physical and emotional toll of their work. Nearly a thousand health workers died from Covid-19 in 2020. If Clarke’s very prosaic needs were met, those hundreds might still be with us. What kept Clarke going were the “tiny eruptions of kindness” and “improvised altruism” that cushioned the blows delivered by negligence and poor governance. Though such benevolence ultimately reminds and convinces her of humanity’s fundamental goodness, I couldn’t help but despair at the thought of what Clarke and her colleagues went through when the third wave of Covid-19 hit Britain in January, driven by a more infectious variant of SARSCoV-2 that increased the number of daily new cases many times over. Since the book’s publication in January, Clarke has written for The Guardian about the “daily abuse” and hostility she encounters online for daring to share her perspective from inside the NHS. If we can’t take adequate care of our caregivers, it damages their ability to take care of us—and who in their right mind wants that? It would be tragic enough if the British government’s dereliction of duty was an anomaly—an exception to the rule. Yet countries like India, several in South America, and certainly the United States are currently suffering from betrayals just as dire, if not more. Around the world the same story seems to repeat endlessly. How many people must die and healthcare workers must suffer for more substantial public health interventions to take place? How much more pain must the combined effects of governmental failure and moral injury inflict on the world before national leaders take responsibility for their mistakes and take action to ensure this never happens again? As a chronicle of the early days of the pandemic in Britain, the government’s ineptitude, and the incredible calamities unfolding at the frontlines, the significance of Breathtaking will persist long after Covid-19 is behind us. But it is as a powerful testimony of the challenges frontline health workers face that Breathtaking has the most impact, for this pandemic period and those to come. 924
This article originally appeared in Forbes and is available online here: Written From The Frontlines Of The Pandemic, Rachel Clarke’s Memoir ‘Breathtaking’ Is A Must Read
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Understanding The Neurological And Psychological Effects Of Covid-19 Forbes | April 29, 2021 | Article
More than a year into the Covid-19 pandemic, the subject of “long Covid,” the symptoms of the disease that go on for weeks or months, is gaining in prominence and importance. Of particular interest are the neurological and psychological complications that can linger on in Covid-19 survivors long after they’ve left the hospital and returned to their homes. Reports of long-term fatigue, “brain fog,” and post-traumatic stress disorder are increasing in number, but still lacking in clarity as far as underlying mechanisms are concerned. Some of these neuropsychiatric effects, like the loss of taste and smell, are transient, appearing as the disease progresses and subsiding once the virus clears. But others are more persistent—and potentially, even lifelong, like damage from stroke. Though neurological and psychological complications can be collapsed into one category, the more evidence that emerges, the more imperative it becomes, for the purposes of care and treatment, to distinguish between the two. Neurological symptoms pertain specifically to damage the virus causes, whether directly or indirectly, to the nervous system, while psychological symptoms encompass behavioral, emotional, and cognitive impairments. Neurological Covid-19 symptoms in particular have been difficult to round up and pin down due to their variability. Milder forms include fatigue, headaches, and the now infamous loss of taste and smell, while severe symptoms range from strokes and seizures to encephalopathy (brain disease), encephalitis (brain inflammation). And it may happen rarely, but some Covid-19 patients develop either an autoimmune condition known as Guillain–Barré syndrome (GBS) or acute transverse myelitis—inflammation of the spinal cord. About two percent of patients experience ischemic stroke, which occurs when clotting blocks the flow of blood to the brain.
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Psychological complications, on the other hand, are not just wide-ranging, but more ubiquitous. It is common for patients who end up in the ICU—those with severe Covid-19 certainly, but other emergencies as well—to at some point experience delirium due to the acute stress of invasive procedures like surgery and intubation. Many who leave the hospital after being treated for critical illness go on to develop post traumatic stress disorder (PTSD). Even Covid19 survivors who only had mild cases of the disease might struggle with “brain fog,” the term attributed to the muddledness in memory and mental clarity that can linger on months after the virus has cleared. We can’t say for sure how SARS-CoV-2 causes neuropsychiatric complications in those it infects. But the presence of certain neurological symptoms has also been linked to a greater risk of either longer hospital stays or in-hospital mortality. The risk of death for hospitalized patients who develop toxic metabolic encephalopathy, for example, is 24 percent higher, according to a recent study completed by researchers at NYU. In other words, these symptoms signal a need for more intensive care, even if they’re not accompanied by the more recognizable signs of distress, like breathing difficulties. What is certain is that strokes big and small could either damage the brain permanently, or create blood clots that resolve over time and induce brain fog. The vascular systems of critically ill Covid-19 patients also produce a wide variety of inflammatory cytokines—the namesake of the cytokine storm, an immune reaction capable of sending the body into hyperdrive and inducing damage so pervasive, it reaches the brain. Our brains are so vascularized that tiny blood vessels known as capillaries surround almost every single neuron. If these capillaries are made leaky and more permeable by extensive inflammation and clotting, that could leave the door open for extensive neurological damage. One of the biggest questions up for debate is whether or not SARS-CoV-2, the virus that causes Covid-19, can directly enter and infect the brain. Its ability to do so depends on the presence of ACE2 receptors in our neurons—the most fundamental unit of the nervous system—and our astrocytes, star-shaped cells that populate the brain and spinal cord and serve many protective and communicative functions. Some researchers have observed ACE2 expression in 927
laboratory-grown cell cultures and deemed this enough evidence to substantiate the hypothesis of direct infection. But at least one brain autopsy report, compiled by neuropathologists at Columbia University, ruled against the possibility when no virus was detected in the brains of 41 patients who lost their lives to Covid-19 during their respective hospitalizations. More studies that distinguish between neurological and psychological symptoms but examine them in conjunction are needed for us to understand how they coalesce and interact. One of the largest studies to examine both, a retrospective assessment published in The Lancet earlier this month, pooled the health outcomes of almost 240,000 Covid-19 patients—reported over a period of six months—and cross-analyzed them with survivors of other respiratory infections. Compared to the flu, the researchers found their subjects were 44 percent more likely to develop neurological or psychiatric complications. Most of these patients had mental health conditions like depression or anxiety, while those with severe illness experienced a greater share of dementia and stroke. As the NYU study, reflecting the opinions of Dr. Steven Galetta, makes clear, it can be difficult to distinguish between the long-term neuropsychiatric effects normally seen in patients who have spent extended periods of time intubated or in intensive care. In any case, the effects Covid-19 has on the brain are too apparent to be negligible, even if we don’t know exactly why or how they manifest. Physicians caring for Covid-19 patients must allow the evidence amassed so far to inform their clinical practices and recommendations for care. Significantly more research is also needed to understand how neuropsychiatric Covid-19 symptoms work and how to treat them. Last but not least, those of us lucky enough to have evaded Covid-19 infection must take note and take caution as more infectious variants of SARS-CoV-2 spread far and wide. This virus only continues to surprise us with its capabilities—no need to learn about them the hard way. This article originally appeared in Forbes and is available online here: Understanding The Neurological And Psychological Effects Of Covid-19
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An Antibody Cocktail To Lay Low A Mighty Foe Forbes | April 29, 2021 | Article
As SARS-CoV-2 variants grow in type and frequency, Covid-19 researchers are on the hunt for parts of the virus that remain consistent across variants in order to create Covid-19 treatments that work for multiple strains of the virus. This is the second in a series discussing these potential Achilles’ heels for Covid-19. Read more from this series in part one. Viruses like SARS-CoV-2, influenza, and respiratory syncytial virus, are escape artists. These viruses evade immune recognition by mutations that reduce immune recognition yet preserve the ability to infect and cause disease. SARS-CoV-2 changes many sites of the exterior spike protein to avoid neutralization, all while maintaining replication competency and in some cases, boosting competency and receptor binding avidity. However, there are some amino acids of the spike protein that are not often changed. These conserved areas may be an Achilles’ heel of the virus. Understanding these conserved regions is vital to both therapeutic and prophylactic antibody design, as well as design for future generation coronavirus vaccines. In a recent paper, Starr et al. describe SARS-CoV-2 antibodies that neutralize not only the B.1 virus but also all variants tested as well as SARS-CoV, several bat coronaviruses and even a bat coronavirus that binds to a different receptor. Most therapeutic antibodies in use today were isolated based on avidity for the SARS-CoV2 receptor, the cell surface protein ACE2, and for neutralization potency. In contrast, the Starr et al. antibodies were selected for both neutralization and their ability to neutralize a diverse set of coronaviruses, most of which bind to the ACE2 receptor. The breadth of neutralization rather than potency was a primary selection criterion. In a series of experiments, they determined the binding sites of each of twelve antibodies on the SARS-CoV-2 receptor-binding domain (Figure 4). They also developed a detailed map of possible escape variants of each amino of the entire domain (Figure 3). 929
Finally, they measured the ability of each antibody to neutralize a broad set of SARS-CoV-2 variants of concern as well as an ACE2 binding, including SARS-CoV and one non-ACE2 binding coronaviruses of diverse origin (Figure 2). The twelve antibodies studied naturally sort themselves into three classes, those that bind to the region of the receptor-binding domain that interacts directly with the ACE2 receptor, those that bind near the ACE2 binding (the receptor-binding motif), and a third category that binds to a distal region named the core region. Antibodies targeting the receptor-binding motif and ACE2 contact epitopes neutralize SARS-CoV-2 effectively but fail to effectively neutralize many of the variants and all of the non-SARSCoV-2 viruses. There is one exception, S2E12, which both neutralizes a broad range of viruses and which is unaffected by almost all amino acid substitutions in the receptor-binding domain. The S2E12 exception is attributed to the recognition of contacts between the subunits of the trimeric receptor that are constrained to maintain consistent protein interactions even though individual amino acids at the contact points may vary. The core receptor-binding domain antibodies bind to sites distant from ACE2 binding have lower potency than those which bind to the receptor-binding motif. However, these antibodies typically neutralize most variants and non-SARS-CoV-2 viruses (Figure 2). The binding and neutralization of these antibodies are impervious to most amino acid substitutions in the receptor-binding domain. As an analogy, think of the receptor-binding domain having a mushroom shape, with a cap and a stem. In this analogy, the ACE2 binding site occupies the top of the cap. Some of the conserved sites occur on the stem and to some extent the edges of the cap. Specifically, S309 and S2X35 bind high up on the stem and the underside of the cap. Others including S304 and S2H97, bind on the lower parts of the stem (Figure 1). The four most effective core receptor-binding domain antibodies were S2H97, S304, S309, and S2X35. These binding sites of the antibodies are pictured in Figure 1. The part of the ACE2 receptor to which the spike binds is colored pink. The intensity of the color blue of the receptor-binding domain denotes how well the
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region tolerates amino acid substitutions. Notice that the base of the receptor domain is highly conserved. The four antibodies shown in figure 1 neutralize SARS-CoV-2, most of the variants of concern tested, as wells many non-SARSCoV-2 coronaviruses. All, but S309, effectively neutralize the Kenyan bat coronavirus BtKY72. S2H97 and S304 effectively neutralize European bat coronavirus BM48-31. S2H97 takes it one step further than the rest and also neutralizes a number of Asian coronaviruses that use a different receptor altogether (Figure 2). To generate the data in figure 3, amino acids in the spike protein receptor-binding domain were changed to every other possible amino acid. The majority which remain functioning were then tested to examine whether or not the spike, with these mutations, could be neutralized. In every case, some laboratory-generated mutations are capable of eliminating antibody binding. The letters denote the amino acid substitutions at that site and the height represents the reduction in the binding capability of the antibody. For example, S2H97 has reduced binding when E516 and L518 mutations are introduced, whereas those mutations can be sustained by S309. Each antibody recognizes epitopes that, if mutated, render the virus resistant to neutralization. For S309, mutations to P337 and E340 confer 12-fold increase in resistance. For S2H97, mutations to S514, E516, and L518 can reduce neutralization three-fold. For S304, mutations to S383, T385, and K386 result in 15-fold or more reduction. Finally, for S2X35, mutations to G504 can induce neutralization 18-fold or more. resistance. While these mutations have not appeared in variants of concern and are relatively rare due to the region in natural isolates, they do still appear in GISAID database sequences, ranging between 9 and 759 viruses (Table 1). Figure 4 depicts the binding footprints of the antibodies on the receptor-binding domain of SARS-CoV-2 of all twelve of the antibodies analyzed in this study. The black areas are those regions in which it appears that amino acid changes result in substantial loss of receptor binding domain stability and/or function. The red areas are regions of the receptor-binding domain where amino acid changes are functionally tolerated, but substantially reduce the binding of the antibody to that region.
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This research provides a blueprint for future anti-SARS-CoV-2 antibody drug development. Some of these antibodies are impressive on their own, such as S309, the basis for VIR-7831 and VIR-7832 drug candidates currently in clinical development. Cocktails containing two or more of these antibodies may be even more effective in countering resistance and neutralization of variants than will any one alone. I suggest an ideal cocktail would contain two bispecific antibodies covering all four conserved core footprints. It might help to add the modifications in the Fc portion of these antibodies that increase the half-life of the antibodies, mucous membrane transport, and antibody-mediated cytotoxicity as was done to create the in the VIR-7831 and VIR-7832 drug candidates. Conservation of the “mushroom stem” binding sites amongst distantly relates coronaviruses does necessarily not mean they are immutable. There are two potential interpretations of such conservation. The first is that there is no selective pressure to change because the virus has been successful in diverting immune attention away from these conserved regions, specifically to the ACE2 binding site and to epitopes of the N-terminal domain of the S1 protein. The second is that the conserved areas are functionally relevant and cannot be changed. The first interpretation may have merit, as one report noted that the cold-causing coronavirus’s receptor-binding domain naturally varies in amino acid composition by as much as 17% and yet remains functional. An additional caution: The Starr et al. studies are restricted to the receptor-binding domain, a small but critically important region of the entire S protein. The development of antibodies to the receptor receptor-binding domain alone may not be the only winning strategy. Mutations in the spike protein within and outside of the receptor-binding domain as well as in the extra-spike proteins of the virus may have compensatory effects. Decreases in viral infectivity and transmission lost by changes in the conserved regions may be made up for by increases in the activity of the replicative complex, the stability of the virus particle, and increases in the activity of the accessory proteins. Indeed, all variants characterized to date have more mutations in proteins other than the spike than they do in the spike protein itself. Infectivity, pathogenesis, and neutralization are composite properties of all viral functions.
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These and other studies may have found at least one Achilles’ heel of SARS-CoV-2. I doubt that will be the end of the story for this wily escape artist. In time believe we will finally throttle this many-headed hydra with a combination of antiviral drugs, each targeted to a different essential viral protein, combined with a cocktail of antibodies such as those so elegantly described by Starr et al. This article originally appeared in Forbes and is available online here: An Antibody Cocktail To Lay Low A Mighty Foe
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How Fintech Can Help Break The Health Poverty Trap Forbes | April 29, 2021 | Article
There has never been a better argument for Universal Health Coverage (UHC) than the devastating global impact of the Covid19 pandemic. As widespread infectious disease outbreaks are increasing in frequency and the number of people with chronic conditions continues to rise, we must find new ways to ensure that everyone is able to access and pay for the health services they need. As Covid-19 has demonstrated, no one is safe from health threats until the entire population is protected. WHO estimates that more than 100 million people around the world are pushed into poverty every year because of healthcare costs. In most countries, the process of paying for health coverage is not just costly, but complicated, stressful, and time consuming. If exorbitant prescription drug prices and out of pocket expenses were not already enough, healthcare consumers must also navigate payment systems known for their obscurity and susceptibility to error. We only need to look at the recent example of Americans who are being incorrectly billed by their insurers for Covid-19 vaccines that are meant to be free. An error that could have grave consequences if it deters someone from seeking out a vaccine. These systems not only overwhelm current users, but also discourages new users from finding the coverage that is right for them. Fintech brings new and improved digital financial service models into the healthcare space. Fintech companies are leveraging powerful innovations such as blockchain, artificial intelligence, and machine learning to eliminate the inefficiencies and knowledge gaps that exist in our current systems. This is the topic of a new whitepaper, “Breaking the health-poverty trap: How fintech can improve access to healthcare in Asia” co-authored by ACCESS Health International initiative Fintech for Health and the MetLife Foundation. Fintech for Health represents a call to action to bring the financial and healthcare sectors together in service of meeting UHC 934
goals. The population that is unbanked or underbanked is disproportionately low-income and is the same population that both financial inclusion and UHC policies seek to support. The development goals of UHC and universal financial access are essentially the same, to ensure that people are financially sound while pursuing both a better quality of life and health. The financial services sector has a direct and important role to play in creating financial solutions for healthcare. The best solutions will be bundled, integrated, and comprehensive. Fintech can be used to deliver three types of solutions: information, healthcare services, and financing. Information may include health education, doctor appointment scheduling, and transparent pricing. Examples of healthcare services would be telehealth consultations and e-pharmacies. Financial products and services may include personalized insurance marketplaces, micro insurance plans, claims processing, digital savings and lending, and crowdfunding. Paying for healthcare out of pocket is one of the biggest drivers of exorbitant, unpredictable costs, almost any form of prepayment through a plan is preferable. Fintech has and continues to make remarkable contributions toward increasing access and usage of financial services among lowincome people. In just the past six years, 1.2 billion people worldwide have gained access to bank and mobile money accounts due to digital financial technology. Access to bank and mobile money accounts makes it easier for governments to distribute payments in a timely manner to pay for healthcare costs. Healthcare costs drive 65 mil people across Asia into extreme poverty every year. Bringing together Fintech and healthcare will make it easier to choose, save for, and pay for high-quality health services. This article originally appeared in Forbes and is available online here: How Fintech Can Help Break The Health Poverty Trap
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May 2021
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Covid-19 And Tuberculosis: A Deadly Combination — We Can Do Better! Forbes | May 3, 2021 | Article
Five years ago, both the World Health Organization (WHO) and United Nations committed to ending tuberculosis by 2035. Today their focus has shifted considerably toward a different infectious disease. The inability to eradicate tuberculosis amid a formidable array of medical and public health resources serves as a cautionary tale for other endemic diseases such as influenza and Covid-19. However, just as our unfinished quest to eradicate tuberculosis should inform our expectations around the current pandemic, the reverse is also true. Valuable lessons have emerged in the past year that we can use to improve efforts to contain not just tuberculosis, but other infectious diseases. Tuberculosis is still the leading cause of death from an infectious disease in adults around the world, with more than 10 million people being infected and around 1.4 million people dying each year. Although global health efforts have saved an estimated 63 million lives from tuberculosis since 2000, the annual rate of infection and mortality reduction appears to be insufficient. Not to mention Covid-19, its lockdowns, and the increasing amount of healthcare resources being directed away from tuberculosis and towards the pandemic has only made the situation worse. Tuberculosis diagnosis is often delayed due to passive case finding, which requires infected individuals to be aware of their symptoms and to have access to health facilities. It is also troublesome as biological sampling can be non-representative, and conventional diagnostic methods aren't always accurate. About half of tuberculosis cases are detected by smear microscopy, which requires culturing the organism for as many as 6 weeks. Treatment distribution is still an obstacle to ending tuberculosis. Two new tuberculosis therapies, Sirutro and Deltyba, deliver cure rates of up to 80%, which is significantly higher than older treatments. However, prices have become a flashpoint because the 937
drugs are often used in conjunction with other therapies, raising the overall care costs even higher. The prices were so high, that the Indian government had to rely on donations from the Stop TB Partnership's Global Drug Facility, a non-profit. Since patents on these drugs prohibit alternative manufacturers from providing lowercost generic versions, and since these patents do not expire until 2023, there is simply not enough of the drugs available in India today to meet the huge public health need. As a result, health-care providers are rationing or even refusing to prescribe the medications for fear of running out. Compared to 2019, in 2020 14 million fewer tuberculosis patients received treatment and 500,000 more deaths occurred, bringing mortality rates close to 2010 levels. In 2019, there were an estimated 3 million active tuberculosis cases that had not been diagnosed. Given the shift in global health priorities, it can be assumed that even more went undetected last year. The WHO’s 2020 guidelines include a renewed emphasis on systematic screening to close the diagnosis-to-care gap. In high-prevalence areas, expanded community screening could help reduce the burden of latent tuberculosis infection. It may be more beneficial to conduct aggressive case finding within higher-risk groups, such as household contacts, HIV-positive people, and incarcerated people. Tuberculosis is a disease of poverty and disadvantage, with wide disparities among and within populations. Marginalized communities, such as indigenous peoples, refugees, and the homeless, are frequently the ones that suffer the most. In most countries, incarcerated populations have a significantly higher risk of tuberculosis infection than the general population. This risk highlights the importance of maintaining health-care involvement while incarcerated and directing preventive assistance toward higher-risk populations, such as people living with HIV, as well as the need for better-designed facilities that can manage infection control. While Covid-19 is not a disease of poverty and disadvantage, it does disproportionally affect certain classes. Incarcerated people were also among the worst hit during the Covid-19 pandemic, with rates as high as one in three people being infected inside US prisons. Uneven vaccine distribution has also been a cause for concern on a local and on a global scale, which tuberculosis has shown us to be an 938
issue we could face long term. India is relying on donations to acquire a tuberculosis treatment which should be considered a global public good. Given the recent waiver India and South Africa obtained from the TRIPS Agreement regarding Covid-19 vaccines, countries should benefit from such an agreement for all lifesaving treatments. The aim of eradicating tuberculosis in the next decade is optimistic, and the current pandemic has slowed progress, but Covid-19 has shown that political will and investment can lead to remarkable public health efforts and scientific developments in the fight against infectious disease. Both viruses have taught us valuable lessons regarding public health and medical care. Learning to build the bridge between the lessons learned from tuberculosis and those learned from Covid-19 will give us a rare chance to reinvigorate the battle against both. This article originally appeared in Forbes and is available online here: Covid-19 And Tuberculosis: A Deadly Combination — We Can Do Better!
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The Logic And Practice Of Strict Border Control In Covid-Free Countries Forbes | May 3, 2021 | Article
Covid-19 is likely to become endemic, yet through both public health measures and medical solutions we can control the virus. This is the first in a series of articles exploring examples of successful Covid-19 Control. The recent travel bans imposed on travelers from India and Pakistan by governments across the Middle East and in parts of Europe and North America will likely do very little to stem the spread of the new Indian variant. The variant has already reached more than 17 countries, and it has doubtless been unknowingly seeded in dozens of others by infected travelers. It is unfortunate that this far into the pandemic we still have not learned our lesson: reactionary travel bans do not work to prevent the spread of Covid19. The good news, however, is that we know exactly the border control policies that do work. A new study out of New Zealand examines the mix of testing and quarantine protocols that are most effective at mitigating the spread of Covid-19 from infected travelers. New Zealand is a great example to learn from as they have kept Covid-19 cases close to zero since May 2020. Since January 1 2021, 397 international arrivals have tested positive for Covid-19 yet none have led to significant outbreaks due to New Zealand’s rigorous quarantine, testing, and tracing policies. The study demonstrates the steps every country should take to control the spread of Covid-19 across borders and within their own countries as well. While the study doesn’t specifically discuss vaccines, it’s important to note the risk of relying solely on vaccines and vaccine passports to control the pandemic and protect the borders. Vaccines are critically important, but the fully vaccinated border worker at Auckland Airport who tested positive for Covid-19 after cleaning planes from high-risk countries is proof that breakthrough cases can and will happen at the border. And given the recent reports of fake
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vaccination cards and the possibility of fraud, there’s no guarantee that a person traveling with a vaccine passport is actually vaccinated. Here are the policies that we know definitively can work: Comprehensive testing of border workers Much of the attention on limiting outbreaks at borders is focused on testing travelers to ensure they aren’t infected, but testing shouldn’t just be restricted to visitors alone. Those working in and around border entry points and those who work in quarantine facilities have a high risk of exposure given the environment they work in. According to the New Zealand study, border workers should be tested on a weekly basis, at minimum. Weekly testing increases the chance of detecting an outbreak in the seed case (namely, the border control worker) to greater than 80%, which can significantly limit the size of a potential outbreak. If the seed case is not detected and the first detected case is a secondary contact, perhaps a family member or friend, then the expected outbreak size is much larger. The study is well crafted and accounts for a number of different scenarios. The study authors modeled the potential size of an outbreak based on whether the seed case was detected or whether the first case detected was in a secondary contact, and based on how frequently each group was tested. They also modeled how these outbreaks are affected by levels of “community awareness” of Covid-19 symptoms. Low community awareness is when 50% of infected individuals seek out testing based on symptoms, high community awareness is when this number increases to 100%. Their findings show that If the community awareness is high, the expected outbreak size from one case is likely to be between 11 and 14, the expected size of the outbreak increases to between 19 and 26 if community awareness is low as seen in Figure 6a and 6b in the below chart. This is why it is so critical to detect Covid-19 in the seed cases through regular testing so that quarantining, testing and tracing can occur immediately and the size of the outbreak can be contained. In addition to the tests, the study authors also recommend symptom checks. Symptom checks that occur 8 days or more after infection increase the probability of a case being identified. Routine testing protocols and mandatory quarantine for international travelers
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Every person should be required to test negative twice for Covid-19 at maximum 36 hours before their travel begins. The first test should be a PCR test, which can show whether a person has an active infection. The second should be an IgM antibody test, which can show whether a person was recently infected and may still be contagious. Some travelers who were recently vaccinated may have a negative PCR test result but a positive antibody test due to the vaccine and not a recent infection. In these cases, an additional antibody test directed at proteins not targeted by the current vaccines would be required. Upon arriving at their destination all travelers should be tested again with a rapid antigen test or PCR test. We know already that these tests miss cases anywhere from 20% to 100% of the time, depending on when during the course of an infection they’re administered. The authors of the New Zealand study are also skeptical of the accuracy of arrival and destination testing only. In their modeling only approximately 50% of travelers test positive from arrival and departure testing, the low detection rate reflects the high probability that an infected traveler will present a false-negative test during the first 5 days after infection. This also means these individuals who have tested a false negative are likely to be highly infectious when they enter the community. For these reasons, a testing-only policy without quarantine risks too many infected individuals entering the community. Due to confusion over what constitutes a quarantine and a lack of individual compliance, a managed quarantine facility run through a hotel or purpose-built facility is the best option. Early in the pandemic, Australia instituted a home isolation policy for returned travelers, but after random checks revealed many had no intention of adhering to a home quarantine period they swiftly moved to managed facilities. Different countries currently require different quarantine lengths, but the data shows that anything less than 14 days has a substantial impact on the rate of infectious individuals released into the community. The New Zealand study has modeled different quarantine lengths and testing regimes during quarantine with different levels of transmission within facilities. They have also modeled two different scenarios, the percentage of infectious (figure 2a) and highly infectious (figure 2b) individuals released into the 942
community after different border control policies. The varying results are seen in the Figure 2 charts below. A 14 day stay in managed isolation with tests on day three and day 12 is proven to be the most effective model in stopping international arrivals from re-introducing COVID-19 into the community. By assuming moderate transmission within quarantine facilities. The risk of an infectious individual being released into the community under this policy is around 2%. The risk of a highly infectious individual (individuals are typically most infectious within 5 days of exposure) leaving quarantine is 1% (figure 2b). If there is high transmission within quarantine facilities due to individuals mixing in facilities, the risk of a highly infectious person entering the community increases to 7%. If the quarantine period is reduced to a five-day stay with a test on day three, approximately 25% of cases would still be infectious when they entered the community in a low or moderate transmission scenario. If there is high transmission within the quarantine facility, this probability increases to around 38% of infectious and 15% highly infectious individuals entering the community. This would lead to multiple border-related cases in the community every week, making an outbreak inevitable. Addressing oral-fecal transmission of Covid-19 in quarantine China has adopted the above policies but has also gone a step further to address the oral-fecal transmission of Covid-19 through quarantine facilities. Those in quarantine in China are required to sanitize their feces and urine with disinfectant tablets in the toilet before flushing. They are also subjected to anal swabs in addition to regular testing before being released from quarantine. This is because recovering patients have continued to test positive through samples from the lower digestive tract days after nasal and throat swabs came back negative. There is some virological evidence that SARS-CoV2 can, in fact, replicate in the gut and shed through feces. One study, conducted in Zhejiang, China, discovered viral RNA in the stool of 59 percent of Covid-19 patients tested, remaining at detectable levels for three weeks on average. Another study found that the virus persisted longer in fecal samples than respiratory samples. These interventions may seem extreme, but the rationale behind them isn’t. Evidence not just from the past year, but the original SARS 943
pandemic shows that SARS-CoV-2 infects the intestines and colon and from there spreads to others, traveling from the toilet to the sewer to the water we use and the air we breathe. These strategies have helped China keep Covid-19 cases at close to zero in a population of over 1 billion. The New Zealand study acknowledges that they did not model for the impact of superspreader style events within quarantine facilities. If confirmed cases are completely isolated then they have found that there is minimal transmission between individuals in quarantine facilities. When designing a quarantine facility it is essential to ensure that guests can stay isolated from one another, even when completing activities such as opening the door to room service or laundry deliveries. In a quarantine hotel in Melbourne, two separate groups of guests staying in adjacent rooms at Melbourne's Park Royal Hotel tested positive for identical strains of the B.1.1.7 variant. The working assumption was that the viral load of one group of guests was so high that the virus traveled into the hotel hallway when the family opened the door to retrieve food or clean laundry. Preventing potential interaction between quarantining travelers and employees at the quarantine facilities is also an important element to consider when designing a quarantine policy. Allegations of sexual activity between quarantined travelers and security guards in a quarantine hotel were reported to be one of the factors behind an outbreak in Melbourne, Australia. For these reasons it is also important to consider the role of aerosol transmission through ventilation systems between rooms in hotel quarantines. Experts in Australia who have encountered this issue, say that we should look to how airflow operates in a Covid ward and replicate that in hotel rooms. There is likely to be resistance towards implementing a quarantine system for travelers, due to the cost and inconvenience but like most public health measures to prevent the spread Covid19, the results are clearly the effort. This article originally appeared in Forbes and is available online here: The Logic And Practice Of Strict Border Control In Covid-Free Countries
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The Logic And Practice Of Strict Border Control In Covid-Free Countries Forbes | May 3, 2021 | Article
Covid-19 is likely to become endemic, yet through both public health measures and medical solutions we can control the virus. This is the first in a series of articles exploring examples of successful Covid-19 Control. The recent travel bans imposed on travelers from India and Pakistan by governments across the Middle East and in parts of Europe and North America will likely do very little to stem the spread of the new Indian variant. The variant has already reached more than 17 countries, and it has doubtless been unknowingly seeded in dozens of others by infected travelers. It is unfortunate that this far into the pandemic we still have not learned our lesson: reactionary travel bans do not work to prevent the spread of Covid19. The good news, however, is that we know exactly the border control policies that do work. A new study out of New Zealand examines the mix of testing and quarantine protocols that are most effective at mitigating the spread of Covid-19 from infected travelers. New Zealand is a great example to learn from as they have kept Covid-19 cases close to zero since May 2020. Since January 1 2021, 397 international arrivals have tested positive for Covid-19 yet none have led to significant outbreaks due to New Zealand’s rigorous quarantine, testing, and tracing policies. The study demonstrates the steps every country should take to control the spread of Covid-19 across borders and within their own countries as well. While the study doesn’t specifically discuss vaccines, it’s important to note the risk of relying solely on vaccines and vaccine passports to control the pandemic and protect the borders. Vaccines are critically important, but the fully vaccinated border worker at Auckland Airport who tested positive for Covid-19 after cleaning planes from high-risk countries is proof that breakthrough cases can and will happen at the border. And given the recent reports of fake
945
vaccination cards and the possibility of fraud, there’s no guarantee that a person traveling with a vaccine passport is actually vaccinated. Here are the policies that we know definitively can work: Comprehensive testing of border workers Much of the attention on limiting outbreaks at borders is focused on testing travelers to ensure they aren’t infected, but testing shouldn’t just be restricted to visitors alone. Those working in and around border entry points and those who work in quarantine facilities have a high risk of exposure given the environment they work in. According to the New Zealand study, border workers should be tested on a weekly basis, at minimum. Weekly testing increases the chance of detecting an outbreak in the seed case (namely, the border control worker) to greater than 80%, which can significantly limit the size of a potential outbreak. If the seed case is not detected and the first detected case is a secondary contact, perhaps a family member or friend, then the expected outbreak size is much larger. The study is well crafted and accounts for a number of different scenarios. The study authors modeled the potential size of an outbreak based on whether the seed case was detected or whether the first case detected was in a secondary contact, and based on how frequently each group was tested. They also modeled how these outbreaks are affected by levels of “community awareness” of Covid-19 symptoms. Low community awareness is when 50% of infected individuals seek out testing based on symptoms, high community awareness is when this number increases to 100%. Their findings show that If the community awareness is high, the expected outbreak size from one case is likely to be between 11 and 14, the expected size of the outbreak increases to between 19 and 26 if community awareness is low as seen in Figure 6a and 6b in the below chart. This is why it is so critical to detect Covid-19 in the seed cases through regular testing so that quarantining, testing and tracing can occur immediately and the size of the outbreak can be contained. In addition to the tests, the study authors also recommend symptom checks. Symptom checks that occur 8 days or more after infection increase the probability of a case being identified. Routine testing protocols and mandatory quarantine for international travelers
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Every person should be required to test negative twice for Covid-19 at maximum 36 hours before their travel begins. The first test should be a PCR test, which can show whether a person has an active infection. The second should be an IgM antibody test, which can show whether a person was recently infected and may still be contagious. Some travelers who were recently vaccinated may have a negative PCR test result but a positive antibody test due to the vaccine and not a recent infection. In these cases, an additional antibody test directed at proteins not targeted by the current vaccines would be required. Upon arriving at their destination all travelers should be tested again with a rapid antigen test or PCR test. We know already that these tests miss cases anywhere from 20% to 100% of the time, depending on when during the course of an infection they’re administered. The authors of the New Zealand study are also skeptical of the accuracy of arrival and destination testing only. In their modeling only approximately 50% of travelers test positive from arrival and departure testing, the low detection rate reflects the high probability that an infected traveler will present a false-negative test during the first 5 days after infection. This also means these individuals who have tested a false negative are likely to be highly infectious when they enter the community. For these reasons, a testing-only policy without quarantine risks too many infected individuals entering the community. Due to confusion over what constitutes a quarantine and a lack of individual compliance, a managed quarantine facility run through a hotel or purpose-built facility is the best option. Early in the pandemic, Australia instituted a home isolation policy for returned travelers, but after random checks revealed many had no intention of adhering to a home quarantine period they swiftly moved to managed facilities. Different countries currently require different quarantine lengths, but the data shows that anything less than 14 days has a substantial impact on the rate of infectious individuals released into the community. The New Zealand study has modeled different quarantine lengths and testing regimes during quarantine with different levels of transmission within facilities. They have also modeled two different scenarios, the percentage of infectious (figure 2a) and highly infectious (figure 2b) individuals released into the 947
community after different border control policies. The varying results are seen in the Figure 2 charts below. A 14 day stay in managed isolation with tests on day three and day 12 is proven to be the most effective model in stopping international arrivals from re-introducing COVID-19 into the community. By assuming moderate transmission within quarantine facilities. The risk of an infectious individual being released into the community under this policy is around 2%. The risk of a highly infectious individual (individuals are typically most infectious within 5 days of exposure) leaving quarantine is 1% (figure 2b). If there is high transmission within quarantine facilities due to individuals mixing in facilities, the risk of a highly infectious person entering the community increases to 7%. If the quarantine period is reduced to a five-day stay with a test on day three, approximately 25% of cases would still be infectious when they entered the community in a low or moderate transmission scenario. If there is high transmission within the quarantine facility, this probability increases to around 38% of infectious and 15% highly infectious individuals entering the community. This would lead to multiple border-related cases in the community every week, making an outbreak inevitable. Addressing oral-fecal transmission of Covid-19 in quarantine China has adopted the above policies but has also gone a step further to address the oral-fecal transmission of Covid-19 through quarantine facilities. Those in quarantine in China are required to sanitize their feces and urine with disinfectant tablets in the toilet before flushing. They are also subjected to anal swabs in addition to regular testing before being released from quarantine. This is because recovering patients have continued to test positive through samples from the lower digestive tract days after nasal and throat swabs came back negative. There is some virological evidence that SARS-CoV2 can, in fact, replicate in the gut and shed through feces. One study, conducted in Zhejiang, China, discovered viral RNA in the stool of 59 percent of Covid-19 patients tested, remaining at detectable levels for three weeks on average. Another study found that the virus persisted longer in fecal samples than respiratory samples. These interventions may seem extreme, but the rationale behind them isn’t. Evidence not just from the past year, but the original SARS 948
pandemic shows that SARS-CoV-2 infects the intestines and colon and from there spreads to others, traveling from the toilet to the sewer to the water we use and the air we breathe. These strategies have helped China keep Covid-19 cases at close to zero in a population of over 1 billion. The New Zealand study acknowledges that they did not model for the impact of superspreader style events within quarantine facilities. If confirmed cases are completely isolated then they have found that there is minimal transmission between individuals in quarantine facilities. When designing a quarantine facility it is essential to ensure that guests can stay isolated from one another, even when completing activities such as opening the door to room service or laundry deliveries. In a quarantine hotel in Melbourne, two separate groups of guests staying in adjacent rooms at Melbourne's Park Royal Hotel tested positive for identical strains of the B.1.1.7 variant. The working assumption was that the viral load of one group of guests was so high that the virus traveled into the hotel hallway when the family opened the door to retrieve food or clean laundry. Preventing potential interaction between quarantining travelers and employees at the quarantine facilities is also an important element to consider when designing a quarantine policy. Allegations of sexual activity between quarantined travelers and security guards in a quarantine hotel were reported to be one of the factors behind an outbreak in Melbourne, Australia. For these reasons it is also important to consider the role of aerosol transmission through ventilation systems between rooms in hotel quarantines. Experts in Australia who have encountered this issue, say that we should look to how airflow operates in a Covid ward and replicate that in hotel rooms. There is likely to be resistance towards implementing a quarantine system for travelers, due to the cost and inconvenience but like most public health measures to prevent the spread Covid19, the results are clearly the effort. This article originally appeared in Forbes and is available online here: The Logic And Practice Of Strict Border Control In Covid-Free Countries
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A New Approach To Treat And Prevent Covid19 Forbes | May 5, 2021 | Article
As SARS-CoV-2 variants grow in type and frequency, Covid-19 researchers are on the hunt for parts of the virus that remain consistent across variants in order to create Covid-19 treatments that work for multiple strains of the virus. This is the third in a series discussing these potential Achilles’ heels for Covid-19. Read more from this series in part one and part two. Antibodies have been at the forefront in the search for drugs to prevent and treat Covid-19. Combination antibodies effectively reduce infection length if given early enough and prevent infection for those exposed. However, there are some inherent difficulties with antibodies as drugs. They are relatively large molecules that are expensive to produce. Additionally, SARS-CoV-2 mutates to resist single and, in some cases, to double-antibody cocktails. Here we describe a new approach to the same end using antibodies derived from camelids, a biological family which includes mammals such as camels, llamas, and alpacas. Camelid-derived antibodies lack a light chain and are composed of two identical heavy chains. These unique heavy-chain antibodies are also known as nanobodies. Camelid nanobodies are less than a quarter of the size of human antibodies. They are more stable, more simply modified, and less expensive than traditional monoclonal antibody drugs. These unique qualities have prompted researchers to develop camelid-derived nanobody drugs for Covid-19. In a study by Koenig et al., a llama and an alpaca were immunized with a SARS-CoV-2 spike protein from an inactivated virus. They then identified four nanobodies that resulted from immunization that potently neutralized SARS-CoV-2: E, U, V, and W. Three of these—U, V, and W—bind to the Covid-19 spike protein as indicated in the figure below. In contrast, E is bound to an extended loop overlapping the receptor-binding domain. Each of the four nanobodies effectively neutralized SARS-CoV2 by roughly 50% in a plaque-reduction assay on their own. To 950
improve the activity, combinations of two individual nanobodies were joined by a flexible linker to create drug candidates that might be more effective by binding to two different sites simultaneously. The receptor-binding domain that binds to ACE2 resembles a spring-loaded “up-down” device. When the receptor-binding domain is in the “down” position, it is not primed to bind to ACE2. However, when in the “up” position, the receptor-binding domain is open to ACE2 binding. A series of experiments were done to link the nanobodies in sets of two or three to determine which combinations were the most potent neutralizers. The ones which were selected were V and E. lV+E neutralized at a dilution 62 times greater and had an affinity at least 22 times greater than singular nanobodies, indicating a highly neutralizing combination nanobody. The E nanobody seems to bind to the “up” position in the stead of ACE2, releasing the fusion activity of the trimeric protein prematurely and inactivating the structure. On the other hand, the V nanobody improves the ability of V+E to bind by stabilizing the receptor-binding domain in the two-up position, allowing the E nanobody a better opportunity to bind and prematurely activate the trimer. The researchers also aimed to find a multivalent nanobody that neutralizes rapidly spreading variants found to resist neutralizing antibodies from convalescent sera and vaccines. The V nanobody avoids the high-escape amino acids of 417, 484, and 501, suggesting it could potentially neutralize variants like B.1.1.7 and B.1.351, which contain mutations at those positions. However, the E nanobody contains binding at both 484 and 501, indicating it would be less tolerant of changes at these positions. Therefore, the V+E combination nanobody may not have the neutralizing prowess against variants as it does against the wild type. The other nanobodies—U and W—were overcome by spike mutations at positions 371 and 378. While mutations at these positions are less common than mutations at positions 417, 484, and 501, they still denote a shortcoming in these nanobodies. While they may be potently neutralizing, it seems they may not overcome rapidly spreading variants of concern. The V+E combination nanobody is a potent neutralizer and could be used as a new approach to prophylaxis, therapeutics, and improving upon existing antibodies. However, this is not a universal 951
solution, as mutations in the spike protein decrease the binding of individual camelid-derived nanobodies. This can be partially overcome by combining nanobodies, but not entirely because mutations may arise in both domains, which reduce potency. It may be possible to use the camelid approach to find conserved epitopes which do not affect antibody neutralization, such as those described by Starr et al. in part two of this series. Combination nanobodies could potentially target these conserved regions, in addition to the binding regions, to produce a highly potent and versatile neutralizing bispecific nanobody. With further research, combination nanobodies to prevent and treat highly infectious and immune-evasive SARS-CoV-2 variants may well be on their way. This article originally appeared in Forbes and is available online here: A New Approach To Treat And Prevent Covid-19
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New Antiviral Drug Cocktail Could Help India Control Brutal Covid-19 Surge Forbes | May 5, 2021 | Article
As a brutal second wave of Covid-19 infections rages on in India, more and more states are reporting critical shortages of ventilators and vaccines. The relative scarcity of these provisions means they’ll be difficult to wrangle in time to staunch further suffering and death. But there are drug therapies that could—in fact, they might be sitting on the shelves of physicians and pharmacists across the country. Experts have known for some time that no single therapy will effectively prevent and treat Covid-19. What we need, especially now that highly infectious variants of SARS-CoV-2 are on the loose, is a veritable cocktail of drugs that overwhelms the virus through multiple lines of attack, giving it little opportunity to resist, evolve, or escape. The results of a new study, published in Cell magazine last month, suggest that a cocktail of one polymerase inhibitor—in this case remdesivir—and two hepatitis C drugs might do the trick. The RNA-dependent RNA polymerase makes a good drug target because it is so essential to the replication strategy of SARSCoV-2. Viewed in terms of the entire viral genome, this enzyme consists of three nonstructural proteins: nsp7, nsp8, and nsp12. Another exemplary target—what the seven different hepatitis C virus (HCV) drugs used in this study inhibit—are two proteases, enzymes that break down proteins into pieces a virus can use to copy itself. The researchers behind the Cell study predicted that certain protease-inhibiting HCV drugs might inhibit also the main protease of SARS-CoV-2, known as nsp5. When they used a supercomputer to model and test their theory, all seven HCV drugs did indeed dock at nsp5. Interestingly enough, however, it was blockage of another protease, nsp3, that significantly boosted antiviral activity. Given that nsp3 precedes nsp5 in the virus’s replication strategy, it makes sense that blocking one has synergistic effects while the other is additive. 953
But when combined with remdesivir, each of the four HCV drugs that inhibited nsp3 increased the potency of the treatment in cell cultures tenfold. The tenfold increase in potency means the adverse effects of each drug can be mitigated using lower doses. If successful, these treatments should be effective not only at treating the disease, but very importantly preventing it in people who are likely to be exposed. This strategy is used routinely in malaria zones and even for HIV. No vaccine was ever invented for HIV, but high-risk individuals can still protect themselves from infection through a regimen known as pre-exposure prophylaxis (PrEP). India has the pharmaceutical research, development, and manufacturing capacity to produce large quantities of such a treatment and, more importantly, sell it to consumers at low cost, which is how generic drug prices in India are among the cheapest in the world. But for Covid-19, the choice of which treatment to scale up for mass consumption wasn’t easy or obvious—until now. Of course, discovering a breakthrough product in the laboratory is one thing. Rolling it out with great haste is another. Before rush orders of the HCV drug and polymerase inhibitor combo can be placed, the therapy must be tested in animal models and clinical studies. At this stage, more convenient substitutes for remdesivir— which at present can only be administered intravenously in hospitals—should be considered and tested alongside it. One polymerase inhibitor, developed by Ridgeback Biotherapeutics LP and Merck & Co, that comes in pill form and has promising preliminary data behind it is molnupiravir. Pfizer is also developing an oral drug that should inhibit nsp5 as well, which would make it another viable addition to the cocktail. Then comes the question of how to scale up production and distribution using existing infrastructure. Egypt did this with tremendous success with its 100 Million Healthy Lives program, which eliminated hepatitis C from the country in a matter of months by screening more than 60 million adults and providing free treatment to all who tested positive. The India-based multinational Cipla already manufactures HCV drugs en masse at low prices. In fact, they may have the capacity to produce the entire combination at scale. India has the added benefit of being able to supply its own active pharmaceutical ingredients (APIs). Hepatitis C treatments that 954
cost US customers thousands of dollars cost only $25 to $35 in India. There is no good reason why Covid-19 combination therapy shouldn’t cost less than $5. Were India to succeed at leveraging existing HCV drugs and pharmaceutical infrastructure alongside Covid-19-specific therapies, the strategy could have considerable import in countries facing similarly dire straits. It is impossible to know when the vaccine shortages plaguing not just India, but many countries around the world, will resolve. We also can’t expect new variants of SARSCoV-2, many of which have learned to evade immune detection, to cease appearing in the meantime. Government and public health officials should take advantage of the opportunity to pump out combination drug therapies while they still can. Otherwise, many more countries may soon find themselves in circumstances not unlike India’s—overwhelmed to the point of paralysis. These drugs may be their only way out. This article originally appeared in Forbes and is available online here: New Antiviral Drug Cocktail Could Help India Control Brutal Covid-19 Surge
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Vaccines Vs Variants: Three Studies Provide New Insight Forbes | May 6, 2021 | Article
Two new studies have shown the real-world effectiveness of the Pfizer-BioNTech vaccine rollout against two deadly Covid variants, B.1.1.7 and B.1.351. The news is decidedly positive, especially when considered alongside data from a third study, released today, on the effectiveness of a Moderna booster shot against B.1.351 and the P.1 variant. But despite the positive momentum, it remains far too soon to call the game in our favor nor trust too much in vaccines alone to end the virus’ spread. The first set of data comes out of Qatar, which launched its mass immunization campaign with the Pfizer-BioNTech vaccine in late December just as its second major wave of infection was beginning to rise. By mid-March, at least half of all cases in Qatar were caused by the B.1.351 variant and 44.5% were caused by B.1.1.7; around that point roughly 385,000 Qataris had received at least one vaccine dose and roughly 265,000 had received both doses. The study found that, despite the prevalence of the variants, the vaccine was still highly effective at preventing infection. Two weeks after the second dose, the Pfizer vaccine’s effectiveness against infection from the B.1.1.7 variant ranged from 87-89.5%. Against the B.1.351 variant it ranged from 72.1-75%. More promising still, the vaccine was 97.4% effective at preventing severe or fatal Covid19 from any SARS-CoV-2 virus, including both variants. This is excellent news, but it bears noting that for the B.1.351 South African variant, the vaccine was still 20% less effective at preventing infection than in the initial clinical trial. Also worth noting is the difference in effectiveness after one dose compared to two. There were 6689 breakthrough infections and 5 deaths reported among those who had received only one dose of the vaccine and only 1616 breakthrough infections and 2 deaths in those who received the full two.
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A second study — using national surveillance data from Israel during the first four months of its campaign which began just as the country reached the peak of its second big wave — echoed the positive findings from Qatar. The B.1.1.7 variant is by far the dominant strain across Israel, accounting for nearly 95% of all cases. In this study, seven days or more after the second dose, the Pfizer vaccine proved 95.3% effective at preventing infection and 97.5% effective at preventing severe or critical Covid-19. This study also went a step further, analyzing vaccine uptake and its impact on the scope of the nationwide epidemic. It notes that as the percentage of vaccinated people in each age cohort grew, the number of coronavirus infections in that age group fell and that even in the face of the country’s phased reopening, reductions in new infections continued. Taken together, the authors note that this suggests that high vaccine coverage might prove to be a sustainable path towards resuming normal activities. Again, excellent news but also not without caveat. The study contains only seven weeks of follow up data following the second dose of the vaccine — the longest follow up data we have to date but still not long enough to determine whether protection against the variants lasts as long as protection lasted against the non-variant strain dominant in the clinical trials. What both the Israeli and Qatari studies do show us definitively is that high titers correlate to broad protection, which will be important for measuring new vaccines and the effectiveness of booster shots. And that is where the third study comes in, a Phase 2 study from Moderna on the effectiveness of its booster shot against variant strains of the virus. While the full data has yet to be released, Moderna’s press release shows a single dose booster shot given to someone who has already received both doses of the vaccine raises the body’s neutralizing antibody titers against both the B.1.351 variant and the P.1 variant which was first identified in Brazil, the only two variants seemingly tested in the study. Beyond that important finding, Moderna also tested a strainmatched booster shot and compared its effectiveness against the original booster. The strain-matched shot was designed specifically to match the B.1.351 variant — that boost raised even higher neutralizing antibody titers against the B.1.351 variant than the original. This too is excellent and welcome news. 957
Despite the positive notes that run throughout all these findings, it’s important to note that none of these studies give us any indication of how well our vaccines and potential boosters will perform against other variants, both the ones we know of today and the ones — perhaps even deadlier or more transmissible — that may emerge tomorrow. In addition, and perhaps more importantly, if people don’t agree to vaccination the vaccines won’t do any of us any good, no matter how effective they may be. In many countries around the world, including here in the United States, widespread vaccine acceptance is not a given. Because of this, any discussion of reopening or resuming pre-pandemic activities must take other public health precautions like mask-wearing and social distancing into careful consideration. We haven’t won the game just yet, but as these studies show, the opposing team can definitely be beaten. This article originally appeared in Forbes and is available online here: Vaccines Vs Variants: Three Studies Provide New Insight
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mRNA Vaccine Booster Shots Likely Required Within Six Months To Protect Against Covid-19 Variants Forbes | May 11, 2021 | Article
The majority of new infections in the US, Europe, and most other countries are now driven by variants. Until recently, the B.1.1.7 variant was the most dominant strain in the UK and throughout Europe and is prevalent in the United States as well. In South Africa the dominant strain is the B.1.351 variant; in South America, the P.1 variant. Now in India, three closely related strains, B.1.617.1, B.1.617.2, and B.1.617.3, are now running rampant. The B.1.617.2 variant has appeared in the UK as well. These variants of SARSCoV-2 are highly transmissible, capable of reinfection, and cause more serious disease. They also introduce the distressing possibility that current generations of Covid-19 vaccines may not protect as well against these variants as they do original strains. A new preprint study conducted by Moderna describes both the hope and challenge of booster vaccines as an approach to the solution to the problem of variants. Their booster shots appear to be effective at neutralizing at least two of the new variants, B.1.351 and P.1. But importantly, their preprint study also revealed the first-generation Moderna vaccine doesn’t protect against the variants for as long as we initially hoped. The phase II study compared the efficacy of two different additions to the existing two-dose regimen: half a dose more of the vaccine developed based on the original strain, or a full dose of a new vaccine based on the B.1.351 variant first detected in South Africa. (A version that combines the two is also in the works, though the data has yet to be released.) Using lab-grown virus, the researchers found that both approaches raised neutralizing antibody levels to impressive new heights (see Figure 1C). No indication was given as to when these boosters might be available to the general
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public, but it is probably safe to assume these will be fast-tracked for approval. The commendable performance of the booster shots wasn’t the only finding to emerge from the study, however. The researchers also confirmed what we’ve long suspected based on laboratory studies. When tested for its ability to neutralize the P.1 and B.1.351 strains, the antibodies generated by the Moderna vaccine against the original strain dropped to low or undetectable levels six to eight months after the second dose (see Figure 2). For months we have speculated as to how long immune protection from the first-generation vaccines would last against the original strain and new variants. Thanks to this new study, the answer is becoming clearer for the Moderna vaccine, which together are considered substantially more potent than other vaccines. I’ve called the mRNA vaccines created by Moderna and Pfizer the Lamborghini of vaccines for a reason. If two doses of the Moderna vaccine amount to six months of protection against the variants, other vaccines are likely to guarantee less. No surprise is it that the protection afforded by vaccination is less against the variants. The only factor we didn’t adequately consider was timing. Studies published in the spring and summer of 2020 indicated that neutralizing antibodies induced by natural infection were quick to fade. We can now predict that this is the case for vaccine-mediated antibodies too. This doesn’t necessarily imply a direct loss of immune protection. When antibodies fade, the combined defenses of T cells, memory B cells, and other components of the immune response may suffice. But given that neutralizing antibodies have been our most reliable measure of immunization thus far, it would be irresponsible and shortsighted to disregard the correlation and hope for the best. Optimism is a salve in times of crisis, but it can’t prevent or cure mass infection. In most countries, new SARS-CoV-2 variants have superseded the original strain as the predominant form of the virus. The highly infectious B.1.617 variant is thought to be one of the main drivers of the Covid-19 surge in India, where the number of new cases recorded in a single day toppled 400,000 multiple times in past weeks. B.1.617 is now wreaking havoc on India’s smaller next-door neighbor, Nepal; in just two weeks cases have shot up almost 700 960
percent. The same variant has recently been detected in the Philippines, France, Singapore, and the UK. On Monday England’s chief medical officer warned the prevalence of B.1.617 had “gone up sharply”—a sign of foreboding in a country where the B.1.1.7 variant overwhelmed health systems earlier this year. Notably, the B.1.617 variant wasn’t included in the new Moderna study. Compared to the B.1.351 and P.1 variants that were, B.1.617 is both more evolved and more dangerous. Whether it requires a homologous booster of its own remains to be seen. For now, we can at least take comfort in the fact that variant-proof booster shots are attainable, effective, and on their way. To anyone who has already been fully immunized with the mRNA vaccines, either from Moderna or Pfizer, I recommend you note in your calendar when you received your second shot. Six months from then, it might be time for your booster. If you’ve had any other vaccine, the time window is likely shorter. At present we can’t say with certainty how much shorter. The safest bet, given our current understanding of vaccines and variants, is to plan for relatively frequent boosters for some time to come. This article originally appeared in Forbes and is available online here: mRNA Vaccine Booster Shots Likely Required Within Six Months To Protect Against Covid-19 Variants
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Newly Discovered Antibody Neutralizes Covid Variants By Locking Receptor-Binding Domain In A Closed Position Forbes | May 11, 2021 | Article
Monoclonal antibodies have proved effective in the prevention and treatment of Covid-19. Their effectiveness depends on the recognition of specific structures on the surface of the viral spike protein. Over the past six months, we have learned that many of these shape-specific determinants change in ways that abrogate the effectiveness of individual antibodies and even of antibody cocktails. This is the fourth in a series that describes a search for monoclonal antibodies that may successfully address the problem of antigenic variation. Read more from this series in parts one, two, and three. Cocktails of monoclonal antibodies are valuable therapies for the prevention and treatment of Covid-19. However, their utility has been compromised by variants of SARS-CoV-2 that evade one or more of the antibodies in the mix. A new paper by Scheid et al. describes a new monoclonal antibody—BG10-19—that has a valuable set of characteristics. It is highly potent and active against a broad range of variants. BG10-19 and other antibodies analyzed in the study bind to the receptorbinding domain of the spike protein. The receptor-binding domain can be either open or closed. It must be in the open configuration to bind the ACE2 receptor to initiate infection (Figure 1). The BG10-19 antibody acts by bonding tightly to the top of the trimeric receptor and locking all three receptor-binding domains in the closed configuration (Figure 2). The special properties of BG10-19 derive, in part, its ability to bind to two adjacent receptor-binding domains simultaneously. In figure 3, the majority of the interactions are pictured with the receptor-binding site “RBD-A,” while binding simultaneously to the adjacent receptor-binding domain of the trimer designated as “RBD-B.” BG10-19 binds to two N-linked glycans on RBD-A as well. 962
This versatile antibody was discovered through a selective process of elimination. B cells from 14 patients who had recovered from mild cases of Covid-19 were isolated. The researchers selected 6,113 B cells that either bound to the SARS-CoV-2 S-protein or to the receptor-binding domain. They narrowed the search to B cells originating from four of the 14 patients who had the highest concentration of neutralizing antibodies against SARS-CoV-2 lentivirus pseudotyped with the B.1 spike protein, derived from the wild-type Wuhan strain carrying the D614G spike mutation. The FAB fragments of 92 monoclonal antibodies isolated from the four patients were added to an IgG1 framework. They then screened the 92 antibodies for polyreactivity, nonspecific binding to unrelated antigens, testing for binding to single-stranded DNA, double-stranded DNA, insulin, bacterial lipopolysaccharide, and streptavidin-APC. They found that 11 of the 92 monoclonal antibodies showed reactivity against two or more of the listed antigens. These were eliminated from future consideration. The search narrowed further by selecting those that bound the SARS-CoV-2 spike protein and the receptor-binding domain. Forty-two of the antibodies bound to both, nine bound exclusively to the spike protein, and five bound exclusively to the receptorbinding domain. Next, they screened the antibodies for neutralization capability against both SARS-CoV-2 pseudotypes and live virus (the B.1 variant of SARS-CoV-2). Twenty-seven of the 92 showed neutralizing activity with IC50 values ranging from 3 ng/ml to 25 µg/ml. They narrowed their search to six potential antibody candidates based on neutralization potency. BG10-19 was selected for further study as it was one of the most potent neutralizing antibodies and capable of neutralizing two variants of concern, the B.1.1.7 variant first isolated in the UK and the B.1.351 variant that was discovered in South Africa (Figure 4). The set of antibodies was also tested for its ability to bind to spike proteins, each of which carried a single mutation on the spike found in many variants of concern. The heat map of figure 5 summarizes the decrease in binding affinity of each antibody to each variant spike protein, the deeper the red coloration the greater the decrease in binding. Two of the tested antibodies, BG10-19 and BG1-28, are largely unaffected by any single mutation and bind to both SARS-1 963
and the WIV1 spike proteins. Sequence conservation at the BG1019 epitope explains the cross-neutralization against SARS-1, as 23 of 29 residues are conserved between SARS-1 and SARS-CoV-2 RBDs. Notably, despite strong binding to the WIV1 spike protein, there is little neutralizing activity, despite a highly parallel amino acid sequence to SARS-1. Again, BG10-19 was selected for further study as it binds and neutralizes SARS-CoV-2 much with a much lower IC50 than does BG-1-28 (Figure 5). This result is somewhat surprising as at least five of the spike proteins tested alter amino acids well within the binding footprint of BG10-19, specifically the mutations R433S, V367F, N439K, N440K, and V445E. Two of the naturally occurring mutations, N439K and V445E, do reduce binding affinity modestly between 1 and 5 fold. It is notable that the binding site of BG10-19 does not overlap with the residues of the receptor-binding domain that interact directly with the ACE2 receptor. Additionally, the binding site of another broadly neutralizing monoclonal antibody selected for clinical development S309 overlaps that of BG10-19 (Figure 6). This is not to say there are no escape variants that reduce binding and neutralization to the BG10-19 antibody. In fact, they found two mutations that reduce BG10-19’s neutralizing capability: G339R and L441P. The G339R mutation reduces neutralization as much as ten-fold and the L441P mutation reduces neutralization about one hundred-fold. While these mutations have not yet been sequenced and deposited into the GISAID mutation database, there have been other mutations at both positions. There have been 238 sequenced mutations at position 339, including changes to aspartic acid, serine, valine, as well as some deletions. Additionally, there have been 101 sequenced mutations at position 441, including changes to isoleucine, phenylalanine, arginine, as well as some deletions. While these are not the mutations that inhibit neutralization, their existence indicates that mutations to these positions are tolerated. All of the antibodies discussed in this paper are very interesting in terms of their potential use. They could be used in various combinations. We suggest the BG10-19 antibody be combined with the S309 and S2H97 antibodies described by Starr et al. to create a cocktail that recognizes conserved epitopes and that is both potent and resistant to naturally arising variants. 964
This article originally appeared in Forbes and is available online here: Newly Discovered Antibody Neutralizes Covid Variants By Locking Receptor-Binding Domain In A Closed Position
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A Possible Cure For ‘Bubble Baby’ Disease And Hope For More Discoveries To Come Forbes | May 12, 2021 | Article
Thanks to a half century of scientific research and effort — an effort that I am proud to have been a part of — there is finally hope for a new cure to one of the most devastating genetic disorders affecting young children today. Severe combined immunodeficiency (SCID) is known most widely by its nickname, the ‘bubble baby’ disease. The genetic disorder robs a person of a working immune system and the functional B cells and T cells that normally protect us from disease. Most children born with the disorder — caused by genetic defects — die from opportunistic infection during their first year or two of life, unless they receive regular twice-weekly antibody infusions, which can be both costly and cumbersome to manage. SCID first became part of America’s collective consciousness in the 1970s thanks to a young boy named David who lived almost his entire life inside a series of sterile plastic bubbles. His life as a “bubble boy” was the subject of endless media fascination, and it earned the disease a place in pop culture through movies and TV. But for whatever entertainment the boy in the plastic bubble brought to the screen, David’s actual life only led to sorrow — he passed away at the age of 12 after a failed bone marrow transplant. Until recently, a stem cell or bone marrow transplant was the only hope of a permanent cure, though these types of procedures came with a great deal of risk. But now, thanks to the efforts of researchers at the University of California, Los Angeles and Great Osmond Hospital in London, there is renewed hope for a safer cure. In a study published in the New England Journal of Medicine, the researchers show how an experimental form of gene therapy could restore the immune system of those living with SCID. Fifty patients were given the treatment — 30 patients in the United States and 20 in the UK. After 36 months, 90% of the US patients and 100% of the UK patients had fully reconstituted immune systems and were able to discontinue 966
their antibody infusions. The children were essentially returned to normal life, able to play with friends, go to school, and fight off the common colds and normal infections that in the past could have killed them. Among the patients in the trial, there were no complications with the treatment and most adverse events reported were mild or moderate. The experimental gene therapy used in the study takes advantage of a viral vector that I worked on years ago in my lab at the Dana Farber Cancer Institute with my colleagues Joe Sodroski and Mark Poznansky. At the time, we were studying retroviruses — mainly HIV — which is a type of virus that replicates by inserting a copy of its RNA genome into the DNA of a host cell. Before HIV came along, the common belief was that retroviruses could only enter cells and insert RNA while the cells are dividing. This limited the virus’ ability to reproduce. But with HIV, we found it was able to enter cells that were quiescent, essentially dormant cells not yet dividing. This was a critical benefit to the virus — if it could enter dormant and non-dormant cells alike to drop its genetic payload, its ability to thrive was increased exponentially. At the time we realized the potential impact of this new discovery. If you could remove the fangs of the AIDS virus, rendering it free of its disease-causing genetic material, you could conceivably insert new genetic material into its viral genome and create a path to rapid replication and a cure for the disease. We were confident enough with the approach that we even patented the idea, with the hope of using these viral vectors to develop a treatment for HIV. In the SCID study, the UCLA and Great Osmond researchers used these same viral vectors, called lentivirus vectors, in their treatment. They removed blood-forming stem cells of each patient, then used a disabled AIDS virus to insert the healthy genetic material the patient was lacking. When the cells were returned to the patient through an intravenous infusion, the retrovirus did its trick with the new material — replicating quickly throughout the body, essentially curing the child of the disease. Whether the cure will last a lifetime is still to be seen, but at least at the three-year mark the results are very encouraging. While I am delighted by the results of this study alone, I am also very pleased by the thought of what more could come from this next 967
stage of discovery in gene therapy. Scientific discoveries are based on incremental progress. A delicate thread ties our early work on retroviruses to this SCID discovery and even to the mRNA-based Covid vaccines distributed today. The vaccines use an entirely different approach but the same concept is at play — use RNA to teach our bodies how to respond to a disease more effectively. Generations of well trained virologists working on a myriad of diseases have allowed us today to shed light on some of the darkest corners of human biology. With continued investments in this type of research over time, imagine what more we could do. This article originally appeared in Forbes and is available online here: A Possible Cure For ‘Bubble Baby’ Disease And Hope For More Discoveries To Come
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A New Twist To Antibody Cocktails To Prevent And Treat Covid-19 Forbes | May 13, 2021 | Article
Monoclonal antibodies have proved effective in the prevention and treatment of Covid-19. Their effectiveness depends on the recognition of specific structures on the surface of the viral spike protein. Over the past six months, we have learned that many of these shape-specific determinants change in ways that abrogate the effectiveness of individual antibodies and even of antibody cocktails. This is the fifth in a series that describes a search for monoclonal antibodies that may successfully address the problem of antigenic variation. Read more from this series in parts one, two, three, and four. Monoclonal antibodies have been successful in both prevention and early treatment of Covid-19. The monoclonal antibodies that have been studied to date bind to and interact with the spike protein, and more specifically, the receptor-binding domain. Over the past several months, as reviewed in this series, new monoclonal antibodies have been discovered that have broad neutralizing capabilities. All of these antibodies bind to the receptor-binding domain, either to the receptor-binding motif, which interacts directly with the ACE2 receptor, or to other parts of the receptorbinding domain to inhibit function. Despite the broad activity of these antibodies or camelid nanobodies, none are entirely neutralizing. SARS-CoV-2 is capable of mutating, leading to viral variants which inhibit antibody function that escape neutralization, triggering a search for effective neutralizing antibodies that recognize epitopes in regions outside the receptor-binding domain which might be constrained functionally, and therefore, less likely to mutate. In a new study by Garrett et al., a complete set of overlapping linear peptides on a phage display backbone was developed, which spanned the entire spike protein. For reference, the receptor-binding
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domain is only about 15% of the full spike protein, stretching from amino acid 332 to 523 (Figure 1).
FIGURE 1: SARS-CoV-2 Spike Protein. N-terminal domain (NTD); receptorbinding domain (RBD); ... [+] GARRETT ET AL.
To examine naturally occurring antibodies that recognize these epitopes, they identified those linear regions which are recognized by convalescent sera. The figure below shows the regions in which naturally occurring convalescent antibodies bind linear epitopes (Figure 2). It is important to note that these are very different from what is seen when the entire spike protein or receptor-binding domain is used as a target. When the spike protein or receptorbinding domain are targeted, the recognized structures are threedimensional and yield different binding actions. Whereas in this study, linear epitopes are recognized and the receptor-binding domain is nearly ignored. This is notable as the receptor-binding domain is the principal source for neutralizing monoclonal antibodies in most previous studies. Additionally, antibody responses vary from patient to patient, as no two immune responses are identical.
FIGURE 2: Major regions of antibody binding GARRETT ET AL.
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The antibodies were next exposed to the linear epitopes and examined their ability to neutralize a pseudotype virus. Their samples indicated that 0% to 59% of the neutralization activity present in patient plasma is directed at non-receptor-binding domain epitopes. After depleting the neutralizing antibodies targeting the receptor-binding domain, the researchers found that non-receptorbinding domain antibodies, while not completely responsible for virus neutralization in patients, are at least partially responsible for residual neutralization, and are therefore important to the neutralization process. The linear non-receptor-binding domain epitopes of interest map into four specific regions. These are the carboxy-terminal, the n-terminal domain, the fusion peptide, and the carboxy-terminus of the S2 subunit. To grasp whether these antibodies could tolerate amino acid mutations in these regions, the researchers developed a heat map of every mutation to individual positions. For example, in the figure below for the fusion peptide, the red indicates a reduction in binding affinity, and the blue indicates a boost. The intensity of the color shows the magnitude of reductions or promotions (Figure 3).
FIGURE 3: Heat map of positional mutations affecting antibody binding GARRETT ET AL.
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Using this technique, they were able to divide these regions into two classes: those in which amino acid mutations in the region affect binding and those that are relatively resistant to amino acid mutations. It is this second class that provides the most interest. These results may have identified linear regions outside the receptorbinding domain that are constant regardless of variation, most likely because they are required for a conserved function. In summary, these results suggest that it would be valuable to add to the current cocktails that recognize the receptor-binding domain. One or two additional antibodies that recognize highly conserved epitopes, perhaps in the vicinity of the fusion peptide, may be most useful, as this region was conserved across many variants and viruses. Additionally, we have commented that highly effective cocktails for treatment and prevention might be combined with combination chemoprophylaxis with alternate drugs for maximum effect, creating multiple targets on the spike protein for neutralization (Figure 4). It is unlikely that variants can quickly arise that are resistant to antibody and drug cocktails simultaneously. As new variants spread through populations, this combination strategy may be successful in the prevention of new variant-associated outbreaks.
FIGURE 4: SARS-CoV-2 antibody and drug targets WRAPP ET AL.
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This article originally appeared in Forbes and is available online here: A New Twist To Antibody Cocktails To Prevent And Treat Covid-19
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A Third SARS-CoV-2 Variant Of Interest (Potentially Concern) Emerges From SubSaharan Africa Forbes | May 18, 2021 | Article
Travel cases and distribution of B.1.620 infections across Africa and Europe DUDAS ET AL
It seems that not a week goes by without the report of a new SARS-CoV-2 variant of interest and possibly, a variant of concern. A variant of interest is the discovery of a cluster of new infections with a SARS-CoV-2 variant with mutants not previously identified. A variant of concern is a mutant virus that spreads rapidly in a population, in some cases displacing new cases of previous, less infectious variants. Here we describe a new variant of interest, B.1.620, that likely first appeared in Central Africa, but has also been detected in several European countries. The strain has mutations that suggest it may become a variant of concern. As Dudas et al. suggest in their analysis of the B.1.620 variant, despite the variant first being detected in Europe, flight records and patient data suggest that it likely emerged in the Central African 974
Republic and Cameroon. As passengers traveled between these African countries and European nations like Lithuania, Germany, and France, the variant created a foothold and spread in Europe. This reinforces the probable origin of the B.1.620 variant in Central Africa and the global nature of this pandemic. Covid-19 disease anywhere is of grave concern for everyone. As of yet, there are only 278 sequences of B.1.620 in the GISAID virus database, but there are likely many more cases throughout Europe and Africa. At the time of writing, Lithuania is within the top eight of rates of confirmed Covid-19 cases per day, according to the New York Times coronavirus tracker. The B.1.620 variant may be a force behind their high case rate due to its mutations. These mutations are displayed in the figures below in both the spike protein and the larger genome. There are 13 mutations in the S protein and 7 in other proteins in the genome. We have colorcoded these figures to show unique mutations to B.1.620 in black, mutations in common with B.1.1.7 in red, and mutations found in other variants of interest in blue (Figures 1 and 2).
FIGURE 1: B.1.620 spike mutations with those that are unique to the variant in black, those in ... [+] ACCESS HEALTH INTERNATIONAL
FIGURE 2: B.1.620 mutations external to the spike protein with those that are unique to the variant ... [+] ACCESS HEALTH INTERNATIONAL
The authors summarize these graphics in the following chart, showing the mutational differences and similarities between B.1.620 and other variants of interest and concern (Figure 3). 975
There are a few mutations of special interest in the B.1.620 strain. These are the mutations S477N, E484K, and P681H. The S477N and E484K mutations occur in the receptor-binding domain and have been previously shown to affect avidity, the virus’s ability to resist neutralization, and the virus’s ability to replicate to higher titers. The P681H mutation lies in the cleavage region of the spike protein, which contributes to the transmissibility of the virus. These three mutations, in different ways, may work in concert to create a more infectious and immune-evasive virus. Among the unique mutations to B.1.620, two are located in the N-terminal domain and others are located outside of the spike protein, which is commonplace in SARS-CoV-2 variants. More specifically, these mutations are found in NSP2, NSP3, and NSP13 of ORF1ab, ORF9b, and the nucleocapsid protein. The mutation labeled P314L in figure 3 is typically labeled P323L in NSP12 as we have done in figure 2, which is common to nearly all strains circulating today. What is the potential origin of this virus? Citing Occam’s razor, the simplest, and therefore the most likely explanation is that it is originally derived from the B.1 variant via an undetected intermediary variant. The B.1 variant contains both the D614G mutation in the spike protein and the P323L mutation in NSP12. We also note there is a nucleotide substitution in the 5’ untranslated region at the start of the genome in B.1 variants which is involved in the regulation of RNA transcription and the mutation provides 976
important protection from degradation by its own activity. Other mutations in this region deserve more attention. We believe B.1.1.7 and B.1.620 had a putative predecessor that contained the following mutations: Δ69-70, Δ144, D614G, P681H, and D1118H in the spike protein, Δ106-108 in NSP6, P323L in NSP12, and the nucleotide mutation in the 5’ UTR. B.1.1.7 contains mutations in the spike not found in B.1.620 and vice versa. Therefore, we suggest that both variants are derivative of that predecessor, as displayed below (Figure 4).
The origin of a new variant of interest from Cameroon points to the need for continued global surveillance in Africa, which, up until now, has been notably absent with the exception of South Africa. Given what is happening in other parts of the world, such as India and Brazil, this is a continent we should be paying close attention to for emerging variants. In recent weeks, another variant was identified out of Tanzania in an Angolan airport, which carries a similar wealth of dangerous mutations from an entirely separate lineage. As the virus continues to spread around the world, new variants will only continue to appear, which will be a challenge for detection, mitigation, therapeutic treatment and prevention, and vaccines. This article originally appeared in Forbes and is available online here: A Third SARS-CoV-2 Variant Of Interest (Potentially Concern) Emerges From Sub-Saharan Africa
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Making The Best Of A Tough Situation: How To Respond To The CDC's New Mask Guidance Forbes | May 18, 2021 | Article
The confusion caused by the Centers for Disease Control when it issued new masking guidance for those vaccinated has already been well debated. The CDC claims that vaccinated people can remove their masks indoors and out, since they pose little risk of spreading Covid-19 or becoming infected. A rather broad statement that glosses over a more nuanced reality — people vaccinated by some vaccines are well-protected against Covid-19 and some of its variants, but most likely for a finite period of time. No matter my opinion on the decision itself (which, for the record, I believe to be premature at best), the end result is that many of us — including many of my closest friends and family — have been left both confused and fearful of how to live in a world in which more and more people are maskless and all of us are unsure of who is vaccinated and who isn’t. This fear is by no means unfounded — our vaccines are not an impenetrable shield against infection and disease. Studies have shown that some vaccines protect very poorly against some variants. And even our topline vaccines, which do protect against most of the variants, are significantly weakened when faced with some of the virus’ trickier iterations, like the B.1.167 variant in India. It’s important to remember just how violent this virus can be. To bring this home in a very real sense, let me speak a bit about my friends in India and my colleagues working there with my foundation. Some of these great people we have already lost to this latest surge. Most have family members suffering and severely ill, some luckier than others in that they’ve at least found a spare bed in a healthcare system that is completely overwhelmed. These people aren’t just the ones that are old and infirm, but the young as well. They aren’t the people who have been careless, but the ones who have been cautious in the face of the pandemic. This virus is tricky
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and the Indian variant may be the most transmissible version that we’ve seen yet...but it can still get worse. When friends have asked how to navigate this new world where masks may no longer be the norm, I’ve given them an analogy that I hope may prove useful to you as well. I talk about the pandemic in terms of the weather. If it’s sunny outdoors, you can head out and enjoy the day without fear of rain. When it’s drizzling, you may pop open an umbrella. When it’s pouring, you slip on a raincoat and rainboots as well. But when there’s a hurricane warning, you head to the safest part of your home and hunker down until the danger has passed. That’s how we have to think about this pandemic and how we protect ourselves. Let’s say you live in Vermont, the state with the highest percentage of people vaccinated with at least one dose. There were only 29 new infections reported yesterday in the state, only one person with Covid in an ICU bed, and a positive test rate of just 1.1%. Consider it then a sunny, beautiful day in Vermont, with little likelihood of rain. If you’re vaccinated, following CDC’s new mask guidance and resuming pre-pandemic activities without a mask and without social distancing is likely a fine way to approach your day. Infections around you are low, vaccination rates are high — combine that with the protection afforded you by the vaccines and you are likely very safe when unmasked. On the other hand, if you live in Tennessee, you may already feel the drizzle. Tennessee has one of the lowest vaccination rates in the country, there were more than 1000 new infections reported yesterday, and recent reports confirm that the highly transmissible Indian variant has arrived in the region and may be circulating in the community. The positive test rate in Tennessee is also high, just above 5%. This high percentage indicates that either the virus is spreading widely or that not enough people in the community are being tested to understand the full scope of the potential outbreak. If you’re vaccinated and heading out in Tennessee today, I would not recommend that you leave your home without your mask — just like you wouldn’t head out into the rain without your umbrella. Infections are relatively high, a variant known to weaken even our best vaccines is potentially circulating, and the likelihood that people around you are vaccinated is low. The risk of infection makes the relative inconvenience of wearing a mask worthwhile. 979
But, just like the weather, this too can change. If the winds shift in the right direction — vaccination rates go up, the India variant does not take root, and the number of new infections declines — Tennessee may soon be as sunny as Vermont and vaccination without masks may be sufficient. But it is just as possible that instead of shifting the winds will intensify and even darker clouds will start rolling in. Do not underestimate the power of SARS-CoV-2 and its variants. Singapore has been one of the countries that has performed the best against Covid-19. The country started its reopening in June 2020 and has remained open ever since, all while maintaining the lowest death rate from Covid-19 in the world. And yet today, the B.1.167 variant has the country shutting down schools, indoor dining, and other large gathering places once more, as a preventative measure to stop its spread. The Singapore health minister has warned that B.1.167 appears much more virulent than previous strains and seems to attack younger children. What we’re hearing out of Singapore is potentially the first faint echo of a hurricane warning siren that will soon start wailing on our own shores. We’ve seen what the B.1.167 variant has done in India, where the healthcare system has been completely overwhelmed. That variant took India by surprise, but here in the United States we know it’s coming and the havoc it can wreak. We should not be so foolish as to relax our restrictions too soon. The largest nursing union in the US has already called out the CDC over their new guidance, citing concerns over how long and how well vaccine protection lasts and whether they can protect against known and emerging variants that are “more transmissible, deadlier, and may already be or may become vaccine resistant.” They do not want to face what we faced in spring of 2020, when we saw into the eye of the hurricane, and nor should we. Before heading out of your home today, check the weather — Are infections high in your community? Are there variants of concern circulating? Is the positive test rate hovering near 5% or higher? If the answer to any of those questions is yes, mask up, stay outdoors if you can, and avoid large gatherings, even if you’re vaccinated. The rule I follow, for myself and my family, is to wear masks whenever I’m with someone who I don’t know to be
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vaccinated — that means anyone outside my immediate bubble and close circle of friends. We once wore masks to protect those we love around us, but today, with the confusion of CDC’s new guidance, wearing masks may now be the best thing we can do to protect ourselves as well. We are now living daily Bertrand Russel’s famous paradox, summed up so well this week in a New Yorker cartoon: A woman steps out onto her front stoop and confronts two maskless men she must pass by to move on with her day. One turns to her and asks the million dollar question, “One of us always tells the truth; the other always lies. You can ask us each one question. How do you figure out if we’re anti-maskers or vaccinated?” This article originally appeared in Forbes and is available online here: Making The Best Of A Tough Situation: How To Respond To The CDC's New Mask Guidance
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Discovery Of A Novel Monoclonal Antibody That Neutralizes A Broad Range Of Coronaviruses Forbes | May 19, 2021 | Article
B6 binding to the MERS-CoV-2 spike SAUER ET AL
The Covid-19 pandemic is no isolated incident. Coronaviruses have been coming after us for years. In the past 60 years, there have been as many as five seasonal cold-causing coronaviruses. In the past 20 years, we have dealt with three lethal coronaviruses: SARS-CoV, MERS-CoV, and SARS-CoV-2, the last of which has conservatively killed 3.5 million people and counting. The SARS-CoV-2 virus belongs to the B sarbecovirus clade, along with SARS-CoV. There are also C clade viruses, including MERS-CoV, and A clade viruses, which include many cold-causing coronaviruses. As we search for treatments for SARS-CoV-2, the question is raised: can we find measures to treat all broad classes of coronavirus unilaterally? This search has already begun and one approach of note is monoclonal antibodies. These antibodies have been found to 982
effectively treat and prevent early infection when used as a therapy. Within monoclonal antibodies, researchers aim to find those which potently neutralize not only SARS-CoV-2 but also SARS-CoV and viruses from the A and C clades as well. In a study by Sauer et al., researchers aimed to find a broadly neutralizing monoclonal antibody not in human convalescent sera, but in that of mice. To do this, they inoculated the mice twice with a stabilized MERS-CoV spike trimer and once with a stabilized SARS-CoV-2 spike trimer. Their aim was to locate antibodies that broadly combated both viruses. The researchers gathered Fab fragments from the vaccinated mice and connected them to human Fc receptors. After introducing the antibodies to the different coronaviruses, they selected one antibody, B6, which strongly bound to A and C clade viruses, but not for B clade viruses (Figure 1). Additionally, B6 was only able to potently neutralize A and C clade viruses, namely MERS-CoV and cold-causing coronaviruses. SARS-CoV and SARS-CoV-2 were left unneutralized (Figure 2).
FIGURE 1: B6 binding at the amino acid level. SAUER ET AL
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FIGURE 2: B6 neutralization of MERS-CoV, SARS-CoV, and SARS-CoV-2. SAUER ET AL
It seems, however, that the B6 antibody is capable of binding in SARS-CoV and SARS-CoV-2 to what the researchers label a cryptic epitope. Why, then, does the binding and neutralization fall off? To examine this, the researchers used cryo-electron microscopy to see exactly where the antibody was binding. In A and C clade viruses, the cryo visual of the region to which the antibody bound was clear (Figure 3). In SARS-CoV and SARS-CoV-2, however, the binding was disordered. This is surprising as this is usually a highly ordered area. They investigated the hidden binding by taking higher resolution pictures of the unusual binding between B6 and SARS-CoV-2.
FIGURE 3: Cryo-electron microscopy of B6 binding to MERS-CoV. SAUER ET AL
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Testing individual peptide fragments across the general region of binding noted in other viruses, the researchers found their clearer picture. It seemed that in A and C clade viruses, the trimer is less tightly bound than in B clade viruses. The looser trimer stem helix bundle in MERS-CoV and cold-causing coronaviruses was unraveled during binding, allowing a clearer picture during cryoelectron microscopy (Figure 4). In SARS-CoV and SARS-CoV-2, the trimer bundle is much tighter and did not unravel during antibody binding. This is consistent with the distortion during cryoelectron microscopy and likely explains the lack of neutralization by the B6 antibody. Another study by Garrett et al., which located a number of linear binding epitopes in this region was unable to locate the cryptic epitope Sauer et al. describe, most likely because it is hidden by the stem helix bundle.
FIGURE 4: B6 unwrapping the stem helix bundle. SAUER ET AL
What good is an antibody that does not neutralize SARS-CoV2, as we are in the midst of a pandemic? We may have a way around this shortcoming. In a study by Koenig et al., a nanobody derived from camelid mammals was able to neutralize SARS-CoV-2 by binding tightly to the receptor-binding domain. The nanobody locked the receptor-binding domain in the open configuration and nullified its binding to ACE2 receptors. Why is this relevant? Perhaps when combined with this camelid nanobody, they will open the structure, exposing the cryptic epitope hidden by the tightly bound stem helix bundle in SARS-CoV and SARS-CoV-2. Then, B6 could be able to enter SARS viruses and neutralize them. This combination therapy would, however, be dependent on the conservation of the targetted region: positions 1147 to 1161 (Figure 5). In the GISAID database, there are some mutations in these areas, but many are likely dead viruses as they include long strings of 985
deletions or insertions. The most common mutations include H1159Y, which has been sequenced 329 times, S1147L, which has been sequenced 385 times, and D1153Y, which has been sequenced 689 times. While these are no insignificant numbers of sequencing, none of these mutations appear in major variants of interest or concern, which suggests that this region is significantly conserved, not only cryogenically, but also in over 1.5 million GISAID entries.
FIGURE 5: Conserved region among coronaviruses. SAUER ET AL
This reminds me very much of the first effective vaccine against the feline leukemia retrovirus that I made in the early 1980s. The peptide in use was a membrane-spanning peptide that covered the carboxy terminus of the exterior glycoprotein, which deleted the membrane-spanning region, and included a small portion of the cytoplasmic domain. This vaccine provided then and still provides broad protection against leukemia in cats. That shows that peptide vaccines to conserved regions of spike proteins can be very important vaccines. Therefore, as the authors imply, peptides spanning this region may play a role in neutralizing many different variants. We echo their calls for increased research on this and other antibodies in the name of pandemic preparedness, as well as to find combination therapies that may control the SARS-CoV-2 virus today. This article originally appeared in Forbes and is available online here: Discovery Of A Novel Monoclonal Antibody That Neutralizes A Broad Range Of Coronaviruses
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The Premonition By Michael Lewis Highlights A Longstanding Need For Structural Reform Of The US Public Health Service Forbes | May 20, 2021 | Article
In the face of horrific death tolls and unspeakable trauma, there has been a continued refrain of “never again” through the pandemic. We want the small comfort of knowing that the deaths have not been entirely in vain. Yet history demonstrates that without radical change to the culture in which our infectious disease authorities operate, we are destined to repeat similar if not the same mistakes. Many have placed the blame for America’s disastrous pandemic response on the atrocious leadership or lack thereof, of former President Donald Trump. While Trump has much to answer for, the blame does not lie solely with him, but also with the public health institutional failures. Public health decisions regarding infectious disease outbreaks need to be just that, data-backed decisions that prioritize the health and lives of our entire population above all else. They need to be free from political and economic pressures and guided by experts, not the reactions of the public. Public health officials should not live in fear of being fired for making evidence-based but publicly unpopular decisions when the cost is human lives. Containing an infectious disease outbreak takes swift and courageous decisions, yet the culture that has existed at the CDC for decades is one of complacency and caution which results in reckless endangerment to human lives. The focus is on procedure and precedent when one of the defining characteristics of an infectious disease outbreak is often novelty. They waste precious time trying to reach a consensus when it is often an impossible task. The very fact that the director of the CDC is appointed by and can be fired by the president rather than a council of scientific peers, creates a culture of biased decision making and yes-men.
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Those who dare to make risk-based recommendations about infectious disease outbreaks or implement policies that go against the grain of this culture, are not just rebuffed and ignored to the detriment of the population but told that the organization will actively work against them. This is the experience of real-life characters in Michael Lewis’s latest nonfiction book The Premonition. The book tells the story of a team of “dissenting doctors” who predict the impact of the Covid19 pandemic and know what needs to be done to redress the situation yet are roadblocked by institutional dysfunction at each turn. Lewis writes about the time Dr. Charity Dean, Public Health Officer for Santa Barbara County is investigating multiple cases of Meningitis B on the USCB college campus. Knowing how short the window is for administering prophylaxis and how a few cases could spread, she moves quickly to shut down the college fraternities, and sororities and give 1200 students a prophylactic drug. The CDC disagrees with her decision and threatens to put their disapproval in writing, citing a lack of evidence for her approach (there is only one case every 4 years) and the fact that if she pursues multiple strategies they won’t know which one works. Dr. Dean goes ahead with her plan regardless and the cases cease. Her strategy is listed amongst other best practices in a report by the CDC on how to handle outbreaks of Meningitis on college campuses, published two years later. Despite her track record of success in this and other cases, Dr. Dean continues to butt heads with CDC and remains an outsider. When she tries to raise the alarm in January 2020 predicting the exponential growth of Covid-19, she is told to stop referring to Covid-19 as a pandemic. I also have personal experience as an outsider whose warnings about another pandemic went unheeded by public health authorities. When AIDS emerged, people were content to think of it as a gay man’s disease, something that happened to “them” and not to “us.” While terror and anxiety gripped those in the gay community in the early 1980s, the rest of the country kept on with the status quo. Similar to how so many believed that Covid-19 would not have a global impact outside of China. I was an outlier in believing that heterosexual individuals could be at risk for HIV/AIDs and publicly attacked in published a book published 988
Journalist Michael Fumento, titled “The Myth of Heterosexual AIDS”. Early on, I tried to convince major pharmaceutical companies to develop a drug to treat HIV and prevent its spread. I met with the research heads for all the major companies – Bristol-Myers Squibb, Pfizer, Roche, Johnson & Johnson, and others – but I heard the same story everywhere: “Sorry, Bill, funds are already fully budgeted for this year.” Likewise, when I approached the chairs of the infectious disease and microbiology departments at the country’s leading universities, I was told that, “It’s scientifically interesting, but we just don’t have the money.” Worse, I was even told that “AIDS will never be an important enough disease.” I also advocated for home testing of HIV in the 1980s, given the stigma surrounding HIV/AIDs, it seemed natural that allowing people to test in the privacy of their homes could dramatically reduce new infections. The CDC’s own survey confirmed this hypothesis, revealing that 29% of Americans would get tested for HIV if a home HIV test was available versus just 9% who intended to test using existing alternatives. Yet in meetings with federal health officials, I was laughed at for suggesting such a concept. Federal officials continued to insist that home tests were unsafe and unreliable, but the data from clinical trials summarized in the 1987 submission for premarket approval of a home test unambiguously demonstrated safety and efficacy. Both the FDA and CDC continued to oppose home tests. Again, I can draw parallels between this experience and the fact mass rapid antigen testing has never been adopted in the U.S. as a containment policy for Covid-19. The price of all this early complacency and ignorance towards containing the HIV/AIDs Pandemic was tens of thousands of lives lost. Like the doctors described in Lewis’s book I experienced the unique agony of understanding the solutions needed to save lives, but meeting roadblocks at every turn. Countries like Sweden, Italy, France, and the UK who have strong healthcare systems were still subject to multiple waves of infection throughout the pandemic because of sluggish and meek decisions or complacency by their public health authorities. Countries like China, Singapore, and New Zealand implemented swift and bold infectious disease control measures and were rewarded with astonishingly low case numbers and quick return to normal life. 989
But distressingly, the CDC continues a campaign of complacency announcing a surprising national rollback of mask mandates for vaccinated individuals that is not linked to a case or infection rates but instead seems somewhat random. Many have speculated that this announcement was made to encourage vaccination. But with no way to prove vaccination, this just gives the unvaccinated a dangerous license to spread infection unmasked. Infectious disease control is a noble yet unrewarding job, successes in containing disease outbreaks go unnoticed but mistakes bear the weight of human lives. The pressure is intense and as discussed warnings often go unheeded. Public health officials often garner little respect and low salaries for their qualifications. Lewis’s book ends with Dr. Charity Dean frustratedly leaving public service and launching a consulting company for infectious disease control, believing she will have a greater impact in the private sector. But infectious disease control is not an issue that should be handled by the private sector and we cannot afford to lose the talent that could help defend ourselves against the next pandemic. We cannot afford to keep making the same mistakes. This article originally appeared in Forbes and is available online here: The Premonition By Michael Lewis Highlights A Longstanding Need For Structural Reform Of The US Public Health Service
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Singapore’s Outbreak Highlights A Challenging Road Ahead For Covid-19 Containment Forbes | May 24, 2021 | Article
Singapore has largely been spared from astronomical Covid-19 case counts and lengthy lockdowns due to an early response and an elaborate surveillance system. Before the virus even had a name in late January 2020, Singapore had implemented travel restrictions and an efficient test, trace, and isolate system with penalties in place for those who disobeyed. Yet, Singapore is now experiencing a new surge of cases, despite having vaccinated a quarter (25.3%) of the population. Similar outbreaks in Vietnam and Taiwan who have previously controlled the virus well should serve as a warning to countries that are rolling back restrictions and opening up. As of 24 May 2021, the Singapore Ministry of Health has confirmed 24 new cases of locally transmitted COVID-19 infections. Of these cases, 22 are linked to previous cases, amongst which 12 have already been placed on quarantine, and 10 were detected through surveillance. The remaining 2 cases are presently unlinked to previous cases. In total 36 new cases were reported as of May 24, 2021. Singapore has been able to effectively trace and link the majority of new cases to 24 active clusters, involving locations such as Changi Airport, Tock Seng Hospital, Changi Prison Complex, and a tutoring center called Learning Point. There are 78 vaccinated individuals who have been infected with Covid-19 and are mostly frontline workers, compared with about 300 unvaccinated cases, according to Health Minister Ong Ye Kung. Vaccinated cases were either asymptomatic or mildly symptomatic, yet it emphasizes how we must factor breakthrough cases into our public health strategies. Teo Yik Ying, Dean of the National University of Singapore’s Saw Swee Hock School of Public Health, told The Washington Post the outbreak was a “stark reminder” that people who have been vaccinated can still be infected, although they are unlikely to progress to a severe disease stage where they need to go to a hospital. 991
The Changi Airport cluster is now linked to 100 cases and the largest of 24 active clusters in Singapore. This cluster is named after a fully vaccinated 88-year-old Singaporean man who works as a cleaner at the airport who tested positive for Covid-19 on May 5. At least 22 cases in the cluster have tested preliminarily positive for the B.1.617 India variant. The third-largest cluster is the Learning Point Center, which is linked to 28 cases as of Thursday May 20, 2021. 15 cases are children and 13 are adults, driving concern about the level of transmissibility of the new variants between unvaccinated children. Classmates of infected children were originally given stay-at-home orders but later shifted to hotel quarantine. Health Minister Ong Ye Kung, citing a conversation he had with the ministry's director of medical services Kenneth Mak, said that the B.1.617 strain "appears to affect children more" While these case numbers may seem insignificant compared to global case counts, these cases are leaking from a tightly controlled Covid-19 response where cases are closely traced and contacts are tested and efficiently quarantined. Countries that do not have an effective testing contact tracing and quarantine system in place or who relaxes their systems would suffer from a far greater outbreak. Plunging case counts in the U.S. and the U.K. have some wrongfully assuming that the impact of the variants was overstated, but we must not get complacent. Vaccine rates in the U.S. are beginning to plateau and breakthrough cases are occurring. Quarantine rules for international travelers entering the U.S. are largely based on the honor system. As cities reopen and bars, restaurants and offices start to fill up with unmasked individuals we will find ourselves vulnerable to similar outbreaks This article originally appeared in Forbes and is available online here: Singapore’s Outbreak Highlights A Challenging Road Ahead For Covid-19 Containment
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How COVID Changed Science
Scientific American | May 25, 2021 | Article
Rarely in recent memory has the world faced such an immediate and widespread global threat as complex as COVID-19. In its face, a select few have risen to the occasion, none more cherished and admired perhaps than the health care workers staffing the front lines. But standing close behind them in the trenches are the scientists and researchers who are among the very few who truly understand the scope of our evolutionary battle with the virus. Since the start of the pandemic, our scientists have acted with unprecedented speed and coordinated action to deliver us an armamentarium of medical weaponry to confront this global threat. For someone who has spent a lifetime in science, someone who understands the pressures and constraints faced each day in every lab, it has been phenomenal to witness the transformation that has taken place within the scientific community. It is not just the speed and focus with which the scientific community responded, nor simply the use of new technologies to draw out new discoveries, but rather the singular willingness of scientists, all over the world, to share new ideas and data immediately and transparently, in some cases well before the idea or the research is fully formed. Within weeks of the first case of COVID being reported, Chinese researchers had identified the virus they suspected of causing the disease and had decoded an initial genome sequence. It was a remarkable achievement in such a short amount of time, made more remarkable by the fact that the researchers published the sequence in an open discussion forum online, and encouraged a fellow researcher in Sydney, Australia, to share it via Twitter with the world. During the first 24 hours after publication, an evolutionary biologist in Scotland had figured out the similarities between this virus and SARS-CoV-1 and, like the Chinese researchers, shared the findings immediately online. A researcher in the U.S. openly published the new virus’ phylogenetic tree. And another started reverse-engineering a live virus from the sequence, letting colleagues 993
around the world know that the first steps towards developing an antibody test were already underway. At each moment, the goal was not acclaim or attention, but rather the possibility that openly sharing an early finding may influence the work of others and inch the world ever closer to a treatment or a cure. Of all the arenas in life that COVID has upended, science is perhaps the field that has been transformed the most. The pandemic has created an entirely new research environment, one that is now structured for collaboration and communication above all else. This revolution was inspired by the initial transparency of those early researchers but has since been institutionalized by some of the most well-respected research institutes in the world today, including our very own biomedical nerve center in Boston. Shortly after the virus emerged, Harvard Medical School pulled 20 Boston-area universities, medical schools and research institutes together to launch the Massachusetts Consortium on Pathogen Readiness (MassCPR). The initial goal was to formally join forces with researchers in China to answer the call to action to take down the emerging threat, with the hope that any lessons learned from this outbreak would enable a more rapid response to future emergencies. This alone was a notable step. The scientific community in Boston typically works in relatively isolated fashion, with barriers built up between departments, disciplines and entire institutions. But with COVID-19 and MassCPR those floodgates between institutes upriver and down were quickly opened. With a collaborative research grant from the Evergrande Group, MassCPR began funding dozens of new research projects, some of which have led to field-defining studies on the epidemiology, pathogenesis and immunopathology of COVID-19. Over the past year, MassCPR clinicians have written clinical management guidelines that have influenced patient care across the globe, and the consortium’s investigators have conceptualized, designed and developed the single-dose Johnson & Johnson vaccine and spearheaded clinical trials for the Moderna one. The dean of Harvard Medical School, George Daley, leads the effort, along with Arlene Sharpe, Bruce Walker and David Golan. As Daley describes it, “Our collective efforts over the last year have given us demonstrable proof that we are strongest when we work together across institutional boundaries, when we reach out across 994
geographic and national borders. We are strongest when we transcend scientific silos and build bridges across disciplines. Cooperation to confront a common threat is what MassCPR represents, and the achievements speak for themselves.” MassCPR’s immediate efforts are focused on the basic biology of SARS-CoV-2 and the pathogenesis of COVID-19—developing new diagnostic tools, vaccines and therapies. But while the researchers stay firmly focused on the now, they are also looking towards tomorrow. “We must refine our capacity to track the rise of new viral variants,” warns Daley. “We must refine our prevention strategies—an armamentarium of treatments—by developing new antiviral drugs, panviral therapies, and polivariant vaccines. And we must anticipate the post pandemic realities of COVID-19. A major goal of MassCPR 2.0 will be to define the scope of post-COVID19 syndrome and understand the long-term effects of multiple organ systems. The knowledge will have relevance beyond this pandemic and, indeed, beyond this pathogen.” Beyond MassCPR, other critical global partnerships have emerged over the course of the past year to bring recent scientific advancements on the virus to the masses, not the least of which is the Access to COVID-19 Tools (ACT) Accelerator and its vaccines pillar, COVAX. The ACT Accelerator is a global philanthropic partnership—not a new agency or institution but rather a framework for collaboration launched by the WHO, the European Commission, France and the Bill & Melinda Gates Foundation in April 2020. ACT is focused on accelerating the development and production of COVID-19 tests, treatments and vaccines (via COVAX) and, perhaps most critically, on ensuring that all people, and all countries, can access and afford these miracles of science. While richer countries have been able to roll out vaccines at no cost to residents, lower-income countries are still struggling to determine how to procure and pay for the vaccines in the first place, much less distribute them fairly across their countries. Rough estimates suggest that it would cost around $30 billion to mass-vaccinate the world— a price rich countries may not choose to shoulder. Take for example the United States, whose portion of the cost to help vaccinate the world is $7 billion. That figure is less than 0.5 percent of what was
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approved as part of the March 2021 economic stimulus package, mere pennies in relative terms but critical to ending the pandemic. Global fundraising for health is by no means without precedent, but what makes the ACT Accelerator unique is the burden-sharing formula it proposes to generate the funds. Every country is given a recommended range to contribute, which is adjusted based on GDP and the size of the country itself. The goal is to create a fair and equitable framework to respond to this crisis and future emergencies, including other pandemics—a systematic plan to prevent any country from having to choose again between who lives and who dies. This collective solution to the problem at hand also has scientists in the lead, with researchers monitoring the vaccine landscape and advising COVAX on the most suitable candidates based on scientific merit and scalability and with major pharmaceutical companies committing to providing hundreds of millions of doses—eventually billions—to distribute around the world. Scientists have not only worked together to develop COVID treatments and vaccines, but they are among the loudest voices calling for rich countries to collaborate and to deploy their wealth across all countries to end the disease. Yet even with these remarkable scientific efforts, there is perhaps no better indicator of the extent to which the scientific community is focused on collaboration than by how entirely the scientific publication process has been upended. Publication in a wellrespected journal is a competitive and highly prized honor, considered so by even the most accomplished scientists. Whereas in the past, researchers were willing to wait months and sometimes more than a year for the distinction, those imperatives have since been set aside. Researchers now proactively share preprint versions of their studies immediately after they determine their results, not only for recognition but in the hopes that their discoveries will help other scientists further their own. Between the start of the pandemic in December 2019 and November 2020, around 75,000 scientific papers were published on COVID-19, with one third published as preprints, released to other scientists and the public at large, before being fully reviewed and accepted for journal publication. As scientists choose to forgo some of the academic recognition that comes with waiting for traditional publication, the journals 996
themselves have shifted their approach as well, rethinking work flows to publish COVID-related papers much faster than normal. Yet this has not been without consequence. In the spring of 2020, two COVID studies were famously retracted over concerns about the veracity of the primary data. Some journals have admitted they may need to slow the process down again to ensure the quality of the work. Still, the knowledge gained has arguably outweighed the risks, given that the rapid advancements on vaccines, treatments and our understanding of the disease are owed in large part to the immediate and transparent release of new data. The question still remains whether this sense of shared purpose and transparent cooperation is a temporary measure or the beginning of a new era of scientific collaboration and global partnership. I can’t help but hope that this is indeed the beginnings of a new milestone in human achievement. Science is a tradition built on thousands of years of incremental progress. Imagine the exponential increase if our collaborative efforts continued—a global community united against the most pressing economic, social and environmental problems of our time. As Daley of the Harvard Medical School and MassCPR put it, “I cannot help but think that [it] provides a blueprint for moonshot projects that bring together the strongest and most dynamic forces of our formidable, biomedical ecosystem. What if we could marshal these forces against future pandemics, other diseases and larger global challenges? I dare to imagine the possibilities.” With all the tragedy of the past year and the losses we have suffered, this revolution in the scientific community and beyond may be the one exquisite thing to emerge. This is an opinion and analysis article. This article originally appeared in Forbes and is available online here: How COVID Changed Science
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June 2021
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United Kingdom Data Show Population Based Rapid Antigen Tests Are A Potent Covid Control Tool Forbes | June 1, 2021 | Article
Of the many different strategies countries are adopting to combat Covid-19, an increasing number include rapid antigen testing. Austria recently committed to the purchase of rapid tests, while in Canada a program was launched that aims to distribute rapid tests for workplace screening. Rapid tests can be administered free of charge and can be rapidly deployed. Yet, while rapid antigen testing could be an important step, a new study confirms that without a comprehensive testing regimen that includes PCR follow-up and contact tracing, rapid tests fall short as a method of Covid-19 control. A study conducted as part of national Covid-19 surveillance in England looked into the performance of antigen lateral flow devices. A lateral flow device is used to process a nose and throat swab sample for testing. When a person is infected with Covid-19, the lateral flow device recognizes a Covid-19 antigen that is generated. A coloured strip on the lateral flow devices will appear to show a positive result if this antigen is present. Data from community and hospital PCR testing in England was linked with national contact tracing data between September 1st 2020 and February 28th 2021. The data analyzed comes from two main sources: PCR-positive index cases and their close contacts. Index cases were defined as PCR-positive individuals with a community-based test from three national testing facilities which reported Ct values indicating a viral load. The Ct value, which stands for cycle threshold, represents the number of PCR cycles after which a virus can be detected. Contacts of index cases were defined as individuals notified to the national tracing service who were in close proximity to PCR-positive cases 48 hours before their symptom onset to ten days afterwards. Within 10 days of their test, about a million index cases had nearly three million contacts reported, of which 21 percent tested PCR positive. 999
The next step was running simulations that test what proportion of positive contact cases antigen lateral flow devices would detect. The study focused on viral loads of contact cases as antigen lateral flow device sensitivity differs by viral load. A positive or negative lateral flow device outcome was simulated for each source case by drawing at random from the likelihood of a positive lateral flow device based on the source case's Ct value. Each simulation was carried out 1000 times. Results indicated that the rapid antigen tests can detect 83 percent to 89.5 percent of infections leading to onward transmission. A limitation to this study is that the calculated benefit is particular to demographic and pandemic specifics . Nonetheless they do show that rapid testing can and does work when coupled with other mitigation measures. Rapid antigen tests are not accurate enough to be used as a standalone, and should be used only if the necessary follow-up is available. Singapore has had an effective test, trace, and isolate system since the pandemic started. With the country’s recent surge in cases, the government has been rolling out rapid antigen tests to speed up contact tracing. Following this approach, I would like to see more countries introduce a program called test, trace, isolate, prevent. Rapid antigen tests can be used for weekly testing in order to detect the most infectious cases and to prevent onward transmission. Positive cases should be confirmed using a PCR test and then isolated for fourteen days. Contact cases should then be traced and quarantined for at least ten days, and may only be allowed out of isolation if they are PCR-negative. Rapid antigen tests are not reliable enough to replace PCR testing, but are an essential preventative tool that could give us the upper hand against Covid-19. If governments have the resources to adopt a test, trace, isolate, prevent program, lateral flow devices offer an additional line of defense which allows for people to go outside more safely. This article originally appeared in Forbes and is available online here: United Kingdom Data Show Population Based Rapid Antigen Tests Are A Potent Covid Control Tool
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Don’t Let Children Be The Casualties Of Covid19 Complacency Forbes | June 3, 2021 | Article
Collecting comprehensive data on how children are affected by Covid-19 has been neglected in favor of competing priorities during the pandemic. Yet as overall cases currently decline in the U.S., an increasing percentage of cases are children, the issue demands urgent attention. As Covid-19 restrictions are rolled back across the country, unvaccinated and unprotected children will be casualties of complacency towards the virus. There is an immediate need to prioritize the vaccination of children and remain vigilant about public health measures such as masks and social distancing. The American Academy of Pediatrics reported that as of May 27, 2021, children represented almost a quarter (24.3%) of the new U.S. weekly cases. Cases as always can also be unreported, with the true number being higher. Research from the CDC also shows that over 90 percent of Covid-19 cases under the age of 18 may have been missed during a surge in Mississippi in August 2020. In early April, the case rate in young children and early teens began surpassing that of those 65 and older, according to the CDC. And hospitalizations for children with Covid aren’t falling as much as for those 18 and up. The increase is likely related not only to a return to in-person learning and the country’s reopening but also to the higher transmissibility of the circulating variants. A new preprint study confirms this hypothesis, providing evidence that children can be significant carriers of more contagious variants, such as the UK and California variants. The study’s authors sequenced the genome of 2,119 tests from Covid-19 patients age 18 or younger, from March 2020 to April 2021, to identify variants of concern, along with key mutations that increase transmissibility or help the variants hide from the patient's immune system. In total, the researchers identified 560 of these mutations, and 75% (420/560) were in children less than 12 years of age. The tests came from nine
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different children’s hospitals representing a diverse geographic and socioeconomic population within the U.S. Similar warnings have emerged out of Singapore, where several children were infected through a Covid cluster at an education center and schools are presently closed to avoid further outbreaks. Singapore Education Minister Chan Chun Sing was quoted in Reuters saying "some of these (virus) mutations are much more virulent, and they seem to attack the younger children,". Health Minister Ong Ye Kung also stated that the B.1.617 strain "appears to affect children more". The threat of Covid-19 and the current variants to unvaccinated and unprotected children is currently understated. Many have dismissed the danger citing “only” 300 children dying from COVID-19 , but any preventable death of a child is a tragedy. There is also much we are still learning about Multi-Inflammatory Syndrome and Long Covid in children. A small preprint study from Italy of 129 children, suggests that more than half of children with COVID-19 have at least one persisting symptom over 17 weeks after being diagnosed. Among them, 43% reported being impaired by their symptoms during daily activities. Yet many children struggle to have their unusual symptoms diagnosed as Long Covid or access treatment and therefore we cannot glean an accurate picture of how widespread the disease really is. “The pediatric piece of this is pretty neglected,” Amy Edwards, associate medical director of pediatric infection control at University Hospitals in Ohio told Bloomberg, “Kids with long haul have brain fog, chronic fatigue, fevers on and off, weird rashes. Long-haulers don’t go to the hospital. They suffer at home.” The symptoms of Long Covid are wide-ranging from anxiety and cognitive difficulties to extreme fatigue, chronic pain, and shortness of breath. This makes it difficult for parents to access the multidisciplinary team needed to treat their children. The Children’s Hospital in Cleveland and Yale New Haven Children’s Hospital are both working to change this with respective dedicated clinics and programs that are focused on treating Long Covid in children and provide access to experts in multiple specialties in one visit. But even with proper treatment, many children still have a long, painful, and likely expensive recovery ahead. With so much at stake, we must be 1002
doing everything in our power to protect children from being exposed to Covid-19. This article originally appeared in Forbes and is available online here: Don’t Let Children Be The Casualties Of Covid-19 Complacency
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New Drug May Bypass SARS-CoV-2 Blockade Of Innate Immune Response Forbes | June 3, 2021 | Article
Scientists have identified a small molecule drug that might prevent and treat Covid-19 by targeting a cellular gene that bypasses SARSCoV-2 blockade of the innate immune response. The drug, diABZI, is currently undergoing phase II clinical trials as a potential cancer treatment. So far, the search for Covid-19 drugs has yet to yield a product comparable in efficacy and utility to the mRNA vaccines created by Moderna and Pfizer. Remdesivir and monoclonal antibodies, the two FDA-approved treatments we currently have on hand, may be moderately effective, but they can only be administered intravenously in hospital settings. Early on in the pandemic, experts thought interferon-based drugs would make a potent Covid-19 treatment. Interferon is a signaling protein the body relies on to activate critical immune sensing pathways, and studies showed that SARS-CoV-2 either actively inhibited or evaded it. If a virus goes to great lengths to avoid triggering interferon, it makes logical sense that loading up on interferon would succeed as a countermeasure. But clinical trials testing interferon drugs fell short of expectations, yielding mixed results. Interferon may have been an obvious choice, but obvious in theory doesn’t always translate to success in practice. The problem isn’t necessarily that interferons don’t work. Using them so directly might just be too blunt an approach. New research, published in the journal Science Immunology in May 2021, suggests that using a small molecule drug to preemptively trigger the innate immune response downstream from interferons—specifically, the STING pathway— might do the trick instead. Immunity typically transpires in two waves. The first line of defense the virus encounters when it enters the body is the innate immune response, followed by an adaptive immune response that 1004
mobilizes T cells and B cells to recognize and attack specific pathogens. Innate immunity is necessary to trigger adaptive response. Innate immunity involves proteins known as pattern-recognition receptors that, over the course of evolution, have been hard-wired to identify pathogen-associated molecular patterns, or PAMPs. Some of the better known PAMPs include bacterial lipopolysaccharides, acids, bacterial DNA, and both single- and double-stranded RNA. A Science Immunology study led by microbiologist Sara Cherry and her colleagues at the University of Pennsylvania is the latest to show that the virus can evade these receptors adroitly enough to delay innate immunity for a significant period of time. To document this delay, the team infected respiratory cells with SARS-CoV-2 and monitored them for antiviral activity. A full 24 hours later, the cells exhibited very few transcriptional changes. It took 24 hours more— 48 hours total—for innate immunity to kick into gear and begin expressing interferon-stimulated genes. The suppression of gene expression is evidence of immune evasion, but not necessarily antagonism—a recurring theme throughout this research paper. The 24-hour timeline may be hypothetical, but the evolutionary advantage these mechanisms give the virus is not. So long as SARS-CoV-2 eludes detection, it can replicate unimpeded across the ACE2 receptors of bodily tissues and exit the body via nasopharyngeal and gastrointestinal passages, dispersing into the air and entering new hosts. Across several more laboratory experiments, Cherry and her research team observed SARS-CoV-2 evading immune sensing pathways, interferon activation, and detection by patternrecognition receptors. If a drug could stimulate these pathways independently, they reasoned, it might bypass viral suppression of the initial immune response. A second Science Immunology study, released at the same time as Cherry’s but conducted by a team from the University of Massachusetts, had the same hypothesis. The target selected for both studies was the Stimulator of Interferon Genes, otherwise known as STING. Interferons induce STING, which in turn activates a cascade of downstream factors, including STAT6 and IRF3, through the coding gene TBK1. Activation of the STING pathway leads to activation of both the innate and adaptive immune response, suppressing viral replication before it can overwhelm our bodily systems. 1005
Critically, the STING pathway appears to bypass the many blockades SARS-CoV-2 mounts against the innate immune response. Spurred by this observation, Cherry and her team screened 75 potential STING agonists for their ability to block SARS-CoV2. Of all the candidates, nine suppressed infection more than tenfold. Two cyclic dinucleotides showed particular promise but, as negatively charged molecules, they crossed the cell membrane at too inefficient a rate to warrant further examination. Instead, Cherry and her team chose diamidobenzimidazole, or diABZI, a small molecule drug that mimics cyclic dinucleotides in most respects—except it readily crosses the cell membrane. It is currently in trials for cancer treatment. The University of Massachusetts researchers chose diABZI-4, a new compound of the same drug. Both studies found that diABZI potently inhibited infection in both cell cultures and mice models, inducing the expression of hundreds of antiviral genes the virus would otherwise delay. Cherry and her team treated respiratory cells with diABZI and observed that it induced expression of more than 400 genes, nearly 40 percent of which link back to interferon signaling pathways. Compared to cells treated with interferon beta, upregulation of interferon-stimulated genes in diABZI-treated cells was more transient—meaning the risk of overstimulation is much less. Despite differences in duration, diABZI still suppressed the virus at a potency comparable to type I interferon treatment, blocking SARS-CoV-2 replication about 1000-fold in air-liquid interface cultures. In mice models, the results were even more promising. A single dose, delivered intranasally six hours prior to infection, helped prevent early weight loss and enable their full recovery. Rather than an oral or intravenous point of entry, the researchers focused on the respiratory tract because it is typically the first site of infection and, once the immune system is activated, the first line of defense. In subsequent dose-response experiments, even the lowest dose of diABZI resulted in about 1000-fold inhibition. The potency of the immune reaction triggered by diABZI, the researchers also found, was as robust against the B.1.351 (South Africa) strain as the original (Wuhan) strain. This suggests the treatment might be effective at deterring respiratory viruses more broadly.
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The Science Immunology studies mostly focused on diABZI as a potential prophylactic—a drug administered prior to infection, with the aim of prevention. But given to the mice therapeutically, with the aim of mitigating the severity of symptoms post-infection, diABZI still proved effective at reducing viral loads. Furthermore, unlike monoclonal antibody drugs, use of a chemical-based drug like diABZI isn’t affected or restricted by antibody resistance. These are just the kinds of drug treatments we need to deter a virus as wily and elusive as SARS-CoV-2—powerful, broadly protective, and capable of disarming the virus with molecular precision, from multiple directions. This article originally appeared in Forbes and is available online here: New Drug May Bypass SARS-CoV-2 Blockade Of Innate Immune Response
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Can We End the Pandemic? Project Syndicate | June 4, 2021 | Article
The emergence of dangerous new coronavirus variants is threatening the progress that we have made with the help of COVID-19 vaccines. It is now clear that our pharmaceutical research efforts and public-health interventions will need to be redoubled – and without any sunset clauses CAMBRIDGE – At the start of the year, there was reason to hope that we were beginning to see the end of the COVID-19 pandemic. In the United States, the daily rate of new cases from the holiday surge began to drop precipitously, and the vaccine rollout accelerated soon thereafter. Although Europe lagged in the early months of 2020, there, too, the tide started to turn by April, as the pace of vaccination finally picked up. But now that summer is almost upon us, the tide has turned once again, and not in our favor. New infections have been skyrocketing across South America, with countries like Argentina, Brazil, and Colombia approaching all-time highs of new infections in the past week. India crossed its own grim milestone last month with more than 400,000 new infections in a single day – a nearly unimaginable surge that overwhelmed hospitals and left families scrambling for any kind of care, oxygen, or medicines they could find. Even here in the US, states like Michigan and Oregon have struggled with recent spikes. These resurgences should remind us that even with millions of vaccines being administered in some countries, the pandemic is far from over. We are certainly not back where we started, but nor can we ignore the challenges that await us. MARKING THE VICTORIES The good news is that the first generation of mRNA-based COVID-19 vaccines (from Pfizer-BioNTech and Moderna) are working even better than most had hoped. Not only do they protect against mild, moderate, and severe disease, but recent evidence suggests they also protect against infection. They have been proven effective in those 12 years and older and are already being tested in 1008
children as young as six. Even if the other vaccines don’t perform up to the same standard, having two vaccines capable of removing transmission from the equation will do wonders for pandemic control. That said, we don’t yet know how long the protection from these vaccines will last, especially against new variants of SARSCoV-2, the virus that causes COVID-19. The latest studies suggest that the strength and duration of vaccine-mediated immunity depends on the initial concentration of neutralizing antibodies following completion of immunization. The higher the concentration, the more potent and longer-lasting the protection – against both the original strain and new variants. Again, though, not all COVID-19 vaccines are created equal. According to one preprint study that used existing data and statistical modeling to predict the performance of seven vaccines, the protection offered by the Moderna and Pfizer-BioNTech vaccines – currently the most powerful of the bunch, with 95% efficacy – could last as long as nine months, whereas vaccines with under 70% initial efficacy might lose their potency much faster. That doesn’t bode well for the widely distributed Johnson & Johnson and OxfordAstraZeneca vaccines. How do these predictions compare to what we know about natural immunity? One answer, based on a recent Singapore-based study, is that natural immunity is more variable than vaccinefurnished immunity. Researchers found that COVID-19 patients fall into five groups: those whose antibodies never reached detectable levels; those whose antibody levels were detectable within 20 days of infection, but dropped in fewer than 180 days; those who still tested antibody-positive 180 days after infection; those whose antibody levels showed little to no sign of decay for many months; and those who, against all odds, experienced a surge in antibody levels later in their recovery, as opposed to soon after infection. Most patients in the study ended up in the middle three groups. What we are looking at is a vast patchwork of immune responses. This variability means that there is no dependable front of recovered patients confronting SARS-CoV-2. Together with the uneven pace of vaccinations worldwide (not to mention the disproportionate allocation of the most efficacious vaccines), this could make herd immunity more difficult to achieve. 1009
OTHER BREAKTHROUGHS Beyond vaccines, there has also been progress in the development of prophylactic drugs that can prevent infection and disease from SARS-CoV-2. In recent clinical trials, monoclonal antibody treatments developed by Eli Lilly and Regeneron both performed well in nursing homes, reducing the risk of contracting symptomatic COVID-19 by 80% and 100%, respectively. Owing to drug resistance among new variants of the virus, the FDA has since halted the use of the Eli Lilly treatment, bamlanivimab, in isolation; but the drug may still be used in combination with others, and thus remains viable when deployed strategically. The downside of these treatments is that they must be administered through intravenous infusions. But on April 12, Regeneron released the results of a clinical trial testing the drug by subcutaneous injection. In this case, the risk of symptomatic infections was reduced by 81%, on average. It would of course be even better if prophylactics could be administered orally, like the pre-exposure prophylaxis for HIV. The two most promising candidates here are the antiviral molnupiravir and a protease inhibitor currently in development by Pfizer. According to a press release published by Merck, one of the companies behind molnupiravir, the drug performed well in a small case-control study of adults: none of those who received a dose tested positive for the virus, whereas 24% of the placebo group did. Like molnupiravir, Pfizer’s protease inhibitor is intended to be administered orally and would be ideal for workplaces, schools, and congregate living environments, including long-term care facilities, prisons, and family homes. Integrating prophylactic drugs like these into our public-health strategies would help seal up some of the cracks in the current vaccination strategy. With several other promising antiviral drug candidates under development, the longterm hope is that some combination of oral prophylactics will reliably prevent infections in those who are exposed. COVID’S REVENGE Set against this good news in drug development is the fact that new variants are constantly emerging. From what we know so far, almost all are more infectious, many have the ability to evade or 1010
mitigate the immune response (be it natural or vaccine-mediated), and some are more virulent (capable of causing disease in the host). To understand SARS-CoV-2’s variants, it helps to look at the entire life cycle of the virus. Regardless of whether the virus moves through the air, by intimate contact, or via a fecal-oral or fecalaerosol route, it must survive the journey so that it can attach to and enter a cell on a mucosal surface. Successful transmission thus depends on the amount of virus shed by the infected person, the stability of the virus particle, its affinity for the receptors at the mucosal surface, and the efficiency of entry. Once inside the cell, the virus then needs to reproduce and spread to other cells. The extent of disease will be determined by the rate of virus replication and the efficiency of the immune response. In those who have recovered from a prior infection or been vaccinated, the virus’s fate depends on the strength of the immune response and its own ability to evade it. Each new variant can affect any number of these variables, from virus load, stability, and attachment to cell entry, replication, and evasion of the immune response. Several variants – including the most widespread one first detected in the United Kingdom, B.1.1.7 – have a higher affinity for the SARS receptor (ACE2), are less sensitive to neutralizing antibodies, and reproduce more prolifically than the parent virus. B.1.1.7 infections can last up to 14 days before the virus is cleared from the body. As such, the variant has been shown to be around 60% more transmissible and more than twice as deadly as the original strain (though at least two studies cast doubt on the latter finding). Most of the research on new variants has focused on the coronavirus’s spike protein. This makes sense, because the protection offered by vaccines comes largely from antibodies recognizing and responding to it. Nonetheless, we should remember that increases in transmission and disease result from a combination of the interactions between all of the viral genes and proteins within the host, not just the spike protein. Changes that affect any part of the infectious cycle can and will contribute to transmission and virulence – for better or worse. SARS-CoV-2’s ability to evade the immune system’s response is an emerging area of study. Insofar as the initial immune response acts as an early-warning system, it is in the virus’s best interest to develop 1011
ways to slow down the system or slip through its grip. Unfortunately for us, SARS-CoV-2 has a trove of proteins it can devote to this task, as well as a special microcellular compartment that obscures its intracellular activities from the immune system, allowing it to produce double-stranded RNA unseen. The virus can also disguise itself by mimicking the host cell’s own messenger RNA, thus evading a second trigger of the innate immune response. And SARS-CoV-2 has a set of “accessory proteins” capable of foiling specific early-warning signals that normally trigger a prompt immune response. Among these are proteins that inhibit interferon production and activity, which is the primary sign to the immune system that an invader has arrived. Worse, mutations in SARS-CoV-2’s accessory genes may lead to more efficient viral replication and prolonged virus growth. The result would be an increase in the number of virus particles shed, leading to increased transmission and – not incidentally – more serious disease and deaths. These are not theoretical conjectures. All the variants of concern spread rapidly in the population and carry mutations in many of these genes – including those that mask viral RNAs and that modulate the immune system to the virus’s advantage. The same variants also feature mutations that accelerate viral replication. The effect of other mutations, especially those that modulate immune function, can only be evaluated in animals that closely mimic the human disease. To date, almost all of our knowledge of these variants is derived either from epidemiological studies or analyses of the virus in cell cultures. We would do well to study the contribution of each of the mutations in all of the viral genes to determine the overall transmissibility, potential to evade immune responses, and virulence of the variants. When the new variants first began to emerge, many experts – including me – worried that they would eventually become dominant, disrupting public-health interventions around the world. Sadly, this fear has since been borne out. On April 7, 2021, the US Centers for Disease Control and Prevention reported that B.1.1.7 had become the most common SARS-CoV-2 strain in the US. And the same variant is tied to almost 75% of new cases in France and a doubling of case counts in Germany.
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Moreover, over 50% of new infections in the US now trace back to a collection of new variants, some imported and at least three homegrown. In early March, a second-generation version of B.1.1.7 that carries an additional spike mutation – the feared E484K, nicknamed Eek! – was discovered in Oregon. And since then, a variant spreading rapidly in India, B.1.617, has reached the US, causing a growing percentage of infections in California and a sublineage, B.1.617.2, is spreading quickly in the UK. New variants of concern have also been detected in Belgium, the Philippines, and Tanzania. Surprisingly, the Tanzania variant, which was first discovered in a traveler to Angola, derives from the SARS-CoV-2 A lineage, not the B lineage that prevails in much of the world. ADAPTING TO THE ADAPTATIONS Some have suggested that the coronavirus can have only so many tricks up its sleeve. But in light of how thoroughly the variants have blindsided us, this seems like a naive assumption. Looking across the topology of the SARS-CoV-2 genome, there appear to be endless possibilities for the generation of novel viable variants. Like the influenza viruses that never seem to run out of ways to evade the previous year’s vaccines, cold-causing coronaviruses evade our immune responses every year. Moreover, humans aren’t SARS-CoV-2’s only host species, and the evidence suggests that some of the new variants have an even broader range of hosts than their predecessors. Among the latest animals to join the ranks, according to data from French researchers, are common breeds of laboratory mice – a finding disturbing in and of itself when we consider how densely these animals populate our cities. All told, scientists have already identified 80 species that are very likely to serve as welcoming hosts for SARS-CoV-2. In other words, COVID-19 is on its way to becoming endemic not just to Homo sapiens but also to many other animals with whom we share an ecosystem. The greater the host range, the more opportunities the virus has to incubate in animal reservoirs without human interference – only to come back to haunt us in a deadlier, more infectious form. This phenomenon has already been documented on Danish mink farms, where the virus infected 1013
farmers, crossed over into minks, and then leaped back into human handlers. Now that multiple variants have caught the world by surprise, we need to invest in a more systematized, standardized, and actionable approach to surveillance and detection. International cooperation will be crucial to making this a reality, as not all countries have the funds or infrastructure in place to do it alone. First and foremost, this challenge demands a vast expansion of genome-sequencing efforts, so that we can detect and anticipate patterns in viral variation before they interfere with ongoing publichealth interventions. This calls for more ongoing testing, an area where the US has faltered, despite the proliferation of technologies and evidence-based models that would make mass diagnostics feasible. Still, as of mid-April, the US government had committed $1.7 billion to improving variant surveillance through genomic epidemiology research initiatives and a National Bioinformatics Infrastructure for data collection. Such frameworks will increase responsiveness both to the current pandemic and to pathogens that lie in our future. Equally promising, the UK is beginning to roll out a hometesting program that will allow everyone to test themselves at least twice per week for free. Britain also continues to lead the world in genomic-sequencing capabilities, thanks to the COVID-19 Genomics UK Consortium, a year-old group that has succeeded in looping its own data-collection processes into existing health systems (namely, testing programs in hospitals and community care centers). BOOSTERS AND BEYOND The first generation of COVID-19 vaccines was developed using essentially the same antigen. As such, the major difference between each vaccine is the strength of the antibody reaction it elicits – as demonstrated by studies linking the strength and length of vaccinemediated immune protection to that of the antibody response. In terms of the current vaccines’ ability to protect against the new variants, however, a reduction in efficacy has been observed across the board. The second generation of vaccines is already in development, with the focus primarily on the B.1.351 and P.1 variants, since these 1014
both have the immune-evasive E484K mutation. With the third generation, there will be an opportunity to create vaccines that are more broadly protective, raising higher, longer-lasting antibody titers. A platform in its early stages that has already shown promise in this regard is known as nanoparticle immunization technology, which combines fragments of different viruses into a single particle for loading into a shot. Two research papers covering two approaches to developing a nanoparticle vaccine have been published to date. The first study uses a ferritin-based cage to aggregate bits of spike protein from different viruses, while the second study uses nanoparticles of the “mosaic” variety, consisting of 60 spike protein fragments that were identical in appearance and function, but were taken from up to eight different coronaviruses. Both studies found that in animal models – macaque monkeys in the first, and mice in the second – the vaccines performed remarkably well. Recall that SARS-CoV-2 disarms our immune defenses through a highly coordinated attack that weaponizes the entire genome against us. As such, one drug – and target – isn’t enough. What we need is a combination of drugs that inhibits a broader spectrum of activity, and that can be taken orally. But even if we have viable drugs on hand, we still need a strategy for combining and delivering them in conjunction with vaccines and other public-health interventions. The best use of orally ingested drugs, for instance, would be in congregate living environments like dormitories, nursing homes, and prisons, where they are easy to administer quickly and widely in the event of infection. PERMANENT PREPARATION Looking ahead, we must not repeat the mistake we made after the first two lethal coronavirus pandemics this century, SARS and MERS, when we allowed initial waves of research to recede. Pandemic preparedness and international cooperation must not be abandoned out of a false sense of safety. In some countries – like New Zealand, Australia, China, and Singapore – public-health measures have been sufficient to control the pandemic. Their strategy is simple but rigorous, involving broad surveillance, rapid case identification, contact tracing, assisted 1015
isolation, and strict border control. But even this is not bulletproof. Singapore, for example, has just recently reinstituted a lockdown, shutting down schools, restaurants, and other public gathering places after a spike of new infections tied to the B.1.167 variant. For countries like Singapore, vaccination is a critical backstop for COVID-19 containment. In countries that have enforced various combinations of these public-health measures with much less success, hopes now hinge mainly on mass vaccination and drug development. We need to increase our capacity for vaccine production and invest in more expansive, long-term solutions like mosaic vaccines. We also need to broaden existing vaccinedistribution channels so that no country is left behind. The virus still poses a grave threat in many countries, which means it still poses a grave threat to us all. This article originally appeared in Project Syndicate and is available online here: Can We End the Pandemic?
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Pediatric Mental Health Is In Crisis Forbes | June 4, 2021 | Article
Colorado Children's hospital has declared a pediatric mental health emergency having witnessed suicide attempts and psychiatric helpcalls for children spike during the pandemic. The hospital says they have seen a 90% increase in demand for behavioral health treatment in the past two years. Despite expanding their behavioral health services, they cannot keep up with the demand. Emergency transport teams have been reporting three to four suicide attempts per week and have requested additional training on how to deal with these situations. Suicide is now the leading cause of death for children over the age of 10 in the state Unfortunately, the crisis is not limited to Colorado. According to the Centers for Disease Control and Prevention, the proportion of mental health-related emergency room visits increased 24% for young children and 31% for teens from March to October of last year compared to 2019 as seen in the below chart (Figure 1). Colorado Children's Hospital Chief Medical Officer Dr. David Brumbaugh says in 20 years, he's never seen such a demand for services.
Number of pediatric mental health-emergency visits per 100,000 in the United States. ACCESS HEALTH INTERNATIONAL. DATA SOURCE: CDC
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As we begin to control and develop defenses against Covid-19, we need to give equal priority to the syndemics that have evolved from the pandemic. Covid-19 will leave deep scars on our psyche and impact the mental health of our population for years to come. I have previously written about the increase in depression, anxiety, loneliness, and substance abuse in young adults aged 18-24. But the crisis in pediatric behavioral health is just as urgent and can also lead to greater health and socioeconomic disparities later in life for these children. With the many interruptions that Covid-19 has brought to the developmental needs of children and the multiple chronic stressors, many children are losing their resilience and are sometimes unable to deal with the disappointments of everyday life. Dr. Brumbaugh has noted this worrying trend, recalling a father who brought in his ninth-grade son who tried to take his life after he didn't get on a baseball team. Jenna Glover, MD, child psychologist and Director of Psychology Training at Children's Colorado, said many children are “feeling a sense of hopelessness,” which is one predictor of suicidal ideation. With the spike in mental health issues in children, organizations and medical professionals that serve these populations are overburdened and hampered by long wait lists for appointments. When parents arrive with their children in the emergency room, it is often as a last resort or as a result of untreated conditions. But emergency rooms are ill-equipped for mental health care and often the experience of staying in the emergency room is a traumatic one, further exacerbating issues. Yet what is known as “emergency room boarding” continues to rise. In Massachusetts, emergency room boarding has been up between 200% and 400% throughout the pandemic. After their release from the emergency room, pediatric patients still face long wait times for follow-up care. For children admitted for suicidal ideation or attempted suicide, they can not afford this disturbing delay in treatment. We must invest heavily in treatment and preventive services to begin to address this crisis. Children’s hospitals should be the last line of defense in fighting this crisis. Hospitalization is the most expensive option and least effective option and frequently comes too late to address the underlying causes of illness. We can provide training to teachers and school administrators to recognize the early signs of 1018
mental health issues, we can use school curriculums to raise awareness and provide resources. Schools can lead dialogues around stressors that have plagued children long before the pandemic such as social media addiction, anxiety about grades, and bullying. Most importantly we can create links between schools and treatment services, to address these issues at the root. This article originally appeared in Forbes and is available online here: Pediatric Mental Health Is In Crisis
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Hepatitis-C Drugs And A Remdesivir Metabolite As New Anti-Covid-19 Drugs: The Viral Protein NSP3 Emerges As A New Target. Forbes | June 4, 2021 | Article
The GS-441524 Remdesivir metabolite alongside ADP-ribose; HCV drug BOC binding to the NSP5 protease ... [+] NI ET AL. // BAFNA ET AL.
In the search for new ways to use small molecule drugs to prevent and treat Covid-19 infections, a surprising synergy has emerged. Two drugs—Remdesivir metabolite GS-441524 and combination Hepatitis-C antivirals—both of which target NSP3 hold immediate promise for prevention and treatment of infection by SARS-CoV2. Some of these drugs are highly synergistic, as much as tenfold, and show few adverse toxic effects. Here is the story of how they were discovered. It is also a surprising story about repurposing old drugs
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for new uses, and the discovery of an unlikely new target of antiCovid-19 drugs, the viral protein NSP3. We are now halfway through year two of the Covid-19 pandemic. The end is not yet in sight given the recent surge in India, the increase in infections in Latin American, and flare-ups in countries such as Japan, Taiwan, Singapore, Thailand, Vietnam, and Australia. Vaccines will be the backbone of Covid-19 control as evidenced by the positive results in Israel, the United Kingdom, and most recently the United States. However, the variability of protection offered by different vaccines over time and against viral variants warrants consideration for other means to prevent infections of the unvaccinated, for cases of vaccine breakthrough, and infection of those with underlying immune dysfunction. I believe that the successful Covid-19 control strategy will be multi-modal, combining vaccines, anti-SARS-CoV-2 antibodies, and combinations of antiviral drugs. Our ongoing series outlines rapid progress in progress in anti-SARS-CoV-2 monoclonal antibodies and nanobodies. Here we begin a new series devoted to progress in the development of small molecule drugs designed to prevent and treat Covid-19. Viral protein NSP3 as a target for antiviral drugs The genome of SARS-CoV-2 (SARS-2) is both large and complex, encoding at least 30 distinct proteins. The proteins can be divided into three function groups: Those that specify the replication-transcription machinery necessary to assure copying of the genome and production of messenger RNAs from which all the viral proteins are made, the structural proteins comprising the nuclear core, the outer membrane, and the spike proteins of the infectious virus particle, and the accessory genes, those that specify functions vital for successful propagation in adult immunocompetent animals but dispensable for growth in cell culture (Figure 1A).
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FIGURE 1: (A) SARS-CoV-2 genome. Orange indicates the SARS-CoV-2 replication complex; blue indicates ... [+] FRICK ET AL
The two long open reading frames at the 5’ end of the genome comprising roughly two-thirds of the entire genome specify the proteins designated NSP1-NSP16. NSP stands for non-structural proteins as they are not found in infectious viral particles. All of these proteins, NSP1-16, are essential for prolific replication in both cell culture and in animals. As such, they provide a wealth of targets for antiviral drug development. In this series, I will enumerate the functions of each of these early essential genes and proteins and evaluate them as targets for antiviral drugs. We will begin with considering NSP3 (nonstructural protein 3) as a potential target. NSP3 as a target for antiviral drug development NSP3 is the largest and most complex of the SARS-2 proteins. The mature form of the NSP3 is almost 2000 amino acids long. It is synthesized as part of two much longer polypeptides, the product of the initial long open reading frame (orf1a), and from the orf1b, the orf1ab polypeptide. NSP3 frees itself in an autocatalytic process, along with NSP1 through NSP4 (Figure 2).
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FIGURE 2: The NSP3 papain-like protease (PLpro) releases NSP1, NSP2, NSP3, and NSP4 during the ... [+] ACCESS HEALTH INTERNATIONAL
The central role of NSP3 in early viral replication All nidoviruses, of which the coronavirus are a subset, specify NSP3-like proteins, including SARS-CoV (SARS-1) the causative agent SARS. It is noteworthy that the greatest divergence of SARS2 from SARS-1 extends over the entire orf1a open reading frame, including the region that encodes NSP3 (Figure 1B). The marked difference in this region of the genome points to an as yet unknown non-human precursor virus of SARS-2. The difference also suggests that the difference in biology—the long asymptomatic period, decreased pathogenicity, eventual pathogenesis, and late sequelae of SARS-2 as compared to SARS-1—might be in large measure determined by these differences in the orf1a proteins. Indeed, differences in pathogenicity of the porcine reproductive and respiratory syndrome virus are attributed to mutations in the orf1ab proteins of the NSP9 and NSP10 proteins. Structural studies of the mature NSP3 reveal that the protein folds into seven discrete domains. Each domain species has one or more discrete functions. Table 1 summarizes what is known about the function of each of these domains. Also shown are the structural similarities of each domain with other cellular proteins of known function, aside from the two ends of the protein, which are relatively disordered. The following figure shows the full crystallization structure of NSP3 (Figure 3).
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FIGURE 3: The NSP3 crystal structure. UNIVERSITY OF MICHIGAN
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TABLE 1: Function of each domain ACCESS HEALTH INTERNATIONAL Many of the crystal structures of these domains have been determined independently, and each and every one of these domains may prove to be viable targets for small molecule drugs (Figure 1C). The picture that emerges from the collection of these studies is that NSP3 is a linchpin of early functions required for virus replication. NSP3 is critical to: 1025
1. The formation of the double-membrane vesicle within which viral replication and transcription occur (Figure 4). 2. Exit of the mRNAs from the double-membrane vesicle to the cytoplasm for translation of viral proteins via a highly structured pore . 3. Anchoring the replication complex to the inner surface of the double-membrane vesicle via interaction with both the membranes and the nucleoprotein (N) via tight association with the viral nucleoprotein (N) that binds viral RNA. 4. Protection of viral proteins from degradation. Modification of proteins by the addition of either ADP-ribose or ubiquitin marks the modified protein for degradation by cellular enzymes. One domain of the NSP3 removes ADP-ribose from modified viral proteins and others de-ubiquitinate marked proteins. 5. Proteolytic cleavage of the orf1a and orf1ab precursor polypeptides proteins to release the NSP1, NSP2, itself, and NSP4 of mutations that abrogate the NSP3 protease function are lethal to virus replication in cell culture and in animals.
FIGURE 4: The SARS-CoV-2 double-membrane vesicle, which is primarily constructed by NSP3, NSP4, ... [+] WOLFF ET AL.
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FIGURE 5: The pore created by NSP3. UNCHWANIWALA ET AL.
High-resolution structures of the entire NSP3 protein as well as most of the individual domains have been determined by X-ray crystallography, cryo-electron microscopy, and nuclear magnetic resonance. The detailed structures facilitate computational docking with many thousands of potential drug candidates. Here, the focus falls on two specific domains, but we reiterate that there are many domains that could and should serve as potential targets for future antivirals. Inhibitors of the NSP3 protease A study analyzing hepatitis C antivirals assessed the ability of 10 available HCV protease inhibitors to suppress SARS-2 replication. Due to the structural similarity of the HCV protease to the SARS-2 NSP5 protease, the researchers hypothesized that the HCV drugs may also inhibit the NSP5 protease. Subsequent studies report three drugs, boceprevir, narlaprevir, and telaprevir, inhibit NSP5 protease proteolytic activity and bind into its active site.
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Using virtual docking experiments, the researchers confirmed their suspicions, finding that all 10 of the HCV antivirals they tested can bind into the NSP5 protease binding cleft (Figure 6). Seven of the drugs inhibited both SARS-2 NSP5 protease activity and SARS2 virus replication in Vero and/or human 293T cells. Surprisingly, they found that four of the 10 also inhibited NSP3 protease activity. Their encouraging finding was that HCV drugs that inhibit the NSP5 protease and/or the NSP3 protease can suppress SARS-2 virus replication.
FIGURE 6: HCV antiviral BOC binding to the NSP5 protease binding pocket. BAFNA ET AL.
While the active site of the NSP3 protease does not have much structural similarity with the HCV or NSP5 proteases, the researchers carried out virtual docking studies of these same 10 HCV drugs into the substrate-binding cleft of NSP3 protease. The known NSP5 protease inhibitor GRL0617 was used as a reference. They found that four drugs inhibited the NSP3 protease to similar levels as GRL0617. These proof-of-concept docking studies suggested that, surprisingly, some HCV protease inhibitors may bind in the substrate-binding clefts of both NSP3 and NSP5 proteases (Figure 7). 1028
FIGURE 7: HCV antiviral papain-like protease inhibitors. ISG15 (interferon stimulated gene 15); ... [+] BAFNA ET AL.
The researchers further demonstrated that these four drugs also acted synergistically with remdesivir to inhibit SARS-2 replication, thereby increasing remdesivir antiviral activity as much as 10-fold. In contrast, the HCV drugs BOC and NAR, which inhibit the NSP5 protease but not the NSP3 protease acted additively rather than synergistically with remdesivir. This suggested that the combination of an HCV protease inhibitor with an RNA polymerase inhibitor could potentially function as an antiviral against SARS-CoV-2. They conclude by remarking that “more generally, our results strongly motivate further studies of the potential use of PLpro protease inhibitors in combination with RNA polymerase inhibitors as antivirals against SARS-CoV-2.” Inhibitors of the NSP3 ADP-ribose phosphatase In addition to the HCV drugs, there is another that targets the NSP3 macrodomain. The macrodomain and its ADP-ribose removal function are important for efficient viral replication, as viruses harboring inactive macrodomains exhibit reduced replication ability and pathogenicity and are sensitive to interferon pretreatment.
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ADP-ribose removal has also been linked to the function of viral proteins involved in viral replication or in immune antagonism. The central role of the SARS-2 macrodomain in viral replication and immune responses suggests that this protein module may offer a target for combating the disease. Some subtle structural differences between SARS-2 and other coronaviruses have been observed, suggesting that macrodomain may possess some degree of plasticity, opening a possibility for the binding of diverse small molecules, which researchers investigated in a study by Ni et al. To understand the macrodomain plasticity, they crystallized the domain in an apo state. The atypical presence of five and three molecules in their asymmetric units suggested potential flexibility. Then, a structural comparison of the macrodomain’s chains revealed some differences in the residue conformation lining the ADP-ribose binding pocket. The researchers observed diverse conformations of residues in the phosphate-binding site. The flexibility of phenylalanine and isoleucine indicated the pocket may be open to binding a diverse set of ligands. Overall, the structural changes revealed the potential intrinsic plasticity of the macrodomain, especially within its ribose-phosphate binding pocket, indicating the potential binding of ligands. This plasticity prompted the researchers to speculate the potential binding of antiviral nucleoside analogs. They selected a set of diverse antivirals, including abacavir, entecavir, acyclovir, gemcitabine, remdesivir, and remdesivir metabolite GS-441524, and tested the binding of these drugs using cocrystallization. Electron density maps revealed that the remdesivir metabolite GS-441524 was the only ligand that showed binding in the crystal structures. The interaction of this compound was rather unexpected because this metabolite and its active triphosphorylated form have been designed to target the NSP12 RNA-dependent RNA polymerase of several coronaviruses. Notably, an earlier study this year showed remdesivir metabolite GS-441524 potently inhibits SARS-2 infection in mouse models. Additionally, GS-441524 is also a proven treatment for cats with naturally occurring feline infectious peritonitis. The researchers’ structural comparison demonstrated that the binding mode of GS-441524 in the macrodomain highly resembled that of the adenosine moiety of ADP-ribose, indicating that the metabolite can bind to the macrodomain in place of ADP-ribose (Figure 8). 1030
FIGURE 8: GS-441524 metabolite crystal structure alongside ADP-ribose. NI ET AL.
The researchers additionally note that the NSP3 macrodomain is highly conserved, not only in SARS-2 variants but in SARS-1 and MERS-CoV as well. This opens the possibility of a broadly neutralizing antiviral. The issue with convalescent sera as a treatment to Covid-19 is that this virus adapts, developing mutations, and becoming resistant to older neutralizing antibodies. When we develop antivirals that target highly conserved areas, the potential escape of SARS-2 mutants is reduced as the target remains the same. This could ease the burden brought by highly infectious SARS-2 variants, as well as prepare us for potential coronavirus pandemics in the future. The researchers conclude, “targeting the MD offers an attractive target for the development of antiviral agents against SARS-2 and other viruses.” It is intriguing that these two classes of inhibitors target two different proteins. HCV antivirals inhibit both proteases and the Remdesivir metabolite inhibits ADP-ribose in the macrodomain, as well as the NSP12 polymerase through its active intermediate. These are powerful arguments for the combination of these two classes of antiviral to make an excellent prophylactic and therapeutic for prevention and treatment of Covid-19. A combination therapy could be developed taking advantage of the synergistic effects of the HCV drugs and the potent neutralizing capabilities of the remdesivir metabolite. We already know HCV antivirals boost the potency of remdesivir, so it is possible that a 1031
similar effect could take place with the metabolite. As an added advantage, the protease, the ADP-ribose inhibitor, and remdesivir are available to be administered orally, meaning a combination could likely come in this form as well. These are just two of many antivirals that could be combined in a unilateral attack on NSP3. The protein has so many crucial targets; we must take advantage. This article originally appeared in Forbes and is available online here: Hepatitis-C Drugs And A Remdesivir Metabolite As New Anti-Covid-19 Drugs: The Viral Protein NSP3 Emerges As A New Target.
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Baseline Temperature Dropped Over 100 Years: The Importance Of Knowing Your Normal Temperature To Detect Fever Forbes | June 4, 2021 | Article
Fever is among the most common symptoms of Covid-19. It also is the symptom that is most commonly checked for when determining whether someone has been infected or not. Whether you are entering a hospital, a store, or a school, temperature is often the only indicator of infection that is monitored. The question arises, though, how reliable body temperature is as an indicator of sickness. Our global standard for typical body temperature is 98.6 degrees Fahrenheit. Carl Reinhold August Wunderlich, a German physician, made that norm prominent when he published it in a book in 1868, after taking the temperature of 25,000 patients several times. We based our definition of fever on that number, and have defined it to be 100.4 degrees Fahrenheit. Modern research, on the other hand, has cast doubt on Wunderlich’s findings, claiming that our typical body temperature has decreased. A study published earlier this year argues that that number is not only outdated, but a poor universal indicator to measure sickness. Researchers from Stanford University analyzed data from Civil War soldiers and veterans, as well as data from two more recent cohorts, to confirm that body temperatures in men averaged around 98.6 degrees Fahrenheit back then, but have steadily declined over time, and that temperatures in women have also fallen. According to their findings, the average temperature for men and women is 97.5 degrees Fahrenheit. This means that humans have altered physiologically during the last 200 years, with a mean body temperature that is 1.6 percent lower than in the pre-industrial age. In a recent interview with Stanford, senior author Julie Parsonnet explained that one of the main reasons why the Civil War soldiers and veterans had a higher temperature was that “they may have just raised their metabolic rate because their whole lives they 1033
are fighting infectious diseases which we do not do anymore”. The metabolic rate is the amount of energy we use. The scientists speculate that this decrease is linked to a decrease in inflammation across the population due to a drop in infectious diseases. Inflammation raises the metabolic rate, which raises overall body temperature. When the Civil War soldiers and veterans had their temperature taken, they might have had tuberculosis, syphilis, chronic diarrhea, and all types of other diseases that could raise their metabolic rate. Today, children grow up without having to fight off many infectious diseases. The other main reason Parsonnet mentions for this reduction in temperature is economic development. Since the 19th century, increased living and sanitation standards, fewer chronic infections from war injuries, increased dental hygiene, the fading of tuberculosis and malaria infections, and the start of the antibiotic era have all likely reduced chronic inflammation. We eat less inflammatory foods, and have access to heating and air conditioning, meaning our bodies do not have to work as hard anymore to keep a constant temperature. Our bodies are more at ease, so when we do get sick, while our temperature might be lower than 100.4 degrees Fahrenheit, we might still be running a fever. This is especially true among the elderly, who rarely mount fevers as people, or an average physician would define it, but who are sick. Another variable which Wunderlich failed to take into account is that a person’s body temperature varies depending on the time of day. As the body's requirements and activities fluctuate throughout the day, a healthy person's body temperature varies by roughly 0.9 degrees Fahrenheit, with lower temperatures in the morning and higher temperatures in the late afternoon and evening. These findings are not common knowledge yet, but are critical in light of the pandemic. My recommendation is to take your own temperature and that of your children enough times during the day to know what is normal and what is a fever. What may be a normal temperature for some, is a serious fever for others. Above all, if you or a child feels sick, assume that the feeling is correct regardless of temperature. This article originally appeared in Forbes and is available online here: Baseline Temperature Dropped Over 100 Years: The Importance Of Knowing Your Normal Temperature To Detect Fever 1034
Restoring Vision To The Blind. Regenerative Medicine Offers New Hope For Retinitis Pigmentosa Forbes | June 8, 2021 | Article
Imagine what suffering from retinitis pigmentosa is like. Imagine gradually losing your vision over the course of forty years, waking up every morning with a tiny bit more of your peripheral vision grayed out, until you succumb to complete blindness as more and more photoreceptive cells start failing in your eyes. RP is considered a rare disorder. Although current statistics are not available, it is generally estimated that the disorder affects roughly 1 in 4,000 people, both in the United States and worldwide. This was the life of a 58-year-old man until a team of scientists restored useful sight by injecting genetically engineered viruses into his eyes. From having no vision for the last two decades (due to the defective photoreceptors not being able to deliver visual information from the eyes to the brain), to being able to see small objects such as a notebook and a staple box with the help of light-stimulating goggles, the breakthrough described in a paper published in the journal Nature Medicine relied on optogenetics. While he could identify the notebook 92% of the time, he could only touch the smaller staple box 36% of the time and was even reported being able to see the white stripes of a pedestrian crosswalk. The team of international scientists discovered that activity in the visual cortex of his brain changed depending on whether or not an item was there, demonstrating its relationship to the retina, using non-invasive electroencephalography (EEG) readings. The results were described as "remarkable." “I think that a new field is being born,” University of Basel professor and researcher Botond Roska told reporters during a recent conference call announcing the team’s results.
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Optogenetic therapies to restore vision have been utilized for over a decade by scientists to treat people with degenerative eye diseases, such as retinitis pigmentosa. It combines optics and genetics to allow researchers to regulate individual neurons in vitro using visible light. Brain cells are first exposed to light-sensing molecules, which are then activated by light pulses from fiber-optic threads. The chemical turns light into an electrical impulse, causing the neuron to fire as well. This allows researchers to stimulate specific neurons on demand, potentially affecting the subject's behavior and responses. The method is based on algal proteins that move in response to light sources. In the therapy, scientists injected these genes into the retina's remaining functional ganglion cells, causing them to create the light-sensitive protein ChrimsonR. “It’s exciting. It’s really good to see it working and getting some definite responses from patients,” says David Birch, a retinal degeneration expert at the Retina Foundation of the Southwest in Dallas. Birch has conducted clinical trials of other optogenetic therapies but was not involved in this study. As part of their PIONEER 1/2a investigation, the University of Basel-UPMC team used GenSight Biologics technology to apply the core theories of optogenetics to the retina. The two-prong approach was adopted using both biological and technological components. The biological aspect addressed the RP issue as the researchers targeted the patient’s retinal ganglion cells to receive a genetic therapy that would make them photoactivatable. Normally the rods and cones are photosensitive, but given that RP had essentially damaged and destroyed the patient's rods and cones, the ganglion cells (that mainly focus on carrying electrical charges generated by those photoreceptive cells) would have to be modified. To do this, the researchers isolated a gene from a light-sensing species of green algae into one of the patient's eyes. This leads to the gene encoding a photoactivatable protein called ChrimsonR. “These proteins are very special,” Dr. José-Alain Sahel, Distinguished Professor and Chairman of the Department of Ophthalmology at the University of Pittsburgh School of Medicine, co-founder of Gensight Biologics and co-lead investigator for the PIONEER study, told Engadget. “They were discovered in the late ‘90s and early 2000s. These proteins exist in algae, capturing light and triggering an electrical response that enables the algae to move 1036
towards or retract from light, and it's a single protein so it's a very fast response.” After a few months, the ganglions produced sufficient amounts of ChrimsonR. Given that ChrimsonR is most responsive to light in the 590nm wavelength (amber), this is when the technological aspect came in. As this is far brighter than ambient lighting can generally produce, Gensight (founded by Dr. Sahel and his colleagues) developed a proprietary set of goggles that collect image data from an incorporated event camera and beam high intensity, 590nm wave light directly into the patient’s eyes. “We developed a bioinspired camera that functions at every single pixel by detecting any change in light sensitivity,” Sahel explained. “These cameras can detect very low levels of changes, can function at low levels applied and high levels of light. We are functioning pixel by pixel and we are processing the image in real-time.” This is the first reported case of partial functional recovery in a neurodegenerative disease after optogenetic therapy. However, this current PIONEER study is a very preliminary start to this form of therapy. Before optogenetics can become a standard treatment for some forms of blindness, further positive clinical trial findings are needed. For the time being, Dr. Sahel and his colleagues are bringing in additional volunteers for training, as well as testing stronger dosages of the virus and updating their goggles to thin spectacles that are more comfortable and deliver more information to the retina. In comparison to the Orion Visual Cortical Prosthesis System, which requires probes to implant a control unit chip in your skull, optogenetic therapy can serve as a less invasive approach. Sahel and Roska stress that the therapy is not a cure for blindness. “For now, all we can say is that there is one patient … with a functional difference,” Roska says. Sahel adds, “it’s a milestone on the road to even better outcomes.” This article originally appeared in Forbes and is available online here: Restoring Vision To The Blind. Regenerative Medicine Offers New Hope For Retinitis Pigmentosa
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The Perils Of Covid Complacency Forbes | June 9, 2021 | Article
Every COVID-19 headline from the other side of the world is a warning for us here — the writing on the wall if we continue to be complacent about controlling the pandemic. Yes, new infections are on an overall decline in the US. And yes, more people are fully vaccinated. But our defensive shield against the virus is still quite weak, and what’s happening across Asia and Australia reminds us that the virus’s weapons are improving. Until very recently, countries like Australia, China, Singapore, and Taiwan had their pandemics completely under control. New COVID cases were down to the single digits and their cities and economies had been reopened for nearly a full year. But in each of these countries, new outbreaks have emerged, ones that have proven dangerous enough to lead to new lockdowns, with schools shutting down and restaurants and other public gathering places closed. The first signs of trouble started brewing in Singapore in early May, a country with some of the most stringent COVID-19 restrictions in the world. Within the country, cases were well contained. When they occurred — which was rare — new cases were quickly identified, immediately isolated, and everyone who had come into contact with the person infected was asked to quarantine, under penalty of law. Travelers to the country were also subject to mandatory quarantines, in government-supervised hotels where they were required to test negative multiple times before being allowed into the community. But the one place they overlooked was the airport itself, where travelers from high-risk countries arrived and rubbed shoulders with airport staff before being ferried to quarantine. Those airport workers, many of them vaccinated but some of them not, dined in the public food court alongside other airline staff, passengers, and local Singaporeans who often visited the airport for its food, gardens, and entertainment attractions. While these containment measures may have been enough to keep the virus at bay throughout the last 1038
year, when confronted with new highly transmissible variants, they proved a poor match. A fully vaccinated 88-year-old airport worker was the first to test positive for COVID-19, having been infected by the highly infectious Delta variant, which was recently linked to the huge outbreak in India. That single infection expanded into an outbreak that saw up to 40 new infections per day and forced the lockdown of the entire country — another circuit breaker to buy the country time to identify and contain all those potentially exposed to the highly infectious virus. Meanwhile, in Taiwan and Australia, similar stories were unfolding. Taiwan had been extremely successful at keeping the virus from entering the country — for more than a year, the country had kept new infections near zero and had successfully contained new cases at the border. But those low case counts bred complacency. There was little testing done within the country itself, limited surveillance, and no rush to roll out the vaccines. In April, confident of their success, Taiwan changed the rules for the airline crews on arriving flights, allowing them to quarantine for just three days instead of 14. Within the month, cases went from single digits into the thousands, with airline crews bringing the virus into local bars. This time, it was the Alpha variant that managed to sneak in, a variant with mutations that are known to disable the first line of our immune defenses, giving the virus more time to multiply and spread. By May, Taiwan too was forced to start shutting down public venues, nonessential services, and limiting gatherings to all but a handful of people. Cases have now spread to the chip factories, causing a global shortage which has hit everything from cars to consumer electronics. Australia enacted a much more forceful lockdown in the face of its own breakthrough variant, this one brought in not by airline staff but by a passenger dutifully following hotel quarantine rules — a Melbourne man quarantined on the same floor as another traveler who eventually tested positive for the highly infectious Kappa variant. Though the two individuals had no direct contact with each other, they opened the doors to their hotel rooms within 30 minutes of each other, a seemingly innocuous event that has led to more than 300 potential sites of exposure and more than 17,000 people potentially exposed to the virus. Genomic sequencing confirmed 1039
that both individuals had the same strain of the virus. A similar event occurred earlier in April where two families quarantining in rooms next to one another were found to share the same viral sequence, after briefly opening their doors 30 minutes apart. The lockdowns unfolding in Asia and Australia should be a warning to us all that we cannot be complacent in the face of these new variants. It will take a single infection to spark a renewed outbreak across our country, one that could lead us back into the lockdowns of 2020 that we are already struggling to recover from. Many assume our higher vaccination rates will help prevent this from happening, but there are a few flaws with this thinking. First, less than half of all Americans are fully vaccinated, meaning the majority of Americans are still at risk today. Additionally, the case rate among the unvaccinated seems to still be hovering at around the same rate as it was in January, when we were seeing upwards of 200,000 new cases a day in the US. While thankfully the total number of new infections is now significantly lower — though not nearly as low as it was in places like Singapore, Taiwan, and Australia — the case rate among the unvaccinated reminds us that the virus, and these new variants, are still circulating widely within our midst. Even in vaccinated individuals breakthrough cases can occur and as we saw in Singapore and Australia those cases can be patient zero in a new outbreak. Those with compromised immune systems will also not receive the full benefits of vaccination and will be left vulnerable with other public health measures in place. With Covid-19 cases declining to more manageable levels in the U.S. now is a critical time to adopt the lessons of other countries to keep cases at those levels or lower and avoid the trap of complacency. First, we need a return to basics, a public health strategy that has been proven to contain outbreaks; test, trace and isolate. To make long-term testing for Covid-19 sustainable and to encourage compliance, we need to continue to invest heavily in mass rapid testing that can be done at home across the country. Tests need to be free and widely accessible. This needs to be accompanied by public health messaging that encourages the public to get tested if they have symptoms or are exposed, even after vaccination. One of the initial cases in the most recent Australian outbreak, experienced symptoms for over 10 days before getting tested, mistakenly 1040
believing Covid-19 to no longer be a threat in the country. Hospitals in Taiwan stopped aggressively testing people for Covid, even those with a fever. In February, Taiwan was administering just 0.57 virus tests per 1,000 people in mid-Feb. Contract tracing has largely been a dismal failure in the U.S. and a recent study showed that 2 of 3 individuals with COVID-19 were either not reached for an interview or named no contacts when interviewed. A mean of 0.7 contacts were reached by telephone by public health authorities, and only 0.5 contacts per case were monitored, a lower rate than needed to overcome the estimated global SARS-CoV-2 reproductive number. We witnessed how effective contract tracing and quarantining was in containing and extinguishing Ebola in West Africa in 2014 and 2016. Yet we failed to apply these hard-won lessons in the U.S. Australia did not have a strong contact-tracing system from the outset, they learned the perils of complacency the hard way. A weak contact tracing system was one of the triggers that led to the second wave of Covid-19 cases in Melbourne in August 2020. This surge resulted in a 112-day strict lockdown. However, when restrictions began to ease, contact-tracers had adopted the Japanese practice of backward-tracing contacts for the previous 14 days, and the Vietnamese practice of quarantining first- and second-order contacts. This meant that the majority of cases in a recent outbreak in Melbourne were already in isolation when they tested positive. Public health departments in the U.S. have been underresourced through most of the pandemic to trace the astronomical case numbers. But now, as cases reach a more manageable level, is the perfect time to invest in contact tracing to keep cases at those levels or lower. Yet as previously stated, the virus is constantly evolving and mutating. We need to be tracking these changes so we are prepared to act responsibly. Yet between December 2020 and April 2021, the U.S. has sequenced about 0.3% of individuals testing positive for Covid-19, with wide variation between states. By contrast, the United Kingdom has consistently been sequencing 10% or more. The low rate of sequencing provides an incomplete picture and puts us at risk of missing new variants with more transmissible qualities. We need to dramatically ramp up genomic sequencing efforts and create better coordination between labs across the country. 1041
Finally, one of the most important lessons we can take from this pandemic is to be prepared to act quickly and swiftly for the most effective result. Australia is known to act swiftly based on incoming data whether it be snap lockdowns, being among the first countries to implement drive-through COVID-19 testing clinics in March 2020, or quickly changing policies from home isolation to hotel quarantine, when it was clear some returned travelers were not complying. A new study has highlighted how locking down quickly and responsively in a high-income country like Australia yields significantly better health and economic results than a “wait and see” approach that ends with a delayed lockdown 21 days later or unmitigated spread. A co-author of the study Professor Quentin Grafton compared Australia's lockdown strategy with the early strategy of the UK. "The UK has lost 128,000 lives to COVID-19 and in 2020 suffered its biggest annual decline, 9.9 percent, in GDP in over 300 years. By comparison, Australia's GDP is now higher than it was just before the pandemic and has, to date, suffered less than 1,000 fatalities.” As difficult as it may be, the UK would be wise to delay their planned reopening and lifting of all restrictions as Covid-19 cases have steadily been increasing in recent weeks. Co-author Professor Tom Kompas stated that the study demonstrates “elimination of community spread in Australia is best for both health and economic outcomes. There is no question about this.” The study examines different scenarios. In one model, early mandated suppression in Australia was highly effective at both ‘flattening and shortening’ the curve. The total number of active cases peaks at approximately 4,850 cases, with 100 deaths and 6,650 total cases. With a 21-day delay mandated suppression strategy, the number of active cases peaks at 241,000 and the number of deaths increases to 9,074. In the scenario of unmitigated spread, with no restrictions, the total number of cases is nearly 16 million, with a peak of 5.7 million active cases. Fatalities without control are roughly 260,000. Victoria’s recent lockdown is a perfect example of this policy in action. To many other countries, 23 cases would seem insignificant, but at the time of announcing the lockdown, the Victorian 1042
government knew from contact tracing that the exposure sites were at 150 and counting, some including nightclubs and bars. Naturally, as time passed, those cases increased but all were already isolated, preventing further community transmission. After two weeks, the “circuit breaker” lockdown was lifted, with some public restrictions still in place. It is understandable that many do not want to comprehend the reality that Covid-19 will likely remain endemic. They are weary and fatigued, after immeasurable trauma and over a year of constant risk calculations. But the reality is, even as we celebrate our successes with vaccination, we cannot become complacent. We must take the lessons of other countries and implement them into our public health strategies. The cost of lives and livelihoods will be far too great if we do not. This article originally appeared in Forbes and is available online here: The Perils Of Covid Complacency
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Success And Challenges In Mass Screening For Covid-19 Control: The Andorra Story Forbes | June 10, 2021 | Article
Once again, Andorra is setting a global standard for Covid-19 testing. The small European nation undertook a mass SARS-CoV2 serological screening during its first wave, making it the first and most comprehensive seroprevalence study of its kind in the world, assessing the whole population of a country. This begs the question: is testing enough to help control a pandemic? Andorra is a small country in the Pyrenees that attracts millions of tourists, primarily for skiing and other outdoor activities. It has been severely impacted by the pandemic, as have its neighboring countries, Spain and France. The country has always had rigorous testing programs, among which was a nationwide distribution of rapid antigen tests to all residents over the age of six last December. Yet Andorra is proof that testing is not enough and needs to be followed up with efficient contact tracing and isolation. All of Andorra’s population was invited to participate in the mass screening through television and social media advertisements. Almost 91 percent voluntarily participated in at least one of two cross-sectional serological surveys that were conducted in 59 drivethrough or walk-through checkpoints in Andorra, using a fast serological test on a finger prick blood sample. The screening took place over the span of a little over three weeks in May 2020, with the second survey taking place four days after the end of the first. At the time, the country had been in lockdown since mid-March, with borders being heavily restricted, only allowing essential workers to enter from neighboring countries. Overall seroprevalence was 11%, and was highest in older age groups, as well as seasonal workers and families with larger households. Researchers also recorded a decrease in seroprevalence between the two surveys, which they claim to be largely due to a decrease in antibodies in asymptomatic patients over time, as
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antibody levels decline early after infection and could have been at undetectable levels during the second survey. While the study does have some limitations, such as the fact that the epidemiological situation has drastically changed since the first wave, researchers are confident that the study helped pinpoint infection hotspots and will aid in the development of targeted measures to prevent SARS-CoV-2 spread in Andorra. Andorra has accumulated over 17,000 cases per 100,000 people since the pandemic began. That is more than France and Spain combined, who have reported around 8,500 and 7,900 cases per 100,000 respectively. This does not mean that Andorra performed worse than its neighboring countries when trying to contain the virus, but rather that testing rates were much higher. When looking at the number of SARS-CoV-2 tests performed, Andorra carried out nearly 2,500 tests per 1,000 inhabitants. Comparatively, Spain has not yet reached 1,000 tests per 1,000 people. Andorra was thus left with a much better understanding of its infection rates, and was able to detect asymptomatic cases. The strategy, however, was not successful as a Covid control tool. Andorra’s cumulative death count is very close to that of France and Spain’s, which had much less rigorous testing regimes, with about 164 deaths per 100,000 inhabitants. The amount of information that Andorra has accumulated and hopefully will continue to amass, has put the country in a better position to control future waves if a systematic program is put in place. Testing must be combined with efficient contact tracing and mandatory isolation. Countries that follow this program will not only know how the virus will spread among their population, but will be able to control it. This article originally appeared in Forbes and is available online here: Success And Challenges In Mass Screening For Covid-19 Control: The Andorra Story
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Will COVID-19 Improve Long Term Care? Forbes | June 21, 2021| Article
While much of the world is reopening and life for those vaccinated has returned to a new normal, many nursing home residents are still living under lockdown after lockdown. A single COVID-19 case in a nursing home can trigger a two-week lockdown for all residents— longer if cases have spread—and a return to the isolation that has impacted so many of us throughout the course of last year. Even before the pandemic, there were questions around the quality of care delivered in long term care facilities, but throughout the pandemic the vulnerability of nursing home residents became ever more apparent. When the pandemic hit, all of us were at risk of infection, but nursing home residents were in a uniquely hazardous position. This was partly because of the communal nature of long term care housing, but also because of how closely residents interact with a rotating cast of caregivers and staff, many of whom care for multiple residents in ways that can easily spread disease, like feeding them or brushing their teeth. Though nursing home residents and staff were among those who needed the most protection in the face of the disease, they were often last on the list of those to receive it. Across the US, there were widespread reports of understaffing and a lack of personal protective equipment in nursing homes, two areas of neglect that were later shown to be key drivers of the spread of COVID-19 in long term care facilities. The unfortunate result is seen in the lives of those lost—nearly 31 percent, or roughly one-third, of COVID-19 deaths in the US are linked to nursing homes. In five states alone, the number of deaths of nursing home residents due to COVID-19 accounts for either half or more of all recorded fatalities. While the fatality rate for COVID-19 across the US hovers around two percent, in nursing homes the rate is significantly higher, at ten percent. While a reckoning with our failures over the past year may help us improve
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nursing home care in the years to come, the challenges to delivering higher quality care have only grown. Nursing home costs have skyrocketed due to the pandemic, with many for-profit homes no longer able to keep up. Demands for personal protective equipment and other needed supplies have driven part of the increases in costs, but the real burden is the demand for additional staff to provide better care. Prior to the pandemic, many nursing homes weren’t meeting Medicare’s minimum staffing requirements, which are undoubtedly one of the key factors in determining a nursing home resident’s quality of care. Now, with the failures of the past year, nursing homes have been asked to not only meet these requirements but ensure there are necessary staff on hand to ensure these requirements are met even when a number of staff are out on sick leave or required to quarantine due to exposure to COVID-19. In response, some smaller foundations have provided grants to improve the quality of care delivered to patients in long-term living facilities. The Hartford Foundation, for example, recently released a free COVID-19 Rapid Response Network for nursing homes across the United States. This program offers homes that are certified in Medicare and Medicaid programs the opportunity to participate in a training course with immediate access to specific, pragmatic guidance from federal and state policymakers on clinical and operational issues confronting the nursing home community today. The Rapid Response Network includes a twenty-minute National Nursing Home Huddle twice a week. In these meetings, faculty from select nursing homes, government policymakers, and state regulators explore real-time solutions that can be implemented in nursing homes. Some of these include acquiring funding to increase personal protective equipment supply, improve COVID-19 testing methods, and increase staff capacity in individual facilities. But no matter how well-intentioned, small scale initiatives like the one above can only do so much to solve such a widespread problem. The American Health Care Association and National Center for Assisted Living (AHCA/NCAL) is pushing for an increase in reimbursement rates for nursing home services offered by Medicare and Medicaid. As of 2020, Medicaid remains the primary payer for nursing home care, covering more than sixty percent of all nursing home residents. Medicaid reimbursements, in turn, cover 1047
seventy to eighty percent of the total cost of nursing home care, leaving a large gap in funding. As costs rise due to COVID-19, federal payments are falling short of what nursing homes need to provide a higher quality of care. In result, the AHCA/NCAL is asking that Medicaid increase funding to reflect the increasing costs providers are facing by matching the total cost of care. While Americans wait for changes in the nursing home system, many are choosing to take matters into their own hands and care for their loved ones at home. The pandemic has created an explosion in demand for at-home caregivers, with the workforce expecting to increase by more than a third by 2029. When done correctly, inhome nursing can offer a high quality of life for those in need of care. In a pandemic, in-home care provides better odds for safe visitations with family members and, in caring homes with adequate resources, the most comfort in the final stage of life. Traditionally, in-home care has been highly undervalued in the United States. With COVID-19, however, this care was the only feasible option for families looking after their seniors. One of the few bright lights in the midst of the pandemic is the attention now being paid to the benefits of home care. In a speech delivered to Congress earlier this year, President Biden committed $400 billion for home care. Much of that money is dedicated to developing and expanding the workforce as the demand for caregivers continues to rise. His speech jolted the attention of the public and increased hopes of shining light on in-home care to better provide for our seniors. Perhaps a sign of hope for the future, born out of the tragedy of this past year. This article originally appeared in Forbes and is available online here: Will COVID-19 Improve Long Term Care?
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We Need to Prioritize Mental Health for Healthcare Workers Psychology Today | June 25, 2021| Article
KEY POINTS •
Between 35 and 54 percent of nurses and doctors were already experiencing burnout before the pandemic.
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During the pandemic, healthcare workers had to work with a lack of protective equipment and faced many instances of moral injury on the job.
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Roughly 3 in 10 healthcare workers have weighed leaving their profession. Some fear stigma or losing licensure by seeking mental health care.
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Removing stigma can be a first step toward getting healthcare workers the mental health support they need.
Healthcare workers were already under immense strain prior to the pandemic. A report by the National Academy of Medicine in October 2019 found that between 35 and 54 percent of nurses and doctors experience burnout. Among medical students and residents, the percentage is as high as 60 percent. Burnout can lead to symptoms of depression, substance abuse, and suicide. In the United States, approximately one doctor was dying of suicide every day. According to a 2018 literature review of physician suicide, the suicide rate among physicians is 28 to 40 per 100,000, more than double that in the general population. An analysis by Ohio State University College of Nursing and The American Journal of Critical Care found that a majority of critical-care nurses scored themselves low on physical and mental health status even before the pandemic began. Survey results 1049
collected from August 2018 to August 2019 found 61% of more than 700 critical care nurses rated their physical health a score of five or lower out of a possible 10, while 51% reported their mental health with a score of five or lower. Fear of seeking healthcare Compounding this crisis is the fact that many healthcare workers are discouraged from seeking mental healthcare for fear of risking their medical licensing or malpractice insurance. In one survey, around 1 in 15 surgeons cited recent suicidal thoughts, but more than 60 percent were deterred from seeking out mental health care because of concerns that it might affect their license. Physicians face intense levels of scrutiny when disclosing any form of mental health treatment to state licensing boards. This goes against the recommendation of the American Medical Association. Early treatment of mental health issues is so critical, licensure applications should be amended to remove broad questions regarding mental health history and focus on a clinician’s ability to function. Lack of protection for healthcare workers An ongoing pandemic in which healthcare workers were underresourced, unprotected, overwhelmed, and traumatized by the lack of effective leadership and ambivalence of the public, has only worsened and amplified this already precarious mental health crisis. According to a survey conducted in April 2020, nearly half of participating healthcare workers experienced serious psychiatric symptoms as a result of the COVID-19 pandemic. Two-thirds of participants reported some level of clinical anxiety and nearly a fifth reported moderate to severe depressive symptoms, while 17% met the criteria for posttraumatic stress disorder. A prior history of mental health disorders increased the likelihood of COVID-19-related psychiatric distress, though many without a prior history of mental health disorders also reported experiencing anxiety and depression. When COVID-19 patients first filled our hospitals, we knew so little about how the virus was transmitted, how severe the symptoms could be, or even how to care for patients. Due to inadequate pandemic planning and supply chain issues, there was simply not enough PPE available to keep healthcare workers safe. This created an immediate uncontrollable stressor for doctors and nurses working in hospitals, who were updating their wills and end-of-life directives 1050
while concurrently worrying about infecting their families, loved ones, or roommates. Emergency Physician and asthmatic Brittany Bankhead-Kendall told The New Yorker she felt so vulnerable “Whenever I got coughed on, it felt like a death sentence...every day I thought, this could be the end.” Moral injury In addition to fearing for their own lives, while working long and chaotic shifts. Doctors and nurses were experiencing the traumatizing moral injury of not being able to provide high-quality care and healing to patients through factors they could not control. The lack of effective treatments, ICU beds, and ventilators in the early days of the pandemic meant mass casualties were a frequent occurrence. The ongoing death toll from COVID-19 is astronomical by anyone's standards. So many physicians consider medicine a calling rather than a career path; they push themselves through years of schooling, grueling work hours, and take on significant financial debt, motivated by a desire to help people. Megan Brunson, a night-shift nurse in Dallas echoed these sentiments to The Washington Post. “Most of us got into this to save lives. But when death is blowing around you like a tornado and you can’t make a dent in any of it, it makes you question whether you’re making any difference.” As if these layers of stress and trauma were not enough to cope with, healthcare workers also had to endure the moral trauma of inaction by global leaders and ambivalence by some members of the public towards the virus. In return for risking their lives, U.S. healthcare workers watched former President Trump ignore science and mock others for protecting themselves while wearing masks, stoking the flames of division at a time when unity was essential to save lives. Sharon Griswold, an emergency room doctor in Pennsylvania told The Washington Post, “You feel expendable. You can’t help thinking about how this country sent us to the front lines with none of the equipment needed for the battle.” Doctors and nurses have also felt a deep sense of betrayal and hypocrisy from the public during the pandemic. Public tributes such as the nightly cheering and clapping and hero-worship were juxtaposed with a refusal to wear masks and take other public health precautions. As pandemic isolation fatigue set in and thousands 1051
flouted warnings and traveled over the holiday period, healthcare workers witnessed the tangible impact as hospitals were once more overwhelmed with COVID-19 patients during the winter surge. Healthcare workers leaving the profession The burden of all this trauma will lead to an exodus of healthcare workers. According to a Washington Post-Kaiser Family Foundation poll, roughly 3 in 10 healthcare workers have weighed leaving their profession. Losses to the medical workforce could mean dire consequences for an already strained U.S. healthcare system, as years of training are needed to produce a single doctor or nurse. Many burdened by student loans will not even have the option of quitting but will suffer from festering, unaddressed mental wounds unless urgent action is taken. Medical workers should not feel like their only option to preserve their mental health is quitting. Mental healthcare solutions for medical workers Solutions begin with removing obstacles to accessing mental healthcare resources for medical workers by removing the culture of stigma and shame in workplaces. Lorna Breen, an emergency room doctor in New York, died by suicide in April 2020. In the months since, her sister and brother-in-law, Jennifer and Corey Feist, have strived to prevent further deaths by creating mental health resources for health workers. Corey Feist, who is also the CEO of the University of Virginia Physicians Group, penned an op-ed for Modern Healthcare decrying the neglect of physicians' mental health. “Traditionally, clinicians have dealt with the trauma of their experiences away from the workplace and alone. We saw this in my sister-in-law when Lorna often talked about the importance of maintaining a stiff upper lip ... The old approach of telling clinicians to maintain a stiff upper lip and download meditation apps for stress relief is not the antidote," writes Feist. Jennifer and Corey Feist created a foundation in Dr. Breen’s name and got a bipartisan bill called the Dr. Lorna Breen Health Care Provider Protection Act introduced in the Senate. Some recommendations from the legislation were included in the American Rescue Plan relief bill, including $140 million allotted for medical training, hospital programs, and a mental health awareness campaign. Feist also found through extensive polling that “complex and cumbersome electronic health record systems and other administrative inefficiencies” were also “a chief culprit of burnout." 1052
Physicians report spending on average one to two hours a night inputting patient data instead of resting after a long shift. We should be listening to those in the medical community about what they need to process the ongoing trauma of COVID-19 and to reform the problematic workplace culture that contributed to this mental health crisis. Then we should be swiftly delivering those initiatives with the same priority given to other COVID-19 interventions. This article originally appeared in Psychology Today and is available online here: We Need to Prioritize Mental Health for Healthcare Workers
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How COVID-19 Changes Our Understanding of Mental Health Psychology Today | June 28, 2021| Article
KEY POINTS •
The stress of dealing with COVID-19 has long-term implications for our mental health.
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Burnout, depression, anxiety, PTSD, and other mental health issues are becoming more prevalent.
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It's time to prioritize mental health care and reduce the stigma around getting help.
In the early months of 2020, city after city, country after country, began to lock down; businesses were closed, schools shut down, and public events canceled. As each of us began an undefined quarantine, all of us were asked to drastically change our lives, often isolating us from critical support networks like close family and friends. Regardless of our level of privilege or security, we all took immediate and damaging hits to our psyche. There was so much fear in the unknown; even the experts had limited information on how the virus was transmitted, what the symptoms were, how to treat patients, and what interventions were most effective. Our bodies physically responded to COVID-19 the same way we respond to any immediate threat, like an earthquake or flood: We went into survival mode. This adaptive response is beneficial in the short run, as the sequence of hormonal changes and physiological responses in our bodies prepare us to face the unknown. But though survival mode may be useful in a car accident or a weekend encounter with a bear, it has a wealth of ill effects in a situation where we stay in survival mode for too long. Persistent adrenaline surges damage blood vessels and arteries, increase our blood pressure, and raise the risk of heart attacks and strokes. When 1054
that extra adrenalin and energy isn’t used up in fight or flight, we’re left nervous, jittery, and with a general sense of anxiety that is near impossible to shake. It also leads to insomnia or trouble sleeping, which, in turn, has its own far-reaching impact on our mental health. The effects of COVID-19 on mental health Beyond the clinical impact of the disease, the most immediate effect the pandemic has had on all of us, no matter what our background, is the toll it has taken on our mental health. As the pandemic progressed, we were able to quantify anecdotal evidence of increasing mental health conditions with data. According to the Kaiser Family Foundation, 4 in 10 adults in the U.S. have reported symptoms of anxiety or depressive disorder during the pandemic, a dramatic increase from the 1 in 10 figure reported from January to June 2019. As the pandemic began to impact the economy and the layoffs, furloughs, and pay cuts were rife, many of us were hit with financial stress in addition to anxiety about our health and safety. Research from prior economic downturns shows that job loss is associated with increased depression, anxiety, distress, and low self-esteem. Aside from the financial impact of unemployment, many see their work as a fundamental part of their identity and struggle to find purpose and fulfillment during a time of isolation and few distractions. Even those who have not been impacted financially or have experienced the loss or illness of a loved one have still had their lives disrupted and live with the daily uncertainty that the pandemic brings. In a CDC survey of 5,412 Americans during June 2020, 40.9 percent of respondents reported at least one adverse mental or behavioral health condition, including symptoms of anxiety disorder or depressive disorder (30.9 percent), symptoms of trauma, and stress-related disorder arising from the pandemic (26.3 percent). Of course, different demographics have been affected in different ways by the pandemic. With the closure of schools and offices, parents were left to bear a particularly heavy burden, caring and calming children who had been locked out of their schools, all while struggling to transition to remote work. Single parents who worked on the frontlines had to make unbearable choices, leave younger children home alone or risk unemployment and a lack of income. Even parents who could continue to work while at home with 1055
school-age children and the ones that didn’t work at all felt the pressure—levels of stress, anxiety, and depression among parents are on a steady rise. Health care workers have endured unimaginable moral trauma, risking their lives to care for COVID-19 patients, often without sufficient PPE. In return for their service, they have watched members of the public carelessly violate public health guidelines. For many months, they witnessed inaction by leaders and then tangibly experienced the impact as hospitals filled up with COVID-19 patients, which will undoubtedly contribute to their PTSD. Young adults appear to have been hardest hit by loneliness, anxiety, and depression. A CDC online survey indicates that young people between the ages of 18-24 are more likely to suffer mental health problems during the pandemic than any age group. According to this survey, 63 percent of young people are suffering significant symptoms of anxiety or depression. Nearly a quarter of respondents reported that they had started or increased their abuse of substances, including alcohol, marijuana, and prescription drugs, to cope with their emotions. Many have been robbed of the critical developmental experiences that teenage and young adult brains are wired for. While anxiety and depression have been frequent topics of discussion during the pandemic, less time has been spent analyzing how vulnerable many will be to developing post-traumatic stress disorder as a result of the pandemic. Perhaps this is because we are still deeply immersed in the crisis, that we are unable to anticipate future damage, or that we typically associate PTSD with military combat. COVID-19 has created so many stressors, from strained finances to grieving the death of loved ones to the moral trauma of global leaders mishandling or ignoring the crisis. It is highly likely that an unprecedented amount of people have and will experience PTSD related to the effects of COVID-19. A recent study demonstrated the prevalence of PTSD in 30.2 percent of patients after acute COVID-19 infection, but it is not just the infected who will suffer. Paying attention to mental health However, with every crisis comes opportunity. The pandemic has played an important role in destigmatizing mental health issues, turning a spotlight on the need for more integrated care, where 1056
attention is paid to the physical, mental, and social needs of every patient. Issues like substance abuse and addiction and domestic violence are at the forefront of more conversations. The syndemic of mental health conditions gives governments around the world a mandate to introduce unprecedented and ambitious mental health care policies. We need to be rapidly expanding the mental health care workforce to meet an influx of patients and protect providers against burnout. Concurrently, we need to look for opportunities outside traditional health care settings; we need to be investing in community health programs and start thinking about how to conduct screenings and provide support through schools, workplaces, religious groups, and other community organizations. Finally, we need to acknowledge the mental health impact of economic relief and social support policies; for some, easing financial stressors can be more impactful than therapies like counseling. The psychological scars of COVID-19 will likely outlast the pandemic itself, and as we take steps towards recovery, we must be mindful of the multitude of mental health issues that have or will emerge. But by looking at mental health as the foundation of all health care and prioritizing it accordingly, we can emerge as a healthier society. This article originally appeared in Psychology Today and is available online here: How COVID-19 Changes Our Understanding of Mental Health
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Infection Through “Fleeting Contact” With The Delta Variant Leads To Lockdowns Across Australia Forbes | June 28, 2021| Article
Australia struggles to keep new cases of the Delta variant under control. Sydney and Darwin have both entered lockdown due an outbreak of the Delta variant. Melbourne has come out of lockdown and Queensland and Western Australia have just recorded new local cases. While many are celebrating declining cases rates in the U.S. due to vaccination, other parts of the world are telling a different story. We are no longer dealing with the original Covid-19 virus that first emerged from Wuhan. Instead, we are dealing with a far more deadly virus, better-termed Covid-21. We have not yet seen the worst of this virus as it continues to evolve and adapt to outsmart prior interventions. The previously successful methods used to control the virus in some countries are no longer proving effective. Despite keeping cases close to zero for almost a year, China now finds itself locking down multiple regions to curb ongoing outbreaks. Taiwan is now in a similar position, experiencing its first surge after holding a record for the world’s longest Covid-free streak. More people have died from Covid this year worldwide than in all of 2020. The official global death toll stood at 1,813,188 at the end of 2020 and more than 2 million people have died as a result of Covid so far this year, according to WHO. The increased transmissibility of the Delta variant is a dire concern. In Sydney, Australia, several people were infected in “fleeting” non-physical contact in a cafe and a shopping mall. CCTV footage revealed two people walking past each other while at a mall transmitting the virus. NSW Premier Gladys Berejiklian told reporters in Sydney that "We also need to recognize that this Delta variant... is actually a gold medallist when it comes to jumping from one person to another,". As the cluster of cases grew to 110, Sydney 1058
has entered a two week lockdown to curb further spread of the highly infectious variant amongst a largely unvaccinated population. The city of Darwin has also entered a separate two-day lockdown after a handful of cases were linked to a Delta variant outbreak on a remote mine. Queensland’s chief health officer, Dr. Jeannette Young decided to close the state’s borders to people from Sydney hotspots, telling The Guardian, “with the Delta variant, we’re seeing very fleeting contact leading to transmission. At the start of this pandemic, I spoke about 15 minutes of close contact being a concern. Now it looks like it’s five to 10 seconds that’s a concern. The risk is so much higher now than it was only a year ago.” Several individuals in Australia were also infected with the Kappa variant through lingering virus aerosol particles in the hallway of a quarantine hotel in May. Though the individuals had no direct contact with each other they opened the doors to their hotel rooms within 30 minutes of each other and tested positive for the same strain. The incident led to more than 300 potential sites of exposure and more than 17,000 people potentially exposed to the virus, resulting in the state of Victoria locking down. A similar event occurred earlier in April where two families quarantining in rooms next to one another were found to share the same viral sequence, after briefly opening their doors 30 minutes apart. These instances of transmission through “fleeting non-physical contact” should serve as a warning to the US and the rest of the world. Compared to the Alpha variant, the Delta doubles the risk of a person being hospitalized. An analysis of genomic surveillance data released by the Centers for Disease Control shows that the Delta variant now accounts for 20.6% of America’s Covid cases, up from 9.5% in the previous two-week period. Given the low and fragmented level of genomic surveillance in the US, it’s likely that this percentage is even higher than what is being reported. We are also hearing similar reports of the rapid transmission of the Delta variant around the world and have witnessed how the Delta variant contributed to the most devastating wave of infections in India so far. Ninety percent of newly-detected COVID-19 cases in Moscow are being identified as the Delta variant as the city reported its highest ever death toll. The share of COVID-19 infections identified as the Delta variant of the coronavirus has 1059
doubled in Germany. Africa is facing a devastating resurgence with cases rising for five straight weeks since the beginning of May and a 21% increase this month. 14 African countries have reported cases of Delta variant. In Australia, these cases that emerge from ‘fleeting’ exposure are controlled by vigilant testing, contact tracing, and isolating systems but we have no such protections in the U.S., and vaccination uptake is continuing to stall. As cities across the US are reopening and removing restrictions, we can’t let public health measures like contact tracing and continued testing fall by the wayside also. With only 45% of all Americans (of all ages) fully vaccinated, over half the country is vulnerable to this more lethal variant. Children under 12 are still currently not eligible for vaccination. In some states, only about a third of the population has been fully vaccinated. Globally there are also discrepancies between the efficacy of vaccines in use against the variants. The stalling of vaccination comes even after a slew of vaccine incentives including; lotteries, college scholarships, gift cards, and free beer. The Biden Administration has also offered tax credits to employers that provide paid time off for people to get immunized, erected mass-vaccination sites, sent funds to community health centers, and partnered with local organizations, celebrities, and volunteers to get shots in arms. However, the initiatives have not had the expected impact, with the Biden Administration conceding that they will fail to meet their desired goal of 70% of adults vaccinated by Independence Day. The case rate among the unvaccinated seems to still be hovering at around the same rate as it was in January, when we were seeing upwards of 200,000 new cases a day in the US, demonstrating that the variants are still a powerful force in the US. A recent Covid outbreak at a Florida government building killed two people and hospitalized several others who were unvaccinated. With the rapid rate at which the virus is evolving and the persistence of vaccine hesitancy, it is clear that the “vaccine only” approach will not be the pathway that leads us out of the pandemic. Vaccine breakthrough cases will continue to occur and those with compromised immune systems such as cancer or transplant patients are also not able to experience the full benefits of vaccination. Instead, we should be focusing on a multimodal strategy that utilizes 1060
preventative drugs, treatments, mass testing accompanied by dramatically scaled-up genomic sequencing in conjunction with vaccines. Only then can we create the multiple layers of protection needed to outsmart this ever-evolving virus. The recent investment of $3.2 billion by the Biden Administration, to support the development of antiviral pills, is a wise decision and a great start, yet we need more focus on long-term strategies beyond the vaccines, impressive as they are. This article originally appeared in Forbes and is available online here: Infection Through “Fleeting Contact” With The Delta Variant Leads To Lockdowns Across Australia
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July 2021
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The Delta Dilemma: Loosening Covid-19 Controls At A Time Of Increased Danger Forbes | July 13, 2021 | Article
At a time when the United States and many other countries are beginning to lift restrictions, a new, more dangerous variant of SARS-CoV-2 has appeared that has prompted serious rethinking around what containment strategies should look like moving forward. The Delta variant is not only far more transmissible than its predecessors, but it appears to be more lethal to people of all ages as well. And it doesn’t look like vaccines will be the barrier that stops it. When the Delta variant surged across India in March and April 2021, fomenting the conditions that pushed the country’s Covid-19 death toll past 400,000 (now estimated to be two million), we knew little about how it compared to preceding strains—only that where it went, havoc followed. Today, the Delta variant has spread to more than 100 countries and become the dominant strain in most, including, as of last week, the United States. Not only is the risk of death from Delta twice as high, it is so transmissible that outbreaks in Australia have been traced back to moments of “scarily fleeting” contact. These characteristics don’t just demand caution, but a reevaluation of current public health policy. What we have going for us are the mRNA vaccines. Against Delta’s predecessors they perform almost immaculately, with a twodose regimen preventing nearly all infection, disease, and death in those who received it. But the Delta variant, according to data from Israel (where 80 percent of adults are fully vaccinated), has proven a more challenging immunization target. While the Pfizer vaccine protected 93 percent of immunized Israelis from hospitalization and death, nearly 40 percent were still vulnerable to infection. The British government reported that for symptomatic infection, that rate was about 20 percent. And a recently published study, conducted through May and June in Guangzhou, China, begins to illustrate why. 1063
The study gathered viral samples from 62 Covid-19 patients who were infected during the first Delta outbreak in mainland China and cross-analyzed them with those of 63 individuals infected in 2020 with a prior strain. It focused on two epidemiological parameters that, when it comes to determining infectivity, are particularly telling. The first is viral load, or the amount of virus particles replicating in the respiratory tract. The second is the amount of time that elapses between the moment of exposure to the moment of detection via PCR or antigen test. On both fronts the findings were startling. The viral load of patients infected with the Delta variant was about 1,000 times as high. And on average, it took four days for viral titers in these patients to replicate to detectable levels—a full 48 hours sooner than last year’s strain. Data analyst Tomas Pueyo, who also referenced the Gunagzhou study in his most recent article, compared the R naught (R0) values—a mathematical measure of contagion—of the Delta and original variants. His comparative model, which placed the R0 of the original strain at 2.7 and that of Delta at 6, shows a similarly exponential rise. Evidently the difference in transmissibility isn’t just a matter of percentage points, as was the case with the Alpha variant, but orders of magnitude. The change in viral dynamics is drastic enough to necessitate a corresponding shift in pandemic controls. Only through a rigorous, large-scale testing and tracing program could Chinese health officials obtain data granular enough for the purposes of the Guangzhou study. That same infrastructure allowed them to implement policy changes proportional to the increase in infectivity. When outbreaks intermittently sent Guangzhou into lockdown in 2020, travelers using public transport to leave the city were required to submit negative Covid-19 test results within seven days of their departure. As of June 7, the local government has shortened the time window to just 48 hours—a rapid turnaround, to be sure, but befitting in its urgency. Travelers arriving in China now have to quarantine for three weeks due to increased reports of delayed or long-lasting effects. The policies of most other countries, however, haven’t budged an inch, especially in places where vaccines have gradually displaced other public health measures as the primary containment strategy. In the United States, the genomic sequencing efforts so critical to 1064
tracking and curbing the spread of new variants remain slow and encumbered. Last month the US government committed billions of dollars to antiviral Covid-19 drug development, but none of the treatments to emerge in the past year and a half have proved deployable at scale. And as vaccination rates climb and stall, safety measures like masks and social distancing are falling out of fashion. All this despite the fact that in the United Kingdom, another country where more than half the population is vaccinated, infections are once again on the rise. As incredible as the mRNA vaccines may be, placing too many eggs in the same basket never ends well. Every tool we have at our disposal—testing, tracing, surveillance, cooperation—we must put to work. Every drug or vaccine candidate that shows promise, we must finance and bring to fruition. This multilayered strategy, which I call multimodal therapy, is the only way to seal all the cracks that the Delta variant and its successors will exploit. Ultimately, the success of multimodal therapy depends on the cooperation of scientists, researchers, and vaccine and drug manufacturers around the world. In the face of the Delta variant, no country—no matter the rate of vaccinations or duration of border controls—can possibly remain an island. We have no time to waste before the next more transmissible and even more virulent variant appears. It may already be circulating in the form of the Delta plus or Lambda variants. This article originally appeared in Forbes and is available online here: The Delta Dilemma: Loosening Covid-19 Controls At A Time Of Increased Danger
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An Argument For Covid-19 Booster Shots To Protect The Vulnerable Forbes | July 16, 2021 | Article
On Monday, amid reports that the highly infectious Delta variant is causing surges in new Covid-19 infections in states with low vaccination rates and countries with vaccine shortages, Pfizer announced plans to seek emergency authorization as early as next month for booster shots that would complement its existing twodose regimen and ideally, protect against emergent and future variants of SARS-CoV-2. Almost immediately the drug company’s statement was met with fierce criticism from the World Health Organization (WHO) and equivocation from US health officials. WHO director-general Tedros Adhanom Ghebreyesus said at a press conference that such ventures reflect a conscious choice “not to protect those in need”— referring to countries where the vast majority of the population has yet to receive even one shot—while the CDC and FDA also questioned the timing of the proposal, claiming the evidence that might justify the urgency is lacking. The real issue, however, isn’t whether we should develop boosters or not, but who and what is to blame for the lack of progress in worldwide vaccination efforts. The WHO posits that pharmaceutical giants like Pfizer and wealthy nations like the United States have taken more than their fair share of available resources, creating conditions of scarcity for populations who need them most. However, Tedros’ argument only deflects attention from the glaring reality that low-income countries are in dire need not of more vaccine donations, but more vaccine manufacturing capacity—a root cause that delaying the production of booster shots won’t fix. There is no denying that the disparity in vaccinations between high- and low-income countries is vast. Just six countries, the US and UK among them, have in their possession about 70 percent of the nearly three and a half billion vaccine doses administered to date, while low-income countries have less than one percent. COVAX 1066
(COVID-19 Vaccines Global Access), an initiative co-led by the WHO, Coalition for Epidemic Preparedness Innovations (CEPI), and Gavi, has to some extent helped the haves redistribute their excess doses to the have-nots. But the entire continent of Africa still has less than ten manufacturers to its name that are capable of producing Covid-19 vaccines, while most Asian countries—with the major exception of China—have underinvested in vaccine manufacturing capacity as well. Some attempts to bolster domestic production are underway. According to Ngozi Okonjo-Iweala, Director-General of the World Trade Organization, Africa is set to join forces with the European Union and erect vaccine manufacturing hubs in Senegal, South Africa, Rwanda, and possibly Nigeria. The Institut Pasteur has committed to running the Senagalese manufacturing plant based in Dakar, which will produce an estimated 25 million monthly doses by late 2022. Meanwhile Thailand has begun clinical trials for its own mRNA vaccine, at the same time that Moderna, another mRNA vaccine maker, is considering the possibility of setting up shop in Asian countries like Japan. Inevitably it will take time for these plans to come into fruition. But in the meantime, castigating wealthy nations and pharmaceutical companies for moving forward with booster shots seems misplaced. Further protection in the face of increasingly contagious variants, especially for high-risk populations like older and/or immunocompromised adults, is not a matter of greed or frivolity. For these individuals, just like those who remain unvaccinated, a booster shot could mean the difference between life and death. And so long as the Covid-19 virus, SARS-CoV-2, continues to evolve in ways that promote not just transmissibility but immune evasion, they’re not the only ones who will remain vulnerable. If adults aren’t sufficiently protected, children 12 and under—who don’t yet have their own vaccine—will also be at higher risk of contracting infection and developing severe disease. The general consensus, shared by WHO and US senior officials both, appears to be that until hospitalizations and deaths are on the rise among the vaccinated, it is safe to assume that current vaccines offer adequate protection from disease. But nothing feels safe about the present state of the pandemic in the United States, where
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vaccination rates are stalling, restrictions loosening, and highly infectious variants circulating in several states. In no small part due to inadequate testing and tracing capabilities, epidemiological data on the direct impact of the Delta variant on immunizations is so far scarce, with the exception of case studies like one recently published (and awaiting peer review) on medRxiv about an outdoor, fully vaccinated wedding in Texas that led to six breakthrough infections and one death. Virological research on the variants, however, has established that the SARS-CoV-2 genome encodes several mechanisms that allow it to antagonize, suppress, and evade our immune defenses. Since the surest way for one variant to eclipse its competitors is through increased fitness, we can expect this capacity to only grow in succeeding versions of the virus, as studies that played out such scenarios in the laboratory already suggest. In addition to the latent vulnerability of high-risk groups and children, the emergent condition known as long Covid promises to be a major stressor on already overburdened health systems. Though usually not so grave as to require hospitalization, long Covid afflicts thousands with debilitating symptoms long after the virus should have cleared. Nearly 40 percent of people who recover from Covid19 in the UK still have symptoms twelve weeks after the fact. That the US would want to protect its population from these risks isn’t just expected, but justified. Booster shots and global vaccination efforts more broadly cannot and should not be mutually exclusive. But the duty of the leadership of any country is to protect its people. To truly achieve vaccine equity and end the Covid-19 pandemic once and for all, governments everywhere should honor this commitment. Otherwise the opposing sides of the two-track pandemic are doomed to become ever more divergent. This article originally appeared in Forbes and is available online here: An Argument For Covid-19 Booster Shots To Protect The Vulnerable
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Λ!!: A New Threat On The Rise In South America Forbes | July 16, 2021 | Article
Once again, Covid-19 is on the march around the world. Most infections are due to the Delta variant ravaging the Indian subcontinent in the spring and early summer. A second variant, Lambda, is wreaking similar havoc in South America. The Lambda variant, also known as "C.37," is driving a rapid increase of Covid-19 throughout South America, Central America, and parts of the Caribbean. First detected in Peru as early as August 2020, the variant is now present in over 30 countries and is now the dominant strain in various Latin American countries. Early studies by the University of Chile indicate that the variant confers significant resistance to neutralizing antibodies induced by the inactivated CoronaVac vaccine, one of the major vaccines used in South America. The study showed a 3-fold drop in neutralization against the Lambda variant relative to the wild-type virus, compared to a 2.3-fold drop for the Gamma variant, and a 2-fold drop for the Alpha variant. The effectiveness of the mRNA vaccines the variants has yet to be reported. The Lambda Genome Figure 1 illustrates the nucleotide mutations and related amino acid substitutions or deletions of Lambda versus the canonical Wuhan strain.
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FIGURE 1: Common mutations external to the S protein in the lambda variant genome. Color code: ... [+] ACCESS HEALTH INTERNATIONAL
Beginning at the 5' end of the genome, we note C241U in the 5' untranslated terminal region (5' UTR). The 5' UTR change, as well as NSP12-P323L and S-D614G, are present in all G-clade variants. The G-clade arose in February 2020. It is now the rootstock of most variants of interest or concern. The D614G mutation in the S protein is critical to increased transmissibility. The contributions of the 5' UTR and NSP12 mutations to increased infectivity are speculative. Lambda contains six common mutations in the NSP3 gene, three of which are silent and three that change the protein sequence. NSP3 is a complex seven domain protein essential to the establishment of productive infection. NSP3 contributes to creating the doublemembrane vesicle, which shields the replication-transcription complex from recognition by the innate inane system. NSP3 also encodes deubiquitinase and de-ADP-ribosylation activities. Additionally, NSP3 comprises the pore through which viral genome and mRNA enter the cytoplasm. We note that two of the amino acid changes, P1469S and F1569V, lie in transmembrane domains. The NSP4 protein also participates in the formation of the replication-transcription double-membrane vesicle. Both of the mutations in NSP4, L438P, and T492I, also lie in transmembrane domains. NSP6, the third protein involved in creating the doublemembrane vesicle, likewise contains a three amino acid mutation that alters a transmembrane domain. This observation underscores the relevance of these mutations to the biology of SARS-CoV-2 that one of these changes, L438P, is found in the Iota variant, which arose independently in New York. The contribution of changes in these three proteins is worthy of study to clarify their potential role in increasing the replication competence of the Lambda variant. The S protein of Lambda harbors eight common mutations, one of which is synonymous. Six of the remaining mutations, three in the amino-terminal domain (NTD) and two in the receptor-binding domain, and one in the amino terminus of the S2 protein, are unique to the Lambda variant. (Figure 2). The three NTD mutations likely contribute to escape from neutralizing antibodies, as do mutations in the NTD of other variants. 1070
FIGURE 2: Common mutations to the S protein in the lambda variant genome. Color code: synonymous ... [+] ACCESS HEALTH INTERNATIONAL
The L452Q mutation is the receptor-binding domain that results in the substitution of leucine for glutamine. This is a change from a hydrophobic residue to a hydrophilic and polar one. The effect of this change is likely to be similar to the L452R (leucine to arginine) mutation found in other armed variants, such as the delta variant and the B.1.427 and B.1.429 strains first identified in California. As reported for the L452R mutation, this change likely increases the avidity and decreases neutralizing antibody recognition of the S protein. The S protein also includes the amino acid change F490S. The F490S mutation is unique to Lambda among major variants. However, identical mutations arose in two in vitro experiments. Schreiber et al. searched for mutations that increased the avidity of the S protein for the ACE2 receptor. An independent set of experiments mapped S proteins mutations that contribute to escape from neutralization by convalescent antisera. The F490S change likely contributes to both properties of the Lambda variant. The only mutation of the 3' Orf proteins occurs in Orf9b, P10S. Orf9b plays a central role in the suppression of the innate immune system, inhibiting the mitochondrial antiviral signaling protein (MAVS), the TNF receptor-associated factor 3 (TRAF3), and TRAF6. Over-expression of Orf9b is characteristic of the Alpha variant. The possibility that this mutation increases the activity of Orf9b deserves attention. The nucleocapsid protein (N) contains five mutations, all of which change amino acids. N is a multifunctional protein. The core of the virus particle is an N protein-virus genome complex. Early in infection, the N protein suppresses innate immunity by antagonizing interferon beta, inhibiting cyclin-cyclin-dependent kinase, and inhibiting nonsense-mediated decay. Late in infection, the N protein is reported to contribute to hyper-immune activation. Three of the mutations (P13L, G214C, and T366I) are unique to the Lambda 1071
variant. Many variants of concern and interest (Alpha, Gamma, B.1.1.298, and B.1.1.28.3) harbor mutations identical to R203K and G204K. The contributions of N to the properties of variants are well worth additional investigation. Researchers generally ignore synonymous nucleotide changes when describing the properties of variants. However, a recent study shows that nucleic acid changes in the genome contribute to the success of variants. Thorne et al. describe what appear to be cisacting nucleotide changes that contribute to an astonishing 80 fold increase in the N/orf9b messenger RNA. A complete account of the properties of variants may well require an understanding of the contributions of mutations that affect both protein and non-proteincoding genome variants. The figure below shows an aggregation of mutations throughout the genome found both in Lambda and other variants of interest and concern as described by the World Health Organization (Figure 3).
FIGURE 3: Mutations in the lambda variant genome that appear in other variants of interest and ... [+] ACCESS HEALTH INTERNATIONAL
We are just beginning to understand the full complexity of Covid-19 as a pandemic and as a disease. To understand both, we must understand SARS-CoV-2, the virus that lies the source of our troubles. This is a pathogen that has successfully evolved over millions of years to infect populations much like ours. In order to survive, the virus must infect and reinfect animals with well-honed innate and adaptive immune systems. It is naïve to assume that changes in the spike protein alone account for all the properties of variants that afflict us today. I am convinced that each new variant provides a clue to the virus's success, ones we can exploit as 1072
weaknesses if we only knew enough. Fortunately, we have the tools and the experts that are more than up to the task. This article originally appeared in Forbes and can be read in full here: Λ!!: A New Threat On The Rise In South America
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Keep it local: How America can meet its vaccine challenge The Hill | July 19, 2021 | Article
The COVID-19 pandemic, like many of the greatest challenges facing us today, is a global problem that requires both a coordinated worldwide response and collective and individual action. Vaccines are one of our best tools to fight the spread of disease, a tool developed through a worldwide scientific effort but only useful if delivered and administered to every individual. In America today, less than half of all people are fully vaccinated against COVID-19, not primarily because of lack of access, but rather due to hesitancy around side effects and the newness of the vaccine, along with a belief that, for healthy individuals at least, the vaccines are unnecessary. No outreach program or vaccine incentive will ever be large enough to overcome that central barrier without concrete data and information about the real dangers that exist to each of us. Broad data and advice, delivered by the latest young celebrity or the president or a government expert on late night TV, will do little to move the needle. But local information tailored to each of us in our own communities can and would. I first saw this dynamic at play when I was in my early 20s and I, along with others of my generation, were actively protesting the war in Vietnam. I grew up on a naval weapons base, so when I saw cluster bombs raining down on Vietnamese civilians and soldiers, I knew exactly what they did to a person’s flesh. The danger and suffering was real to me, and I was motivated to act. But for many others, the war was a distant drama, unconnected to their daily lives — until they learned it wasn’t. Many activists like myself spent much of our time traveling to communities where U.S. war efforts were taking place — not in the jungles of Khe Sanh or on the front lines, but in the classrooms, campuses and community buildings where bomb casings and ammunitions were being made and where young recruits were being 1074
educated in the torturous tactics of the war. It’s one thing to watch despair and destruction on the evening news; it’s another entirely to know your school or your community is directly contributing to it. More often than not, once people knew how close the danger was to their own lives and experience, their desire to act escalated exponentially. These same levers of change should be at play today to boost vaccination rates. The government has done a decent job in recent months of gathering data and delivering COVID-19 guidance at the national and state levels (though that has not been without its missteps). But now it’s time to move those messages down to the grassroots, where people live and work. First, we must collate local data more effectively, showing new infections, hospitalizations, deaths and vaccinations in every county, city and small town in America every single day. The CDC is theoretically already tracking this data, but even an expert would struggle to drill through the material to find the information and then to put it into context. Throughout this pandemic, in absence of clear data, local newspapers and media outlets have tried to deliver in the government’s stead. But while an outlet like the New York Times may have the resources to do it well, a small town or community often does not. Public health data from each state is notoriously inconsistent. In one state the total number of vaccines delivered may refer to the total number of doses ever administered; in another it refers to the number of people who’ve received doses. For cases as well, the numbers often differ between newly confirmed infections and the total number of both probable and confirmed cases. More than a year and a half into the pandemic, it should not be so hard for people to understand how many people in their neighborhood have been exposed and infected, and may be putting them at risk. Beyond compiling the data, the onus is on the government to deliver that data through more effective means. Already, the government brings together journalists, national leaders and public health experts to brief them on the latest developments in our national pandemic. They should now be filtering those same briefings down to the community level. Whom do you trust more knocking on your door — a nameless stranger
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with a pamphlet or your doctor or church leader or local community leader? If the White House asked me what more we could do, my answer would be clear: Marshal the data at the most local level possible. Pinpoint the local leaders, be they store owners, fire chiefs, school leaders or mayors. Communicate the data. Convince them of the danger. Persuade them to act. If every doctor’s office, community center and even barbershop had access to daily data on local infections, the spread of disease and the risk to every community, I am convinced that more Americans would not stand helpless in the face of it. This article originally appeared in The Hill and can be found in full here: Keep it local: How America can meet its vaccine challenge
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New Studies Highlight Promising Candidates For Second-Generation Covid-19 Vaccines Forbes | July 20, 2021 | Article
The first generation of Covid-19 vaccines has performed more spectacularly than we ever could have hoped. But as more variants of SARS-CoV-2 emerge that spread faster and hit harder than their predecessors, it has become clear that the mRNA vaccines created by Pfizer and Moderna and adenovirus vaccines of AstraZeneca might not be enough to stem the incoming tide. While distribution of these vaccines should continue full speed ahead, the time is ripe for us to take a step forward and ask, what’s next? Second-generation Covid-19 vaccines will hopefully build upon the accomplishments of their forebears in a number of ways. Of first and foremost concern is their ability to protect against any current and future variants, no matter how infectious or virulent. They should also continue to reduce viral load and elicit high titers of neutralizing antibodies. And perhaps more importantly, if they’re to play a role in redressing vaccine shortages across the globe, secondgeneration vaccines should be cheap and convenient to produce and administer en masse.
S protein trimer with receptor binding domain highlighted
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ROHAN BIR SINGH, MD HTTPS://WWW.NCBI.NLM.NIH.GOV/BOOKS/NBK55477 6/FIGURE/ARTICLE-52171.IMAGE.F3/ Two subunit vaccines, only recently brought to our attention by a pair of just published research papers, are contenders that have shown particular promise in animal models. Unlike vaccines that use live virus to initiate immunization, subunit vaccines—such as those available for hepatitis B and the human papillomavirus (HPV)—are loaded with specific bits of the virus particle, which being only fragments usually require an adjuvant, or booster shot, to amplify the subsequent immune reaction. While other vaccine types can cause complications or adverse effects in people with chronic immunodeficiencies, nearly everyone can withstand the immune response a subunit vaccine triggers—a general level of tolerance suited to epidemics of global proportions.
Receptor binding domain
Both subunit candidates are created using the receptor binding domain, a region of the spike protein of SARS-CoV-2 that facilitates attachment to human cells. The scientists who developed the first coupled a yeast-based vaccine manufacturing platform with the adjuvant 3M-052, a synthetic molecule that activates the immune signaling proteins called toll-like receptors 7 and 8. The results, available to read in Science Immunology magazine, show that in rhesus macaques, the RBD+3M-052-alum vaccine succeeded at stimulating neutralizing antibodies as early as four weeks following a first shot; reducing the number of viral particles that replicate in the 1078
respiratory tract; and lessening the severity of any lung disease. The yeast-expression technology also happens to be easily scalable—ideal, in other words, for large-scale production. For the second subunit vaccine, its corresponding paper published in the journal ACS Infectious Diseases last week, a team of researchers used glycan engineering to create a multimeric derivative of the SARS-CoV-2 receptor-binding domain, then fused it to a trimerization motif taken from a human cartilage matrix protein (hCMP). Administered to mice and guinea pigs in tandem with a squalene-in-water emulsion adjuvant, the hCMP-mRBD vaccine proved highly immunogenic, generating titers of neutralizing antibodies that surpassed those of natural infection (more on this shortly). Some of the best Covid-19 vaccines we already have on hand have one major limitation: they perish if not stored at ultralow temperatures. But this so-called “warm vaccine” is designed to have a high tolerance for heat. According to the study, it remains stable for up to a month at 37 degrees Celsius (98.6 degrees Fahrenheit). From that point of comparison we arrive at another—how the immune responses triggered by the subunit vaccines compare to those of the preceding generation, not just against the original SARS-CoV-2 strain but the new variants that have emerged since. Making a one-to-one comparison is difficult due to differences in experimental design. But examining the fluctuations in antibody titer documented from study to study, we can gather that subunit vaccines might perform as well as our current mRNA vaccines. The antibody titers elicited in monkeys by the first subunit vaccine, RBD+3M-052-alum, reached levels comparable to mRNA vaccines against the Alpha (B.1.1.7) and Beta (B.1.351) variants. Also like mRNA vaccines, the antibody titers generated by the subunit vaccines were more robust than those produced through natural infection. In mice and guinea pigs the second, heat-tolerant subunit vaccine, hCMP-mRBD, generated neutralizing antibody counts higher than those of convalescent sera, both against the original strain and the Beta variant.
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Red dots indicate antibody titers generated by RBD+3M-052-alum subunit vaccine
"A YEAST EXPRESSED RBD-BASED SARS-COV-2 VACCINE FORMULATED WITH 3M-052-ALUM ADJUVANT PROMOTES PROTECTIVE EFFICACY IN NON-HUMAN PRIMATES" HTTPS://IMMUNOLOGY.SCIENCEMAG.ORG/CONTEN T/6/61/EABH3634
On the right: antibody titers generated by hCMP-mRBD vaccine in guinea pigs
"IMMUNOGENICITY AND PROTECTIVE EFFICACY OF A HIGHLY THERMOTOLERANT, TRIMERIC SARSCOV-2 RECEPTOR BINDING DOMAIN DERIVATIVE" HTTPS://PUBS.ACS.ORG/DOI/10.1021/ACSINFECDIS.1C0 0276 1080
Pfizer and Moderna’s mRNA vaccines represent the cream of the current crop—and many low- to middle-income countries have only restricted access to both. Their reserves are stocked with Covid19 vaccines that still possess protective capabilities, but pack a more modest punch, especially against new SARS-CoV-2 variants. According to one study, against the Beta variant, the ability of the Pfizer-BioNTech vaccine to protect from severe illness and death remains at 97 percent. For the AstraZeneca vaccine, according to another study, that percentage is just 10.4. The Delta variant, which now accounts for the lion’s share of new Covid-19 infections in many countries, is even more infectious and lethal than the Beta variant—yet another reason why we need more tools in our arsenal capable of generating vigorous immune protection. We can expect clinical trials for at least one candidate, the heat-tolerant hCMP-mRBD vaccine, to be held later this year. My hope is they arrive at our doorstep before a variant even more infectious than Delta gets there first. This article originally appeared in Forbes and can be found in full here: New Studies Highlight Promising Candidates For Second-Generation Covid-19 Vaccines
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The UK's Dangerous And Deadly Gamble Forbes | July 20, 2021 | Article
The United Kingdom is today engaged in a dangerous and very likely deadly experiment, as it eases nearly all Covid-19 restrictions across the country. Over the weekend the UK counted 54,000 new Covid cases in a single day, near its all time high of early January. Still, as the new Freedom Day policy fell into place at midnight Sunday, Londoners flocked to music venues and clubs, reveling in their newfound liberties in what, to me, appeared nothing short of a dance macabre. Just slightly more than half of the UK population, 54%, are fully vaccinated against Covid-19. Around 70% have received one dose. To think that these numbers are high enough to end restrictions is a tragic error, one that will be paid in lives lost and permanently destroyed by Covid-19. The country to watch is Israel, where around 58% of the population has been fully vaccinated with the top of the line mRNA vaccines. Public health restrictions were eased in Israel in early June, but quickly reimposed when, during an outbreak of the Delta variant, the Israeli Ministry of Health noticed that half of those infected were fully vaccinated. The effectiveness of the vaccines against infection had apparently dropped from 94% to 64% in the face of Delta. The vaccines did still seem to be highly protective against severe disease, at 93% though recent reports suggest that protection may actually be lower. In the UK, restrictions have been eased for a population that is significantly more fragile. Not only are vaccine rates lower than in Israel, the vaccines administered include the Oxford/AstraZeneca vaccine, which is less effective than Pfizer or Moderna against the Delta variant, at just 60% effectiveness for preventing symptomatic disease. Freedom Day is a tragedy for all those in the UK who will no doubt be infected, who will suffer Covid’s long-term effects, and who will die, but it is also a tragedy in the making for the rest of the world, as it creates the ideal environment for a new vaccine-busting variant to emerge. 1082
Think about SARS-CoV-2 as a highly tuned artificial intelligence machine, constantly mutating and adapting until it lands on a combination of mutations that gives the virus the upper hand. A recent study of the B.1.1.7 Alpha variant, less transmissible than Delta, shows how mutations to the SARS-CoV-2 spike protein makes it better able to evade our protective antibodies while mutations in other regions of its genome increase the effectiveness of early immune suppression. Remember, vaccines act more like an alarm rather than a foolproof barrier to infection. The vaccines teach our bodies how to recognize SARS-CoV-2 quickly and summon a rapid immune response to rid the virus from our system. But the virus has already learned how to shut off some of those alarms. That gives it more time to replicate inside us, and with each copy it makes of itself, it has the chance to introduce an error or mutation that may be more capable at overcoming our vaccine induced or natural immunity, creating a variant that even vaccines cannot control. We’ve seen this already with influenza. We have refined our influenza vaccines over decades, but the flu virus, like SARS-CoV2, has learned to adapt. Each year the virus mutates enough to allow it to continue to infect broadly, sicken millions, and kill hundreds of thousands. This is what we face today with Covid-19, except the Covid-19 virus is deadlier and more transmissible than anything seen in recent years with the flu. It has already sickened hundreds of millions and has killed at least four million. In India, Brazil and other parts of Latin America it has shown us already that it can reinfect those who have fallen ill before. The good news is that we are not helpless. With the right approach, we can contain SARS-CoV-2 and return to relatively normal life and economic activity. But it will take sacrifice, and when infections are skyrocketing it will take a return to some of the restrictions that the UK and parts of the United States are so eager to leave behind. Our first line of defense against the virus is still, as of now, our vaccines. But as countries like Australia, China, New Zealand, Singapore, and Taiwan have shown us, widespread testing, exhaustive contact tracing and mandatory isolation could and should make up a solid second second line of defense. Testing, tracing and mandatory isolation can significantly reduce the number of new 1083
infections within a country’s borders, and tight border controls and quarantine can keep the numbers low. Once a new outbreak of infections takes hold, mask wearing, social distancing and lockdowns can quickly contain its scope, giving time for renewed testing, tracing and quarantine efforts to reverse the rise in new cases. Unfortunately both the UK and the US have failed to mount an effective second and third line of defense, which leaves vaccines alone to carry the full burden. It seems as though we are condemned to repeat our sins of the past. In World War One, England learned what it was like to throw a generation of brave young men into a hopeless situation — the flower of the country’s youth no match for the machine guns and automatic weaponry the enemy brought to bear. Now, against this new enemy, it seems the graveyards in the UK will once again be filled with the country’s young, lions led by donkeys to the slaughter. It is my fervent hope their fate will not be ours. This article originally appeared in Forbes magazine and can be read here: The UK's Dangerous And Deadly Gamble
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Potential New Biomarker To Guide Treatment For Severe Covid-19 Forbes | July 21, 2021 | Article
A new wave of Covid-19 cases driven by the delta variant has arrived. Hospitalizations will follow suit. There is an urgent need to discern which patients will need the most support. Those arriving at the hospital with Covid-19 may have significantly varying outcomes and some hospitalized patients will develop serious symptoms. Biomarkers are badly needed that allow hospitals to allocate scarce resources to save the lives of those most likely to die. A recent report from Zheng et al notes the observation of such a marker in severe Covid-19 patients: a small RNA fragment known as microRNA. Although it was originally believed that microRNAs, or miRNAs, were a product of eukaryotic cells, over the past few years studies have suggested that some viruses also produce miRNAs as well, some of which are functional like in H5N1 influenza and Dengue viruses. These miRNAs negatively regulate genes that serve as part of the cell’s innate immune recognition of infection. Some miRNAs produced by cells and viruses can be found in host blood circulation. Presumably, miRNAs circulate packaged in exosomes, which bud from the cell surface. Analyzing the blood samples of 159 patients, Zheng et al. uncovered a total of eight miRNA, five of which were detected in severe patients. Because miRNA precursors usually fold into stemloop hairpin structures, the five candidates were cross-referenced with the SARS-CoV-2 genome. This survey resulted in one miRNA of particular interest. Derived from an 85 nucleotide precursor of the NSP3 gene of the virus, the miRNA, denoted miRnsp3-3p, was conserved among SARS-CoV-2 strains and appeared regularly in severe Covid-19 patients. Figure 1 below denotes the location of NSP3 within the SARS-CoV-2 genome and figure 2 shows the nucleotide sequence of miR-nsp3-3p and its position within the NSP3 protein, which lies in the acidic C-terminal domain. 1085
FIGURE 1: NSP3 WITHIN THE SARS-COV-2 GENOME, HIGHLIGHTED IN RED.ACCESS HEALTH INTERNATIONAL
FIGURE 2: Genomic position and stem-loop structure of the 85 nucleotide precursor of miR-nsp3-3p. ... [+] ZHENG ET AL
The discovery of this miRNA in severe Covid-19 patients was followed by the monitoring of a 20 patient testing cohort. As patients were progressing from moderate to severe Covid-19, miR-nsp3-3p was detected on a consistent basis. The detection of miR-nsp3-3p accurately predicted the severe 7.4 days in advance of symptom appearance with a 97.1% accuracy (Figure 3). To reiterate, the detection of miR-nsp3-3p, which is produced by SARS-CoV-2 early in infection, accurately captures the risk of critical illness over a week before symptom appearance.
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FIGURE 3: The cumulative accuracy rate of miR-nsp3-3p compared to the four others detected in severe ... [+] ZHENG ET AL
Larger studies are needed to confirm this finding, but a result of 97% accuracy is remarkable. Through the surveillance and detection of miR-nsp3-3p, hospitals will have a much stronger understanding of which patients need the most treatment and attention. This will not only serve to save many lives but also will allow the efficient allocation of resources, which are oftentimes limited, particularly in low and middle-income countries. If these results turn out to be reproducible in general, we would do well to propel this biomarking technique to widespread use. This article was originally published in Forbes magazine and can be read here: Potential New Biomarker To Guide Treatment For Severe Covid-19
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Liberté, Egalité, Fraternité, Rationalité: Covid Control French Style Forbes | July 22, 2021 | Article
In the face of a fourth Covid wave, the President of France — a country as tied to the values of personal liberty and freedom as any in the world — made a gutsy move by mandating vaccines for all adults in cafés, restaurants, and many other public gathering places. It is a dizzying about-face for a person who, in November of last year, promised that vaccines would not be compulsory. But as distasteful a turnaround as it may be, it is, in the end, a necessary one. Liberté, egalité, fraternité, rationalité — would that this revolutionary battle cry be heard by us all. This week, the French government begins to debate and test its new plan. The policy, announced earlier this month, requires all adults to show a health pass demonstrating proof of vaccination before entering any shopping center, restaurant, museum or movie theater. The same applies to those hoping to board a train or other public transport to travel domestically. People who refuse vaccination can still be given entry, assuming they show a negative result on a recent Covid test. But these individuals have been warned. PCR tests will no longer be free starting in the fall, unless obtained with a prescription. And, if test results come back positive, people will be required by law to be isolated for a minimum of ten days. Businesses and individuals who refuse to comply are subject to fines into the tens of thousands of euros. While the mandate would be rolled out among those 18 and older at first, the requirements are expected to trickle down to those as young as 12 by the end of next month, coinciding with a new vaccination campaign for high school, secondary school and primary school students in September. Beyond the mandates to the broader public, the government is also proposing mandatory vaccination for all health workers by mid-September, under threat of salary stoppages and, eventually, job termination.
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The new policy goes further than anything yet attempted by any Western country. While a majority of the French seem to agree with the new mandates, the announcement has triggered widespread protests, lawsuits, and endless controversy, forcing the government to soften some of its measures, lessening the amount of some fines and pushing back some of the deadlines. Still, the move has already had an impressive impact on vaccination rates in France. Within 48 hours of the President’s announcement, more than 2.2 million new vaccine appointments had been booked. Meanwhile, here in the US and the UK, masks are dropping, doors are opening, and vaccination appointments remain unbooked. Instead of building a barrier to stop the oncoming surge of new infections, we seem to be opening the door to let the virus in, and creating the conditions for a new vaccine-busting variant to emerge. Our governments could impose restrictions similar to those in France and some organizations have even encouraged it. The nation’s largest hospital group, the American Hospital Association, recently released a statement supporting mandatory vaccinations for all healthcare workers as did seven other medical associations. The idea is also not foreign — we have long required travelers to the US to show proof of vaccination, and we still require all public school students and workers in some fields to be immunized against some diseases. But with Covid, the challenges are greater due in large part to the novelty of the vaccines. In the US, for example, recent surveys have shown that the main barrier to vaccinations today is not lack of access, but fear of side effects and a desire to wait and see how the vaccines affect others first. Some explicitly mention the lack of full FDA approval as a primary cause of concern. If the FDA won’t move beyond Emergency Authorization without longer-term data about safety in particular, why should anyone be convinced that the vaccines are worth the potential risk? Full FDA approval may lessen the hesitancy around vaccination but it would definitely open the door to the possibility of new mandates. Without full FDA approval, the government has its hands tied — they cannot mandate vaccines in schools like they do for other diseases or in their own military, and they certainly can’t require that businesses or colleges do it in their stead. Eliminate this
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barrier, and you have the opportunity to introduce more stringent measures to keep all Americans safe. Whether Americans would accept vaccine mandates may be unlikely, as many have not even accepted the more minor inconvenience of masks. And whether our leaders will have the political fortitude to enforce a mandate is perhaps even more improbable, as they have shown no willingness to do so for masks, testing or quarantines. But it’s possible that the force of this next wave of infections will change the minds of more people. Still, though liberté, egalité, fraternité, rationalité may ring true for the French, I fear that here in America we will follow the more familiar rallying cry: Give me liberty or give me death. This article was originally published in Forbes magazine and can be read here: Liberté, Egalité, Fraternité, Rationalité: Covid Control French Style
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Humanizing Healthcare: A Model For Consumer-Based Care Forbes | July 23, 2021 | Article
Picture a healthcare system where the human approach takes precedence. One where physicians constantly act in the best interest of the consumer and empower their clients to take charge of their own health needs. Where merging electronic health records update coexisting providers daily and one where we combine the beauty of healthcare and social services to create an ongoing network of support. Dr. Summer Knight, paramedic-turned-physician executive and Deloitte Managing Director, explains this improved and compassionate model in her new book Humanizing Healthcare. Here, she insists there is a clear guide to how we can improve the healthcare system to positively impact all parties involved. Over the past year and a half, the COVID-19 pandemic has diminished individuals’ ability to make in-person, human connections with their providers. For many, seeing their regular physician became difficult as the focus was projected onto hospitals and emergencies. Some were even discharged early from these hospitals due to an overflow in COVID-19 inpatients. While the pandemic has left millions distraught and our country at an all time low, there is now an opportunity to improve connections with patients and restore quality management of healthcare systems across the globe. Dr. Summer Knight advocates for providers to use this model now more than ever and provides detailed examples of how we can achieve consumer-based care in a recent interview with my foundation, ACCESS Health International. She insists advances such as artificial intelligence and sophisticated data analytics hold the potential to create an efficient future for healthcare that can restore human connection. Early on in the book, she draws opposition from an intelligence quotient, used by healthcare providers, to an emotional quotient. While the intelligence quotient is important in properly caring for a 1091
client, the emotional quotient is even more critical because it establishes a “therapeutic alliance” between providers and the subject being treated. Dr. Knight defines this therapeutic alliance as “a bond between the healthcare consumer, their healthcare team, and their natural support network based on a mutual sense of caring, core goal toward health optimization, and trust.” She also argues that in order for this strategy to work, these relationships must be scaled across a population which requires digital care activation platforms where humans and machines work together. In strengthening and facilitating a therapeutic alliance between clinicians and consumers, virtual health is an important step on our journey to humanizing healthcare. Digital health is embedded in electronic devices associated with living daily life more so than just caring for sickness. The healthcare industry is continuously preparing for a spike in the virtual health market with an estimate of 3.5 billion in revenue by the end of 2022. Through telehealth, humanizing healthcare comes to life allowing information sharing between physicians, easier access to providers, improved patient evaluation and management, and remote patient monitoring among many others. Virtual health authorizes stakeholders to continue the work they have already started and address critical consumer priorities along the way. Notice that throughout this text, I have refrained from using the word “patient”. This is another important point Dr. Knight makes in Humanizing Healthcare. She makes clear that this term places customers in a submissive and dehumanizing position. Her proposition is that individuals being treated be called “activated consumers” or “clients” instead. This suggests clinicians move away from implying what they will do to or for them, and instead describe what they will do with them as proactive partners. Because modern day activated consumers are ready to take responsibility for their health, these terms are both more respectful and more in touch with putting the client first. By using a therapeutic approach to virtual health, we have the ability to share data and content and create personalized interactions remotely while offering high-quality access to enhance consumerbased care. In a time filled with desperation and hardships amid the COVID-19 pandemic, her message could not be more critical. I urge you to go pick up a copy of this new book and immerse yourself 1092
in her groundbreaking work to create a more sound, client based model business to business. It starts with you, but together we can lead this healthcare revolution to begin using medicine for the better and improve, not the patient but, the consumer’s journey one client at a time. This article was originally published in Forbes magazine and can be read here: Humanizing Healthcare: A Model For Consumer-Based Care
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Overwhelmed U.S. Hospital Systems: A Look Into The Future Forbes | July 26, 2021 | Article
A new study conducted via the U.S. Premier Healthcare Database revealed nearly one in every four COVID-19 deaths may be attributed to hospital strain related to case overload. The results exposed staggering mortality rates suggesting that, despite improvements in COVID-19 survival between March and August 2020, surges in hospital COVID-19 caseload remain detrimental to survival and potentially erode benefits gained from emerging treatments. The lack of preparation from hospitals experiencing high surges and even higher mortality rates is devastating and, furthermore, reveals an opportunity for the United States to take steps forward to prevent this from happening again. Hospitals around the globe have contended with large surges in COVID-19 patients throughout the pandemic. The U.S., in particular, has been met with a rapidly escalating demand due to staff availability and burnout, limited space and supplies, and a decrease in personal protective equipment (PPE) to effectively treat patients. Insufficient intensive care unit (ICU) bed availability and increasing community case burden have also been implicated as risk factors for poor COVID-19 patient outcomes. Prior to the pandemic, hospitals were already met with a shortage of supply, limiting their ability to provide proper care for patients. A study published in April of 2021 suggested that sixty-three percent of intensive care unit (ICU) beds in U.S. hospitals were occupied prior to the pandemic, leaving the health system with approximately 32,000 unoccupied intensive care unit beds at baseline. Now, with the COVID-19 virus spreading exponentially, healthcare systems are left with an even heavier burden and consequences at a much higher cost. The challenge moving forward is to make sure these hospitals are not only properly equipped and staffed in normal times, but also that they have the ability to manage a surge in cases by providing the 1094
necessary staff, personal protective equipment, and beds to deliver quality care in the midst of a national health crisis. If done properly, many COVID-19 deaths may be preventable and public healthcare organizational interventions will minimize the effect of surges on individual patients nationwide. Some counties, however, had already taken these steps leading to the successful prevention and management of surges during the COVID-19 pandemic. Perhaps the most sophisticated of these is China. The Chinese approach included strategies such as proper management of human resources, communication, security, hygiene, and planning. Their hospitals also provided specific COVID-19 training for staff, focused on the well-being of healthcare workers, implemented sophisticated technologies, and involved various government healthcare organizations while handling the first wave of the COVID-19 crisis. E-health, telemedicine, and internet hospital interventions also made healthcare more approachable and affordable for many vulnerable groups across the country. One of China’s most impressive approaches to handling the COVID-19 pandemic included building prefabricated and fully equipped hospitals, in the span of nearly two weeks, to halt the virus from spreading throughout Wuhan and other local districts. The purpose of these facilities was two-fold: to keep infectious patients isolated and to allow routine hospitals to continue caring for other patients. While other countries, such as Japan, were quick to follow this approach, the United States lacked the planning and resources to undergo such a judicious task. In another example, Taiwan implemented a series of procedures to follow in response to surges in their emergency departments. During early stages of the pandemic, their hospital systems designed an indoor infection isolation area for each department, including two negative-pressure isolation rooms and two isolation areas with an independent ventilation system and four beds each. In accordance with incoming surges, however, they advanced their system by adding ten well-ventilated single-room tents at outdoor parking lots immediately outside emergency department entrances. They also transformed an outdoor concrete chemical decontamination area into a radiograph room, personal protective equipment removal corridor, and shower service. High-risk patients with oxygen 1095
demand or critical conditions were transported to indoor infection isolation areas for any resuscitation support. While other countries such as China and Taiwan have added proper preventative measures to ensure bespoke service amid the pandemic, the U.S. is falling significantly behind. The treatment paradigm for COVID-19 is rapidly evolving and hospitals have grown situational awareness, but more lead time for planning and federal and state support must be gained over time. Countries where a substantial portion of the population has been vaccinated show new surges in rapid variants highlighting the continuous need for improved emergency response systems. Although we can learn from other hospital systems, the U.S. certainly has the capability to manage COVID-19 as well or better than any country in the world. A coordinated effort must be implemented across all states to ensure that hospitals have the capacity to deliver high quality care even in the midst of a crisis. Such a systematic rethink also requires long-term planning as COVID-19 will not be the last pandemic this generation of Americans will experience. Plans must consist of fundamental training so that every county is prepared for surge capacity, necessary equipment and instruction provided by state and federal governments, routine audit spot checks to ensure hospitals have supplies on hand to protect healthcare workers and patients, and proper education for local hospital employees to handle distressed systems. Other options for future surges also include building advanced temporary hospitals as seen in China and Japan. These changes will allow for improved care in COVID-19 facilities and normal medical procedures including serious surgeries and elective procedures which should not be interrupted by case surges. Unless we learn from the past, we are doomed to repeat the tragedies of the last year and a half. Altogether, it is time for our hospitals to learn from the best, so that all patients, no matter where they are treated and no matter what current state, are given the best chance medicine can offer. This article was originally published in Forbes magazine and can be read here: Overwhelmed U.S. Hospital Systems: A Look Into The Future
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A Situation Update On Covid-19 Variants And Vaccines Forbes | July 28, 2021 | Article
The article that follows is complex, so I will first and foremost summarize its major points. The fundamental advice I must begin with is that if you’re not vaccinated, get vaccinated, because it will likely prevent your hospitalization or death. Second, that being said, some vaccines are much better than others. The mRNA vaccines have proved to be much better than the rest, including the adenovirus and inactivated whole virus vaccines. Third, all currently approved vaccines wane in efficacy over time, for some populations more than others. Those who are 65 and older, along with others high-risk groups, can anticipate having a level of immune protection that is less robust and sooner to fade. Boosters will very likely be required, first for older adults, then the general population, within six months of their last shot. Lastly, it is very likely that new and even more dangerous viruses than the Delta will emerge, and it’s unclear how well existing vaccines will protect from hospitalization and death from such new variants. All these considerations and more I will elaborate on in the succeeding paragraphs. As we close in on the end of another month with Covid-19, the outlook for the rest of the year is decidedly unclear. Though about a quarter of the world’s population has received at least one dose of a Covid-19 vaccine, in many countries the virus is still circulating at worrisome, if not outright alarming, speeds. Even in countries with high vaccination rates, like the United Kingdom and Israel, new variants of SARS-CoV-2—each, it seems, more infectious than the next—have contributed to sharp increases in new cases, some of which are breakthrough infections. How to explain this paradoxical state of affairs? It depends where you turn for answers. Public Health England published a study in June declaring that two doses of either the Pfizer or AstraZeneca 1097
vaccine were more than 90 percent effective at preventing severe disease and hospitalizations from the Delta variant. But last month, the number of daily new Covid-19 cases in the UK still reached a peak that rivaled the country’s record highs last winter. Even though new infections now appear to be on the decline, in the past week hospitalizations rose more than 30 percent, sending National Health Services executives and health workers into yet another downward spiral. Recent data reported by Israel’s Ministry of Health on July 23 tells a slightly different story about vaccine efficacy against the Delta variant. According to their study, which has yet to be released in full, the Pfizer vaccine is 88 percent effective at preventing hospitalizations and 91 percent effective at preventing critical illness from the Delta variant, but just 39 percent effective against infection—a significant drop from previous estimates of 64 percent effectiveness. The report came as hospital admissions rose more than 50 percent across the country in the span of one week. It is in light of Covid-19 surges not just in Israel and the UK, but across the globe that the topic of immune protection has resurfaced, with new and increasing urgency, in discussions of pandemic control. Research on the mRNA vaccines created by Pfizer and Moderna has repeatedly confirmed that they trigger the most robust immune response against SARS-CoV-2. But how long vaccine-mediated immune protection lasts remains uncertain, especially for their less effectual counterparts: AstraZeneca and Johnson & Johnson’s adenovirus vaccines, China’s Sinopharm vaccine, India’s Covaxin vaccine, and so on.
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Comparison of reductions in efficacy over time based on data from the modeling study "NEUTRALIZING ANTIBODY LEVELS ARE HIGHLY PREDICTIVE OF IMMUNE PROTECTION FROM SYMPTOMATIC SARS-COV-2 INFECTION" HTTPS://WWW.NATURE.COM/ARTICLES/S41591-02101377-8 Not all vaccines, it has become clear, are created equal. In May 2021, a study published in Nature Medicine made this claim based on the aggregated clinical trial results of seven different Covid-19 vaccines. Using predictive modeling techniques to plot the strength and duration of their immune protection over a theoretical timeline of 250 days, the study’s authors showed that some vaccines dropped to 50 percent efficacy much earlier than others. Leading the pack were Pfizer and Moderna’s mRNA vaccines, which performed at 95 percent efficacy initially and took a full 250 days to fall to 50 percent. The AstraZeneca vaccine rounded out the bottom with 62 percent initial efficacy and a half life of 48 days, though the Sinopharm vaccine fared even worse, having just 50 percent efficacy to begin with.
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Relationship between neutralization level and protection from SARS-CoV-2 infection "NEUTRALIZING ANTIBODY LEVELS ARE HIGHLY PREDICTIVE OF IMMUNE PROTECTION FROM SYMPTOMATIC SARS-COV-2 INFECTION" HTTPS://WWW.NATURE.COM/ARTICLES/S41591-02101377-8
The authors of the Nature Medicine study, like many researchers before them, use antibody titers as their selected measurement of immune protection, rather than T cell or memory B cell counts. While all of the above ultimately make inexact correlates of protection, based on vaccine data and previous encounters with viruses like influenza, antibodies are most likely the best we’ve got. And until a standardized immunological assay is created for SARSCoV-2, they’re the best we’re going to get. Early studies of Covid-19 patients established that antibody levels generated by natural infection are quick to fade. Today, studies of vaccinated individuals are beginning to emerge that report similar findings. According to one conducted across the UK in June and published in the Lancet on July 15, antibody levels of adults fully immunized with either the Pfizer (BNT162b2) or AstraZeneca (ChAdOx1 nCoV-19) vaccines dropped significantly over the 1100
course of 70 days. For participants who received two doses of Pfizer, the drop was two-fold; for those who received AstraZeneca, fivefold.
Total antibody counts following second doses of BNT162b2 (Pfizer) and ChAdOx1 nCoV-19 (AstraZeneca) ... [+] "SPIKE-ANTIBODY WANING AFTER SECOND DOSE OF BNT162B2 OR CHADOX1" HTTPS://WWW.THELANCET.COM/JOURNALS/LANCET/ARTICLE/P IIS0140-6736(21)01642-1/FULLTEXT#CORONAVIRUS-LINKBACKHEADER
But just as the strength and duration of immune protection varies from vaccine to vaccine, the Lancet study suggests it varies from individual to individual, too. The supplementary figures below show that antibody levels are generally lower and faster to wane in adults 65 and older. Strikingly, by the end of the 70-day period, the lower limit of antibody levels in older adults who received the AstraZeneca vaccine reached nearly zero. The same was true for individuals categorized as “clinically extremely vulnerable” due to presenting certain comorbidities, like chronic respiratory disease, obesity, diabetes, and specific cancers. In other words, the populations at highest risk of developing severe illness upon infection were ostensibly the least protected.
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Total antibody counts following second doses of BNT162b2 (Pfizer) and ChAdOx1 nCoV-19 (AstraZeneca) ... [+] "SPIKE-ANTIBODY WANING AFTER SECOND DOSE OF BNT162B2 OR CHADOX1" HTTPS://WWW.THELANCET.COM/JOURNALS/LANCET/ARTICLE/P IIS0140-6736(21)01642-1/FULLTEXT#CORONAVIRUS-LINKBACKHEADER
This is to say nothing of the variants. In a virtual presentation for the Zuckerman Institute at Columbia University, infection analytics expert Miles P. Davenport made one more addition to the predictive model I discussed previously—the CUREVAC vaccine. Like the Pfizer and Moderna vaccines, CUREVAC was designed using mRNA, raising expectations of its success. But in phase 3 clinical trials, it demonstrated only 47 percent efficacy. One interpretation 1102
of the lackluster performance is that previously approved vaccine candidates did not have to contend with variants in their respective clinical studies. What will happen if more variants emerge that are even more infectious than what we’re seeing now?
Performance of CUREVAC vaccine "RELATING IN VITRO NEUTRALISATION LEVEL AND PROTECTION IN THE CVNCOV (CUREVAC) TRIAL" HTTPS://WWW.MEDRXIV.ORG/CONTENT/10.1101/2021.06.29.21259 504V1
I cannot stress enough that any Covid-19 vaccine—meaning those deemed safe and effective, of course—is better than no vaccine. And rates of hospitalization and incidence of severe illness are indeed both down from their respective highs last year. But the combination of a fast-evolving virus and, if the antibody counts are to be believed, fast-fading immunity is too inauspicious for my liking. Though the global vaccine rollout remains uneven and inequitable, booster shots—especially for the elderly and other highrisk populations—are inevitable. When booster shots are eventually made available, anyone over the age of 65 or at a similar risk level should seek them out. The rest of us should monitor our antibody counts and take action when we register a significant drop. After all, it is always better to be safe than sorry.
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This article was originally published in Forbes magazine and can be read here: A Situation Update On Covid-19 Variants And Vaccines
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New Hope On The Horizon For Many Women With Breast Cancer Forbes | July 28, 2021 | Article
There is new hope on the horizon for many women with breast cancer. New drugs have been discovered that could treat 10 to 20 percent of women with breast cancer, especially those who have an inherited predisposition to the disease due to defective BRCA1 and BRCA2 genes. For some time we knew that either inherited or spontaneously mutated genes caused cancer. But we’ve also learned that two genes in particular, BRCA1 and BRCA2, play a role in both. Women with a BRCA1 mutation have an estimated 55 to 65 percent chance of developing breast cancer before the age of 70. For women with a BRCA2 mutation, that number is 45 percent. Most of these mutations occur spontaneously, though a smaller fraction—about five to 10 percent—are inherited. Why these genes? BRCA1 and BRCA2 are involved in the repair of double-stranded breaks in DNA, which occur regularly in all cells as they grow and multiply. Ongoing repair is especially important for cancer cells, which grow at a faster rate than healthy ones, and even more so for BRCA deficient cancer cells, which require additional support to survive. Two enzymes, it turns out, can step in to assist with DNA repair if BRCA1 and BRCA2 cannot. One is poly-ADP ribose polymerase, which acts by binding to the site of a double-stranded break and producing a long ADP ribose chain that attracts other DNA repair enzymes. The other is DNA polymerase theta—one of the enzymes that poly-ADP ribose polymerase attracts. In the past 10 to 15 years, researchers have developed drugs that selectively kill cancer cells by inhibiting poly-ADP ribose polymerase. These poly-ADP ribose polymerase inhibitors have been successful in causing remission of both spontaneous and inherited BRCA deficient tumors. The main drawback is that within a year to 18 months, cancer cells can develop resistance to these 1105
drugs, meaning the patients who take them cease to benefit. But according to two recently published research papers, new drugs that target polymerase theta instead might be able to help. First, a bit of backstory. For many years Alan D’Andrea, a cancer researcher and former student of mine, has worked on DNA damage and repair, first as an undergraduate and now as director of both the Susan F. Smith Center for Women's Cancers and Center for DNA Damage and Repair at Dana-Farber Cancer Institute. Some years ago, D’Andrea was studying a rare genetic blood disorder called Fanconi anemia. While conducting research interviews at a summer camp that had pediatric Fanconi anemia patients, he fortuitously encountered a mother and child—an 11year-old girl with Fanconi—who held the key to his next scientific breakthrough. The mother, D’Andrea noticed, had her arm in a sling; she had breast cancer and was recovering from a recent mastectomy, despite being younger than 40. Her husband, on the other hand, was in good health, but his own mother had ovarian cancer. D’Andrea later discovered that both parents were carriers of defective BRCA genes, which led him to speculate that might be linked to their daughter’s disease. This speculation proved correct. Two copies of a damaged BRCA gene causes Fanconi anemia. “I studied this disease with the idea that if we could clone BRCA genes and figure out their pathway,” D’Andrea told me in an interview, “we would learn something fundamental about cancer and the general population.” He was right. In the years that followed D’Andrea began examining other requirements for DNA repair, finding that in addition to poly-ADP ribose polymerase, BRCA detective cancer cells also depended on polymerase theta to retain viability. His work stimulated his colleagues and others to commence an intensive search for potential polymerase theta inhibitors. Two promising candidates have been identified since, one by D’Andrea’s laboratory and another by a research team based mostly in London. Both drugs, used alone or in addition to polyADP ribose polymerase inhibitors, have great potential to treat BRCA defective tumors. Of the thousands of molecules D’Andrea and his team tested that might inhibit polymerase theta, the antibiotic Novobiocin was most effective. The results of their experiments, published in Nature Cancer in June, show that by latching onto the polymerization site directly, 1106
Novobiocin could selectively eliminate cells that were either BRCA deficient or resistant to poly-ADP ribose polymerase inhibitors in both cell lines and animal models. The latter mechanism in particular is incredibly significant. In D’Andrea’s words, “Overcoming PARP [poly-ADP ribose polymerase] inhibitor resistance is what this story is really about.” The other study, which appeared almost simultaneously in Nature Communications, investigates a small molecule drug that does this allosterically instead: ART558. Like Novobiocin, ART558 can be used to selectively damage and kill BRCA1/2 defective cancer cells and combat resistance to poly-ADP ribose polymerase by inhibiting DNA polymerase theta. The study’s authors also suggest that ART558 will augment the benefits of poly-ADP ribose polymerase inhibitors while mitigating their adverse effects. The need for polymerase theta inhibitors is dire, as the correlation between defective BRCA1 and BRCA2 genes and an increased risk of breast cancer is significant. As I mentioned previously, these defects can either appear spontaneously or through inheritance. Of the latter, women of Ashkenazi Jewish descent are at higher risk, in large part due to the loss of genetic diversity that occurs when a population shares only a small number of ancestors— otherwise known as the founder effect. According to the CDC, one in 40 Ashkenazi Jewish women inherit at least one BRCA founder mutation, increasing the chance they will develop breast cancer at an early age. In recent years studies have also linked BRCA1 and BRCA2 mutations to ovarian, prostate, and pancreatic cancers. Given the high stakes, these recent discoveries are worth celebrating. If both drug candidates prove safe and effective in clinical trials, the implications for cancer patients and their loved ones will be vast. According to D’Andrea, using Novobiocin as a polymerase theta inhibitor could reduce up to 50 percent of highgrade ovarian cancers; 10 to 20 percent of breast cancers; 10 to 20 percent of pancreatic cancers; and 10 percent of prostate cancers. Dana-Farber is already launching a Novobiocin trial that will test its effects in cancer patients who are BRCA1/2 deficient and PARP inhibitor resistant. The pharmaceutical company Artios is doing the same for ART558. Watch this space—it could be where history is made.
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This article was originally published in Forbes magazine and can be read here: New Hope On The Horizon For Many Women With Breast Cancer
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Ventilated Classrooms Are Critical To Protecting Our Children Forbes | July 29, 2021 | Article
The death of hundreds of children from Covid-19 in Indonesia in recent weeks should serve as yet another dire warning that children are at risk of severe illness and death from new variants. More than 800 children in Indonesia have died from the virus since the pandemic began, but the large majority of those deaths have occurred in the last month as Indonesia has become the new epicenter of the pandemic. More than 150 children died from Covid-19 during the week of July 12. The Delta variant is largely responsible for rising cases (particularly in unvaccinated populations) across the world including a steep incline in the US. The variant is highly contagious and a recent study from China shows that those infected with the Delta strain can carry up to 1,000 times more virus in their nasal passages. It is in this high-risk environment that we are sending our children back to classrooms, unvaccinated and highly vulnerable. Yet there is one critical action we can take to protect our children as they return to school; well-ventilated indoor spaces. The body of scientific evidence pointing to airborne transmission as the main route by which SARS-CoV-2 spreads is now overwhelming. In outbreaks and super spreader events, there are often three common elements; an indoor space, an absence of masks, and a low level of ventilation. We need to re-evaluate the perspective that the spread of airborne pathogens in indoor spaces (whether they cause the common cold or Covid-19) should be considered to be an inevitable part of daily life. Aerosol scientists and researchers have long advocated for this, but a lack of research into and long-held misunderstandings about airborne transmission of pathogens has contributed to a lack of recognition for this important issue. For decades, governments worldwide have invested heavily in food safety, sanitation, and drinking water quality for public health 1109
purposes. Food and waterborne disease have largely been eliminated in developed countries, due to a combination of research, legislation, the development of authoritative bodies, and infrastructure funding. It is time we give the same priority to achieving clean, pathogenfree air in buildings and indoor public spaces. Many critics of such a policy will cite significant costs as a barrier, However, the economic losses of even an average flu season cost the United States $11.2 billion, primarily due to reductions in productivity and absenteeism. The total cost of the Covid-19 pandemic was estimated at more than $16 trillion, or approximately 90% of the annual gross domestic product of the US in October 2020. As the pandemic rages on these costs will only grow. Beyond the direct financial costs, the trauma and turmoil inflicted by the pandemic make it clear that taking these preventative steps is not only economically sound but also the most ethical option. The goal should be the explicit inclusion of protection against indoor air hazards (including airborne infection control) in the statements of purpose and definitions of all relevant building design and engineering standards, regulations, and codes. Comprehensive ventilation standards must be developed by professional engineering bodies. New approaches must be developed to encourage the implementation of standards, one option is implementing “ventilation certificates” similar to food hygiene certification for restaurants. Over time, all new buildings would ideally be designed to ensure good indoor air quality, while existing buildings will be retrofitted. In a publication for the journal Science, a group of experts including Aerosol Physicist, Lida Morawska argued that the recently published WHO Ventilation Roadmap was “an important step but falls short of recognizing the hazard of airborne respiratory infection transmission and, in turn, the necessity of risk control”. A national fund will also need to be established, to enable the rollout of indoor environment modernization measures addressing both immediate emergencies, such as Covid-19, as well as a longterm transition process. Controlling airborne pathogens does present challenges that controlling food and waterborne disease do not. Air as a contagion medium is nebulous, widespread, not owned by any entity, and uncontained. Furthermore, buildings and their airflows are complicated, and measurement methods for such studies are 1110
complex and not generally standardized. The rate of viral emission also differs depending on the physiology of the respiratory tract, the stage of the disease, and the type of respiratory activity such as speaking, singing, or heavy breathing during exercise. For these reasons, infection-focused ventilation rates must be risk-based rather than absolute. This is not to say every indoor space needs to become a biosafety facility, but a building should be designed and operated according to its purpose and the activities conducted there, so that airborne infection risk is maintained below an acceptable level. Specialized training should also be provided to building operators and owners. With children still not eligible for vaccination, our first priority should be on ensuring pathogen-free air in classrooms and school buildings. All states should be following the lead of Virginia which is investing $500 million to improve ventilation and air quality in public schools. Not only will we be protecting our children from a deadly virus, but there are also positive long-term impacts. Children show improved cognitive performance in better-ventilated areas and they also report fewer instances of illness-related absenteeism. Like many other issues of public health, the Covid-19 pandemic has highlighted the desperate need to prioritize air quality in indoor spaces and the government’s role in regulating this issue. According to the EPA, Americans, on average, spend approximately 90 percent of their time indoors. Just as we expect clean water to come out of the tap and we expect sanitary food preparation, we should also expect to breathe clean air. This article was originally published in Forbes magazine and can be read here: Ventilated Classrooms Are Critical To Protecting Our Children
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What We Need To Know About The Future Of Variants Forbes | July 29, 2021 | Article
For the past year, variants of SARS-CoV-2 have upset our best-laid plans for recovery. As I write, the global spread of the Delta variant has darkened prospects for an early end to the pandemic. Delta outstaged the Alpha variant in recent months, overtaking it as the most prevalent strain in SARS-CoV-2 infections (Figure 1). Virologists disagree on the following question: is Delta as destructive as they come, or is an even more potent variant on the horizon?
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FIGURE 1: A: Rise of B.1.1.7 in England from September 2020 to April 2021. B: Rise of B.1.617 in ... [+] THE ECONOMIST
Some argue that SARS-CoV-2 has a limited repertoire. Others, including me, believe that the virus has a capacity for change that exceeds anything we have seen to date. The optimists focus on recurring independent mutations in the Spike protein as evidence of a limited capacity for change. If that is true, a broadly protective vaccine may be just around the corner. Those less optimistic look to our failure to create a pan-protective influenza vaccine, one requiring annual re-vaccination to keep pace with influenza variants. In time, we will have an answer. Until then, we can only seek to understand SARS-CoV-2 in greater detail, both by an intensive study of the virus itself and by analogy, with what we know from the study of other viruses. I am distressed to report that even now, with all the marvelous tools at our disposal, we know too little to answer the question, but what we do know I find disturbing. A cursory examination of the SARS-CoV-2 variants reveals that there are as many mutations (nucleotide changes) in non-Spike protein areas of the genome as there are in the Spike protein itself (Figure 2). Many of these mutations likely affect the structure and function of viral genes in addition to the Spike protein. Almost all 1113
discussions of variants either ignore or dismiss the potential relevance of these mutations. Given what we know about viral replication and pathological subtleties, this seems to be a serious oversight. The subtle difference between the virulence and vaccine genomes of polio makes the point. The critical difference between a pandemic strain of poliovirus and the live attenuated vaccine, the Sabin vaccine, is a single nucleotide change that does not change a single amino acid!
FIGURE 2: A: Nucleotide changes in the Alpha variant Spike protein. Pink denotes nonsynonymous ... [+] ACCESS HEALTH INTERNATIONAL
A recent paper by Thorne et al. reiterates the warning of impending danger. The researchers found that a mutation in the Alpha variant that changes a single amino acid in the N protein gene results in an 80 fold overexpression of the overlapping gene for the Orf9b messenger RNA. The authors attribute overproduction not 1114
to a significant change in the function of the N protein, but rather to the underlying change in the nucleotide sequence that dramatically increases the relative abundance of the Orf9b messenger RNA. They also speculate that the overproduction of Orf9b protein may increase the transmission and lethality of the Alpha variant. Why? Because the Orf9b protein contributes to suppression of the innate immunity allowing the virus more time to replicate before immune recognition impedes its progress. It is worth noting that another suppressor of innate immunity, Orf6, is also over-expressed by the Alpha variant. Why remains a mystery. Understanding the contributions of mutations to the epidemiology and pathogenesis of the Alpha variant is like looking through glass in the dark. We lack essential information about SARS-CoV-2 to guide us. Similarly, the detailed information regarding the structure and function of HIV that guides our ability to develop new drugs to prevent and treat AIDS infections is lacking. Underinvestment in coronavirus research hampers our ability to predict where and how the next variant may emerge. One remedy is to dramatically increase the budget for fundamental research on coronaviruses, a strategy I successfully championed for HIV in 1985. Another is to search for clues in other better-studied viruses. Here are three examples from the study of three different viruses that illustrate how subtle genomic mutations can have unexpected effects on viral replication and pathogenesis. Example 1. Most influenza vaccines today are dead-virus preparations made from large batches. Vaccinologists discovered that fragments of the virus genome completed with the whole virus dramatically decreasing viral yield. The race was on to understand what favored replication of these fragments over that the whole genome. Scientists were surprised when they tracked the culprit to several single amino acid changes in the viral NS2 gene, which until then believed to function only to shepherd viral RNA out of the nucleus and not play a direct role in genome replication. Example 2. In an attempt to adapt specific strains of hepatitis C to growth in cell culture for research purposes, Chan et al. isolated a strain that replicated to a 1000-fold higher titer in cell culture than its parent. Further analysis revealed that subtle amino acid changes in six viral proteins, including structural and nonstructural proteins, were responsible. The major contribution was from a nonstructural 1115
protein that stabilizes and increases the half-life of the free virus particle by three to four-fold. However, the sum of the individual contributions to increased infectivity was less than that of the ensemble. Example 3. The third example is from another coronavirus, one that causes hepatitis in mice. In seeking to understand the signals required for the production of new copies of the viral genome, researchers introduced a mutation that almost eliminated the ability of the virus to grow. Eventually, strains emerged that grew rapidly despite the deleterious mutation. They then sought to discover how the virus overcame its disadvantage. The answer came as a complete surprise. Mutations in the genes encoding viral proteins, NSP8 and NSP9, were responsible. These two genes are located far from the site of the original mutation. The experiment revealed previously unsuspected roles of these two proteins in virus replication. The lesson for the study of SARS-CoV-2 variants is clear. Research should broaden the focus from studies of the Spike protein alone to include studies of every other protein, both singularly and multiple combinations, both concerning virus replication in tissue culture and organoids, as well as the ability to evade immune recognition. I raise these three examples to illustrate the complexity and subtleties involved in understanding increases in virus transmission and virulence. We should not underestimate our viral foe. Until we know much, much more than we do today of fundamental aspects of coronavirus replication, pathogenesis, and variation, our watchword must be vigilance, not complacency. A virus far more transmissible and dangerous than Delta may be on its way. This article was originally published in Forbes magazine and can be read here: What We Need To Know About The Future Of Variants
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How to End the Pandemic
Project Syndicate | July 29, 2021 | Article
Even with effective vaccines, the coronavirus and its new variants will continue to subject us to successive epidemic waves. Returning to normal life ultimately will require a multi-layered strategy featuring vaccines, prophylactics, public-health measures, and deeper global cooperation. BOSTON – The United States has now entered its fifth wave of COVID-19 infections. In each one, the country has paid a high price for doing far less than it could. In the first wave, lockdowns and other restrictions were spotty. Then came untested and unproven treatments. With the vaccine rollout, new infections were pushed down substantially, but now the Delta variant has started pushing them back up in unvaccinated populations. At each stage, the SARS-CoV-2 virus that causes COVID-19 was underestimated. From what we know of its ability to adapt and thrive through random mutations, there is only one viable option for long-term disease control: a strategy that combines a rapidly growing arsenal of vaccines and antiviral drugs with strong publichealth measures and deeper global cooperation
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Vaccines comprise the first ring of defense against COVID-19. The first generation of vaccines in the US are highly effective, and the second, third, and subsequent generations will be even stronger. But even with booster shots in hand and next-generation vaccines tailored to new variants, vaccination alone is unlikely to end the pandemic. Vaccines won’t work for everybody. In the best-case scenario, against the original wild-type virus, vaccines still fail about 5% of the time. And the Delta variant has proven more adept than previous strains at breaking through vaccine protections. Even if the entire US population was vaccinated, 17.5 million Americans would still be at risk of infection and disease if exposed to the virus. Moreover, there are substantial populations of people with underlying conditions that diminish vaccine efficacy; these include organ-transplant recipients, people taking immunosuppressant drugs, cancer patients, and a fraction of the elderly population. And like the protection offered by the annual influenza vaccine, early evidence suggests that vaccine-induced immunity against COVID-19 may fade over time.
Antiviral drugs and prophylactics will be needed to fill the gaps and provide a second ring of defense. The US government recently committed $3.2 billion to develop antiviral therapies for COVID19. While most of the focus has been on using these drugs as a treatment, their true potential lies in pandemic control, because
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administering prophylactically can prevent people who have been exposed to the virus from becoming ill or passing on an infection. True, the current generation of these drugs cannot be used widely, owing to their high production costs and the need for intravenous infusions in a clinical setting. Nonetheless, we have achieved proof of principle. Ideally, the next generation of antivirals will come in pill form, giving them enormous potential for use in high-risk settings such as long-term care homes, where there are many immunosuppressed individuals who cannot rely on vaccines for protection. The same approach applies to schools, businesses, professional sports teams, and even ships at sea. If one person tests positive for COVID-19, everyone around him could take a pill to help stave off infection.
The next ring of defense will come from public-health measures to contain the spread of the virus. Countries such as Australia, China, New Zealand, Singapore, and Taiwan have made effective use of widespread testing, exhaustive contact tracing, mandatory isolation, tight border controls, and quarantines for new arrivals. Such strategies have been critical methods of protection in the face of nearly every infectious disease in recent history. But in the US and other countries around the world, testing and contact tracing have stalled (or never got off the ground in the first place). Fortunately, new antiviral prophylactic drugs can help make up for some of these failures. As opposed to “test, trace, and quarantine,” the mantra may become “test, trace, and swallow a pill” 1119
– a much more attractive alternative. These drugs also may help open new opportunities for travel, eliminating the need for long quarantines.
The first three rings of protection form an excellent defense. But they will be insufficient unless they are implemented everywhere. To provide the final ring of protection, the international community must work together to improve disease surveillance, and to provide universal access to tests, treatments, and vaccines. Here, the Access to COVID-19 Tools (ACT) Accelerator and its vaccines pillar, COVAX, were an important first step. But the power of the platform has been diminished by self-interest and vaccine nationalism. Still, there is hope for the future now that many high-income countries have a surplus of vaccines. There are also efforts underway to increase local vaccine production in underserved areas. In addition to these efforts, the international community needs to invest in global disease surveillance to identify new outbreaks, especially ones caused by highly infectious variants that can quickly take hold and spread. This requires an enhanced surveillance presence, increased sequencing of the virus across all communities, and a near-real-time method of sharing the data broadly. With the proper frontline mechanisms in place, the global community of scientists, researchers, and pharmaceutical manufacturers will have to determine how vaccines and treatments
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fare against each new variant, and what can be done to mitigate their spread and reduce their likelihood of emerging. Eighteen months into this pandemic, we have what we need to end it. Now, we must apply our knowledge and tools. No single approach will ever be enough. But, together, the four defensive rings – vaccines, antivirals, public-health measures, and international cooperation – can help us eliminate COVID-19 as a life-threatening disease and allow for the dawn of a better life than the one we left behind. This article was originally published in Project Syndicate and can be read here: How to End the Pandemic
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August 2021
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A New Study Documents Efficient COVID-19 Transmission From Infected Children And Adolescents To Household Contacts Forbes | August 4, 2021 | Article
A hotly debated question is how efficient is the transmission of COVID-19 from children and adolescents to household contacts. This question has immediate resonance as we anticipate reopening schools for children of all ages, especially those twelve and under who will be unvaccinated at the start of the school year. A recent study provides an answer to this question: children and adolescents transmit SARS-CoV-2 efficiently to household contacts and some of these contacts require hospitalization. The study, done last year, was completed before the advent of the still more contagious and dangerous Delta variant. The study was published by The New England Journal of Medicine in July of 2021. The SARS-CoV-2 infected children that returned from camp — 88% of whom had symptoms — had 526 household contacts, mainly parents and siblings. Twelve percent of those household contracts that agreed to be tested were infected. Ten percent of those infected required hospital care. The hospital stays ranged from five to eleven days. No one younger than eighteen required hospitalization. While none of the household contacts died, several have underlying medical conditions that put them in danger. Testing was voluntary and participants reported results themselves. For that reason, the secondary attack rates are likely underestimated. Another confounding effect on that study includes a third of the index patients who began to have symptoms while still at camp. These campers may have been less infectious by the time they got home, compared with those whose symptoms started after they returned. While two-thirds of campers adopted social distancing measures upon their return home, transmission was likely reduced throughout the household.
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Children ill from COVID-19 pose a special risk for parents and caregivers. They must try to minimize their exposure and this of other household members, particularly those who might be a risk. Dr. Victoria Chu, a lead researcher involved in the study suggests, “the child should be cared for and monitored using the proper combination of physical distancing, isolation when feasible, and mask use to prevent household transmission as much as possible”. In the absence of clear guidance, most parents do not know what to do to follow this sage advice. A mother of two young grade school children I spoke with summarized the challenge for parents and children alike, “This study sends chills up my spine. With schools reopening this fall and the options for remote learning much more limited than they were last year, this study is a reminder of how risky indoor activities are for our kids and for their families. I can only hope that our government, community leaders, and school administrators will ensure that kids are properly protected with masks, social distancing, and ventilation—all the things that can keep them safe indoors, especially for those who are too young to be vaccinated. Imagine the burden a child would have to bear if they were to bring a life-threatening disease home to their families, from the simple act of going to school or to camp—this year has already taken an unimaginable toll on our kids. We should do everything possible to ease their burden this fall if we can.” The study is an eye-opening look into what the fall could look like with schools reopening and children gathering without proper social distancing measures. With the more infectious and dangerous Delta variant on the rise, it is important, now more than ever, that we limit the spread and vaccinate children over the age of twelve who are eligible. We must also take the steps to mentally prepare children for their return to the classroom by explaining to them the necessary precautions to ensure their family’s safety during a global pandemic. While no mother or father wants to see their child sick, the government and school districts must take steps forward to ensure the safety of our children, while parents must also be educated in doing what is best for their child as COVID-19 is a continuous risk to the nation’s health.
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This article was originally published in Forbes and can be read here:A New Study Documents Efficient COVID-19 Transmission From Infected Children And Adolescents To Household Contacts
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A Warning About The Future Of Covid-19 From The Scientific Advisory Group For Emergencies Of The United Kingdom Forbes | August 4, 2021 | Article
We have watched SARS-CoV-2 develop for 18 months and have some idea of its trajectory. The Delta variant is the prime example of strains succeeding each other, becoming progressively worse in waves of infection. According to a recent report from the Scientific Advisory Group for Emergencies (SAGE) in the United Kingdom, the virus is very likely to evolve into a still more dangerous form. We must be prepared for this outcome, for we are already behind the curve as SARS-CoV-2 is outpacing our response. Intended for reference by Prime Minister Boris Johnson and key public health decision-makers, the report compiled by leading physicians, scientists, and epidemiologists outlines what is known about viral evolution presents scenarios we are likely to encounter in the coming months and years as the Delta variant continues to evolve into something even more dangerous. The report assigns probabilities for each scenario and recommends strategies to limit the damage and control the pandemic. The report outlines four scenarios: Scenario one: The Delta variant mutates to a point of increased lethality. Under this scenario, the virus has the potential to kill between 10 and 35% of people infected, as did SARS-CoV and MERS-CoV, up from the 1 to 2% lethality, characteristic of the current strains. Scenario two: The Delta variant mutates to evade vaccines. Scenario three: The Delta variant mutates to a point of multidrug resistance, challenging antiviral treatments designed to prevent and treat disease. Scenario four: The Delta variant mutates to become less harmful, similar to the four coronaviruses circulating today, such as the common cold. 1126
Before dissecting these scenarios, it is important to recognize the basis of their conclusions. The report is cognizant of the behavioral patterns of viruses and coronaviruses in particular. They can alter their genetic structures by mutation and recombination, leading to substantial changes in fundamental characteristics, including replication rate, transmission efficiency, and pathogenesis. Wisely, the SAGE report considers the entire viral genome in its analysis, not just the potential changes in the Spike (S) protein, as is common in many other discussions on the topic. They note that the efficiency of transmission and evasion from immune surveillance is largely driven by the S protein. However, they also recognize that many other regions of the virus may contribute to both pathogenesis and transmission. In considering how much more transmissible the virus can be, we note a study by Schreiber et al. that indicates that certain S mutations can increase avidity between the ACE2 receptor of the host cell and the virus by 600-fold, creating a far more transmissible variant. The progression from the original Wuhan virus to Alpha and then Delta seems to be following a path of increased avidity, as well as increased immune evasion. So far, the avidity appears to be increased by only four to eight-fold, far from the range that is theoretically possible. In what follows, we provide a detailed summary and analysis of each scenario. Scenario One: Increased Lethality The SAGE report considers the development of strains with increased lethality a realistic possibility. The Delta variant has driven a rise in cases to levels we have not observed in the United States since mid-February, and recent data shows a surge in deaths related to Delta variant infection in the UK, their highest rates since mid-March. The SAGE report highlights the possibility of recombination between two aggressive variants, resulting in a new, substantially more lethal and virulent virus. Specifically, the report highlights the possibility of an alpha and beta variant recombination. Were these variants to recombine, the variant could be comprised of the best of both worlds, forming a variant of dangerous transmission and immune evasion. The report highlights another likely origin of a more pathogenic virus through the current advent of antigenic drift. Orf and structural 1127
proteins are particularly important in the suppression of host immune responses. Orf9b, for example, suppresses innate immunity by targeting mitochondria and the mitochondrial antiviral signaling protein (MAVS), TNF receptor-associated factor 3 (TRAF3), and TRAF6. In the alpha variant, a single amino acid mutation in the latter portion of the genome enabled the virus to replicate Orf9b mRNA to 80-fold greater amounts than in non-alpha variant samples. As the report notes, the “likelihood of genotypic change in internal genes...is high.” So long as infections continue, the virus will continue to mutate to better adapt to its host environment: us. If a single amino acid outside the S protein could enhance an immune suppression function by 80-fold, imagine the evolutionary capacity of dozens of other fine-tuned mutations down the line. Scenario Two: Evading Vaccines The SAGE report considers the possibility that the virus will develop into what I call “vaccine-busting variants” to be an almost certainty. Influenza is an effective model for their concern. In addition to successive antigenic mutations that avoid immune suppression, a coronavirus has the evolutionary capability of antigenic shift, which involves substituting one or more genomic segments from a prevalent strain to an unrelated strain of animal origin. Such antigenic shifts of Influenza have occurred three times over the past century, each time giving rise to a new strain of flu, which evades existing prior immunity. We note that a number of human and other animal retroviruses make use of the same ACE2 receptor as SARS-CoV-2, and given that hundreds of millions of people around the world have been and will be infected with SARS-CoV-2, it is highly likely that such a recombination event could take place. At present, we are witnessing real-time antigenic drift, which could also result in “vaccine-busting variants.” Each variant, as they arise, contains a series of point mutations in the exterior spike protein, which serve to reduce the potency of extant vaccines and monoclonal antibodies. Observations based on the annual recurrence of cold-causing coronaviruses indicate that the virus has nowhere near exhausted its capacity to reduce recognition by antibodies produced by previous infection or vaccine. 1128
Scenario Three: Anti-Viral Drug Resistance The SAGE report considers the possibility that the virus will develop antiviral drug resistance to be likely. The development of potent small-molecule antiviral drugs has been slower than originally anticipated. A problem plaguing the development of antiviral drugs is a long asymptomatic period prior to the onset of symptoms. By the time symptoms typically appear, the concentration of the virus has rapidly dropped in infected people and further treatment by anti-viral drugs yields limited efficacy. There are two strategies to counter. One is much more vigorous, which is the early identification of the infected, contact tracing, and use of antiviral drugs for prophylaxis. That has been a successful approach with monoclonal antibodies. The Regeneron combination monoclonal antibody was recently approved by the United States for preventing infections in nursing homes and other congregate living settings. Resistance to single and, in some cases, multiple monoclonal antibodies is already apparent. Many of the variants can no longer be neutralized by monoclonal antibodies that were produced early in the pandemic. Reports from separate laboratory studies show that single combinations of small molecule drugs also result in rapid adaptation and resistance. The lessons learned from successful treatment and prophylaxis of HIV show that combinations of antiviral drugs are critical for both the prevention and treatment of HIV infections. Combination treatment with two or more drugs dramatically reduces the possibility that the virus would rapidly develop resistance. Currently, there are more than 25 drugs, focusing on at least five or five to six different HIV targets that are used in combination. It is likely that a successful program for chemoprevention and treatment of coronaviruses requires a similar large pharmacopeia to cope with the virus’s propensity for developing resistance. The report urges dramatically increased research on the development of antiviral drugs. The model could be the recent drug, Xofluza, which was developed to prevent household transmission and length of influenza, and has been shown to reduce infection duration by 80% when administered promptly post-exposure to active Influenza infection. Scenario Four: Decreased Virulence 1129
The SAGE report considers the possibility that the virus will develop decreased virulence to be a realistic possibility, only in the long term. It is possible, but by no means certain, that over time the virus could mutate through a form that is highly transmissible but far less lethal. This may have been the case for the four coronaviruses currently in circulation, although there is no hard evidence to support this speculation. The report mentions that it is unlikely that the virus will mutate to become less lethal in the near future. They suggest that if the virus does mutate to a less lethal form, such mutations may occur over a period of many years to many decades. This report is not entirely pessimistic. It offers a number of different approaches; many of these involve additional research and vaccines which may produce better immune responses, capable of protection from many different viruses. The report also calls for major increases in fundamental and applied research of coronaviruses to fill in glaring gaps in our knowledge necessary to create new generations of vaccines and antiviral drugs. Finally, the report mentions that we are not helpless in the face of these viral changes. Human behavior is a driving factor in the spread of the virus. Behavior modifications including mask-wearing, isolation, lockdowns, contact tracing, all combined with vaccines and antiviral drugs—something I am calling “Multimodal Covid Control”— holds a prospect for effective management of the Covid-19 pandemic. This article was originally published in Forbes and can be read here: A Warning About The Future Of Covid-19 From The Scientific Advisory Group For Emergencies Of The United Kingdom
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Opinion: Be careful about covid-19 optimism. There are still plenty of ways for things to go wrong. The Washington Post | August 4, 2021 | Article
William Haseltine is a former Harvard Medical School professor and founder of the university’s cancer and HIV/AIDS research departments. He serves as chair and president of the think tank ACCESS Health International. A curious case of optimism — dangerously unfounded, I fear — has permeated our public discourse on covid-19, even as cases surge. Media outlets, even those that have long highlighted the severity of the pandemic, are now fixated on the hopeful, noting that deaths have not yet surged and that vaccines are working to prevent severe disease. These are welcome facts indeed. But our enthusiasm for what is going right is limiting our ability to appreciate how badly things can still go wrong. A new report from Britain’s Scientific Advisory Group for Emergencies (SAGE) warns there is no end too bad with this virus. It is a remarkable shape-shifter, able to mutate every nucleotide of its genome hundreds of times over in every infected person. Given this evidence, the study warns that the emergence of new variants that can evade vaccines and that may be as lethal as Middle East respiratory syndrome, killing more than 3 of 10 infected, is not just theoretically conceivable but a “realistic possibility.” The study also suggests that the widespread deployment of vaccines has created new selection pressures that could increase the transmission advantage of a variant. Think of the virus as a highly tuned artificial intelligence machine, constantly mutating and adapting until it lands on a combination of mutations that gives it the upper hand. The fear is that when more people have vaccineacquired immunity, the virus has more opportunities to adapt. This is in no way an argument against vaccination; we need immunity 1131
now to blunt the virus’s effects. But it is a warning that a single global round of vaccinations is unlikely to contain this virus forever. The study argues the countdown has started on the emergence of a vaccine-busting variant. I, like most people I imagine, would prefer to ignore the SAGE study and other warnings like it. But the paper reminds us that everything is a moving picture, and whatever comfort we feel today may only be short-lived. We must prepare for and try to prevent the worst of what could come. The SAGE experts provide some recommendations, which I fully support. First, they call for increased research on vaccines that can not only reduce the likelihood of severe disease but also the likelihood of infection and onward transmission of the virus. This is especially urgent given the recent data from the Centers for Disease Control and Prevention on breakthrough infections among those vaccinated. I would also stress the need for research on pancoronavirus vaccines that are capable of defending against a broader spectrum of coronaviruses and covid-19 variants. The SAGE study authors also recommend enhanced vaccination efforts worldwide to drive down the global viral load and reduce the likelihood of variants emerging from other parts of the world. To this I would add other known strategies to drive down viral load beyond vaccinations, including mask-wearing, social distancing, widespread rapid testing, contact tracing and mandatory quarantine. And, when necessary, targeted lockdowns to contain the scope of new outbreaks and the spread of new variants. The use of antiviral drugs to treat those who fall ill and prevent the further spread of disease is also addressed in the study, though the authors urge caution regarding the potential for drug resistance and the use of antivirals in immunocompromised people, which may eventually lead to new, more dominant variants. From my own experience working on HIV treatments, I second these notes of caution while reinforcing how critical combination drug therapies could be to reducing the scope of the pandemic if used to prevent illness. The same warp speed effort we put behind vaccines should be powering our search for safe and effective antiviral cocktails and combination therapies in pill form. None of these strategies will be enough to counter this virus on their own. To protect ourselves from the worst of what it has to 1132
offer, we must use a multimodal strategy that combines the best of what we have on hand. This includes antivirals, vaccines and public health strategies, for sure, but also long-term, global strategies on genomic surveillance, research on the potential evolution of this virus and others like it, and an unwavering focus on developing second- and third-generation vaccines and treatments. Beyond this, we need to accept that, whether we like it or not, we live in a world full of viruses. We can’t eliminate all viral threats, but we can build a culture of care that can help protect us from many diseases. In the same way we walk through a forest with an eye to the ground for poison ivy, so too should we walk through our days: aware of the risk of, for example, a public transit commute and adopting mitigative strategies. Hope and optimism can be powerful motivators. Today, these forces compel us toward greater vaccination rates. But hope, we must remember, was also the last evil left in Pandora’s box. This virus is a mighty opponent, and we have underestimated it at every step. Hope that we are winning the battle today may prolong the war tomorrow as we pull down our masks, relax our defenses and open up new avenues for attack. This article was originally published in The Washington Post and can be read here: Opinion: Be careful about covid-19 optimism. There are still plenty of ways for things to go wrong.
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Healing Ruptured Eardrums With A New 3-D Printed Graft Forbes | August 9, 2021 | Article
With over 200,000 cases a year, ruptured eardrums due to traumatic injury and patients with chronic ear infections are a common illness among many. Following the Boston Marathon bombing in 2013, however, there was a rush of cases that emphasized the need for improvement in standard surgical techniques. As a result of the extensive damage inflicted by the shockwave, the ruptured eardrums of most patients were beyond self repair and a tympanoplasty, originating in the 1950s, was no longer the most efficient treatment thought to date. During a tympanoplasty, the ruptured eardrum is commonly patched with a graft of the patient’s tissue, either a connective tissue called fascia or the tragus. The surgeon slips the new tissue behind or on top of the hole in the eardrum. To hold the tissue in place, a tiny wad of material is packed behind the ruptured area. The procedure is done with a microscope in an operating room, though more recently endoscopes have allowed for less invasive procedures. While the current treatment is often successful, no tissue can conduct sound in the eardrum quite like the eardrum tissue itself. This is where regenerative medicine comes into play- the process of using a patient’s own cells to restore the human body whether injured by trauma, damaged by disease, or worn by time. Recently, researchers contacted biomedical engineers from the Wyss Institute, Nicole Black and Jennifer Lewis, to work on a new graft which they later named the “PhonoGraft”. Soon thereafter, the 3D-printing company Desktop Health acquired the small synthetic device as they saw its potential to replace tympanoplasties, a much more complex and less advanced treatment. The Phonograft, having been worked on for a total of six years, was identified via biodegradable materials which work within the ear and leaves behind a healed eardrum that ideally works as well as it did before it ruptured. This material can be 3D-printed and cut into custom sizes 1134
and shapes at the time of surgery, making it adaptable to perforations of various sizes and locations to best suit a patient’s needs. Because the Phonograft is biodegradable, it decreases the risk for ear infections and serves as a medium for the eardrum itself to grow back rather than relying on donor tissue. The Phonograft is also made from a completely synthetic material, making it relatively cheap to produce and easier to transport than a device that uses biological materials like proteins or cells. Moving forward, this treatment is designed to transform repair of a ruptured eardrum from one requiring general anesthesia to one using local anesthesia, and it could shorten current tympanoplasty procedures from around 150 minutes to 20 minutes of a surgeon’s time, along with eight hours of outpatient care to a single hour. For decades, regenerative medicine has enhanced medical treatments and brought the most innovative procedures to life. Regenerative medicine rehabilitates the body and restores it to its original function. Treatments such as tissue regeneration, organ transplant, and advanced stem cell research have broadened the scope of this $156 billion global industry. These processes reinstate hope in patients where there is very little light at the end of the tunnel. Now, with the new Phonograft, regenerative medicine is doing just that by conquering one of the most common diseases and traumatic injuries. Using this material to heal a ruptured eardrum is just the beginning, researchers say. Micheal Jafar, President and CEO of Desktop Health said, “I immediately thought of at least five — we know that would potentially be 10 — use cases beyond just the eardrum … the synthetic material and the way it was tooling was very interesting to me, I’ll bet we’ll learn a lot about what this property can do in the body beyond just the eardrum.” With regenerative medicine, there is hope for new procedures such as the Phonograft to advance less efficient and more time-consuming treatments. Together, let us educate ourselves on these topics so we can continue to advance medical innovations and provide the best possible care for our family and friends. This article was originally published in Forbes and can be read here: Healing Ruptured Eardrums With A New 3-D Printed Graft
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How Peer Counseling Can Address Barriers to Student Mental Health Forbes | August 9, 2021 | Article
When Dr. Sarah Lipson, a Boston University Professor and Associate Director of the Healthy Minds Network, worked in higher education as residential life staff, she soon found that mental health problems on college campuses were more prevalent than commonly thought. “Mental health was the biggest barrier to students thriving in college, both academically and socially.” While her introduction to the student mental health epidemic occurred over 15 years ago, mental health issues on college campuses have continued to grow, exacerbating college resources, and have led to a dangerous treatment gap which has only been amplified by the pandemic. Colleges have attempted to address this treatment gap in past years; however, one solution that is often overlooked takes the form of peer counseling Peer counselors are non-professionals who are trained in active listening and in guiding their peers through emotions without offering specific advice. The goal of peer counseling programs is not to treat symptoms or crises, but to provide a necessary form of community support and intermediate care that could prevent further escalation of poor mental health. Although the practicality of nonprofessional mental health resources has prompted skepticism, studies suggest that preventative resources such as peer counseling may be an important aspect of campus mental health support systems. According to Dr. Lipson’s research through the Healthy Minds Network, “About half of students appear to be struggling to some degree, with their mental health.” Despite this, less than 50% of those students struggling actually sought support from counseling resources. Although studies have consistently demonstrated a huge increase in the number of students suffering from mental illnesses, according to data collected by the Association of University and College Counseling Center Directors (AUCCCD), the percentage of students served by counseling services has largely remained the 1136
same. Dr. Lipson has seen that this especially affects certain demographics, “On a population level, on average, first-generation, low-income and students of color have lower rates of accessing treatment.” In response, colleges have been pouring greater resources into hiring new counseling staff, but from the above statistics it is evident that students have been encountering significant barriers to accessing mental health support Lack of available staff, costs, and stigma are three of the main barriers encountered. Despite increased staffing, counseling sessions remain difficult to secure. According to the AUCCCD, a student can only obtain an appointment after an average wait time of about six days. While a week’s wait may seem standard, for students in mental health crises long wait periods can be deadly— suicide is still the second most common cause of death in college student age groups. Additionally, free counseling sessions are often limited. At Indiana University, students are only allotted two free counseling sessions each semester before having to pay $35 per visit. Stigma surrounding mental illness and seeking psychological support has also remained a large barrier to students accessing care. A study on the relationship between perceived stigma and the inclination to seek mental health support found that perceived stigma especially affects certain minority populations as well as men, causing them to seek resources at much lower rates than other demographics. By utilizing students as a resource for preventative care, colleges can begin to lessen the burden of clients in their counseling centers. Peer counseling also provides a mental health support system to students that is free of cost and that contains a greater diversity of counselors whose common experiences may help to reduce the perceived stigma of mental health care. Dr. Lipson supports a preventative approach to mental healthcare, “It’s not as if every student who has a positive screen for depression or anxiety necessarily needs intensive one on one therapy… there is a need to have resources and services that meet students all the way across the continuum of mental health.” Active Minds is one example of a successful peer-based outreach program that has implemented chapters on more than 800 campuses. Through the organization, student leaders hold mental health awareness campaigns and outreach events to college students in hopes of reducing stigma across campus. For Maddie Paoletti, the 1137
President of Active Minds at Wellesley College, the value of peerbased mental health resources has become apparent on her campus, “Peer health education groups are able to key into the areas that more established institutions like professional counseling resources can’t reach… Peers just understand each other better than we would adults.” Research has shown that the presence of mental health outreach entities such as Active Minds is associated with increased knowledge of mental health issues and decreased stigma on campuses over time. While research on peer counseling in college education settings is still limited, a number of studies suggest that peer counseling methods have been linked to decreased hospitalizations, increased social functioning, increased quality of life and decreased self-stigma in adults. In establishing peer counseling programs institutions must be wary of the potential liabilities of placing students in roles where they risk encountering people in mental health crises. Programs must be implemented in a way that protects both peer counselors and students who are seeking help. While this might be done by investing in adequate training and supervision, colleges and universities must also conduct further research to determine how peer counseling programs can be implemented safely and effectively on their own campuses Poor mental health has run rampant through our college campuses for too long. As counseling centers remain underresourced, peer counseling offers a beacon of hope for students and counseling professionals who have struggled with the overwhelming demand for greater mental health resources in the past decade. It is time for college administrations and counseling centers to hear their students and address the need for diversified support systems that are accessible, effective, and can help put an end to this epidemic. This article was originally published in Forbes and can be read here: How Peer Counseling Can Address Barriers to Student Mental Health
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It Is Time To Pay Close Attention To The Lambda Variant Now Devastating South America Forbes | August 10, 2021 | Article
Rise of Lambda variant in Peru NEWS.MEDICAL.NET
It is time to pay more attention to the Lambda variant of SARSCoV-2. As the Delta variant ravages communities in Asia, Europe, and the United States, another variant of interest, Lambda, is spreading rapidly throughout South America. The Lambda variant, or C.37, was first identified in Peru as early as August 2020. Initially, Lambda infections were relatively rare. However, in recent months Lambda has become the dominant variant in Argentina, Brazil, Chile, and Colombia. Lambda has been identified in most US States, though the strain has yet to gain traction. Lambda now accounts for less than one percent of all infections but given its trajectory in Latin America, it is well worth watching closely. Understanding the Lambda variant’s mutations and how they correspond to virological features like transmissibility, virulence, immune escape, and pathogenesis may help us prepare for its eventual spread. We have previously described the mutations of the Lambda variant in some detail outlining the reasons for our concern. 1139
A recent study by Kimura et al. examines the Lambda Spike (S) protein, commenting on certain mutations’ virological effects, specifically T76I, L452Q, and a 7-amino-acid deletion from positions 246 to 253. To assess the contribution of each mutation in the S protein to infectivity, Kimura et al. introduced the mutations singularly and in combination. One of the amino acid changes, G75V, in reduced infectivity. On the contrary, they found that when paining G75V with T76I, the latter compensates for the decrease attributable to G75V alone. (Figure 1).
FIGURE 1: Percentages of infectivity compared to the virus pseudotyped with parental S D614G. KIMURA ET AL
A similar effect was noted for the combination of L452Q and F490S. While F490S posted a slight decrease in infectivity, combination with L452Q enhanced infectivity. The researchers conclude that the T76I and L452Q mutations are largely responsible for the significantly higher infectivity of the Lambda variant. While direct comparisons of Lambda and Delta are yet to be widely available, epidemiology suggests that Lambda is far more transmissible than the D614G variant which drove the second wave, and potentially the Alpha variant which drove the third. Next, the researchers tested mutations against the Pfizer mRNA vaccine. As shown in the figure below, the seven-amino-acid deletion from positions 246-253, L452Q, and F490S all convey contribute to neutralization escape (Figure 2). Notably, L452Q and 1140
F490S individually escape neutralization between 1.22 and 1.38 times more effectively, whereas in tandem, the combination escapes 1.62 times more effectively. The only Lambda mutation the abrogates neutralization by a monoclonal antibody (4A8) here specific to the N terminal domain is the 246-253 mutation that lies entirely within that domain (Figure 3).
FIGURE 2: Neutralization assay performed using the pseudoviruses featuring individual and ... [+] KIMURA ET AL
FIGURE 3: Antiviral effect of an NTD-targeting 603 NAb clone 4A8. KIMURA ET AL
Figure 4 below is an elegant summary of the contribution of each of the Lambda spike protein mutations to infectivity and neutralization by Pfizer vaccine-derived antibodies and NAb clone 4A8.
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FIGURE 4: Graphical abstract of the findings in Kimura et al. Projected on the S protein are the ... [+] KIMURA ET AL
Kimura et al. is a valuable contribution to understanding some of the dangers posed by Lambda. Exclusive analysis of the S protein is unlikely to discuss the full potential of the Lambda variant. Lambda differs by 23 nucleotide changes and 18 amino acid changes from the original Wuhan strain. 16 nucleotide mutations and 11 amino acid mutations lie outside the S gene that encodes the spike protein (Figure 5). The effect of any of these changes may be mitigated by changes in the ability of Lambda to enhance replication and improve down-regulation of the innate and adaptive immune response early in infection. Such changes are unlikely to be apparent in tissue culture.
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FIGURE 5: Common mutations external to the S protein in the lambda variant genome. Color code: ... [+] ACCESS HEALTH INTERNATIONAL
Dr. Gregory Poland of the Vaccine Research Group at the Mayo Clinic notes that “any time a variant is identified and demonstrates the capacity to rapidly spread in a population, you have to be concerned.” The epidemiology of Covid-19 in South America tells us what we can expect if Lambda, in addition to Delta, gains wide circulation in the US. We are forewarned to prepare for a double onslaught. This was originally published in Forbes and can be read online here: It Is Time To Pay Close Attention To The Lambda Variant Now Devastating South America
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We Must Support The Children Orphaned By Covid-19 Forbes | August 10, 2021 | Article
Much of the focus of Covid-19 has been on the astronomical death toll and case numbers, yet this fixation neglects to consider the impact on those left behind by loved ones. A recent study in The Lancet estimates that globally 1,134 000 children experienced the death of primary caregivers, including at least one parent or custodial grandparent, and 1,562 000 children experienced the death of at least one primary or secondary caregiver. Between two and five times more children had deceased fathers than deceased mothers. The study used mathematical modeling and mortality and fertility data from 21 countries with 76 percent of global deaths from Covid-19 to estimate the number of children who lost a caregiver. These countries included Argentina, Brazil, Colombia, England and Wales, France, Germany, India, Iran, Italy, Kenya, Malawi, Mexico, Nigeria, Peru, Philippines, Poland, Russian Federation, South Africa, Spain, United States, and Zimbabwe. The countries with the highest numbers of children who lost primary caregivers (parents or custodial grandparents) included South Africa, Peru, United States, India, Brazil, and Mexico. The scale of family loss from Covid-19 has not been seen since AIDS first rampaged through sub-Saharan Africa. As global vaccine disparities widen, lower-income and underresourced countries will begin to shoulder a greater burden of caregiver deaths associated with Covid-19. In reality, the number of children who have lost parents is probably far greater than the study estimates due to international coronavirus testing and reporting gaps. In the US, the CDC only records deaths from Covid-19 and not the survivors left behind. We need to establish domestic and global institutions to collect this data and allocate resources to provide evidence-based psychosocial and economic support to children who have lost a caregiver. After 9/11, the federal government orchestrated a significant effort to support the families who lost loved ones. Almost 20 years 1144
later, those families are still receiving support; why can we not orchestrate a similar effort for children who have lost a caregiver from Covid-19. With a study from JAMA Pediatrics, estimating more than 40,000 children in the United States have lost a parent to Covid-19, such a program should be a priority in our pandemic recovery. When a child loses a parent or caregiver, they are not just affected emotionally but also lose financial support and become at greater risk of dropping out of school, developing anxiety, depression, alcohol, and other substance abuse issues. These impacts could be compounded by the circumstances and stressors of the pandemic. The authors of the JAMA Pediatrics study highlight that “Covid-19 losses are occurring at a time of social isolation, institutional strain, and economic hardship, potentially leaving bereaved children without the supports they need.” There are also racial disparities involved in the loss of a parent or caregiver. By age 20, a Black child is twice as likely to experience the death of a mother and 50 percent more likely to experience the death of a father. Support for a grieving child can take several forms, including individual counseling and camps or group programs. The National Alliance for Grieving Children provides resources and a regional directory for helping children deal with loss. But we must not overlook access to financial and material support either, less than 50 percent of children who experience the loss of a parent are estimated to receive Social Security survivors’ benefits which they may be entitled to. The timing of providing this aid is crucial, according to psychologist Dr. Kathryn Cullen who wrote in a 2018 editorial in The American Journal of Psychiatry that “the first two years after losing a parent is a period of critical risk for developing depression.” We must not continue to overlook this vulnerable population and begin building programs to support them. This article was originally published in Forbes, and can be read online here: We Must Support The Children Orphaned By Covid-19
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The Delta Variant: A Guide To Evaluating Personal Risk Forbes | August 10, 2021 | Article
As the Delta variant spreads rapidly across the United States, fueling Covid-19-related hospitalizations in regions with low vaccination rates, Americans remain unsure of the effect this highly infectious mutant will have on their lives. While vaccines reportedly prevent critical illness and death in those who received them, stories of deadly breakthrough infections in individuals of all ages are causing a stir, leading some to speculate that vaccine-mediated immune protection might not be as strong or last as long as previously hoped. To be clear, any protection is better than no protection, so mass immunizations should and must continue. But the growing dominance of Delta, which is significantly more contagious than previous strains of SARS-CoV-2, does demand we reconsider our current approach to situational awareness and safety. These adjustments required needn’t be undertaken in panic or confusion. The onus to reinstate basic safety measures remains on government and health officials, but individuals can take steps on their own to determine their personal risk level and act accordingly. The question on the minds of many is simple: if I’m vaccinated, am I still protected? But the answer is much more complicated. Even the best of the current generation of Covid-19 vaccines, the mRNA vaccines created by Pfizer and Moderna, don’t erect an impenetrable barrier between the body and the virus. Instead they trigger an immune response that teaches the body to recognize and neutralize the virus on sight. If the virus mutates beyond immune recognition, then the vaccine loses all or most of its potency, hence the recently popularized term “vaccine-busting variant.” Here are some practical considerations we can make as we await more clarity and guidance on variants to come. First, as long as new variants continue to appear, get comfortable with maintaining some level of situational awareness. What are infection rates like in your 1146
neighborhood? What about the communities of people you interact with on a daily basis? The higher the prevalence, presumably, the higher your personal risk. Second, remember that “Covid-21” is not the same as Covid19. The Delta variant appears to be up to ten times as infectious as the parent SARS-CoV-2 strain that originated in Wuhan. It also appears to efficiently infect people of all ages, including teens and young children, in some cases causing critical illness and even death. This means the basic safety measures we relied on for the better part of 2020 to protect ourselves—mask wearing, handwashing, social distancing—only go so far. Even people who followed CDC guidelines religiously for the past 18 months may find themselves infected. So long as our public health controls aren’t as aggressive as the virus itself, it will fall to individuals to exercise caution than before. Third, reevaluate and upgrade your mask wearing and social distancing habits. Until we know how proficient non-clinical grade masks are at protecting against the new variants, I recommend wearing an N95 mask when meeting with anyone outside your immediate bubble, whether indoors or outdoors. I also recommend avoiding large groups of people even outside and limiting indoor exposure to as few people in as short a time as possible. Remember that the Delta variant is so contagious, Australian health officials have documented transmission through “fleeting” non-physical contact in cafes and shopping malls. But what of vaccination status? This brings me to my fourth and final point: if you’re vaccinated, do what you can to monitor your personal level of immune protection. This involves two main variables. First, your concentration of anti-SARS-CoV-2 antibodies. Two kinds of antibodies, which are similar but not identical, have been established as adequate correlates of immune protection from Covid-19: those that bind to the spike protein and those that inhibit it. The latter, also known as neutralizing antibodies, have the tightest correlation, but spike protein antibodies are a reasonable surrogate. A combination of clinical safety and efficacy data and computational modeling studies shows that the higher your antibody titer, the higher your likely level of protection. Different vaccines elicit different antibody titers, with the mRNA vaccines generating the highest. My recommendation is, beginning two weeks after 1147
vaccination, to get tested for antibody count and have the same test—no standardized assay is available yet—repeated every four months. Your antibody titer will give you a rough approximation of your protection from infection. The second variable is time. In addition to your antibody count, which is determined in large part by the type of vaccine you received, monitoring how much time has passed since your last shot can also help you estimate your level of protection. According to one study, vaccine-generated antibodies can wane as much as 50 percent in as few as 10 weeks. All anti-SARS-CoV-2 antibodies fade, but how quickly they fade depends on your age and medical history. This is why some countries are in the process of making booster shots available to older adults, whose immune responses tend not to be as vigorous or long-lasting. No magic number of antibodies or anything else can guarantee immunity against existing and future variants of SARS-CoV-2. But it’s time we accept the reality that with a highly contagious variant on the loose, the chances of someone who is vaccinated falling ill and dying are inevitably higher. At least 100 individuals were lost to such circumstances in Massachusetts, according to a new report. Studies also show that the Delta variant generates higher viral loads in our nasal passages, irrespective of vaccination status, increasing opportunities for transmission. To circle back to where we started, if protection is likely to falter or fade, is it worth getting vaccinated in the first place? Absolutely yes—on this question I’ve no equivocation. But only with vigilance around situational awareness, the threat presented by new SARSCoV-2 variants, and the strength and length of our antibody titers can we ensure we’re protecting ourselves and each other to the best of our ability. All in all, we have to up our game when it comes to countering and defending ourselves against more infectious and dangerous forms of the Covid-19 virus. If our governments and local health officials won’t intervene, we need to take responsibility for our individual actions and behaviors to minimize risk to ourselves and the people around us. Over time we can end this pandemic through more broadly protective vaccines, prophylactic drugs, and rigorous public health measures. But until these reinforcements materialize, we need
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to keep our collective guard up, or risk letting everything we’ve built up to ensure our recovery fall apart. This article originally appeared in Forbes, and can be read online here: The Delta Variant: A Guide To Evaluating Personal Risk
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Busting 12 Covid-19 Myths That Could Kill Forbes | August 10, 2021 | Article
We have underestimated the force that is SARS-CoV-2 and its impact on global society since the beginning. Our miscalculation of everything from how the virus spreads to how much it can adapt and change has led to the loss of millions of lives worldwide, with infections and deaths still on the rise to this day. You think we would have learned our lesson by now—and yet in the face of increasingly dangerous variants, a rhetoric of relentless optimism undergirded by complacency and inaction continues to cloud our better judgment. Last year, neither the first appearance of the virus in Wuhan in late 2019 nor the dire situation that capsized Italy in March and April 2020 constituted a wake up call. Only after the first waves of Covid19 cases hit Europe and the United States hard did either population begin to take the pandemic more seriously. This year, once again, the catastrophic outbreaks that slammed through India this past spring didn’t seem to be a sufficient warning that worse was to come. Instead many countries, the US among them, began to systematically dismantle the web of protective measures they spent the better part of last year building. Until now. From where we’re standing, we can see even the most successful pandemic response strategies have missed the mark in some critical way. Those who relied extensively on rigorous lockdowns and border controls are now struggling to stamp out major new reinfections, for example in Australia and China. In the United States, where our masks and mass vaccinations have been our primary defense, case counts are escalating in many regions, particularly where these public health interventions failed to gain much traction. How did we get here? By telling ourselves stories that were convenient truths until they proved false—in other words, mythologizing a virus when it needed rigorous, evidence-based demystifying. Below I unpack a number of such myths, explaining the difference between what we thought then and what we know now. 1150
Myth #1: Covid-19 originated in a foreign country, so it will remain a foreign virus. Infectious diseases neither recognize nor abide by geopolitical boundaries. The world stood by and did nothing as Covid-19 infections escalated in China, when we should have known full well that nothing would stop it from reaching our respective shores. Myth #2: Closing borders will keep Covid-19 out. Blunt border controls didn’t thwart the virus from entering and circulating in Europe, the United States, or—as we’re now seeing with the rise of more infectious variants—countries where they were enforced most stringently, like China and Australia. The highly contagious Delta variant has proven adept at penetrating even the most drastic containment protocols. Only in the small country of New Zealand, where government officials have combined dramatic limits on foreign travel with rigorous screening, contact tracing, and mandatory isolation of all travelers, has this strategy continued to reap significant rewards. Myth #3: Covid-19 will be no worse than seasonal flu. Initially it was thought that Covid-19 might come and go like the seasonal flu, killing thousands but affecting most only mildly. The number of documented deaths from Covid-19-related causes now exceeds four million; clearly this wish did not come true. Myth #4: Covid-19 will disappear on its own. Many predicted the virus would vanish in the summer of 2020 or 2021, either quietly becoming endemic or succumbing to warm climates. But both summers the pandemic only intensified, proving SARS-CoV-2 can withstand tropical and even scorching temperatures, as has been the case in Indonesia. The virus is also on the rise in the US despite one of the hottest summers on record. Myth #5: Covid-19 isn’t transmitted by aerosols, only droplets. It took more than a year of research, surveillance, and health communications for us to collectively grasp that SARS-CoV-2 is an 1151
airborne virus. Once expelled, virus particles linger in the air like cigarette smoke, retaining structural stability and infectivity for up to several hours. In some cases, transmission of the Delta variant has been documented to occur outdoors. Myth #6: Covid-19 cannot be transmitted by asymptomatic carriers. Public health authorities dismissed the possibility of asymptomatic transmission from the beginning, without good reason. The notion that only symptomatic carriers could spread infectious virus was one of the reasons many countries kept their guard down early on—only to discover months later that asymptomatic spread was not only possible, but likely the main mode of transmission for SARS-CoV-2. If the new variants are better at delaying immune detection than prior strains, as experts including myself suspect, their asymptomatic period could last longer. Myth #7: The Covid-19 virus changes, but slowly. The first major mutation researchers detected in the parent SARS-CoV-2 strain, called D614G, developed near universal prevalence as early as spring 2020. But at the time, despite warnings to the contrary, many believed the virus had a limited repertoire of potential changes. The rapid appearance of new variants has since disproved this. With each passing variant of concern we learn more about the tremendous capacity SARS-CoV-2 has for persistence and adaptation. These changes affect replication, incubation, stability, transmissibility, and more. Myth #8: Covid-19 vaccines offer long-lasting protection against infection. The natural history of coronaviruses is comparable enough to that of influenza viruses that we could have anticipated the mutability of SARS-CoV-2—as well as the transience of our immune defenses against it. The first generation of Covid-19 vaccines has done an exceptional job at preventing severe illness and death, but how long that protection will last remains a gap in our knowledge too large for comfort. Even the best vaccines we have 1152
on hand, the mRNA vaccines created by Moderna and Pfizer, don’t erect an impenetrable barrier between the body and the virus. Instead they trigger an immune response that teaches the body to recognize and neutralize the virus on sight. If the virus mutates beyond immune recognition, then the vaccine loses all or most of its potency, hence the recently popularized term “vaccine-busting variant.” Myth #9: Individuals vaccinated against Covid-19 won’t fall ill or die. Again, now that more than two billion people around the world have received at least one dose of a Covid-19 vaccine, hospitalizations and fatalities aren’t reaching the precipitous heights we saw in 2020. But both are still on the rise, not just in populations with low vaccination rates but due to breakthrough infections in those who are vaccinated. While these events remain rare, if immune protection wanes over time, presumably they will become more commonplace. Any authorized vaccine is better than no vaccine, but we must be realistic about how much protection they actually guarantee us, or leave ourselves unnecessarily vulnerable. The recent death of seven Belgian nursing home residents due to the as yet unnamed B.1.621 variant, despite being vaccinated with Pfizer’s two-shot regimen, is a warning that protection from the most serious consequence of Covid-19 infection may soon obtain mythical status. Myth #10: No matter how infectious the Covid-19 virus becomes, children will be spared. In the 18 months that SARS-CoV-2 has lived among us, it has been consistently reported that Covid-19, with rare exceptions, doesn’t put most children and teens at risk for severe illness or death. This was fortunately true of earlier strains, to which younger individuals were far less susceptible than the average adult. But it no longer appears to be the case with the Delta variant. A higher proportion of children and teens are contracting infections; pediatric hospitals are filling up that last year, were all but spared; and child deaths are surging in Indonesia, where the Delta variant has claimed
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the lives of more than 100 children a week in the past month. The more children infected, the more will transmit virus to adults. Myth #11: Covid-19 will weaken over time to become harmless, like a cold virus. While this remains a possible outcome in the long term, given the trajectory of recent variants towards higher infectivity and virulence, it is unlikely to come to fruition anytime soon. Myth #12: We are helpless in the face of new variants of Covid-19. There is one more myth I will do the duty of busting: that we must resign ourselves to a future in which Covid-19 continues to wreak havoc around us. If we level up our pandemic response based on everything we’ve learned about SARS-CoV-2, we can still alleviate further suffering and death. An intensive, multilayered strategy that combines broadly protective Covid-19 vaccines, prophylactic and therapeutic drugs, public health measures, and international cooperation—which I’m calling Multimodal Covid Control—would gives us the boost we need to outmaneuver the virus for the foreseeable future. Given what we know now, why wait? This article was originally published in Forbes, and can be read online here: Busting 12 Covid-19 Myths That Could Kill
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Israel’s Recent Surge Confirms We Need A Multimodal Strategy To Fight Covid-19 Forbes | August 11, 2021 | Article
With a surge of Covid-19 infections at the highest levels since February, Israel is now contemplating further lockdowns and the possibility of extending booster vaccine shots to those over 50 years old. This comes after administering booster shots to about 2,000 immunocompromised people weeks ago before extending the shots to all those over 60 on August 1. Cases are occurring in both vaccinated and unvaccinated populations, yet with one of the highest vaccination rates in the world, Israel’s experience confirms that no single modality will control Covid-19 alone, as the virus continues to evolve and mutate. We need a multi-modal strategy to contain Covid-19. A July report from the Israel Ministry of Health found that Pfizer/BioNTech’s Covid-19 vaccine is just 39% effective in Israel, where the Delta variant is the dominant strain but still provides strong protection against severe illness and hospitalization. According to the report, the vaccines still work very well in preventing severe cases, demonstrating 88% effectiveness against hospitalization and 91% effectiveness against severe illness. But this is still is a steep decline from the earlier estimate of 64% efficacy rate released on July 5, and steeper still from the initial 95% efficacy rate Israel published in May, based on records from Jan. 24 to April 3, 2021. The Israel report contrasts with data from the UK government that shows the Pfizer/BioNTech vaccine was 88% effective against symptomatic disease from the Delta variant two weeks after the second dose, compared to 93% effectiveness against the Alpha Variant during the period from 5 April to 16 May. Interpreting vaccine efficacy data is a complex task that requires considering many nuances such as the size of the study’s population, the dates and length of observation, multiple types of vaccines in circulation, and many other variables. But one thing is clear, there is 1155
a distinct waning in the effectiveness of the immunity and protection that the vaccine provides over time. As one of the quickest countries to roll out the vaccine, Israel acts as the canary in the coal mine for us all, especially in the United States, where we have few other modes of public health protections. As weary as many of us are about Covid protocols and interventions, we must not remain complacent, as this virus is far from running out of tricks. Israel once had a robust contract tracing system that kept the virus under control even before the vaccines were available. In late May, spurred on by false confidence from low daily cases rates and the swift vaccine rollout, Defense Minister Benny Gantz and military chief Aviv Kochavi closed the army’s contact-tracing center, known as Alon, transferring the responsibility to the Health Ministry and slashing staff. At the height of its operations, Alon had around 3,000 contact tracers capable of carrying out 6,000 epidemiological investigations a day. With 10,000 new cases reported in Israel over the last few days, contract tracers were only able to conduct epidemiological investigations on 40 percent of cases. There has been a strong focus recently by Israel and many other countries on booster shots as a solution to waning vaccine immunity. But we cannot make the mistake of relying on one modality, vaccines are a critical tool in our fight against Covid-19, but they must be paired with other layers of protection. To fill any gaps in vaccine protection, we can create a second layer of defense with the prophylactic use of antiviral drugs. The US government recently committed $3.2 billion to develop antiviral pills for Covid-19. While this is a valuable contribution, we urgently need to supercharge the development of antiviral drugs with the same priority we did for vaccines. Many have focused on antiviral drugs purely as a treatment for Covid-19, when their real power is in their prophylactic use, preventing people exposed to the virus from ever becoming ill or passing on an infection. Similar to how Xofluza, an antiviral used for Influenza reduces transmission by 80% in a close-quarter family context. With a good safety profile, antiviral drugs could be taken by anyone exposed to Covid-19 in a congregate living situation. By attacking the virus before it has a chance to replicate we have the opportunity to prevent the spread of infections and mutation of future variants. Of course, for this 1156
prophylactic use of antivirals to be successful it needs to be combined with a mass rapid antigen testing and robust contract tracing program to quickly determine exposure. As the virus continues to evolve so must our defense strategy. A multimodal strategy that utilizes antiviral drugs ensures that we can protect our current population and rebuild a world that is prepared for future Covid and other disease outbreaks. This article was originally published in Forbes, and can be read online here: Israel’s Recent Surge Confirms We Need A Multimodal Strategy To Fight Covid-19
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A New Killer On The Loose: B.1.621 Forbes | August 12, 2021 | Article
A group of seven residents in a Belgian nursing home died after infection with a new variant, all of whom were fully vaccinated according to virologists on the scene. Though the vaccine used in these residents was not made public, it was likely either AstraZeneca or an mRNA vaccine such as Pfizer and Moderna, among those most frequently used in the country. The new variant, B.1.621, has yet to receive a greek letter designation from the World Health Organization. The variant already accounts for around 2% of coronavirus infections in the United States, and as much as 10% in Miami, according to Carlos Migoya, CEO of Jackson Health System. The variant can be traced back to identification in samples from Colombia in March 2021 and according to the GISAID coronavirus database, the variant has been identified in as many as 28 countries, but potentially more. Despite not having the official label of Variant of Interest or Concern, it should be noted that B.1.621 has certain characteristics that suggest it may be worth watching, as it could become a variant of interest or concern in the near future. Here we analyze those mutations and summarize what we know about their likely effects on transmissibility, virulence, vaccine evasion, and pathogenesis. Figure 1 shows both the nonsynonymous nucleotide mutations that result in amino acid changes and synonymous “silent” nucleotide mutations in B.1.621 versus the original Wuhan strain. What follows is a brief tour of the potential impact of the mutations beginning at the 5’ end of the genome and extending to the 3’ end. Altogether, there are 17 nucleotide mutations, of which 13 result in amino acid mutations.
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FIGURE 1: (A) Common mutations external to the S protein in the B.1.621 variant genome. Color code: ... [+] ACCESS HEALTH INTERNATIONAL
The 5’ most mutation is C241U. This mutation in the untranslated noncoding region, along with P323L in nonstructural protein (NSP) 12 and D614G in the Spike (S) protein, appear in almost all currently circulating strains today. These first appeared in late January and early February 2020 and have since become the dominant strain around the world. Almost all variants of interest or concern harbor these three mutations derived from the early variant. The D614G mutation in the S protein is critical to increased transmissibility and P323L in NSP12 is speculated to increase the replication efficiency of the virus. Here we speculate that the C241U 5’ end mutation may confer increased production of full-length genomic RNA and packaging efficiency. This mutation is located in loop three of the leader sequence of genomic and subgenomic RNAs. We also note this mutation may affect the frequency of translation as it is located 25 nucleotides 5’ to the Orf1ab initiation codon. The B.1.621 variant has two mutations in NSP3—one silent and one amino acid altering. NSP3 is a multi-domain protein with a number of different functions. C3037U is a synonymous mutation 1159
that lies in the Acidic C-terminal (Ac) domain. The next mutation, T720I, lies in the SARS-specific unique domain (SUD). The SUD is involved in the formation of G-quadruplexes, which play a role in the modulation of host cell response to infection. Threonine to isoleucine is a major, polar-to-hydrophobic change, indicating a potentially major contribution to the SUD’s operation. Q160R is found in NSP6. This mutation is another major change from polar uncharged glutamine to positively charged arginine, which has a potential effect on protein structure and function. NSP6 is involved in a protein involved in the formation of the double-membrane replication vesicle, major inhibition of human immune responses by inhibiting STAT1 and STAT2 phosphorylation, and inhibition TANK binding kinase 1. We speculate that this mutation may contribute to pathogenesis by increased suppression of the immune response allowing the virus additional opportunity to replicate. C18877U is located in NSP14 and C20148U is located in NSP15. As silent mutations, they may have an effect on the stability of the messenger RNA. The S protein of B.1.621 carries six common mutations in GISAID sequenced samples. The most 5’ mutation in the S protein is T95I in the N-terminal domain. The N-terminal domain is a major binding site for monoclonal antibodies and other antiviral treatments. Mutations to this domain have been shown to increase virus escape from these medical interventions. T95I is a change from polar threonine to hydrophobic isoleucine. We speculate this could eliminate a binding site, potentially contributing to immune evasion. The significance of this mutation is heightened by the independent observation of the T95I mutation in the Iota variant of interest. There are two mutations in the receptor-binding domain. The receptor-binding domain interacts directly with the host receptor ACE2. The mutations in the receptor-binding domain are found in many variants of interest and concern. E484K is reported to increase viral resistance to monoclonal antibodies and convalescent sera. N501Y is consistently noted to highly increase avidity between the receptor-binding domain and ACE2 receptor. Both are present in a number of VOIs and VOCs, including Alpha, Beta, Gamma, Eta, and Iota. 1160
The S protein also carries the P681H mutation. Both this and D614G are associated with enhancing the furin cleavage site in the middle portion of the S protein, which again contributes to highly increased transmissibility. D614G is a major change from negative aspartic acid to uncharged glycine. P681H is uncharged proline to positive arginine, again indicating a significant change. The P681H mutation is notable for its observation in the Alpha variant, the fuel behind the third wave of Covid-19 in late 2020 and early 2021. The final S protein mutation is D950N. The mutation is located in heptad repeat 1. The change from aspartic acid to asparagine is negative to polar uncharged, indicating a major shift in charge and polarity. Although the exact function of this mutation is unknown, it is also found in the currently pervasive Delta variant, likely indicating some unknown increase in viral infectivity. Below is a comprehensive summary of the B.1.621 S protein and the documented and potential effects of its mutations (Figure 2).
FIGURE 2: Projected on the S protein are the different B.1.621 mutations, accompanied by arrows ... [+] ACCESS HEALTH INTERNATIONAL
There are two additional mutations in Orf3a. The first mutation is the Q57H. A major change from polar uncharged glutamine to positive histidine, this mutation has also been observed in the Iota variant, as well as B.1.427/429 first identified in California. The 1161
second mutation is a deletion from nucleotides 26158 to 26162 is commonly noted, which affects amino acids 256 and 257 and is unique to this variant. Evidence suggests Orf3a is important for viral pathogenesis These mutations may enhance Orf3a efficiency. There is one mutation in Orf8, S67F. This mutation is unique in relation to VOIs and VOCs, though that does not rule out its potential impact on the protein. Orf8 is a major immune regulator, inhibiting B and T cell recognition and downregulating major histocompatibility complex I (MHC-I). The serine to phenylalanine mutation is polar to hydrophobic, again indicating a major change. We suspect that the S67F mutation could very well improve the immune suppressive nature of Orf8 and the virus as a whole. Near the 3’ end, the Nucleocapsid (N) protein contains the mutation T205I. Found in the Beta VOC, Eta VOI, and B.1.427/429, this mutation may have a strong impact on the immune suppression conducted by the N protein. In addition to packaging and protecting viral RNA, the N protein has a number of suppressive functions, including antiviral RNAi and INF-β antagonism, cyclin-cyclin dependent kinase inhibition, nonsensemediated decay inhibition, and late infection immune activation. The N protein is an immune suppressive workhorse and T205I, polar threonine to hydrophobic isoleucine, likely contributes to this efficiency. As this is a significant change in the amino acids, it is worth a significant effort to understand the mutation’s impact on the multifunctional N protein. Our conclusion from the extensive set of mutations found in this particular variant is that it deserves to be observed closely. We have been informed through private communication that because of the Orf3a deletion, it may not routinely be included in the GISAID catalog. Therefore, the representation of its true frequency in populations around the world is underrepresented. B.1.621 clearly has the potential to be lethal in vaccinated elderly patients and may have the potential to become more transmissible as well. Given the described changes, we can begin to understand why the B.1.621 variant should be considered certainly a variant of interest, if not a variant of concern, and merits much closer observation in the coming weeks and months.
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This article originally appeared in Forbes, and can be read online here: A New Killer On The Loose: B.1.621
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part One) Forbes | August 12, 2021 | Article
This is the first article in a 15-part series called “Relevance of Immune Suppression by SARS-CoV-2 to Understanding and Controlling the Covid-19 Pandemic,” which will explore an under-appreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Macavity’s a Mystery Cat: he’s called the Hidden Paw— For he’s the master criminal who can defy the Law. He’s the bafflement of Scotland Yard, the Flying Squad’s despair: For when they reach the scene of crime—Macavity’s not there! T.S. Eliot, The Naming of Cats (1939) I write this series to celebrate the power of the science and medicine that provide us with deep insight into the nature of the virus that causes Covid-19 and the vaccines and drugs that prevent and treat the disease. But I also write this as a warning not to underestimate our adversary. Anyone who has engaged in hand to hand combat—for that is what it feels like—with cancer, AIDS, or any of the other great diseases of our time knows how formidable our foe is. Evolution, the same force that gifted us with the intelligence to understand our world, has crafted diseases of great subtlety that seem to slip through our grasp just as we think we have a firm grip. Yes, we have had success in developing Covid-19 vaccines, and new and effective treatments appear to be just around the corner. Yet at the same time, a chill wind of doubt disturbs our optimism, as viral variants begin 1164
to break through our vaccines and sicken and even kill a small fraction of those who seek protection. This is the third major pandemic of my lifetime. I remember polio and all the forbidden summer activities—swimming in public pools, playing with more than two other friends, or enjoying the latest serials in the cool, dark movie theaters I loved. No doubt similar to what today's children will remember of the restrictions around Covid-19. As a young Harvard researcher working on cancer and AIDS, I remember the War on Cancer and our hopes that we would vanquish the disease in a few short years or, conservatively, a decade or two at most. I remember the HIV epidemic, first for the sluggish reaction of our public health officials and leaders, then for the rapid science advances that led to a deep understanding of the virus and drugs to prevent and treat the disease. With some sadness, I see our dashed hopes for an early vaccine to end the pandemic and now, forty years and 35 million deaths later, see that HIV/AIDS lingers on with a million or more people dying each year. I have seen too many premature announcements of victory over disease that I hesitate to declare our imminent success in controlling Covid-19. I remain confident that a return to normal life can and will be the end result, but only if we remain dedicated to using the full power of our science, medicine, public health, and international organizations to understand and control SARS-CoV-2. How do we understand what has happened? How and why SARS-CoV-2 infects so many, why it causes severe disease in some yet affects most others only mildly, how it confounds natural immunity, and what is behind the variants? It is a tale of stealth and disguise worthy of any great mystery novel. Each revelation offers not just insight into our collective experience but new hope that we might prevail against this most dangerous pathogen. First and foremost, SARS-CoV-2 is a master at evading both the defenses of an infected cell and the entire immune system. The primary story, perhaps paradoxically, is one of immune suppression—not hyper-activation, which is seen so strikingly in those who fall seriously ill. To establish infection all viruses must first defeat the body's well-honed defenses. SARS-CoV-2, as we shall see, has proved exceptional at this task. Early on, the virus acts at multiple levels to counteract innate immunity, the first line of defense against microbial invaders, allowing enough time for the 1165
virus to enter and exit before the full set of antiviral defenses can mobilize. Upon entry into a susceptible cell, the virus conceals its presence by creating a privileged subcellular organelle in which it replicates unseen by intracellular alarms and by camouflaging its messenger RNAs to resemble those of cellular RNAs. In addition, SARSCoV-2 carries an impressive arsenal of proteins that actively suppress both the induction of interferon, the primary trigger of innate and adaptive immunity, and of interferon-induced genes and proteins. This early immune suppression may account for the generally weak antibody response in those infected, facilitating reinfection within months by variants that produce key neutralization epitopes. The second element of this tale is the puzzling pathogenesis of the virus. The peak of viral replication occurs before the onset of symptoms—meaning even mild symptoms occur only after the virus is on the wane. Perturbation of our initial immune defenses may be largely responsible for the violent reaction that seems to cause the most severe consequences of Covid-19. Last but not least is the capacity SARS-CoV-2 has for evolution. SARS-CoV-2 is protean, capable of changing its exterior to re-enter previously infected hosts. New variants of SARS-CoV-2 have proven strikingly more infectious than the original strain, both because of spike proteins that enhance binding affinity and evade antibody detection, and because some variants are more potent in repressing innate immunity. Troubling though these strategies to circumvent innate immunity may be, they offer exciting opportunities for prevention and treatment. The first bit of good news is that vaccines circumvent most viral defenses, inducing a much more robust and durable antiviral immune response than infection itself. The second piece of good news is discovery of new drugs that can overcome virus immune suppression. We can and will defeat Covid-19 by combining good public health practices with effective vaccines and new generations of antiviral drugs. This article was originally published in Forbes, and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part One)
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part Two) Forbes | August 13, 2021 | Article
This is the second article in a 15-part series called “Relevance of Immune Suppression by SARS-CoV-2 to Understanding and Controlling the Covid-19 Pandemic,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read part one. Asymptomatic infection Like Covid-19, SARS emerged from long-incubating animal reservoirs. Why then did only Covid-19 spread far and wide? The reason is very likely the relative lethality between the two. People infected by SARS and MERS knew almost immediately, so severe were the symptoms. This made it easy for health officials to identify and control almost every case. Not so for Covid-19. Though SARS-CoV-2 is certainly capable of causing severe illness and death, neither is the primary outcome. This virus is characterized first and foremost by its propensity for asymptomatic infection, which causes more than 50 percent of new infections. Proliferation, not pathogenesis, is its selective advantage. SARS-CoV-2 has evolved mechanisms that allow it to evade and suppress innate immunity, many of which kick in early, allowing the virus enough time to enter, proliferate, and exit before the immune system can respond.
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Figure 1: Virus particles per milliliter in nasal secretions over time. Symptoms appear one or two days after the peak of virus load.ACCESS HEALTH INTERNATIONAL
Methods of immunosuppression The moment SARS-CoV-2 infects a cell, it begins to counter both the innate and adaptive immune response. The primary target is interferon, the protein that protects the infected cell and alerts surrounding cells to the presence of an invading pathogen. Studies show that Covid-19 patients are at higher risk of severe illness and death when their ability to produce a robust interferon response is compromised. Upon infection, SARS-CoV-2 initiates a multilayered program that assures that little to no interferon is made and that which is made cannot reach its target. Several viral proteins specifically block the production and function of interferon and interferon-stimulated genes. This is no coincidence—it is the interferons alpha and beta that induce both the innate and adaptive immune responses. Once inside, the virus creates a special organelle that conceals both viral proteins and the replicating structure, including doublestranded RNA, from several cellular watchdogs that would normally trigger the alarm system. By building this special compartment, the double-membrane vesicle, the virus avoids inducing the production of interferon and interferon-responsive proteins. In addition to concealing its replicative activities, SARS-CoV-2 disables cellular protein synthesis. In doing so, it not only clears the way for the preferential synthesis of its proteins, but also prevents the synthesis of interferons. 1168
The virus disguises its messenger RNAs as if they were cellular, eluding yet another defensive tripwire. The first viral protein made obstructs ribosomal messenger RNA entry, preventing translation of all messenger RNAs while opening the gate to the messages of SARS-CoV-2. Viral proteins also block nuclear export and splicing of newly made messenger RNAs, including interferon messenger RNAs. Another pair of viral proteins compromise export of all cellular proteins, ensuring that any warning signals made by an infected cell will not alert neighboring cells to the trouble nearby. An array of viral proteins prevents the initiation of messenger RNA synthesis of both interferon and interferon-induced genes. Another viral protein stymies interferon and interferon-induced proteins by inhibiting signaling protein transport and entry into the nucleus. In other words, SARS-CoV-2 mounts a full-court press against the initiation of both the innate and adaptive immune response. This covert strategy fends off the immune reactions long enough for the virus to enter and exit before a naive or memory response kicks in. The virus has several additional strategies for re-entering previously exposed populations. As a free particle, it remains vulnerable to high concentrations of neutralizing antibodies directed for the most part at the surface glycoprotein, the spike trimer. Mutations in the spike that retain the ability to infect, yet elude the neutralizing antibodies of the previously infected, allow endless cycles of infection of adult immunocompetent populations. Such is the natural history of cold-causing coronaviruses, and such would likely be the story of SARS-CoV-2 without our intervention. Mutations may also increase the avidity of the spike protein for the receptor or stabilize the spike, increasing infectivity. Still other mutations may increase the half-life of the free virus particle. Variants may also arise that replicate more rapidly dramatically increasing the concentration of exhaled particles. All of the above is only a brief overview of the many immunological tricks SARS-CoV-2 has in its repertoire. Next up in this series I will examine how they evade our first line of defense: innate immunity.
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This article was originally published in Forbes, and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part Two)
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part Three) Forbes | August 16, 2021 | Article
A classic example of a Rube Goldberg machine. Note how many pieces and processes need to come together for the light at the end to illuminate. Block one and the light won't turn on.GETTY This is the third article in a 15-part series called “Relevance of Immune Suppression by SARS-CoV-2 to Understanding and Controlling the Covid-19 Pandemic,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read part one and part two. A complex genome and replication strategy offers many new opportunities to develop drugs that prevent and treat SARS-CoV-2 infections. The SARS-CoV-2 genome is one of the largest of any RNA virus. On either side of the sequence are 5 prime and 3 prime untranslated regions, necessary for making new copies of the virus 1171
genome and initiating messenger RNA synthesis. The untranslated regions also contribute to control of viral replication and messenger RNA synthesis and translation.
Figure 2: (A) The SARS-CoV-2 genome with each protein labeled, including NSP116, S, E, M, N, and Orf3a-10; (B) An expanded view of the SARS-CoV-2 3 prime end. ACCESS HEALTH INTERNATIONAL
SARS-CoV-2 encodes 30 proteins. A set of 16 proteins, designated as the nonstructural genes NSP1-16, are encoded by the 5 prime two-thirds of the genome. Upon infection, the full-length viral RNA—which closely resembles a cellular messenger RNA with a 5 prime cap and a polyadenylate tail—serves as the template for the synthesis of these 16 proteins. Together these early proteins create the intracellular conditions for replication and transcription. The NSP proteins are originally made as long polypeptides, with Orf1a encoding proteins NSP1-10 and an extension, Orf1ab, encoding all 16 NSPs. The individual NSP proteins are cleaved from
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these precursors by the actions of two proteases, one specified by NSP3 and others by NSP5. The virus also encodes the four proteins of the infectious virus particle: the S protein that forms the surface spike, the E and M proteins embedded in the viral membrane, and N, the nucleocapsid protein, that forms a complex with the viral genome (Figure 3).
Figure 3: SARS-CoV-2 particleACCESS HEALTH INTERNATIONAL; ENCYCLOPEDIA BRITANNICA, INC. HTTPS://WWW.BRITANNICA.COM/SCIENCE/CORONAVIRUSVIRUS-GROUP
Interspersed among the structural genes are the accessory genes designed as open reading frame proteins 3-10 (Orfs 3-10). SARS-CoV-2 is a member of the nidovirus family, so-called because of their unique means of producing 3 prime terminal messenger RNAs. The messenger RNAs of structural proteins and 3 prime Orf proteins are made from a nested set of transcripts. The 3 prime messenger RNAs are made from subgenomic fragments, each of which serves as a separate replicon, resembling minigenomes. Messenger RNA synthesis of the 3 prime genes begins with transcription of the positive genome, creating a nested set of negative strand partial copies that contain both the original 5 prime and 3 prime untranslated terminal sequences. Transcription of a minus strand messenger RNA temple is truncated at the transcription regulation sequences (TRS), followed by a jump to the 5 prime 1173
untranslated region. The minus strand is then copied to produce a positive strand. Each subgenomic replicon serves as a template to produce positive-strand messenger RNAs via a process akin to the production of full-length genomic RNA (Figure 4).
Figure 4: The messenger RNA replication and transcription strategy of SARS-CoV-2. Note the nested set of 3 prime messenger RNAs made by jumping from the 3 prime to the 5 prime transcriptional regulatory sequence.ACCESS HEALTH INTERNATIONAL; HTTPS://WWW.MDPI.COM/20770383/9/4/1225/HTM
We must understand the large complex nature of the viral genome and proteins both for understanding the disease and how to thwart it. As will become clear, many of the viral genes contribute to the virus's ability to evade the immune system early on, allowing the virus to enter and escape before detection. Disease that occurs two to three weeks later is likely due to dysregulation of the immune system that occurs earlier. Detailed knowledge of exactly how the virus functions is essential for the development of antiviral drugs that can be used alone or in combination to prevent and treat infections. We are still at an early stage in our understanding. We only know enough to know 1174
that we need to know much more. We are in desperate need of a well-funded, highly focused global effort to develop the detailed knowledge we need to create the next set of safe and effective antiviral drugs. The complex genome and replication strategy of the virus also suggest there are many ways the virus can respond to immune pressure and public health containment strategies. Current efforts focus almost exclusively on interpreting viral variation in terms of changes to the function of the spike protection. Evidence is beginning to emerge suggesting that increases in replication efficiency and immune suppression also contribute to the increase in transmission and virulence of SARS-CoV-2 variants. This unique means of messenger RNA production may provide a selective advantage over many other RNA viruses that must produce all their viral proteins from a single messenger RNA. I speculate that this strategy allows the virus to preferentially amplify the 3 prime messenger RNAs in response to selective pressure, as recently documented for the Alpha variant. As we shall see in the next piece in this series, preferential messenger RNA amplification contributes to increased immune suppression by the Alpha variant. This article originally appeared in Forbes magazine, and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part Three)
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Study Shows Covid-19 Can Be Detected In A Single Asymptomatic Person Through Wastewater Surveillance Forbes | August 16, 2021 | Article
A new study from UC San Diego demonstrates that wastewater surveillance can detect Covid-19 in a single infected, asymptomatic person living or working in a multi-unit dwelling such as a university campus building. Wastewater surveillance can detect a case up to 3 to 4 days before individual testing can. Early detection means that those infected can quickly isolate and if necessary receive treatment, preventing rapid spread of the virus. Wastewater surveillance is an underused yet cost-effective, noninvasive mass testing strategy that can detect virus shed by symptomatic and asymptomatic people alike. Highly localized wastewater surveillance provides an alternative to contact tracing, an intervention that has been difficult to implement in many countries. With a small enough group, testing everyone potentially exposed is justified and usually acceptable. With highly vulnerable, unvaccinated children returning to classrooms wastewater surveillance could be a valuable tool in keeping them safe. People infected with SARS-CoV-2, Covid-19, are known to shed in their stool and urine, even if they aren't experiencing any symptoms. Unlike individual testing, wastewater surveillance paints a broader picture, detecting exactly when new viral variants enter a community, providing valuable data and an early warning to public officials. Time is one of the most valuable modalities of infectious disease control. Wastewater testing can predict new outbreaks with a lead time of one to two weeks. This surveillance can and should be used with other interventions to facilitate a safe return to university campuses, schools, and workplaces The study released by the University of California San Diego School of Medicine was conducted on campus. Researchers used a large-scale geographic information systems to build a wastewater 1176
monitoring system that was associated with the on-campus residences of 7,614 individuals. Wastewater surveillance led to the early diagnosis of nearly 85% of all Covid-19 cases on campus. Covid-19 testing rates increased by 1.9 to 13 following wastewater notifications. A team of students and staff were deployed each morning to collect sewage samples from 126 collection robots set up to monitor 350 buildings. Each auto-sampler collects wastewater into a prelabeled sample bottle. Both the auto-sampler and the sample bottle are associated with a unique barcode . The result for each sample is uniquely identified by time and place. When the researchers receive the samples they process the sewage using a different kind of robot, one that concentrates the virus using magnetic nanoparticles, and extracts RNA—the genetic material that makes up the genomes of viruses like SARS-CoV-2—from the samples. Polymerase chain reaction (PCR) testing is used to detect the virus' signature genes. If the sequencing reveals all three viral genes tested, the sample is considered to be positive. The RT-qPCR results are integrated with the campus database to trace the potential sources of observed positive cases based on which buildings are upstream from an auto-sampler in the campus sewer network. For instance, if sampler B was positive but an upstream sampler A was negative, only the buildings contributing waste into the sewer between samplers A and B are assumed to be potentially associated with the positive wastewater signal.Rescuers estimate that use of automation reduces turnaround testing time by 20-fold and exceeds the scale of similar surveillance programs by 10to 100-fold. An automated notification system is used to alert residents to a positive wastewater sample associated with their residence and to encourage uptake of campus-provided asymptomatic testing at no charge. The data is also added to a public dashboard for full transparency and accessibility. Study co-author Smruthi Karthikeyan, Ph.D., an environmental engineer and postdoctoral researcher at UC San Diego School of Medicine says that this surveillance is uniquely beneficial for a college campus. “University campuses especially benefit from wastewater surveillance as a means to avert COVID-19 outbreaks, as they're full of largely asymptomatic populations, and are potential
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hot spots for transmission that necessitate frequent diagnostic testing," The system is part of the University’s Return to Learn program, which aims to allow for safe in-person teaching and research. The program has three pillars; risk mitigation, viral detection and intervention which includes other policies like mask-wearing, symptomatic and asymptomatic testing, and case isolation. All of these policies complement wastewater surveillance providing layers of protection and the strongest possible defense against Covid-19. The success of the Return to Learn should be an adopted not just by colleges, but schools, workplaces, and other congregate living situations such as nursing homes and prisons. Wastewater surveillance is not a new concept. Wastewater testing provided an early warning for outbreaks of hepatitis A and norovirus in Sweden and helped eradicate polio in Israel and India. As early as the 1930s, U.S. researchers recognized that the very same markers of disease that clinicians look for in stool samples could be measured in wastewater to track disease in entire populations. The Covid-19 pandemic has prompted the CDC to partner with other federal agencies and states to develop a National Wastewater Surveillance System. The system is currently being piloted in 31 states, three cities, and two territories and the Department of Homeland Security and the National Institute of Standards and Technology are leading efforts to identify standards for wastewater sampling, testing, analysis, and reporting to public health officials. Under the American Jobs Plan, the Biden administration has allocated $56 billion in grants and low-cost loans to upgrade and modernize drinking water, wastewater, and stormwater systems in the U.S. If the infrastructure push succeeds, we will be well placed to invest in a permanent, national wastewater-based epidemiology network that could prove vital in preparing for faster and more effective control of this and future pandemics. The network could trace other stool-borne pathogens, including influenza while also revealing health disparities and vulnerabilities among communities by monitoring for biomarkers of noncontagious diseases, all key challenges to tackle in the coming years.
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This article originally appeared in Forbes magazine, and can be read online here: Study Shows Covid-19 Can Be Detected In A Single Asymptomatic Person Through Wastewater Surveillance
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Covid-19, No End In Sight Forbes | August 17, 2021 | Article
Everyone is desperate to understand how the pandemic ends, what will be the silver bullet that saves us all. The answer is not that simple nor is it a comfortable easily digestible narrative. Everyone has a different definition of what an “end” looks like. As the virus changes and evolves, the answer will also change. The first issue we must grapple with is time. Over time I believe that the efficacy of all the Covid vaccines will wane with respect to protection from infection, transmission, illness, and even death. With the Biden Administration’s announcement of boosters for all Americans 8 months after their initial vaccination, it is clear that I am not alone in this opinion. Receiving booster shots to protect us from new variants is not unlike how we receive an influenza vaccine each year to protect us from new strains. The second issue is virus evolution. Delta has changed the equation. Having observed the first increase in transmissibility by the B clade that appeared in Europe in February 2020 (not even dignified by a Greek letter) followed by Alpha, Delta, and a host of others, I think it highly likely that a variant more transmissible and deadly will appear that once again changes our calculus. Particularly, as the US once again reaches a daily case load of over 250,000. Such an astronomical case number gives the virus ample opportunity to mutate as it moves from host to host. Such a variant may be either still more transmissible, more deadly, more capable of evading vaccines, and possibly all three. Covid-19 has also become endemic in domestic species from cats and dogs, to field mice and farmed mink. Antibodies to SARS-CoV2 have been detected in 40% of wild white-tailed deer in four U.S. states. An animal reservoir of the virus means that the virus may possibly mutate and transmit back and forth between animals and humans, becoming deadlier with each mutation. However, there are some things that are certain, no one modality will end the pandemic, not vaccines, not rigid public health 1180
enforcement, anti-viral drugs nor international cooperation. We need all four modalities working together in what I call Multimodal Covid Control. In addition to these modalities, we need wastewater surveillance, genomic sequencing, and a paradigm shift to prioritize pathogen free-air in our buildings. Our vaccines can and must be improved. I believe we can and will develop vaccines that are more potent and broadly protective against multiple variants. Recent research published in the journal Advanced Science demonstrates that the use of biomaterials and oxygen to improve the delivery of a vaccine can boost the immune response. Research is also underway on a universal conronavirus vaccination that protects against all variants. Such vaccines and the research needed to develop them are deserving of "Warp Speed” subsidies by multiple governments. We are missing a critical arm of medical control, namely inexpensive, injectable, or orally available, long-acting prophylactic drugs. By attacking the virus before it has a chance to replicate we have the opportunity to prevent the spread of infections and mutation of future variants. These drugs would need a strong safety profile so they are suitable for administration to all who are exposed to the virus. Similar to how Xofluza, an antiviral used for Influenza reduces transmission by 80% in a close-quarter family context. I am confident such drugs can be developed based on the success of similar drugs for the prevention of HIV protection, and my knowledge of SARS-CoV-2. They do not exist today save for cumbersome to administer and expensive cocktails of monoclonal antibodies. Here too we need multinational ‘Warp Speed” drug development programs. The combination of potent broadly effective vaccines and powerful prophylactic drugs will give us the medical capability to end the pandemic and eliminate Covid-19. Resistance to the vaccines and be countered by combinations of effective prophylactic drugs and vice versa. Having the medical capability to eliminate a disease does not guarantee its eradication as we have learned from bitter experience. Each country must do its part to ensure that appropriate public health mitigation measures are effective. Central to Covid control is the identification of the infected in the form of truly effective contract tracing or hyper-localized wastewater surveillance, and prevention 1181
of onward transmission from those exposed and infected. Today that means isolation of the exposed. Tomorrow, hopefully, with the advent of prophylactic treatments, it will mean treatment of the exposed in lieu of isolation. Only a handful of countries today, alas the US and European nations not included, have effective contact tracing programs. While wastewater surveillance has grown in prominence during the pandemic, most programs are still in pilot stages. There is an urgent unmet need to develop and implement such programs in all countries if we ever wish to control the pandemic. Finally, many nations still fail to place the health of their people at the top of their agenda. Many spend less than 2% of their GDP on health with predictable results. Wealthy nations cannot make up for the deficit in the intention and will of governments to ensure a healthy present and future for their people. We have learned in times of plague that the health of one is the health of all. However challenging it may be, we must prioritize working toward a future in which all people no matter where they are have access to highquality affordable healthcare. This article originally appeared in Forbes magazine and can be read online here: Covid-19, No End In Sight
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part Four) Forbes | August 17, 2021 | Article
Cary Grant hiding on top of roof in a scene from the film 'To Catch A Thief', 1955. (Photo by Paramount/Getty Images) GETTY IMAGES
This is the fourth article in a 15-part series called “Relevance of Immune Suppression by SARS-CoV-2 to Understanding and Controlling the Covid-19 Pandemic,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read part one, part two, and part three. What follows is the conclusion of the section of this series written for general audiences. Before this exploration of the immunology of SARS-CoV-2 branches off into more technical
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detail, I will summarize what we have learned so far using the multilayered analogy of a serial burglar. Imagine the virus is a burglar not dissimilar to the one Cary Grant plays in Alfred Hitchcock’s 1955 masterpiece To Catch a Thief—a master of slipping in and out of hostile environments undetected. This burglar is so adept at their craft, they can execute a job even at a crowded cocktail soiree. The first thing the burglar must do upon arriving at the scene is avoid immediate recognition. When he appears at the door, it is as an invited guest, not an intruder—just as SARS-CoV-2, upon entering a human cell, has already changed its exterior so as to evade immune detection.
(Original Caption) Grace Kelly and Cary Grant in 'To Catch a Thief' by Alfred Hitchcock. (Photo by Paramount Pictures/Sunset Boulevard/Corbis via Getty Images)
CORBIS VIA GETTY IMAGES Second on the burglar’s agenda is surreptitiously anesthetizing the guests. The virus, as we’ll see in upcoming pieces in this series, has an impressive capacity for arresting the many checkpoints the cell normally has in place to impede infection. Next the burglar must disarm the security system. The equivalent of this for SARS-CoV-2 occurs when the virus silences the many signals an infected cell typically sends to alert nearby cells to the presence of an intruder. Last but not least, to top it all off, the burglar breaks the fire alarm and starts a fire to cover his tracks and divert attention away from 1184
himself before moving on to the next function. The fire stands in for the immune dysregulation the body can experience if a Covid-19 infection progresses to more critical stages of illness, potentially ending in death. However facile this analogy may seem, it bears a close resemblance to what actually occurs when SARS-CoV-2 imposes itself upon a human host. I will now describe the mechanics of the first part of this process, when the virus disarms our first line of immune defense. Evasion of innate immunity When an invading pathogen activates the body’s extensive, interferon-led warning system, it triggers three types of immune response. The first is the innate immune response. This line of defense goes on the offensive when the identity and purpose of a pathogen is unknown. The second is the adaptive immune response, which is composed of antibodies and T cells that recognize and attack specific pathogens. The third and final wave is the T and B cell memory response. Innate immunity involves proteins known as pattern-recognition receptors that, over the course of evolution, have been hard-wired to identify pathogen-associated molecular patterns or PAMPs. Commonly found in many pathogens, recognition of these molecules allows the body to respond immediately to invaders old and new. Some of the better-known PAMPs include bacterial lipopolysaccharides, acids, bacterial DNA, and both single- and double-stranded RNA. Activation of these pathways is also necessary to trigger the adaptive immune response. Is innate immune suppression observed in newly infected Covid19 patients? The answer, according to lab studies of cultured virus and Covid-19 patients, appears to be yes. One group of researchers conducted an exhaustive survey of proteins and peptides excreted in the urine of uninfected and infected but asymptomatic or mildly ill patients. Many proteins involved in the innate immune response were markedly downregulated, while proteins characteristic of a hyperimmune state were present in patients with severe disease. Another study monitored the expression of immune-related genes in the respiratory cells of infected patients. They found very few 1185
changes in the activation of innate immune response genes within the first 24 hours post-infection. Together, these experiments demonstrate the ability of SARSCoV-2 to suppress the immune response in the first few days following infection. Remember, the first obvious symptoms of infection are the consequence of the immune reaction to the virus, not to virus-induced damage itself. My next piece for this series will be the first of several that explores the virus’ mechanisms of immune suppression in depth. We’ll begin with the specialized compartment SARS-CoV-2 erects to hide its replication activities from the rest of the cell. This article originally appeared in Forbes magazine, and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part Four)
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part Five) Forbes | August 18, 2021 | Article
3D illustration of a besieged castle GETTY
This is the fifth article in a 15-part series called “Relevance of Immune Suppression by SARS-CoV-2 to Understanding and Controlling the Covid-19 Pandemic,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read part one, part two, part three, and part four. The second section of this series, which begins with this piece, will discuss language and an amount of detail suitable for the lay person with a serious interest in science and medicine. If viral proteins were manufactured out in the open, they would run the risk of drawing attention from innate immune sensors 1187
suspended in the cytoplasm of the cell. To minimize risk, the virus sets itself up in a privileged compartment, a double membrane vesicle, which serves as a replication site where viral enzymes can whir away unnoticed. Like soldiers under siege in a well-armed fortress, so long as the structure holds, they will remain protected and out of sight. These compartments are a recurring motif among viruses, including poliovirus, hepatitis C, and coronaviruses more broadly. Their biogenesis is not completely understood, but it is expected they derive from the membranes of well-worn cellular pathways that conduct routine functions for the cells, such as disposal of damaged cellular components. The formation of these is facilitated by the interaction of virus-specific proteins, which modify the formation of such vesicles to the virus’ advantage.
Coronavirus-induced DMVs revealed by cryo-ET. "A MOLECULAR PORE SPANS THE DOUBLE MEMBRANE OF THE CORONAVIRUS REPLICATION ORGANELLE" HTTPS://SCIENCE.SCIENCEMAG.ORG/CONTENT/369/6509/1395
A double membrane vesicle serves two main purposes. First, it concentrates viral proteins and host factors in one central location. The second I alluded to previously—it helps the virus obscure its replication intermediates from possible immunodetection. In particular the cell has a series of alarms that detect single and double stranded RNAs. Secreting the secondary intermediates required for such a vesicle prevents detection by what are called toll receptors. 1188
The outer membrane of the double membrane vesicle interconnects with the endoplasmic reticulum (ER) and other virusinduced membranes. For SARS-CoV it was suspected that replication sites were formed using the ER membrane, while budding sites also used membranes from the Golgi apparatus and endoplasmic-reticulum–Golgi intermediate compartment. According to prior research on SARS-CoV and MERS-CoV, the nonstructural proteins NSP3 and NSP4 play a likely role in the formation of these privileged compartments. NSP6 and other host factors might be involved also. All three proteins have transmembrane domains that recruit the scaffolding of host cell membranes for their own purposes. NSP3 has membrane disordering and proliferation abilities that allow it to either participate in membrane production or expand existing membranes. It contains two transmembrane regions that interact with ER membranes and cause membrane buildups in infected cells. The luminal loops of NSP3 and NSP4 interact with counterparts on the opposite side of the ER, inducing membrane pairing. NSP3 and NSP4 also associate with NSP6 during the assembly of the replication complex. Study of NSP6 in other viruses has established that it can induce autophagosomes, a particular type of double membrane vesicle that delivers cellular detritus to lysosomes for degradation. NSP6 might interfere with adaptive immunity by ensuring any immunomodulatory proteins end up in autophagosomes, thus halting their ability to counteract the invading pathogen. Some viral replication organelles, like those seen in picornaviruses, have open configurations that accommodate easy mobility between the compartment and surrounding cytosol. In coronaviruses, they’re closed—which raises the question of how newly minted viral mRNAs are exported for translation.
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Architecture of the molecular pores embedded in DMV membranes.
"A MOLECULAR PORE SPANS THE DOUBLE MEMBRANE OF THE CORONAVIRUS REPLICATION ORGANELLE" HTTPS://SCIENCE.SCIENCEMAG.ORG/CONTENT/369/6 509/1395 The solution, cryo-electron microscopy studies have identified, is a pore that spans the inner and outer membrane of the vesicle—a bridge connecting the cloistered interior to the surrounding cytosol. NSP3 is the primary building block behind this complex, though NSP4 and NSP6 are likely fellow constituents. In the next piece for this series, I will discuss at length another element of the virus’ immune suppression strategy: mRNA mimicry. This article originally appeared in Forbes magazine, and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part Five)
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Children Born During Pandemic Show Lower Cognitive Scores Forbes | August 19, 2021 | Article
A new preprint study presents the alarming finding that children born during the pandemic in the US show reduced verbal, motor, and overall cognitive performance compared to children born prepandemic. In the decade preceding the pandemic, the mean IQ score on standardized tests for children aged between three months and three years of age hovered around 100, but for children enrolled in this study born during the pandemic that number dropped to 78. The study’s authors from Rhode Island Hospital and Brown University used a large ongoing longitudinal study of child neurodevelopment, known as the RESONANCE study at Brown University to examine general childhood cognitive scores in 2020 and 2021 against the preceding decade (2011-2019). Analyses of cognitive development were assessed using the Mullen Scales of Early Learning, a population normed and clinically administered tool that assesses function across the five primary domains of fine and gross motor control, visual reception, and expressive and respective language via direct observation and performance. The study included 672 healthy children between 3 months to 3 years of age from the state of Rhode Island in the United States. The study population was controlled for age, gender, demographic, and socioeconomic indicators. The first 1,000 days of a child’s life are an important and sensitive period of child development. Environmental factors, including maternal mental and physical health, nutrition, stimulation, and supportive caregiving can affect the developing fetal and infant brain. The researchers found that even in the absence of direct infection, the environmental changes associated with the pandemic are significantly and negatively affecting infant and child development. Males and children in lower socioeconomic families were the populations most affected. Given this data comes from a relatively affluent part of the US, I am deeply concerned about the 1191
neurodevelopment of already marginalized low socioeconomic populations both domestically and internationally. The study’s authors write that “infants are inherently competent in their ability to initiate relationships, explore, seek meaning, and learn; but are vulnerable and depend entirely on caregivers for their survival, emotional security, modeling of behaviors, and the nature and rules of the physical and socio-cultural world that they inhabit.” With the isolation, lack of family or caregiver support, and limited stimulation and socialization enforced by Covid-19 public health guidelines, many infants have been deprived of normal developmental experiences. Due to the financial stressors of the pandemic and limited childcare options, home environments have also become more stressful and unstable. Forced to simultaneously juggle work and childcare, parents may not be able to devote significant time to creating enriching environments for infants. Lead study author Sean Deoni, associate professor of pediatrics research at Brown University, told the Guardian “Parents are stressed and frazzled … that interaction the child would normally get has decreased substantially.” With such dramatic results in a small sample size, we must consider the variables that may have influenced or biased the result. The study’s authors acknowledge that they did not investigate the impact of mask-wearing by the study staff during child visits and assessments. The inability of infants to see full facial expressions may have eliminated non-verbal cues, muffled instructions, or otherwise altered the understanding of the test questions and instructions. Yet the children born before the pandemic and followed through the initial stages, do not show a reduction in skills or performance, despite also completing the assessments with mask-wearing staff. Whether these lower cognitive scores will have a long-term impact is presently unclear. But given the magnitude of the problem uncovered in this study, a more substantive body of global research on this issue is urgently needed to develop evidence-based guidelines of care for expectant mothers, design effective strategies for followup care and support of affected infants. Such research could also provide informed guidance for school and daycare reopening and the provision of in-person and virtual learning. This article originally appeared in Forbes magazine, and can be read online here: Children Born During Pandemic Show Lower Cognitive Scores 1192
How SARS-CoV-2 Evades And Suppresses The Immune System (Part Six) Forbes | August 23, 2021 | Article
Couples at the masquerade ball. GETTY
This is the sixth article in a 15-part series called “Relevance of Immune Suppression by SARS-CoV-2 to Understanding and Controlling the Covid-19 Pandemic,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read part one, part two, part three, part four, and part five. In the most recent installment of this series, I described how SARS-CoV-2 evades immune sensors by constructing a secret compartment, a double membrane vesicle, for replication and messenger RNA synthesis. But not only does the virus have to conceal their synthesis, it must camouflage the messenger RNAs 1193
themselves so they can continue to evade detection beyond the confines of the compartment. To be translated by the ribosomes, messenger RNAs must leave the compartment. If they leave unprotected, they will trigger the immune sensors. Normally a class of innate immune receptors called Toll receptors would immediately pick up on the presence of messenger RNA that wasn’t cellular, either by recognizing the naked 5 prime end or lack of methylation, or absence of a polyadenylate 3 prime terminus. Detection by such receptors is followed by activation of secondary messages that in turn activate type-I interferons, which stimulate internal cellular pathways which destroy the RNA and that alert nearby cells to the presence of an invader. By masquerading its genome and messenger RNAs as cellular, SARS-CoV-2 produces enough virus to escape and infect other human hosts before immune defenses are fully mobilized.
Costume Ball at the Opera - after engraving by Jean Francois Bosio after 1800. Paris. With harlequin figure in centre (Commedia dell'arte character). (Photo by Culture Club/Getty Images) *** Local Caption ***GETTY IMAGES
For all the privileges double membrane vesicles afford SARSCoV-2, they do exclude ribosomes, a piece of cellular machinery the virus needs to make the proteins required for successful replication. For that reason, messenger RNAs must be released into the cytoplasm. And they too must closely resemble cellular messenger RNAs. 1194
Synthesis of proteins required for replication As it enters the cell, the viral genome in effect serves as the messenger RNA for synthesis of the first set of proteins required for replication. These proteins are specified by the initial two thirds of the viral genome. They are encoded by two long open reading frames, designated Orf1a and Orf1b. They are translated as a full length Orf1a protein and an Orf1a1b protein. Elongation of the Orf1a into the Orf1ab protein occurs by a -1 frameshift as the ribosomes translate the viral genome.
Figure 1: Schematic of the SARS-CoV-2 viral genome.ACCESS HEALTH INTERNATIONAL
Figure 2: Schematic diagram of translation.ACCESS HEALTH INTERNATIONAL
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Figure 3: A schematic representation of the SARS-CoV-2 genome and polyproteins Orf1a and Orf1b.ACCESS HEALTH INTERNATIONAL
Some of these proteins help create the special compartment. Four of these replication proteins, NSP10, NSP13, NSP14, and NSP16, add the 5 prime cap and methylation so they closely resemble messenger RNAs. The genome also comes equipped with a polyadenylate tail, as do all messenger RNAs. The formation of the complex requires a combination of enzymes that use cellular constituents to build a cap. Cellular mRNAs have the cap put on in the nucleus, where they are transcribed. However, the viral genome never reaches the cell nucleus. Therefore the cap must be attached during the process of genomic synthesis. That requires a minimum of four virally encoded enzymes. These enzymes are among the first made by translation of Orf1a. One is made from Orf1a, NSP10, and the remaining three are made from Orf1a1b. The next step is producing 3 prime messenger RNAs. To do this SARS-CoV-2 uses a methodology unique to its family of viruses, Nidovirales, by which 3 prime messenger RNAs are made beginning with transcription of the positive genome, creating a nested set of negative strand partial copies that contain both the original 5 prime and 3 prime untranslated terminal sequences.
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Figure 4: The messenger RNA replication and transcription strategy of SARS-CoV-2. Note the nested set of 3 prime messenger RNAs made by jumping from the 3 prime to the 5 prime transcriptional regulatory sequence. ACCESS HEALTH INTERNATIONAL
Once viral messenger RNAs exit the compartment through the specialized molecular pore into the cytoplasm for translation, they’re methylated with a cap at the 5 prime end. Presumably the polyadenylate tail is derived from the original genomic polyadenylate tail. The primary enzyme that adds polyadenylates to nascent cellular messenger RNAs is found in the nucleus. However, there is a second polyadenylation enzyme present in the cytoplasm which may add additional adenylate residues to the 3 prime end of the messenger RNA. Collectively these processes thoroughly disguise the viral messenger RNAs as cellular.
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Figure 5: Nonstructural proteins that participate in formation of the cap and methylation complex.ACCESS HEALTH INTERNATIONAL
Figure 6: (A) Also involved in this process are the RNA/NTP triphosphatase (TPase) and helicase activity, which is part of the NSP13 protein. NSP13 is essential for cap formation, breaking down nascent RNA so a guanosine monophosphate moiety can ACCESS HEALTH INTERNATIONAL
Fortunately the three-dimensional structure of each of these proteins is known in great detail and forms the basis for finding small molecule drugs that will interfere with viral activity. Any one of these, used alone or in combination, should be sufficient to inhibit the virus. Their discovery will bring us significantly closer to the day when we’ll have multimodal Covid-19 therapies to prevent infection and disease.
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In my next piece for this series I will discuss how SARS-CoV-2 promotes selective translation of messenger RNAs through the nonstructural protein NSP1. This article originally appeared in Forbes magazine, and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part Six)
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Babies And Toddlers Are Highly Contagious For Covid-19 Forbes | August 24, 2021 | Article
A new study by Public Health Ontario, published in JAMA Pediatrics, finds that infants and toddlers (0-3 years) are less likely to bring SARS-CoV-2 into the home but are more likely to transmit SARS-CoV-2 compared with older children (14-17 years). This study reinforces the urgent need to protect children and those they live with as they return in person to schools, and prevent further transmission in the home. During the early stages of the pandemic, many public health officials claimed that children were not at risk from infection or transmitted the virus. With a total of 180,175 pediatric Covid-19 cases reported from August 12 to 19 and children representing 22.4% of overall reported cases, this has clearly been proven wrong. “I think they were biased by the fact that children were sequestered at home,” Dr. Tina V. Hartert, a respiratory epidemiologist at Vanderbilt University told the New York Times, who was not involved in the new study. “They were recommended not even to play with neighbors, they didn’t go to school, they didn’t go to day care” The study looked at records of Covid-19 cases and positive coronavirus tests in Ontario from June 1 to Dec. 31, 2020. The researchers identified all positive tests associated with private households and then identified the “index case”, which was the first person to develop Covid-19 symptoms or test positive for the virus in each household. The study looked at 6,280 households in which the first person to catch the virus was under 18. Researchers then looked for secondary cases or others in the same home who got sick in the two weeks after the first child fell ill. In most cases, they found, the chain of transmission stopped with the infected child, but in 27.3 percent of households, children transmitted the virus to at least one other resident. Children from 14 to 17 made up 38 percent of all the index cases and were most likely 1200
to bring it into the home. However, the odds of household transmission were roughly 40 percent higher when the infected child was 3 or younger than when they were between 14 and 17. Some of these findings can be partially explained by behavioral factors, infants and toddlers cannot be isolated when sick, leading to more chances for transmission. Teenagers are also often spending time in close quarters, touching and even sharing drinks and food, creating more opportunities for them to contract the virus and bring it back to the home. With children under 12 not yet vaccinated and highly vulnerable to infection, it is critical we ensure masks and physical distancing are used in schools. Good ventilation, testing, contract tracing, and wastewater surveillance are also important tools to protect children and their caregivers. This article originally appeared in Forbes magazine, and can be read online here: Babies And Toddlers Are Highly Contagious For Covid-19
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part Seven) Forbes | August 23, 2021 | Article
This is the seventh article in a 15-part series called “Relevance of Immune Suppression by SARS-CoV-2 to Understanding and Controlling the Covid-19 Pandemic,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read parts 1, 2, 3, 4, 5, and 6. Part six of this series delved into the details of how SARS-CoV2 masquerades its viral messenger RNAs as cellular messenger RNAs. Now I will take a moment to zoom out and introduce a framework that will guide us through the next few installments: specific vs. nonspecific SARS-CoV-2 immune suppression. To recap, SARS-CoV-2 encodes many proteins in its genome that modify and suppress the immune system. New variants appear to improve upon these existing capabilities, allowing the virus to replicate to high concentrations without drawing the attention of cellular immune sensors. The primary objective is downregulation of interferon and interferon-stimulated genes. SARS-CoV-2 has nonstructural proteins (NSPs) and accessory genes, including open reading frames (Orfs), that contribute collectively to this effort. Like Swiss army knives, the viral proteins of SARS-CoV-2 are multifunctional, with many performing several highly specific tasks. NSP3 alone encodes seven distinct functional domains, including protease cleavage, de-ubiquitination, de-ADPribosylation, and autophagy modulation. All the virus’ mechanisms of immune suppression can be generally described as specific or nonspecific. Nonspecific refers to viral proteins that block entire pathways, such as export of viral 1202
proteins from the cell. Specific pathways are those that interfere with one or two cellular functions of immunoregulatory pathways only. Nonspecific immune suppression Nonspecific suppression, such as the obstruction of protein synthesis and export, indiscriminately affects entire cellular processes, even the machinery that potentiates viral propagation. This blunt apparatus of suppression forms an intensive blockade against immune signaling pathways, activated in coordination with counterbalancing elements that allow SARS-CoV-2 to continue replicating even as general cellular functioning is disrupted. NSP1, for example, has a unique and highly significant role: to block the translation of cellular RNA, yet permit translation of viral messenger RNA. So efficient is this gatekeeping mechanism, which obstructs the entry of cellular messenger RNA into the ribosome, that eight hours following infection, the majority of new proteins made are viral, not cellular. NSP1 also interacts with the host messenger RNA export receptor NXF1-NXT1 to retain cellular messenger RNAs in the nucleus. By blocking export of cellular messenger RNAs, NSP1 also inhibits the production of new signaling molecules that could activate the innate immune response. This permits translation of viral proteins and their synthesis and export to the ribosome, which occurs entirely in the cytoplasm. Another nonstructural protein of SARS-CoV-2, NSP16, engages in nonspecific immune suppression by inhibiting the splicing of cellular RNAs, while NSP8 and NSP9 shut down signal sequencing that would warn surrounding cells. In addition, the SARS-CoV-2 Orf8 protein, recent studies show, interferes with the functionality of the major histocompatibility complex type-I (MHC-I). Evidently MHC-I proteins accumulate in the lysosomes of Orf8-expressing cells, suggesting that Orf8 selectively targets the molecule for degradation and inhibits its involvement in the antiviral response. Notably, an additional benefit of the sum total of all the mechanisms SARS-CoV-2 uses to suppress RNA is to limit the ability of microRNAs, several of which have the capability of interacting with genomic RNA, to inhibit viral replication. Many 1203
microRNAs are in fact capable of binding and possibly inhibiting both SARS-CoV-2 genomic stability and messenger RNA translation.
Mechanisms of nonspecific immune suppression. Studies show that SARS-CoV-2 interferes with cellular messenger RNA nuclear export (via NSP1); signal peptide membrane transport (via NSP8 and NSP9); phosphorylation and other post-translational ACCESS HEALTH INTERNATIONAL
Specific immune suppression Specific suppression is more precise as a mode of attack, zeroing in on microscopic structures, interactions, and processes with equally specific effects. Many of the Orfs, as far as we know, only interact with select innate immune signals, like interferon and interferonresponsive genes, while NSP1, in addition to its nonspecific functions, also specifically inhibits proteins that specifically trigger alarms, either at the beginning or further down the chain of an immune pathway.
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NSP1 inhibiting RIG-I. SARS-CoV-2 and its effect on interferon. RIG-1 (retinoic acid-inducible gene 1) is inhibited by NSP1; MAVS (mitochondrial antiviral signaling protein); IKKε (inhibitor of nuclear factor kappa-B kinase subunit epsilon) is ACCESS HEALTH INTERNATIONAL
The importance of such inhibition in virus replication and pathogenesis is clear. Mutations that disrupt the function of any of these genes and protein pathways dramatically decrease the replication and pathogenesis of the mutant virus, as experiments in cell cultures and animal models have shown. Whether specific or nonspecific, any one of these mechanisms can, with the right mutations in place, increase in effectivity, which in turn will allow the virus to replicate more prolifically and reach higher titers. We now have evidence that this is what happened with the Alpha variant. A study that used deep sequencing techniques to investigate differences in protein transcription and expression between the original and Alpha strains found an 80-fold increase in the amount of Orf9b subgenomic RNA produced by the Alpha variant and a ten-fold increase in the messenger RNA corresponding to the Orf6 proteins. Both Orf9b and Orf6 are inhibitors of innate immunity. While we don’t yet understand the evolutionary trajectory of the Delta variant in depth, there is reason to suspect that its immunosuppressive capabilities are heightened compared to previous, less infectious variants. Even single point mutations in 1205
various genes are enough to substantiate change, the consequences of which have affected the development of influenza vaccines and hepatitis C drugs. We’re still learning about these immunosuppressive pathways, but their sheer number is impressive. It now appears that some variants have even longer asymptomatic periods than their predecessors and replicate to higher titers. Although some researchers attribute these qualitative changes to only one of the viral genes, the envelope protein, I believe that given the complexity of the overall replication cycle, that’s highly unlikely. We must consider the virus’ capacity to create conditions conducive to its own replication and propagation. High on this list is suppression of the innate immune system. In the next series we’ll highlight specifics. Each of these presents several opportunities to understand what is happening with viral variation and opportunities to create new drugs. As we’ll see, there is a plethora of opportunities for drug development which will require substantial engagement with global research capitals in the US and elsewhere, in academia and the biopharmaceutical industry. This article originally appeared in Forbes and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part Seven)
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Decoding The Gordian Knots At The Ends Of The SARS-CoV-2 Genome Forbes | August 25, 2021 | Article
This is the first in a series describing the role of the beginning and end of the SARS-CoV-2 genome in the virus life cycle. I summarize what we know and point out what we need to know about these ends in order to develop new antiviral drugs. Unraveling the details of the life cycle of the SARS-CoV-2 virus is much like reading a mystery novel. The truth is often deeply buried and the journey laden with misleading clues. As every reader knows, the first and last pages are inevitably the most important. The analogy is closer than you may imagine. The bookends of the viral genome are responsible for many of the virus’s critical functions, including initiation of replication, protein synthesis, and messenger RNA synthesis. Unraveling the details of exactly how these functions occur requires puzzling out the most intricate mysteries. The first observation is that both the beginning five prime (5’) end and terminal three prime (3’) end are complex (Figure 1).
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FIGURE 1: (A) 5’ end of the SARS-CoV-2 genome; (B) 3’ end of the SARS-CoV-2 genome; (C) Gordian Knot GORDIAN KNOT
RNA is a self-folding polymer. The 30,000-nucleotide long genome self-assembles into elaborate stem-loop structures. The stems are base-paired, G pairs with C and A with U (or T in the case of DNA), while the loops are unpaired (Figure 2).
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FIGURE 2: (A) Theoretical stem-loop structure; (B) Schematic representation of a stemloop. IGEM.ORG
Alternatively, these structures can fold into pseudoknots, emerging in various forms (Figure 3).
FIGURE 3: Theoretical pseudoknot stem-loop structures RUTGERS UNIVERSITY
Collectively, these are called secondary structures. The secondary structures of diverse coronaviruses are relatively well conserved, even though the primary genome sequences differ. The similarity of these structures suggests that the structure itself, in addition to the primary nucleotide sequence, plays an essential role in virus replication. Moreover, understanding the details of how the ends of the viral genome interact with viral and cellular proteins is a prerequisite to the discovery of new antiviral drugs. 1210
The recent introduction of a new drug to prevent and treat influenza illustrates exactly how important this research is in finding new drugs to prevent and treat SARS-CoV-2 infection. A study from July 2020 found that the anti-influenza drug baloxavir marboxil (also referred to as Xofluza), reduced close-quarters transmission of Influenza A by 80%. The influenza virus uses a process called cap snatching to reproduce, effectively snatching host RNA and reusing it in the reproduction process. Xofluza binds to and inhibits the proteins involved in the cap snatching process. My hope is that these brief descriptions of what we know and don’t know about the termini of SARS-CoV-2 will stimulate scientists around the world to develop drugs similar to Xofluza for the virus at hand. Entry of the viral genome and production of the viral replication complex Upon fusion of the viral and cellular membrane, the viral genome is deposited into the cytoplasm of the cell. The first requirement of the viral RNA is to avoid triggering the antiviral defenses, collectively called the innate immune response. A primary trigger of the innate immune response is the entry of foreign RNA. The cellular alarm signals recognize naked RNA 5’ termini, unmethylated RNA, and RNA that does not carry a polyadenylated (poly-A tail). The SARS-CoV-2 genomic RNA skirts all these alarm signals as it is properly capped and methylated by the virus's own proteins. It also carries a poly-A tail. In other words, it masquerades as a cellular messenger RNA. Once safely inside the cytoplasm, replication begins. As it enters a cell, the viral genome is organized as a compact package bound to multiple nucleocapsid capsid (N) proteins (Figure 4). The viral genome itself serves as a template for the synthesis of the very first viral proteins located in a long open reading frame that begins at the “AUG” initiation codon located 266 nucleotides from the 5 prime end of the genome, buried deep within the 5’ stem-loop structures.
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FIGURE 4: Viral RNA bound to the N protein. LIJI THOMAS / NEWS MEDICAL
Question: How do the translation machinery, translation initiation, and associated initiation factors recognize the genome RNA complexed with the N protein. Does the N protein disassociate from the RNA on entry spontaneously or is it displaced by cellular proteins and the ribosome during protein synthesis? Virus protein synthesis begins when the ribosomes bind the 5' end of the genome and initiate synthesis (Figure 5).
FIGURE 5: Messenger RNA being translated by a ribosome. ACCESS HEALTH INTERNATIONAL
It is no mean feat for the ribosome to navigate the intricate 5’ structure. Ribosomal entry likely requires the assistance of a cellular 1212
unwinding enzyme (a helicase) allowing slippage of the ribosome along the RNA until it encounters the “AUG” initiation codon. Initiation of the Orf1a and Orf1b proteins begins at position 266 with stem-loop 5 (Figure 1). We note that there is the possibility of initiation at position 107. There is an “AUG” codon within the reading frame at this position which would proceed to yield a nine-amino acid long peptide before encountering two termination codons I wonder if initiation at position 107 followed by reinitiation at position 266 is possible. A similar 5’ “AUG” occurs in SARS-CoV. As the structure of the stem-loops is nearly identical and the resulting theoretical peptide in SARS-CoV from the first “AUG” closely resembles that of SARS-CoV-2, this is not an anomaly confined to SARS-CoV-2 (Figure 6). It would be interesting to learn if this small peptide is functional and we will continue to research this sequence in an effort to elucidate it.
FIGURE 6: SARS-CoV and SARS-CoV-2 5’ ends, denoting the initial “AUG” codon that results in a nine amino acid long peptide before the Orf1ab initiating “AUG” downstream in the sequence. Note the resultant amino acid peptides in both SARS-CoV and SARS.
ACCESS HEALTH INTERNATIONAL Question: Why does Orf1a protein start at the second “AUG” at position 266 and not the first “AUG” at position 107 (Figure 1). The general rule is that protein synthesis in mammalian cells begins at the initiation codon closest to the 5’ end. Is it possible that initiation actually begins at position 107 to yield a nine amino acidlong peptide of unknown function followed by re-initiation at position 266? 1213
The first proteins made are the two products of the Orf1a and Orf1b genes. These long polypeptides are cleaved into 15 proteins, called the non-structural proteins (NSPs1-16: there is no NSP11) that are required for the synthesis of small messenger RNA that direct the synthesis of the proteins of the virus particle S, M. E, and N, as well as the regulatory proteins.
FIGURE 7: Frameshift between Orf1a and Orf1b ACCESS HEALTH INTERNATIONAL
The very first viral protein made, NSP1, plays a critical role in virus replication. The protein blocks the production of cellular proteins while permitting the production of viral proteins. NSP1 acts by obstructing the entry of cellular RNAs into the ribosome (Figure 8).
FIGURE 8: Ribosomal translation ACCESS HEALTH INTERNATIONAL
Recent studies show that the N protein binds to an RNA sequence of the 40S subunit of the ribosome obstructing the entry tunnel. Preferential synthesis of viral proteins allows much of the cell’s energy to be devoted to producing viral components. 1214
How then are viral proteins made? The mystery was solved by studies that show any message with stem-loop 1 located near the 5’ terminus can be translated in the presence of NSP1. Both the viral genome and all viral messenger RNAs meet this requirement. A brief description of viral messenger RNA synthesis explains why all viral messages carry the requisite 5’ stem-loop. The structure protein S, M, E, and N of the virus particle and regulatory genes Orfs by the 3’ end of the genome. The template for their synthesis is a nested set of negative-strand RNAs that all share a 3' and 5' termini (Figure 9).
FIGURE 9: The messenger RNA replication and transcription strategy of SARS-CoV2. Note the nested set of 3’ messenger RNAs made by jumping from the 3’ to the 5’ transcriptional regulatory sequence. ACCESS HEALTH INTERNATIONAL
As the negative strand elongates, the growing end encounters what’s called termination regulatory sequences (TRS-B). Transcription pauses after copying the TRS sequences (Figure 10) and then resumes by pairing with the complementary TRS-L sequence located near the 5’ terminus. 1215
FIGURE 10: 5’ End through TRS-L at nucleotide position 75. ACCESS HEALTH INTERNATIONAL
The messenger RNAs all begin with the same 5 ’end that extends from nucleotide 1 through nucleotide 75 and includes stem-loops 13, but not stem-loops 4-7. Question: How does the presence of stem-loop 1 relieve the NSP1 translation block? Does NSP1 bind to stem-loop 1? If so is NSP1 recognition of stem-loop 1 determined by the sequence or structure. Can stem-loop 1 of SARS-CoV-2 relieve the NSP1 block of other coronaviruses? What is the role of cellular translation initiation factors in viral messenger RNA translation? Question: Why does transcription pause at TRS-B sequences. Does the topology of the replication complex facilitate the post pause jump to the 5’ TRS? Can the jump occur only in cis to the same genome or is a trans jump possible to a second replicating genome? Can a jump occur to any TRS sequence or only the one closest to the TRS-L sequence 5’ end? Do cellular proteins participate in messenger RNA synthesis? The second part of this series will describe the role of the 5 and 3’ end in the initiation of replication and transcription. 1216
This article originally appeared in Forbes, and can be read online here: Decoding The Gordian Knots At The Ends Of The SARS-CoV-2 Genome
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Depression And Anxiety Double In Youth Compared To Pre-Pandemic Forbes | August 25, 2021 | Article
At the beginning of the pandemic, the CDC advised that children and adolescents were considered the lowest-risk group with regards to medical concerns and complications from Covid-19. As the pandemic rages on, we are seeing a rise in pediatric Covid-19 cases and hospitalizations and we are witnessing a global syndemic of mental health issues in young people. I have written about the pandemic’s profound mental health impact on young people in the past but a new study from the University of Calgary, showing that depression and anxiety symptoms have doubled in children and adolescents globally when compared to pre-pandemic times is more than cause to raise the alarm again. This study is further evidence that many different demographics will suffer from Covid-19 related post-traumatic stress disorder (CV-PTSD). The University of Calgary study is a meta-analysis, which pools together data from 29 separate studies from around the world, including 80,879 youth globally. The meta-analysis includes 16 studies from East Asia, four from Europe, six from North America, two from Central and South America, and one from the Middle East. Prior to the pandemic, rates of clinically significant generalized anxiety and depressive symptoms in large youth cohorts were approximately 11.6% and 12.9%. The meta-analysis found that the pooled estimates of clinically elevated child and adolescent depression and anxiety were 25.2% and 20.5%, respectively, suggesting that both had likely doubled. The most alarming finding was that mental health difficulties were more prevalent as the pandemic persisted. Indicating that as the pandemic continues, mental health issues are worsening and compounding among young people. A potential delay of 2-4 years is often observed between the traumatic event and the development of a mental health disorder, meaning that while we may be seeing 1218
some of the initial effects of the pandemic, we will continue to see more over the next 2-4 years. Dr. Sheri Madigan, PhD, co-author of the paper and UCalgary clinical psychologist believes that the unpredictability of the pandemic is contributing to this increase. “We’re continuing to see compounding effects of the pandemic,” she says. “It’s disjointing for kids because they can’t predict what their environment is going to look like, and we know when their world lacks predictability and controllability, their mental health suffers.” The researchers also found that females and older youth were both at greater risk for both depression and anxiety difficulties. For many children and adolescents, life during the pandemic barely resembles a typical childhood. Critical developmental needs go unmet as children are isolated from friends, and miss out on typical school activities such as sporting teams and performing arts productions or milestones like prom and graduation. In particular, adolescent brains are wired for seeking out new social and romantic connections that allow them to achieve a sense of status and self worth, critical in managing symptoms of depression and anxiety. Family members cannot often fill the void left by decreased socialization with peers, leading to increasing rates of loneliness among youth. Lead author of the study and clinical psychologist, Dr. Nicole Racine, PhD, believes that this could be a contributing factor to these dramatically rising rates of depression and anxiety. “Once you enter adolescence you begin differentiating from your family members and your peers can actually become your most important source of social support,” says Racine. “That support has been greatly reduced, and in some cases absent altogether, during the pandemic.” Research shows that routines support healthy social-emotional development in early childhood, however, with the constant reopening and closing of schools, daycares, and after-school activities, this can be difficult to maintain. A structured and predictable home environment can also help children develop their self-regulation skills to identify and manage their feelings and not become overwhelmed. But with the financial impact of the pandemic and the increased psychological stress placed on parents and caregivers juggling work and childcare, it may also not always 1219
be possible to provide such an environment. But rebuilding and maintaining routines with children around sleeping, eating, and taking care of their bodies will be critical in their recovery. But the burden cannot be solely on parents and caregivers. As this issue continues to escalate, we need to be implementing a recovery plan now. Children’s hospitals in Canada are reporting a 100% increase in mental-health-related admissions and McMaster Children’s Hospital specifically has reported a 200% increase in pediatric suicide attempts. As a result, Canada’s children’s hospitals and advocacy organizations have united to create a #codePINK campaign. The term “Code Pink” is used to declare a pediatric emergency, and the campaign is calling on the federal and provincial/territorial governments to act immediately to address this emergency. We need a similar call to action both in the US and globally, a rapid expansion and increase in access to mental health services. Youth have some of the highest unmet needs in mental health care. The development of specialized services such as youth mental health hubs will go a long way in addressing that disparity. Finally, the impact on youth mental health is yet another reason to ensure our schools and daycares are implementing vaccination, masking, physical distancing, testing and tracing policies, and using ventilation and wastewater surveillance to reopen safely. Only then can children begin to reclaim the experiences required for healthy social and emotional development. This article originally appeared in Forbes, and can be read online here: Depression And Anxiety Double In Youth Compared To Pre-Pandemic
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How The Pandemic Is Fueling Eating Disorders In Young People Forbes | August 27, 2021 | Article
I just needed more control” Anne, a college student from Massachusetts, took a deep breath as she recounted her experiences with disordered eating during the pandemic. Anne had been aware of her struggles with food for much of her life, but it wasn’t until the pandemic hit that she started to feel completely out of control, “… I was acutely aware that I wasn’t moving (exercising) as much… I needed to compensate.” While she has since been able to receive treatment for her eating disorder, Anne’s case represents a surge of young people who have struggled with new or relapsed eating disorders since the beginning of the pandemic. Many of these young people are still struggling without access to treatment. During the first 12 months of Covid-19, the number of hospital admissions among adolescents with eating disorders at the University of Michigan Medical School has more than doubled. According to an analysis of medical record data from 80 hospitals, there has been a 25% increase in the number of adolescent eating disorder patients since March 2020. Over the course of the pandemic, the National Eating Disorder Association helpline has reported a huge 40% increase in call volume. Isolation, lack of structure, and heightened anxiety are three possible triggers for the increase in eating disorders. While the majority of the population faced all three as the world entered lockdown, Anne describes the unique pressures that young adults and adolescents faced on social media, “there was a general discourse on social media about not gaining weight during Covid or focusing on getting fit during Covid. So many people were equating selfimprovement with weight loss or changing eating habits and it really affected me.” Dr. Jillian Lampert, the Chief Strategy Officer at a treatment center called the Emily Program, is unsurprised by the impact of social media on young people, “given the isolation that Covid 1221
brought, all of the messages on social media platforms were one of the main interactions that people had with the world… we’ve seen a huge influx in the need for care.” Despite the demonstrated need for eating disorder care, it has become clear that telehealth models used during the pandemic are no substitute for in-person treatment. In a survey of eating disorder patients, 74% of participants who had transitioned from in-person treatment to telehealth during the pandemic found that telehealth was less effective than their in-person treatment, “It became so easy to hide… all that my treatment team could see was my face so I would throw away certain parts of my meal or go to the bathroom immediately after the session.” Anne says. Telehealth has addressed geographical barriers to care, yet significant financial barriers to eating disorder treatment still exist, indicating that there may be an even greater number of adolescents suffering from eating disorders that are unaccounted for by treatment center or hospital statistics. The average cost for in-patient eating disorder treatment in 2016 was $19,400 and lasted approximately 14 days. Many insurance companies will provide some form of financial support, but sometimes insurance only provides coverage for outpatient or shortterm mental health treatment. Dr. Lampert notes that a lack of proper insurance coverage is one of the greatest barriers to people receiving care for their eating disorders, “Right now, if you have diabetes—another nutrition related illness, you’ll have coverage to see a dietician… if you have an eating disorder, you won’t. It really makes no sense to not have nutrition related coverage for a nutrition related illness… When insurance doesn’t cover people’s healthcare, they tend not to get the care they need.” The financial barriers to eating disorder treatment are especially relevant as recent studies have demonstrated that food insecurity, which predominantly affects low-income households of color, can be a significant indicator for eating pathology. In a review of studies that examined the relationship between disordered eating habits and food insecurity among adults, it was found that food insecurity was associated with binge eating, weight controlling behaviors, and bulimia. While it is an emerging area of research, this relationship is
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significant within the context of the pandemic where food insecurity more than doubled in households with children and adolescents. Dr. Christine Peat, a psychologist and professor in the Center of Excellence for Eating Disorders at University of North Carolina Chapel Hill, has seen the effects of food insecurity in her own patients, “Patients have come to me and said listen, I grew up in a food insecure household and it almost set me up for this pattern where at the beginning of the month when we had our SNAP benefits I might just eat everything in sight because I wasn’t sure when we were going to have food again… when those benefits were low, they were then forced into restrictive eating patterns.” Because of this relationship, individuals from low-income, foodinsecure households are especially at risk for eating disorders but are less likely to have access to treatment, which has only been exacerbated by the pandemic. Covid-19 has exposed a huge number of mental health trends and disparities that exist in our current healthcare system. As the prevalence of adolescent eating disorders continues to rise, it is up to us to recognize these faults in our treatment systems and to rally for policy changes and insurance models that can support the growing mental healthcare needs that are being demonstrated across the nation. If you or a loved one is struggling with an eating disorder; you can call the toll-free, confidential NEDA Helpline, Monday-Thursday from 9:00 a.m.- 9:00 p.m. and Friday from 9:00 a.m. - 5:00 p.m. at 1-800-931-2237. This article originally appeared in Forbes, and can be read online here: How The Pandemic Is Fueling Eating Disorders In Young People
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part Eight) Forbes | August 27, 2021 | Article
STUCK SHIP EVER GIVEN, SUEZ CANAL — MARCH 26, 2021: Maxar's WorldView-2 collected new high-resolution satellite imagery of the Suez canal and the container ship (EVER GIVEN) that remains stuck in the canal north of the city of Suez, Egypt. Please DIGITALGLOBE/GETTY IMAGES
This is the eighth article in a 15-part series called “Relevance of Immune Suppression by SARS-CoV-2 to Understanding and Controlling the Covid-19 Pandemic,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read parts 1, 2, 3, 4, 5, 6, and 7. SARS-CoV-2 Multilevel Blockade of Cellular Gene Expression 1224
In this section, I will discuss how SARS-CoV-2 blocks expression of almost all cellular genes and proteins to favor its own messenger RNA and protein synthesis. More specifically I will discuss transcription initiation, messenger RNA splicing and stability, messenger RNA export to the cytoplasm, and protein translation. Blockage of transcription initiation The first step in assembling this blockade consists of inhibition of initiation of transcription of a specific messenger RNA species, those which specify type 1 interferons and interferon responsive genes. We will discuss these specific pathways in a later installment of this series. Splicing inhibition Next comes the inhibition of splicing. The nonstructural protein NSP16 inhibits the splicing of cellular RNAs. Primary nuclear gene transcripts are in general rapidly degraded, unless spliced and exported. While most cellular RNAs are spliced, SARS-CoV-2 messenger RNAs do not require nuclear splicing. NSP16 allows for preferential production of viral RNAs and proteins over their cellular counterparts.
Figure 1: Splicing of cellular messenger RNAs. This process occurs within the nucleus. Cellular messenger RNAs are made in the nucleus and exported to the cytoplasm. SARSCoV-2 messenger RNAs are not spliced, made in the cytoplasm, and not found in ACCESS HEALTH INTERNATIONAL
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Following transcription, messenger RNAs must be spliced before they can be exported and translated into proteins. The spliceosome, a protein-RNA complex, catalyzes the splicing reaction by removing introns, a specific type of nucleotide sequence, from cellular messenger RNA transcripts (Figure 1). Central to the action of the spliceosome are two RNA sequences, designated U1 and U2, which bind to nascent RNA to initiate the splicing process. A recent study found that NSP16 binds to the spliceosome RNA. To be more precise, it binds to both the U1 and U2 sites of the spliceosome RNA, which play a critical role in recognition of the ends of the introns to be removed. Binding of NSP16 prevents the spliceosome from recognizing the corresponding intron sequences and blocks splicing altogether (Figure 2). The net result is nascent cellular messenger RNAs are not matured. In confirmation the authors also reported a marked increase in intron retention in cells infected by SARS-CoV-2, evidence that many transcripts went unspliced due to NSP16-mediated interference.
Figure 2: NSP16 Binds to U1 and U2 at Their mRNA Recognition Sites “SARSCOV-2 DISRUPTS SPLICING, TRANSLATION, AND PROTEIN TRAFFICKING TO SUPPRESS HOST DEFENSES” HTTPS://WWW.CELL.COM/CELL/FULLTEXT/S0092-8674(20)31310-
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There are several important consequences of degrading messenger RNA. First and foremost, cellular signals that might be newly initiated to protect the cell from infection are never made. This includes any protein, such as interferons, or other proteins which the cell may use to defend itself, meaning the virus has a free pass to continue replicating. It also means the infected cell cannot make new proteins that will signal to nearby cells or the immune system that the cell is infected. Replication of viruses may also be inhibited by several different classes of cellular RNA. One of the most intensively investigated are microRNAs. MicroRNAs are small, non-coding RNAs that help cells control gene expression. They act by binding to corresponding sites on viral RNA, leading to its degradation. Blocking splicing and subsequent degradation of nuclear messenger RNA is very likely to inhibit the synthesis and activity of microRNAs as well and any other RNA species of which there are several that are postulated to have antiviral capabilities. Blocking splicing is therefore a critical step in ensuring a favorable environment for viral replication. If cellular messages that have been initiated and transcribed cannot be spliced, they are degraded, reducing the total number of cellular messenger RNAs. Not only that, but because microRNAs are carved from full length messenger RNAs, I speculate this substantially downregulates the cellular production of microRNAs as well, which might otherwise have antiviral activity. Blockage of nuclear export If NSP16-mediated splicing inhibition is not complete or messenger RNA contains no introns, there is still a possibility they will be exported. However another block occurs at the nuclear pore (Figure 3). For messenger RNA to be translated it must be shuttled out of the nucleus and into the cytoplasm via a nuclear pore complex, an elaborate structure that mediates both exit and entry of macromolecules like proteins and RNA.
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Figure 3: Nuclear pore complex THE SCIENTIST MAGAZINE HTTPS://WWW.THESCIENTIST.COM/INFOGRAPHICS/INFOGRAPHIC-THE-NUCLEARPORE-COMPLEX-32456
NSP1 blocks the export of messenger RNAs by binding to two critical components of the transport complex, nuclear RNA export factor 1 (NXF1) and NTF2-related export protein 1 (NXT1). The result is messenger RNAs, if they are made, are retained in the nucleus. If they can’t be translated, they’re marked and destroyed. Once again, nuclear export of cellular messenger RNAs and RNAderived molecules like microRNAs is blocked. Preferential synthesis of viral proteins: NSP1 blocking translation of cellular messenger RNAs Last but not least, SARS-CoV-2 favors translation of its own proteins over cellular proteins. In addition to assisting with the blockage of nuclear export, NSP1 also blocks the translation of cellular RNA—while permitting the translation of viral RNA. So efficient is this gatekeeping mechanism that eight hours following infection, the majority of new proteins made are viral, not cellular. Blocking the translation of cellular messenger RNAs by NSP1 also 1228
inhibits the synthesis of interferon and any other cellular protein that might activate an immune response. NSP1 acts by obstructing the entry of messenger RNA into the ribosome (Figure 4 & 5). A finger of NSP1 extends into the entry port of the ribosome to recognize and bind a sequence of the 18s ribosomal RNA that lies within the channel.
Figure 4 & 5: NSP1 blocks ribosome entry of cellular messenger RNA. NSP1 permits ribosome entry of viral messenger RNA carrying a five prime loop. ACCESS HEALTH INTERNATIONAL
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Figure 6: NSP1 Binds to 18S Near the mRNA Entry Channel to Suppress Translation“SARS-COV-2 DISRUPTS SPLICING, TRANSLATION, AND PROTEIN TRAFFICKING TO SUPPRESS HOST DEFENSES” HTTPS://WWW.CELL.COM/CELL/FULLTEXT/S0092-8674(20)313106?_RETURNURL=HTTPS%3A%2F%2FLINKINGHUB.ELSEVIER.COM% 2FRETRIEVE%2FPII%2FS0092867420313106%3FSHOWALL%3DTRUE
How then are viral proteins made? A recent study offers some clues. Each viral messenger RNA shares the same 5 prime untranslated terminus. The 5 prime terminus contains several stemloop structures. The loop structure proximal to the 5 prime end is required for translation in the presence of NSP1. Hybrid messenger RNAs that carry this 5 prime end of the genome, including the loop, are also translated in the presence of NSP1. The location of the stem-loop structure relative to the 5 prime end is critical. The still untested hypothesis is that NSP1 recognizes the 5 prime viral messenger RNA terminus and releases blockage of 1230
the entry channel. As far as I know, this is a unique mechanism of translational regulation. The consequence of blocking cellular messenger RNAs is not only that it blocks any newly made cellular messenger RNAs, but it blocks existing messenger RNAs as well, providing a favorable environment for viral replication. The messenger RNAs already in the cytoplasm of the cell can no longer be used. The effect of this is twofold, limiting the production of cellular proteins altogether, allowing viral RNA proteins to be made.
View of the multiple barriers at “Checkpoint Charlie” between East and West Berlin. (Photo by Hulton Archive/Getty Images) GETTY IMAGES
Summary To recap, SARS-CoV-2 first ensures that the transcription of some cellular messenger RNAs cannot be initiated. If they are initiated, some are not spliced. If they are not spliced, they remain stuck in the nucleus. And if they exit the nucleus, some are not translated. In part nine of this series, I will discuss how SARS-CoV-2 prevents cells from signaling their neighbors and by blocking recognition of the infected cell by immune killer cells. This article originally appeared in Forbes, and can be found online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part Eight) 1231
The Mystery Of The False Start At The 5’ End Of SARS-CoV-2 Forbes | August 30, 2021 | Article
This is the second in a series describing the role of the beginning and ends of the SARS-CoV-2 genome in the virus life cycle. I summarize what we know and point out what we need to know about these ends in order to develop new antiviral drugs. Read more from this series in part one. In every mystery story, there are unsolved questions, loose ends, and false leads. Here we discuss an anomaly that may be either an important clue in SARS-CoV-2 replication and pathogenesis or may turn out to be irrelevant. There is a short string of nucleotides in SARS-CoV-2, as well as most coronaviruses, that has the potential to initiate protein synthesis between 150 and 200 nucleotides prior to the initiation of the first major protein in the virus, Orf1a. To recall, protein synthesis beings with the codon “AUG.” This codon specifies the amino acid methionine. Elongation of a protein continues as the translation machinery reads the nucleic acid sequence in groups of three until it terminates at well-defined groups of three nucleotides called stop codons. The stop codon comes in three forms: “UAA,” “UAG,” and “UGA.” We have observed that for SARS-CoV-2, there is an “AUG” in stem-loop four at position 107, preceding the “AUG” in stem-loop five at nucleotide position 266, which is the initiation codon used for the precursor proteins Orf1a and Orf1ab. The stem-loop four “AUG” codon and following nucleotide sequence could potentially encode a peptide nine amino acids long in SARS-CoV-2 between positions 107 and 133 (Figure 1).
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FIGURE 1: SARS-COV-2 5’ END SECONDARY STRUCTURE WITH BOTH THE UORF AND ORF1A INITIATING “AUG” CODONS HIGHLIGHTED. THE RED BOX INDICATES STEM-LOOP FOUR, WHERE THE UORF AND UORF KOZAK SEQUENCE ARE CONTAINED.ACCESS HEALTH INTERNATIONAL
We note, as have others, that many other coronaviruses contain an “AUG” 5’ to the Orf1a initiation codon in a similar position within the stem-loop structure, such as mouse coronavirus (MHV), bovine coronavirus (BCoV), MERS-CoV, and SARS-CoV-1 (Figure 2). Many of these also have the potential to code short peptide sequences ranging in length from three to thirteen amino acids. These sequences are not well conserved.
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FIGURE 2: COMPARISON OF SECONDARY STRUCTURE MODELS OF THE 5′ REGIONS OF MHV-A59, BCOV, MERS-COV AND SARSCOV-1. YANG AND LEIBOWITZ
The figure below illustrates the similarities and differences of the peptide sequences. We note that SARS-CoV-1 and SARS-CoV-2 are similarly terminated with double stops. Additionally, six of the nine amino acids are identical, indicating some conservation between SARS-CoV-1 and SARS-CoV-2.
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FIGURE 3: COMPARISON OF CORONAVIRUS 5’ UORFS. FROM TOP TO BOTTOM: NUCLEOTIDE SEQUENCES FOLLOWING THE 5’ “AUG” CODON FOR VARYING CORONAVIRUSES; RESULTANT AMINO ACIDS FROM NUCLEOTIDE SEQUENCES; FIGURE LEGEND.ACCESS HEALTH INTERNATIONAL
Hung-Yi et al indicate that more than 75% of coronavirus genomes share the characteristic AUG-initiated 5’ uOrf, indicating remarkably high cross-species conservation. For the remaining 25%, Hung-Yi and colleagues note an anomalous potential “CUG” codon-initiated open reading frame. These sequences are ultimately defined in a larger context by the Kozak sequence, which is a nucleic acid motif that facilitates ribosomal initiation in eukaryotic cells. The optimal Kozak sequence is GCCGCC(A or G)CCAUGG. The RNA sequence in question does not need to match the Kozak sequence exactly, but higher similarity correlates to greater translation success. The sequence leading up to the 5’ “AUG” of SARS-CoV-2 is CUCGGCUGCAUGC. Although this sequence does not perfectly match the Kozak sequence, it should suffice to allow some level of translation of the SARS-CoV-2 uOrf peptide. These sequences are relevant only if they are translated into functional polypeptides. Hung-Yi et al investigated this issue with the mouse coronavirus. They observed that the small polypeptide in 1235
MHV was synthesized. They also investigated whether the 5’ uOrf was functional. They found that mutations that prevented the synthesis of uOrf but maintained the secondary structure, appeared to be fully viable in cell culture. However, serial passage of these mutant variants resulted in a reversion to the wild type, indicating that the “AUG” does confer a selective advantage in replication in cell culture. Hung Yi et al suggest that a functional uOrf peptide sequence 5’ to the initiation codon for Orf1a has the potential to decrease ribosomal translation efficiency. The attenuation of Orf1a and Orf1ab synthesis is required for the balanced stoichiometry of virus particle formation. That is the ratio of the 5’ replicative proteins necessary to create the replication complex to 3’ structural and regulatory proteins. While a full functional analysis of the 5’ uOrf in different coronaviruses remains to be completed, there are some indications that they play some role in replication. A study by Raman et al notes that the stem-loop structure which contains the 5’ uOrf amino acids for BCoV, when deleted, decreases the replication competence of defective interfering particles. This is indirect evidence to suggest that at a minimum, the stem-loop containing the uOrf is positively correlated with viral replication competency. Missing from the collection of studies on the 5’ uOrf is its role in replication and pathogenesis in animal disease models. This lacuna in our knowledge should be promptly addressed experimentally with MHV, MERS-CoV, SARS-CoV-1, and SARS-CoV-2. This article originally appeared in Forbes, and can be read online here: The Mystery Of The False Start At The 5’ End Of SARS-CoV-2
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part Nine) Forbes | August 31, 2021 | Article
Bank vault closeup side view. 3D Render GETTY
This is the ninth article in a 15-part series called “Relevance of Immune Suppression by SARS-CoV-2 to Understanding and Controlling the Covid-19 Pandemic,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read parts 1, 2, 3, 4, 5, 6, 7, and 8. Closing the door on innate immune signaling Inhibition of signal peptide membrane transport 1237
Innate immunity not only acts within cells to suppress microbial invasion and signal nearby cells to impending danger, but also initiates the adaptive immune response. To execute this task, the signaling proteins responsible must exit the cell by traversing the cell membrane. The principal pathway for signaling protein exit is via interaction with a signal peptide sequence located at the amino terminus of the protein. The signal recognition particle contains both proteins and RNA. The signal peptide sequence ferries signaling proteins to a port on the endoplasmic reticulum. It binds to the first peptides, transports them to the membrane, and from there extrudes them into the lumen, eventually allowing the protein to leave the cell when the endoplasmic reticulum fuses with the membrane. Almost all proteins that exit the cell, including interferons and other signaling molecules induced by interferons, must follow this pathway. Anything that blocks the pathway will prevent signals from the infected cell from exiting to alert nearby cells or activate other components of the immune system.
Figure 1: Signal peptide sequence HTTP://WWW.SIGNALPEPTIDE.DE/
Evidence suggests that SARS-CoV-2 interference with the transport of signal peptides is mediated by nonstructural proteins NSP8 and NSP9. A study published in October 2020 found that NSP8 and NSP9, both alone and together, bind to the 7SL region of the signal recognition particle, preventing cellular membrane protein trafficking. 1238
Figure 2: “The locations of the NSP8 (blue spheres) and NSP9 (red spheres) binding sites on the S ... [+] HTTPS://WWW.CELL.COM/CELL/FULLTEXT/S0092-8674(20)313106?_RETURNURL=HTTPS%3A%2F%2FLINKINGHUB.ELSEVIER.COM% 2FRETRIEVE%2FPII%2FS0092867420313106%3FSHOWALL%3DTRUE
Inhibition of signal peptide export not only prevents an infected cell from signaling its neighbors, but also shields infected cells from T cell recognition and destruction. T cells are the killer cells of the immune system; if they remain unactivated, the virus can replicate to ever higher concentrations. Downregulation of MHC-I There is another way SARS-CoV-2 disrupts T cell functioning. Molecules classified either as major histocompatibility complex typeI (MHC-I) and major histocompatibility complex type-II (MHC-II) molecules make up cell surface proteins that are involved in stimulating adaptive immunity. MHC-I molecules work by presenting fragments of foreign proteins to T helper cells, teaching them to distinguish between self and not-self and initiating the adaptive immune response. In displaying these peptides, MHC-I molecules become targets for killer T cells.
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Figure 3: (A) SARS-CoV-2 Orf8 interference (B) MHC-I and MHC-II molecules ACCESS HEALTH INTERNATIONAL AND IMMUNOPAEDIA
In addition to degradation, signal peptide signaling is required for proper processing of the MHC-I proteins. Therefore, SARSCoV-2 inhibits MHC-I by at least two separate processes. According to a preprint study from May 2020, the SARS-CoV2 open reading frame 8 (Orf8) protein obstructs the surface expression of MHC-I. While the exact mechanism is unknown, the authors of the study observed an accumulation of MHC-I proteins in the lysosomes of Orf8-expressing cells, suggesting that Orf8 selectively targets the molecule for degradation and inhibits its involvement in the antiviral response. SARS-CoV-2 isn’t the only virus to possess MHC-I-targeting mechanisms. The Nef proteins of HIV help the virus also reroute MHC-I molecules for certain destruction, transporting them to the lysosome where they will be degraded, rather than the plasma membrane for export. This article originally appeared in Forbes, and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part Nine)
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September 2021
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One Fifth Of Adults Report A Relationship Breakdown During The Pandemic Forbes | August 31, 2021 | Article
A study from the University College of London finds over a fifth (22 percent) of adults say they have experienced a complete breakdown of a relationship with either family, friends, colleagues, or a partner in the past year. The results are part of a larger 72-week study with 70,000 participants that seeks to examine social patterns and overall mental health of adults during the Covid-19 pandemic in the UK. While many of us may be well aware of the stressors that Covid19 has introduced into our relationships, the data from the study provides interesting nuances. A decline in relationship quality in 2021 compared to 2020 was most prominent for relationships with other relatives (not parents or children) outside of the household (20% in 2021 vs 14% in 2020). This aligns with a wealth of anecdotal accounts of those exasperated with relatives who hold anti-vaccine or anti-mask views, but could also be due to a lack of in-person contact with travel and physical distancing restrictions in place for a large portion of the above mentioned time period. Young adults aged 18-29 (35%) and people with a mental health diagnosis (37%) had the highest proportion of relationship breakdowns, demonstrating yet again the disproportionate impact of this pandemic on this age group. People living with children (27%) and people with lower household income (24%) also had higher rates of relationship breakdowns. Twenty five percent of young adults aged 18–29 reported a worsening of their relationships specifically with their spouse or partner and a worsening of relationships with colleagues or coworkers. In more positive news, 46 percent of young adults said the quality of their relationships with their spouse or partner has been better than usual over the last year. This is a higher proportion than in adults aged 30-59 and those aged 60 and over, with 27 percent and 21 percent of these age groups reporting a better relationship 1242
with their spouse or partner respectively. The researchers suggested that young adult couples may have benefitted from remote working allowing them to spend more time together. The researchers suggested also that job losses, anxiety over finances, and a lack of in-person contact could have played a role in overall relationship breakdowns. Digital and online communication, such as a misinterpreted text message, lack nonverbal social cues and therefore can cause small misunderstandings. These would normally be cleared up face-to-face, but during lockdowns are left to fester. Social media also presents an often unrealistic and idealistic portrait of people's lives, leading to an increase in jealousy and loneliness. Rising rates of depression, anxiety and loneliness in youth during the pandemic should also not be underestimated as a driving factor in these relationship breakdowns. Research shows that when we feel lonely, we are more likely to interpret interactions with friends negatively and thus loneliness often begets loneliness. Loneliness is a risk factor for many health conditions. Studies have reported an association with cardiovascular disease, sleep quality, increased inflammation, and decreased viral immunity, even after controlling for various other factors. Studies of elderly people and social isolation concluded that those without adequate social interaction were twice as likely to die prematurely. The increased mortality risk of loneliness is comparable to that from smoking. A Harvard study on adult development which has run for over 80 years found that close relationships, more than money or fame are key to maintaining lifelong happiness. The study follows 268 Harvard sophomores from 1938 and their offspring. They found that close relationships help delay mental and physical decline, and are better predictors of long and happy lives than social class, IQ, or even genes. While there have been many anecdotal accounts of fractured or broken relationships during the pandemic, we now have the data to quantify this trend. Given the substantial impact of our relationships on our mental and physical health, this is a trend we should all be paying attention to. This article originally appeared in Forbes, and can be read online here: One Fifth Of Adults Report A Relationship Breakdown During The Pandemic
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Is This The Next Variant Of Concern— C.1.2? Forbes | September 3, 2021 | Article
A new and unusual variant of SARS-CoV-2 has appeared and is on the move. First noted in South Africa in May, the C.1.2 varian is now found in eight countries. Although C.1.2 is at present a minor variant wherever it occurs, the virus shares several mutations with all of the variants of concern, Alpha, Beta, Gamma, Delta, and Lambda. It also has several novel mutations that cause concern in their own right (Figure 1). To this point, the majority of research on SARSCoV-2 variants has focused on the Spike protein. This leaves mutations in nonstructural proteins, 3’ structural proteins, and 3’ regulatory (accessory) proteins relatively uninvestigated, despite playing a significant role in host immune suppression and pathogenesis. Here we describe the potential effects of each mutation, within and external to the Spike protein, on replication, immune evasion, and pathogenesis.
FIGURE 1: Mutations found in the C.1.2 variant that are also found in variants of concern. The ... [+] ACCESS HEALTH INTERNATIONAL
Mutations in the 5’ region that encodes the non-structural proteins (NSP1-16) proteins of the replication-transcription complex 1244
The mutation closest to the 5’ end of the genome is the C241U nucleotide substitution. This mutation, along with P323L in nonstructural protein 12 and D614G in the Spike protein, constitute a highly conserved triad in almost all SARS-Cov-2 strains today. The trio initially arose very early in the pandemic and is found today in all variants of tests or concerns. I speculate that C241U changes the structure of stem-loop 5, potentially increasing replication, transcription, and translation. Such conservation would be unusual for a mutation of little consequence.
FIGURE 3: Common mutations in the nonstructural proteins in the C.1.2 variant genome. Color code: ... [+] ACCESS HEALTH INTERNATIONAL
NSP1 The E102K amino acid mutation appears in NSP1, the first protein to be translated on entry. NSP1 is responsible for selective translation of viral mRNA and inhibition of cellular mRNA translation, and inhibition of nuclear exit of cellular messenger RNAs. Additionally, NSP1 aids in RNA export from the nucleus. 1245
The E102K mutation is located in the N-terminal RNA binding domain of the NSP1. NSP1 binds to the 40s ribosomal RNA and blocks the translation of cellular RNAs. NSP1 also recognizes stemloop 1 of the extreme 5’ end of the genome. NSP1 recognition of stem-loop one permits translational of viral messenger RNAs recognition of The mutation results substitutes glutamic acid (E) for lysine (K), a change from negative to positive charge. The positive charge may increase the affinity of NSP1 for negatively charged RNA. This change may increase the replication rate and preferential expression of viral RNA in the infected cell, thereby conveying a selective advantage. The E102K variant is also found in the Tanzanian variant. NSP3 The NSP3 protein is mutant at toe positions, T428I and T819I. NSP3 is a complex seven domain multifunctional protein. The T428I substation lies in the SARS-specific unique domain (SUD). The change for the polar threonine (T) to the hydrophobic isoleucine (I) might affect the proposed interactions with Gquadruplexes which may favor increased replication rates. The second T819I mutation lies in the papain-like protease, responsible for processing the Orf1a polyprotein. An increase in the efficiency of protein processing may increase the efficiencies of the earliest steps in viral replication. NSP3 T819I has been previously observed in the Lambda variant, suggesting that it conveys a selective advantage. We also note three synonymous nucleotide mutations in the NSP3 gene, C2475U, C3037U, and A7699G. Such nucleotide changes may alter viral RNA’s structure stability and packaging without altering protein sequence, suggesting a selective advantage. NSP4 The NSP4 protein plays an essential role in the sequestration of the replication-transcription complex within the double membrane vesicle. The change from leucine (L) to proline (P) is likely to alter the structure of NSP4. The occurrence of the identical mutation in two variants Lamba and Iota, that arose in distant geographies suggests that this mutation conveys a selective advantage to C.1.2 1246
NSP5 The G15S mutation in NSP5 is unique to the C.1.2 variant. NSP5 is the major viral protease responsible for cleaving the C terminal proteins of the Orf 1a and Orf1a polypeptides. The protease encoded by NSP5 is the target of several anti-viral drugs currently in clinical trials. It is well worth investigating the properties of the mutated protease both concerning function and sensitivity to protease inhibitors. NSP6 The NSP6 protein has at least two functions critical for the efficient replication of SARS-C0V-2. NSP6 plays a crucial role in limiting the innate immune response that would otherwise block virus replication. Specifically, NSP6 inhibits type I interferon synthesis in response to infection by binding to the regulatory protein TANK1 and inhibiting its phosphorylation by the TANK1 binding protein required to activate the interferon pathway. The C.1.2 variant carries a three amino acid deletion of residue 106, 107, and 108 in the NSP6 protein. NSP6 also plays a less direct role in virus survival by restructuring membrane vesicles, limiting the autophagosome pathway that might otherwise degrade viral proteins and nascent virus particles. The deletion mutation likely confers a selective advantage as the identical mutation arose independently in most of the variants of interest and concern, including Eta, Iota, Lambda, Gamma, Beta, and Alpha. There is a pressing need to investigate the effect of the 106-108 deletion on the structure and function of NSP6 and virus replication and pathogenesis. NSP12 I and others have commented previously on the likelihood that the P323L mutation in NSP12 confers a selective replication advantage. NSP12 is the RNA-dependent RNA polymerase. The P323L mutation is located in the interface domain of the polymerase. As mentioned above, the P323L mutation has conserved a part of the triad in the vast majority of SARS-CoV-2 stains currently in circulation as part of the triad. The effects of these mutations of the 1247
structure-function and biological consequences are well worth the investment. One polymerase inhibitor of note is molnupiravir, which we have previously commented on and which has recently launched as an oral Covid-19 antiviral in human trials. We also note two synonymous nucleotide mutations: C13554U in NSP12 and C20148U in NSP15. Mutations in the Spike gene that encodes the Spike Protein
FIGURE 4: Common mutations to the Spike protein in the C.1.2 variant genome. Color code: ... [+] ACCESS HEALTH INTERNATIONAL
The Spike protein contains 16 mutations. 12 have been found in other variants of concern and four are unique to C.1.2. The first is P9L in the signal peptide. This domain is the steering wheel of the Spike, guiding the protein’s transportation to the membrane. Proline (P) to leucine (L) is not a significant change, as both are neutral in charge and nonpolar, though it is still worth noting the appearance of the mutation. The following domain in the Spike is the N-terminal domain. There are six mutations in the C.1.2 N-terminal domain: C136F, R190S, D215G, deletions at positions 144 and 243, and the synonymous nucleotide mutation C22219U. R190S is observed in gamma, and D215G is observed in beta. The N-terminal domain hosts antibody binding sites, meaning mutations to this domain could enhance immune resistance. Cysteine (C) to phenylalanine (F) is polar to nonpolar, arginine (R) to serine (S) is positive to uncharged, and aspartic acid (D) to glycine (G) is negative to uncharged, all indicating a significant change. Notably, the C136F mutation additionally abolishes a disulphide bond in the N1 loop in the N-terminal domain, liberating the entire N-terminus. This likely results in strong increases in antibody evasion. Following the N-terminal domain is the receptor-binding domain, in which there are three mutations: Y449H, E484K, and N501Y. The receptor-binding domain is the part of the virus that contacts the host ACE2 receptor to initiate infection. Mutations here 1248
increase the transmissibility of the virus. While Y449H is unique to this variant, E484K and N501Y are widely pervasive. E484K has been observed to vastly increase infectivity while N501Y is known to increase Spike protein binding to the host ACE2 receptor. These mutations have been observed in alpha, beta, gamma, eta, and iota, among other non-WHO-designated variants. Tyrosine (Y) to histidine (H) is a neutral to positive change, indicating a new potential concerning mutation in the receptor-binding domain. There are six more Spike protein mutations to discuss: D614G, H655Y, N679K, T716I, T859N, and the synonymous nucleotide change C23731U. The first four of these likely impact furin cleavage based on their position between amino acids 614 and 716. Cleavage results in greater viral transmissibility, and these mutations may work to enhance this function further. D614G is the most canonical of these and has been noted in every major variant dating back to the early months of the pandemic. D614G is known to increase the affinity between subunits one and two of the Spike protein, as well as increase the probability of the receptor-binding domain remaining in the “up” position. H655Y has previously been observed in gamma and T716I in alpha, Were all these mutations to contribute towards enhanced cleavage, the C.1.2 virus could feasibly be much more transmissible. T859N falls out of major domains and is likely too far 3’ to affect cleavage, therefore its function remains to be determined. Mutations in the 3’ structural proteins: Envelope (E), Membrane (M), and Nucleocapsid (N)
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FIGURE 5: Common mutations in the non-Spike structural and regulatory (accessory) proteins in the ... [+] ACCESS HEALTH INTERNATIONAL
E The L21I mutation is found in the Envelope protein. The Envelope protein is critical for the assembly of the virus. It is an ion channel, allowing certain ions to pass through the channel pore. The protein is involved in virus trafficking through the cell. It also inhibits the cell response and is involved in virus particle release. The L21I mutation is located in the transmembrane domain (Figure 6), which may affect ion channel activity.
MANDALA ET AL
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FIGURE 6: Linear and three-dimensional structure of the SARS-CoV-2 Envelope protein. MANDALA ET AL
Mutations in this highly conserved region may increase the stability of the virus particle. Leucine (L) to isoleucine (I) is not a major polarity or charge shift. Although this is only a modest mutation, it may still have an effect ion channel structure. This could impact the size of the endoplasmic reticulum Golgi intermediate compartment. This compartment swells to accommodate virus particles. We suggest that this mutation results in the Golgi compartment being more suitable for virus release. It may also impact virus release from the surface of the cell, as the transmembrane domain is involved in that process as well. The result of both modified functions is a potential increase in released virus particles.
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M The I82T mutation is found in the Membrane protein. The primary function of the Membrane protein is to act as a membrane between the host environment and the virus. It is also involved in host immune response inhibition, targeting interferon signals like RIG-1 and MDA-5. The I82T mutation is found in the transmembrane III domain of the Membrane protein (Figure 7).
FIGURE 7: Linear and three-dimensional structure of the SARS-CoV-2 Membrane protein. Transmembrane ... [+] MAHTARIN ET AL
Additionally, the protein is involved in packaging, allowing the virus to become enveloped. This is a result of M interacting with RNA that carries the genomic packaging signal, as well as interactions with N and E proteins. Isoleucine (I) to threonine (T) is a nonpolar to polar shift, indicating a major mutation that may enhance these speculative functions. This mutation could create a more stable virus particle, alongside the Envelope protein mutation, resulting in increased transmission. There may also be an increased packaging efficiency, as well as greater immune suppression efficiency. N
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Finally, there are five mutations in the Nucleocapsid protein: P13L, R203K, G204R, Q384H, and the synonymous nucleotide mutation C29311U. The Nucleocapsid protein is a complex structural and regulatory protein. Its principal function is the packaging and protection of viral RNA, but it also has many immune antagonism functions, including suppressing interferon factors, biological processes, immune modulators. Additionally, the N protein has been observed to bind with RNA and the transcription replication complex and NSP1 mRNA translation. The first three of these mutations appear in several variants of interest and concern, including eta, gamma, lambda, and alpha. P13L is a minor change as proline (P) to leucine (L) is non-polarity or charge altering. Neither is R203K, as arginine (R) and lysine (K) are positively charged. Glycine (G) to arginine (R) is a major change, however, shifting from neutral to positive, as it glutamine (Q) to lysine (K). These mutations may all enhance the function and efficiency of the Nucleocapsid. Mutations in the 3’ regulatory (accessory) genes Orf3a The sole mutation to the Orf regulatory genes is a deletion at position 255 in Orf3a. This protein regulates apoptosis, which is a major factor in viral pathogenicity. This deletion may work to enhance this function, though this remains speculative. Notably, the Orf genes lack significant mutation. As shown in the table below, major variants of concern and interest often contain numerous point mutations in the regulatory proteins, as they likely modulate the host immune response.
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TABLE 1: Frequency of mutations to regulatory Orf genes in variants of concern. ACCESS HEALTH INTERNATIONAL
The final point we would like to elucidate is that many of these mutations which we have analyzed are likely to be important for virus replication. We reiterate that most research has focussed exclusively on the Spike protein. Here we focussed on mutations both within and external to the Spike protein. As shown in Figure 1, many variants carry mutations that are the same, even though they are independently derived from vastly different geographical regions. One in particular, the Tanzanian variant A.30, which lacks the triad of D614G, NSP12 P323L, and 5’ UTR C241U, also carries some of these precise mutations. To dismiss this evidence that viruses are adapting via changes external to the Spike protein to increase transmission, virulence, and immune evasion is not a reasonable assumption. We take the time to denote and understand these mutations because of the destructive capabilities of some of the variants. We first wrote about the Delta variant and its predecessor B.1.617 in early April, well before it became a variant of concern and fueled a major infection wave. Recently, we described the B.1.621 variant, which has recently been designated as a variant of interest by the World Health Organization. If we understand the potential of variants before they wreak havoc, we can potentially blunt the impact they have on society. This article originally appeared in Forbes, and can be read online here: Is This The Next Variant Of Concern— C.1.2?
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part 10) Forbes | September 7, 2021 | Article
Princess Leia and her partners in crime attempt to escape a trash compactor in the film Star Wars: ... [+] CONFERENCES THAT WORK HTTPS://WWW.CONFERENCESTHATWORK.COM/INDEX.PHP/FACI LITATING-CHANGE/2015/05/TRAPPED-IN-A-GIANT-TRASHCOMPACTOR-YOU-ALWAYS-HAVE-A-CHOICE/
This is the tenth article in a series called “How SARS-CoV-2 Evades And Suppresses The Immune System,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV-2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read parts 1, 2, 3, 4, 5, 6, 7, 8, and 9. Dodging the Trashman 1255
One of the things SARS-CoV-2 and other viruses must do to evade immunity and survive is change the environment of host cells in its favor. These mechanisms I call nonspecific since they affect cellular function broadly and indiscriminately, as opposed to specific mechanisms that have very precise targets. In previous installments I described how nonspecific suppression manifests during protein translation. In this piece I discuss how SARS-CoV-2 avoids ending up in the cell’s waste disposal systems. The first is sparing viral proteins and nascent virus particles from destruction by autophagocytosis—literally the process by which cells eat their own proteins. The autophagosome is a double membrane vesicle. Its main task is to shuttle cellular detritus to the lysosome, an organelle containing digestive enzymes, where it can be chewed up and recycled. This process, called autophagy, clears out damaged and or dysfunctional proteins. The second notable change occurs in another process, apoptosis. Similar to autophagy, apoptosis rids the body of that which it no longer needs, though instead of damaged cell parts, it eliminates actual cells—billions of them. In the average adult, apoptosis triggers the death of 50 to 70 billion cells within a single day. Apoptosis is distinct from necrosis, another form of cell death, in that it is highly controlled and thus doesn’t cause inflammation. We have a fairly clear picture of how SARS-CoV-2 might inhibit autophagosomal activity. According to a study published in April 2020, mutations identified in the nonstructural protein NSP6 and open reading frame Orf10 likely prevent autophagosomes from delivering material to the lysosome. In NSP6, the authors of the study noted the presence of certain residues that, if consistent with previous studies of the first lethal human coronavirus SARS-CoV, promote stronger affinity for the endoplasmic reticulum and curb autophagosome expansion. The net result is the cell no longer has full capacity to degrade viral proteins and nascent virus particles which might otherwise be destroyed. It may be the case that the same gene is involved in helping create and modify the endoplasmic reticulum Golgi intermediate compartment (ERGIC). In so doing, it would essentially remodel the intracellular membrane architecture, by expanding the dimension of the ERGIC to a size sufficiently accommodative of virus particles. 1256
For apoptosis, our understanding is a bit murkier. It is unclear based on currently available data whether SARS-CoV-2 prevents apoptosis or encourages it. In general, cell death is not ideal for the virus. But if it is something of an inevitability, apoptosis would be the ideal pathway for elimination, or risk detection by the immune system. A study from June 2020 shows that the SARS-CoV-2 open reading frame Orf3a is capable of inducing apoptosis (also the case for Orf3a of SARS-CoV. Comparisons of the two, however, revealed that the pro-apoptotic activity of SARS-CoV Orf3a was greater. The authors of the study speculate that the reduction in apoptosis-mediated cell death could be linked to the diminished virulence of SARS-CoV-2 relative to its predecessors. It is due to its ability to assume milder manifestations than SARS and MERS that Covid-19 spreads so far and wide. It is notable that mutations in Orf3a are amongst the most frequent in SARS-2 variants with the exception of changes in the spike protein. In the next part of this series, I will discuss how SARS-CoV-2 inactivates individual proteins required for innate immune signaling. This article originally appeared in Forbes, and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part 10)
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part 11) Forbes | September 9, 2021 | Article
American football players in action on the playing field. GETTY
This is the eleventh article in a series called “How SARS-CoV-2 Evades And Suppresses The Immune System,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV-2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read parts 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. Targeting key players in interferon induction Discussions of innate immunity typically focus on the exterior— what happens outside the virus. But another way of approach is to
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focus, once the virus gets in, on the interior of the infected cell and its neighbors. In the previous few installments of this series I discussed nonspecific mechanisms of SARS-CoV-2 immune suppression, which affect entire cellular processes and structures. Now I will shift our attention towards specific immune suppression. In addition to mounting a more targeted offensive, this component of the virus’ strategy yields very precise effects, in some cases limited to just one element of one immunological pathway. But the consequences of these minute shifts, as we shall soon see, can be far-reaching. For example, many of the Orfs (open reading frames), as far as we know, only interact with select innate immune signals, like interferon and interferon-responsive genes, while the nonstructural protein Nsp1, in addition to its nonspecific functions, also specifically inhibits RIG-I, a pattern recognition receptor critical to the activation of the innate immune response. The virus devotes a tremendous array of proteins to blocking not only the induction of interferon and its export but also interferonstimulated genes. Interferon-orchestrated innate immunity must be overcome for the virus to be successful. Many of the viral proteins are devoted precisely to this task: nonstructural, structural, and a whole set of specific proteins we call regulatory or accessory genes. Here we look at the first half of their blockage of interferon synthesis (see left panel of Figure 1). Clinical data shows more adverse health outcomes for Covid-19 patients who either inherit genetic deficiencies in interferon or develop autoantibodies against interferon. If the body’s ability to produce interferon is compromised, it will be in serious trouble. This is also very important for the virus’ overall masking of infection. If interferon is not induced, cells won’t be able to alert the immune system to the presence of a pathogen. One of the primary tricks SARS-CoV-2 has for expedited entry and exit is blocking not just interferon itself, but multiple steps along the interferon signaling pathway.
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Figure 1. SARS-CoV-2 and its effect on interferon. RIG-1 (retinoic acid-inducible gene 1) is ... [+] ACCESS HEALTH INTERNATIONAL
First, a bit of context on the significance of RIG-I. Innate immunity involves proteins known as pattern-recognition receptors that, over the course of evolution, have been hard-wired to identify pathogen-associated molecular patterns or PAMPs. Commonly found in many pathogens, recognition of these molecules allows the body to respond immediately to invaders old and new. Some of the better-known PAMPs include bacterial lipopolysaccharides, acids, bacterial DNA, and both single- and double-stranded RNA. Activation of these pathways by pattern recognition receptors like retinoic acid-inducible gene I (RIG-I)-like receptors and Toll-like receptors is necessary to trigger the adaptive immune response. RIG-I is one of the pattern recognition receptors that detects PAMPs. The primary function of RIG-I is to recognize and bind to double stranded RNA, the key intermediates in SARS-CoV-2 replication and transcription. Upon binding to double stranded RNA, RIG-I activates mitochondrial antiviral adaptor protein (MAVS), which in turn sets off a cascade of downstream factors: kB kinase ε (IKKε), TANK binding kinase 1 (TBK1), and interferon regulatory factor 3 (IRF3). If phosphorylated, IRF3 translocates to the nucleus and initiates transcription of type-I interferons.
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One study, published in October 2020, identified four viral proteins in SARS-CoV-2 that obstruct the RIG-I pathway and therefore interferon production: the nonstructural proteins Nsp1, Nsp6, and Nsp13 and the open reading frame Orf6. If the RIG-I pathway is activated, Nsp6 and Nsp13 bind to TBK1 to halt the phosphorylation of IRF3. And if IRF3 is phosphorylated, Orf6 interferes by blocking the translocation of IRF3 to the nucleus. Let’s dive deeper into these various points of interference, beginning with Nsp6 and Nsp13. If the RIG-I pathway is functioning as it should, IKKε and TBK1 phosphorylate IRF3. Phosphorylation, or the addition of a phosphate group, is a biochemical reaction that regulates proteins, playing a critical role in glycolysis and other activities essential to maintaining a healthy cellular metabolism. When Nsp6 binds to TBK1, the authors of the study found, the interaction inhibits phosphorylation of IRF3. When Nsp13 binds to TBK1, it reduces TBK1 phosphorylation and IRF3 activation. Normally, once IRF3 is phosphorylated, it is translocated to the nucleus, where interferon and interferon-stimulated genes are then transcribed. Simultaneously, the transport receptors karyopherin α 1–6 (KPNA1–6) import transcription factors that facilitate translocation, including IRF3. Karyopherins are proteins that help with the transport of molecules between the cytoplasm and nucleus by shuttling their cargo through the nuclear pore complex. They regulate what goes in and out, with different karyopherins assuming different gatekeeping tasks. But according to the October 2020 study, Orf6 inhibits translocation by binding to KPNA2. The net result, as is the case with suppression mediated by Nsp6 and Nsp13, is less production of interferon beta. The role of Nsp1 in interferon blockage has been studied more extensively, not just in SARS-CoV-2 but SARS-CoV and MERSCoV. The Nsp1 of SARS-CoV-2, as well as Nsp6, is more efficient at suppressing interferon production than its counterparts in SARSCoV and MERS-CoV. In a previous installment of this series I discussed how Nsp1 broadly inhibits the synthesis of cellular proteins by binding to the 40s subunit of the ribosome. According to another study, the downstream effects of this shutdown likely reach the interferon signaling pathway. For my next piece I’ll explain how 1261
Nsp1 and a host of other viral proteins block STAT1 and STAT2 (signal transducer and activator transcription proteins). This article originally appeared in Forbes, and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part 11)
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part 12) Forbes | September 10, 2021 | Article
Ganging up to tackle the receiver. Fozzy Whittaker (43) is tackled during Super Bowl 50 between the ... [+] AFP VIA GETTY IMAGES
This is the twelfth article in a series called “How SARS-CoV-2 Evades And Suppresses The Immune System,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV-2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read parts 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11.
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Ganging up to knock out the key players Interferon is a key player in the innate immune response. But interferon doesn’t operate in isolation. Its broad effectiveness is contingent on the recruitment of other genes. Once activated, many of these interferon-stimulated genes inhibit virus replication directly, whereas others rally the immune system’s second line of defense, the adaptive immune response, into action. In Part 11, I examined the left half of the diagram below, which illustrates how SARS-CoV-2 blocks the induction of interferon (see Figure 1). We saw how SARS-CoV-2 blockade prevents synthesis of type-I interferons, limiting its action within the cell. Should any interferon escape suppression, other factors restrict its exit from the infected cell to alert nearby cells of impending danger. Now we will turn to the latter half of the signaling pathway, more specifically how SARS-CoV-2 blocks induction of the interferon type-I induced genes and proteins.
Figure 1. SARS-CoV-2 and its effect on interferon. RIG-1 (retinoic acid-inducible gene 1) is ... [+] ACCESS HEALTH INTERNATIONAL
When type-I interferons are secreted, they bind to interferon receptors that trigger a cascade of downstream factors culminating in the expression of many interferon-stimulated genes. Two of these are the kinases Janus kinase 1 (JAK1) and Tyrosine kinase 2 (TYK2). 1264
Kinases are responsible for phosphorylation of target proteins. In this case, JAK1 and TYK2 add phosphate groups to STAT1 and STAT2, or signal transducer and activator of transcription proteins. Once phosphorylated, STAT1 and STAT2 assemble into a heterodimer. The STAT 1/STAT2 heterodimer then activates interferon regulatory factor 9 (IRF9). It is this interaction that produces interferon-stimulated gene factor 3 (ISGF3). The complex then migrates to the nucleus, where it stimulates interferon-sensitive response elements. The phosphorylation of STAT1 and STAT2 makes a key point of interference for SARS-CoV-2, which dispatches several proteins to apprehend STAT1/STAT2 before they produce ISGF3. According to a study of SARS-Cov-2 obstruction of interferon signaling pathways published in October 2020, inhibition of STAT1 phosphorylation involves the nonstructural proteins Nsp1, Nsp6, and Nsp13; the open reading frames Orf3a and Orf7b; and the M protein. The inhibition of STAT2 phosphorylation also involves Nsp6, Nsp13, and Orf7b, but Orf7a as well. The exact mechanisms of suppression are unknown, but without either phosphorylation, the STAT1/STAT2 heterodimer cannot form and therefore interferon-stimulated genes cannot be produced. The last leg of the interferon signaling pathway that SARS-CoV2 inhibits is the translocation of ISGF3, or the STAT1/STAT2/IRF9 complex, to the nucleus. Once there, ISGF3 can bind to interferon-stimulated response elements and thus activate the transcription of many hundreds of interferon-stimulated genes that engage in antiviral activity. Recall that in the first half of the pathway, which I described at length in my most recent article, Orf6 blocks translocation of IRF3 to the nucleus by binding to the transport receptor KPNA2. It appears that Orf6 also blocks translocation of STAT1 to the nucleus, effectively preventing the expression of interferon-stimulated genes. Mutations that disrupt the function of any of these genes and protein pathways dramatically decrease the replication and pathogenesis of the mutant virus, as studies of new and emergent variants have shown. This will be the focus of a later article in this series. Next up, I will discuss how SARS-CoV-2 interferes with the germinal centers of infected cells.
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This article originally appeared in Forbes, and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part 12)
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Animal Reservoirs Of Covid-19 May Trigger New Rounds Of Human Disease Forbes | September 13, 2021 | Article
Cocker spaniel relaxing with a cat, Canis familiaris, indoors. (Photo by: Auscape/Universal Images ... [+] UNIVERSAL IMAGES GROUP VIA GETTY IMAGES
Cave Canum (et cattus quoque) New variants of SARS-CoV-2 are lurking below the streets of New York City. A recent paper by Smyth et al. extracted SARSCoV-2 samples from fourteen wastewater treatment plants in the City. The team developed methods to detect mutations in a critical region of the genome, the receptor-binding domain of the Spike protein. As expected, they found a number of different Covid-19 variants in their samples, including Alpha, Beta, Delta, and Gamma. They also found four distinct “cryptic" lineages, WNY1, 2, 3, and 4, from three of the wastewater sites. These four cryptic variants yield surprising and troubling results. The receptor-binding domain RNA extracted from the samples contained up to 29 mutations in the four detected variants, some previously observed in the variants of concern or interest and others unique to these samples. Figure 1 illustrates the overlap of the mutations found in many other variants. 1267
Many of the mutations unique to the sewershed variants are extraordinarily rare among the 3.5 million sequences found in the GISAID SARS-CoV-2 database.
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FIGURE 1: Mutations found in the sewershed variants that are also found in variants of concern. The ... [+] ACCESS HEALTH INTERNATIONAL
The mutations pictured in figure 1 all occur in the small region of the viral genome sampled by the sewer sleuths. This region specifies the receptor-binding domain, the site of attachment of the virus to the ACE2 receptor on the host cell surface. The receptorbinding domain is also the target for the great majority of protective antibodies. Mutations within this region can profoundly affect transmission and immunity. Most of the cryptic variant mutations occur between amino acid positions 437 and 508. This is the part of the Spike protein that is in direct contact with the ACE2 receptor.
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FIGURE 2: Full SARS-CoV-2 genome with Spike protein highlighted; Spike protein with receptor-binding ... [+] ACCESS HEALTH INTERNATIONAL
The extensive mutations in the receptor-binding domain are functional. The authors report that pseudotyped viruses carrying a receptor-binding domain substituted with that of the cryptic variants are infectious. This is not entirely unexpected as polymorphisms shared with variants of interest and concern enhance Spike protein function. The shared amino acid substitutions at positions N440, L452, and N501 enhance receptor-binding affinity. The mutations at positions K417, N439, K444, N460, E484, Q493, and S494 reduce virus neutralization by convalescent sera and selected monoclonal antibodies. Evidently, the amino acid substitutions at the twelve novel sites are viable. This is especially notable for the deletion at position 484, a site known to interact with both ACE2 and neutralizing antibodies directly. It is important to determine the potential role of each of these cryptic mutations in immune escape and enhanced function. They may anticipate changes yet to be seen in new variants of concern. Smyth et al. speculate that these variants arose not from human sources, but from nonhuman hosts. The speculation is based on several observations. First, the cryptic variants are only observed in some, but not all samples. The authors argue that if variants were prevalent in the human population, they would be found throughout the City and not confined to specific sewer sites. The 1269
second is that their observation of pseudotyped viruses carrying the “cryptic” receptor-binding domain are capable of infecting nonhuman ACE2 receptors, specifically those of rats and mice. Finally, we know that SARS-CoV-2 can infect many species other than pangolins and humans. Up to 40% of all dogs tested in the US have antibodies to SARS-CoV-2. Several variants infect feral house and field mice. Up to 30% of all white-tailed deer in the northeast test positive for Covid-19 antibodies. Reports of infection of both domestic and large cats held in zoos were reported in the early days of the pandemic. SARS-CoV-2, like the influenza virus, can engage in zoonotic volleyball. Infections from animals can make their way into humans. SARS-CoV-2 strains have infected mink, and mink have returned the favor by infecting humans. As early as January 2021, farmed mink in Denmark showed signs of SARS-CoV-2 infection. These viruses were relayed back to human populations and subsequently sequenced. A study by Bayarri-Olmos et al. indicates that a mutation directly derived from the mink zoonotic transmission, Y453F in the receptor-binding domain, results in up to four-fold higher ACE2 receptor affinity, suggesting a far more transmissible virus. In the future, we must be aware of new variants emerging from fauna that inhabit our ecosystem. Smyth et al. examined the resistance of pseudotyped viruses carrying the mutant receptor-binding domain to monoclonal antibodies currently approved for treatment: etesevimab, bamlanivimab, and imdevimab. They report that WNY1 and 2 are partially neutralized by etesevimab and imdevimab. The WNY3 and 4 variants are completely resistant to all the monoclonal antibodies tested. All four variants are also completely resistant to bamlanivimab. The researchers also tested these mutations against naturally-developed antibodies in convalescent antisera. Convalescent sera neutralize both WNY1 and 2 but are far less effective against WNY3 and 4. The neutralizing titers of the sera from fully vaccinated individuals were also significantly reduced.
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FIGURE 3: Antibody resistance of WNY 3 and 4 to patient plasma of those previously infected and ... [+] SMYTH ET AL
Smyth et al. note that as the pseudotyped virus used to test antibody neutralization only includes receptor-binding domain mutations, whereas the full variant is far more likely to decrease antibody neutralization to a greater extent. They conclude that “the characteristics of these variant lineages provide them the capacity to be an increased threat to human health.” Looking at this small region of the virus has been instructive. The cryptic variants display the full range of variations that may occur within SARS-CoV-2 RNA. The receptor-binding domain shows here a broader degree of mutability. This epitomizes the potential for viral variation, not only in the receptor-binding domain, but in the rest of the Spike protein and viral genome as well, potentially enhancing virulence, vaccine and monoclonal antibody resistance, immune suppression, and transmission. As a final thought, it would be remiss not to add the possibility that the extreme variation seen in highly localized New York City cryptic variants is not due to zoonotic variants but rather the effluent from highly regional clusters of variants replicating in human populations, perhaps wards treating immunocompromised patients. Extreme variation of the S protein is documented to occur in such patients. In either case, the final take-home message is that variants documented to date represent only a subset of what we may expect from future SARS-CoV-2 infections. This article originally appeared in Forbes, and can be read online here: Animal Reservoirs Of Covid-19 May Trigger New Rounds Of Human Disease
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I'm an Infectious Disease Expert and Warn You Don't Go Here Eat This, Not That | September 14, 2021 | Article
This month, more and more of us are tentatively stepping into our old routines: headed back to school, back to offices, and, for some, even back to travel. But even though many places across the country are reopening fully, it doesn't mean that those venues are necessarily safe. The US is still near the peak of a surge in COVID19 infections, which puts us all at risk. Even those who have been fully vaccinated against COVID-19 can still become infected and spread the virus, and while vaccinated people are far more protected than those unvaccinated, the risk of severe illness and death is still not at zero. Below are five places I would avoid, even though I am fully vaccinated. These choices are not dictated by the government or the CDC but are based instead on my own educated understanding of the virus, how it spreads, and how we can best contain it. I count myself among the fortunate, able to work remotely and decline any work trips abroad. There are many others who are unable to do the same, and I know that they may not be able to follow the same strict rules. If you do have options though, here are five places where I personally would choose not to go, even as a fully vaccinated American. Read on—and to ensure your health and the health of others, don't miss these Sure Signs You've Already Had COVID. 1. Football Games, Music Festivals, Rallies, or Any Large, Tightly-Packed Outdoor Gatherings Over the past month, we've seen rather disconcerting news from Michigan and Oregon tying COVID-19 outbreaks to two separate outdoor music festivals held in each state. In Michigan, at least 96 cases can be traced to the Faster Horses Festival in July. That same month, Oregon held the Pendleton Whisky Music Fest which led to at least 62 new infections. While neither event required people to 1272
be vaccinated, attendees were required to wear masks and to maintain an appropriate distance, though images from the events suggested not all attendees followed the rules. In other parts of the world, outdoor music festivals have led to much larger outbreaks, into the thousands. For now, consider any large event, either indoors or outdoors, a risky gathering. 2. Any Indoor Event or Gathering, Unless…. ….unless everyone is masked or I'm sure everyone's vaccinated or tested. While very large indoor gatherings are off the books, like concerts or performances, I still consider some indoor gatherings safe if I'm certain that everyone around me is either vaccinated, tested or is wearing masks. If I'm invited over for dinner to a vaccinated friend's house, I am still more comfortable spending time with them outdoors, but I'm not as concerned as I was in the past if it rains and we head indoors for a short spell. The same thinking applies to work and school. If you can avoid time indoors and can learn or work remotely, take advantage of the option. But if you must head into a building, do your best to ensure that everyone around you is masked, vaccinated, or is required to test regularly. Unfortunately, not everyone can control all these factors, but we should strive for it still. 3. Airports and Airplanes When you think about travel by plane, you must consider your time in the airport as well. Both airports and airplanes involve being in close quarters with large groups of vaccinated and unvaccinated people. While most airlines require passengers and staff to be tested, there have been reports of people testing positive before their flights and still being allowed on planes. Even in countries with very strict testing and quarantine rules like Singapore, airports have been a source of new outbreaks. Until the global pandemic is under better control and vaccines are more widely available across the world, I would recommend sticking to safer forms of domestic travel whenever possible.
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4. Bars, Nightclubs, Raves …or anywhere else where people under the influence may let down their guard. While many of us have returned to dining at restaurants, I would caution against following a dinner out with a trip to your local bar or nightclub, even if those venues have COVID-19 policies in place. Bars were an early COVID-19 infection hotspot, no doubt tied in part to our general nature to let down our guards the more we drink or consume other intoxicants. These are venues where people are often speaking loudly, pulling their masks down regularly as they drink, and where people are generally more focused on having a good time rather than staying conscious of risk. 5. Restaurants, Museums or Any Other Non-Essential Venues …in communities where infections are spreading rapidly. All the guidelines above apply in communities where the pandemic is not spiraling out of control. If, however, you are in a community where cases are soaring and hospitals are overwhelmed with new COVID19 cases, all of those rules should be thrown out the window. In these cases, even for those vaccinated, stay home. Venture to the grocery store or pharmacy if need be, but put a hold on all nonessential outings for the time being. There will be a moment when the usual routines will return, but that time will be significantly delayed if people don't take the necessary precautions during a COVID spike. William A. Haseltine Ph.D. is a scientist, businessman, author and philanthropist. He was a professor at Harvard Medical School and Harvard School of Public Health from 1976-1993 where he was Founder and Chair of two academic research departments, the Division of Biochemical Pharmacology and the Division of Human Retrovirology. He is well known for his pioneering work on cancer, HIV/AIDS and genomics and, today, for his work on COVID-19. He has authored more than 200 manuscripts in peer reviewed journals and more than a dozen books, including six books on SARS-CoV-2 and the COVID-19 pandemic. His newest book is CVPTSD: What It Is and What To Do About It.
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This article originally appeared in Eat This, Not That, and can be read online here: I'm an Infectious Disease Expert and Warn You Don't Go Here
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The Covid virus is sneaky. Booster shots can protect us from it CNN | September 14, 2021 | Article
(CNN) — The United States and many other countries around the world are still debating the rollout of an additional dose, or "booster" shot, of the Covid-19 vaccine. On Friday the US Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee will meet to discuss Pfizer's application to administer a third dose of its Covid-19 vaccine to people ages 16 and older. Though a recent Lancet article advises caution in administering boosters before we have the evidence to fully support that the immunological benefits outweigh any risks, to me, the science seems clear: for those in the US who received mRNA vaccines, a third dose is the minimum we should pursue for Covid19 protection, and people should prepare themselves for the possibility that they will need additional doses or annual shots in the months and years to come. For those who received the Johnson & Johnson vaccine, there is not enough data so far to say with certainty whether a booster is advisable. First, let's lay the groundwork for the concept of a three-dose Covid-19 vaccine. Many of the vaccines that are part of our routine immunization schedule in the US are three-dose regimens, or more. Hepatitis B, rotavirus and HPV vaccines are all delivered in three doses, generally with the first two doses closer together and the third one delivered a few months on. Other vaccines, like ones for diphtheria, tetanus, and polio are four doses or more. Despite the novel delivery system of the mRNA Covid vaccines, it is now clear that their potency wanes over time, as it does for more conventional vaccines. So the fact that our understanding of vaccine-induced Covid immunity has led me to the conclusion that we need a third dose, should come as no surprise. What is yet to be understood fully, is whether three doses alone will be enough. Science is not static, and our determination of what is needed to protect us against SARS-CoV-2 will change as our 1276
understanding of the virus evolves. But if you look at what we know today about the virus and our vaccine-induced and natural immunity, the likelihood is that we will need additional shots. I wouldn't be surprised to see annual or semiannual shots for Covid-19, at least over the course of the coming few years. The reason for this is not because of the failure of the vaccines but because of the nature of the virus. Coronaviruses, like influenza viruses, are masters at evading the immune system. Their ecological niche is in long-lived animals with competent immune systems. These animals typically have been infected many times over by the virus' own predecessors. Think of the annual waves of influenza infections and you will have a pretty clear picture of what could potentially lie in store for us with SARSCoV-2. Contrary to what many may believe, vaccines do not form an impenetrable shield. Rather, vaccines trigger memory that allows the immune system to mount a rapid response and nip infections in the bud before the virus has a chance to spread within the body. What we don't know with exact certainty, but we suspect, is that you need a certain level of neutralizing antibodies to stop replication and that the window of time to stop that replication is likely short. This is based on our understanding of the nature of the virus and immune suppression. To winnow it down to a quick one-liner: SARS-CoV-2 can turn off our body's ability to mount an innate immune response which means, for protection, vaccine-induced neutralizing antibodies must be significant and powerful. SARS-CoV-2 acts at multiple levels to counteract innate immunity. As a result, a few hours following infection, the majority of proteins produced by the cell are viral, allowing the circulation of more viral particles among surrounding cells. In addition, SARSCoV-2 suppresses signals that might activate an immune response. This prevents any alarm bells from sounding inside our bodies, buying the virus more time to replicate to high concentrations. High levels of anti-SARS-CoV-2 neutralizing antibodies can circumvent these mechanisms of immune suppression by attaching to the virus and preventing it from attaching to other healthy cells. No magic number exists in terms of the levels of neutralizing antibodies required for immune protection. But studies of immunity, 1277
both from a prior infection and stimulated by a vaccine, suggest that the more antibodies you have, the better. If the virus has tools that help it sneakily disarm our immune system, then what better way to quell it than with a crushing tidal wave of antibodies that leaves no room for surprises? This takes us back to the idea of a booster vaccination. Israel is the case study. It was the first country to vaccinate a majority of its citizens against Covid-19. By the end of March, more than half of the population had received two doses of the highly effective mRNA vaccines. In June, all domestic restrictions were removed, including indoor masking, and by early July things looked like they had finally returned to normal. Then, with the arrival of highly infectious new variants like Delta, the tide turned. A July 31 study found that protection from Covid had faded in proportion to the length of time since vaccination. According to the authors of the study, "Individuals who were vaccinated in January 2021 had a 2.26-fold increased risk for breakthrough infection compared to individuals who were vaccinated in April 2021." What this study told us was that the levels of vaccine-induced neutralizing antibodies mattered, and when antibodies drop, infections go on the rise. The flicker of hope was that, despite the increase in infections, the vaccines would still work against the variants to prevent severe disease. That hope dimmed somewhat when the Israeli Ministry of Health found in August that almost 60% of those hospitalized with Covid were vaccinated. Just over 60% of the entire population in Israel are vaccinated today. It should be noted that it is natural that as a nation's vaccination level increases, a higher percentage of its Covid-19 infections will be in vaccinated individuals. What is still unknown are factors such as the severity of those breakthrough infections and the overall health of those who were infected. Being vaccinated was still better than not being vaccinated when it came to the likelihood of severe disease and death, but it wasn't wholly sufficient to prevent hospitalizations. Israel has already started rolling out a third dose of Covid-19 vaccine. The early data shows a dramatic improvement in defense: after 14 to 20 days, there was a 70-84% reduction in the risk of infection. What that follow-up study from Israel tells us, when combined with the first, is that boosters 1278
aren't just an option. They should be considered a necessary third dose of the Covid-19 vaccine. The need for three doses is increasingly clear. New data released by Moderna shows that a third dose of its vaccine significantly improves antibody levels for all variants, including Beta by 32-fold, Gamma by 43.6-fold and Delta by 42.3-fold. What's not as clear is where SARS-CoV-2 will lead us from here. We know the virus will change and that new variants will inevitably emerge with regularity, and perhaps be more infectious than the ones that have already taken root. In addition to the three doses of the current vaccines, we may need to prepare ourselves for the possibility of annual or semi-annual Covid vaccines in the years to come, and the possibility that other means of protection -- mask-wearing, testing and quarantine, and the development of prophylactic treatments and drugs -- might need to be used for many, many months to come. In the end, the major determinant of our ability to control Covid-19 is human behavior, not the behavior of the virus itself. This article originally appeared in CNN, and can be read online here: The Covid virus is sneaky. Booster shots can protect us from it
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A Second East African Variant: A.23.1 Forbes | September 15, 2021 | Article
A new and unusual variant of SARS-CoV-2 has been found in Africa. First detected in Uganda as early as October 2020, the A.23.1 variant is now found in at least 26 other countries. A.23.1, at present, accounts for under 2,000 sequences of the 3.5 million in the GISAID SARS-CoV-2 database. A.23.1 is not yet classified as a variant of concern or interest, but is definitely worth careful observation. A.23.1 contains several mutations found in variants of concern as well as six unique substitutions, four of which are in the Spike protein (Figure 1). Here we describe the potential effects of each mutation, within and external to the Spike protein, on replication, immune evasion, and pathogenesis. The first observation is that A.23.1 does not share a common origin with all of the variants of interest or concern, including Alpha, Beta, Gamma, Delta, or Mu. All of these variants carry a triad of mutations: C241U mutation in the 5’ untranslated region, D614G in the Spike protein, and P323L in NSP12. This reflects their common origin from the first major variant to sweep the globe. A.23.1 shares four amino acid changes with a previously described variant, A.30, originally detected in Angola, but thought to originate in Tanzania. Neither of these two East African variants contains the triad of other variants of concern.
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FIGURE 1: Mutations in A.23.1 found in other variants. Those in red are unique to A.23.1. ACCESS HEALTH INTERNATIONAL
FIGURE 2: Spike Mutations in A.23.1 found in other variants. Those in red are unique to A.23.1. ACCESS HEALTH INTERNATIONAL
FIGURE 3: Common mutations in the nonstructural proteins in the A.23.1 variant genome. Color code: ... [+] ACCESS HEALTH INTERNATIONAL
The Spike Protein (S) Most discussions of variants focus on the receptor-binding domain, specified by the S gene, that interacts directly with the ACE2 receptor (Figure 3). The mutation V367F lies in the receptorbinding core, the base of the receptor-binding domain that stabilizes the receptor-binding motif which binds directly to ACE2. Two nonsynonymous mutations are present in the N-terminal domain, R102I and F157L. Both of these mutations are unique to the A.23.1 variant. The substitution of arginine (R) for isoleucine (I) 1281
is a change from positive charge to neutral charge. Phenylalanine (F) to leucine (L) does not create a major polarity or charge shift, however the change in amino acid structure might nonetheless impact N-terminal domain immunogenicity. We note that the dominant variant in the world today, Delta, is mutated in amino acid positions 157 and 158. Typically, mutation in the N-terminal domain reduces recognition by some therapeutic monoclonal antibodies and convalescent sera. We also note the synonymous mutation C22000U. The two remaining mutations lie outside major domains and instead are located near furin cleavage sites (Figure 4). Furin cleaves the Spike protein into two distinct subunits. The common mutation associated with furin cleavage is D614G, is notably absent in this variant. However, Q613H is likely to increase sensitivity to furin cleavage as well. At present, no specific function is assigned to amino acid 681. However, this position is mutated in a number of variants of interest and concern, including Alpha, Delta, Mu, A.30, and B.1.620. We additionally note one more synonymous mutation: U24097C.
FIGURE 4: Cleavage region in the Spike protein between S1 and S2. The mutations in black from A.23.1 ... [+] ORD ET AL
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FIGURE 5: Common mutations external to the S protein in the A.23.1 variant genome. Color code: ... [+] ACCESS HEALTH INTERNATIONAL
FIGURE 6: Transmembrane regions of NSP6. Blue mutations are those found in A.23.1. Red mutations are ... [+] PANDEY ET AL
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Non-Structural Protein 6 (NSP6) The NSP6 gene of Orf1a in A.23.1 is heavily mutated, as it is in several other variants of concern. NSP6 is a transmembrane protein that is required for the formation of the double-membrane replication/transcription vesicle. As such, it plays a central role in the ability of SARS-CoV-2 to evade the innate immune response by sequestering the replication-transcription complex from RIG-1 and other single and double-stranded RNA sensors. NSP6 also directly inhibits the induction of type-I interferon. The NSP6 protein binds to TANK binding protein kinase-1, inhibiting phosphorylation of interferon regulatory factor 3 required for initiation of type-I interferon synthesis. Two of the amino acid changes, M86I and M183I, are located in transmembrane regions: M86I in region S3 and M183I in region S7 (Figure 6). Both methionine (M) and isoleucine (I) are hydrophobic uncharged amino acids. M86I is notably also found in the A.30. The L98F mutation lies in what is likely to be the cytoplasm face of the protein between the S3 and S4 transmembrane domains. We note that NSP6 is mutant in many variants of interest and concern including Alpha, Beta, Gamma, Lambda, Kappa, Iota, Eta, and Mu. There are five mutations throughout Orf1ab that are synonymous or do not result in an amino acid change. While these do not affect protein structure, they may play a role in RNA transcription and replication. These include C4753U in NSP3, C8782U in NSP4, C10747U in NSP6, C16575U in NSP13, and C17745U in NSP12.
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FIGURE 7: Common mutations in the non-Spike structural and regulatory (accessory) proteins in the ... [+] ACCESS HEALTH INTERNATIONAL
The Nucleocapsid Protein (N) There are two mutations in the N protein of A.23.1. One changes the amino acid at position 202 from serine to asparagine. The second is silent. N, like many other viral proteins, is multifunctional. In addition to forming the helical nucleocapsid, N is reported to be required for packaging the viral into infectious particles. Other functions of N include facilitating replication of the viral genome and synthesis of viral messenger RNAs. The N protein is also reported to suppress innate immune responses to viral infection. Amino acid 202 is located at a critical junction, connecting several active domains which modulate the RNA binding, oligomerization, and physical-chemical properties (phase separation) of the N protein (Figure 8). The Tanzanian variant A.30 also carries the S202N mutation.
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FIGURE 8: The domains of the SARS-CoV-2 N protein ZHIHUA ET AL
The Open Reading Frame Protein-8 (Orf8) The Orf8 protein of A.23.1 is mutant at amino acid positions 84 and 92. Both mutations are predicted to alter the structure and possibly the function of the Orf8 protein. The L84S mutation is a substitution of leucine for serine, a nonpolar-to-polar shift. The mutation E92K results in a change of glutamic acid to lysine, a shift from a negative to the positively charged residue. Orf8 interferes with immune recognition and destruction of SARS-CoV-2 infected cells. Summary The discovery of two distinct but distantly related variants in East Africa is concerning in and of itself. The observations that these variants arose independently from all others in the world, lacking the distinctive triad of mutations that link all other current variants demonstrates the versatility of SARS-CoV-2 adaptations to local conditions. These findings heightened the urgency for vigorous global surveillance and early detection of new variants focused on 1286
the sequence of the entire viral genome, not select regions, such as the S gene, only. This article originally appeared in Forbes, and can be read online here: A Second East African Variant: A.23.1
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What US policymakers can learn from the UK's COVID-19 response The Hill | September 16, 2021 | Article
British policymakers have begun weighing the future of Great Britain’s pandemic state, deciding which initiatives are worth keeping, which need revamping and which need scrapping altogether. We should be doing the same here in the United States. Both the UK and the U.S. have had their fair share of troubles. But for all its early shortcomings, the UK is now arguably better placed than the U.S. to handle the pandemic and similar future crises. For example, in the UK, large-scale genetic-sequencing was initially ridiculed as a “stamp-collecting” exercise but soon proved to be useful in keeping track of the myriad SARS-CoV-2 mutations and their effects on transmission. While other highly effective interventions, such as test-and-trace, are being downsized due to financial and political costs, there are still a host of other emergency policies and interventions that are now being absorbed into state infrastructure. The UK Health Security Agency (UKHSA), a new executive agency formed during the pandemic to replace Public Health England (PHE), a much-criticized predecessor, plays a central role in this process. The aforementioned genetic sequencing and contact tracing efforts are set to become the responsibility of the UKHSA. The Joint Biosecurity Center, created to provide real-time data on the spread of COVID-19, and lauded by some as having been critical to the UK’s pandemic response, will now also reside within the UKHSA. The U.S., in contrast, seems to still be playing catch-up, recently again snatching the global record for the highest number of new daily COVID-19 cases. It continuously fails to implement the most basic public health measures: testing of the infected, tracing them and their contacts, and isolating them as needed. Masking, another very basic pandemic control measure, is similarly sparse.
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Although the U.S. surgeon general, under the Public Health Service Act and with permission from the secretary of the Department of Health and Human Services, has the authority to prevent the spread of disease between states and from other countries, most public health functions fall within the responsibility of the Centers for Disease Control and Prevention (CDC). Even so, experts at the CDC (in charge of hard science, data collection and disease surveillance) generally lack the means to enforce policy and ultimately depend on individual states to make their own public health decisions. This means the COVID-19 response ends up being spread out across more than 2,000 state, local and tribal public health departments. As has been repeated many times, viruses have little respect for country, state or county lines. A scattered, decentralized pandemic response runs the risk of forgetting this and punishes those who act with the consequences of those who don’t. In many ways, these failures hint at the limitations of a federalist system of governance when faced with a public health crisis such as this one. Lacking federal authority to enact nationwide policy, it is unsurprising that a period of immense political polarization, as we are witnessing today, leaves public health matters divided across party lines rather than scientific consensus. The Biden administration’s move to enforce vaccine mandates for all federal employees, employees of larger businesses and most health care workers is a step in the right direction. As is its proposed pandemic preparedness plan, which would have the U.S. spend $65 billion to improve our ability to develop and manufacture vaccines, treatments and tests, and provide new money for early detection and warning systems. But these measures still don’t solve the root problem of enforcement. In addition to these measures, we might strive to establish an independent public health agency that, during times of crisis, has the political authority to put the necessary policies in place. An independent agency would have the added benefit of being less vulnerable to political whims. Recall that the CDC’s flagship Morbidity and Mortality Weekly Report, its main vehicle for sharing COVID-19-related developments, was subject to political influence in the midst of the pandemic. At a time of deep skepticism towards the state, these kinds 1289
of missteps only serve to further erode public trust, and with it the epistemic literacy so vital to an engaged pandemic response. In contrast, the Federal Reserve Board managed to withstand political pressures similar to those directed at the CDC precisely because of its institutional grounding as an independent agency; long terms, budgetary independence and job protections mean the Fed’s governors can focus on what they are meant to, market fundamentals. Slow start aside, the UK recognized an area of need in its pandemic response and acted accordingly. Now it has a new executive agency, the UKHSA, that is being given the necessary tools and funding to properly deal with this pandemic and any others to come. Given the U.S.’s shortcomings in implementing the most basic of public health strategies, it’s clear that a similar area of need exists here. The difference? A noticeable lack of action. The result? Depending on your postal code, you may have been given coherent guidelines and mandates or left with a policy that actively stymies efforts in COVID control. Whether it’s revamping of the CDC and its legislative weakness or forming a new independent public health agency, the U.S. needs to act. This article originally appeared on The Hill, and can be read online here: What US policymakers can learn from the UK's COVID-19 response
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Kids & Covid: What You Need To Know About Schools, Vaccines, And Risk Forbes | September 17, 2021 | Article
With schools across the country now fully reopened our public education system has become a powder box, ready to explode. After declining in early summer, Covid cases among children are skyrocketing. More than 243,000 new cases among children were logged last week alone, the second highest in a week since the pandemic began, and around 2,000 children were hospitalized. Last year around this time, I released a book called A Covid-19 Back To School Guide in which I described countless conversations with family and friends who were struggling over whether to send their kids back to school. Now here I find myself, one year later, once again lamenting the life and death decision parents and students are facing, except this year with fewer options: all of the 100 largest districts in the country, including the biggest urban districts in every state, have chosen to eliminate online learning options in favor of full reopenings. Schools started reopening in late July and almost immediately Covid-19 cases among children in those states started rising. The predominant variant circulating in communities this year, Delta, is significantly more transmissible than the versions of the virus we were facing in the 2020/2021 academic year. Mississippi, for example, reported more positive Covid cases among K-12 students in the first month of school this year compared to the entirety of the previous school year. In Georgia, about 60% of outbreaks in the state over the last two months are happening in K-12 schools, a sevenfold increase from July. A CDC study released in August confirmed how quickly the Delta variant can spread in schools. The study found that one infected teacher, who removed her mask as she read a book to students, directly infected half of the children in the class. The CDC has said they would not be revising their school reopening guidelines, which they claim to be effective when applied fully. The 1291
guidelines include recommendations — but not requirements —- to maintain a 3 foot distance between students, to screen and test students and staff regularly and ensure universal indoor masking, while encouraging vaccinations for all eligible students and staff. The lack of enforcement is a critical issue. According to a recently released Washington Post survey, one quarter of the nation’s 200 largest school districts are ignoring the primary CDC recommendation to mandate masks. Even those schools trying to follow recommendations are confused by the CDC’s screening and quarantine recommendations when a student is exposed. Current CDC guidelines give schools the option of 14, 10, or 7 day quarantines. Some school districts are abandoning them altogether. So where does that leave our youngest students and their families? The good news is that top of the line mRNA vaccines for children under 12 may soon be available. Pfizer has said they would apply for approval for their vaccine for kids 5-12 by early October and for younger children by November. Currently, the drugmaker is experimenting with three different dosages in its Phase 3 of its clinical trial for kids 5-12: two low-level doses of 10mcg delivered 21 days apart, two mid-level doses of 20mcg delivered on the same time frame, and two high-level doses of 30mcg. Moderna is running a similar trial with their version of the mRNA vaccine though no word yet on when it might be approved. But even when vaccines are approved for younger children, they alone will not be enough. First, while vaccines may help prevent children from becoming seriously ill, they are unlikely to prevent infection entirely. This means that the virus could continue to spread, especially if other measures, like masking, are not in place. And if the virus continues to spread, it means that it will continue to mutate and adapt, potentially emerging as a new variant that is more adept at evading our immune response and making us, and our children, ill. The Biden administration recently had the courage to enforce vaccine mandates for all federal employees, most healthcare workers, and employees of larger businesses. Though already they are under pressure to renege. But if anything, they should go a step further now to protect the youngest and most precious among us. The federal government has said they would use every means available to enforce mask mandates across all public schools, which they should 1292
continue. When approved for all students, they should do the same for vaccines. Beyond these efforts, they should ramp up enforcement of other life-saving measures, clarifying testing and quarantine requirements and ensuring that masking, distancing, testing and quarantine strategies stay in place, even after vaccines are approved. Our most recent wave of infections was a result of lifting restrictions too soon. Many are talking today about "pandemic equilibrium”, learning to live with the virus as we do with influenza. But with this virus, which mutates and adapts with alarming regularity, equilibrium is no certainty. For parents today who have no choice but to send their children into schools, I have little advice other than to remain vigilant. Eligible students and parents should be vaccinated, with a third dose or booster shot if they received their first set of vaccines more than five months ago. Unvaccinated students should stay masked at all times, and maintain their distance as much as possible from other students and teachers, especially if those students and teachers aren’t wearing their masks. Many parents have appealed to their pediatricians, asking them to provide vaccines for their kids, based on the doses used in the clinical study. Most pediatricians will likely decline these requests, as such off-label use is unauthorized and leaves providers open to liability claims. Still, some doctors are likely offering the option, though not advertising it. Until all Covid-19 protection measures, including masks, testing, quarantine and vaccines, are enforced equally across all schools, the safety of our children is a fallacy, a fairy tale we tell ourselves to lull ourselves into a sense of security. This article originally appeared in Forbes, and can be read online here: Kids & Covid: What You Need To Know About Schools, Vaccines, And Risk
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A New US/Japan Variant To Watch Forbes | September 20, 2021 | Article
A new variant has been detected in a Kentucky nursing home, infecting 45 residents and health care personnel. Many of these infections arose in fully vaccinated individuals. The variant, which originated in Japan, has over 10,000 entries in the GISAID SARSCoV-2 database. The variant contains five mutations previously noted in variants of concern or interest, two of which are in the Spike protein (Figure 1). It also contains many unique mutations. Here we describe the potential effects of each mutation on replication, immune evasion, and pathogenesis.
FIGURE 1: Mutations in R.1 found in other variants. Those in red are unique to R.1. ACCESS HEALTH INTERNATIONAL
The Triad The R.1 variant shares a common origin with all variants of interest or concern. They are marked by what I call the Triad, three mutations, one the 5’ untranslated region: C241U, a second in the viral polymerase NSP12: P323L, and the third D614G in the exterior S1 domain of the spike protein. The D614G mutation increases the infectivity. The contribution of the other two members of the Triad remains a mystery. Together these three mutations characterize the first major variant first observed in early 2020. That 1294
virus soon displaced almost all of the original Wuhan isolates. The Triad virus is the parent of all variants of concern or, interest including Alpha, Beta, Gamma, Delta, Lambda, and Mu. Only two currently circulating variants, A.30 and A.23.1, both of East Africa origin, lack the Triad and are most likely independent descendants of the original Wuhan virus. The Spike Protein (S) The spike protein of SARS-CoV-2 binds the host ACE2 receptor and initiates infection. The R.1 variant contains three Spike mutations, two of which are previously noted in other variants the other which is unique (Figure 2).
FIGURE 2: Common mutations in the nonstructural proteins in the R.1 variant genome. Color code: ... [+] ACCESS HEALTH INTERNATIONAL
One of the frequently mutated domains of the spike protein is the receptor-binding domain. The R.1 variant contains one mutation in this domain, E484K. The 484 mutation conveys increased resistance to antibodies in convalescent sera and to neutralizing monoclonal antibodies. The E484K substitutes the negatively charged residue glutamic acid for the positively charged lysine. The E484K is present in the Beta, Gamma, Eta, Iota, and Mu variants. R.1 contains the W152L mutation in the N-terminal domain. This region of the spike protein is also the target of neutralizing antibodies in convalescent sera and is the target of several neutralizing monoclonal antibodies. An identical mutation at position 152 is present in one of the minor variants of the Delta strain found in India. The very same amino acid is mutant in several variants first detected in California, B.1427/429. The 152 tryptophan is substituted for leucine in the California variants. Multiple independent mutations of the same amino acid imply functional advantage. The mutation, G769V, falls in an interdomain region between positions 732 and 780. It is unique to the R.1 variant. The Non-Structural Proteins 1295
FIGURE 3: Common mutations external to the S protein in the R.1 variant genome. Color code: ... [+] ACCESS HEALTH INTERNATIONAL
FIGURE 4: Mutations found in the Orf1ab non-structural proteins. Color code: noncoding nucleotide ... [+] ACCESS HEALTH INTERNATIONAL
The Non-Structural Protein 13 (NSP13) The NSP13 protein is the helicase and part of the replication transcription complex. The G439R mutation of R.1 is unique to this variant. The 439 residue lies adjacent to an active ATP-binding site (Figure 5 and 6). The Glycine to arginine mutation is a change from a neutral amino acid to one that carries a positive charge. The effect of this mutation on replication and helical activity is worth further study.
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FIGURE 5: The G439R mutation in NSP13. The mutation falls in the Rec1A domain, noted by the black ... [+] WHITE ET AL
FIGURE 6: Position G439 located near the ATP-binding site in NSP13. WHITE ET AL
The Non-Structural Protein 14 (NSP14) NSP14 is an exoribonuclease that, like the NSP13 helicase, is a part of the replication transcription complex. The exoribonuclease has an error-editing function and also confers resistance to chainterminating nucleotides. The NSP14 protein of R.1 carries the unique P412H mutation. NSP14 is also is a methyltransferase that participates in the formation of capped viral messenger RNAs. The 1297
capping of viral messenger RNAs is required to circumvent triggering the innate immune response. A change from the amino acid proline to histidine substitutes a neutral amino acid for one that carries a positive charge, again indicating a major charge shift and may enhance the properties of the protein. The site of the mutation lies within the N7 methyltransferase capping domain of the protein adjacent to SAH and GpppA binding (Figure 7).
FIGURE 7: The P412H mutation in NSP14. The mutation is located in the N7MTase subdomain near SAH ... [+] YUANYUAN ET AL
We also observe a number of synonymous nucleotide changes, which could impact the RNA replication and transcription processes. In the nonstructural proteins, we note C3037U, C14340U, C18877U, A19167G, and T19839C. It is possible that, while these do not change amino acids, they could change the secondary structure of the RNA which may result in functional consequences.
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The Structural Proteins
FIGURE 8: Common mutations in the non-Spike structural proteins in the R.1 variant genome. Color ... [+] ACCESS HEALTH INTERNATIONAL
The Membrane Protein (M) The Membrane protein is key to the formation of virus particles. It is embedded in the membrane that surrounds the virus. M is reported to assist in the packaging of viral into mature virions. M also is active in the suppression of innate immunity. The F28L is unique to R.1. The amino acid change lies within the first of three transmembrane regions domains. Phenylalanine and leucine are both nonpolar and uncharged amino acids. Nonetheless, the variant could impact the multiple functions of M including the stability of the virus particle.
FIGURE 9: The F28L mutation in the M protein. The mutation is found in a transmembrane region (TMR). ACCESS HEALTH INTERNATIONAL
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The Nucleocapsid Protein (N) The N is the most active of the virus structural proteins. N wraps the viral genome into a helical structure and is required for replication and transcription. During early infection, N is reported to play an important role in the suppression of innate immunity. N is highly antigenic and most people infected people have significant titers of anti-N antibodies. R.1 is mutant at four positions with N. R.1 shares the R203K and G204R mutations with three variants of concern Alpha, Gamma, and Lambda and with other reported variants as well. The amino acids change in the neighboring amino acid at positions 203 and 204 are always found as a pair. The two mutations lie near the center of the linker domain that connects the RNA binding domain of N with the dimerization domain. The change from glycine to arginine at position 204 introduces a second positive charge into a region that is predominantly neutral. One of the N mutations S187L is also located in the linker domain. The Q418H adds a positive charge to the extreme carboxy terminus of N.
FIGURE 10: R.1 mutations in the N protein, found in the linker and C-terminal domain, followed by a ... [+] CUBUK ET AL
R.1 is a variant to watch. It has established a foothold in both Japan and the United States. In addition to several mutations notably in the spike and nucleocapsid protein in common with variants of 1300
concern, R.1 has a set of unique mutations that may confer an additional advantage in transmission, replication, and immune suppression. This article originally appeared in Forbes, and can be read online here: A New US/Japan Variant To Watch
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Pandemic Cycles Of Covid-19: SARS-CoV-2 Immune Suppression Helps Us Understand Repeated Cycles Of Viral Infection And Vaccine Breakthrough Forbes | September 21, 2021 | Article
So far in this series, I’ve described the intricate dance between SARS-CoV-2 and innate immunity. The net result is the virus can arrest and delay the innate immune response long enough to enter and exit, initiating a new round of infections, both in those who have been infected for the first time and those who have had prior immunity either as a consequence of natural infection or vaccination. Fortunately, the news is not all bad. The more we understand what SARS-CoV-2 must do to evade our natural immune defenses, the more opportunities we have to create new ways to prevent and treat disease. What follows is a summary of what we’ve learned so far. What accounts for asymptomatic transmission? Innate immunity is the body’s first line of defense against invading pathogens. If a virus can succeed at disarming the innate immune response, it gains a critical advantage. The advantage is time—time to reproduce in abundance and infect others before alarm bells begin to sound. SARS-CoV-2 can spread from one person to another asymptomatically—that is, without any obvious symptoms. Studies show that asymptomatic transmission is the primary mode of transmission of Covid-19, making up more than half of all infections. Children, though they rarely suffer serious disease, often spread the virus amongst each other and to adults. We now know why this happens. The first symptoms of infection are not a consequence of SARS-CoV-2 replicating in the 1302
body. Rather, most Covid-19 symptoms, such as fever, muscle aches, and fatigue, are caused by an immune reaction to infection, not from damage caused by the infection itself. It is common for similar symptoms to appear in reaction to vaccinations against Covid-19 and other infectious diseases. Again, these aren’t a result of the virus replicating, but the body’s reaction to immunization.
Figure 1. SARS-CoV-2 virus particles per milliliter in nasal secretions over time. ACCESS HEALTH INTERNATIONAL
Figure 1 shows that concentration of SARS-CoV-2 peaks well before people feel ill. It is during this phase, when the virus is actively suppressing the innate immune response and more specifically, inhibiting of interferons and interferon-stimulated genes, that most infection takes place. Once innate immunity kicks in, viral concentrations fall precipitously, as does transmission. (For more detail on this topic, revisit the first twelve parts of this series.) Why do some people fall severely ill and die? Most infections with SARs-CoV-2 do not end up with serious disease. Depending on the variant, up to half people never know they’ve been infected, while another 25 percent may experience only mild cold-like symptoms. But some Covid-19 cases can be very serious and even life-threatening. After evaluating the literature, I have come to the conclusion that the major determinant of critical illness is how rapidly and efficiently the body engages the immune system by activation of interferon to suppress virus replication days three through eight. If 1303
interferon is induced and the innate immune system finally kicks in despite the virus’ best efforts to thwart it, people will go on to have either no symptoms or very mild symptoms. However if there is any glitch in the late activation of innate immunity, trouble is likely to ensue. Recent data suggests one of the reasons children have a lower instance of disease is because their innate immune system is more active, in large part due to early and robust interferon synthesis that induces broad viral protection. One of the reasons people of advanced age may suffer more serious consequences of infection is the declining activity of the innate immune system as well as higher incidence of anti-interferon antibodies, which I will discuss shortly. The primary agent in the activation of the innate immune system is interferon. People who are defective in generating an interferon response have a far greater chance of being hospitalized and falling ill than those who aren’t. Those who have mutations either in the interferon genes themselves or the pathways that induce interferon are more likely to fall ill. Either you have defective interferon, you have defects in inducing interferon, or you have defects in interferon-stimulated genes. An additional cause are those people who have antibodies to interferon itself. The difference in severity isn’t a matter of whether SARS-CoV-2 suppresses the immune system, but how well the body recovers and restores the interferon response. Another indication that interferon plays a critical role in disease severity is that pre- or late treatment with interferon in cell culture prevents virus replication. Regretfully this isn’t as easy to accomplish in humans, as interferon itself induces flu like symptoms, though it has been approved as a drug for diseases like cancer. There is an alternative pathway to induce the genes that interferon would normally activate, the proinflammatory STING (Stimulator of Interferon Genes) response. STING activates many of the same downstream effector proteins that interferon does. Critically, the STING pathway appears to bypass the many blockades SARS-CoV-2 mounts against the innate immune response. We know that STING is activated by small cyclic dinucleotides. Researchers have taken advantage of this understanding to devise drugs such as cyclic nucleotide antagonists. One such is diABZI.
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Why can the virus reinfect people who have already been infected or vaccinated? We now know that protection against infection and hospitalization wanes dramatically, particularly with respect to some of the variants, Beta, Gamma, and Delta. We’re still waiting for the second shoe to drop vis-a-vis serious disease and death. As immunity continues to wane, it seems likely that not only will protection against infection and hospitalization wane, but also serious disease and death. We now know that protection against serious disease and death wanes for natural infections either because the virus escapes immune detection or because levels of protective neutralizing antibodies fail to protect against progressive infection. The evidence that the virus can cause substantial incidence of severe illness and death has emerged from new waves of infections in populations previously infected. For example in Manaus, it is estimated that in the first wave over 70 percent of people were infected. Even so, the subsequent wave by the Gamma variant caused as much, if not more, severe disease and death than the previous wave. The experience of India was similar. Despite a massive first wave, the second wave wrought absolute havoc, with an official death toll of 400,000 that is estimated to be anywhere between two and four billion. I for one do not expect our vaccines to perform much better protecting against infection than natural protection. This view may be overly pessimistic, but without further evidence it seems to be the safest assumption. Data from Israel shows us that a third dose of the mRNA vaccine can significantly improve a person’s level of immunity and protect against severe disease. Efficacy increased from about 39 to 41 percent to 88 to 91 percent when a booster was administered five to six months after the second dose.
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Figure 2. Bar graph of increase in activity against variants with booster shot in two different age ... [+] SARS-COV-2 NEUTRALIZATION WITH BNT162B2 VACCINE DOSE 3 HTTPS://WWW.NEJM.ORG/DOI/FULL/10.1056/NEJMC2113468?DOW NLOADFILE=DOWNLOADFIGURES&ID=F1&DOI=10.1056/NEJMC211 3468
Up to now I’ve explained how the virus facilitates its entry and exit by repressing innate immunity long enough to enter the cell, replicate to high numbers, and infect others. Interestingly it is the same phenomenon that allows the virus to reinfect people who have been already infected or vaccinated once their initial first antiviral antibodies fades, which occurs inevitably. After the initial antibodies are no longer fully effective, protection depends on immunological memory that is carried out by long term memory B cells and T cells. Not surprisingly, the same tricks the virus uses the first time to ward off the innate immune system work the second time as well. Once a high level of immunity is no longer there, the virus can enter, suppress immunity, shield itself from recognition by memory B cells and T cells, replicate, and exit before memory kicks in. It is this observation that allows us to understand why coronaviruses have repeated cycles of infection. In the United States, we are in the midst of our fourth wave, as are many other countries. The only thing so far that distinguishes the cycles of infection of Covid-19 from the cold viruses and influenza is there are two waves, one in the summer and one in the winter, likely driven by our gregarious behavior. 1306
The current hope that many hold out for protection against severe disease and death mediated by an immune memory response distinguishes the patterns of infection of Covid-19 from cold and influenza virus epidemics is that for Covid-19 triggers two waves of infection, possibly because of increased transmissibility relative to the other two infections. What does this tell us about our future? Suppression of innate immunity is vital to asymptomatic spread of SARS-CoV-2 and its ability to get in and out quickly before the immune system can be triggered and get in again before memory can be effective. Anything we can do to limit the virus’ ability to either strengthen innate immunity as children have or knock out specific pathways the virus uses to counter innate immunity will give us a definite advantage. We now know the proteins the virus has. Each one of these proteins plays a critical role in immunity and gives us a wealth of targets. Each one is a new target. With HIV, we had about eight targets. With SARS-CoV-2, we could have as many as, if not more than, 25 targets. Table 1 shows these targets of opportunity. It is time to have a warp speed effort to develop many classes of antiviral drugs. We are just scratching the surface.
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Table 1.1: Genes involved in SARS-CoV-2 immune suppression ACCESS HEALTH INTERNATIONAL
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Table 1.2: Genes involved in SARS-CoV-2 immune suppression ACCESS HEALTH INTERNATIONAL
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Table 1.3: Genes involved in SARS-CoV-2 immune suppression ACCESS HEALTH INTERNATIONAL
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Table 1.4: Genes involved in SARS-CoV-2 immune suppression ACCESS HEALTH INTERNATIONAL
This article originally appeared in Forbes, and can be read online here: Pandemic Cycles Of Covid-19: SARS-CoV-2 Immune Suppression Helps Us Understand Repeated Cycles Of Viral Infection And Vaccine Breakthrough
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How SARS-CoV-2 Evades And Suppresses The Immune System (Part 13) Forbes | September 22, 2021 | Article
This is the thirteenth article in a series called “How SARS-CoV-2 Evades And Suppresses The Immune System,” which will explore an underappreciated but highly significant aspect of SARS-CoV-2 replication. The ability of SARS-CoV-2 to delay, evade, and suppress the immune system has myriad implications for drugs, vaccines, and other aspects of our pandemic response. The first set of pieces in this series are intended for a general audience; the second set, for the medical community; and the third and final set, for biomedical researchers looking for a deeper understanding of variants, how they’re generated, and what we might do to control them. Read parts 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. In previous installments of this series I discussed how different SARS-CoV-2 viral proteins suppress innate immunity by inhibiting production of interferons and induction of interferon-stimulated genes. Recall that one of the ways the virus suppresses innate immunity is by interfering with multiple steps along key interferon signaling pathways (see Figure 1). In Part 11 and Part 12 of this series I described how SARS-CoV-2 inhibits the retinoic acid-inducible gene-I (RIG-I) pathway through the nonstructural proteins NSP1, NSP6, and NSP13; the open reading frames Orf3a, Orf6, Orf7a, and Orf7b; and the membrane (M) protein. In those pieces I mainly examined the role played by the nonstructural proteins and open reading frames. Today we turn our attention to the last remaining piece of the puzzle, the M protein.
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Figure 1. SARS-CoV-2 and its effect on interferon. RIG-1 (retinoic acid-inducible gene 1) is ... [+] ACCESS HEALTH INTERNATIONAL
The primary function of RIG-I is to recognize and bind to double stranded RNA, a key intermediate in SARS-CoV-2 replication and transcription. Upon binding to double stranded RNA, RIG-I activates mitochondrial antiviral adaptor protein (MAVS), which in turn sets off a cascade of downstream factors: kB kinase ε (IKKε), TANK binding kinase 1 (TBK1), and interferon regulatory factor 3 (IRF3). If phosphorylated, interferon responsive factor 3 translocates to the nucleus and initiates transcription of typeI interferons. A study published in October 2020 found that overexpression of the M protein in cells infected with SARS-CoV-2 led to enhanced viral replication and inhibition of the innate immune response. More specifically, the researchers found that the M protein directly targets MAVS, the protein that recruits downstream antiviral genes into initiating interferon transcription. In antagonizing MAVS, the M protein obstructs the formation of the polyprotein complex that facilitates phosphorylation and dimerization of interferon responsive factor 3. It does this by binding to MAVS directly. Another study, published more recently in May 2021, took a closer look at this mechanism to see whether, in addition to inhibiting MAVS, the M protein interferes with RIG-I, MDA5, or TBK1. The authors of the study identified TBK1 as another target of the M protein, a kinase critical to the phosphorylation of 1313
interferon responsive factor 3 (see Figure 2). Evidently the SARSCoV-2 M protein inhibits TBK1 by introducing a post-translational modification, in this case a ubiquitin, that facilitates its degradation, effectively terminating downstream signaling.
Figure 2. TBK1 is the central kinase of the MAVS, STING, and TRIF signaling complexes TBK1 directly ... [+] TBK1, A CENTRAL KINASE IN INNATE IMMUNE SENSING OF NUCLEIC ACIDS AND BEYOND HTTPS://WWW.RESEARCHGATE.NET/FIGURE/TBK1-IS-THECENTRAL-KINASE-OF-THE-MAVS-STING-AND-TRIF-SIGNALINGCOMPLEXES-TBK1-DIRECTLY_FIG3_341710443
Figure 2 illustrates two interrelated but independent pathways that stimulate responses to viral infections. RIG-I recognizes uncapped cytoplasmic RNAs and short, double-stranded RNA, whereas MDA5 recognizes longer double-stranded RNAs. Both trigger production of interferons, which in turn stimulate many genes and proteins that interfere at multiple stages with virus replication. On the right hand side of the figure, note that STING bypasses the M protein and many other sites along the RIG-I pathway by directly stimulating TBK1, which in turn stimulates interferon responsive factor 3 (IRF3). In a recent story, I described how dinucleotide activation of STING has a potent anti-SARSCoV-2 effect in hamster models. This observation provides independent support of the critical role of viral proteins in innate 1314
immune suppression and virus replication and pathogenesis. On the left hand side lies a separate but interacting pathway that begins in the endosome. I’ll describe the role of the proinflammatory pathway in severe Covid-19 in my next piece. In conclusion, evidence has established M to be yet another of the viral proteins that SARS-CoV-2 uses to suppress innate immunity, buying time to enter, replicate, and exit before the innate immune system kicks in. This article originally appeared in Forbes, and can be read online here: How SARS-CoV-2 Evades And Suppresses The Immune System (Part 13)
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A Missed Opportunity: A Decision To Regret Forbes | September 21, 2021 | Article
The FDA advisory panel got it wrong — or at least they only got it half right — when it approved boosters only for those who are at high risk of severe Covid and those 65 and older. In failing to approve vaccines for all adults over the age of 16, the FDA missed a major opportunity to get ahead of the Covid-19 pandemic. This was a critical mistake, as approving vaccines for all adults could have allowed us to finally get ahead of the curve and control the course of the pandemic. One can only hope that the FDA, in considering the panel’s recommendations, will side instead with the White House and the wealth of evidence that shows three shots of the mRNA vaccines are necessary to protect ourselves from Covid-19. The President and his advisory team have made it clear that they are willing to take a more aggressive stance on boosters and are able to roll it out, starting as early as this week. This move could have created a much-needed fire break to stop the unceasing waves of new infections in our country. While we would still need to encourage those unvaccinated to accept the shots, for those who have already agreed to vaccines this would have been an important step. The FDA panel’s half measure and failure to support an all out attack is a decision I can’t help but think they will eventually look back on with regret. The evidence presented on Friday and in numerous studies published in recent weeks is clear: A third dose of a Covid-19 mRNA vaccine is essential for protection. One need look no further than the data published by Pfizer on whether neutralization titers waned after two doses of their vaccine and what the impact of a third dose would be. Previous studies, such as this one, had already shown that the vaccine’s efficacy waned, in this case from 95% approximately two months after a second dose to 84% between four and six months after. The Pfizer study found that neutralization titers dropped considerably between one and eight months after a second mRNA 1316
dose, far more rapidly than the efficacy numbers might indicate (see Figure A below). The study also found that one month after a third dose of the vaccine, neutralization titers skyrocketed beyond the levels achieved after the second dose, for all ages 18-85. This confirms that the best protection is provided by three full doses, not two. Moderna’s data confirms the same.
Bar graph of increase in activity against variants with booster shot in two different age groups. This shows that over time the neutralizing antibodies decline to very low levels and in many cases, as time progresses, fall until there is no effectiveN ENGL J MED 2021; SARS-COV-2 NEUTRALIZATION WITH BNT162B2 VACCINE DOSE 3
Moreover, though the Pfizer study was with an admittedly small sample size, there were no safety issues or side effects beyond the side effects seen after the first and second doses. We have a sense already, from hundreds of millions of people in more than 125 countries, that the mRNA vaccines are safe for all aged 12 and older. We also have a sense from countries like Israel who have already started administering a third dose of the Pfizer vaccine that a third dose is safe as well. This of course begs the question of why the FDA panel called the safety of a booster dose into question in rejecting it for all Americans. Odd too given that they were willing to approve the dose for the most vulnerable among us, who would presumably be most affected if there were real safety concerns. It’s possible that the panel members made their decision based on hope and an overestimation of the duration and efficacy of Covid vaccines against
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serious disease and death. Unfortunately, the data out of Israel shows that, if this is indeed their thinking, it is faulty. Israel had fully vaccinated more than half its population by the end of March and then reopened in June. Within a month and a half, new Covid cases tied to the Delta variant started to rise exponentially despite the high vaccination rate. A study published in late July found that protection from Covid had faded in proportion to the length of time since vaccination, a finding echoed by Pfizer’s finding. But more troublesome was the data that came in August, which showed that severe illness among the vaccinated was also on the rise, particularly in those aged 60 and older. The Israeli Health Ministry also noted that a seemingly modest decline of just 12% in vaccine effectiveness could translate into a 5-fold increase in severe cases among the vaccinated.
Covid-19 cases and deaths in Israel JUSTIN STEBBING, VITRUVIAN PARTNERS
I don’t believe that anyone who has followed this pandemic closely since it emerged would find any of the above a surprise. When it comes to inducing immunity, vaccines rarely perform better than natural infection. We knew, from the devastating outbreaks in India and Manuas, Brazil where there were widespread infections in early waves and then equally widespread reinfections in subsequent waves, that natural infection offered no guarantee against reinfection, severe illness or death. It was folly to assume our vaccine-induced immunity would act any differently. 1318
What we didn’t know before was why it was happening, but we have a better sense of that now. SARS-CoV-2, much like the influenza virus, has learned tricks that can inactivate our immune systems, essentially shielding itself with a cloak of invisibility so it can enter our bodies, replicate quickly, and exit to infect others, all before our primary and innate immune response kicks in. This essentially gives the virus a free ride for anywhere from two to five days, perhaps longer. The virus, in less than two years, has mutated to such an extent that it is now able to unleash a trifecta of trouble: able to evade the immune response from natural infection and vaccination, able to replicate more rapidly once infection is established, and to replicate for a more prolonged period of time, increasing the total amount of virus in the respiratory tract by 1000fold. Moreover it appears the Delta variant is more pathogenic, as people infected with the Delta variant are twice as likely to be hospitalized, compared to those infected with previous strains. Given the clear need for a third dose and the apparent lack of safety issues, some have hinted that the FDA panel members may have been frustrated by the President’s public announcement of a booster rollout, before the FDA had even debated the issue, a case of poorly timed pique. No matter the motivation, we may be in the process of blowing the one real chance we have now of getting ahead of the pandemic. That, I believe, is what the current administration was trying to achieve by announcing their readiness to deliver boosters for all. It’s a strange moment to find ourselves with a President and a team of advisors ready to charge forward to protect the nation while scientists block the way. This article originally appeared in Forbes, and can be read online here: A Missed Opportunity: A Decision To Regret
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A Snapshot Of SARS-CoV-2 Evolution: Observed Increase Of Infectivity In The Covid19 Virus Forbes | September 28, 2021 | Article
A sports car today is far more advanced than those from the 20th century. A recent scientific report underscores how rapidly SARS-CoV2 adapts to selective pressure. The experiments examine how rapidly the virus can adapt to life in a Petri dish. The results are startling, explaining in part the emergence of an entire Greek alphabet of variants over that past year and a half. No matter what the original source, the virus becomes 100 times more infectious, and does so in short order. No wonder new variants seem to pop up no matter where or when we look. The experiments follow a hallowed tradition of medical science: passaging dangerous human pathogens multiple times through nonnatural hosts to derive altered viruses that may be used as a vaccine. That is what Louis Pasteur did to develop the first Rabies vaccine and what Max Theiler did to develop the first and only vaccine for Yellow Fever. It does not always work that way. Sometimes the virus that emerges from multiple passages in animals in Petri dishes is more dangerous than the original. For example, serial passaging of alphaviruses results in mutations that, in some cases, result in higher neurovirulence in mice. The same can be said for feline enteric coronavirus, which when passaged multiple times, results in furin cleavage mutations that correlate with transformation to a more pathogenic biotype. Shiliaev et al. use two different sources of virus. The first was a sample as close to the original Wuhan strain they could find, designated WA1/2020. It had been grown successively (passaged) four times on cells in Petri dishes. The second source was derived from a DNA copy of the GenBank sequence NC_045512.2, a clone closely related to the Wuhan strain. To recover infectious virus, the 1320
DNA was first transcribed into RNA then introduced into a cell that constitutively produced the N protein. In both cases, both virus stocks were remarkably heterogeneous. The first evidence of heterogeneity is dramatic variation in plaque size, the dimensions of the clear area of dead cells surrounding infection of a single virus particle. Figure 1A and 1B show the variation in plaque of the Wuhan strain (1A) and the cloned strain (1B) when grown on Vero E6 cells. Moreover, the ratio of total virus particles (the genome equivalents-GE) to those viruses capable of infecting cells in culture and in forming a plaque (The plaque forming units —PFU) was low, roughly 27.6 compared to over 1000 in the unpassaged viruses.
FIGURE 1: Increase in plaque size after five passages for the (A) natural virus and (B) cloned ... [+] SHILIAEV ET AL.
The viruses were then passaged. Viruses were introduced to Vero E6 cells with the human ACE2 receptor in five rounds. They infected the cells, were allowed to spread, then diluted and reintroduced. They repeated this process for the two different viruses five times. Through several of these passages, the researchers noted that infectivity rose dramatically, as demonstrated by the ratio of genome 1321
equivalent to plaque-forming units (GE:PFU) decreasing starkly. In original virus stocks, the great majority of the viruses were incapable of infecting and forming plaques, whereas in the passaged viruses, the GE:PFU ratio was much closer to one, a 100-fold increase in the particle to infectivity ratio. Both virus stocks when passaged only five times became far more infectious, as measured by the plaques forming test.
FIGURE 2: Decrease in genome equivalent to plaque forming units (GE:PFU) ratio in the (A) natural ... [+] SHILIAEV ET AL.
Mutations Found Post-Passaging The mutations resulting in the 100-fold more infectious viruses were dramatic changes in the structure of the gene that encodes the Spike protein. After the final passage of the live virus, they find a high prevalence of an insertion of 21 nucleotides in the N-terminal domain coding sequence. This insertion added the peptide GLTSKRN (glycine-leucine-threonine-serine-lysine-arginineasparagine) between Spike protein positions 214 and 215. Additionally, they found S247R (serine to arginine) downstream in the N-terminal domain and H655Y (histidine to tyrosine) in the furin cleavage region.
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FIGURE 3: Mutation selection in the natural virus after five passages. SHILIAEV ET AL.
The seven amino acid insertion introduces two positive charges to an otherwise neutral or negative region of the Spike protein. The other N-terminal domain mutation also introduces a positive charge. Measurements of the ratio of the full-length genome to the cleaved protein show that the changes in and around the furin cleavage site decrease the efficiency of cleavage by the furin, but do not eliminate the site altogether. However, the mutations still allow the passaged viruses to be fully infectious as they do not change the second cleavage site earlier in the Spike genome.
FIGURE 4: Spike protein domains with cleavage sites (noted in green), mutations in the natural virus ... [+] ACCESS HEALTH INTERNATIONAL
Notably, the researchers found that the mutations were already present in low frequencies. After five rounds of passaged, those mutations were selected as favorable for the virus. 1323
In the cDNA passaged virus, different mutations were observed. Before passaging, there was a collection of small and large plaques, but then after five passages, all large plaques were observed. The GE:PFU ratio dropped dramatically, as in the live virus. Though the researchers found different mutations: the S686G mutation directly following furin cleavage and the I68R and N74K mutations in the in vitro N-terminal domain.
FIGURE 5: Mutation selection in the cloned virus after seven passages. SHILIAEV ET AL.
As demonstrated by Figure 5, the researchers found that in the clone, mutations were again found in low frequencies among the early rounds of passaging. Those mutations that conveyed significant advantages to the virus were selected in greater frequency as passages advanced while those that were not advantageous were left behind.
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FIGURE 6: Mutations in natural viruses (noted in blue) and cloned viruses (noted in red). SHILIAEV ET AL.
Consequences of the Mutations These mutations impose similar results on the passaged cDNA virus. The N-terminal domain mutations increase the overall positivity of the region, albeit less so than the live virus insertion, and the furin cleavage mutation reduces furin cleavage. We can therefore conclude that SARS-CoV-2, whether naturally passaged or passaged in vitro, will replicate and mutate rapidly in Vero E6 cells containing the human ACE2. The authors then speculate that the N-terminal domain mutations allow the virus to bind more tightly to negatively charged glycans on the surface of cells. They test that by testing the binding affinity of the virus to bind to negatively-charged molecules that resemble the glycans called heparin. The passaged viruses bound to heparin more tightly, and thus the cell surface glycan. Binding to these negatively-charged glycans can facilitate infection, as facilitated by the N-terminal domain mutations.
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FIGURE 7: Heparin efficiently inhibiting infectivity of high passage, but not low passage natural ... [+] SHILIAEV ET AL.
Let us pause to understand exactly what was happening in these experiments. When we describe a virus, such as Wuhan, Alpha, Beta, we are not measuring a pure collection of viruses. Viruses exist as a swarm, or quasi-species as described by Manfred Eigen, each of which contains slightly different mutations from the set, despite originating from the same strain. This is why some viruses from the same strain can form small plaques versus large plaques. This is a critical distinction, as the population of viruses in an infected person are not uniform, but represent a collection of slightly different viral genomes. Passaging in culture has a powerful selection of the properties of the virus that emerge. Pre-existing variants emerge rapidly under these conditions. If that is the case, what then does the sequence of a variant mean? The published sequence is an average of the viruses in the collection. The description of any particular variant is the average of the predominant mutations in that particular viral isolate, whether derived from patient blood samples or culture passaging. We have seen this process in immunosuppressed patients that developed long Covid-19. The virus continues to adapt to the patient’s weakened immune systems, selecting mutations continuously to avoid detection and expulsion. The cDNA experiment additionally allows us to conclude that even in cloned viruses, the RNA polymerase used to transcribe the clone makes transcription errors. These errors may occur in low 1326
probability, but if present are selected and propagated throughout a virus swarm. Conclusions Both the natural and cloned viruses adapt rapidly to cell culture. They adapt by selecting from mutations that appeared at a lowfrequency in the quasi-species to become high-frequency mutations. The low-frequency mutations originate from polymerase mistakes when copying the virus. In the cloned virus, the authors suggest errors occur when the DNA clone is copied by an error prone polymerase in vitro. In both viruses, RNA virus particles emerge that are heterogeneous. Through cell culture passage, low-frequency mutations that confer enhanced viral characteristics are selected under the conditions used. This same phenomenon occurs in nature as well. When SARSCoV-2 infects a host, they begin to make copies of themselves. Each copy has, on average, three different mutations. In nasal fluids, the concentration of virus per milliliter in the Wuhan strain is 108 particles/mL (100,000,000). For the Delta variant, it is 1,000 times larger (1011 or 100,000,000,000 particles/mL). Therefore, there are between 300 million and 300 billion mutations per mL in an infected person. These mutations are selected via passage for viability, stability, infectivity, and replication capability, meaning each passaging infection selects a more virulent virus. This is how variants arise. Given these numbers, it should be no surprise that variants arise so frequently. Three final questions on this research: First, is the SARS-CoV-2 virus selected in tissue culture also more infectious in animals, including humans? That could be tested in mice, hamsters, and primates, and those answers would be instructive. Second, the authors only examine the Spike protein. Under natural selective conditions, the virus varies along the entire length of the genome, both synonymous and nonsynonymous mutations in the Orf1ab proteins, structural proteins, and regulatory (accessory) proteins. Does viral selection mutate amino acids in the 29 other
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viral genes? Might some of the changes in infectivity be attributed to these changes? Finally, there has been controversy over potential “gain of function” experiments. The live SARS-CoV-2 in these experiments is far more infectious, at least in human cells, than some of those strains circulating around the world. There is a history of these viruses being even more pathogenic in animals than in cell culture. For instance, deletions in the furin cleavage site in the feline enteric coronavirus increase pathogenicity in animals. There are some strains that emerge from passage that acquire neurotropism, causing brain disease. The natural and clone viruses in Shiliaev et al. both contain furin cleavage mutations that may have a similar proclivity. The authors describe conducting their experiments under P3 containment conditions. Such a dramatic increase in infectivity as they noted causes us to wonder whether these experiments should be done under more restrictive containment conditions. This article originally appeared in Forbes, and can be read online here: A Snapshot Of SARS-CoV-2 Evolution: Observed Increase Of Infectivity In The Covid-19 Virus
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October, 2021
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A Neanderthal Gene That Protects Us From Covid-19 (Part 14) Forbes | October 5, 2021 | Article
OAS1 as St. Michael, slaying the dragon SARS-CoV-2 via multiple points of attack. “Archangel Michael ... [+] THE WALTERS ART MUSEUM HTTPS://ART.THEWALTERS.ORG/DETAIL/37741/ARCHANGELMICHAEL-SLAYING-THE-DRAGON/
This is the fourteenth article in a series called “How SARS-CoV-2 Delays, Evades, and Suppresses the Immune System.” Read parts 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13. Science continues to unveil the secrets of Covid-19 one paper at a time, decoding how the virus works and what the body does to protect itself in response. A new study offers a deep glimpse into this perennial battle between humans and infectious diseases by way of a gene that appears to have the power to knock out SARS-CoV-2.
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One of the fundamental mechanisms the body uses to destroy incoming threats is attacking the genome. Since the SARS-CoV-2 genome consists of RNA, our cells can digest it. But that same ability isn’t tightly controlled, it can become deleterious to the host, digesting cellular, rather than viral, RNA. What unleashes the destructive force that can potentially annihilate the cell? In the case of SARS-CoV-2, and for many other viruses as well, it is ribonuclease L, which normally exists as a single entity but becomes active when it receives a specific signal and forms a dimer that can digest RNA both viral and cellular. What triggers RNAse L? The short answer is interferon. Whenever a virus invades a human cell, a series of pathways comparable in complexity to a Rube Goldberg apparatus is activated to induce interferon production (see Figure 1). Interferon in turn induces hundreds of interferon-stimulated genes. Viruses like SARSCoV-2 do their best to prevent this cascade from happening, but their attempts at blockade can only go so far or last so long. In a recent publication in Science, Wickenhagen et al. show that one interferon-stimulated gene, 2’-5’ oligoadenylate synthetase (OAS1), controls SARS-CoV-2 infections. The OAS1 protein exists in two forms: a longer 46 thousand dalton (46K) protein and a shorter 42K version. The ability to make either the long 46K or short 42K form of the OAS1 protein is genetically determined. The longer 46k form carries a signal that allows it to be modified by the addition of a lipid, a process called prenylation. The addition of the lipid allows OAS1 to associate with cellular membranes. It is the longer 46K prenylated form of OAS1, not the shorter 42K unprenylated version, that provides the signal that activates ribonuclease L upon SARS-CoV-2 infection.
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Figure 1. (a) Diagram illustrating induction of interferon-stimulated genes. (b) Interferon ... [+] ACCESS HEALTH INTERNATIONAL
In another tour de force, Wickenhagen et al. decipher the precise signal that triggers OAS1 activity. Previous studies show that OAS1 is activated when it detects double-stranded RNA. How then do the single stands of viral and messenger RNAs active OAS1? The answer is unexpected. OAS1 binds to two short segments of viral RNA near the 5’ end of the viral RNA called stem-loops 1 and 2. By pairing with itself, this region of the SARS-CoV-2 genome forms the requisite double-stranded stem-loop structures (Figure 2). The authors reveal the intimate interactions between the stem-loops at the beginning of the viral genome and viral messenger RNAs. Once OAS1 binds to the stem-loops 1 and 2, it produces a small molecule called 2’-5’-oligoadenylate (2-5A). It is 2-5A that activates RNAse L. In the presence of 2-5A, inactive monomers of RNAse L—held in reserve in case of viral attack—dimerize to form the active enzyme that shreds the viral RNA.
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Figure 2. OAS1 binds to two short segments of viral RNA near the 5’ end of the viral RNA called ... [+] ACCESS HEALTH INTERNATIONAL
Prenylation is key to OAS1 recognition of viral RNA. Virus replication occurs in a special compartment walled off from the rest of the cell by a double membrane vesicle. The researchers show that prenylated 46K OAS1 binds to the double-membrane vesicle whereas the unprenylated 42K form does not. In other words, the longer form of OAS1 penetrates one of the virus’s primary defenses, the shield of protection afforded by the highly structured replication compartment. Wickenhagen et al. report that the double membrane replication compartment is fragmented by the active OAS1-RNAse L duo. The authors find that the 46K version of OAS1 inhibits many other pathogenic viruses that like SARS-CoV-2 replicate within their own double-membrane vesicle concealment, including encephalomyocarditis virus and some other coronaviruses. We have known for some time that ribonuclease L is an enemy of SARS-CoV-2. This series describes the many ways by which the SARS-CoV-2 inhibits interferon and interferon stimulated genes (Figure 1). Wickenhagen et al. of this study have advanced our understanding of one of the primary reasons why SARS-CoV-2 must deactivate interferon and interferon induced genes to survive. Why is this important? Wickenhagen et al. confirm that those who inherit the 42K version of OAS1 are much more likely to end 1333
up severely ill, in the ICU, or dying from Covid. Sequencing samples from almost 500 hospitalized Covid-19 patients, the authors of the study found that the median transcript abundance of 46K OAS1 was lower in patients with severe Covid-19 by more than 100-fold. The long 46K version of OAS1 is what we might call a survival gene (more technically a survival allele). It should be possible to test incoming patients for this inherited trait to predict disease outcomes.
Figure 3. Comparative diagrams of exon structures of 42K and 46K OAS1. The difference in the alleles ... [+] ACCESS HEALTH INTERNATIONAL
Population studies show that this Covid-19 survival allele is not evenly distributed in populations throughout the world. At the low end of the spectrum is a cohort from Lima, Peru at 11 percent; at the high end, another from Esan, Nigeria at 70 percent. Most people in the United States lack the protective variant of OAS1 (Figure 4). It might be worth knowing your person of the OAS1 gene to understand at least one component of your risk from Covid-19.
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Figure 4. Frequency of alleles with G at Rs10774671 in different human populations (1000 genomes ... [+] SOURCE: HTTPS://WWW.SCIENCE.ORG/DOI/10.1126/SCIENCE.ABJ3624
Wickenhagen et al. also confirm an early observation that the protective form of OAS1 is inherited from our Neanderthal ancestors. It is now well established that up to two to five percent of our genes survive from interbreeding with our Neanderthal predecessors. The 46K variants is one of those traits. It seems likely that prevalence in the population reflects successful defense against past and present encounters with lethal viruses. Note that two viruses, MERS-CoV and SARS-CoV, are resistant to RNA cell defense OAS1. We know how MERS-CoV and at least one of the cold-causing coronaviruses evade RNA cell destruction. They encode a protein, NS4b, that cleaves 2-5A, limiting RNAse L activation. At present it is unknown how SARSCoV-1 evades RNAse L as it has no protein equivalent to the other coronavirus NS4b. Nonetheless evasion of this pathway appears to increase lethality. SARS and MERS kill approximately 10 percent and 30 percent of those infected, respectively. We can only hope SARS-CoV-2 never acquires the accessory the ability to inactivate 2-5A either by evolution or recombination from bat or cold-causing human coronaviruses. The authors also describe several other interferon stimulated genes that inhibit SARS-CoV-2 replication. A deep exploration of the role of these genes and others yet to be discovered is needed. 1335
A final note. Drug candidates exist that mimic 2-5A. Such drugs may help Covid-19 patients who cannot fight the virus on their own. This article originally appeared in Forbes, and can be read online here: A Neanderthal Gene That Protects Us From Covid-19 (Part 14)
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Making the Transition from an Academic to a Biobusiness Entrepreneur GEN News | October 4, 2021 | Article
When I became an assistant professor at Harvard in the mid1970s, creating a company was never part of my plan. I had only a dim understanding of how corporations were organized and no understanding of finance. But I was slowly becoming aware of how biotech businesses could be a positive force for health. I had been keeping tabs as close friends from various universities gave up their tenured positions to join nascent companies gaining an early foothold in the new field of biotechnology. All were racing to apply the new techniques of recombinant DNA (gene splicing) to make new drugs and vaccines. I was beginning to realize that the work I was doing as a research scientist might create a conceptual breakthrough, but the businesses were the ones taking that breakthrough and delivering it in the form of drugs to patients in need. I was working at the time on retroviruses and their potential role as a cancer-causing agent in animals. I’d planned a trip to the West Coast to build up my collection of mouse leukemia viruses, which is where I learned from my friend Richard Lerner, a research chemist at Scripps who had been studying protein structures, that you could accelerate an antibody response by using peptide fragments, as opposed to using whole viruses or virus proteins. I understood the impact of the discovery immediately: using peptide fragments would be a faster, cheaper way to make vaccines. That was the tipping point. I knew that this knowledge could shorten the time it took to develop new drugs, which at that time required at least ten years and many tens of millions of dollars. I also knew that pets and livestock suffered serious viral infections. If we could test the idea in animals, we wouldn’t need to go through the FDA. I could create a company that would be a shortcut to demonstrate that a vaccine can prevent retrovirus infections that cause cancer. 1337
I worked with Deborah Ferris, who had helped get Biogen off the ground, to develop the business plan for a company that would develop animal vaccines with this new technology. I went to every Wall Street banker and venture capitalist I knew, and I eventually landed myself a $5 million commitment. These financiers understood the power of knowledge and the economic benefits it could bring. I thought, after securing financing, that I had jumped over the hardest and highest hurdle in the process, but I was wrong. I didn’t yet realize the political hurdles I still had to jump at Harvard. There was no precedent for a Harvard assistant professor starting a company. Even for full professors, the idea was highly controversial. Harvard’s president had voiced skepticism, and faculty across the university grumbled, some with outrage, at the notion that biologists or biochemists might turn discoveries developed at Harvard into a personal fortune. This, despite the fact that many of the university’s history and economics professors were making tens of thousands from the sale of their books. I was faced with many setbacks but managed to overcome them after a bit of luck followed me onto a plane flying from New York to Boston early the next year. I ended up seated beside Larry Fouraker, dean of the Harvard Business School at the time. I pitched him my idea for a company and explained the challenges I was running into at the university. He told me something I had not realized: thanks to the Bayh-Dole Act, which had been passed during a lame-duck session of Congress just months before, universities were now required to create a technology transfer office to turn new ideas into companies. The law’s intent was to promote commercialization of research funded by the federal government. Birch Bayh, Democrat of Indiana, and Bob Dole, Republican of Kansas, were the legislation’s sponsors in the Senate. Jimmy Carter signed the bill into law. The law states that all universities and research institutes that receive federal funding must file patent applications on all discoveries with practical application and must make best efforts to transfer the technology to businesses for commercial development. That was my green light. Larry became a close friend and mentor to me. The only requests he ever made of me were to speak to his students at the business school from time to time about 1338
entrepreneurship and to pledge some shares of the company I would found, Cambridge BioScience, to the university’s endowment fund. I ended up offering Harvard 5% equity, but they turned it down. They hadn’t worked out what they thought the ethics might be of such a transaction. I can assure you that by now they have. Far from harming my career, creating Cambridge BioScience turned out to be a huge plus. I developed powerful relationships with some of the department chairs and became a role model and adviser to other faculty members in starting their companies. Eventually, Harvard’s governing board and administration embraced the benefits of professors starting companies, and I was asked to chair a university-wide committee that would clarify the rules governing relationships between professors and the companies they seek to start. Ironically, the university now requires faculty to pledge a percentage of the founding shares as well as royalties received for startups based on a professor’s patents. As I noted earlier, Harvard never accepted my 5% offer. But after Cambridge BioScience went public, I sold the 5% and donated the cash. They were happy to accept it. I learned through the process that our scientific reputation is our capital. I also learned that no person or company ever becomes a success without people like Larry to support and mentor them. This is why I am so pleased to have been invited to contribute to this commemorative, 40th Anniversary edition of GEN. The magazine’s founder, Mary Ann Leibert, has been a great support to me over many years, but especially at two inflection points in my life. The first was in the early years of the HIV/AIDS crisis, when I suggested that we create a journal to help cover some of the most exciting, but often neglected, developments in the field. Mary Ann jumped at the idea and took no more than two seconds to agree, and we founded the Journal of AIDS Research and Human Retroviruses. Fifteen years later, I conceived of the idea of regenerative medicine and began to work with Tony Atala and others to create awareness of the new field and its motto: Regenerative medicine is any medicine designed to restore a person to normal health, including cell and stem cell therapies, gene therapy, tissue engineering, genomic medicine, personalized medicine,
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biomechanical prosthetics, recombinant proteins, and antibody treatments. Mary Ann responded immediately and positively once again, offering to create the Society of Regenerative Medicine and another new journal, initiatives that were soon launched. Mary Ann, through her journals, publishing company, and GEN, has always been the wind in the sails of the biotechnology industry. This article originally appeared in GEN News, and can be read online here: Making the Transition from an Academic to a Biobusiness Entrepreneur
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Origin: Very Close Relatives Of SARS-CoV-2 Identified In Laotian Bats Forbes | October 6, 2021 | Article
The pandemic SARS-CoV-2 virus likely originated from bats in Southeast Asia. There are over 450 million people sharing the region with the bats that live in limestone caves in countries like Vietnam, Thailand, Myanmar, and Laos. One of the predominant genera of bats in the region is the Rhinolophus (horseshoe bat). Bat species falling in this genus contain an ACE2 receptor that closely resembles that of humans. The ACE2 is so similar, in fact, that many of the coronaviruses in these bats have the potential to infect humans as well. The exact origins of the SARS-CoV-2 virus are shrouded in mystery and some controversy. Recent estimates of the number of people infected by coronaviruses of horseshoe bat origin in Southeast Asia are between 400,000 and two million. A recent study from the Pasteur Institute, Temmam et al., investigates viruses endemic to the bats of this region. The researchers sampled 645 bats from four different Laotian sites. The bats were classified into 46 different species. It should come as there are over 1,400 different species of bats throughout the world. They extracted the coronaviruses from the bats’ blood, feces, urine, and saliva. The first finding is that as many as seven different species of bats harbored the same type of coronavirus, known as a sarbecovirus. These are a subgenus of betacoronaviruses, to which the SARSCoV-2 and SARS-CoV species of virus belong. In a startling discovery, the authors report that several of the viruses isolated from bats caves in the Vientiane Province are very closely related to SARS-CoV-2. In fact, they are so closely related that the idea that SARS-CoV-2 originated from RaTG13 coronavirus isolated from horseshoe bat in southern China in 2013 is no longer tenable. The receptor-binding domains of SARS-CoV2 and RaTG13 differ too greatly. 1341
The original SARS-CoV-2 Wuhan strain has 17 amino acid contact points between the virus and the ACE2 receptor. Several of these are modified in the RaTG13 coronavirus. However, two of the viruses analyzed by Temmam et al.—BANAL20-52 and BANAL-20-103—differ by only one of the 17 amino acids. Another analyzed virus—BANAL-20-236—differs by only two amino acids. By contrast, in RaTG13, there are six amino acid modifications. We note that a change of only one or two residues in the contact points is well within the range of various naturally occurring variants of SARS-CoV-2, which carry as many as three amino acid changes in these residues. The authors conducted several experiments to determine whether similarity in the receptor-binding domain region of the Spike protein of the BANAL-20-52, 103, and 236 translated to a similar function to that of SARS-CoV-2. Their first question was whether the receptor-binding domain of the viruses is capable of infecting cells that carry the human ACE2 receptor. Using a pseudotype virus on cells in culture, they found that the answer is a resounding yes. They went on to show that the complete genome of BANAL-20-236 is plaque-forming when introduced to human cells. In fact, it formed plaques more so than the Wuhan strain of SARS-CoV-2. These two observations demonstrate that not only does the bat virus receptor-binding domain recognize human ACE2, but the whole virus is capable of infecting humans.
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FIGURE 1: Infectivity and Plaques of BANAL-20-236 on human VeroE6. Figure from Temmam et al. TEMMAM ET AL
Their second concern was to understand exactly how similarly the bat coronaviruses bind ACE2 compared to SARS-CoV-2. Using binding modeling and structural analyses, the researchers showed exactly how the bat virus receptor binding domain could interact with the ACE2 protein, offering a biochemical explanation of exactly how the bat Spike bind. The similarities between SARSCoV-2 and the two bat viruses extend across the entire genome with one marked exception, Orf8. Within SARS-CoV-2 variants, Orf8 is among the most frequently mutated genes. To understand the interaction of bat receptor-binding domains with ACE2 and the functional dynamics of the relationship, the researchers performed a biolayer interferometry assay with the different viruses to analyze the nanomolar range of binding affinity. In layperson terms, they tested to see if the bat viruses bound to ACE2 in a similar tightness to SARS-CoV-2, which they did. Finally, to analyze the binding structure, they used x-ray crystallography at 2.9-angstrom resolution for both SARS-CoV-2 and BANAL-20-52. The figure below displays the structural similarities and differences between the two complexes, particularly the mutated residues in the receptor-binding domain and the structural complexes in the helices. As expected, most of the interactions observed between the ACE2 and SARS-CoV-2 receptor-binding domain were also present for BANAL-236.
FIGURE 2: Ribbon representations of the crystal structures of hACE2 peptidase domain (cyan) in ... [+] TEMMAM ET AL
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Recombination is frequently observed among naturally occurring coronaviruses. The Laotian bat viruses are no exception. The authors were able to decipher recombination events amongst the broad family of coronaviruses infecting bats, which likely contribute to the origin of SARS-CoV. The picture that emerges is a continual reassortment of genes leading to a mosaic of viruses. For both SARS-CoV-2 and the bat viruses, there appear to be two separate origins of the exterior Spike protein, one for the N-terminal domain and another for the receptor-binding domain. The one question that remains is the origin of the Furin cleavage site. A recent survey of the viruses found that there are many coronaviruses with independently-derived Furin cleavage sites. Many genera of coronavirus, including alphacoronavirus, gammacoronavirus, and betacoronavirus contain some viruses with the naturally-derived site. We note that some viruses that pairs of viruses that are otherwise identical over their entire lengths may differ in the presence or absence of a Furin cleavage site. For instance, SARS-CoV-2 contains one, whereas SARS-CoV lacks one. In fact, the Furin cleavage site is often lost merely by growing SARS-CoV-2 in human tissue culture. It is likely that the Furin site arises in some SARS-CoV-2 variants and bat viruses by natural recombination, as it may have been the case for SARS-CoV-2.
FIGURE 3: Furin cleavage sites at spike S1/S2 naturally occurred independently for multiple times in ... [+] YIRAN ET AL
The authors speculate that the Furin cleavage site could be acquired upon coinfection with either another bat or some other exotic species. I would add here that it could have been acquired by coinfection with humans in the region previously coinfected with 1344
another bat virus which contains a Furin cleavage site in a separate recombination event, What is the significance of this finding? As we have already experienced, the Covid-19 pandemic is not a one-off event. Humans are repeatedly infected and perhaps quite frequently infected with coronaviruses of bat and other species origin. It is believed that MERS-CoV, for example, was acquired from camels, which in turn was acquired from viruses prevalent in humans and bats in Africa. Many of the cold viruses that sweep through our population also have an animal origin, such as OC43, which originated in domestic farm animals like cows and pigs. In the recent past, there have been reports of canine coronaviruses infecting children in Indonesia. Moreover, SARS-CoV-2 variants have shown that coronaviruses can continually adapt to their host, resulting in a more infectious and pathogenic virus. With respect to the current pandemic, we should be alert to the possibility of new, more transmissible, dangerous versions of COVID-19 may emerge. Many hundreds of millions have already been infected with SARS-CoV-2, as well as domestic and feral fauna. It is possible that new adaptations via animal coinfection may emerge, such as those found in mink. Additionally, recombination events between SARS-CoV-2 and other coronaviruses that exist in the human population could give rise to new and more dangerous forms of the pandemic. This article originally appeared on Forbes, and can be read online here: Origin: Very Close Relatives Of SARS-CoV-2 Identified In Laotian Bats
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Successful Multimodal Covid Control In Summer Camps Forbes | October 7, 2021 | Article
A new CDC report demonstrates how using multiple Covid-19 prevention strategies at nine US overnight summer camps was highly effective in preventing transmission of Covid-19, even in the wake of the Delta variant. Amongst 7,173 campers and staff members at nine overnight camps between June and August 2021, there were only nine laboratory-confirmed cases and no secondary infections detected. This is in striking contrast to many other summer camps that used few mitigations and experienced rapid outbreaks. This group of summer camps serves as a microcosm for how we can approach effective Covid control nationwide. The CDC report did not attribute the success of this strategy to a single modality, instead, it was the multiple layers of protection that ensured zero secondary transmission of the virus. The success of this multimodal Covid-19 control can serve as a guide for other congregate settings. The layers of protection used by the summer camps included; vaccination (93% of eligible children were vaccinated), pre-arrival and frequent screening testing (both rapid and PCR), creating social “pods” or cohorts within the camp, masking, physical distancing, and hand hygiene through the use of sanitizing stations. Pods began as groups of campers and staff members who shared a cabin. Pod residents were allowed to interact with each other without masking or physically distancing. Pods were then gradually merged in stages, growing from one cabin to multiple cabins, to age groups. Through this method, three out of nine camps eventually reached camp-wide pod expansion. One camp also used wastewater surveillance testing three times per week. Wastewater surveillance has been an underused yet costeffective, non-invasive mass testing strategy throughout the pandemic that can detect virus shed by symptomatic and asymptomatic people alike. A study from UC San Diego demonstrates that wastewater surveillance can detect Covid-19 in a 1346
single infected, asymptomatic person living or working in a multiunit dwelling such as a college campus building. This makes wastewater surveillance a highly effective intervention for congregate living situations. In addition to these on-site interventions, each camp also requested that staff members and campers adhere to masking and physical distancing when interacting with persons outside their immediate family for 10–14 days before arrival and while traveling to camp. Campers across all nine camps were required to submit at least one negative SARS-CoV-2 RT-PCR test result from a test performed within 72 hours before the start of camp, regardless of vaccination status. The frequency and type of screening testing during camp varied across the camps and by vaccination status. In addition to a prearrival RT-PCR screening test, at least three screening tests were required by all camps for unvaccinated campers through the first 12 days after arrival. Six camps used a combination of rapid antigen and RT-PCR testing for screening; the remaining three used only RT-PCR testing for screening. RT-PCR test results were returned within approximately 12–24 hours. The screening testing was successful in identifying six confirmed Covid-19 cases (one in a staff member and five in campers) by RTPCR testing. Three additional cases (in two staff members and one camper) were identified based on symptoms and were confirmed by RT-PCR testing. A successful isolation and quarantine program for those cases meant that there were no secondary cases of Covid-19. The nine cases were spread across four camps. Three of the nine cases occurred in vaccinated staff members and six in unvaccinated campers aged 8–14 years. The three staff member cases were identified before the arrival of campers. One case in a vaccinated symptomatic staff member occurred during the initial staff week, and the other two cases in vaccinated staff members (one asymptomatic, one symptomatic) occurred between sessions. Two of the six campers with cases were asymptomatic and identified by prearrival screening; these campers did not enter the camp. Three additional cases were identified by screening testing, and one was identified because the camper was symptomatic; all were identified within the first 8 days of camp.
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The study's authors provide great detail about the impact of testing and pod interventions on virus transmission rates, but further research is needed on how masking, hand hygiene, wastewater surveillance, and physical distancing impacted virus transmission. Camp locations were spread across the nation in New England, Middle Atlantic, the South, Midwest, and West. This means that the data obtained was not influenced by local case prevalence. Summer camps (outside of the study’s group of nine) that focused only on measures such as pre-arrival testing without subsequent testing or other preventative measures experienced rapid outbreaks. A boys’ overnight summer school retreat in Wisconsin required all attendees to provide documentation of either a positive serologic test result within the past 3 months or a negative RT-PCR test result less than 7 days before traveling to the retreat, or selfquarantine within their households for 7 days before travel, and to wear masks during travel. This kind of policy ignores the reality of reinfection and the strong possibility of becoming asymptomatically infected in transit to the retreat or within the 7-day testing window. Unsurprisingly, this retreat experienced an outbreak that was traced back to a single student who had received a negative test result less than one week before the retreat and led to 116 (76%) diagnosed Covid-19 cases among the campers. The lack of other mitigation measures meant that the virus spread quickly throughout the camp. The RT-PCR screening tests used at the nine camps had a quick turnaround time of 12-24 hours for results. But with the reopening of schools and workplaces increasing demand for PCR testing and putting a strain on labs, the turnaround time is significantly slower, rendering the tests far less effective. In Pittsburgh, the turnaround time is presently between 4-6 days as opposed to the usual 1-2 days. This is where rapid testing can be incredibly effective in preventing the rapid transmission of the virus in congregate settings. Rapid tests are better suited than PCR tests for identifying and containing the pre-symptomatic spread of the virus. A UK study, published in the Lancet, found that schools using a test-to-stay protocol had similar rates of symptomatic Covid-19 infection to those using quarantines. However widespread accessibility to rapid tests in the US is presently hampered by a cumbersome F.D.A. process intended for high-tech medical devices. To be approved, the rapid tests must demonstrate that they are nearly as sensitive as the 1348
gold standard PCR. tests. But rapid tests do not need to be as sensitive, PCR tests often identify small amounts of the Covid virus in people who had been infected weeks earlier and are no longer contagious. Rapid tests can miss these cases while still identifying approximately 98 percent of cases in which a person is infectious. Rapid tests are the “public health gold standard” and should therefore be regulated as a Public Health Good. President Biden could accomplish this with a simple Executive Order, increasing competition among manufacturers and flooding the market with inexpensive, high-quality rapid tests. In an ideal scenario, tests should be provided free to all households to encourage their frequent use, like they are in many countries. But Federal bulk orders of rapid tests would also bring the price down closer to a dollar, making them accessible for all who need them. By taking advantage of rapid testing and implementing the multiple successful preventative strategies used by these summer camps we can prevent high levels of transmission in schools, colleges, workplaces, and other congregate settings. This data is particularly useful for schools given the youth demographic involved. Our focus needs to shift to multiple layers of prevention and protection working in tandem with medical interventions. This article originally appeared on Forbes, and can be read online here: Successful Multimodal Covid Control In Summer Camps
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Will Covid Overwhelm Our Vaccines? Forbes | October 8, 2021 | Article
The chaotic booster rollout — with the White House calling for boosters for all, the FDA recommending them only for a few, and the CDC overruling both to provide them to some but not everyone — left many confused over vaccine protection. The vaccines work, but not equally for everyone. Determining how effectively your vaccine may be protecting you from symptomatic illness, severe disease, or death is not a simple yes or no equation — it’s conditional. Like most other vaccines, Covid vaccines don’t act as a foolproof barrier to infection but rather as a fire alarm. The virus enters your body, vaccine-induced antibodies quickly recognize the threat, and they launch an all out attack to stop the virus from replicating and rid it from your system. Even though you may have technically become infected, the infection is non-productive and you never become symptomatic or ill. That is successful vaccine protection. With that in mind, the first condition of Covid vaccine success is the development of a high concentration of antibodies that can detect SARS-CoV-2 infection and prevent the virus from replicating. Right now, two doses of an mRNA vaccine produces a high level of neutralizing antibodies that can recognize most known variants of SARS-CoV-2 and, in the months immediately after the second dose, effectively clear the virus before a person becomes sick. For a select few, like some recent organ transplant recipients, the vaccines don’t achieve this goal. But for most, two doses of the mRNA vaccines work. The challenge though, is time. Antibody levels generally spike immediately after infection or vaccination and then fall over time. All of us can expect our initial antibody levels to drop eventually, somewhere around five to eight months, but for some of us — those with weaker immune systems either from age or other illnesses — those levels may drop sooner and more quickly. We also know that our antibodies perform less effectively against some SARS-CoV-2
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variants, even among the healthy. Against some variants, effectiveness drops just four months after the second dose. That leads us to the second condition, which is tied to the first: the number of doses required to reach high levels of neutralizing antibodies over an extended period of time. Initial FDA emergency approval was granted to the mRNA vaccine manufacturers for a two-dose Covid vaccine, given the urgent need to contain the spread of the pandemic and early clinical trial results. But more recent studies have shown that a third dose can significantly improve both the potency and breadth of neutralizing antibody levels, providing even greater protection against all known variants than occurs after the second dose. Even if the initial spike in antibodies drops, it is dropping from a much higher level, meaning it will take longer for the vaccine to lose its effectiveness. Knowing this, I would say that you can consider yourself protected against Covid-19 only if you meet both the first and second conditions on this list — if you received your first two vaccine doses more than four or five months ago, you need a third dose to be sure that you have a high enough level of neutralizing antibodies to knock out the virus before you become ill. The mRNA vaccines are, in reality, a three dose regimen, not two. Now we move to the next condition: long term immunity. The initial surge in antibody protection after vaccination or infection for any disease is always expected to fall — our bodies couldn’t possibly continue churning out antibodies to combat every threat they have ever encountered. But we have a longer term immune response that steps in, led in part by memory B cells. These B cells are a little like bouncers standing inside the door of your local bar. They’re often at rest but always on the alert for threats. If they’ve seen an unwelcome visitor from the past return, they try to kick them out immediately before they can cause any trouble. The way B cells do it is by kicking off a series of reactions that generates a new surge in antibody production to knock out the virus. But this effort takes time — first the time needed to detect the threat and then the time needed to generate enough antibodies to overwhelm and overcome the virus. When it comes to long term immunity for Covid-19, the question — still unanswered — is whether our long term memory cells are able to act quickly enough to mount an immune response. For some diseases, like the measles, vaccine-induced immunity lasts 1351
for nearly a lifetime or, as with diptheria, over multiple years. For viruses like the flu, however, vaccine protection is much shorter lived not because of any inherent failure of our immune system, but rather due to the nature of the virus. Like Covid, the influenza virus mutates and adapts; every mutation is like a new disguise the virus wears to enter our bodies undetected. The bouncer B cells may eventually recognize the virus as a threat, but it takes them longer, giving the virus more time to replicate and spread before a person even knows they’re infected. During that extended period of time the virus can escape to infect others, which is a critical challenge to controlling new infections and the spread of disease. The other major challenge, more critical to the person infected, is that by the time the B cells notice the threat and mount a response, the virus may have replicated to such an extent that it becomes even harder for the immune system to knock it out. This explains why people who have been vaccinated can still become quite severely ill from infection. Given our nascent understanding of long term immunity against SARS-CoV-2, none of us can yet know whether this condition will be met over time. What we can expect, however, is that at least in the short run we will need regular Covid vaccines, beyond the first three doses. We’ve already become accustomed to annual vaccinations for the flu. Each year, the vaccine primes our bodies for the most likely influenza strains circulating that year, provoking an initial vigorous antibody response and giving our long term memory cells an indication of the disguises — or rather the mutations — the virus is wearing this year. Not only does this reduce the reaction time for our memory B cells, some studies also suggest that the repeated exposures help us build better and broader immune reactions. The final condition to consider when discussing vaccine protection is age and the quality of your immune system. We know the effect of aging on the immune system in general and on long term B cell production. A Covid-19 study from earlier this year shows the magnitude of the memory B cell response after a second mRNA dose was lower with increased age, confirming age as a key variable in vaccine-induced immunity. We also know there are other conditions that can weaken the immune systems in people of any age, such as inflammatory conditions and inherited 1352
predispositions to infectious diseases often caused by a genetic inability to mount a robust interferon response. What that means in terms of vulnerability to death and severe disease is still unclear, but this much is true: if you are older than 65 you are not going to have as robust an initial response to the vaccine and your long term immunity may be diminished too. Here’s what all these conditions of vaccine protection described above mean for the average person. If you meet all the conditions — you are young, with a healthy immune system, have received three doses of the mRNA vaccine and return for regular Covid vaccinations if and when future boosters become available —- you will most likely be very wellprotected against symptomatic illness and disease, but you can still become infected and spread the virus. With this in mind, be cautious still with your interactions and do your part to prevent others who may be more vulnerable from becoming infected. If you meet some, but not all of those conditions — you are older but have received all three doses, for example, or you are younger but don’t yet qualify for a third dose — you are likely wellprotected from the worst Covid can offer, meaning severe illness and death, but may still be susceptible to symptomatic illness and the threat of long-term complications from milder infections. Consider continuing other protections like mask-wearing and avoiding large, crowded gatherings at all times, even if these requirements are no longer the norm for those vaccinated where you live. And finally, if you’ve chosen to forgo vaccination or decided not to get your third dose, consider yourself at risk of symptomatic or severe disease and, unfortunately, death. Plan your outings and engagements wisely and use other means of protection at all times. This virus is with us for the long haul. Vaccines may not be foolproof protection but they do offer us remarkable protection, a protection that can save our lives and the lives of those we love around us if we use them effectively. This article originally appeared on Forbes, and can be read online here: Will Covid Overwhelm Our Vaccines?
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Anti-Covid Drugs Are Coming, But At What Cost? Forbes | October 8, 2021 | Article
A debate is raging over the cost of drugs in the United States and around the world. For at least three billion people in India and China, drug costs are determined by the manufacturing price, plus a modest market profit for suppliers and pharmaceutical wholesalers and retailers. Not so in the more “regulated markets” of North America and Europe. One example I have described in detail is the cost of a two-drug, three-month curative therapy for hepatitis C, which is about $80,000 in the United States and $45 (no zeros missing) in Egypt and India. At that cost, the government of Egypt, until recently the country with the highest per capita burden of chronic hepatitis C, eliminated the disease from the entire population in less than a year. Meanwhile many hepatitis C patients in the US continue to suffer from this life-threatening disease as a consequence of the high cost of treatment. Now comes the hope for what might be life-saving treatments for Covid-19: new antiviral drugs. Combined with vaccines, these drugs have the potential to end the pandemic. The hope is that upon exposure, popping a pill for several days will either prevent infection altogether—once vaccine protection has waned—or in those infected, prevent disease. Merck/Ridgeback's molnupiravir is the first of what will be a mini-flood of such drugs over the next several years. The next question is, at what cost? My own investigation of multiple India suppliers puts the manufacturing cost of the raw material for molnupiravir, the active pharmaceutical ingredient (API), at about $2.50 dollars a treatment. The total price per treatment in the non-regulated markets will be no more than $20, factoring in the cost of manufacturing the pill, and a modest profit for all the intermediaries between the manufacturer and the patient. That is 35 times less than the Merck/Ridgeback government price, which is about $700. 1354
The companies will undoubtedly argue that their price covers the costs of discovery and development—that without extraordinary profit margins of 95% or greater there would be no incentive to develop new drugs. Molnupiravir was discovered at a US university supported by federal research dollars. The plan is for it to be purchased by federal funds, at least initially. Let’s make a reasonable cost projection. Treating 100 million Americans over the next two or three years with a $700 drug would cost taxpayers $700 billion, but only $2 billion at $20. Which begs the question whether we will once again price gouge our citizens while depriving them of life-saving medicines to control a pandemic that has ravaged our lives, jobs, and our economy while other countries benefit from our investments. Beyond the action cost of the drugs themselves, one dangerous toll we may be forced to pay for the use of this drug is the creation of more viral variants. Molnupiravir, much like SARS-CoV-2 itself, is a literal shape-shifter, stopping viral replication through a process called lethal mutagenisis. First the drug tricks SARS-CoV-2 into using it to replicate. Then, once the replication process is underway, molnupiravir inserts errors into the virus’ genetic code. Called a tautomer, the drug assumes two forms, one which closely resembles uracil (U) and the other cytosine (C). Once it is recopied, the replicating polymerase develops transition mutations, where a U nucleotide is converted to a C and a C to U. That’s the drug’s second trick. When you have enough of those copying errors you essentially kill the virus, stopping replication, shortening the length of a person’s infection, and limiting onward transmission. The problem is that suboptimal concentrations of the drug could also supercharge the creation of viral variants, introducing a wealth of mutations that aren’t quite enough to stop replication but are enough to drastically change how SARS-CoV-2 operates, either its transmissibility, stability or virulence. While we consider the monetary costs of the drug, we cannot overlook the evolutionary costs of introducing such a powerful mutagen into our Covid-19 environment. The FDA should ensure the safety of the drug before approval, and insist on a full accounting of all data on the drug’s potential to supercharge viral variants.
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The possibility of a new drug to ward off the most serious symptoms of Covid-19 is welcome news indeed, but we still must question whether the financial cost and the risk of new variants is a price we’re willing to pay. This article originally appeared on Forbes, and can be read online here: Anti-Covid Drugs Are Coming, But At What Cost?
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Covid-19 Variation: Past, Present, And Future Forbes | October 14, 2021 | Article
The Greek God Proteus could foresee the future, but the only way to extract the truth was to hold him firmly by the neck as he went through fearsome shape changes. We view SARS-CoV-2 as protean, assuming multiple forms. We must keep our grip firm to anticipate and counteract these changes of shape. This is the first in a three-part series examining the past, present, and future of the pandemic and viral variants. For the last year and a half, we've been consumed by successive waves of Covid-19 both in the United States and around the world. We have witnessed the rise of variants that are both more transmissible and more dangerous. Now as the fourth wave in the United States, driven by the Delta variant, may be on the wane, it is time to reflect on our past and contemplate the future. In this threepart series on viral variants, we look at what has happened, what is happening, and what the future might hold. By late January and early February 2020, the Chinese government sounded the alarm: there is a new infectious coronavirus that is highly transmissible and more lethal than Influenza. There were private communications at the highest level between the US and the Chinese government that the coronavirus was likely airborne. In reaction, the Chinese government took swift and rigorous action to contain the virus through stringent public health measures, including identification of those exposed and infected, as well as the implementation of aggressive quarantine strategies not only of individuals but in some cases entire cities and provinces. That prompt action contained the coronavirus within China and continues to contain it to this day. Unfortunately, by that time, the virus had begun to spread globally, including Europe, North America, and Southeast Asia. Other nations did not institute standard public health measures as promptly or thoroughly as the Chinese. Consequently, most countries have experienced successive waves of SARS-CoV-2 1357
infection. In retrospect, we now know that the Wuhan strain, while highly infectious and dangerous in the sense that 1.5 to 2 of 100 people died following infection, was the first in a succession of much more transmissible viruses. In January 2020, a new strain of the virus became evident, most commonly identified by a mutation in the Spike protein, called D614G. This single amino acid change has two effects on increasing transmissibility of the virus. First, it stabilizes theS1/S2 complex after cleavage and secondly, it favors an open, rather than closed, configuration for the receptor-binding domain—the configuration required for infection.
FIGURE 1: D614G mutation noted on the cryo-electron structure of the SARS-CoV-2 Spike protein. LOS ALAMOS NATIONAL LABORATORY
Although D614G is featured as the predominant discussion of this early variant, we note that in addition, there are actually two other mutations that occurred, which today are inseparable from their D614G counterpart. These include an amino acid change observed in the NSP12 polymerase, P323L, and a single nucleotide change occurred in the five prime untranslated region, C241U. For this reason, we refer to this variant as the Triad variant. Intensive study of this Triad variant found that it was roughly twice as infectious as the original strain. In a matter of weeks, this modified virus displaced the Wuhan virus almost entirely across the world. 1358
The takeover of the Triad variant is virtually complete by May 2020 and is the primary driver of the wave of infections that hit in Summer 2020. Many states in the United States and countries around the world failed to implement public health measures to halt viral spread and furthermore, those measures they did install were promptly removed state by state throughout 2020.
FIGURE 2: Transition from Wuhan virus to D614G mutation in SARS-CoV-2 infections in Europe. LOS ALAMOS NATIONAL LABORATORY
At this point, many began to predict that the virus was stable and would not mutate further, based on expectations that the virus’s error-correcting machinery would eliminate further variance. Unfortunately, that expectation has turned out to be incorrect. In December 2020 and into January 2021, a number of new variants began to predominate. At first, these variants were largely regional, but all were derived from the Triad blueprint. Among these were the Alpha variant first identified in England, Beta first identified in South Africa, Gamma in Brazil, Lambda in Peru, Mu in Colombia, among others. By Spring 2021, Alpha was the predominant strain around the world, barring South America in large part due to its aggressively transmissible nature. Beta became dominant in Southern Africa, but failed to gain global traction, despite a strong immune-evasion property. In South America, Gamma became dominant with a combination of transmissibility and immune-resistance, but was largely contained to the continent. In the United States, there were several different viruses that were circulating and formerly were variants of interest, such as Iota and Epsilon, but neither of them became totally dominant. Again, all of these Greek-alphabet of variants contain the first three mutations descended from the Triad variant, but each one had its own set of unique mutations. 1359
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FIGURE 3: Mutations commonly observed in the full genome and Spike protein of SARS-CoV-2 in major ... [+] ACCESS HEALTH INTERNATIONAL
As we have noted repeatedly in our ongoing analysis of viral variants, it is important to monitor mutations outside the Spike protein with as much vigilance as those within the Spike protein. Any mutation which allows the virus to transmit more readily, must be carefully monitored, regardless of its viral location. For that reason we show figure three, which is the range of mutations that occur both within and outside the Spike protein in major variants. Please note that every major variant has significant mutations in the Orf1ab replicative complex, the non-spike structural proteins E, M, and N, and the regulatory protein. Any of these mutations has the potential to increase transmissibility and immune evasion. Some of these mutations modify highly antigenic proteins, such as Orf3a, which could affect convalescent or monoclonal antibody binding. These are just some of the many potential impacts non-spike mutations could confer, and thus they should be monitored intently. Most recently, as we will describe in part three, the Delta variant, first identified in India, has other variants to become the world’s most dominant strain, even displacing Gamma as the dominant strain 1360
in Brazil, due in part to its elevated transmissibility over other variants.
FIGURE 4: Transition between emerging lineages from the Triad variant to the emergence of the Delta ... [+] STEBBING
The figure above illustrates that SARS-CoV-2 is less so an isolated crisis, but an evolving offensive we must continue to counteract. Akin to how Influenza reemerges in different forms year on year, we can expect a similar pattern from SARS-CoV-2. What drives the evolution of variants? It is clear that in natural settings, each successive variant has transmission advantages over its predecessor. The Triad is more transmissible than the Wuhan strain. Each of Alpha, Beta, Gamma, and so on is more transmissible than the Triad. Alpha was more transmissible than other variants and displaced them, and now Delta has become the most transmissible, displacing nearly every other strain around the world. These viral advantages are derived from mutations that begin as one of the many billions of differences found in the swarm of SARSCoV-2 viral particles. Over time, mutations that confer enhanced properties to the virus appear more and more until they are the nucleotide in the genome, akin to natural selection in humans and other fauna. Transmission advantages are among those selected to become dominant in the virus. There may also be a selection for immune evasion. A number of changes, particularly in the Spike protein, allow the virus to escape monoclonal antibodies. These include, but are limited to N501Y in Alpha, Beta, and Gamma, E484K in Beta and Gamma, K417N/T in Beta and Gamma, and L452R in Delta. These are among the most 1361
well-researched antibody-resistance mutations, but others likely confer similar effects. In addition, some of these Variants are less sensitive to neutralizing antibodies from convalescent sera, particularly Beta, which is also less sensitive to vaccines. All other variants seem to be relatively equally sensitive to vaccines. Therefore, with the possible exception of Beta, it may not be escape from neutralization that gives these viruses that advantage. Rather, there seem to be other factors, including replication for a longer period and replication to a higher concentration. What gives a replication advantage to Alpha is not clear because they seem to be reasonably well neutralized by both convalescent sera and vaccination. There are subtle changes in the envelope glycoprotein that give it a better transmission advantage, but it is also possible that other mutations in non-spike proteins lead to other effects that should be investigated further. The engine driving the emergence of variants is random mutation. It is estimated that there are about three nucleic acid substitutions per genome per replication cycle. If there are between 10 and 100 billion virus particles in any given infected person, that means there are 30 to 300 billion mutations in a given replication cycle. Many of those will either be dead or will have a replication disadvantage, but some will be stronger than the virus that came before. Emily Anthes of the New York Times describes this phenomenon as winning the genetic lottery, as very rarely does a new advantageous mutation emerge, but when it does, it does so overwhelmingly. Advantage mutations will be selected, further replicated, and new variants are formed, the strongest of which can infect the entire planet. In the next entry, we will examine the evolution of the Gamma variant over the past several months in South America. In the final entry, we will examine the ongoing evolution of the Delta variant and its implications for the future of the pandemic. This article originally appeared on Forbes, and can be read online here: Covid-19 Variation: Past, Present, And Future
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Blockchain Technology, A Practical Solution To Vaccine Verification Systems Forbes | October 20, 2021 | Article
Vaccine verification is critical to any country’s ability to control the course of the pandemic. Having a reliable, secure, and accurate verification system gives governments, businesses, schools, or any other institution the opportunity to assess the safety of indoor and outdoor gatherings and provides real-time statistics into vaccinated populations. Though many countries around the world have developed their own vaccine verification systems, often evolved from previous contact tracing apps, developing a reliable, secure and accurate system remains a challenge. Part of this is due to data storage and retrieval protocols. Another major obstacle is information sharing, especially when you consider how important it is that vaccine verification systems are accepted across domestic borders and international ones. Dr. Tom Frieden, the director of the Centers for Disease Control and Prevention from 2009 to 2017, voiced his concerns about the long-term difficulties of having multiple Covid-19 vaccination verification systems. “Its own user interface, validation, data storage, retrieval processes, and security protocols, will make it difficult to quickly and securely verify vaccination status.” In order for a system to work, he advocates for five essential requirements. • Accuracy should be maintained by utilizing a computerized immunization information system i.e., an online record of vaccinations received by people. • Proper assurances and safeguards must be implemented to ensure the security and privacy of everyone’s personal data. • For unforeseen circumstances, options to use other forms of identity should also be allowed. For instance, having the ability to use paper vaccination records with additional personal verification, such as a photo ID.
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The system must only be used to verify vaccination records and should avoid adding information about previous tests and results to avoid clustering data. And must be accessible in real-time, “such as when people are going through airport security.”
Blockchain technology can provide a practical solution to the challenges of vaccine verification and can help meet the requirements Frieden describes. Due to the decentralized and encrypted nature of blockchain technology, information stored on the blockchain ledger is extremely tough to tamper with. That addresses a very crucial requirement of a vaccination verification system, which is ensuring the security and privacy of personal data. By scanning serial numbers of vaccine shipments and storing them on a blockchain ledger, goods can be authenticated at any point of the supply chain. To understand the process of how exactly the blockchain technology solves the question of data storage, retrieval processes and information sharing, we can look at ‘VacciFi’ , an architectural framework for Covid vaccination passports provided in a study which looked into a GDPR-Compliant Blockchain-Based Covid vaccination passport.
Figure 1: The proposed architectural framework for VacciFi. TOWARDS A GDPRCOMPLIANT BLOCKCHAIN-BASED COVIDVACCINATION PASSPORT , AKM BAHALUL HAQUE, BILAL NAQVI, A. K. M. NAJMUL ISLAM AND SAMI HYRYNSALMI
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Let’s say we’re applying this framework to travel. With this framework, an unvaccinated person would register through their local health authority for vaccination. After registration, they would be issued a vaccination ID, which they would take to the hospital or clinic where they would be vaccinated. During the visit to the hospital, the front desk will record all necessary information about the person getting vaccinated. Information such as traveler’s name, passport number, contact number, etc will be stored off-chain due to regulations such as general data protection compliance purposes. The hospital would store two types of information on the blockchain: 1) Passport number and generated hash of the vaccination ID and, 2) date of administered vaccination dose. This will generate a QR code which can be pasted on the passport and is also shared by email as an electronic copy. The purpose of the QR code is for verifying vaccination details and validity. In the off-chain systems, four operations can occur: create (the right for the creation of a new record in the off-chain), read (the right to read and view record), update (the right to update existing records) and delete (deletion of records). Here is the proposed access privileges by different authorities based on VacciFi’s framework:
Figure 2: Access privileges of different authorities TOWARDS A GDPRCOMPLIANT BLOCKCHAIN-BASED COVIDVACCINATION PASSPORT , AKM BAHALUL HAQUE, BILAL NAQVI, A. K. M. NAJMUL ISLAM AND SAMI HYRYNSALMI
Here, all parties have the ability to read the existing records and in the process verify a citizen’s vaccination records. The only party that is allowed to create or delete the file is the vaccination authority. When traveling, the QR code is presented by the traveler to the immigration staff. Upon a scan of the QR code, all relevant vaccination details and the hash code (generated at the hospital) from the local off-chain storage. The hash is then verified by comparing it to the hash stored onto the permissioned blockchain, via a smart 1365
contract. If there is a match, the blockchain will return the validity and dates of vaccination (Figure 3), thus completing the verification process.
Figure 3: Verification system process ADAPTION FROM TOWARDS A GDPRCOMPLIANT BLOCKCHAIN-BASED COVIDVACCINATION PASSPORT , AKM BAHALUL HAQUE, BILAL NAQVI, A. K. M. NAJMUL ISLAM AND SAMI HYRYNSALMI
The security associated with only QR code-based digital health evidence systems, which many vaccine passports adopt, is a big source of concern. With personal data being involved, any leaks or insufficient safeguards will harbor the possibility of complete invasion of privacy. Blockchain technology is already being deployed to fight counterfeit vaccines and scams that threaten our long-term stability. This dilemma extends beyond just vaccines. Reports of fake vaccination certificates in circulation are constantly making the news, alluding to the need for a more trustworthy technology to mitigate these unintended and deadly consequences. The World Health Organization says that fake vaccines and other ill-intended alternatives to bypass our vaccine verification systems "pose a serious risk to global public health". With vaccine inequality also posing as a negative catalyst in our fight against Covid-19, fake vaccines are a more prominent issue in poorer countries, which already have a low supply and vaccination rates. George Connolly, president OneLedger Technology Inc., oversaw the development of the OnePass vaccine passport, a scalable and secure blockchain-based vaccine passport. He explains in an article that these passports, issued by a medical provider, include a 1366
private key individual to the user. To each private key is a corresponding public key, which is stored in the blockchain ledger. Using the ledger, a QR code is generated to confirm the vaccination of an individual. Users of blockchain-based passports have the freedom to decide what information they choose to disclose, such as name, date of birth and or nationality. This reinforces privacy protections and encourages the creation of reliable and accurate vaccination records. Though blockchain can’t solve the questions around the inclusivity and equity of vaccine verification systems, it can provide a platform for success for countries trying to implement their systems safely, securely and with the capacity to manage information flow in real time. This article originally appeared on Forbes, and can be read online here: Blockchain Technology, A Practical Solution To Vaccine Verification Systems
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Covid-19 Variation: What Comes Next? The Amazonas Experience Forbes | October 22, 2021 | Article
This is the second in a series examining the past, present, and future of the pandemic and viral variants. Each successive iteration of SARS-CoV-2 variant to date was more transmissible than the last. New variants drove multiple waves of Covid-19 throughout the world. Here, examine what happened in the past and present of the pandemic in order to understand what may lie in our future. Having written the book Variants! The Shape-Shifting Challenge of Covid-19, one of the most frequent questions I am asked is ‘what comes next?’ To begin to answer this question, we examined the underlying dynamics of virus variation in part one. Here, in part two, we will delve more deeply into the topic with an analysis of the Gamma variant in Brazil. A recent paper by Naveca et al. analyzes the virology of the Brazilian SARS-CoV-2 experience. The Amazonas region of Brazil experienced two major waves of infection and Naveca et al. used deep genomic sequencing to understand the strain of virus causing these waves.
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FIGURE 1: Amazonas region of Brazil and its capital Manaus. WIKIPEDIA
Generating 1,188 SARS-CoV-2 whole-genome sequences from infected Amazonas residents from January to July, the researchers confirmed that 99.7% of infections were driven by the Gamma variant. However, the researchers found several mutations in their sequences uncommon to the traditional Gamma variant, which is illustrated in Figure 2.
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FIGURE 2: Original Gamma genome and Spike mutations. ACCESS HEALTH INTERNATIONAL
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Although there was a major initial wave of the P.1 original Gamma variant, Naveca et al. describe what they believe are nextgeneration variants, which they collectively refer to as “Gamma Plus.” The researchers hypothesized that the endemic state of the original Gamma variant in Amazonas allowed the rise of these second-generation variants. The Gamma sublineages contain mutations that enabled not only increases in transmissibility, but the potential for vaccine breakthrough cases. These factors strongly indicated that the Gamma sublineages drove the Gamma wave of infections in Brazil further than solely the original Gamma variant. As many as seven “Gamma Plus” variants were detected that carried all the mutations of its parent, but a few more in key regions of the virus. Even though Gamma infections are waning currently in Brazil, it is worth analyzing the Gamma Plus variants to see how a dominant variant can vary still further to drive higher levels of infection and death. Naveca et al. summarize that continuous evolution of the P.1 (Gamma) variant of concern was the likely cause of steady-state SARS-CoV-2 cases from May to July 2021, and were partially responsible for infections as early as January. This period resulted in the most Covid-19 related deaths, both regionally in the Amazonas region and throughout the whole of the country.
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FIGURE 3: Covid-19 related deaths in Brazil—around 603,000; Covid-19 related deaths in ... [+] NEW YORK TIMES
FIGURE 4: Distribution of emerging lineages in SARS-CoV-2 infections in the United States and ... [+] STEBBING
What are the Gamma Plus sublineage mutations that Naveca et al. associate with still higher levels of infection than Gamma? The researchers’ attention was primarily directed to the Spike protein, in two regions in particular: the N-terminal domain and the Furin cleavage region. In the N-terminal domain, the researchers note deletions at positions 144, 142-144, and 141-144. These mutations are observed in major variants of concern or interest such as Alpha and Eta, as well as other circulating variants like C.1.2 and A.30. The researchers estimate that roughly 10% of infections by Gamma sublineages contain one iteration of these N-terminal domain mutations, most of which are conveyed in the P.1.3 variant.
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FIGURE 5: SARS-CoV-2 Spike protein N-terminal Domain. GENENG NEWS
In addition to playing an important, but a nonspecific role in attracting the virus to the host cell surface, the N-terminal domain is critically involved in the antigenic binding of a large portion of neutralizing antibodies to the Spike protein. This fits with the history of many variants. Among those that undergo deletions or insertion of positive charges via point mutations in this region to avoid neutralizing binding by antibodies and convalescent sera are Alpha, Beta, Delta, and Lambda. The deletions in the Gamma sublineages may work to accomplish a similar feat.
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FIGURE 6: Common NTD deletions in major variants of concern and interest. ACCESS HEALTH INTERNATIONAL
The second of the major modified regions in Gamma sublineages is the Furin cleavage site.
FIGURE 7: SARS-CoV-2 Spike protein Furin cleavage site. CHEMISTRY WORLD
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Most coronaviruses have a single cleavage site called “S2.” This site is activated when the virus binds to its target. Some coronaviruses, such as SARS-CoV-2, have an additional cleavage site known as the “Furin cleavage site.” Furin is a protease enzyme that cleaves the SARS-CoV-2 virus as it buds from the cell. This cleaving is what activates the Spike protein. The Spike protein must be activated to initiate viral entry. In the original Wuhan strain of SARS-CoV-2, cleavage is not 100% efficient, meaning virus particles are not uniformly cleaved. Mutations in this region can improve this efficiency, resulting in more consistent cleavage of SARS-CoV-2 particles, and yielding a more infectious virus. Near the Furin cleavage site, the researchers found two mutations in four of the Gamma sublineages. The first Gamma sublineage mutation in this region is N679K. Notably unobserved in major variants of concern or interest, this mutation is found in the C.1.2 variant originating in South Africa. Asparagine to lysine is a major change in charge, from neutral to positive. This means the Furin cleavage region in P.1.3 and P.1.4 is changed significantly both in charge and structure, potentially reinforcing cleavage. The second mutation that the researchers note is P681H/R. This mutation has been previously noted in Alpha, Mu, and A.30. Additional mutations at this position are noted in Delta, Kappa, and A.23.1, showing that modifications to this position likely result in enhanced Furin structure. Proline to histidine is another neutral to positive shift, also pointing to a net positive increase in regional charge. The figure below demonstrates the positive charge shift due to the Furin cleavage mutations.
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FIGURE 8: Gamma Plus Furin cleavage mutations and corresponding changes in charge. NAVECA ET AL
Again, this follows a trend of previous variants containing Furin cleavage region mutations, such as Alpha, Delta, and Kappa, which demonstrate mutations at position 681. We can expect new variants to continue these trends. Both the N-terminal domain and the Furin cleavage region are very flexible, via positive charge alteration or antigenic site deletions, the virus will change whatever it needs to enhance its capabilities. We should monitor mutations in these regions for both neutralization and transmission in tissue culture.
FIGURE 9: Gamma Plus Spike protein mutations. ACCESS HEALTH INTERNATIONAL
We note that the mutations in the Gamma Plus variants are found in the Furin cleavage region and N-terminal domain, but not the heavily examined receptor-binding domain. There is one minor 1375
amino acid change in P.1.8, but this is among the least prevalent Gamma Plus sublineages. The major lineages, P.1.3 through P.1.7, all lack receptor-binding mutations. In addition, we note that while the Spike protein is certainly important, there are other mutations in the nonstructural proteins and regulatory Orfs that must be considered. In the Orf1ab replicative proteins, the researchers observed six mutations in four of the seven sublineages analyzed. In the NSP3, there are three observed mutations. The first is T133I, found in the Acidic C-terminal domain. The second is I441V, found in the SARS-specific unique domain. The third is T1018I, found in the papain-like protease, which is the most important of the NSP3 subdomains and oversees translational cleavage of NSP1-4. The researchers noted A446V in NSP4 of one of the sublineages. NSP4 is vital to the formation of the double-membrane replication vesicle. The final Orf1a mutation is T141M in NSP8, which provides stability to the polymerase replication complex. In NSP12, the RNA-dependent RNA polymerase of SARSCoV-2, the researchers note P918L. This protein is the engine of the transcription-replication complex, reading nucleotide sequences and copying them for the creation of new RNA. We note that all mutations in the Orf1ab replicative proteins are unique to the Gamma Plus variants among major variants of concern or interest to this point. There are no mutations to the structural proteins of the sublineages, but there are four noted mutations in the regulatory (accessory) proteins that play a role in viral pathogenesis. In Orf3a, the protein that oversees apoptosis, or cell death, the researchers note the S261L mutation. In Orf7b, which is involved in the subversion of interferon signals like STAT2, as well as modulation of virus particle interaction with the cell via tetherin interaction, the researchers note the M24T mutation. Finally, in Orf8, which downregulates the major histocompatibility complex (MHC-I), the researchers note H17Y and G8stop. The G8stop mutation is notable in the P.1.8 subvariant as this effectively destroys the whole of the Orf8 protein, rendering its functions incapacitated. The regulatory protein mutations described here are unique to the Gamma Plus variants, as we noted about the replicative protein mutations.
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FIGURE 10: Gamma Plus non-Spike protein mutations. ACCESS HEALTH INTERNATIONAL
Variants are continuously selected from increased transmissibility and because Delta is now overtaking Gamma and its sublineages, that suggests that Delta is a far more transmissible virus than variants that came before. We can use our understanding of Gamma and its sublineages to further examine the more transmissible Delta, its own sublineages, and their higher transmissibility and immune evasion. This article originally appeared on Forbes, and can be read online in full here: Covid-19 Variation: What Comes Next? The Amazonas Experience
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The Growing Threat Of The Delta Pluses At Home And Abroad Forbes | October 28, 2021 | Article
This is the third in a series examining the past, present, and future of the pandemic and viral variants. Each successive variant of the SARS-CoV-2 virus to date was more transmissible than the last. New variants drove multiple waves of Covid-19 throughout the world. Here, examine what happened in the past and present of the pandemic in order to understand what may lie in our future. First, there was the Triad variant that drove infections in the Summer of 2020. Then, there were regional variants of interest and concern such as Alpha, Beta, and Gamma that drove infections in the Winter of 2020 into 2021. Most recently, Delta is the major variant fueling infections around the world.
FIGURE 1: Distribution of emerging lineages in SARS-CoV-2 infections in the United States and ... [+] STEBBING
Delta seems to have similar properties to the Triad variant, in that it is now being displaced by different regional variants that appear to be more transmissible. For example, akin to how the more transmissible Delta variant displaced the Alpha variant, an even more transmissible variant of Delta—AY.4—displaced the original Delta. More recently, a new variant—AY.4.2—appears to be displacing 1378
both, as shown in Figure 2. In the United States, Delta seems to be regionally displaced by a number of AY variants, one of which— AY.33.1—appears more transmissible than its predecessors.
FIGURE 2: Proportion of SARS-CoV-2 infections by different viral variants sequenced in England from ... [+] SANGER INSTITUTE
The ongoing theme throughout the pandemic is that variants are selected for increased transmission. Some variants vary by antibody neutralization capability, whether by natural infection or vaccine. The South African-originated Beta variant is one example. The primary driver, however, is clearly transmissibility. What we mean by transmissibility is how readily the virus transmits from one person to another. This is influenced by a number of factors, including but not limited to the stability of the virus in the air, the avidity of the virus Spike protein to the host cell, the efficiency and concentration to which the virus replicates, and how days a person is contagious. By all accounts, the Delta variant excels in all categories, replicating faster and producing greater concentrations in nasal fluids. Delta is neutralized about as well as predecessor strains, so its universal dominance for the past several months lies squarely with its transmissibility. The question that now arises is whether there are currently or will be variants of Delta that transmit even more rapidly, akin to the Gamma variant described in part two. Recent reports suggest the answer is a qualified yes. According to the GISAID SARS-CoV-2 sequence database, Delta has more than 40 sequenced sublineages. The AY.4 Delta Plus Variants 1379
Some Delta sublineages are labeled ‘AY.#’. Many thousands of individual Delta variants are cataloged in an international repository named GISAID. One of the Delta sublineages, AY.4, has outpaced the original B.1.617.2 strain (Delta) in terms of directed infectious strains. The AY.4 sublineage has caused more infections worldwide than the original Delta variant. Following the virological pattern of Gamma, Delta has developed a number of Delta Plus variants that are likely more transmissible and potentially more immune evasive than the original that came before. Here we describe two Delta sublineages of note: AY.4/AY.4.2 fueling new cases in Europe and AY.33 that appears to be spreading more rapidly than others the American Northeast
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FIGURE 3: Original Delta genome and Spike protein mutations. Mutations in red are canonical to the ... [+] ACCESS HEALTH INTERNATIONAL
The figure above illustrates the mutations found in the original Delta variant that emerged in India earlier this year. It differs significantly from the Triad variant that fueled infections in the Summer of 2020. Denoted as B.1.617.2, the variant contained 27 amino acid mutations and four amino acid deletions. While a detailed study of these individual mutations is, as of yet, unavailable, we speculate that each may play some role in increases in transmissibility, immune evasion, replication, and pathogenesis.
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With each continuous passage of the virus through a new host, new mutations are selected for their impacts in these listed viral traits. If the mutations are successful, they are maintained and new variants are formed. This is how the Gamma variant developed into a number of “Gamma Plus” sublineages and is how Delta is now divided into dozens of Delta Plus sublineages. The previously mentioned AY.4 variant, for instance, contains all the original Delta mutations shown in Figure 1, but contains an additional Spike protein mutation—T95I—and an additional mutation in the replicative complex proteins—NSP3 A1711V. This variant rapidly overtook the original Delta strain to fuel cases over the past several months in Europe and elsewhere. The mutation of only two amino acids yielded a virus that was significantly more transmissible than the original Delta variant, reaching similar levels of infection in less time. While Delta swiftly overtook Alpha as the dominant strain, AY.4 with its two additional mutations rapidly predominated in a matter of weeks. The simple amino acid substitutions appear to yield a significantly more transmissible variant. In the bottom right of the figure, there is a growing presence of another variant. Just as AY.4 altered two amino acids to improve its viral efficiency, a new variant, AY.4.2, seems to have done the same. Using the AY.4 template, this new Delta Plus variant adds two additional Spike mutations to its genomic makeup—Y145H and A222V. Early data indicates that the variant is around 10-15% more infectious than previous major strains. Following suit with the AY.4 Spike mutation, these lie in the N-terminal domain. This follows a pattern of continued modification in this region, as also discussed with the Gamma Plus sublineages. Nearly every major variant of concern or interest to this point of the pandemic has contained at least one, and often multiple N-terminal domain mutations. We note that major changes to the charge and polarity in this region could have significant effects on virus affinity to target cells, as well as the efficiency monoclonal and convalescent antibodies can bind to the virus. If our past experience with variants is prologue, the AY.4.2 Delta Plus variant may drive yet another wave of infections. The AY.4 Delta sublineage overtook Delta rapidly, as did the Gamma Plus
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sublineages. There is some evidence that suggests we may be witnessing a similar phenomenon.
FIGURE 4: AY.4.2 as a share of cases in the United Kingdom as compared to the Alpha and original ... [+] FINANCIAL TIMES
Reports have emerged noting AY.4.2 is now representative of about 6% of infections in the United Kingdom. The frequency of infection of AY.4.2 doubles every 28 days. Moreover, the AY.4.2 is now present in dozens of countries, including the United States, Russia, and Israel. Current waves of infection in Eastern Europe, such as the Baltics, Germany, Hungary, may be driven by this variant. The AY.33.1 Variant In addition to AY.4.2, there is a new variant growing in the Northeastern United States that is beginning to look like a cause for concern. AY.33.1 is growing in infection frequency in the Northeast and is another independent derivative of the Delta variant. Just like AY.4 and AY.4.2, AY.33.1 maintains the mutational framework of B.1.617.2 and thus the transmissibility advantages it already displays. The key mutation of note in AY.33.1 is Q613H within the Spike protein. The mutation is located immediately before the Triad mutation D614G. This close proximity suggests that Q613H is a key mutation that may impact infectivity, particularly by the stabilization of the S1/S2 complex after cleavage and the favoring of an open, rather than closed, configuration for the receptor-binding domain— 1382
the configuration required for infection. Early indications from the Northeast suggest that AY.33.1 has between a 10 to 20% replication advantage over Delta itself. While AY.4.2 and AY.33.1 have yet to infect the sheer volume of people Delta or Alpha had in similar timeframes, likely due to widespread vaccinations, it may still come to infect in greater numbers. Recent studies suggest that antibody titers from mRNA vaccination wane heavily after six months. Vaccinations peaked in April and May, meaning the six-month deadline is arriving for many people in the immediate future. While third-shot vaccinations are promising, many may not be in a rush to get another dose due to speculation that it is necessary or whatever other reason. This could aid Delta sublineages with a winter wave as the weather grows cooler and populations move to indoor spaces. In conclusion, we urge that government agencies and the scientific community continue and expand their efforts to understand virus variation globally. Expanded sequence surveillance programs could give us an early warning, allowing us to prepare in advance for the next devastating wave of infections. This article originally appeared on Forbes, and can be read online here: The Growing Threat Of The Delta Pluses At Home And Abroad
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The Role Of Nucleases In Innate Immune Escape (Part 15) Forbes | October 28, 2021 | Article
This is the fifteenth article in a series called “How SARS-CoV-2 Delays, Evades, and Suppresses the Immune System.” Read parts 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14. In previous installments of this series we’ve unpacked how SARS-CoV-2 is sensitive to the innate immune response, a complex assemblage of immune sensors and responders that, for high-risk Covid-19 patients especially, can mean the difference between life and death. Over a long period of time the coronavirus family has developed biochemical mechanisms that allow it to counter our innate immune defenses. Some are novel and without precedent, while others have survived generations of selective pressure due to the essential role they play in viral replication. Among the oldest in the SARS-CoV-2 genome are two viral proteins associated with the replication complex common to all coronaviruses. One is an exonuclease, nonstructural protein 14 (NSP14). The other is an endonuclease, nonstructural protein 15 (NSP15). Both are involved in critical aspects of viral replication, but also in suppression of the innate immune response. Combined, they neutralize some of the primary triggers for production of interferon and interferon-stimulated genes. Although SARS-CoV-2, like all other coronaviruses, is a positive-sense, single-stranded RNA virus, double-stranded RNA replicates are formed during the viral replication process that typically set off the innate immune response. Upon infection, receptors like RIG-I and MDA5, which induce the production of interferon and the activation of protein coding gene OAS1, detect foreign double-stranded RNA and activate their respective innate immune pathways. Unless something interferes, that is. This might be the reason why one of the functions of the SARSCoV-2 exonuclease NSP14 is to chew away at double-stranded RNA. One purpose of this mechanism is error correction, which 1384
allows the production of longer, proofread pieces of RNA. But in chewing double-stranded RNA from the 3 prime end to the 5 prime end, NSP14 also functions to silence innate immunity, delaying detection by RIG-I and MDA5. It has the remarkable ability to destroy errant double-stranded RNA while leaving potential double-stranded RNA intermediates intact. Corroborating this theory are studies of other coronaviruses and arenaviruses that encode exonucleases which show that viruses lacking exonuclease activity are more susceptible to interferon. In the absence of the NSP14 exonuclease, conditions become inauspicious for viral infection and replication, a finding that suggests the exonuclease plays a significant role in antagonizing the innate immune response. The endonuclease NSP15 also participates in innate immune suppression, though by other means. Positive-strand RNA has a cap at one end and a poly(A) tail at the other. The negative-sense viral RNA formed during genomic synthesis, on the other hand, has a tract of polyuridines at the 5 prime end (Figure 1). These polyuridine extensions, like double-stranded RNA replicates, serve as a potential signal for innate immune receptors. But the 5 prime uridine residues also happen to be where the SARS-CoV-2 endonuclease cleaves, further restricting the sensing capabilities of MDA5 and OAS1.
Figure 1. “Nsp15 is a central regulator of SARS-CoV-2 RNA processing. Upon viral entry, the single-strand SARS-CoV-2 positive-sense genomic RNA (+gRNA; yellow) is released into the cytoplasm and translated by host ribosomes to generate viral polyproteins pp1a and pp1ab. Subsequent proteolytic cleavage of the polyproteins results in a variety of
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nonstructural proteins (Nsp) essential for diverse viral functions. Transcription of the positive-sense genomic RNA produces a negative-sense genomic RNA (-gRNA; green) intermediate. The negative-sense strand is a template for reverse transcription (RT) generating a series of positive-sense subgenomic RNAs (+sgRNA; brown), which are translated into diverse structural proteins. In addition, the negative-sense strand is also the template for viral replication. The non-structural protein Nsp15 (orange) is a poly-(U) specific endonuclease that cleaves 3¢ to uridines within the viral genomic RNA. Nsp15 cleavage sites (blue arrowheads) have been mapped all along the positive-sense genomic RNA and 5 prime end of the negative-sense genomic RNA. Nsp15 viral RNA processing plays an important role for evading detection by the host innate immune response.” Source: https://staticcontent.springer.com/esm/art%3A10.1038%2Fs41467-020-20608z/MediaObjects/41467_2020_20608_MOESM1_ESM.pdf ACCESS HEALTH INTERNATIONAL
One study shows that infected cells deficient in the endonuclease NSP15 displayed less viral shedding and replication. The flipside of this, according to another study, is a greater concentration of 5 prime polyuridines and increased sensitivity to the antiviral effects of interferon. The authors of the study hypothesize that when the endonuclease cleaves away these polyuridines, it prevents them from folding up into stem-loop structures that might otherwise stimulate innate immune receptors into action (Figure 2).
Figure 2. “Model depicting EndoU cleavage of PUN RNAs. This model depicts how EndoU activity limits the generation of PUN RNA (5′-polyuridines from negative-sense viral RNA), which can act as a PAMP (pathogen-associated molecular pattern). We
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found that PUN RNAs with variable lengths of polyU sequences are generated in the absence of EndoU activity. We predict that these PUN RNAs can fold back and generate stem−loop structures by hybridizing with an A/G-rich domain located within the PUN RNA or on adjacent RNAs. This stem−loop structure may be recognized as dsRNA (double-stranded RNA) by host PRRs (pattern recognition receptors), thus stimulating the host innate immune response. The function of EndoU during replication is to reduce the length of polyU sequences, thus limiting the potential for generating PAMPs.” Source: https://www.pnas.org/content/117/14/8094/ ACCESS HEALTH INTERNATIONAL
The last series of observations suggesting SARS-CoV-2 nucleases participate in innate immune suppression focuses on the virus’ low U content. One observation is that the SARS-CoV-2 genome has a composition of four nucleotides significantly different from that of other viruses. The low prevalence of uracil sequences is connotated by an enrichment for guanine and cytosine sequences. According to the authors of this study, the evidence suggests this “increases the observed relative frequency of CpG and most other dinucleotides as frequencies must sum to one.” It also may reflect another mechanism of escape from innate immunity, as many of these cellular nucleases activated by interferon, such as RNAse L, cleave preferentially at uracil residues. To recap, one of the most critical differences between people who don’t suffer severe consequences from Covid-19 infection and those who do is the performance of the innate immune system. If interferon-induced immune defenses are compromised, so is the likelihood of a mild disease progression and smooth recovery. That a small fraction of Covid-19 patients become seriously ill or succumb to disease is in large measure due to the inability of the innate immune system to ward off the virus within the first five to 10 days of infection. The nucleases NSP14 and NSP15 seem to form one of the earliest and most troubling defenses the virus has evolved to defang the cell’s immune defense. This article originally appeared in Forbes, and can be read online here: The Role Of Nucleases In Innate Immune Escape (Part 15)
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The Next Big One: Drug-Resistant Airborne Tuberculosis Forbes | October 28, 2021 | Article
Even prior to the Covid-19 pandemic, there has been much discussion of what will be the next big pandemic and how do we prepare for it. New research has found that tuberculosis bacteria can spread via airborne and asymptomatic transmission similarly to SARS-CoV-2. This finding upends the conventional wisdom that coughing was the main route of transmission. It is these two characteristics that make SARS-CoV-2 so dangerous. Therefore I believe the next big pandemic might well be drug-resistant tuberculosis. The pre-print study from South Africa has found that greater than 90 percent of tuberculosis bacteria released from an infected person may be carried in aerosols that are expelled when a person breathes out. Aerosols released from normal breathing will also linger in the air for longer than droplets released from coughs. Study coauthor Ryan Dinkele told the New York Times “if an infected person breathes 22,000 times per day while coughing up to 500 times, then coughing accounts for as little as 7 percent of the total bacteria emitted by an infected patient”. Tuberculosis is caused by a bacterium called Mycobacterium tuberculosis, which usually attacks the lungs. The researchers were concerned about how diagnosis and treatment of tuberculosis had changed very little over the decades and sought a better understanding of how Mycobacterium tuberculosis aerosolizes and transmits. With South Africa (a high burden tuberculosis country) reporting that nearly 60% of individuals with bacteriologically confirmed pulmonary tuberculosis were asymptomatic. The researchers were particularly intrigued by how transmission occurs in these asymptomatic cases that were cough-independent. The researchers developed a platform combining non-invasive bioaerosol capture technology and fluorescence microscopy to accurately measure the viable Mycobacterium tuberculosis released 1388
by confirmed tuberculosis patients. They created three separate respiratory scenarios for comparison, including Tidal Breathing, otherwise known as restful breathing, Forced Vital Capacity, in which the person takes the maximum inhale and exhale they can and Cough. Viable Mycobacterium tuberculosis bacilli were detected in 66%, 70%, and 65% of Tidal breathing, Forced Vital Capacity, and Cough samples respectively. While coughing increases particle aerosolization compared to Tidal breathing, this was not associated with increased Mycobacterium tuberculosis aerosolization. Instead, Tidal breathing produces more Mycobacterium tuberculosis per particle than coughing. If we assume the number of viable Mycobacterium tuberculosis organisms detected provides an accurate measure of patient infectiousness, Tidal breathing could be considered the main route of tuberculosis transmission. These results should have a significant impact on the public health, diagnostic and medical guidelines for tuberculosis. We should be implementing some of the methods used to limit Covid transmission such as high-quality masks and ventilation and encouraging outdoor gatherings and events to limit tuberculosis transmission in countries with a high volume of cases. The results also cause concern for transmission of tuberculosis during air travel and the continual seeding of cases globally. While this is presently not reported as a common occurrence it is possible. From 1992 to 1994, the CDC worked with state and local health departments, conducted contact investigations for seven index cases of infectious tuberculosis. When investigating close contacts they found evidence of transmission of tuberculosis infection during a flight in two of the seven index cases. In one event, transmission from a cabin flight attendant was detected in 2 of 212 crew members who had worked in close proximity with the index case during a 6-month period. Both of those infected were exposed to the infectious source for at least 12 hours. In the other event, there was a probable transmission from an infectious case to 4 passengers (seated in close proximity to the index case in the same cabin section), out of a total of 257 passengers tested on a flight longer than 8 hours. We need to seriously reevaluate the way we diagnose and screen for tuberculosis. The Covid pandemic disrupted access to health care and supply chains around the globe. Lockdowns often prevented 1389
people from accessing care and in many countries, human, financial, and other resources were diverted from tuberculosis to the Covid19 response. As a result, 5.8 million people were diagnosed with tuberculosis in 2020, yet a WHO report estimates that about 10 million people were infected and more than 1.5 million died from tuberculosis, the first increase in a decade. With the increase in asymptomatic cases, many may be unwittingly infecting others. Instead of waiting for patients with symptoms to seek out care, we should be screening entire populations as some countries have successfully done with Covid. As the pandemic continues to rage, we must not continue to delay or ignore public health screenings. A recent Lancet study reports nearly half (47%) of the global population has limited or no access to key tests and services that are essential for diagnosing common diseases, such as diabetes, hypertension, HIV, and tuberculosis, or basic tests for pregnant women such as hepatitis B and syphilis. Egypt’s 100 Million Healthy Lives initiative provides an example of how we could screen entire populations. Egypt previously had the highest rate of Hepatitis C in the world. In 2018, Egypt launched the 100 Million Healthy Lives program. The goal was to screen all Egyptians over the age of 12 for active hepatitis C virus replication along with other chronic conditions such as hypertension, diabetes, and obesity. Treatment was offered for free in government clinics for those who tested positive for hepatitis C, hypertension, and diabetes; free counseling was available for those considered obese. Approximately 4 million people with active hepatitis C were identified and treated with the antiviral medication Sovaldi (sofosbuvir), a nucleotide analogue that inhibits the polymerase enzyme of hepatitis C and blocks its replication, effectively eliminating hepatitis C from Egypt. Once initiated, the program was completed in 18 months. The cost to the Egyptian government was about $45 per 3-month treatment. Patients electing to receive treatment at a private clinic paid $75. The program was primarily funded by a World Bank loan of $530 million. About half of the loan was to expand screening and treatment and the remainder was for health system strengthening. A similar program could be put in place to control tuberculosis in almost any country. Countries that can not presently afford the cost, can seek out similar loans or grants. Implementing these 1390
screening and treatment programs could save millions of lives in the immediate future and avoid the global disruption Covid has caused. As we have learnt from Covid, no one is safe from infection and disease until we are all safe. This article originally appeared on Forbes, and can be read online here: The Next Big One: Drug-Resistant Airborne Tuberculosis
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An Approaching Storm: What To Expect With Covid This Winter Forbes | October 29, 2021 | Article
Nearly two years into the pandemic, Europe is facing a new wave of infections and death, with parts of Eastern Europe already well under water. This week, Russia, Ukraine and Romania each broke national daily death and case records. There has been a discernible uptick in well-vaccinated Western European countries as well. Cases in the United Kingdom, where more than two-thirds of the population is fully vaccinated, are fully out of control, never having dropped significantly since the country reopened in July. The factors at play in the European wave are the same factors that we face here in the United States: vaccine hesitancy and fading immunity, a triad of new more transmissible variants, and a failure to implement the ABCs of public health. If past is prologue and the history of the pandemic is a guide, the next target is the United States. In my view, the only way to stop the approaching storm is to shift our behavior and our response, building higher walls of protection around us that may, if we’re lucky, keep us safe. The first challenge is with vaccines. The high death toll in Eastern Europe is partly due to low vaccination rates in the region. In Ukraine, only 16% of the adult population is fully vaccinated; Russia has barely reached one-third; and in other countries with rising new cases and hospitalizations, the vaccination rate is somewhere in between. Now, those countries are feeling the tragic effects of their inaction, as not only cases reach all time highs, but also hospitalizations and deaths. In Western Europe and in the US, vaccination rates are higher. But people in those countries are facing another key issue: fading immunity. Israel, the country with arguably the best vaccine rollout in the world, was the first to face this problem in the summer. Despite nearly 60% of their population being fully vaccinated with the top of the line mRNA vaccines, they too faced a wave of new infections. Further studies found that the increase in cases was tied 1392
to waning vaccine-induced immunity, which had begun to decline about four to six months after Israelis had received their initial vaccines. That waning immunity coincided with the introduction of a new and more transmissible variant, Delta. To contain the new outbreaks, Israel reinstituted some of the restrictions they had lifted and pursued another solution that many Western European countries and the US are now playing catch-up on: boosters, or as I prefer to think of them, a necessary third dose of the Covid vaccine regimen. After making boosters available to all adults, Israel showed a dramatic and near immediate improvement: after 14 to 20 days, there was a 70-84% reduction in the risk of infection; shortly after, hospitalizations and deaths began to drop dramatically as well. This is a signal to those of us not yet subsumed by the next Covid wave, especially those of us in the US who are facing down colder temperatures and the increase in indoor activities that those temperatures bring: we need to renew efforts to vaccinate the unvaccinated and accelerate the approval and delivery boosters to all individuals, not just those deemed high-risk. What we can’t control is the possibility of new, more transmissible variants taking root. As I wrote about previously, the waves of infections that have washed over us since the emergence of SARS-CoV-2 have been driven by new variants. First the Triad variant that drove infections last summer, then the regional variants — Alpha, Beta, and Gamma — that took root last winter and bled into spring. This summer, it was Delta that gained dominance and now new Delta variants — AY.4, AY.4.2 and AY.33.1 — appear even more transmissible than its predecessor and may drive larger waves of new infections this fall and winter. While higher vaccination rates and boosters will protect us to a good degree, we cannot overlook the basic public health protection measures that, when strictly implemented, have been able to protect countries like China from every single variant we have ever faced: mask-wearing, comprehensive testing, tracing and quarantine, and a willingness to impose stricter measures like lockdown to contain emerging outbreaks. The story unfolding in Europe tells us that we still know too little about the virus and our own immunity to make reliable predictions about how the new Delta variants or other emerging 1393
variants may affect us over the cold winter months. Today, I am not optimistic about our winter Covid season here in the United States. I hope I am mistaken. What I do know, without a doubt, is that stricter adherence to basic public health measures — wearing masks indoors in any public space, avoiding large gatherings indoors, testing ourselves regularly and quarantining if we know we’ve been exposed — could help us limit what could become a repeat tragedy, and another season of death the likes of which we saw last winter. This article originally appeared on Forbes, and can be read online here: An Approaching Storm: What To Expect With Covid This Winter
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November, 2021
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Supercharging New Viral Variants: The Dangers Of Molnupiravir (Part 1) Forbes | November 1, 2021 | Article
An image showing mutations caused by NHC, the active component of molnupiravir to all genes and ... [+] J VIROL. 2019 DEC 15; 93(24): E01348-19
As much as people are justifiably excited about the prospect for orally available drugs that can prevent and treat Covid-19, I believe the FDA needs to tread very carefully with molnupiravir, the antiviral currently before them for approval. My misgivings are founded on two key concerns. The first is the drug’s potential mutagenicity, and the possibility that its use could lead to birth defects or cancerous tumors. The second is a danger that is far greater and potentially far deadlier: the drug’s potential to supercharge SARS-CoV-2 mutations and unleash a more virulent variant upon the world. My next two articles will explore both of these concerns in much greater detail. But let me be very clear right from the start: I am a strong believer in antiviral drugs in general as a means to control the pandemic, having spent much of my early career focused on developing antivirals for the world’s last major pandemic, HIV/AIDS. But I have also spent many years — at Harvard especially where I founded and chaired the Division of Biochemical Pharmacology — studying mutagenesis and the long term effects of damaged DNA. My concern with molnupiravir is because of the mechanism by which this particular drug works. Molnupiravir works as an antiviral by tricking the virus into using the drug for replication, then inserting errors into the virus’ genetic code once replication is 1396
underway. When enough copying errors occur, the virus is essentially killed off, unable to replicate any further. The FDA will soon be debating the safety of molnupiravir for high-risk individuals with Covid-19, something which I will explore in greater detail in my next piece. But my biggest concern with this drug is much larger than the health of any one person, it is molnupiravir’s ability to introduce mutations to the virus itself that are significant enough to change how the virus functions, but not so powerful as to stop it from replicating and becoming the next dominant variant. In a series of pre-pandemic experiments to determine whether coronaviruses could become resistant to molnupiravir (the answer: yes, they can), researchers tested the active form of molnupiravir against two other highly pathogenic coronaviruses: MERS-CoV and the mouse hepatitis virus (MHV). To identify mutations associated with these phenotypes after passage, the authors sequenced complete genomes of two MHV lineages and two MERS lineages. With MERS, there were up to 41 mutations scattered across the genome (see Figure 1). With MHV, there were more than 100 mutations which occurred at every part of the genome (see Figure 2).
Figure 1. Resistance and mutational profiles of MERS-CoV after 30 passages in the presence of NHC, ... [+] J VIROL. 2019 DEC 15; 93(24): E01348-19.
Figure 2. Resistance and mutational profiles of MHV after 30 passages in the presence of NHC, the ... [+] J VIROL. 2019 DEC 15; 93(24): E01348-19
Overall, the study showed a dose-dependent increase in mutations for both coronaviruses, including in the all important 1397
spike protein which is the focus of so much attention today in SARS-CoV-2 variants of concern, like Delta. Critically, the researchers found that the viruses could survive and replicate to high titers despite such large numbers of mutations in every gene and protein. The viruses tested did show a slight replication disadvantage — though they still replicated to the same high titers, they did so slightly less rapidly compared to the original non-mutated viruses. However, outside of the lab, as the drug is given to millions of people with active infections, this disadvantage may quickly disappear as we would likely provide a prime selection environment to improve the fitness of the virus. While it’s possible that at the optimal concentration, the drug may very well cause enough mutations to prevent replication and onward transmission of the virus, the impact of suboptimal doses is still very much unknown. The current protocol for the use of molnupiravir is an 800mg dose, given as pills, twice a day for five days. At that concentration, molnupiravir would theoretically take no prisoners, leaving not a single viral genome to escape unscathed. But there is a strong likelihood that in the real world, people will not take the full course of pills. A slew of studies on adherence to daily oral antibiotics suggest that many patients — as many as 40% — fail to complete the full course of treatment. At these suboptimal concentrations, molnupiravir could have the unfortunate effect of introducing mutations across every gene and protein of the virus, including the spike, but not necessarily killing it off. The drugmakers, Merck and Ridgeback, as well as the FDA are exploring whether molnupiravir is safe for personal use in high-risk individuals with mild to moderate disease and whether its benefits outweigh any potential risks. But they should also be determining the broader danger, and how to prevent the drug from unleashing new and deadlier variants across the globe. Already SARS-CoV-2 has shown a remarkable ability to mutate and survive under pressure. The drug’s manufacturers, Merck and Ridgeback, are entering into licensing deals that would allow the drug to be made and sold widely in more than 105 countries, which means that, if approved by regulators, we will soon have very little control over the drug’s administration and dosages delivered. We are potentially headed towards a world class disaster. If the FDA does grant approval for the drug — and there is an argument 1398
to be made that better and safer antivirals are already on the way — it should be on a very narrow basis and include a black box warning to emphasize the potential danger of using the drug at suboptimal doses or for large numbers of people for preventive purposes. What we know with certainty is that his drug is far from the magic bullet we might hope for with an antiviral for Covid-19. The next article in this two part series will explore the potential risks and dangers of the drug for patients themselves. This article originally appeared on Forbes, and can be read online here: Supercharging New Viral Variants: The Dangers Of Molnupiravir (Part 1)
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The Urgent Need For Increased Surveillance Of Variants That Arise From Chronic Covid Forbes | November 1, 2021 | Article
This is the fourth in a series examining the past, present, and future of the pandemic and viral variants. In our discussion of SARS-CoV-2 mutant strains, it is important to reflect on how viral variation occurs to inform our surveillance of variant emergence. Where do these mutations come from that yield new variants? Is it possible that the most serious variants arise not in large populations, but in immunosuppressed individuals? There is some evidence, which we will discuss here, that this is, in fact, the case. The virus is capable of surviving for months and upwards of a year or more within immunosuppressed hosts. During this time, SARS-CoV-2 has an opportunity to adapt to immune pressure, both natural pressures from our innate immune responses and treatments like monoclonal antibodies and convalescent sera. These adaptions take the form of genomic mutations. Viruses that emerge from these environments have the potential to be positively selected to become dominant strains. Viruses exist in swarms of billions of particles, each with a nucleic acid sequence slightly different from the others. Those that replicate most efficiently within a host and those that transmit most efficiently between hosts are selected over time, becoming the dominant version of the genome in the swarm, just as fauna develop advantageous traits via evolution. Via this process, there are winners and losers. This is clearly depicted by the progression from the Triad variant to Alpha and Gamma to Delta.
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FIGURE 1: Distribution of emerging lineages in SARS-CoV-2 infections in the United States and ... [+] STEBBING
There may be several traits that SARS-CoV-2 selects for, transmissibility being the foremost. Others include replication efficiency, evasion from neutralizing antibodies, and viral pathogenesis. The next question is whether the rise of major mutations like those in the Triad or the defining Spike mutations in Alpha or Delta arise at random or from patterned sources. While all mutations emerge from passaging the virus through a host, some hosts are different from others. There are two such examples of extraneous viral passaging in human hosts: Covid-19 in immunosuppressed patients and instances of long Covid. As early as December 2020, the scientific community was aware of the threat that Covid-19 cases in immunosuppressed patients represented. One such case was described in the New England Journal of Medicine. A 45-year-old man in Boston with severe antiphospholipid syndrome dealt with ongoing Covid-19 illness for 154 days before succumbing to Covid-related symptoms. The man was given multiple sets of antibody treatments, including remdesivir and Regeneron. After his death, researchers analyzed sera from the patient at different stages of his infection. They found that the virus that had initially infected him was not the same virus that was extracted near his death. Over the course of infection, the virus had selected dozens of mutations at different points of infection. In other words, genomic mutations were selected as normal, but it was as if there were multiple passages of the virus rather than one. 1401
SARS-CoV-2 has a wide variety of mechanisms in its various proteins to surpass innate immune defenses, such as interferon antagonism, RNA camouflage, etc. Immunosuppressed hosts are more easily invaded and the virus is more capable of efficiently replicating upon infection. This allows immune evasive and transmissibility mutations to be effectively selected. For instance, the Boston patient showed instances of the Spike E484K mutation months before that mutation was selected in the Beta variant in South Africa and the Gamma variant in Brazil. Not all long Covid cases are within immunosuppressed hosts, but similar principles apply. The virus remains within the host, replicating, and selecting advantageous mutations. At least five studies similar to the Boston patient were conducted, all of which were treated by convalescent sera or monoclonal antibodies and all of which resulted in distinctly mutant viruses than the strain that infected the patient in the first place. One patient in Pittsburgh yielded numerous N-terminal domain mutations, which later became commonplace in many variants of concern or interest. Another in Italy yielded a mutation in the Spike protein, Q493K, that was notably also noted independently in the Boston patient. Though the question remains, if immunosuppressed Covid-19 patients and long Covid cases are the perfect environment for mutations and new, dangerous variants to flourish, why are we not more engaged in viral surveillance of these cases? There are some governmental bodies attempting surveillance. For instance, the Massachusetts Department of Public Health uses a network of local boards of health, state epidemiologists, state public health labs, clinical labs, and so on to monitor incoming reports of SARS-CoV-2 infection. This data is collected and analyzed for realtime information sharing with local health officials. Aggregated public health data systems like this could survey for long Covid instances. However, these health systems are few and far between. Funding for SARS-CoV-2 monitoring is limited and many states and municipalities believe the pandemic is over, much less that sequence monitoring is worthwhile. This is a call for more such research on immunosuppressed cases of long Covid. Contingent on patient consent and participation, there are plenty of cases that could be studied which may be 1402
illuminating in the ongoing and future state of variants in the pandemic. This data is simply not being examined. These studies could be vital to understand how the Delta variant, specifically, reacts to monoclonal antibody treatment in long Covid cases. This series highlights the dangers that SARS-CoV-2 variation represents. The Delta variant is magnitudes more infectious than the original virus that emerged from Wuhan. Early indications suggest that new Delta Plus sublineages are at least 10% more infectious than Delta. Regardless of whether some believe the pandemic is over, SARS-CoV-2 will continue to infect vulnerable populations, mutate to become more transmissible, and so on. The reality is that this virus will become a consistent aspect of regular human existence. The question is whether we leave it unchecked or if we monitor, surveil, and minimize the virus and its impact. There are thousands of hospitals around the world filled with many patients suffering from long Covid. These patients should be monitored in more detail so that we can be prepared for whatever comes next. We urge governmental authorities to address SARS-CoV-2 surveillance with the gravity it deserves. This article originally appeared on Forbes, and can be read online here: The Urgent Need For Increased Surveillance Of Variants That Arise From Chronic Covid
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Defeating death from COVID: Here's a comprehensive strategy The Hill | November 1, 2021 | Article
In its first nine months in office, the Biden administration has made impressive and significant progress regarding the nation’s COVID-19 crisis. With bipartisan congressional support, it has passed another economic relief measure; encouraged and in some cases mandated vaccinations; tracked the spread of the Delta variant and encouraged safe practices, including a necessary if unpalatable return to mask wearing in many settings; authorized booster shots for some parts of the population; and made pledges of money, as well as actual vaccines, to developing countries. All of this is welcome — but only a good start. We are still not taking COVID-19 seriously enough as a country, or broader international community. This virus is potent, adaptable and dangerous. U.S. COVID death rates of 1,500 or more a day, even if gradually declining now, should be far fewer — and we should aim to have them approach zero within a year. On the current path, by contrast, things could stay bad or even get worse, as they have in several Eastern European countries. Now is the moment to act. The politics of COVID will not allow the Biden administration much time for necessary course correction. At this point, the major remedial and additional measures we recommend can be presented not as an acknowledgement of failure but as a necessary package, given the severity of the Delta variant and the unwillingness of many Americans to be vaccinated this year. In addition, the growing availability of vaccines, and the formal safety approvals for booster shots, as well as immunization of the young, create policy opportunities that were not available before. But if the Biden administration does not act soon, it will have squandered this crucial moment — and the next mutation of the coronavirus could make us all wonder why we did not seize the opportunity to attack the virus across multiple fronts when we had the chance. 1404
As one of us (Haseltine) has outlined in a new paper, a new and expanded strategy against COVID-19 is required along four main lines of effort. Packaged into legislation, they might have a combined annual cost in the general range of $10 billion a year for the next few years — a fraction of the trillions of dollars that this virus has cost the nation and the world in suppressed economic activity and lives lost: Improve and expand vaccines. The current generation of vaccines against COVID using recombinant RNA technology is remarkable. But we still do not have enough vaccine in the manufacturing pipeline — and we should be aiming to develop better vaccines against a virus that seems likely to become endemic in the population for years to come. The current vaccines lose effectiveness after a number of months, meaning that all who can should get boosters. Existing vaccines also fail to prevent those who are vaccinated, but nonetheless infected, from being contagious. We need to understand this virus better and should resource a concerted research effort. We also need more vaccine production capacity at home and abroad, subsidized by the government if need be. Better antivirals. Antivirals are a needed complement to vaccines. But the current antivirals in late-stage development target only two areas of the virus: the polymerase and the protease. This echoes the initial situation for our last great pandemic, HIV/AIDS. We learned then that such a narrow view is not enough. We should take full advantage of the numerous drug targets — more than 16 by our estimation — that could lead to new types of antiviral drugs. These drugs can and should be given to those who contract the disease (whether vaccinated or not) and to those at particular risk of contracting it because of exposure to contagious individuals or weakened immune systems. Again, research is necessary — we need antivirals that are safe, cheap and, ideally, in pill form. Reinvigorated public health measures. While social distancing and indoor mask wearing are important, we need to recommit to ideas that were popular last year in the United States — and that have proved effective in China and some other countries — but that have waned here of late. In particular, beyond much more testing, we need to build that army of 100,000 contact-tracers that once was envisioned (though with luck, the size of that public health force can decline in 2022 or 2023, as progress is made), and 1405
to increase financial incentives for self-isolation. It may be possible eventually to replace the two-week isolation for those exposed with prophylactic antivirals. A global strategy. For all the welcome U.S. donations to the COVAX fund, and promises to share vaccines, the Biden administration and other donors have only mapped out a plan to provide about half the 20 billion or so doses of vaccine that will be needed to inoculate the world. Developing countries must do better at building their own manufacturing capacity, but for now, there is little substitute for an expanded Western effort on this front. China’s and India’s vaccines can help some but are not nearly as good as the Pfizer and Moderna shots. Given the course we are on now, America likely will hit the terrible figure of 1 million COVID deaths — more fatalities than this nation has suffered in all its wars combined since the Revolution — sometime in 2022. It need not be that way. This article originally appeared on The Hill, and can be read online here: Defeating death from COVID: Here's a comprehensive strategyDefeating death from COVID: Here's a comprehensive strategy
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Nature Has Gifted Humans With Intelligence That Can Relegate Covid-19 If Not A Disease Of The Past, Then One That Rarely, If Ever, Is Fatal Forbes | November 1, 2021 | Article
This is the fifteenth article in a series called “How SARS-CoV-2 Delays, Evades, and Suppresses the Immune System.” Read parts 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15. There are many lessons we can take away from the ways in which SARS-CoV-2 works to suppress and evade the innate immune system. The more we understand how and why this virus targets certain components of our immune defenses, the more effective and focused our efforts to strengthen our vulnerabilities can become, in particular for older adults and other populations at high risk for Covid-19. The first lesson is that when we talk about innate immunity, we tend to conflate two arms of the immune system that warrant clear distinction. One is the pathway that stimulates interferon and interferon-stimulated genes. The other is the pathway that triggers inflammation through proinflammatory cytokines like tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-8 (IL8). Evidence suggests that while the interferon pathway has a protective function that weakens as we age, the inflammatory pathway only grows in potency, which can in fact have adverse and even lethal consequences for older adults. The second lesson we’ve learned is that more components of innate immunity are essential to its general functioning than we initially thought. Only in recent years have researchers begun to unpack the full efficacy of innate immunity—as compared to adaptive immunity—as a line of defense against pathogens. Studies of SARS-CoV-2 add to this existing body of work by documenting the various mechanisms viruses can develop to target innate immunity with greater precision. It appears that suppression of 1407
innate immunity allows SARS-CoV-2 to replicate to higher titers more efficiently, peaking before symptoms begin to show. The third lesson, to the previous point, is that the innate immune system is a target-rich environment ripe for drug development. Many studies show that as a Covid-19 drug, interferon—initially thought to be a promising candidate for treatment—counteracts the virus too bluntly and as a result, causes adverse effects in many of the patients who take it. To target SARS-CoV-2 with greater precision and less collateral damage, our therapies need to operate as molecularly as the virus itself. In parts of this series I’ve discussed how we categorize parts of the virus which participate in delaying innate immune response (Figure 1). I think it’s likely that inhibition of one or more of these could allow the immune system to fully suppress the virus in almost everyone.
Figure 1. Production of interferon and interferon-stimulated genes ACCESS HEALTH INTERNATIONAL
The fourth lesson is that we have to begin making a concerted effort to deepen our understanding of how to strengthen the immune systems of older adults. According to the literature, young children appear to mount an especially robust interferon defense against SARS-CoV-2. This trend runs counter to what we see in older adults, who exhibit an especially strong inflammatory response. Several drugs, for arthritis, psoriasis, inflammatory bowel disease, and autoimmune disease, work on the NF-κB pathway, one of many 1408
researchers should explore as an option for reducing inflammation. We also need drugs that strengthen interferon pathways. The fifth and last lesson is that genetic predispositions must also factor into our evaluations of risk for severe Covid-19 and the therapies we develop in response. If two thirds of a population is more sensitive to severe Covid-19 due to a genetic predisposition against interferon, we need to investigate whether we can stimulate AA inheritance types to be more like GC; whether we can stimulate ribonuclease L; whether we might even be able to use CRISPR technology to intervene and correct for potential points of vulnerability. Evolution has prepared our bodies to fend off many diseases, both through our innate and adaptive immune systems. Nature has gifted humans with intentional reasoning, which has given us an additional set of tools that allow us to fight the virus, understand it, and create new drugs for innate immune modulation. If we make the best and brightest use of our natural gifts, I’m confident we’ll be able to relegate Covid-19 if not a disease of the past, one that rarely, if ever, is fatal. This article originally appeared in Forbes, and can be read online here: Nature Has Gifted Humans With Intelligence That Can Relegate Covid19 If Not A Disease Of The Past, Then One That Rarely, If Ever, Is Fatal
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Harming Those Who Receive It: The Dangers Of Molnupiravir (Part 2) Forbes | November 2, 2021 | Article
Yesterday I wrote about the potential dangers the antiviral drug molnupiravir could unleash by supercharging new SARS-CoV-2 variants. Today, my focus is on the people who may receive the drug as a treatment and the possibility that molnupiravir could lead to cancerous tumors in those patients and birth defects in the unborn. Molnupiravir is a relatively new drug, initially developed as an antiviral treatment for influenza. Molnupiravir’s metabolite, an active compound called NHC, has been known and studied for decades. The metabolite works by creating havoc with RNA polymerase, the enzyme critical for viral replication. As I described in yesterday’s article, the drug inserts errors into the virus’ genetic code every time it copies itself. Insert enough errors and you essentially kill off the virus, preventing it from replicating any further. Against other coronaviruses, like MERS-CoV and mouse hepatitis virus (MHV), the drug was found to create up to more than a hundred mutations at every section of the viral genome. Against SARS-CoV-2, molnupiravir’s manufacturers Merck and Ridgeback say that the drug’s antiviral effects are powerfully effective, limiting the virus’ ability to proliferate unchecked and cutting the risk of hospitalization and death by half among those infected. The trouble with the drug, however, is that its mutagenic powers may also create havoc among other enzymes in the body, including the nucleic acids in our own healthy DNA. As far back as 1980, researchers have been trying to understand just how damaging NHC, molnupiravir’s metabolite, can be to our own healthy cells. Earlier this year, a study published in the Journal of Infectious Diseases found that the metabolite could indeed be incorporated into and mutate within our host DNA. As others have pointed out, just because something is mutagenic doesn’t mean it’s entirely bad — even sunlight is mutagenic. But, just like sunlight, 1410
overexposure can lead to long term ill effects, like cancer. In the case of molnupiravir, the drug may not just lead to the growth of cancerous tumours but also, potentially, to birth defects, either through sperm precursor cells or in pregnant women. Molnupiravir has been tested for mutagenicity in animals before being moved to human trials, where it is being tested for safety. But that doesn’t mean the drug is fully in the clear. The pool of participants in the clinical trial — around 1,500 patients — is too small to pick up on rare mutagenic events and the early nature of the trial is too short-term to provide a proper view of issues that may occur months, if not years, down the road. Merck would do well to remember their experience with Vioxx, a painkiller that was deemed safe based on initial studies, but later proved deadly. The FDA originally approved Vioxx based on a safety database that included around 5000 people. Five years later, the drug was recalled after a broader and longer term study found a definitive link between the drug and rare cardiac events. There is evidence that during the time the drug was on the market it may have killed up to 56,000 people and left up to 140,000 with heart disease. I believe Merck and Ridgeback know there are questions around the possible mutagenicity and teratogenicity of molnupiravir that need to be answered. Both male and female participants in the trial were asked to abstain from sex or use contraception during and shortly after the trial. And reporters have asked the manufacturers about potential mutagenic effects, which Merck has answered by saying that, “the drug will be safe if used as intended and at the concentrations where we have looked and in the concentrations which we are achieving in patients.” This isn’t the first time a mutagenic drug has been tested for antiviral activity. In that respect, our prior experience with another antiviral drug, favipiravir, may be of interest. It too is an antiviral that targets RNA polymerase, initially developed as a treatment for influenza and, like molnupiravir, now being tested against SARSCoV-2. The two drugs work in a similar fashion, interchanging two of the four letters of the viral RNA code to create copying errors — molnupiravir switches uracil (U) and cytosine (C), while favipiravir switches guanosine (G) and adenosine (A). Like molnupiravir, favipiravir works by creating enough copying errors during replication to essentially kill off the virus. 1411
The study on mutagenicity of the molnupiravir metabolite in the Journal of Infectious Diseases earlier this year also tested favipirivir. The study found that the molnupiravir metabolite, NHC, was a far more potent mutagen than favipirivir (FAV) (see Figure 1), which is a drug that has widely known issues related to teratogenicity and links to birth defects.
Figure 1. The left side of the panel shows the genotoxicity of molnupiravir metabolite, NHC, in ... [+] SHUNTAI ET AL., THE JOURNAL OF INFECTIOUS DISEASES, VOLUME 224, ISSUE 3, 1 AUGUST 2021, PAGES 415–419
Because of this, favipiravir has not been approved in the US or the UK, and is only approved in Japan under the strictest of regulations and for the most severe form of influenza, for which no other drugs exist. The challenge with approval of any drug, even under the strictest of regulations, is that once approved it can be used for many purposes, off-label. Favipiravir is already reportedly being distributed and used in Hungary as a treatment for Covid-19, despite no clear evidence of its value and its known risks. This is a danger not just to those receiving the drug, but also — as I wrote about in my previous article on molnupiravir — a danger to all of us, given the potential of drugs like these to supercharge the creation of viral variants. In November, the FDA will debate the use of molnupiravir only as a treatment for high-risk individuals with mild to moderate disease. But an initial emergency use approval for the drug may lead to unknown harm to all those who receive it. Yesterday, I wrote that if the FDA approves the drug it should be only on a very narrow basis and include a black box warning to emphasize the potential 1412
danger of using the drug at suboptimal doses or for large numbers of people for preventive purposes. To that, I add the need for specific warnings for men and women who are actively trying to become pregnant and for women who are already pregnant — under no circumstance should these individuals receive this treatment. I hope that Merck, Ridgeback, the FDA and the CDC explore the dangers of molnupiravir thoroughly before granting emergency use approval of the drug, especially as other potentially safer antivirals are already on the way. This drug could harm the very people it’s meant to help, those receiving the drug and all of us around them, should new more powerful variants be unleashed. * Shuntai et al., The Journal of Infectious Diseases, Volume 224, Issue 3, 1 August 2021, Pages 415–419, full caption: HPRT assay to detect genotoxicity of rNHC, RBV, FAV, AZT, 3TC, and TDF in CHOK1 cells. A, 6-thioguanine-resistant colony counts in 2 separate HPRT mutagenesis experiments. In the HPRT experiment 2, an additional round of initial cleansing for spontaneous HPRT mutations was conducted to limit background mutations. Each compound/dose group had 3 replicates. Average numbers of colonies are shown on the top of each bar. Significance compared to vehicle control (* P = .01–.05, ** P = .001–.01, **** P <.0001) was determined using the unpaired t test calculated using the GraphPad Prism version 8.3.0 built-in function. This article originally appeared on Forbes, and can be read online here: Harming Those Who Receive It: The Dangers Of Molnupiravir (Part 2)
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UK Approval Of Molnupiravir May Create New And More Dangerous Covid-19 Variants Forbes | November 4, 2021 | Article
As of this morning, British drug regulators have approved the Covid-19 antiviral drug molnupiravir for use in Covid-19 patients at risk for severe illness, making them the first public health officials to do so. The Medicines and Healthcare products Regulatory Agency released a statement alleging the drug, an oral pill developed by Merck Sharp & Dohme and Ridgeback Biotherapeutics, passed a “stringent review” for safety and efficacy. The public assessment report, which will detail the authorization process, is forthcoming. In October Merck announced that in a global clinical trial, molnupiravir reduced hospitalizations and deaths in Covid-19 patients by nearly 50 percent. The drug, given twice a day for five days, has since been bought up in bulk by governments around the world, including the United States. But missing from the official statements issued by UK regulators and pharmaceutical companies is any mention whatsoever of the potential mutagenic effects of molnupiravir on the virus itself, which I have outlined in a recent article for Forbes. The question isn’t only whether mutagenesis is dangerous for those who swallow the pill. It is a danger to the entire world population, and a glaring blindspot for the review committees involved. Molnupiravir works by tricking the virus into using the drug for replication, then inserting errors into the virus’ genetic code once replication is underway. When enough copying errors occur, the virus is essentially killed off, unable to replicate any further. If the pill is administered to millions, which will likely be the case if this authorization is the first of many, it could introduce mutations to the virus itself that are significant enough to change how the virus functions, but not so powerful as to stop it from replicating and becoming the next dominant variant. It is assumed that when used at the optimal concentration, the drug will prevent onward transmission of virus. Although that may 1414
be the case, we know what happens in laboratory studies when the virus is exposed to suboptimal doses. It produces multiple mutated viable variants, the conclusion evident based on data from a major research paper from 2019. When two coronaviruses, MERS-CoV and the mouse hepatitis virus (MHV), were tested against the active form of molnupiravir, a gaggle of mutations were identified across the genomes. With a half life of only 3.5 hours, it is probable that the drug, within 24 hours of administration at low concentrations, won’t sufficiently counter the survivability of the fast-mutating virus. The possibility for harmful mutagenesis was enough to convince another pharmaceutical company, Pharmasset, to abandon their own studies of the drug back in 2003. Another antiviral drug that works similarly to molnupiravir, favipiravir, also has not received US regulatory approval as a treatment for influenza.
Figure 1. Resistance and mutational profiles of MERS-CoV after 30 passages in the presence of NHC, ... [+] HTTPS://PUBMED.NCBI.NLM.NIH.GOV/31578288/
Figure 2. Resistance and mutational profiles of MHV after 30 passages in the presence of NHC, the ... [+] HTTPS://PUBMED.NCBI.NLM.NIH.GOV/31578288/
The study of MERS-CoV and MHV shows how wildly the virus mutates in culture, but we have no data on whether this is true for live virus in animals and people. In my opinion, fast-tracking molnupiravir for mass use without collecting further data on its mutagenic potential for the virus is a grave mistake that could lead to the emergence of supercharged variants more dangerous and lifethreatening than what we’ve witnessed thus far. The companies 1415
behind the drug must provide data on the effects of mutagenesis at suboptimal doses in primate and rodent models. At a minimum, the virus should be thoroughly examined and characterized in Covid-19 patients receiving the treatment to compare the rate of mutation with patients who aren’t on the treatment course. The fact that this isn’t a firm requirement could very well be considered negligence on part of the pharmaceutical companies and regulatory committees, given the magnitude of the dangers that await us if the virus assumes more lethal forms. The UK authorization of molnupiravir was greenlit on the basis of its ability to reduce the risk of hospitalization and death of Covid19 patients. What we need to know before moving forward, however, is the risk of this drug to the world. Viable alternatives that are at least as effective, if not more so, at treating early symptomatic Covid-19, particularly monoclonal antibodies, some of which may be administered by simple subcutaneous injections. There are several other drugs that don’t have this disadvantage that may be approved shortly. If we were to devise a method for creating more transmissible and virulent viruses, approving molnupiravir worldwide would be one of the best ways I can imagine doing so. As we wrap up our second year living through a global pandemic, that is the last thing we need. This article originally appeared on Forbes, and can be read online here: UK Approval Of Molnupiravir May Create New And More Dangerous Covid-19 Variants
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New Data Suggests mRNA Vaccines Work Best As A Three-Dose Regimen Forbes | November 4, 2021 | Article
A new large-scale study from Israel demonstrates a third Pfizer dose reduced Covid-related hospitalization by 93 percent, Covidrelated death by 81 percent, and severe Covid-19 illness by 92 percent, compared with receiving just two doses. The study took place from July 30, 2021 through Sept 23, 2021 when the Delta variant was the dominant strain in the country for new infections. This is critical data, as the study does not just measure breakthrough infections but instead the rate of Covid-19 related hospitalization, severe disease, and death in those with only two doses, demonstrating the value of a third mRNA dose across all populations. The study published in The Lancet was conducted by Israel’s Clalit Research Institute in collaboration with Harvard University and compared data from 728,321 individuals aged 12 and older who received a third dose of the Pfizer vaccine with the 728,321 individuals who only received two doses at least five months prior. Participants had a median age of 52 years and 51% were female. Data was provided by Clalit Health Services, which provides mandatory healthcare coverage for over half of the Israeli population. The study is very well designed, accounting for a number of variables that could have possibly influenced the results. Individuals who received a third vaccine dose between July 30, 2020, and Sept 23, 2021, were matched at a ratio of 1:1 to demographically and clinically similar controls who did not receive a third dose. The controls included biological gender, place of residence, number of pre-existing chronic conditions considered to be risk factors for severe COVID-19 (as defined by the CDC), calendar month in which each person received the second vaccine dose and number of SARS-CoV-2 PCR tests performed in the 9 months. The last two matching variables were included as markers of healthseeking behavior specifically related to Covid-19. 1417
Eligible participants were also required to have received the second vaccine dose at least 5 months before the recruitment date, had no previous documented SARS-CoV-2 infection, and had no contact with the health care system in the 3 days before recruitment. Individuals who are health care workers, live in long-term care facilities, or are medically confined to their homes were excluded. This ensured that the researchers were able to get a picture of what the risks of Covid-19 related hospitalization, severe disease, and death were for an average person who was not exposed to undue risk of Covid infection.
Cumulative incidence curves comparing COVID-19-related admission to hospital (A), severe disease (B), and death (C) in individuals who received two versus three doses of the BNT162b2 mRNA COVID-19 vaccineBARDA ET AL. EFFECTIVENESS OF A THIRD DOSE OF THE BNT162B2 MRNA COVID-19 VACCINE FOR
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PREVENTING SEVERE OUTCOMES IN ISRAEL: AN OBSERVATIONAL STUDY, THE LANCET, 2021
There were 231 instances of Covid-related hospitalization for participants who had received two doses versus 29 instances for those who received three doses. 157 instances of severe disease for two doses versus 17 instances for three doses. 44 Covid-19 related deaths for two doses versus seven Covid-19-related deaths for three doses. The estimated third-dose vaccine effectiveness against admission to hospital and severe disease was similar between males and females, and between individuals aged 40–69 years and those aged at least 70 years. Due to the relative scarcity of events in individuals younger than 40 years in the study, the authors acknowledge that they cannot accurately assess the impact of vaccination doses on this population. Based on this compelling, real-world, large-scale data, I will continue to advocate for a three-dose regimen as the best protection against the ever-evolving SARS-CoV-2 virus. I urge the CDC to expand access to third mRNA doses for anyone over the age of 12. Even those who are well-protected against symptomatic illness and disease can still become infected and spread the virus to those who are more vulnerable. In the short run, at least we may need to become accustomed to regular Covid vaccinations, in the same way, we’ve already become accustomed to annual vaccinations for the flu. Each year, the flu vaccine primes our bodies for the most likely influenza strains circulating that year, provoking an initial vigorous antibody response and giving our long-term memory cells an indication of the disguises or rather the mutations the virus is wearing this year. It is very likely we will need to take a similar approach with Covid. This article originally appeared on Forbes, and can be read online here: New Data Suggests mRNA Vaccines Work Best As A Three-Dose Regimen
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A Single Point Mutation In The Nucleocapsid Protein Increases Covid Virus Infectivity By More Than 100 Times Forbes | November 9, 2021 | Article
Increased plaque forming capability of N protein mutant viruses carrying either S202R or R203M ... [+] SYED ET AL.
A recent paper by Syed et al. demonstrates that mutations in the Nucleocapsid (N) protein, one of the four structural proteins in SARS-CoV-2 in addition to the Spike protein, plays a critical role in the increased transmission and possibly virulence of the Delta variant. Previous studies of increased transmission and other virological properties of SARS-CoV-2 variants focus almost exclusively on the Spike (S) protein. This work emphasizes that it is of equal importance to look at the effects of mutations throughout the entire viral genome. 1420
SARS-CoV-2 Virus-like Particle and Identification of the Packaging Sequence To study the effects of structural protein mutations on the infectivity of SARS-CoV-2, the authors created a new experimental system which they call SARS-CoV-2 virus-like particles (SC2VLPs). These are particles in which the structural proteins, N, S, the Envelope (E), and Membrane (M), exist as heterologous RNA which contains the SARS-CoV-2 packaging signal. Creating the particles first required identification of the SARSCoV-2 cis-acting packaging sequence. Packaging is the incorporation of RNA into host cell nuclei for replication. Through analysis of previous research on SARS-CoV and Murine Hepatitis Virus, they were able to refine the packaging signal down to a short sequence, specifically nucleotide positions 20080-21171.
FIGURE 1: Visualization of the region where the identified packaging signal (PS9) is located in the ... [+] SYED ET AL.
Isolation of this sequence enabled the fixed packaging of heterologous RNA into the virus-like particles.
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FIGURE 2: Schematic representation of SARS-CoV-2 virus-like particles alongside a SARS-CoV-2 virus. SYED ET AL.
Effects of Mutations on the S Protein The authors used the SC2-VLPs first to examine the transmissibility of key S mutations to the Wuhan wildtype. Exposing the SC2-VLPs to 293T ACE2-imitating cells, the regulation of luciferase activity, which is positively associated with the more efficient assembly of the virus-like particles and subsequently stronger mRNA delivery. Notably, they found that none of the generated SC2-VLPs generated with S mutant genes, including four with the combined mutations found in the Alpha, Beta, Gamma, or Epsilon variants, increased luciferase expression to a significant extent. This observation that the S protein mutations have little to no effect on the ability of the virus to enter ACE2-positive cells differs somewhat from previous studies showing that Spike protein mutations confer some entry advantage. Effects of Mutations on the N protein. As they did for mutations in S protein, the authors generated SC2-VLPs which encoded major N protein mutations found in many naturally-occurring SARS-CoV-2 variants. The researchers note that all variants of concern contain at least one amino acid mutation between positions 199 to 205 of the N protein, indicating great significance in some form. This specific region is the linker domain between the N-terminal and C-terminal domains. The 1422
major mutations in this region are P199L, S202R, R203K/M, G204R, and T205I, at least one of which is found in every major natural variant. Again exposing the SC2-VLPs to 293T ACE2-imitating cells, they found that the natural mutations, such as S199L, S202R, and R203K/M, increase luciferase activity, and thus transmissibility, by four to seven-fold. This observation suggests that the N protein, itself, conveys a replication advantage at least to SC2-VLPs. To confirm their observations of greater luciferase and mRNA delivery activity in SARS-CoV-2 virus-like particles, the researchers then reverse-engineered SARS-CoV-2 cells in vitro using the S202R and R203M N protein mutations, which are commonly found in natural variants like Delta, with an original Wuhan strain genome. Infecting A549-ACE2 cells with wild-type virus, virus with S202R, and virus with R203M, they measured the RNA content and compared. PCR analysis indicated 45-fold higher RNA content and 166-fold higher infectious titers in viruses with S202R as compared to the wildtype. Additionally, R203M viruses posted 23-fold higher RNA content and 51-fold higher infectious titers. In other words, viruses with the mutant N protein bolstered infectiousness by around 50-fold. Infectivity of Viruses Carrying N Protein Mutations Further analysis of the infected cells used in the previous experiment 24, 48, and 72 hours post-infection found that infectious titers were 166-fold higher in viruses with S202R as compared to the wildtype. Additionally, R203M viruses posted 51-fold higher infectious titers. These experiments demonstrate that the N protein is a major contributor to increased replication of natural variants, specifically the Delta variant, which carries R203M, and possibly others. The increased replication efficiency due to N protein mutations is significant, however, it only represents a fraction of the infectious capabilities of viral variants. The Delta variant, for instance, produces roughly 1000-fold more virus in nasal-pharynx secretions than the Wuhan virus. We speculate that the other viral proteins and cis-acting packaging sequences may contribute to the additional 950-fold 1423
increase in replication efficiency. The Delta variant has 15 nonsynonymous mutations outside of the S and N proteins. These include the replicative-transcription complex (NSP1-16), the other structural proteins (E and M), and the regulatory Orf proteins (Orf3a, Orf7a, Orf7b, etc). Amongst these mutations are two mutations that are common to all natural variants along with D614G in the S protein, part of what we refer to as the Triad. These are P323L in the NSP12 polymerase and C241U in the 5’ untranslated region.
FIGURE 3: C241U in the 5’ untranslated region and P323L in the NSP12 polymerase. ACCESS HEALTH INTERNATIONAL
This is a common theme throughout all natural variants of SARS-CoV-2. Below is a figure displaying the mutational capability of the virus.
FIGURE 4: SARS-CoV-2 genome. Bars indicate mutations in non-Spike protein present in at least 1% of ... [+] ACCESS HEALTH INTERNATIONAL
Conclusion
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A single point mutation in the N protein can increase the infectivity of the SARS-CoV-2 virus by 50-fold. Additionally, experimentation via SC2-VLPs is an elegant medium to potentially analyze virological impacts by mutations on other SARS-CoV-2. We hope that similar elegant methods can be applied to investigate the contributions of the other structural proteins, the replicative transcription complex, and the regulatory Orf proteins. Analysis of mutations in these proteins and in the genomic RNA sequence itself, which are plentiful throughout natural SARS-CoV-2 variants, may yield results akin to those found in the N protein. This article originally appeared on Forbes, and can be read online here: A Single Point Mutation In The Nucleocapsid Protein Increases Covid Virus Infectivity By More Than 100 Times
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Spike And Nucleocapsid Protein Mutations In Tanzanian And Ugandan Strains Of SARS-CoV2 Demand Attention Forbes | November 12, 2021 | Article
Virus variation is a major driver of current infections. All SARSCoV-2 variants sweeping almost all areas of the world today, including variants of concern Alpha, Beta, Gamma, and Delta, originally derived from the Triad variant (D614G). This variant was the first major variant of the Wuhan strain and includes D614G in the Spike (S) protein, P323L in the NSP12 polymerase, and C241U in the 5’ untranslated region.
FIGURE 1: SARS-CoV-2 evolution from one emerging lineage to another in the United States and Brazil. STEBBING
We have previously noted two outliers that differentiate from the Triad template, both originating in East Africa. These are the A.23.1 strain in Uganda and the A.30 strain from Tanzania. These two variants warrant detailed analysis as they could provide insight into the range of variations that could yield new waves of the Covid19 pandemic. In that regard, we analyze a new paper by Arora et al. that compares the ability of one of these strains, A.30, which contains a highly mutated S protein, to avoid neutralization by antibodies
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derived from convalescent sera, monoclonal antibody treatment, or vaccine. A.30, which was first detected in patients arriving at an Angolan airport from Tanzania, contains 34 amino acid changing mutations throughout its various viral proteins. In the S protein alone, there are ten amino acid substitutions and five deletions.
FIGURE 2: Spike mutations regularly found in the A.30 genome. ARORA ET AL.
For the purposes of antibody neutralization, the researchers focus on the mutations which affect two major domains of the S protein, the N-terminal domain and the receptor-binding domain. The researchers note that all A.30 deletions along with four substitutions are found in the N-terminal domain of the surface unit S1. The residue positions of these deletions and substitutions lie in an antigenic supersite that is targeted by most neutralizing antibodies. Arora et al. investigate antibody-evasive features of A.30 by creating rhabdovirus pseudotypes bearing the SARS-CoV-2 S protein. These viral models can be used to measure antibody neutralization in vitro, reducing the risk of experimenting with live viruses.
Cellular Host Range of A.30 1427
To test the immune resistance of these mutations, Arora et al. first implanted the A.30 S mutations on rhabdoviral pseudotype viruses. They then exposed the pseudotypes to five different targets to model different organs in a human host. To compare, pseudotypes of the Beta and Eta S proteins are also created and exposed to human-like cell targets. Notably, A.30 seemed to infect some cell types more effectively than others, namely Vero (kidney), 293T (kidney), Huh-7 (liver), and A549 (lung). The authors conclude that A.30 exhibits a cell line preference not observed for other viral variants, possibly changing the disease profile of those infected. Neutralization by Monoclonal Antibodies The infected cells are then treated with bamlanivimab and etesevimab, both separately and in conjunction via antibody cocktail, to emulate Covid-19 therapy. Consistent with previous experiments, they found that Beta was resistant to both bamlanivimab and etesevimab, whereas Eta was resistant to only bamlanivimab. A.30, along with Eta, was bamlanivimab resistant, but susceptible to etesevimab and a bamlanivimab + etesevimab cocktail.
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FIGURE 3: Neutralization of SARS-CoV-2 B.1, A.30, B.1.525, and B.1.351 by monoclonal antibodies used ... [+] ARORA ET AL.
Neutralization by Convalescent Sera 1429
Next, the researchers compared neutralization of the virus by convalescent sera developed through previous infection. Their findings suggest that the Beta variant was the most resistant to convalescent sera, followed by A.30, and then Eta, though all three African variants are more resistant than the Triad variant.
FIGURE 4: Neutralization of SARS-CoV-2 B.1, A.30, B.1.525, and B.1.351 by antibodies in convalescent ... [+] ARORA ET AL.
Neutralization by Vaccine-administered Antibodies Finally, the researchers analyzed the neutralization of each variant by antibodies administered by vaccination, both by adenovirus vaccines like AstraZeneca and mRNA vaccines like Pfizer. This data is the most interesting in reference to the A.30 variant. Arora et al. note that A.30 was significantly more resistant to neutralization by homologous ChAdOx1 nCoV-19 (Astrazeneca) or BNT162b2 (Pfizer) vaccination antisera than either Beta or Eta, by roughly half an order of magnitude.
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FIGURE 5: Neutralization of SARS-CoV-2 B.1, A.30, B.1.525, and B.1.351 by antibodies in the ... [+] ARORA ET AL.
The researchers conclude by noting that the potential spread of the A.30 variant warrants close monitoring and rapid installment of countermeasures. We echo this sentiment. We note that other factors besides S protein mutations may be involved in the A.30 variant’s immune resistance. While there are 15 mutations in the A.30 S protein, there are 19 mutations in nonS proteins throughout the A.30 genome.
FIGURE 6: A.30 mutations found outside the Spike protein. ACCESS HEALTH INTERNATIONAL
N Protein Mutations A recent manuscript demonstrates that single point mutations in the specific region of the Nucleocapsid (N) protein, position 199205, substantially increase the infectivity of the virus, in some cases by over 150-fold. The A.30 variant contains a mutation in this region, S202N, which was not specifically studied in the aforementioned paper, but is remarkably similar to another, S202R, which conferred an increase of infectivity roughly 50-fold. Notably, both A.30 and A.23.1 appear to contain the S202N mutation independently. This article originally appeared on Forbes, and can be read online here: Spike And Nucleocapsid Protein Mutations In Tanzanian And Ugandan Strains Of SARS-CoV-2 Demand Attention
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HPV Vaccine Should Be Universal For Boys And Girls, Ages 9-14 Forbes | November 15, 2021 | Article
The United Kingdom has achieved substantial success vaccinating against a highly contagious virus, human papillomavirus or HPV. In doing so, it has reduced cervical cancer rates among women in certain age groups by 87%, an astounding achievement that underlines the value of vaccination against disease. HPV is a common infection that can easily be passed through skin-to-skin contact, including through sex. It is the cause of many forms of deadly cancers and the driving factor in the fourth most common cancer among women around the world: cervical cancer. Beyond the threat or cervical cancer, HPV has been tied to penile cancer in men and head and neck, oral and anal cancers in men and women alike. In 2008, two years after an HPV vaccine was introduced on the global market, the United Kingdom rolled out a widespread vaccination campaign focusing on girls. The first dose of the twodose regimen became a routine offering to girls aged 12 and 13. It was also offered as a “catch-up” dose to girls aged 14 to 18. Now, a new study published in the Lancet shows the impact of that vaccination campaign, more than a decade on. Compared to previous generations, cervical cancer rates were 87% lower in women offered HPV vaccination when they were 12 or 13, 62% lower from age 14 to 16, and 34% lower from age 16 to 18. The authors say that translates to 450 fewer cases of cervical cancer and 17,200 fewer cases of cervical precancers as of 2019. The success of the UK campaign lends added importance to the efforts by the World Health Organization to vaccinate 90% of all girls by the age of 15 with a goal of eliminating cervical cancer by 2030. Vaccination can achieve significant results for women and girls. But the UK took the campaign even further in 2019 when it rolled out HPV vaccines to all boys as well, at the same age as girls receive it. Given the relatively recent start of the campaign, little is 1432
known about its tangible effects to date, but there is a strong belief that the results will be equally impressive. The hope is that global organizations like the WHO will recognized the importance of the vaccine for all individuals, no matter their sex, and they will soon expand the primary target group for the HPV vaccine to include both boys and girls age 9 to 14. Unfortunately, even if the WHO supports widespread vaccination for boys and girls alike, there are important challenges that stand in the way of young men and women actually receiving the vaccine. In the US, the CDC recommends the vaccine for all kids between the ages of 11 and 12. But despite its approval, the vaccine rollout has been slow, with only 61% of girls age 13-17 having received the full three-dose vaccine regimen in 2020 and just 56% of boys. This is in part due to a fear that allowing young boys and girls to be vaccinated against a virus that spreads primarily through sexual contact is essentially giving them permission to be promiscuous, a theory that has been debunked in study after study. Still, anti-HPV vaccine campaigns, including on social media, have managed to limit vaccine uptake in countries as widespread as Japan, Ireland, Denmark and here in the US, often by limiting the likelihood that healthcare providers will recommend the vaccine and the likelihood that parents will ask for it for their kids. Beyond the social hesitancy, there is the question of price, especially for many low and middle income countries. When the vaccine was first introduced on the global marketplace, the price per dose for the three-dose regimen averaged $130 US each. It wasn’t until nearly a decade later that Gavi, The Vaccine Alliance, was able to negotiate a much lower cost of around $5 US a dose for low income countries. This stalled many campaigns worldwide. In the United States, the price per dose is still high, in the hundreds of dollars per dose. Most health insurance covers the cost, but the uninsured aren’t guaranteed the vaccine and often need to apply for vaccine coverage assistance or negotiate a lower price directly with a healthcare provider, not an easy task for anyone not highly health literate. And then there is also the question of knowledge and understanding, especially among boys and the parents and healthcare providers of young men. Given the common misconception that the 1433
virus only poses a risk to women, vaccine coverage among men and boys continues to lag far behind despite the risk. In the United States alone, HPV led to a five-fold increase of head and neck cancers in young men from 2001 to 2017; the vaccine could prevent more than 90% of those cancers. And then there is also the question of knowledge and understanding, especially among boys and the parents and healthcare providers of young men. Given the common misconception that the virus only poses a risk to women, vaccine coverage among men and boys continues to lag far behind despite the risk. In the United States alone, HPV led to a five-fold increase of head and neck cancers in young men from 2001 to 2017; the vaccine could prevent more than 90% of those cancers. This article originally appeared on Forbes and can be read online here: HPV Vaccine Should Be Universal For Boys And Girls, Ages 9-14
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Epidemiology Answers Key Questions About Delta Variant Transmissibility And Lethality Forbes | November 15, 2021 | Article
Understanding the transmission dynamics of SARS-CoV-2 infection is critical to developing countermeasures that can successfully stop the spread of the virus. For most of the Covid-19 pandemic, computational modeling studies have given us a general sense of when, following infection, SARS-CoV-2 becomes contagious, then symptomatic. But due to difficulties in data collection, the exact timing of this progression eluded us. That is, until this past August, when a group of Chinese researchers published a preprint study of an outbreak of the Delta variant in Guangdong province. Their study pinpoints, with unprecedented precision, exactly when in the disease course infectivity and symptom onset might be expected. And in the broader context of epidemiological research and disease control, the study is an excellent example of the level of insight possible when public health measures, including contact tracing, are systematically combined with cutting-edge virology and pathology. In May 2021, public health officials in Guangzhou, China began tracking an outbreak of Covid-19 cases caused by the highly infectious Delta variant of SARS-CoV-2. Through rigorous PCR testing and contact tracing protocols, they identified infected individuals and controlled the outbreak by June. The authors of the study, Kang et. al, drew from this pool of epidemiological data to determine how long it takes the Delta variant, as compared to the original wild type virus, to become infectious and cause symptoms in the people it infects. They aggregated data on a total of 167 Covid-19 patients. First Kang et. al identified the upper and lower bounds of the latent period, in the interval of time between infection and infectiousness, for each patient by creating a timeline around the dates of their last negative PCR test and first positive PCR test. Then they determined the incubation period, or the interval of time 1435
between infection and the onset of symptoms, again using data collected via contact tracing, monitoring, and routine testing— procedures that in China are now standard safety protocol in the event of any outbreak. Kang et. al also gathered information on close contacts of their patients to see how quickly the virus spread between hosts. Kang et. al organized their findings around two principal epidemiological parameters: R0 and Rt. Calculated together, these measures create a profile of disease infectiousness that provides key insights on its intensity and duration. They allow us to predict how quickly the virus will spread once it becomes infectious. Kang et. al also used statistical analysis to identify time-based trends in viral load, or the concentration of viral particles in the body. Of the 167 cases recorded during the Guangzhou outbreak, Kang et. al had enough data to calculate latent and incubation periods for about 100 symptomatic cases. The latent period between infection and first appearance of the virus was 4.0 days on average, while the incubation period between infection and first symptoms was 5.8 days on average (Figure 1A and 1B). That means SARSCoV-2 is estimated to become infectious four days following infection, with symptoms appearing around day six.
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Figure 1A. Latent period Figure 1B. Incubation period Figure 1C. Infectiousness profile "TRANSMISSION DYNAMICS AND EPIDEMIOLOGICAL CHARACTERISTICS OF DELTA VARIANT INFECTIONS IN CHINA" HTTPS://WWW.MEDRXIV.ORG/CONTENT/10.1101/2021.08.12.21261 991V1
Kang et. al also used data from 94 transmission pairs—pairs of Covid-19 cases confirmed to have an evident epidemiological connection—to estimate the peak of infectiousness (Figure 1C). They found that more than 70 percent of transmission occurred before symptoms appeared, with infectiousness peaking about two days prior to symptom onset. Viral loads remained high before and after patients became symptomatic, then decreased to barely detectable levels by Day 20. To compare the transmissibility of the Delta variant with wildtype SARS-CoV-2, the researchers used data collected in the same city during outbreaks in early 2020. Kang et. al found viral 1437
concentrations in Covid-19 patients infected by wild-type virus to be lower than those in patients infected by the Delta variant. They speculate that the higher viral loads documented in the Delta cases likely contribute to an increase in the speed and intensity of transmission. Far more cases of critical Covid-19 were also recorded in the Delta patient cohort; none developed in the group infected with wild-type virus. The exact R0 obtained by Kang et. al was 6.4, which according to the study is significantly higher than that of the wild-type virus. The researchers calculated the R0 of the Delta variant by estimating Rt when the Guangzhou outbreak was on the rise, as well as the series interval. From May 25 to June 18, over a period of three and a half weeks, Kang et. al estimated that Rt dropped sharply from 9.3 to 0.48 once the Chinese government began implementing lockdowns and isolating those exposed. The rapid drop in Rt was due to these public health measures—an example of how rigorous public health interventions control disease transmissibility. Kang et. al conclude that the public health measures implemented to contain outbreaks caused by the Delta variant, including vaccination but also testing and contact tracing, must be escalated to account for shorter latent and incubation periods and lower the incidence of severe disease. That such a high caliber of data is not the standard in more countries is a failure of our public health systems, but thanks to the Kang et. al study, we have hard data on the Delta variant we’ve lacked for some time. The intrinsic R0 was subject to debate—now we know exactly what it is. We also know how much more lethal and transmissible the Delta variant is compared to the wild-type virus. The clarity and insight we stand to gain from systematic, targeted public health interventions is undeniable. We cannot forget that our efforts to stop the spread of Covid-19 are only as good as our understanding of the virus itself. This article originally appeared on Forbes, and can be read online here: Epidemiology Answers Key Questions About Delta Variant Transmissibility And Lethality
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Stimulating Innate Immunity Stops SARS-CoV2 Infection Forbes | November 17, 2021 | Article
When the worldwide death toll from Covid-19 surpassed five million two weeks ago, it served as a grim reminder that more than lockdowns and vaccines will be needed to end the pandemic. A new study, available now to read online and due to publish in the Journal of Experimental Medicine next year, offers an approach that could make a vital addition to our current arsenal of anti-SARS-CoV-2 countermeasures. According to the study, researchers Mao et. al have identified an antiviral drug that activates the innate immune system and appears to have strong prophylactic and therapeutic potential in mice, meaning it could both prevent and treat Covid-19 in humans. Their findings form the latest contribution to a growing body of work on SARS-CoV-2 and innate immunity, the body’s first line of defense against pathogens. Historically, innate immunity has not been understood as widely or deeply as the body’s second line of defense, the adaptive immune system. Adaptive immunity involves the antibodies—killer T cells, memory B cells, and so on—that have become shorthand, in discussions about vaccines, for protection against the virus. But a series of papers I have analyzed at length in my SARS-CoV-2 immune suppression series for Forbes shows that it is not adaptive immunity but innate immunity that the virus antagonizes so rigorously in the early days of infection. If a drug can stimulate innate immunity and generate protection before SARS-CoV-2 has the opportunity to tamper, it could protect high-risk individuals from severe illness, persistent infection, and death. Innate immunity is driven by the identification of pathogenassociated molecular patterns, or PAMPs, by pattern recognition receptors that have evolved over the course of the millennia-long battle between viruses and humans. Some of the most prominent pattern recognition receptors include toll-like receptors and retinoic 1439
acid-inducible gene I (RIG-I)-like receptors. Detection of PAMPs by these receptors is what activates the signaling pathways that induce production of interferons, interferon-stimulated genes, and inflammatory cytokines, which in turn trigger the adaptive immune response. The drug tested by Mao et. al in mice models is a RIG-I agonist called stem-loop RNA 14 (SLR14). Prior research had already established that SLR14 generates a robust innate immune response in mice and might yield an equally potent reaction in humans. Mao et. al found that SLR14 administered to mice four hours after infection by wild-type SARS-CoV-2 dramatically mitigated symptoms and improved survival prospects. Mice that didn’t receive the drug, by contrast, succumbed to infection by day eight. To test whether the drug also works in immunodeficient mice, Mao et. al administered doses to Rag−/− mice, which lack functional B cells and T cells characteristic of the adaptive immune response. Even in Rag−/− mice SLR14 proved successful at lowering viral replication and clearing infection. That such high levels of neutralization were achieved through activation of innate immunity alone should be impetus enough to investigate the clinical benefits of this approach. Also noteworthy is that SLR14 was successful at reducing mortality and morbidity in mice infected by five SARS-CoV-2 variants, including Alpha, Beta, and Delta. Since studies have shown that SARS-CoV-2 is a virus capable of evolving to become more immune evasive and immunosuppressive, the ability of SLR14 to induce broadly effective protection is significant. Like other drug therapies that aim to trigger the immune system, SLR14 relies on interferon signaling to generate protection against SARS-CoV-2. In mice models the drug stimulated rapid proliferation of interferons in the respiratory tract, where viral replication typically takes place. It is the correlation between a robust interferon response and antiviral resistance that led some researchers to believe that interferon-based therapies would prove effective at preventing and treating Covid-19, especially in patients with autoantibodies against interferon or inborn defects that compromise interferon signaling. While studies of recombinant interferon drugs showed promise, the cost of treatment regimens would amount to many thousands of dollars for patients—according to one assessment, 1440
between $1,120 and $1,962 for one regimen and between $2,156 and $5,887 for another. But SLR14, Mao et. al argue, is a chemically simple synthetic that would be easy to cheaply manufacture on a large scale. Mao et. al also suggest that other innate immune modulators like poly(I:C) and diABZI, a small molecule drug and STING agonist I have written about previously, would make a useful addition to an anti-SARS-CoV-2 drug strategy. (Though in terms of antiviral activity, SLR14 surpassed diABZI in their study.) If this is true for SARS-CoV-2, it is likely to be the case for many other RNA viruses that simulate the RIG-I immune signaling pathway. I eagerly await news of how SLR14 performs in humans. In the meantime, researchers and funders would be remiss to overlook the increasingly evident relevance of innate immunity to antiviral drug development. As new variants of SARS-CoV-2 become more exacting in their ability to antagonize our foremost defenses, we must become more rigorous in our efforts to counteract the virus. The difference between a mediocre and life-saving treatment could be a matter of a single molecule. This article originally appeared on Forbes, and can be read online here: Stimulating Innate Immunity Stops SARS-CoV-2 Infection
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Detailed Description Of A Highly Potent SARSCoV-2 Neutralizing Antibody: Bamlanivimab Forbes | November 17, 2021 | Article
Monoclonal antibodies have been shown to be effective in both the prevention and early treatment of SARS-CoV-2 infections. One of the antibodies currently approved for clinical use by emergency use authorization is a combination antibody treatment of bamlanivimab and etesevimab. A recent paper by Jones et al. describes bamlanivimab and its properties in detail, as well as details how bamlanivimab was discovered, providing a potential blueprint for antibody discovery in the future. Monoclonal antibodies are typically laboratory-produced molecules that mimic the adaptive immune system’s response to invading pathogens. They neutralize a virus by blocking the Spike (S) protein from attaching to the host ACE2 receptor, which reduces viral reproduction and immune reactions. Selecting Bamlanivimab To find potential SARS-CoV-2 antibodies, Jones et al. extracted peripheral blood mononuclear cells (PBMCs) from a convalescent patient 20 days after initial symptoms. They extracted and screened about 5.8 million PBMCs, which contained 2,238 single antibodysecreting cells. Using custom machine-learning-based sequencing, Jones et al. narrowed their search to 440 high-confidence heavy and light chain antibodies. From these 440 candidates, Jones et al. selected antibodies capable of rapid cloning, recombinant expression, and were observed in high frequency, of which there were 175. They further selected for more specific requirements, including SARS-CoV-2 and SARSCoV-1 binding, binding to the S protein receptor-binding domain, and binding to certain receptor-binding domain mutations commonly found in SARS-CoV-2 variants, including V378F and V483A. This led to a lead panel of antibodies for further testing. 1442
Jones et al. tested the neutralizing capacity of the panel antibodies against a SARS-CoV-2 pseudovirus and a live SARS-CoV-2 isolate. In both instances, one antibody, bamlanivimab, was by far the most potent neutralizing antibody, with a half-maximal concentration of about 0.05 micrograms per milliliter neutralizing at roughly 75%.
JONES ET AL.
FIGURE 1: Neutralization of recombinant SARS-CoV-2 encoding a nanoluciferase reporter in the Orf7a/b ... [+] JONES ET AL.
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Bamlanivimab Binding Bamlanivimab had a 10-fold greater neutralization capacity than any other identified antibody candidate. This is despite binding in a similar place and pattern to two other tested antibodies: Ab128 and Ab133, which is notably a similar configuration to advanced antibody candidate etesevimab. To investigate the increased neutralization, Jones et al. performed x-ray crystallography on bamlanivimab and found that in addition to binding the receptor-binding domain, it also was found to bind to an epitope overlapping ACE2 binding sites.
FIGURE 2: Bamlanivimab blocks ACE2 and binds to the spike protein RBD in up and down conformations ... [+] JONES ET AL.
The researchers then conclude that this allows bamlanivimab to bind the receptor-binding domain in both the “up” and “down” configurations, whereas the other antibodies, including etesevimab, only bind in the “up” configuration. Bamlanivimab Protection
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To test for protection by bamlanivimab against Covid-19 related symptoms, Jones et al. used nonhuman primates as a simulation of how the antibody may be accepted by the human immune system. Testing for RNA copies per milliliter in bronchoalveolar lavage fluid, lung tissue, nasal swabs, and throat swabs, the researchers noticed distinct drops in RNA content across the board within days of monoclonal antibody inoculation. In other words, in all areas of the respiratory tract, the monoclonal antibody bamlanivimab reduces SARS-CoV-2 replication and viral load, which in theory results in weakening and waning of symptoms sooner in the infection cycle. This is great news for general and at-risk populations alike. If you were to come in contact with a known SARS-CoV-2 infection or were early on in the symptom onset, taking bamlanivimab could greatly reduce the risk for at-least respiratory-related illness. While bamlanivimab on its own neutralized SARS-CoV-2 more effectively etesevimab in the Jones et al. study, further research indicated that together they neutralize live virus even more effectively. The combination therapy, now produced by Eli Lilly, is now approved by the Food and Drug Administration via emergency use authorization for post-exposure prophylaxis and treatment. In addition to immediate treatment, the antibody can be used in immunocompetent infected patients up to five to seven days postinfection and it remains effective. Additionally, the antibody is successful in preventing infection and disease in those known to be exposed to SARS-CoV-2 infected hosts. However, we note that as SARS-CoV-2 continues to evolve into new and more mutated variants, the virus can and will become more resistant to treatments like bamlanivimab + etesevimab. For example, a recent study of three SARS-CoV-2 variants all originating in Africa indicates some resistance already occurs. The Beta variant from South Africa is completely resistant to the combination cocktail. Additionally, the Eta variant from Nigeria and the A.30 variant from Tanzania are substantially resistant to the cocktail in comparison to the Triad variant which drove infections in the Summer of 2020. In other words, these variants already contain mutations that render major approved monoclonal antibodies less effective or completely ineffective. 1445
Despite this, we implore more such wide studies to be undertaken as hidden gems like bamlanivimab await discovery. More treatments and prophylactics of this nature could greatly reduce the risk for hospitalization and death, especially among at-risk individuals. Using bamlanivimab’s discovery as a blueprint may lead to numerous more to be discovered in the critical months ahead. This article originally appeared on Forbes, and can be read online here: Detailed Description Of A Highly Potent SARS-CoV-2 Neutralizing Antibody: Bamlanivimab
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Covid Ear: Virus Implicated Forbes | November 18, 2021 | Article
You may have heard of “COVID toe,” but what about “COVID ear”? As the pandemic wears on, an increasing number of COVID-19 patients have reported issues with hearing loss and tinnitus, a continued ringing in one or both ears. Some have even complained of sudden troubles with balance and an onset of intense dizziness. All of these symptoms suggest that SARS-CoV-2 may be able to affect the inner ear. Researchers at MIT and Massachusetts Eye and Ear have released a new report studying the mechanisms underlying these symptoms. Their findings, published in Communications Medicine, indicate that the inner ear can, in fact, be infected by SARS-CoV-2. To do this, Minjin Jeong et al. obtained fresh, human inner ear tissue extracted as a byproduct during a special kind of ear surgery. Upon analyzing these tissue samples, they discovered that both hair cells and Schwann cells of the inner ear express the proteins required for SARS-CoV-2 infection, making them potential targets. Angiotensin-converting enzyme 2, generally known as ACE2, is a “receptor” protein that acts as a binding site for SARS-CoV-2’s Spike (S) protein. Once bound, the enzymes FURIN and transmembrane protease serine 2 cleave the virus at two distinct sites along its spike protein, allowing the virus to combine and enter the host cell. Minjin Jeong et al. then tested the ability of hair cells and Schwann cells to support SARS-CoV-2 infection. To do so, they exposed the fresh inner ear tissue to either a mock solution or to SARS-CoV-2. As illustrated in Figure 1, there was no change in the tissue exposed to the mock solution. On the other hand, those samples exposed to SARS-CoV-2 displayed clear signs of viral replication.
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FIGURE 1. Immunofluorescent staining of mock infected vs. SARS-CoV-2 infected human inner ear ... [+] “DIRECT SARS-COV-2 INFECTION OF THE HUMAN INNER EAR MAY UNDERLIE COVID-19-ASSOCIATED AUDIOVESTIBULAR DYSFUNCTION” HTTPS://WWW.NATURE.COM/ARTICLES/S43856-021-00044W#SEC27
Following this experiment, the researchers developed new twoand three-dimensional models to study inner ear infection. Because the fresh inner ear tissue they had received for their studies is usually quite inaccessible, making it difficult to study, Minjin Jeong et al. hope that their new models will facilitate future research. To create these models, the researchers made use of human induced pluripotent stem cells (hiPSC). Most cells are specialized, meaning they have a specific function based on the kind of cell they are. Cells become specialized through a process known as differentiation. Stem cells, however, are cells that have not yet undergone differentiation and are still pluripotent, meaning they can become any kind of cell. By exposing already-specialized cells to specific genetic instructions, they can be reverted back into pluripotent stem cells.
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Minjin Jeong et al. induced pluripotent stem cells from human skin cells, and then slowly differentiated these stem cells to resemble the hair cells and Schwann cells of the inner ear. For the twodimensional models, the hair cells and Schwann cells were differentiated in separate petri dishes over the course of 30 days. In the case of the three-dimensional model, the various stem cellderived inner ear cells were grown together in the same container for 90 days. The result, a self-generated inner ear organoid that reconstitutes “the accurate and complex microenvironment found in living organisms.” The three-dimensional model expressed ACE2, FURIN, and transmembrane protease serine 2, indicating their presence in the synthesized cells, and reflecting what the researchers saw in the fresh inner ear sample. This was also the case for the model of the hair cells. The model of the Schwann cells only expressed ACE2 and transmembrane protease serine 2. When exposed to SARS-CoV-2, Minjin Jeong et al. found that the vestibular hair cells of the inner ear, which help us keep our balance and sense head movements, had an infection rate of 26%, making them particularly vulnerable. The Schwann cells, not so much; in the two-dimensional model they did not readily show signs of infection, whereas in the three-dimensional model, mirroring the results in the fresh inner ear sample, they were infected at a considerably lesser rate. We also have another kind of hair cell inside our inner ear, called “cochlear” hair cells, which help us detect sound. These were not part of the study as they weren’t present in the fresh tissue samples obtained by the researchers. Even so, based on the anatomic and physiologic similarities between vestibular cells and cochlear cells, they believe that these, too, can become infected with SARS-CoV2. Their hunch is supported by studies they performed on mice, in which cochlear hair cells were also shown to express the proteins required for infection. It remains uncertain exactly how the virus enters the inner ear. Minjin Jeong et al. suggest SARS-CoV-2 might enter via the nose, through our “olfactory bulb,” into the central nervous system, at which point it could make its way to the inner ear along a cranial nerve. Another potential pathway is via something called the
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“endolymphatic sac,” a protective buffer between the inner ear and the rest of the body. Although evidence that the inner ear is actually infected is still lacking, these findings serve as a strong proof of principle, suggesting that infection of, and subsequent damage to, the hair cells of the inner ear may be behind the hearing and balance issues reported by some COVID-19 patients. This article originally appeared on Forbes, and can be read online here: Covid Ear: Virus Implicated
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Intramuscular Injection Of Monoclonal Antibodies Simplifies Covid Treatment Forbes | November 19, 2021 | Article
Until effective and accessible SARS-CoV-2 antivirals are available, monoclonal antibodies remain our strongest treatment and prophylactic against Covid-19. These antibodies are typically administered by a drip, which often requires medical assistance. One antibody, however, sotrovimab, could be administered intramuscularly (by shot), making delivery of the treatment far simpler. Here we review a press release by sotrovimab producers GSK and VIR that details the intramuscular administration of sotrovimab. The trial to test sotrovimab was a phase 3, randomized, doubleblind, placebo-controlled study, which is the standard for an efficacy test of this nature. The aim of the trial was to determine whether intramuscular administration of the antibody was similarly effective to intravenous (IV) administration for the early treatment of mildto-moderate Covid-19 in high-risk populations. Primary Outcomes A detailed review of the study is yet to be released, but according to the GSK press release, the results for intravenous and intramuscular administration of sotrovimab were roughly equal. There was a 2.7% rate of progression to hospitalization for more than 24 hours or death among high-risk patients with mild-to-moderate Covid-19 in the intramuscular group. In contrast, that rate in the intravenous cohort was 1.3%. The adjusted difference between the two administration methods was 1.07% with a 95% confidence interval of -1.25% to 3.39%, which falls below the upper bound set by the Food and Drug Administration for non-inferiority. In other words, the receiving sotromivab from a shot in the arm is of the same clinical effectiveness as from an IV drip. 1451
Sotrovimab Structure We have previously described the origins and activities of sotrovimab in greater detail. To recount, the antibody is a derivative of another antibody, S309, which was first isolated from memory B cells from the sera of a recovered SARS-CoV-1 patient. S309, like many other antibodies, targets the Spike protein of the viral genome, which modulates viral entry into host cells and carries several antibody binding sites. S309 targets a specific residue on the Spike protein, N343, which was later determined to be a consistently conserved glycan in the Sarbecovirus subgenus. As SARS-CoV-2 belongs to this subgenus and maintains many similarities to SARS-CoV-1, S309 was a promising neutralizing antibody candidate for inhibition of SARS-CoV-2. Sotrovimab differs from S309 in a particular way. It is purposefully engineered to possess two mutations in the Fc region. These are M428L and N434S, colloquially referred to as the LS mutation. These two mutations confer enhanced antibody binding to the Fc receptor, a critical binding agent for monoclonal neutralization. Studies describe that the two mutations result in an extended half-life of roughly 50 days and enhanced drug distribution to the respiratory system, protecting from significant lung damage or other Covid-related respiratory complications. Caveats and Conclusions While the finding that intramuscular and intravenous administration of sotrovimab is significant, there are several further endpoints that should be considered with this monoclonal antibody and with all antibody candidates. The trial described follows patients through 29 days of trial. As the half-life of sotrovimab is detailed by some studies as roughly 50 days, it would be noteworthy to follow these patients past the 29day marker to investigate the ongoing protection from SARS-CoV2 reinfection that sotrovimab may grant. While the two administration methods were statistically equivalent, more patients were hospitalized or died in the intramuscular cohort than the intravenous cohort. It would be interesting to analyze the health context and complications of those 1452
in the intramuscular group versus the intravenous group to potentially find some correlation in symptom protection. It is worth commenting on the relative merits and disadvantages of a single intramuscular injection of long-acting monoclonal antibodies versus orally-administered pills both for the treatment and prevention of COVID-19. The advantage of pill formulation is that they do not require medical personnel for administration. However, the patient must determine that they are infected, see a doctor, obtain a prescription, and take the pills as recommended, at present a five-day course involving a dose every 12 hours. Moreover, the treatment must begin shortly after infection and usually within three to four days of symptom onset, which translates to between six and 12 days postinfection. Additionally, once oral treatment ceases, the patient is only protected by existing convalescent antibodies. A single muscular injection, however, requires no further treatment or medication past the moment of treatment, though this requires medical personnel for administration. Moreover, the halflife of sotrovimab is roughly 50 days, which means the protection from subsequent infections following exposure could last three months or longer. In the case of one antibody cocktail developed by Regeneron, protection is estimated to last eight months, though that treatment is an IV drip. Perhaps the best use for antiviral drugs occurs prior to infection, either as pre-exposure or post-exposure prophylaxis. In other words, the drug is administered as a preventative either in general or immediately following exposure to a known positive infection. In this context, a single intramuscular injection of an antibody is far superior to orally-administered pills. The single intramuscular injection may provide protection for up to four months, whereas ingestible pills only protect as long as they are taken. Additionally, long-term use of antiviral pills could lead to dangerous side effects, including carcinogenesis. This is the case for aspiring drug candidate Molnupiravir, which is toxic and mutagenic in extended use. One major advantage of small-molecule ingestible antivirals over intramuscular injections is the price. Prices may vary and both Merck and Pfizer have stated that costs will be lower in low-income countries. For Molnupiravir, the cost of production for a full course is roughly $5. Most small-molecule drugs will be of similar 1453
production cost: around $20 or less. In higher-income countries, the five-day regimen of antiviral pills is closer to $500. A full 8-milliliter dose of sotrovimab will cost roughly $2000, which is far from a competitive price point compared to other existing and emerging treatments for Covid-19. Were the sotrovimab treatment closer to the $500 to $1000 range, it may be more competitive in the treatment and prophylaxis market. For congregate living centers, particularly eldercare facilities where the residents are at high risk due to age and comorbidities, we first recommend triple vaccination. Then, if a Covid-19 case is detected, we would recommend all residents and employees receive an intramuscular injection of monoclonal antibodies. We call this the “belt and suspenders” strategy, conferring two layers of significant protection to high-risk populations. This strategy is universally beneficial, as it boosts all recipients' antibody levels tremendously. Were “belt and suspenders” a routine procedure in every potential host, we would all be better protected if exposed to the virus. Orally-administered pills, on the other hand, only provide additional protection so long as the treatment is ingested. We also note that antiviral pills are mostly used in the context of postexposure and post-symptom-onset patients. Their benefits for preexposure prophylaxis have yet to be significantly evaluated. It is welcome news that a variety of approaches for both treatment and prevention of SARS-CoV-2 infectious disease are either here or will soon be available. It will be up to both governments and individuals to decide which treatment is appropriate in what setting to join vaccines in medical control of the COVID-19 pandemic. This article originally appeared on Forbes, and can be read online here: Intramuscular Injection Of Monoclonal Antibodies Simplifies Covid Treatment
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Science Talk: Hope and concern for two novel Covid-19 antivirals Forbes | November 22, 2021 | Article
Public health measures, vaccines and antimicrobials – which kill micro-organisms or stop their growth – are the hallmarks to keeping plague-causing microbes at bay and, in exceedingly rare instances, even to eradicating them. Nearly two years into the pandemic, we now have all three at hand for Covid-19, with the most recent development being announcements by pharmaceutical giants Merck and Pfizer on the effectiveness of their antiviral pills. Oral antiviral drugs could be one of the most powerful tools at our disposal to control the scope of the pandemic. They could be used as a treatment for those infected, to reduce the risk of hospitalization or death. In an ideal world, they could also be used prophylactically to prevent those who may be exposed to the disease from ever becoming ill, just like we do with other diseases like the flu and HIV. No other proven treatments for Covid-19 can be used to this effect. The monoclonal antibodies and convalescent plasma therapies that are known to treat the disease are expensive and must currently be administered intravenously (in the vein) or subcutaneously (under the skin) usually in a clinical setting. That makes the treatments near out of reach for the vast majority of those infected, and largely unrealistic as a method of prevention. Merck and Pfizer's oral antivirals have shown potential as a treatment, but there are still some important questions that need to be answered before either could be considered ready for use on a mass scale, especially for use prophylactically. Let's take a look first at the drug shown to be most effective in clinical trials, Pfizer’s protease inhibitor, paxlovid (PF-07321332), which prevents the virus from replicating by binding to parts of it.
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Paxlovid, a new molecule developed specifically to disable SarsCoV-2, which causes Covid-19, is used in combination with another drug, ritonavir, that has been used for decades in the treatment of HIV. In the clinical trial, among participants who received treatment within three days of the start of symptoms, the risk of hospital admission or death was 89 per cent lower in the paxlovid group than the placebo group. Among those who received treatment five days out from symptoms starting, the reduction was 85 per cent, still a very strong showing. The Merck drug saw a more modest 50 per cent reduction in hospitalisation or death. Merck's drug, molnupiravir (MK-4822), is a nucleoside analogue – part of an important class of antiviral agents used to treat HIV infection and hepatitis, among others. These work by blocking cellular division or viral replication by impairing DNA/RNA synthesis. Molnupiravir carries with it two substantial concerns. The first is whether the drug, meant to attack viral RNA, could also damage healthy DNA. A study published earlier this year shows that the active compound in the drug can indeed be incorporated into and mutate host DNA – which in this case would be the Covid-19 patient. The result of this mutagenesis is not fully clear, but the possibilities could include birth defects or cancers. Certainly, there is enough of a risk with the Merck drug that it should never be used widely and certainly not among pregnant women or for any man or woman actively trying to conceive. Beyond damage to the patients themselves, the Merck drug also carries with it the possibility of introducing mutations to the virus itself which may create Sars-CoV-2 variants that are more transmissible and more deadly than others we've seen. This concern is not entirely theoretical. A study published prior to the pandemic tested molnupiravir against two other highly pathogenic coronaviruses: Mers-CoV – the virulent coronavirus which was first reported in Saudi Arabia in 2012, and the mouse hepatitis virus.
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The researchers found that the drug could introduce hundreds of mutations in the populations of cells infected with the viruses. While most of the mutations harmed the virus, the possibility that the drug may introduce mutations that help the virus does indeed exist, and may be made more likely in real world use, when people forget or choose not to take the full course of treatment. Molnupiravir is meant to be taken as four large pills every 12 hours for five days. If pills are forgotten and suboptimal doses are delivered, it is difficult to say what may arise. One thing we do know is that both antiviral pills may eventually fail over time if administered on their own. HIV taught us that antiviral monotherapies – used on their own – are bound to eventually fail as antiviral resistance develops. Clinical trials should, therefore, begin on the use of combination therapies, for instance, molnupiravir alongside paxlovid, to mitigate this risk. And efforts should be made to answer the main questions around the Merck drug in particular before further regulatory approvals are granted. In the meantime, we must continue to rely on public health measures and top of the line vaccines to hold off the full force of the pandemic long enough to allow affordable and easy to administer treatments to fully develop. We could be on the cusp of total control of Covid-19, but only if all countries are willing to apply the full force of our knowledge and tools – vaccines, antimicrobials and public health measures – against the vaccine. This article originally appeared on Forbes, and can be read online here: Science Talk: Hope and concern for two novel Covid-19 antivirals
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Hong Kong Demonstrates Effective Use Of Covid Public Health Mitigation Forbes | November 24, 2021 | Article
It is clear from surging cases in Europe and in the US that we cannot make the mistake of relying on vaccines alone for population protection. We need to fight Covid fatigue and maintain the effective the public health protocols of test, trace and isolate. Here, I describe a new study from Hong Kong that further validates this approach by demonstrating how effective stringent quarantine policies are in controlling Covid transmission without the need for city-wide lockdowns. Only 6 out of 4198 participants in the study tested positive for SARS-CoV-2 antibodies after three waves of Covid that occurred prior to Hong Kong’s vaccination rollout. Despite a relatively slow vaccine uptake, Hong Kong is one of the few places that has successfully controlled Covid cases throughout each stage of the ongoing pandemic. Daily cases have never risen above 180 a day and the average daily case count in the wake of the Delta variant that has ravaged so many other places has been between two and eight cases. This is particularly impressive in a densely populated city such as Hong Kong. These results are thanks to rigorous contact tracing, targeted testing blitzes, and strict border controls and quarantines. The Hong Kong study authors sought to discover whether there were some asymptomatic or otherwise unidentified cases that were not included in these low daily case counts and designed a study to assess the prevalence of unidentified SARS-CoV-2 infection. A prospective cross-sectional study was conducted in Hong Kong after each major wave of the Covid-19 pandemic (April 21 to July 7, 2020; September 29 to November 23, 2020; and January 15 to April 18, 2021). A total of 4198 Adults who had not been diagnosed with Covid-19 were recruited during each period, and their sociodemographic information, symptoms, travel, contact, quarantine, and Covid-19 testing history were collected. SARSCoV-2 IgG antibodies were detected by an enzyme-linked 1458
immunosorbent assay based on spike (S1/S2) protein, followed by confirmation with a commercial electrochemiluminescence immunoassay based on the receptor-binding domain of spike protein. All participants were tested for SARS-CoV-2 IgG antibodies using an enzyme-linked immunosorbent assay based on spike (S1/S2) protein, followed by confirmation with a commercial electrochemiluminescence immunoassay based on the receptorbinding domain of spike protein. Overall, 6 participants were confirmed to be positive for SARSCoV-2 antibodies. Two participants with positive results were from the first recruitment, 1 from the second recruitment, and 3 from the third recruitment which corresponded to positivity rates of 0.22% (2 of 903), 0.10% (1 of 1046), and 0.13% (3 of 2249). The researchers used these percentages and applied a weighted adjustment according to the sex and age distribution of the general adult population in Hong Kong in order to estimate the number of unidentified SARSCoV-2 infections. The adjusted prevalence of unidentified infection was found to be at 0.15%, with fewer than 1.9 unidentified infections for every recorded case. The findings suggest that stringent isolation and quarantine policies even without complete city lockdown are very successful in minimizing SARS-CoV transmission. Rigorous testing, tracing, and isolating is a highly effective Covid control policy that the US and many other countries have never fully embraced. As we continue to battle vaccine hesitancy and waning immunity in those who are vaccinated, our arsenal needs to include more than just medical defenses. The best strategy will combine the powers of medical and public health defenses to include vaccination with boosters as indicated, antiviral drugs, testing, tracing, quarantining, ventilation and masking when appropriate. This article originally appeared on Forbes, and can be read online here: Hong Kong Demonstrates Effective Use Of Covid Public Health Mitigation
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A New Monoclonal Antibody That Has The Potential To Neutralize All Viral Variants Forbes | November 24, 2021 | Article
Cryo-electron microscopy of neutralizing and non-neutralizing Abs in complex with SARS-CoV-2 Spike ... [+] DAPENG ET AL.
Monoclonal antibodies offer what is now a proven way to prevent and treat Covid-19 infections. Until recently, antibodies were administered by intravenous (IV) injection, which limited their widespread use. Newer technologies allow antibodies to be administered intramuscularly or subcutaneously. Additionally, new data indicates that with minor modifications, monoclonal antibodies can provide protection for many months. These advances add to the ability of monoclonal antibodies to treat and prevent Covid-19. One limitation of Covid-19 monoclonal antibodies is that virus variants can escape neutralization. Single point mutations or deletions in certain areas of the SARS-CoV-2 genome can eliminate or gravely reduce antibody potency. Here we describe a novel 1460
antibody: DH1047. The distinguishing characteristic of this antibody is that it is capable of neutralizing all known variants of interest and concern by targeting highly conserved epitopes. Martinez et al. at the University of North Carolina aimed to identify, isolate, and analyze an RBD-targeting monoclonal antibody with the potential to neutralize beyond just the SARSCoV-2 wild type. Building on the research by Rappazzo et al. that noted that an engineered RBD-directed antibody, ADG-2, could neutralize and protect against multiple SARS-related viruses, Martinez et al. hypothesized that conserved RBD glycans could create potent targets for cross-reactive antibodies. Identifying DH1047 Thousands of antibodies develop within us upon infection with an invading pathogen. To uncover their winning antibody, Martinez et al. built on the foundations of previous research. Beginning with a pool of 1737 monoclonal antibodies isolated from SARS-CoV and SARS-CoV-2 convalescent sera described by Li et al., Martinez et al. then focused on 50 which bound to both SARS-CoV, SARSCoV-2, and other animal sarbecoviruses such as bat virus WIV-1. To further restrict their candidates, Martinez et al. tested the 50 antibodies for neutralizing activity on a mouse-adapted SARS-CoV2 virus, a SARS-CoV-1 virus, bat coronavirus WIV-1, and bat coronavirus RsSHC014. These tests resulted in four primary candidates that displayed broadly neutralizing capability: DH1235, DH1073, DH1046, and DH1047.
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FIGURE 1: The genetic relationships of ACE2 and non-ACE2 using sarbecovirus receptor binding domains ... [+] MARTINEZ ET AL.
Martinez et al. further analyzed their refined group of four against several more sarbecoviruses, including horseshoe bat viruses RaTG13-CoV and RsSHC014, pangolin virus GXP4L-CoV, camel virus MERS-CoV, human cold virus HuCoV OC43, and others. Notably, the four antibodies bound to some viruses but not others. Specifically, they only bound to Group 2B betacoronaviruses, leaving out viruses like MERS-CoV. Martinez et al. conclude that this is likely due to the targeted epitope of the four antibodies existing in Group 2B betacoronaviruses, but not others. Martinez et al. then aimed to analyze the protective activities of the four antibodies to determine whether their binding and neutralization carried over to animal models. Neither DH1235, DH1073, nor DH1046 protected infected mice from SARS-CoV lung viral replication, demonstrating a contrast to the potent neutralization displayed in vitro. DH1047, however, fully protected mice subjects from lung virus replication. Further tests indicated that DH1047 as a prophylactic prevented illness-related weight loss and pulmonary complications as well. Martinez et al. had found their winner. DH1047 Binding Using cryo-electron microscopy, Martinez et al. observed the techniques DH1047 and its related antibody use to bind to a broad range of sarbecoviruses so effectively. They note three antibody fragments bound to three SARS-CoV RBDs in the “up” position. This is the position required for virus interaction with the host cell. The residues making antibody contact are 356-372, 390-404, and 488-492. Two of these sets, 356-372 and 390-404, are located in the receptor-binding core, whereas 488-492 is located in the receptorbinding motif, which is the part of the receptor-binding domain that makes contact with the host ACE2 receptor. Martinez et al. further note that these sets of residues closely resemble that of the SARSCoV-2 spike and others, defining the cross-vulnerability of sarbecoviruses.
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FIGURE 2: Linear representation of the SARS-CoV-2 receptor-binding domain with DH1047 binding ... [+] ACCESS HEALTH INTERNATIONAL
FIGURE 3: Cryo-electron representation of DH1047 binding to the SARSCoV/SARS-CoV-2 Spike protein. MARTINEZ ET AL.
DH1047 SARS-CoV-2 Variant Neutralization Perhaps the most immediate use for a broadly neutralizing crosssarbecovirus antibody is the neutralization of pervasive mutated SARS-CoV-2 variants. Using pseudovirus neutralization assays, Martinez et al. introduced DH1047 to several variants, including the Triad (or D614G), Alpha, Beta, Gamma, B.1.429, B.1.526, Kappa, and Delta. They found that in the case of all SARS-CoV-2 variants, the 50% neutralization assay values ranged between 0.1214 and 0.1609 micrograms per milliliter. In other words, DH1047 potently neutralized all SARS-CoV-2 variant pseudoviruses. They also tested the antibody against live virus samples of the Triad, Alpha, and Beta variants. Again, 50% neutralization assay values were low, running
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from 0.059 to 0.111 micrograms per milliliter, confirming that DH1047 broadly neutralizes SARS-CoV-2 variants. Conclusion We look forward to the rapid development of this antibody and others like it. Cross-neutralizing antibodies such as DH1047 would make an important contribution to the control of the Covid-19 pandemic. This article originally appeared on Forbes, and can be read online here: A New Monoclonal Antibody That Has The Potential To Neutralize All Viral Variants
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December, 2021
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Frequent Rapid Testing Is The Key To Controlling Covid-19 Transmission In Universities And In Our Communities Forbes | December 1, 2021 | Article
The advent of the Omicron variant and the rise in cases across the US is a grim reminder that we will only control this virus through a combination of public health measures and medical interventions, including vaccines, drugs, and easily accessible diagnostic tests. Yet well over a year since the first rapid antigen test was approved, despite desperate pleas from many epidemiologists and public health experts, the US is yet to embrace the power of mass rapid testing. Rapid at-home tests are becoming less scarce on our pharmacy shelves in recent months due to investment by the Biden Administration but their price is still prohibitive for most Americans to use them in the most effective way. At a typical cost of $25 for a pack of 2, many individuals are conflicted about when to use rapid tests. If the tests were cheaper or free, individuals could engage in a twice-weekly testing regime or test whenever they knew they were entering a high-risk, poorly ventilated, or unmasked venue, office, home, or other location. The demand for rapid tests is clear with a recent trial in New Hampshire exhausting their supply of 1 million free tests when 100,000 households signed up within 24 hours. The barrier that remains is cost and supply. Widespread accessibility to rapid tests in the US is presently hampered by a cumbersome F.D.A. process intended for high-tech medical devices. To be approved, the rapid tests must demonstrate that they are nearly as sensitive as the gold standard PCR. tests. But rapid tests are the “public health gold standard”, they deliver the most important public health metric by detecting when someone is infectious and is likely to transmit the virus. Therefore they should be regulated as a Public Health Good. President Biden could 1466
accomplish this with a simple Executive Order, increasing competition among manufacturers and flooding the market with inexpensive, high-quality rapid tests. As the pandemic shows no sign of receding well into its second year, governments around the world are less willing to instigate lockdowns as they weigh the economic impact. Rigorous testing followed by supported isolation can prevent the need for city-wide lockdown and rapid community transmission as proven in a recent Hong Kong study. Industry and institutions could also play a role in promoting the use of regular rapid testing, which would be beneficial both to their bottom line and to the health of their stakeholders. A new preprint study from the University of Bristol has found that both high levels of vaccination and rapid twice-weekly asymptomatic testing are needed to keep infection rates low on university campuses. The researchers adapted an existing mathematical model of Covid-19 transmission in universities, to determine two scenarios. With lowlevel interventions (no asymptomatic testing, 30% vaccinated), 5371% of students become infected during the first term; with high interventions (90% using asymptomatic testing, 90% vaccinated) the incidence of infections is just 7-9%, with approximately 80% of these cases estimated to be asymptomatic. Workplaces could adopt similar interventions. Some have already implemented vaccine mandates, but adopting a twice-weekly rapid testing policy particularly in highrisk settings would keep employees safe and transmission low. This is also a critical time to start requiring rapid tests for domestic travel within the US. The Biden administration is currently preparing stricter testing requirements for all international travelers entering the United States, but with the Omicron variant likely already seeded in multiple states, we need to focus on all travel. As we have learned from bitter experience, no population is safe until we all are. I can only hope that the Omicron variant is the warning we need to embrace mass testing. This article originally appeared on Forbes, and can be read online here: Frequent Rapid Testing Is The Key To Controlling Covid-19 Transmission In Universities And In Our Communities
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Can Our Success with HIV Serve as a Guide for Antiviral Drug Development for Covid-19? Clinical OMICs | December 1, 2021 | Article
To much of the world, the growing realization that vaccineinduced immunity for COVID-19 eventually fades has come as a shock. But for those of us who lived through the beginnings of the world’s last great pandemic, HIV/AIDS, the tremors feel oddly familiar. With AIDS, we never succeeded in developing an effective vaccine, but we did find medical solutions to treat the disease and control its spread. Those same solutions are what we should be thinking about today for COVID-19 to fill in the gaps where vaccine immunity falters. HIV and SARS-CoV-2 are two very different viruses, but they hold remarkable similarities: They’re both novel RNA viruses that crossed from animals into humans. They both gave rise to global pandemics, with HIV killing more than 37 million since the pandemic began and SARS-CoV-2 on its way to killing more than five million in its first two years alone. And perhaps most critically, they both employ similar evolutionary mechanisms that allow the viruses to adapt, even under immune pressure. HIV’s ability to mutate and adapt has made it difficult for us to develop a vaccine against the disease, but we have found other ways to control and slow its spread, primarily through behavior change and antiviral drugs that can treat someone who is infected and, perhaps more importantly, be taken prophylactically by healthy individuals, preventing them from ever becoming infected or ill, even if exposed to the disease. PEP (post-exposure prophylaxis) and PrEP (pre-exposure prophylaxis) are two critical prevention methods for HIV infection that those of us in the scientific community fought long and hard over decades to develop. Today, our community is working at record pace to develop antivirals for COVID-19 but our focus, in my opinion, is far too narrow given all that we have learned with HIV.
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The two COVID-19 antivirals receiving the most attention are a polymerase inhibitor called molnupiravir, developed by Merck and Ridgeback, and a protease inhibitor, PF-07321332, developed by Pfizer. The first HIV antivirals were also directed at these same targets. The first antiviral drug for HIV was a polymerase inhibitor, azidothymidine (AZT). The drug works well to stop HIV replication but when administered to patients as a monotherapy, we found it led to the rapid development of resistance. If the virus acquired one or two minor changes in the polymerase, it could render the drug less effective and that variant of the virus could proliferate quickly. Patients living with HIV who received the drug could develop drug resistance within just a few months. A generation of early AIDS victims were brought back from the edge of death only to die from the virus that was AZT resistant. To overcome challenges of resistance, we broadened the scope to include drugs focused on other targets, like the protease. The idea was to combine drugs that attacked different targets, minimizing the probability of the virus acquiring mutations that would make it resistant to all drugs simultaneously—if one treatment fails to work, other drugs in the cocktail continue the job. The first protease inhibitors against HIV prevented the cleavage of viral polyproteins, which are necessary for both viral replication and the release of mature viral particles from an infected cell. We found that when these drugs were combined with polymerase inhibitors, we could create a combination therapy that was more effective for a longer period of time than protease inhibitors alone. The combination therapy had another beneficial effect that was important for our success, it widened the drug therapy’s therapeutic index. All drugs have a therapeutic index, which is the ratio between the amount of a drug needed for it to be effective and the amount at which the drug becomes toxic. The index even applies to something as simple as water—the right amount of water keeps you alive, but too much of it and you drown. Patients living with HIV would receive antiviral treatments over their lifetime, so it was important that the drugs could be well tolerated not just over the short term but over an extended period of time. With combination therapies, you could use lower concentrations of each of the drugs with greater effect, which meant that people could survive longer on the treatment without severe side effects. 1469
The therapeutic index is also critical for pre-exposure prophylaxis. With PrEP, we are giving drugs to healthy people so those drugs need to have a very low toxicity. With the early HIV combination therapies, the therapeutic index was tolerable for those infected but the risk of side effects and toxicity was nowhere near where it needed to be to be used prophylactically. We knew prophylactic antivirals was an approach that could work to prevent infection, but we wouldn’t be able to deploy it without finding new drugs with a much wider therapeutic index that could be well tolerated by those infected and those who were healthy, but at risk of exposure. That set us off on a thirty-year search for better HIV drugs. Taking lessons from other diseases, like cancer, we began expanding our search beyond the polymerase and protease alone, targeting biochemical processes which are unique to the virus and dissimilar to our biochemistry. Our bodies make and use polymerases and proteases regularly for day-to-day minute-by-minute functions. While a virus’ protease may not be exactly like our own cell’s protease, it may be similar enough that protease inhibitors developed to target a virus may take a toll on a patient’s healthy cells as well. In the end, that hunt was successful. My own work looking beyond the prime protease and polymerase targets led to two additional targets that have proven well worth the time and effort to explore them: the integrase and capsid. Indeed, these two targets are at the root of two new long-acting HIV drugs that have a much higher therapeutic index than any previous. Lenacapivir, a longacting drug from Gilead, is a capsid inhibitor that works on the integration pathway. By binding to the capsid protein, the drug blocks HIV’s ability to interact with a cellular chaperone that would normally allow it entry into a cell’s nucleus. Stop the virus from entering the nucleus and you stop it from replicating. Cabotegravir, developed by ViiV Healthcare, also works on the integration complex, this time focusing instead on a viral enzyme critical to integration: the integrase. An integrase strand inhibitor, it blocks the virus from integration, blocking its ability to replicate and then spread. We also now have a wealth of prime targets for HIV drugs, beyond the integrase and capsid, including anti-Tat protein, antiRev protein, and anti-endonuclease inhibitors.
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Our success with HIV, after decades of trial and error, should now be applied to COVID-19. If we want drugs with a high therapeutic index that we can use prophylactically over the long term, we need to look beyond the polymerase and protease and start thinking about combination therapies. The two COVID-19 antivirals farthest along in development today are, as I mentioned at the beginning of this column, a polymerase inhibitor called molnupiravir and a protease inhibitor, PF-07321332.
Molnupiravir works by attacking SARS-CoV-2’s polymerase, the enzyme that builds the viral genome during replication. The drug tricks the virus into using molnupiravir for replication, then inserts errors into the virus’ genetic code once replication is underway. The drug is a tautomer that assumes two forms, one which closely resembles uracil (U) and the other cytosine (C). Once it is recopied, the replicating polymerase develops transition mutations, where a U nucleotide is converted to a C and a C to U. When enough copying errors occur, the virus is essentially killed off, unable to replicate any further which shortens the length of a person’s infection, and limits onward transmission. If administered prophylactically, it may prevent an infection from ever taking hold. Molnupiravir comes with some important caveats. First, is the potential for resistance, if administered as a monotherapy. This, as we’ve discussed, is common to all antivirals and can be solved through combination therapy. Second though, is its potential to supercharge the creation of SARS-CoV-2 variants if administered in suboptimal concentrations. If rolled out globally, the possibility that not all individuals will take the full five-day course of treatments is very real. It’s possible that at these suboptimal concentrations, the 1471
drug may introduce mutations in SARS-CoV-2 that drastically change how the virus operates, but doesn’t necessarily stop it from replicating. That could lead to new and potentially more virulent variants. Third, and perhaps most importantly, is its potential mutagenicity in human beings. A study published earlier this year finds that, once inside a cell, the active form of molnupiravir may be both genotoxic and mutagenic to our own healthy cells, potentially leading to the growth of cancerous tumors or birth defects, either in a developing fetus or by being incorporated into sperm precursor cells. We know less about the potential red flags with Pfizer’s drug candidate, which targets the protease instead of the polymerase, blocking the activity of the main enzyme that SARS-CoV-2 needs to replicate and preventing the virus from cleaving long protein chains into the parts it needs to reproduce itself. But we know, at the very least, that it will run into the same challenge as all antivirals if administered as a monotherapy, which is resistance. Focusing COVID antiviral drug development solely on the protease and polymerase is short-sighted at best and likely to lead to new variants that are more resistant to these drugs’ effects. The good news is that SARS-CoV-2 offers us a wealth of other exciting drug targets, just like HIV. The image of the SARS-CoV2 genome below shows some of the targets that should be considered for antiviral drug development. NSP 1, for example, is the first protein made and performs critical functions in virus replication by interacting with a very specific RNA, making it a very desirable target. NSP 3 has at least seven different enzymatic functions and inhibition of any one of those functions should inhibit virus replication. It is a target-rich environment, including an ADP-ribosylation site and a papein protease site. Below is a chart that highlights some of the key proteins, their function, and critical antiviral drug development strategies (see page 48). Our years of research and exploration on other infectious diseases like HIV have taught us what works and what doesn’t when it comes to antivirals. With influenza, we have done what we should be doing for COVID-19: deploying antivirals in combination with vaccines to create multiple rings of protection around those at risk of infection. The newer oral antivirals for flu, like baloxavir marboxil, 1472
can significantly reduce transmission of influenza among people living in the same house, meaning that even if one person in a household or communal living space falls ill, they can continue living in the same environment without necessarily infecting those around them. This should be the same focus for COVID drug makers moving forward: continue to improve the quality and durability of our vaccines while developing combinations of antiviral drugs focused on a much wider array of targets, thus ensuring their safety and sustainability over the long term. This can’t be done in a vacuum, however. The efforts of the global research community— universities, research institutes, and biotechnology and pharmaceutical companies—should now expand to include a heavy focus on antiviral drug development, something that can only be done with focused funding and government leadership. The magic drug combination may come from the work of multiple labs, not one single company, and the government is the natural entity to accelerate research and coordinate clinical trials and testing of potential drugs. This was the approach that eventually led to our success against HIV and has become routine for other diseases like cancer. If we are successful with COVID-19, we will not only have created another powerful tool to control this pandemic—alongside vaccine and public health control measures—but we will have laid the groundwork for a more rapid response against future emerging infectious diseases.
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This article originally appeared in Clinical OMICs, and can be read online here: Can Our Success with HIV Serve as a Guide for Antiviral Drug Development for Covid-19?
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Omicron Origins
Forbes | December 2, 2021 | Article
The advent of Omicron is ample evidence that we are not yet done with Covid, and Covid is not yet done with us. To look forward and understand where the virus is heading, we need to understand the origin of Omicron. One thing we can be relatively certain of: where this variant came from, more will come. To begin, Omicron is a variant like no other currently in circulation. Omicron is unlike any other variant currently in circulation. The variant carries 60 (50 nonsynonymous, 8 synonymous, and 2 noncoding) mutations compared to the original Wuhan strain. The three most likely origin are stories are that Omicron emerged from an immunocompromised patient; that it emerged from reverse zoonosis — human to animal transmission followed by animal to human transmission; or that it emerged from treatment of a Covid-19 patient with the mutagenic drug molnupiravir. Here we explore the evidence supporting each hypothesis. An immunocompromised patient Viral variants are well documented to arise in persistently infected immunocompromised Covid-19 patients treated by antiviral drugs and antibodies — the London patient, the Boston patient, Pittsburgh and Italian patients. In the face of our best weaponry of the time, the virus not only prevailed but became ever stronger, learning how to evade our immune defenses. The variations that evolved and emerged from these patients had a wealth of mutations, not just in the spike protein but throughout the entire genome. In the London patient, researchers found an H69-70 deletion in the N-terminal domain of the spike. The Boston patient showed instances of the E484K spike mutation. The Pittsburgh and Italian patients showed far more deletions in the viral genome than any seen to date and in places that were as yet unexpected — including a wealth of mutations in the spike’s N1475
terminal domain and in other proteins, including ORF1a and the N protein. Omicron carries some mutations identical and others similar to those found in these patients. Omicron could quite conceivably be the latest in this long line of such variants. Reverse Zoonosis The next hypothesis to consider is that this particular variant evolved from a reverse zoonotic event. Most are now agreed that SARS-CoV-2 originated in bats, a reservoir for a diverse array of coronaviruses. The theory with Omicron is that a human strain of the virus jumped back into animals and then re-emerged from that animal to infect humans again. The likelihood that this may have occurred is entirely plausible, and may indeed be probable. Since its emergence, this particular coronavirus has infected our entire biosphere, from minks and mice to deer and rats, not to mention our own selves. In each of these animal populations, just like in humans, the virus has evolved and adapted to immune pressure, so far surviving in each population to infect and reinfect. As an example, a virus transmitted back to humans from minks contained the troubling new spike protein N501K, also present in Omicron. A study of the sewage waste in New York City gives us a hint of just how prevalent infection and mutation is across animal species. The New York research, conducted across 14 of the city’s wastewater treatment plants, was originally aimed at exploring human sewage for signs of the virus, but the researchers found four new combinations of viral mutations that had never been seen in humans. These variants were somewhat resistant to human antibodies, which meant that if the variants were to infect humans, they would likely prove harder to neutralize than previously known strains. Marc Johnson, the lead investigator on the project, believes the evidence points not to a human but rather to an animal reservoir for these viruses, most probably rats or possibly dogs. A closer look at the mutations in the Omicron variant and those seen in rats suggest there may be a link (see Image 1). Omicron shares numerous identical and non-identical mutations within the N and S proteins with the wastewater viruses, including 13 amino acid changes in the same position or within one amino acid. Some experts
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believe, due to these similarities, that if Omicron evolved in an animal host, it is likely to be a rodent. Molnupiravir-induced The final theory, and perhaps the most troubling one, is that Omicron is a result of our own doing, through the treatment of a Covid-19 patient with the highly mutagenic antiviral drug molnupiravir. Molnupiravir works by introducing errors into the virus’ genetic code. When enough errors are introduced, virus replication slows and the patient clears the virus. Under less than ideal conditions — when the full dose of molnupiravir is not taken over the full period of five days, for example — the drug could lead to the creation of highly mutated, but viable, strains of SARS-CoV-2. Even under ideal conditions, patients treated with molnupiravir produced viable virus a few days into their course of treatment. The extent of the mutations which appeared due to molnupiravir are significant. In the FDA analysis of Merck’s clinical trial results, the authors note that patients who received molnupiravir showed more viral variation than those who did not, including amino acid substitutions, deletions or insertions in the spike gene, and amino acid changes were scattered throughout the coding sequence. A total of 72 emergent spike substitutions or changes was detected among 38 molnupiravir-treated patients. In South Africa, where Omicron was first detected, molnupiravir has been taken in both ideal and non-ideal conditions. Four different South African locations were used in Merck’s clinical trial of molnupiravir, which began in October 2020. The drug was given to patients at what we now know to be the “optimal” dosage, but also at lower doses to test the drug’s efficacy in smaller amounts. There is by no means a foolproof connection between molnupiravir and Omicron, but molnupiravir is known to induce a preponderance of two types of mutations: cytosine to uridine (C→U) and guanosine to adenosine (G→A). If you look at the difference in the Omicron genome and the original Wuhan variant, these C→U and G→A mutations comprise the majority of differences, with C→U mutations more prevalent to G→A. The same has been observed for molnupiravir-induced mutations in other coronaviruses (see Figure
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below). Agostini et al. note that exposure to molnupiravir resulted in up to 162 mutations in MHV and 41 mutations in MERS-CoV.
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AGOSTINI ET AL.
(A) SARS-CoV-2 genome with wastewater variant mutations observed by Johnson et al. noted as black ... [+] AGOSTINI ET AL.
There is still much more study to be done before we will know with any degree of certainty which of these three scenarios led to Omicron’s evolution. But we know enough today to make a few assumptions and assertions. First, until we can say with certainty that molnupiravir did not and could not create a highly infectious and highly mutated variant like Omicron, it should be pulled from the market and any debate over approval of the drug should be paused. 1478
Second, we need to finally acknowledge the broad range of tools known and unknown that this virus has at its disposal, across its viral genome. While Omicron may be bad, future variants could be far worse. The United States and many other countries are still far behind where they should be when it comes to testing and genomic sequencing of viruses in circulation among humans and in other populations. Until we do better on this front — until we understand what the virus has already achieved and how it succeeded — we will never have a full understanding of what more this virus can do and what is ahead in this pandemic. Omicron tells us that now, more than ever, we need to institute a systematic multimodal approach to Covid control, including public health measures, vaccines, therapeutic and prophylactic drugs, and collaborative global engagement. This article originally appeared on Forbes and can be read online, here: Omicron Origins
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Buckling Up for Omicron
Project Syndicate | December 3, 2021 | Article
Although widespread vaccination against COVID-19 remains the top priority, the emergence of the Omicron variant indicates that additional lines of defense are needed. The most promising complement by far lies in new-generation monoclonal antibody treatments. BOSTON – As yet another new SARS-CoV-2 variant emerges and begins to spread – one with a worryingly large set of mutations that may make the virus more capable of evading our immune defenses – we are all being forced to reassess the strategies we have come to rely on for protection. Instead of relying on a single layer of protection, we should adopt a “belt-and-suspenders'' approach. Vaccines remain the primary ring of support – the belt keeping our protective pants on straight. But we would do well to add a set of suspenders for additional support, just in case the belt breaks under mounting pressure from the virus. Based on what we know, our best bet lies with the wider use of monoclonal antibodies for early treatment of COVID-19 and for long-term prevention and protection from the disease. To see the importance of this approach, imagine a long-term care home in which one resident tests positive for COVID-19, or a ship or submarine at sea, where there would be no possibility of relief from continual and intense exposure in the event of an outbreak. If the people in these congregate settings were immediately administered a single dose of monoclonal antibody treatment, the odds of an infection in that group leading to severe disease would be reduced by up to 70%. And beyond protection from disease, the single dose would also have a powerful preventive effect for future infection, providing ongoing protection for up to eight months (depending on the therapy used). As is the case for most antiviral drugs, monoclonal antibodies will need to be tailored to counter the particular strains circulating at any given moment. But the benefit remains: a single dose could protect 1480
people for up to eight months with no additional pills and no additional doses required. Consider what this intervention could mean for all the people in congregate living settings or at higher risk of severe disease. If you are older, morbidly obese, immunocompromised, or unable to mount an immune response after vaccination, new data show that you are much more likely than your healthier, vaccinated counterparts to have not only a breakthrough infection but also a more severe illness. This single injection could still save you. Moreover, we already have a very good understanding of the potential adverse effects of monoclonal antibody treatments. All are manageable, which is more than can be said of the antiviral pill molnupiravir, which is currently before the FDA for emergency-use approval. Its potential side effects, heatedly discussed among the FDA experts who issued a very narrow approval, include potential birth defects and the possible mutagenesis of the virus itself, essentially supercharging the virus’s ability to create highly mutated variants. The side effects of other pills awaiting further study are still unknown. The challenge with applying the belt-and-suspenders approach in the past has been the cost of production and the burden of delivery of first-generation monoclonal antibodies. Initially, the therapies could be administered only intravenously, in a clinical setting, over a period of hours. To be effective, the dose needed to be delivered shortly after symptoms appeared and before severe illness set in. Between the high costs and the extra administrative demand placed on overburdened health-care systems, this treatment option simply could not have been applied broadly as a preventive tool. Instead, it was limited to the select few who could both afford and access the required facilities. But now there is a new generation of antibody treatments that can be administered by injection in a nonclinical setting, at a cost of roughly $400 per gram (according to my conversations with Indian manufacturers of monoclonal antibodies). At that price, a single dose should cost no more than $500 (while still allowing room for profit). Admittedly, $500 is a relatively steep price if the treatment is used broadly as a means of prevention. Nonetheless, it is far lower than the thousands of dollars a single IV infusion costs, and it pales in comparison to the cost of caring for a person hospitalized with 1481
COVID-19. Either way, these treatments offer a compelling return on investment. What we need now is the same kind of rapid mobilization that delivered safe and highly effective COVID-19 vaccines in record time. That feat was made possible by a coordinated effort between government, global pharmaceutical manufacturers, and health-care payers to streamline the supply chain, improve the speed of delivery, and ensure affordability and accessibility for all those potentially in need. This article originally appeared in Project Syndicate, and can be read online here: Buckling Up for Omicron by William A. Haseltine
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Brain Fog and Seizures: Is Covid-19 to Blame? Forbes | December 8, 2021 | Article
Since the beginning of the Covid-19 pandemic, there have been reports of patients with symptoms related to the nervous system and the brain. These neurological symptoms have been observed both during and after infection, and can range anywhere from fatigue and “brain fog” to seizures and strokes. In many instances, the underlying mechanisms aren’t yet fully understood. A recent report by an international group of researchers, led by Jan Wenzel, Josephine Lampe, and Helge Müller-Fielitz at the University of Lübeck, Germany, begins to provide some answers. Their findings are twofold: first, they show that Covid-19 patients display structural damage to the small blood vessels of the brain and, second, they propose that this is caused by the main protease of SARS-COV-2, Mpro, killing endothelial cells. All of our blood vessels are lined with a thin layer called the endothelium. This layer helps regulate what enters and leaves the bloodstream. Endothelial cells also play an important role in the formation of blood vessels, providing signals that help build the blood vessel walls. As a result, endothelial cell death can bring about something known as “string vessels.” These are dysfunctional remnants of capillaries that cannot sustain blood flow. High levels of string vessels are often an indicator of some kind of brain pathology. To test the association between string vessel buildup and Covid19, Wenzel et al. studied the frontal cortex of 17 people, all over the age of sixty, who had passed away from the illness. They compared these brain samples to those of 23 control subjects, of similar age, who had died of other, non-Covid-19 causes. As predicted, the researchers noticed a significant increase in string vessels in the SARS-COV-2 infected patients, an increase that remained even after adjusting for comorbidities and sex. The same held true in mice and hamster models (Figure 1).
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FIGURE 1. Significantly more string vessels (yellow arrowheads) in SARS-CoV-2 infected mice and ... [+] FROM: “THE SARS-COV-2 MAIN PROTEASE MPRO CAUSES MICROVASCULAR BRAIN PATHOLOGY BY CLEAVING NEMO IN BRAIN ENDOTHELIAL CELLS” WENZEL ET AL., 2021
The researchers also found cells, in the microvessels of the brain, that expressed active caspase-3. When a cell dies or has been damaged beyond repair, it has to be broken down and gotten rid of. This process is called apoptosis. Caspase-3, an “executioner” caspase, plays a vital role in this process by breaking down cell structures. The presence of caspase-3, then, supports the notion that string vessels form as a result of endothelial cell death. 1484
So, there’s evidence of both “string vessel” formation and endothelial cell death in the brains of Covid-19 patients, but how is SARS-CoV-2 causing this? Wenzel et al. first turned to the brain endothelial cells themselves; given that these showed signs of cell death during infection, it would suggest that they were possibly getting infected by SARS-CoV-2 directly. A good way of checking if infection is even possible is by looking for the proteins that SARS-CoV-2 uses to bind to, and eventually enter, our cells. And, although being mainly located in other parts of the blood vessels, the researchers did, in fact, find the requisite proteins to be expressed in brain endothelial cells. Illustrating that, at least in principle, infection by SARS-CoV-2 can occur. Moving from principle to practice, Wenzel et al. decided to expose an in vitro model of cultured brain endothelial cells to SARSCoV-2. Indeed, the researchers soon located SARS-CoV-2’s Spike (S) protein —used by the virus to bind to host cells— around the nuclei of the endothelial cells. But the question still remains, through what mechanism does SARS-CoV-2 bring about endothelial cell death? Here Wenzel et al. turned to a protein called NF-kappa-B essential modulator (NEMO). NEMO plays a key role in activating NF-kappaB, which itself plays a key role in regulating the immune response to infection. Importantly, NEMO is also integral to the survival of some cells. Insofar as SARS-CoV-2 is always trying to stay ahead of our immune response, the researchers hypothesized that it might “cleave,” and thereby inactivate, NEMO to buy itself more time. It’s possible, they thought, that brain endothelial cell death could arise as a byproduct of this immune-suppression tactic. Confirming part of their hunch, the researchers saw an increased presence of cleaved NEMO in the brain cells of SARS-CoV-2infected patients, as compared to the control group. Next, suspecting this might have something to do with proteases, Wenzel et al. exposed mouse-derived brain endothelial cells to two SARS-CoV-2 proteases: main protease (Mpro) and papain-like protease. Sure enough, it turned out that Mpro cleaved NEMO in mouse brain endothelial cells. The same held true for NEMO in human brain endothelial cells. 1485
Not yet satisfied, Wenzel et al. also wanted confirmation that NEMO cleavage actually brings about endothelial cell death. To do so, they inserted Mpro into human brain endothelial cells. As expected, these cells more frequently presented markers indicative of cell death than did those unexposed to Mpro. Endothelial cells exposed to an inactivated form of Mpro, in contrast, were spared NEMO cleavage and subsequent cell death. The nail in the coffin: within a period of two weeks, live mice exposed to Mpro developed string vessel pathology indistinguishable to that of the Covid-19 patients. Those exposed to the inactivated Mpro were completely fine. But, there’s some good news as well. Wenzel et al. discovered that NEMO cleavage induces endothelial cell death through an enzyme called RIPK3. When this enzyme is “knocked out,” endothelial cell death is prevented and, as a result, microvascular pathology is avoided. This opens the door to new treatments and interventions, ones that could help stave off the neurological symptoms reported by a rapidly-growing list of Covid-19 patients. This article originally appeared on Forbes and can be read online here: Brain Fog and Seizures: Is Covid-19 to Blame?
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Omicron: The Sum Of All Fears! Forbes | December 8, 2021 | Article
This is the first of a two-part series. Here we describe the mutations in the Omicron Spike protein. In part two, we will describe mutations in other parts of the genome. A new variant, Omicron, very effectively evades the neutralizing antibodies of the Pfizer vaccine regimen, according to a recent study. The research by Cele et al. demonstrates that neutralization protection dropped over 40-fold against the Omicron variant as compared to the D614G Triad strain. This includes those with the highest protection, having been previously infected and then twodose vaccinated with the Pfizer vaccine. In other words, a two-dose regimen of the Pfizer vaccine will not protect against Omicron. A recent press release by Pfizer claims three doses offer significant protection, though this claim is presented without data. Until more data is available, we speculate that three doses will still be insufficient in protecting against this new variant.
FIGURE 1: Neutralization of Pfizer/BioNTech vaccine for Omicron variant compared to D614G (Triad) ... [+] CELE ET AL.
The Omicron variant has the potential to spark the next great wave of SARS-CoV-2. Dozens of countries are on high alert as Omicron sequence detection is rapidly increasing. Case numbers are
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expected to rise dramatically in the coming days and weeks. See the rise of the Omicron variant in South Africa and globally below.
FIGURE 2: Distribution of SARS-CoV-2 infections by major variants of concern globally and in South ... [+] STEBBING
How does Omicron evade vaccine neutralization? The variant carries at least 50 amino acid-altering mutations and at least 10 silent mutations in coding and non-coding regions. At least 36 of these mutations are found in the Spike (S) protein, which is a major modulator of infectivity and immune evasion. Many of these mutations are shared with other major variants of concern or interest and have been previously shown to increase infectivity and decrease recognition by vaccine-administered and monoclonal antibodies. Other mutations are unique to this variant. All of which may contribute to the increased functionality of the virus. Early returns on transmissibility, including the rate of virus replication, suggest it is high. Omicron is outpacing many earlier variants in terms of new infections, such as the Beta and Delta variants described below.
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FIGURE 3: Incidence of ASRS-CoV-2 infections by variant of concern. Note the rapid rise of Omicron ... [+] STEBBING
Omicron additionally shares several amino acid mutations with other major variants, described in the figure below. Here we are going to focus on the S protein. In the second part of this two-part series, we will discuss the interaction of non-S proteins and their contributions to Omicron’s enhanced virological characteristics.
FIGURE 4: Amino acid mutations in Omicron. Those in boxes are shared with the respective previous ... [+] ACCESS HEALTH INTERNATIONAL
Spike Protein (S) 1489
The SARS-CoV-2 S protein binds the host ACE2 receptor and initiates infection. The Omicron variant S protein is heavily mutated as compared to other major variants. It contains a staggering 36 amino acid-altering mutations, 23 of which have been previously observed in other variants. We call this the sum of all fears because Omicron contains almost all of the S protein mutations that resulted in previous variants of concern, plus a large complement of its own.
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FIGURE 5: Omicron Spike protein mutations. (A) Those in red have been previously identified in other ... [+] ACCESS HEALTH INTERNATIONAL
The first major domain in the S protein is the N-terminal domain. This domain is a target for both binding and neutralizing antibodies in convalescent sera and monoclonal treatments. Deletions are often found in the N-terminal domain, usually indicating the destruction of a binding site, meaning the variant becomes more resistant to antibody binding. There are six deletions in the Omicron variant: 69, 70, 143, 144, 145, and 211. The most likely explanation for these deletions is immune evasion. The only deletion unique to Omicron is 211, whereas all others are found in other variants such as Alpha, Gamma, or Delta. There are two potential explanations for the same mutations occurring in multiple strains. One is convergent evolution, in which strains develop the same mutation independent of each other, and the second is recombination, where two strains exchange genetic 1490
material during some cross-infection event. In other words, it is possible Omicron picked up the deletions from another variant during its evolution. Other mutations in the Omicron N-terminal domain include A67V, which was previously observed in the Eta variant originating in Nigeria, T95I, previously observed in the Iota variant originating in New York, and G142D, observed in the pervasive Delta variant. Because these mutations appeared in regional variants all over the world independently, we hypothesize they have some significant effect on the binding capability of antibodies, meaning Omicron has the potential to be highly resistant to antibody treatment. Additionally, there is an insertion at position 214 which adds three amino acids to the genome. Some have speculated that this insertion is related to recombination with human cold-causing coronaviruses, specifically HCoV-229E. We offer a more likely alternative, suggested by Dr. Roberto Patarca, which is that the change is potentially due to internal recombination and translocation of a segment in the (-) strand of the 5’-untranslated region (UTR) of SARS-CoV-2 that would also explain other insertions at the same position 214. We note that this is a frequent site for insertions in other viruses.
FIGURE 6: Internal recombination and translocation of a segment in the (-) strand of the ... [+] ACCESS HEALTH INTERNATIONAL
The receptor-binding domain is the other major domain of note in the S protein. This is the region that makes direct contact with the host ACE2 receptor and plays a major role in transmissibility. The Omicron receptor-binding domain contains 15 amino acid substitutions, 11 of which have been previously noted in other variants.
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Among the most concerning receptor-binding domain mutations found in Omicron are E484A, N501Y, S477N, and K417N. All of these have been previously observed in major variants of concern like Alpha and Delta. More interesting, however, is the overlap between some Omicron mutations and mutations found in wastewater variants in New York City. The collective mutations are noted to increase the overall positive charge of the receptor-binding domain, yielding salt bridges that boost ACE2 binding affinity. In our previous article on Omicron’s possible origins, we noted the potential of cross-species infection of SARS-CoV-2 resulting in new and aggressive mutations. One study by Johnson et al. revealed dozens of mutations found in wastewater samples likely originating from rats or dogs. Several mutations found in those samples are in positions mutated in Omicron, including K417N, N440K, S477N, E484A, G496S, Q498R, N501Y, and others. This mass overlap may indicate that Omicron may have formed some or all of its mutations in a non-human animal before reinfecting human populations in Africa. With respect to mutations falling outside the receptor-binding and N-terminal domains, there are those that fall near the furin cleavage site. Omicron shares a number of furin cleavage region mutations with other variants of concern and interest. T547K, H655Y, N679K, and P681H all play some role in boosting the efficiency of furin cleavage, which is a function of some viruses to cleave the S protein into two subunits, boosting transmissibility. These mutations have been previously observed in the Alpha, Gamma, Delta, or wastewater variants. A number of mutations occur in the S2 subunit. These are N764K, D796Y, N856K, Q954H, N969K, and L981F. This region is critical for pre-and-post-fusion structures. It is likely that these mutations could contribute to increased infectivity by facilitating S protein fusion. Lessons One lesson to learn from Omicron is that there is a much wider range of variations for naturally-occurring strains in human populations. Omicron is very unlikely to be the last heavily mutated variant of concern. We should be prepared for that eventuality. 1492
Another lesson is that we need to attempt much more research on the origins of variants. Finally, we need to carefully characterize more than just individual proteins. In the second part of our Omicron discussion, we will examine the rest of the viral proteins and how mutations outside the S protein are just as important to analyze in reference to their impact on virulence and pathogenesis. This article originally appeared on Forbes and can be read online here: Omicron: The Sum Of All Fears!
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What Is The Meaning Of Omicron? Forbes | December 9, 2021 | Article
The data on Omicron is still too sparse to allow us to make clear predictions on the exact nature of this new variant, but we know enough about this strain to understand its essential meaning. Omicron is sending a message, loud and clear: this virus is capable of far more changes and far more variation than most ever thought possible and it will keep coming back to haunt us again and again. From an evolutionary biology point of view, Omicron was to be expected. Coronaviruses in general have adapted to develop a wide variety of strategies to continue their replication and to infect and reinfect multiple species over millions of years. Coronaviruses evolved in bats and other long-lived, highly immunocompetent creatures. To survive, the virus had to learn a wealth of tricks — dampening immunity, evading early immune defenses, and shapeshifting to allow for multiple reinfections. Bats, in behavior at least, are a species quite similar to humans, living in densely packed communities but able to travel from one community to another, interacting with other animals and species along the way. Coronaviruses have learned how to thrive not only in a host species but how to infect neighboring species as well. At least seven coronaviruses have made the jump from animals to humans, but SARS-CoV-2 has shown that it can make the jump back into animals to reemerge and invade us again — a process called reverse zoonosis. But that’s not all this virus can do. If we look closely at the genomes of the coronaviruses that have emerged from bats and other species, we see that these viruses can readily recombine amongst each other, in addition to the point mutations we have seen in Omicron and in other known SARS-CoV-2 variants. Recombination, we know from influenza, can lead very quickly to much more virulent variants by picking up components that our immune systems have not previously seen. While the world is now appropriately concerned about Omicron, many continue to overlook what more this virus may 1494
have in store for us. The variations we have seen in SARS-CoV-2 variants across the viral genome show us that this virus has many more tools still at its disposal to increase infectivity. Changes to the regulatory proteins can increase the virus’ ability to suppress our immune system. Mutations in structural and non-structural proteins can help the virus increase its ability to replicate. Changes in the spike, as we’ve already seen, can increase its affinity and allow it to bind more easily to our cells. I believe we can expect a continual barrage of variants for the indefinite future unless we are able to bring this virus under control through a systematic application of public health measures and medical interventions, including vaccines, drugs, and diagnostic tests. I’ve written numerous times about a multimodal approach to Covid control but I fear, still today, not enough countries are taking heed. Our first and best line of defense has and will always be public health, which requires leadership and a culture of understanding and acceptance of tough measures when the situation dictates. Widespread testing, at home and in all public spaces like schools, businesses, and major public events is a basic necessity, which must be tied to rigorous contact tracing and notification of those exposed. When new outbreaks occur, stringent public health measures need to be enforced to control the virus spread: mask-wearing, improved ventilation, social distancing, mandatory quarantine and isolation, and — as challenging as they may be — even lockdowns if necessary. China has proven that this approach can work against the original virus and every known variant. Beyond public health, we have our vaccines — the full threedose regimen of top-of-the-line mRNA vaccines. Even if they cannot neutralize a new variant like Omicron completely, they will still offer some degree of added protection and, in those who mount a particularly robust antibody response, that protection may still be quite high initially. But beyond vaccines, whose potency will no doubt fade against some variants and may fade quite considerably for all variants over time, we need other protections. Right now, our best bet lies with the wider use of monoclonal antibodies for early treatment of COVID-19 and for long-term prevention and protection from the disease. The latest generation of these therapies can be administered
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by injection after exposure to Covid-19 or shortly after symptoms first appear. One single dose of monoclonal antibodies could not only prevent someone infected from a severe case of Covid, but it could also prevent that person from becoming infected again, for up to eight months potentially. Consider what this could mean for longterm care centers, naval ships, or people living in university dorms — if one person in your residence fell ill, all others could take a shot to prevent themselves from getting Covid and from spreading it to others. Eventually, oral antivirals may be used in place of an injection, but for now, we know too much about the dangers of molnupiravir, the antiviral drug currently being considered for approval, to allow for its widespread use. It may not seem like it today, but we do have the tools at hand to control the trajectory of this pandemic. The challenge, from the very beginning, has been in not using them as effectively and rigorously as needed. This article originally appeared on Forbes, and can be read online here: What Is The Meaning Of Omicron?
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FDA Approves Anti-SARS-CoV-2 Monoclonal Antibodies For The Vaccine Insensitive Immune Suppressed Population Forbes | December 10, 2021 | Article
Immunocompromised Americans who are not adequately protected by their Covid-19 vaccination series will now have an additional option for long-term protection in the form of an antibody cocktail drug developed by AstraZeneca. Antibody drugs have been a standard treatment for Covid-19 infections for over a year, but the AstraZeneca drug is the first intended for long-term prevention against COVID-19 infection, rather than short-term treatment. This development demonstrates the potential for monoclonal antibodies to be used in tandem with vaccines for the strongest possible long-term protection against this ever-evolving virus. The FDA has issued an emergency use authorization for AstraZeneca’s drug which will be sold as Evusheld. The drug is a cocktail of tixagevimab co-packaged with cilgavimab and administered together and is authorized for the pre-exposure prophylaxis of Covid-19 in adults and children 12 and older whose immune systems haven't responded adequately to COVID-19 vaccines or have a history of severe allergic reactions to the shots. The drug is given via an intramuscular injection. Specific groups who could benefit from the antibody drug include cancer patients, organ transplant recipients, elderly populations, and people taking immune-suppressing drugs for conditions like rheumatoid arthritis. A study published earlier this year found that out of 3 million insured Americans, 2.8% were taking immunosuppressant drugs. The US has a contract with AstraZeneca to purchase up to 700,000 doses of the treatment which will be allocated proportionally to states and distributed at no cost within the next few weeks. Yet the decision by AstraZeneca to price the drug 1497
commercially while negotiating contracts with governments around the world during the pandemic will broadly constrain the effectiveness of the drug and create issues of equity. Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses. Tixagevimab and cilgavimab are long-acting monoclonal antibodies that are specifically directed against the spike protein of SARS-CoV-2, designed to block the virus’ attachment and entry into human cells. Tixagevimab and cilgavimab bind to different, non-overlapping sites on the spike protein of the virus. AstraZeneca tested the Evusheld drug in approximately 5150 adults who were older than 59, had a prespecified chronic medical condition or were at increased risk of Covid infection in a randomized, double-blind, placebo-controlled trial. In the primary analysis, those who received the drug saw a 77% reduced risk of developing Covid-19 compared to those who received a placebo. In further analyses, the reduction in risk of developing Covid-19 was maintained for drug recipients through six months. Evusheld has not presently been authorized for the treatment of post-exposure prevention of Covid-19. But it is important to ask why and continue to collect data on how monoclonal antibodies can be used prophylactically in high-risk congregate settings such as nursing homes, prisons, and military ships. We also need greater research into how antibodies can match the variant in circulation. Although widespread vaccination against Covid-19 remains the top priority, the emergence of the Omicron variant highlights that additional lines of defense are needed. This article originally appeared on Forbes, and can be read online here: FDA Approves Anti-SARS-CoV-2 Monoclonal Antibodies For The Vaccine Insensitive Immune Suppressed Population
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Omicron: The Sum Of All Fears! Part 2 Forbes | December 10, 2021 | Article
This is the second of a two-part series. In part one, we described the mutations in the Omicron Spike protein. In part two, we will describe mutations in other parts of the genome. The Omicron variant has the potential to drive the next major wave of the pandemic. The figure below illustrates the rapid rise of Omicron in South Africa. Omicron contains at least 50 amino acid mutations and roughly ten non-amino acid-altering mutations, some of which may be in regulatory sequences. Depending on how they are counted, there are at least 36 amino acid changes in the Spike (S) protein alone. These changes likely account for the decreased sensitivity of Omicron to existing protective antibodies, either via previous infection or vaccine. These changes also account for increased infectivity by increasing the affinity of the S protein to the ACE2 receptor, as well as increasing the efficiency of viral entry in the form of membrane fusion. Here we discuss the potential implications of the mutations that occur outside of the S protein, which also have the potential to increase the transmissibility, immune evasion, and virulence of Omicron.
FIGURE 1: Incidence of SARS-CoV-2 infections by variant of concern. SALIM KARIM
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There is increasing evidence that mutations outside of the S protein determine the biological properties of the virus. A recent paper by Syed et al. describes a set of mutations in the Nucleocapsid protein within the Delta variant, as well as many other variants of concern, which increases the ability of the virus to replicate, at least in cell culture. A more recent paper analyzed the entire viral genome in terms of potential contributions to transmission characteristics in variants of interesting concern. Garvin et al. pioneered methods to understand interactions of multiple genes and how they can contribute to an inherited viral trait in many species. An observed trait may be the result of the interaction of changes in two or more genes simultaneously—a phenomenon called epistasis. This process has previously been evoked to understand the properties of the SARS-CoV-2 S protein. For example, one mutation in the S protein may contribute to immune evasion, but decrease affinity. A second mutation is the same gene that can make up for that deficit by increasing affinity. The net effect of these two changes would be to create an S protein with both increased immune evasion and increased transmission. Such theoretical analysis of variants of concern prior to the discovery of Omicron highlighted epistatic changes common to major variants. The genes that have been implicated in improving the transmissibility of various concern in Garvin et al.’s analysis include the S protein, NSP6, and NSP13. There are likely other genes involved as well. Additionally, Kroger and colleagues found that Delta variant mutations in Orf6, Orf9b, and N result in overexpression of those genes. They show that this overexpression, along with S protein mutations, contributes to the ongoing success of the Delta variant by improving the virus’s suppression of the innate immune system. It is with that background that here we examine the full range of changes outside of the S protein. The Triad Omicron, like almost all other variants with the exception of some East African strains (A.30 and A.23.1), stems from the first major variant of SARS-CoV-2, which we call The Triad and others call D614G. This variant includes the well-known D614G mutation 1500
in the S protein, the P323L mutation in the NSP12 polymerase, and the C241U nucleotide mutation in the 5’ untranslated region. The D614G mutation increases the infectivity of the virus by increasing the affinity between the S1 and S2 subunits post-cleavage and increasing “up” formation efficiency of the receptor-binding domain. The C241U mutation in the 5’ UTR does not affect protein sequences, however, it creates a cellular RNA binding site for a cellular TAR binding protein known to affect RNA metabolism, including transcription and translation efficiency. The role of the P323L mutation is currently unknown, but its conservation suggests some impact on virus replication.
FIGURE 2: Triad mutations D614G in the S protein, P323L in NSP12, and C241U in the 5’ UTR. ACCESS HEALTH INTERNATIONAL
FIGURE 3A: Amino acid mutations in Omicron. Those in boxes are shared with the respective previous ... [+] ACCESS HEALTH INTERNATIONAL
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FIGURE 3B: Non-Spike Amino acid mutations in Omicron. Those in boxes are shared with the respective ... [+] ACCESS HEALTH INTERNATIONAL
The above figures highlight why we designate Omicron as a sum of all fears, as it is clear from the overlap of mutations that Omicron contains many of the most troubling mutations found in previous variants of concern, as well as many unique mutations of its own in both the S and non-S proteins. In Omicron, there are ten synonymous mutations not resulting in an amino acid change. In SARS-CoV-2 analysis, there has been a tendency to ignore the potential of mutations in non-proteincoding regions, including the C241U mutation present in the Triad. Of the ten synonymous changes in Omicron, all but C241U are unique. However, such changes may affect what are called cis-acting regulatory sequences by altering structures and key recognition sequences in viral RNA required for replication, transcription, and translation. For example, Thorne et al. point out that overexpression of the N and Orf9b mRNA and proteins in the Alpha variant might be attributed to these synonymous and non-coding mutations. These may change consensus ribosome binding sequences, transcription regulatory sequences, and other structures potentially affecting gene expression and overall biological properties of the virus. In some
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cases, these changes may even lead to novel sets of functional RNAs, proteins, and peptides.
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FIGURE 4: Mutations found outside the S protein in the Omicron variant. Those in italics are ... [+] ACCESS HEALTH INTERNATIONAL
Non-Structural Proteins (NSPs) Most non-Spike proteins lie in the Orf1ab replication complex. This complex is comprised of 16 non-structural proteins. There are 11 mutations in these proteins, seven of which are unique to Omicron. We note that all mutations in Orf1ab are found in Orf1a, with the exception of the Triad mutation in NSP12. The Orf1a proteins are required for the formation of the double-membrane vesicle necessary for virus replication. This observation suggests that Omicron may be more efficient in the formation of the doublemembrane vesicle, in part resulting in increased replicative capabilities. In NSP3, there are four unique mutations. NSP3 is a unique gene with multiple functions. Each function is governed by a separate subdomain. K38R, which lies in the Acidic C-terminal 1503
domain. There is a deletion at position 1265 and L1266I, which lie in the nucleic acid-binding region, and A1892T, which falls outside major subdomains. We note there are numerous wastewater mutations in NSP3, specifically S377I, A465V, K487Q, T820N, D821A, P822G, K977Q, and S1087F. Based on the functions of these subdomains, the Omicron mutations may have some impact on proteolytic processing and nucleic-acid binding efficiency.
In NSP4, there is one unique mutation, T492I, which may be involved in the formation of the double-membrane vesicle. Another unique mutation in NSP5, P132H, may have an impact on the SARS-CoV-2 main protease, which cleaves the polyprotein during replication and transcription. Again, the wastewater variant contains mutations in NSP4 and NSP5, specifically K35R, D217G, and G239S in NSP4, as well as S123C in NSP5. In NSP6, there are a set of deletions between positions 106 and 108 which are common to variants of concern and interest. Specifically, they are observed in Alpha, Beta, Gamma, and many less common regional variants. Additionally, we observe the unique mutation I189V. NSP6 is also involved in the formation of the double-membrane replication/transcription vesicle, and these mutations may play a similar role to the NSP4 mutation. However, NSP6 is also an immune regulator, inhibiting STAT1 and STAT2 activity, binding TANK binding kinase 1, and inhibiting IRF3 phosphorylation. The only other major mutation is P323L in the NSP12 RNAdependent RNA polymerase, which is part of the Triad variant of mutations and is shared among nearly all circulating strains. This is notably the only mutation in Orf1b, the second part of the Orf1ab 1504
replication transcription complex. The speaks to the existing replicative efficiency caused by other mutations in the genome, as Omicron replicates significantly well despite no major mutations in this region. Each of these mutations warrants structural and functional study. As we often note, the S protein mutations are often analyzed with significant depth, but non-S mutations are underexamined. They likely impact virus function in a similar capacity and should be treated as such. Structural Proteins Aside from the NSPs, the SARS-CoV-2 genome also has structural proteins and accessory (regulatory) proteins. Accessory proteins are largely immune regulators, but Omicron lacks mutations in this region, which is interesting as proteins like Orf8 and Orf6 are often heavily mutated, perhaps speaking to the selective pressures of Omicron. The structural proteins include the S protein, Envelope (E) protein, Membrane (M) protein, and Nucleocapsid (N) protein. The E protein is free of amino acid mutations in the Omicron variant. The M protein is a major structural protein in the virus genome, plays a role in RNA packaging, and suppresses the innate immune system via interferon antagonism. There are two mutations in the Omicron M protein: D3G and Q19E. These are unique to the Omicron variant and may have some impact on RNA packaging. The N protein is also multifunctional, including RNA packaging and immune regulation. The Omicron N protein is significantly mutated, including a set of unique deletions and other mutations common to other variants. The unique set of deletions is from positions 31 to 33. Interestingly, Omicron is the only major variant with deletions in the N protein, which may speak to the significant impact of the mutations as either improved replication or immune escape. Omicron also varies the P13L mutation, which was previously observed in the C.27 local to Peru and the C.1.2 first noted in South Africa as well. These mutations are found in the N protein’s N-terminal domain. The final set of mutations to note are the R203K and G204R pair in the N protein. This set of mutations is one of the most 1505
common among naturally occurring variants. The two mutations lie near the center of the linker domain that connects the RNA binding domain of N with the dimerization domain. The change from glycine to arginine at position 204 introduces a positive charge into a region that is predominantly neutral. R203K and G204 were previously observed in the Alpha and Gamma variants of concern, as well as other regional variants such as C.27 in Peru and R.1 in Japan. Recent studies confirm the importance of mutations from N protein positions 199-205. A recent manuscript demonstrates that single point mutations in this region substantially increase the infectivity of the virus, in some cases by over 150-fold. The most likely explanation for both the increased immune evasion and increased replication capacity of Omicron is a synergistic relationship between mutations in the N and S proteins.
FIGURE 6: Subdomains of the SARS-CoV-2 N protein and Omicron variant N mutations. NTD stands for ... [+] ACCESS HEALTH INTERNATIONAL
Conclusions Although the origin of Omicron remains to be determined, it is clear that it has dramatically improved replication properties, which are likely to be due to a combination of epistatic mutations. These 1506
allow the variant to evade the adaptive immune response, suppress the innate immune response, and camouflage itself as it replicates in the double-membrane vesicle. At this early date, Omicron clearly has the potential to trigger a new and dangerous wave of Covid-19 around the world as it is now doing in South Africa. It provides increased impetus to understand the details of the molecular biology of the virus in search of new ways to control the pandemic and prevent and treat SARS-CoV-2 infection. This article originally appeared on Forbes, and can be read online here: Omicron: The Sum Of All Fears! Part 2
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How Omicron Evades Natural Immunity, Vaccination, And Monoclonal Antibody Treatments Forbes | December 17, 2021 | Article
This is the third in our series on the Omicron variant. Find parts one and two here. In a few short weeks, the COVID-19 virus variant Omicron has spread around the world. The incidence of new infections is rising rapidly, even in well-vaccinated populations and those previously infected by earlier variants of SARS-CoV-2. The epidemiologic evidence strongly points to a variant that is resistant to most if not all extant vaccines, and possibly many monoclonal antibodies treatments. Here we explore these concerns. This is the third in our series that outlines what we know about Omicron. We summarize the finding of recent experiments by Cameroni et al. in a bioRxiv preprint from December 14th. Omicron ACE2 Binding The first question asked was how tightly the Omicron Spike (S) protein binds to the ACE2 receptor. The data is summarized in Figure 1. Cameroni et al. show that Omicron’s affinity for the ACE2 receptor is 2.5 times as great as that of the S protein from the original Wuhan isolate. Omicron binds to the receptor as well as the Beta variant, but not as well as Alpha, which binds ACE2 almost six times more tightly. The N501Y mutation in Omicron is universally observed to increase affinity roughly 6-fold, yet other mutations in key sites like K417N, Q493R, and G496S were shown by deep mutational scanning to decrease affinity. Increased affinity for the receptor may account, in part, for increased transmissibility, but that is clearly not the whole story as Omicron is much more transmissible than any previously isolates, including Alpha, Beta, Gamma, and Delta.
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FIGURE 1: ACE2 binding of different SARS-CoV-2 variants. CAMERONI ET AL.
Omicron Host Range They next examined the Omicron host range. The ACE2 receptors of animals differ slightly in amino acid sequences in those regions of the protein which directly interact with the receptorbinding domain of the S protein. To assess the possibility that the extensive variation in the receptor-binding domain might affect the virus host range, the ability of the S protein to bind the ACE2 from three species—mink, pangolin, and mouse—was examined. The data from Cameroni et al. shows that the Omicron S protein binds to the Mouse ACE2, but not to those of mink or pangolin. There was no cross-species binding detected from the Wuhan, Alpha, or Beta isolates. They attribute this cross-affinity to the Q493R mutation in the Omicron receptor-binding domain, which is similar to the Q493K mutation isolated from mouse-derived SARS-CoV2.
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FIGURE 2: ACE2 binding kinetics of different SARS-CoV-2 variants to a mouse and human receptor. CAMERONI ET AL.
ACE2 binding by Omicron prompted us to question the similarity between the amino acid changes that occur when SARSCoV-2 is forcibly adapted for growth in mice. Kuiper et al. identified mutations found in a mouse-adapted SARS-CoV-2 isolate, as summarized in Table 1. Four of the changes found in the mouseadapted virus, Q498R, N501Y, K417N, and Q493R, are also found in the Omicron variant. Position 484 is also mutated, but to a different amino acid: E484A. We also note that many of these mutations are mirrored in sequences pulled from New York City wastewater. Although the origins of the wastewater variants are unknown, one suspected origin is mice. We have previously speculated the possible origin of Omicron lies in reverse-zoonosis. This is the transmission of the virus from human-to-animal-to-human, with significant mutations added during cross-infection. The similarities between Omicron, the mouse-adapted virus, and the wastewater variants add substance to this hypothesis.
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Omicron Convalescent Sera Escape The next question they address is whether Omicron escapes neutralization by convalescent sera. Omicron strongly evades natural infection. Current data suggests that those who have been previously infected have little to no protection against Omicron infection. To analyze the degree to which the highly mutated Omicron escapes vaccine antibody neutralization, Cameroni et al. created Wuhan S and Omicron S pseudoviruses to test against a wide variety of existing vaccines. They tested the pseudoviruses against the sera from patients vaccinated with Moderna’s mRNA-1273, Pfizer’s BNT162b2, AstraZeneca’s AZD1222, J&J’s Ad26.COV2.S, Russia’s Sputnik-V, and Sinopharm’s BBIBP-CorV.
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FIGURE 3: Neutralization of Omicron variant pseudovirus by convalescent and vaccinated sera. CAMERONI ET AL.
In the J&J cohort, no sera samples had neutralizing activity against Omicron. In the Sputnik cohort, only one in the cohort had mild neutralizing activity. And in the Sinopharm cohort, only three had mild neutralizing activity. The data from figure 4 shows that fully-vaccinated sera with the Moderna vaccine saw a 33-fold drop in neutralization against Omicron, Pfizer a 44-fold drop, and AstraZeneca a 36-fold drop. Notably, Recently released data shows that sera from people who received the third dose lost almost ninety percent of its potency against Omicron after two weeks. After three months, most thirddose sera failed to neutralize at all. This data confirms the epidemiological observations that most fully doubly-vaccinated and triply-vaccinated individuals, including those with prior infection, are susceptible to infection by Omicron within three months of the last boost.
FIGURE 4: Neutralization of SARS-CoV-2 Omicron (red) and Delta (grey) variants by different vaccine ... [+] WILHELM ET AL.
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Omicron Monoclonal Antibody Escape There are currently eight approved or emergency authorized monoclonal antibody treatments in circulation. Most of these and other antibodies in development target the receptor-binding domain, and in particular, the receptor-binding motif from positions 437 to 508. In the Omicron variant, there are ten amino acid substitutions in this region of the Omicron S that are likely to reduce antibody binding and neutralization (Figure 5).
FIGURE 5: ACE2 binding map of different monoclonal antibodies. CAMERONI ET AL.
Of the eight approved or authorized antibodies, all but sotrovimab completely or almost completely lost their neutralizing activity against the Omicron pseudovirus. A cocktail of cilgavimab and tixagevimab had a reduced potency of 200-fold. Sotrovimab, conversely, shows a drop of 3-fold drop in neutralization potency. Cameroni et al. also examined a panel of 36 S protein monoclonal antibodies. Four monoclonal antibodies targeted the Nterminal domain, yet none were able to neutralize Omicron. Only three of the 22 antibodies that bind to the receptor-binding motif retained activity including GSK’s S2K146. S2K146 is unique as it makes close contacts with many of the same amino acids as does ACE2 so much so its footprint on the receptor-binding domain closely mimics that of ACE2 itself. Such antibodies may be amongst those preferred for the second generation of anti-SARS-CoV-2 monoclonal antibodies as the virus must bind ACE2 to initiate infection.
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FIGURE 6: SARS-CoV-2 Omicron variant N-terminal domain and receptor-binding domain mutations. CAMERONI ET AL.
We note that Dr. Gideon Schreiber researched the mutated receptor-binding domain to find mutations that would increase the affinity, specifically in ACE2 binding sites. He found mutations that increased the affinity by more than two orders of magnitude. It would seem natural that some of those mutations increase the specificity and affinity of the S2K146 for improved activity and breadth of neutralization. Continuing with the antibody analysis, of the 9 which targeted other areas of the receptor-binding core, only one retained neutralizing activity. Finally, one antibody, S2H97, was capable of neutralizing Omicron significantly and targets a conserved region noted as site V.
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FIGURE 7: (A) Mean Omicron neutralization titers after exposure to monoclonal antibodies and (B) ... [+] CAMERONI ET AL.
In all, most monoclonal antibodies were completely ineffective against the Omicron variant. Some, such as sotrovimab, S2K146, and S2X324 retained neutralizing activity, but at a significant reduction. This points to the immune escape capabilities of Omicron via its distinctly mutated S protein and genome. Conclusion Many seem surprised at the ability of SARS-CoV-2 to mutate to increase resistance against convalescent sera, most vaccines, and most monoclonal antibodies. However, the surprise was unwarranted for those who realized that coronaviruses have evolved over many millions of years to reinfect hosts over time. Those previously infected with earlier strains of the virus, contrary to our 1515
assumptions earlier in the pandemic, are able to be reinfected with Omicron and strains to come. We previously predicted that SARS-CoV-2 would persist, continue to vary, and evade our natural and adaptive immune responses. We have also learned that SARS-CoV-2 has the potential to become far more lethal than it is today. We reiterate that the sister of this virus, SARS-CoV, and its cousin, MERS-CoV, ranged between 10% and 30% lethality. This is presumably due to slight variations in the structural, nonstructural, and accessory proteins. We must be ever alert now and for many years in the future of the possibility of such changes and their consequences. This article originally appeared on Forbes, and can be read online here: How Omicron Evades Natural Immunity, Vaccination, And Monoclonal Antibody Treatments
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Non-Spike Proteins Contribute To Transmission And Virulence Of Sars-Cov-2 Forbes | December 17, 2021 | Article
The success of a SARS-CoV-2 variant depends on many factors, but there are three elements that are particularly crucial: transmissibility, immune evasion, and virulence. Any mutation that productively impacts one of these three factors is a dangerous one. Any variant with higher transmissibility, a better capacity to evade our natural (innate) immunity, or heightened virulence is one to keep a vigilant eye on. More often than not, however, this vigilant eye is reserved for what happens within the spike (S) protein of SARS-CoV-2. Understandable, since the S protein plays a major role in allowing the virus to enter and infect our cells, but perhaps slightly misguided. A new report, led by researchers with the Oak Ridge National Laboratory, prompts us to shift our focus towards the entirety of the viral genome, rather than just the S protein. Applying tools from the field of human genetics, Garvin et al. suggest that mutations outside of SARS-CoV-2’s spike protein may be just as significant as those within. The reason for this? Epistasis. Many traits are polygenic, meaning a variety of different genes all affect the way that trait is eventually expressed. When multiple genes affect the same trait, they can end up interacting with one another in different ways. Epistasis is a kind of polygenic interaction. At its simplest, it’s when the expression of one gene or genetic mutation is modified by the presence of another. By studying a sample of more than 900,000 SARS-CoV-2 genomes, Garvin et al. were able to identify some of the key mutations underlying variant of concern (VOC) and variant of interest (VOI) lineages (Figure 1). They were able to link these mutations to their respective functions and identify the ways in which they interact and modify one another towards improved viral fitness.
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FIGURE 1. Mutations shared across lineages (bottom left). FROM “RAPID EXPANSION OF SARS-COV-2 VARIANTS OF CONCERN IS A RESULT OF ADAPTIVE EPISTASIS” GARVIN ET AL. 2021.
Of course there are those mutations located within the S protein which are, at this point, fairly well known: N501Y, E484K, L452R, and S477N. These mutations are generally associated with an improved ability to enter human cells as well as improved neutralizing antibody escape. Yet, the researchers discovered that these very mutations seem to depend on other, non-spike mutations for their impact on viral fitness (Figure 2).
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FIGURE 2. Lineage defining mutations in S paired with their potential non-S epistatic partners. FROM “RAPID EXPANSION OF SARS-COV-2 VARIANTS OF CONCERN IS A RESULT OF ADAPTIVE EPISTASIS” GARVIN ET AL. 2021.
Take the D614G amino-acid substitution in the receptorbinding domain (RBD) of the S protein, for example. This substitution increases infectivity and is now commonplace among all of the most concerning variants, including omicron. That said, only those variants carrying this substitution in combination with a substitution at L323P of the non-structural protein 12 (nsp12) managed to gain a foothold over their competitors. A similar phenomenon can be seen with the N501Y amino-acid substitution— found in alpha, beta, gamma, and, once again, omicron. This substitution is closely associated with increased virulence, making it especially worrisome. Here, it was only those lineages that expressed this substitution along with a deletion of S106_F108 in the non-structural protein 6 (nsp6) that displayed increased viral fitness. Garvin et al. suggest that these mutations are advantageous because of their ability to suppress the innate immune response. Although mutations in S can greatly enhance both SARS-CoV-2’s ability to enter host cells and its ability to escape antibodies, they’re also prone to quick suppression by our innate immune system. Because of this, the S mutations have difficulty transmitting; the virus is getting stopped before it even gets the chance to show off its improved abilities. This is where the mutations outside of the S protein come into play. For example, Nsp12 L323P might be increasing the replication 1519
rate of the virus, allowing it to produce more of itself in a shorter period of time. The sheer increase in numbers means our defenses can no longer keep up. In the case of nsp6 S106_F108del, Garvin et al. note that it likely also impacts the viral replication process. Nsp6, along with nsp3 and nsp4, is in charge of creating the double-membrane vesicles (DMV) that the virus uses to hide itself from our immune system. Once hidden, it can replicate freely without worrying about any “attacks.” Insofar as they allow for undisturbed replication, these proteins may also share an important role in prolonging the amount of time we shed, and spread, the virus. The researchers suspect that S106_F108del, in particular, may be affecting nsp6’s functional interactions with other proteins. There are three other non-S mutations that Garvin et al. make mention of: nsp13 D260Y, nsp2 I120F, and N R203M. Although the exact function of nsp2 is still not known, the researchers hypothesize that all three mutations work in unison with S mutations to optimize the replication-transcription process. The fact that these non-S mutations continue to crop up across different variants of concern and variants of interest should have our attention. It is improbable that they would be present in this way if they weren’t conferring some kind of selective advantage. We know that polygenic interactions happen, we know that epistasis happens; no reason to think it doesn’t happen between S and non-S proteins. To brush this aside, especially with the rise of variants like omicron, would be an oversight. With this study, the groundwork for wholegenome epistatic analysis has been laid, we would do well to build on it. This article originally appeared on Forbes, and can be read online here: Non-Spike Proteins Contribute To Transmission And Virulence Of SarsCov-2
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Another Variant Emerges From An Immunocompromised Patient Forbes | December 21, 2021 | Article
As the pandemic continues, new waves of infections are driven by emerging viral variants with a menagerie of genomic mutations. The exact origins of new mutations are unknown, but one theory is the cultivation of mutations in immunosuppressed Covid-19 patients. In some instances of Covid infection, lingering symptoms may last for months, often in immunocompromised individuals. This allows the virus to effectively adapt within a single patient over time, resulting in potent mutations to the Spike protein and larger genome, particularly in cases when the patient receives any sort of antiviral drug. Here we examine one such case of a 72-year-old patient who was infected continuously for two months, as detailed by Truffot et al. Patient Background The patient, a resident of France in his early seventies, had chronic lymphocytic leukemia associated with hypogammaglobinemia for four years prior to his Covid-19 infection. Twenty days prior to the disease course, the patient had received his first dose of the Pfizer/BioNTech vaccine. He additionally received chemotherapy-related monoclonal antibodies, venetoclax and rituximab 17 days prior to disease course. After experiencing symptoms of coughing, fever, diarrhea, and asthenia, the patient tested positive by PCR test for SARS-CoV-2 infection three days prior to disease course and was given a 700 mg dose of anti-SARS-CoV-2 monoclonal antibody treatment bamlanivimab three days later. For the purposes of this discussion, the administration of bamlanivimab acts as day 0 for the disease course.
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FIGURE 1: Patient history prior to disease course. ACCESS HEALTH INTERNATIONAL
Patient Treatment The patient's condition rapidly deteriorated, requiring hospitalization on day 6 and oxygen assistance and plasma transfusion on day 10. He was transferred to an intensive care unit on day 13 and was treated with high-dose corticosteroids from days 21 to 26. This improved the patient’s baseline condition, but he still required supplemental oxygen, leaving the ICU and returning to the general hospital on day 33, maintaining a high viral load throughout the month. From days 47-57, the patient received treatment of remdesivir— 200 mg on day 47 and 100 mg on the days following. He was discharged to a rehabilitation center following this treatment and tested negative by PCR test on day 61.
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FIGURE 2: Patient viremia and treatment during the disease course. ACCESS HEALTH INTERNATIONAL
Virus Evolution Truffot et al. later analyzed 12 samples taken throughout the disease course for genomic mutations by performing whole-genome sequencing. Their analysis revealed the initial infection was a result of the Alpha variant, which drove infections in the winter and spring of 2021. That was the sequence found on day 3. On day 6, sequencing revealed a novel mutation, E484Q, not previously detected in sera samples, which was observed at a frequency of 82%. On day 10, this frequency rose to over 99%. The following day, another novel mutation was detected, Q493R, at a frequency of 64%, which rose to 76% by day 17. Position 484 in the Spike protein is often mutated in highly immune resistant variants but was never an often observed mutation in the Alpha variant. Additionally, the typical mutation is E484K, whereas the French patient developed E484Q, which is rarer, found mostly in less frequent, regional variants. Position 493 is interesting as well. Until recently, Q493R in the Spike protein was an uncommon, highly antigenic mutation. Gideon Schreiber described a number of receptor-binding domain mutations for antigenicity, one of which was at positions 493. He described Q493H as a highly antigenic mutation. The Q493R and Q493H mutations are both neutral to positive charges, indicating 1523
Q493R should have a similar effect. This means transmissibility for variants that carry this mutation is much higher. The only instance of Q493R in variants of concern is the current Omicron variant which is reigniting Covid-19 infections throughout the world. Its observation in an individual immunocompromised patient is notable, to say the least.
FIGURE 3: Spike mutations sampled from the patient over time. Those in black are those found in the ... [+] ACCESS HEALTH INTERNATIONAL
Takeaways This is not the only instance of dangerous mutations developing within an immunocompromised individual. There is a long history of these patients, many of which we have analyzed, including the London, Boston, Pittsburgh, and Italian patients. Recently a 58year-old patient who underwent a six-month-long infection developed a few questionable mutations in the Spike protein as well, in this instance, E484G and F490L in the receptor-binding domain and several deletions in the N-terminal domain. These mutations all aid in the transmissibility and immune resistance of major variants. We have recently detailed the potential origins of the new Omicron variant. Understanding how patient zero developed Omicron, or either previous or future variants, may help us gain insight into how to develop strategies to contain these variants before they wreak havoc. Truffot et al. note that positions 484 and 493 are critical in the bamlanivimab antibody binding process. Giving the immunocompromised patient a steady dose of bamlanivimab may have, in turn, resulted in the development of those mutations. Genomic surveillance of long-term immunocompromised cases is essential to prevent the development of these mutations. Resources should be devoted to containing infections in these individuals and continuous sequencing on patient sera is vital for genomic surveillance. 1524
This article originally appeared on Forbes, and can be read online here: Another Variant Emerges From An Immunocompromised Patient
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Omicron Evades Most But Fortunately Not All Monoclonal Antibodies Forbes | December 23, 2021 | Article
The Omicron variant of SARS-CoV-2 has rapidly ricocheted around the world. Reported cases are at their highest since May 2021. There is a growing need for effective monoclonal antibody treatments to prevent and treat Omicron infections. Unfortunately, most approved anti-SARS-CoV-2 antibodies have a diminished potency or are ineffective against Omicron. The Omicron mutations which render the virus resistant to antibodies induced either by natural infection or vaccine also render them resistant to most monoclonal antibody treatments. Most does not mean all. At present, there are at least five well-characterized antibodies that retain potency against most variants of SARS-CoV-2 including Omicron. S2K146 S2K146 is a monoclonal antibody developed jointly by Vir and GSK. Isolated from the memory B cells of a symptomatic Covid-19 patient, S2K146 bind the SARS-CoV-2 S protein, as well those of SARS-CoV-1, bat coronavirus WIV-1. Additionally, the antibodybound and potently neutralized a number of variants of concern or interest, including Alpha, Beta, Gamma, Delta, Epsilon, and Lambda. Structurally, the antibody locks two of the trimer’s three receptor-binding domains in the open configuration while the remaining binding domains remain closed. As outlined by Park et al., the S2K146 antibody footprint mimics that of the ACE2 binding sites. As many as 21 of the amino acids of the receptor binding site of the virus’s spike protein also bind the S2K146 antibody (Figure 1). These amino acids include heavily mutated sites in variants of concern, including N501, E484, and K417. Mutations of these mutations normally reduce antibody binding. The research speculates that neutralization is preserved as 1526
the interaction between the antibody and the receptor occurs over so many contacts. To me, it makes sense that an antibody has a structured surface that closely mimics that of the ACE2 neutralizers most variants. However much it may mutate, the spike protein must bind to ACE2 itself to initiate infection. I expect to see many more such ACE2 antibodies in the future, some with binding affinities that exceed that of S2K146.
FIGURE 1: ACE2 binding of the S2K146 antibodyANTIBODY-MEDIATED BROAD SARBECOVIRUS NEUTRALIZATION THROUGH ACE2 MOLECULAR MIMICRY. PARK ET AL. 2021
CV3-1 The CV3-1 monoclonal antibody also neutralizes several variants of concern and may also retain activity against Omicron. The antibody binds to a structure designated the 485-GFN-487 loop in the receptor binding domain. The three amino acids are well conserved in Omicron and most other variants. (Figure 2, left)
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FIGURE 2: CV3-1 binding with the 485-GFN-487 loop of the receptor-binding motif.STRUCTURAL BASIS AND MODE OF ACTION FOR TWO BROADLY NEUTRALIZING ANTIBODIES AGAINST SARS-COV-2 EMERGING VARIANTS OF CONCERN. WENWEI LI ET AL. 2021
The antibody recognizes the receptor binding domain in the open configuration (figure 2. right). Evidently binding of the antibody triggers a conformational change that mimics that of binding to the natural receptor. Upon binding, the S1 protein dissociates from the membrane-bound S2, laying bare the structures on the S2 protein that drives viral to cell membrane fusion required for virus entry. According to the researchers binding, by CV3-1 triggers premature release of the S1 protein from the virus surface, rending it incapable of infection. In other words, the antibody imitates ACE2 binding and springs a trap before the virus enters the cell. Rather than blocking binding as does S2K146, CV3-1 inactivates the virus prematurely. Wenwei et al. report that this loop structure is critical for S1 activation. CV3-25 A third antibody CV3-25 binds to the S2 protein of the Spike. This region is highly conserved. among betacoronaviruses. Specifically, CV3-25 bindings the stem helix near the membrane attachment site (Figure 3). Wenwei et al. find that the antibody binds to one or two units of the S protein trimer. The main site of interaction between CV3-25 and S2 lies between residues 1153 to 1165. More detailed analysis, including binding to an isolated peptide corresponding to this region, reveals that the antibody recognizes a linear epitope. A three1528
dimensional conformation is not required. The ability of the antibody to bind and neutralize the virus via a linear epitope raises the exciting possibility that it may be possible to develop a vaccine using the linear peptide that directs the immune response to this conserved neutralizing site, a possibility suggested by the authors.
FIGURE 3: CV3-25 binding to the S2 subunit of SARS-CoV-2.STRUCTURAL BASIS AND MODE OF ACTION FOR TWO BROADLY NEUTRALIZING ANTIBODIES AGAINST SARS-COV-2 EMERGING VARIANTS OF CONCERN. WENWEI LI ET AL. 2021
Both CV3-1 and CV3-25 efficiently neutralize the Wuhan wildtype virus, as well as variants of concern Alpha, Beta, Gamma, Delta. We have previously discussed other monoclonal antibodies for SARS-CoV-2 that could be used in conjunction with those described here to create a potently effective treatment. For example, a SARS-CoV-2 camelid nanobody binds across the receptorbinding domain in such a way that the trimer’s receptor-binding domains remain in the closed configuration. Sotrovimab Sotrovimab antibody was developed by Vir and is marketed by VIR/GSK. I have previously described this antibody here. The potency of Sotrovimab is only moderately diminished by Omicron as compared to its activity against other variants of interest. Sotrovimab is approved for emergency use in the United States and elsewhere. The epitopes to which Sotrovimab are moderately 1529
conserved in existing variants of concern. Whether Sotrovimab will retain activity against variants to come is uncertain. Evusheld Evusheld, developed by Astra-Zeneca, is a combination of two antibodies tixagevimab and cilgavimab, both of which were isolated from Covid-19 patients. The two antibodies bind to the receptor binding domain of the S1 protein albeit at the different and complementary sites (Figure 5). The antibodies were engineered to enhance their half-life. Evusheld is designed to be administered as an intramuscular injection, as opposed to an intravenous infusion. Early data indicated that the combination antibody effectively neutralized variants of concern including the Delta variant. Recent studies show that Evusheld is substantially less effective against Omicron as compared to earlier variants. Nonetheless, Omicron retains what appears to be sufficient activity to provide at least some protection against Omicron.
FIGURE 4: Tixagevimab (teal, right) and cilgavimab (purple, left) binding the spike protein RBD. ACCESS HEALTH INTERNATIONAL
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Conclusions As potentially dangerous as Omicron may be— more transmissible than delta and resistant to most vaccines and monoclonal antibodies— at least two approved monoclonal antibody treatments remain in our arsenal; Sotrovimab, and Evusheld. More are in active development. The recent emergency use authorization of Paxlovid, a small-molecule antiviral protease inhibitor for the treatment of the infected vulnerable, is what we hope will be the first of many new drugs that in combination with broadly neutralizing antibodies may effectively treat and eventually prevent SARS-CoV-2 infections. This article originally appeared on Forbes, and can be read online here: Omicron Evades Most But Fortunately Not All Monoclonal Antibodies
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Pfizer’s New Antiviral Drug Could Transform The Pandemic, But Challenges Still Lie Ahead Forbes | December 23, 2021 | Article
The approval of Pfizer’s Paxlovid antiviral pill for Covid by the FDA is a transformative development at this critical stage of the pandemic. Paxlovid has been authorized for use in adults and pediatric patients with mild-to-moderate COVID-19 who are at high risk of progressing to severe illness. The pill could reduce the burden on our overwhelmed hospitals during this current surge of Omicron-driven cases that has already exceeded the peak of the recent Delta wave. Final clinical trial data, conducted during the Delta surge, showed that the drug reduced the risk of hospitalization or death by 88 percent when given to high-risk unvaccinated adults within five days of the start of their symptoms. Pfizer’s laboratory studies indicate that its pills are likely to work against the Omicron variant, but this has not yet been confirmed. Paxlovid consists of nirmatrelvir, which inhibits a SARS-CoV2 protein to stop the virus from replicating, and ritonavir, which slows down nirmatrelvir’s breakdown to help it remain in the body for a longer period at higher concentrations. Paxlovid is administered as three tablets (two tablets of nirmatrelvir and one tablet of ritonavir) taken together orally twice daily for five days, for a total of 30 tablets. Presently, the pill has been authorized for Covid patients age 12 and over who are vulnerable to becoming severely ill because they are older or have medical conditions such as obesity or diabetes. However, once manufacturing increases and supplies are more plentiful there is potential for the pill to be used prophylactically for those potentially exposed in high-risk, congregate settings such as nursing homes, prisons, and military ships. However, there are several challenges that will prevent us from utilizing the full power of this tool. The first is insufficient supplies of the drug. In the coming week, the US is contracted to receive enough pills to cover 65,000 Americans. With a current daily 1532
average of 242,794 cases nationwide that wouldn’t even cover half of the people testing positive for the virus daily. Pfizer needs to be working with other manufacturers to significantly increase production. The US is purchasing the drug at a cost of $530 per patient, a cost significantly out of reach for poorer countries. Based on comparable drugs manufactured in India, I estimate that the true cost should be more like $25 - $30 per patient. By pricing these countries out of the market, we risk making the same mistakes we have with global vaccine inequity. As we have learned from bitter experience, in our highly globalized world, no population is safe until we all are. The second major issue is our woefully inadequate testing infrastructure. Currently, Americans are facing long wait times to access a Covid test and even longer wait times to receive the results. Rapid tests are nearly impossible to find during the holiday period. Paxlovid is only effective if taken within the first few days of symptoms, without an efficient testing infrastructure that cannot be achieved. We need to be dramatically increasing testing sites across the country. I have long been an advocate of free, mass rapid testing to control the spread of Covid-19 since March 2020. Yet well over a year since the first at-home rapid antigen test was approved, despite desperate pleas from many epidemiologists and public health experts, the US is yet to embrace the power of mass rapid testing, focusing instead on vaccines. The Biden administration recently announced they would ship as many as 500 million at-home test kits to Americans in January, but the amount is still insufficient. Widespread accessibility to rapid tests in the US is presently hampered by a cumbersome F.D.A. process intended for high-tech medical devices. To be approved, the rapid tests must demonstrate that they are nearly as sensitive as the gold standard PCR tests. But rapid tests are the “public health gold standard”, they deliver the most important public health metric by detecting when someone is infectious and is likely to transmit the virus. Therefore they should be regulated as a Public Health Good. President Biden could accomplish this with a simple Executive Order, increasing competition among manufacturers and flooding the market with inexpensive, high-quality rapid tests.
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Finally, we should be aware that Paxlovid does carry a number of drug contradictions including blood thinners, (warfarin), hormonal contraceptives (ethinyl estradiol), steroids (prednisone), cholesterol drugs (statins), the full list can be viewed here. The drug may not be right for everyone and those who are prescribed Paxlovid should always give their doctor a full medical history and medication list, including any vitamin or herbal supplements. Despite the transformative impact that antiviral drugs could have on the pandemic, we must still proceed with caution. The FDA has unfortunately approved a second antiviral drug Molnupiravir from Merck today which has the potential to supercharge SARS-CoV-2 mutations and unleash a more virulent variant. A risk not worth taking when the drug only reduces the risk of hospitalization and death among high-risk Covid patients by 30 percent compared to Paxlovid’s 88 percent. We also have two viable treatment alternatives in the form of two monoclonal antibodies treatments Sotrovimab and Evusheld which are effective against the Omicron variant. This article originally appeared on Forbes, and can be read online here: Pfizer’s New Antiviral Drug Could Transform The Pandemic, But Challenges Still Lie Ahead
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Fight COVID-19 with lessons learned from HIV The Hill | December 27, 2021 | Article
Omicron has caught us unprepared. The danger of this variant lies not only in its lightning transmission speed but also in its ability to elude our very best vaccines. Vaccines remain a critical tool to protect us against severe disease, hospitalization and death from the omicron variant, but breakthrough infections are becoming increasingly common. While some hope that this is the last of the variants that will afflict us, that is by no means certain. The capacity for coronaviruses to flourish in immune populations is one of their defining features. The critical question we should be asking is: Will the disease become milder or more severe? It is important to remember how closely linked SARS-COV-2 is to SARS and MERS, which both have significantly higher case fatality rates but are less transmissible. Fortunately, we still have many untapped defenses that we must now weaponize against omicron and future variants. Our first defense is public health. Strong testing, tracing and supported isolation systems can prevent rapid transmission throughout communities. Countries across Asia that have rigorously implemented and invested in these systems from the beginning of the pandemic have fared significantly better during omicron with lower overall case counts and mortality rates. The reports of frustrated Americans stuck in hours-long testing lines and empty pharmacy shelves devoid of rapid tests this week are a stern reminder of the critical importance of consistently investing in public health measures throughout a pandemic. Many who cannot afford to take hours off from work to line up for testing or cannot afford or find rapid tests could be unknowingly infecting their communities and delaying necessary treatment for the virus. It is incomprehensible that we are still facing a testing crisis almost two years into the pandemic. I was among the chorus of experts in early 2020 that called for widely available, free rapid tests as a way to control the pandemic. Each person should be able to 1535
rapid test themselves two-to-three times a week so they might voluntarily modify their behavior and seek help as needed. To achieve this, we can significantly reduce the price of rapid tests. The tests currently retail at an average price of $23. In reality, these tests can be manufactured at a cost of 50 cents. In 2018, Abbott Laboratories provided 100 million rapid Hepatitis B tests to the Egyptian government at a cost of 50 cents per test. A similar deal could be struck to provide all Americans with access to rapid COVID tests. Our second defense is an armamentarium of medical treatments. We must reckon with the unpleasant reality that our vaccines have failed to protect against infection and transmission, as we hoped they would. But they do provide strong protection against severe disease, hospitalization and death, which is not to be underestimated. There remains hope that newer generations of vaccines will provide broad protection against most if not all variants. Indeed, such vaccines are slowly making their way through the testing regulatory process, but I believe it is unwise to put all our eggs in one basket when the stakes are this high. Coronaviruses are a formidable opponent as they have evolved over millions of years to continually reinfect immunocompetent populations with great sophistication. They evade and suppress our immune systems with three fundamental tactics. The first tactic is antigenic variation, in which the virus disguises itself from the existing immune system by changing the outer surface. We see this each year with the influenza virus. Cold-causing coronaviruses infect about one-third of the human population year after year, making it clear that there is no end to the way the virus can adapt and reinfect. Once the virus enters a new host, either because of waning antibodies or antibodies that do not recognize a new variant, the virus encounters a myriad of cellular defenses collectively called innate immunity. With great sophistication, the virus delays alarm signals (which normally allows the body to protect itself) for as long as five to six days. During this interval, the virus prolifically replicates and then exits to be transmitted to others. The third tactic is speed. After vaccination or infection, high levels of antibodies eventually wane, and we depend on our memory cells to create new antibodies. The virus replicates at such blinding 1536
speed that it can outrun the memory response that generally takes three to five days. In that period the virus again has the ability to rapidly replicate, exit and transmit to a new host. The good news is that the residual memory immune response may be what's protecting many people who are vaccinated against severe disease, hospitalization and death. So how do we defeat such a skilled and formidable opponent? One answer was monoclonal antibodies that can be used for treatment and also prophylactically during outbreaks in high-risk populations living in congregate settings such as nursing homes. But the omicron variant has developed resistance to all but two antibody treatments. Fortunately, our experience with HIV provides a clear path forward. We have not succeeded in creating a vaccine for this virus, but thanks to many decades of research into treatment, the virus is far from a death sentence today. Just last week, the U.S. Food and Drug Administration granted approval for the first injectable treatment for HIV pre-exposure prevention. Developed by GlaxoSmithKline, the drug Apretude prevents HIV infection with injections given every two months. We need to follow the strategies used for HIV and create combinations of powerful, long-acting drugs that target a broad range of functions with a high therapeutic index to fill the gaps in our current strategy for long-term protection. There are still many unexplored targets for SARS-CoV-2 drug development. I suggest that we expand our range of targets for drug development far beyond the common protease to the many enzymes and regulatory proteins specific to SARS-CoV-2 that do not exist in humans. This will give us the greatest possibility of developing drugs that are lethal to the virus but harmless to us. Redesigning our SARS-CoV-2 drugs will not be a simple task. It will require accelerated research and global collaboration that not only breaks down geographic borders but also the silos that exist between academia and the pharmaceutical biotechnology industry. It will require similar levels of investment and resources to those we saw used for Operation Warp Speed. But by strengthening both our public health and medical defenses, we can protect ourselves from the next omicron.
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William Haseltine is president of ACCESS Health International. An infectious disease expert, Haseltine was formerly a Harvard Medical School professor and founder of the university’s cancer and HIV/AIDS research departments. This article originally appeared on The Hill, and can be read online here: Fight COVID-19 with lessons learned from HIV
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New Evidence Of Immune Suppression By SARS-CoV-2 Forbes | December 29, 2021 | Article
This is the seventeenth article in a series called “How SARS-CoV-2 Delays, Evades, and Suppresses the Immune System.” Read parts 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16. SARS-CoV-2 is the reigning champion of overcoming natural immunity. Infected cells produce interferon, which in turn stimulates an impressive array of hundreds of antiviral genes. SARSCoV-2 has developed elaborate countermeasures that allow the virus to proliferate. Figure 1 summarizes the course of infection. For the first several days the virus suppresses the host’s ability to defend itself long enough to proliferate and transmit to other people. It is only after viral load peaks that natural immunity, also known as innate immunity, appears to kick in and counteract replication.
Figure 1. Model of SARS-CoV-2 disease course. Viral load peaks before symptoms appear. ACCESS HEALTH INTERNATIONAL
To clarify, natural immunity is the portion of the immune response that precedes adaptive immunity. Adaptive immunity mobilizes the legions of antibodies—killer T cells, memory B cells, and so on—that the general public has become acquainted with by 1539
virtue of their role in vaccination. But a growing body of literature shows that SARS-CoV-2 replication escalates and reaches its peak well before adaptive immunity begins to kick in. It thus falls upon our innate immune defenses to detect and neutralize the virus before any ensuing disease does irreparable damage to the rest of the body. We now have evidence, in the form of three studies, that shows exactly why we call SARS-CoV-2 the champion of immune suppression. All microorganisms have evolved over time to suppress and evade neutralization by the human immune system. SARSCoV-2 not only excels at this tactic, but wields it more proficiently than the previous reigning champion, influenza. Of particular concern is that new variants of SARS-CoV-2 appear to improve upon the immunosuppressive capabilities of their predecessors. While much has been made of the mutations in surface proteins that increase transmissibility, what happens once the virus has entered and established infection remains largely overlooked. In the first study, published in Nature Communications earlier this month, researchers Hatton et.al sampled tissue from the nasal cavity, previously identified as a primary site of SARS-CoV-2 entry and infection. Of the seven different cell types they identified as infectable, the goblet cells in the nasal mucosa were determined to have more susceptibility to SARS-CoV-2 infection due to their expression of both ACE2 and TMPRSS2. The researchers’ aim was to culture the tissue, infect it, and see how innate immunity mobilized in response. Hatton et.al found that type I and type III interferons, as well as downstream interferon-stimulated genes, dominated interactions with the virus, suggesting that a treatment combining both interferon types—administered following exposure—could potentially impede infection in the nasal mucosa.
Figure 2. Delayed induction of IFN-I/III signaling in SARS-CoV-2-infected nasal ALI cultures. "DELAYED INDUCTION OF TYPE I AND III INTERFERONS MEDIATES NASAL EPITHELIAL CELL PERMISSIVENESS TO SARS-
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COV-2" HTTPS://WWW.NATURE.COM/ARTICLES/S41467-021-273180
Interferon is a signaling protein with potent antiviral effects. This is evident not just from the perspective of drug development, but viral immune suppression. Many of the proteins SARS-CoV-2 encodes in its genome target interferon specifically and multiply, forming a blockade across several points along its signaling pathways. Notably, the researchers behind the nasal cavity study reported a delay in interferon production in SARS-CoV-2-infected tissue that did not occur in tissues infected with influenza viruses. Since Covid19 is so often compared to influenza, this difference in pathogenesis demands our attention. Hatton et.al disclose a caveat to their results—that they exclude immune cells like plasmacytoid dendritic cells that might also have a role to play in stimulating interferon. The findings of the second study support and strengthen those of the first by bringing in animal models. Published in Science Immunology in October, Horiuchi et.al infected Syrian hamsters with influenza virus and SARS-CoV-2 to compare their immune responses. Even though influenza-infected hamsters developed high viral loads, reaching levels of 108 viral particles three days following infection, they were able to clear any infectious virus within a week. While hamsters infected with SARS-CoV-2 developed similar viral loads within the same timeframe, viral replication continued apace until Day 7, when at last titers began to drop. Again, this is likely due to delays in interferon production. The third and final study I wrote about previously in the context of the Alpha variant when it was published as a preprint earlier this year. Since then it has been fast tracked for publication in Nature with updated data on the Delta and Omicron variants. In the original paper, Nevan Krogan and his team used deep sequencing techniques to investigate differences in protein transcription and expression between the original and Alpha SARS-CoV-2 strains. They found an 80-fold increase in the amount of Orf9b subgenomic RNA produced by the Alpha variant and a ten-fold increase in the messenger RNA corresponding to the Orf6 proteins. Krogan and his team observed an increase in the N protein as well.
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Figure 3. Left: Replication, IFNβ expression and secretion after infection with 250 E copies/cell. ... [+] "EVOLUTION OF ENHANCED INNATE IMMUNE EVASION BY SARS-COV-2" HTTPS://WWW.NATURE.COM/ARTICLES/S41586-021-04352-Y
Figure 4. SARS-CoV-2 Alpha variant upregulates innate immune antagonists at the subgenomic RNA and ... [+] "EVOLUTION OF ENHANCED INNATE IMMUNE EVASION BY SARS-COV-2" HTTPS://WWW.NATURE.COM/ARTICLES/S41586-021-04352Y_REFERENCE.PDF
Orf9b, Orf6, and the N protein are all inhibitors of natural immunity. A mutation in any one of their immunosuppressive 1542
functions can lead to changes in the properties of the virus. The updated study shows that mutations similar to those expressed in the genome of the Alpha variant also appear in the Delta and Omicron variants. In the exact words of the paper: “The importance of mutations outside Spike in adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the Delta and Omicron N/Orf9b regulatory regions.” These three studies lead to a conclusion that not only can SARSCoV-2 suppress the innate immune system, it can also evolve to do so even more efficiently. This explains at least in part why Omicron is so efficient at transmitting from person to person. It underscores the importance of understanding the three traits that are most important in the pandemic: antigenic variation that allows reinfection of previously infected and vaccinated people; suppression of the innate immune system, which drives asymptomatic transmission; and speed of replication, which allows the virus to outpace the memory response. Here we have focused on the ability of SARS-CoV-2 to delay innate immune responses. In further parts of this series we will discuss the implications for these three traits on reinfection of previously infected and vaccinated and long-term protection from hospitalization, severe disease, and death. This article originally appeared in Forbes and can be read online here: New Evidence Of Immune Suppression By SARS-CoV-2
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Media Inerviews
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January 2020
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Interview With Health Professional Radio January 21, 2020 | Interview
Neil Howard (NH): Hello and welcome to Health Professional Radio. I am your host Neil Howard. Thank you so much for joining us again for another segment. The population over sixty years of age is expected to double to about twenty two percent by 2050, which is about 2.1 billion people over the age of sixty. Our guest this morning is Dr. William Haseltine. He is joining us to talk about his book Aging Well. This book looks into ways to support the health and wellbeing of older adults and also offer caregivers and policymakers and healthcare leaders insights into reducing health spending, especially by means of workflow and novel digital health technology. Welcome to the program Dr. Haseltine. Thank you for taking the time this morning. William Haseltine (WH): Well thank you. It is a pleasure to speak with you this morning. NH: Now, I did of course mention that we are talking about the aging population. Give us a bit of background about yourself as president of ACCESS Health International. WH: I have had an interesting career, a fundamental research scientist working on a number of topics, cancer and AIDS. I have had a career in business creating biopharmaceutical companies and there are eight products on the market from companies I have helped to create. And over the last fifteen years I have been focused on improving healthcare systems both in this country and around the world through a foundation I created, ACCESS Health International. Aging is one of the major unsolved problems in health. When I look at aging as a healthcare problem, I see that the world, not only the United States, is woefully unprepared to deal with what is coming. NH: What is coming? I mean, we all age. Are we talking about a day when we do not age or are we talking about aging in such a way that it is not a healthcare problem, it is just an aging issue?
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WH: When I look at it as a healthcare system, I look at it from both the individual’s point of view and society's point of view. Let us take the second one first. From a society point of view, it is a major problem if there are more older people than younger people. Most older people are not contributing economically to society. They depend on younger people for financial support. And if that population pyramid is inverted so there are more older people than younger people, that is a problem. That is happening in a dramatic way in some countries. I call it the lollipop phenomenon. If you look at the population in Italy or Japan, for example, there is a narrow base of younger people and a big base of older people. That is a double problem because older people have a lot more health issues than younger people, and they need more care. That is the first issue. Almost everybody who is listening knows the second issue I am about to discuss. If you are a spouse, are you taking care of a very ill person? If you are an adult, are you taking care of your parents, or are you also taking care of some of your children who may have disabilities? You may be taking care of both, as a matter of fact. Now as an older person, it is very difficult to know what to do. How do you keep yourself healthy? What kind of doctors do you see? We as a society are not prepared to deal with what we are beginning to experience and certainly what is coming. NH: So we spend a lot of money here in the United States, you know, other countries as well. But here in the United States, we spend a great deal of money. Why are we lagging when it comes to the pyramids, this aging pyramid? WH: Well, we are doing better than some countries, like the ones I mentioned, because we have immigration, and immigration has been a powerful demographic force for us. People who have been in this country for several generations are not having children at a replacement rate, but people who have come into this country more recently are. That has put the US in a relatively good position for the time being, but not a great position in terms of what is coming, and as immigration slows down the problems will become more acute. There are a lot of things that can be done both from a health systems point of view and from an individual point of view. If you are an individual looking at what you might do, our book Aging Well 1547
gives you about ten things that you can think about doing that can make you and your parents or your spouses much happier as they age. As a country, we look at what we can do to restructure our healthcare systems so that we deliver much more care at home in communities, and then we integrate social care with medical care. There are many things we can do, but I do not see our country or almost any country really addressing this problem in a systematic way. That is why I wrote this book. NH: Okay. Speaking of your book, Aging Well, chapter two talks about person centered care. What is person centered care and why is this and value based care so essential? WH: Well, person based care is what we all want. We want our healthcare system to focus on us. But to me, person centered care is a lot more than that. Just a minute ago I mentioned integration of medical and social care. What that means is including social services as part of medical care or, put another way, including medical care as part of social services. Your social service workers generally know you as a person. They know where you live, they know your family, they know your needs. Medical personnel often do not know that. They know you as a patient, not as a person. I believe it is critical to integrate social care and medical care. If you have a combined record of your social status and your social needs and your medical needs, you can treat people in a much more holistic fashion for what they need as a person, not what they need as a patient. NH: Now there has to be some type of balance we are looking for. That balance of what they need as a patient and what they need as a person, because aren’t there many cases where no matter what they need as a person a certain medical approach is necessary or is their health and wellbeing? WH: Absolutely. You are one hundred percent right. I am not advocating to eliminate medicine. I am advocating integrating social care and medical care so that we really understand the person's needs and who they are. Let me give you an example. Suppose you have a person with a chronic issue like diabetes. A social worker will know where that person lives, will know what that person's weight is, will know what that person eats, and may be able to inform the medical part of that person's care. They may be able to work together to prevent diabetes from getting worse. Whereas if you are only dealing with it from a medical perspective, you are only seeing part 1548
of the picture. You are not seeing the whole picture. That is what I find as I look around the world. For example, take one of the best healthcare systems in the world, Sweden. They have a terrible time trying to integrate social and medical care. However, their neighboring country, Finland, has just created a program where there is a government agency or ministry for social and medical care, and they are doing everything to integrate those records and to integrate the care. I think that can make a really big difference to individuals. NH: In wrapping up, how is ACCESS Health International working toward that end? WH: Well, what we do is we are in the first place a think tank. We look all over the world for the best examples of elder care, dementia care, or any type of care. That is the first thing we do. And that is the result of these books. I have got three books out now, Aging Well, Voices in Dementia Care and Stay Young Navigators. They have just come out. That is our think tank work. Second part of our work is advising governments, both the United States government and governments around the world. We have offices all over the world, and we advise governments that have decided they want to make a change and help them do that better. In some rare cases, the governments will ask us to help implement certain programs. Like in India, the ACCESS Health in India is helping develop digital care systems for the entire country. We are actually helping implement it in some cases, but we only help where we are asked. We offer to help anybody, but somebody has to ask us, to come and say, please help us use your knowledge to improve our health system or the way we are working with our elder populations. NH: Well, if he could give our listeners a website doctor where we can go and get some more information about ACCESS Health International and learn how to possibly get involved or even on a local level when it comes to integrating social services and medical services, where can we go and get some more information? WH: Well, I think let me just, I will give you our website. It is www.accessh.org and that is a good place to start. You can write to us and we will be happy to direct you to more local agencies. NH: And obviously we can get links to your books as well at that website.
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WH: Right. Amazon is a great place to get these books either as a hard copy or as a digital copy. NH: Right. Great. Well I thank you so much for joining us here on Health Professional Radio. Been quite eye opening and I am really hoping that we will get to talk again and learn some more about how to age well here in the United States and abroad. WH: Thank you very much for your time.
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Interview With NBC News Radio January 21, 2020 | Interview
Note: The questions asked during this interview were not available for transcription. What follows is a transcript of Dr. Haseltine’s answers. William Haseltine (WH): Hi, this is William Haseltine speaking, calling in. Speaker: --WH: Absolutely. Speaker: --WH: Yes. The book is called Aging Well and it is a book that describes a number of eldercare systems, both in Northern Europe and the United States, that do an excellent job of taking care of older people. The idea is to help people find a good place to take care of their loved ones. Speaker: --WH: When it comes to elder care, everybody is behind where they should be. That is the sad lesson that we have learned. I wrote a previous book on elder care in Sweden. It is true that Sweden has one of the best healthcare systems in the world—as long as you are not old. But when it comes to taking care of older people, they do not do much better than we do. In fact, they had a crisis that was so serious that the government fell apart almost entirely due to the issue of elder care. It is true that we do not do as good a job as we could, but it is not true that we are worse than anybody else. We are all in the same boat. The whole issue of elder care is woefully inadequate in almost every country. Speaker: --WH: It is, in my opinion, a political issue. We know what some of the solutions are, but unless older people make demands on their Congresspeople, their senators, their mayors, their city councils, it is not going to happen. Fortunately, older people make up the biggest voting bloc in the country, and that voting bloc is getting bigger by the day, so I believe that we will see major efforts to address the issues of elder care. However, these are really complicated issues. I 1551
think that we at ACCESS Health, the foundation I created to look around the world at best examples of healthcare, have some ideas about ways we can change the way we handle health that would be of enormous benefit for those who are older. Speaker: --WH: It starts with something we call integrated care. Healthcare systems today are hospital centric. If you are sick, you go to the hospital. An integrated system is a system that delivers healthcare in the home, in the community, in outpatient centers, and, if need be in a hospital. It is coordinated. A fully integrated healthcare system has an information system which is seamless between the home and the hospital. That is the first piece. The second piece is integrating medical care with social care. We have two very important systems that help older people, medical systems and social care systems, that send people to homes to look after those who cannot take care of themselves or provide a wide variety of other social services. But all too often, those are completely different services. By integrating those, making sure that we know what the lifestyle issues are, what the health issues are, we have all that information in one place. We can start delivering personal person centered healthcare and person centered social care all in the same package. That is a tall order. It means we have to change what we are doing now. But it is the direction for the future. Speaker: --WH: It is available on Amazon. It is available in, I am happy to say, Barnes and Noble. And it will be available at airports for anybody who flies. It will be available in Hudson News in about a month at airports. Speaker: --WH: Sure. It is very nice of you to ask. Our website ACCESS Health International is http://www.accessh.org/. Speaker: --WH: You are welcome. Thank you.
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Interview With Alzheimer’s Speaks Radio January 21, 2020 | Interview
Lori La Bey (LL): I am so excited about the conversation we are going to have today. We are going to be talking with Dr. William Haseltine, a dynamic player in dementia care and advocacy. He is also a renowned scientist and his book, Voices in Dementia Care: Re-imagining the Culture of Care, just came out. I know this is going to be a great conversation because this is something I too am passionate about and I have been pushing for kind of shifting that dementia care culture from crisis to comfort around the world for what I thought was years, but nothing in comparison to this man. In the book, healthcare professionals describe the challenges of delivering high quality dementia care with limited resources. I hear people talking about that constantly. The book provides critical analysis of best practices that can be adapted and applied not just for institutional and home care providers, but also for families, which I think is really important too. By now most of us have noticed an increase in media awareness, from funding to medical research, in the area of Alzheimer's and dementia. But Dr. Haseltine stresses that there is also a lack of firsthand information about the experience of living with these disorders and caring for people with dementia. His book really raises the voices of care professionals, caregivers, care partners, depending on where you are in the world and how you turn them and people who actually have a diagnosis to describe what are some of the best practices. So welcome Dr. Haseltine. I am just so excited to have you with us today. William Haseltine (WH): Thank you. LL: Well, I always start out asking every guest the same question and that is, have you been personally touched by dementia in your own family circle or friends? WH: I would certainly say friends. No parents, but I have lived with different kinds of mental disorders. Not myself, but my parents
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and my children. So I have been surrounded by issues like this for most of my life. LL: Okay. Thank you for sharing. It just kind of gives people a little bit of background in terms of conversation. WH: Right. I think nobody is free from these issues. LL: I agree. WH: Whether either a parent or a spouse, friend, the issue is all around us. LL: I totally agree. I think there are still so many people who are not comfortable even acknowledging that, and to me, that is something that we need to change because we cannot fix it if we do not. WH: I think it is changing. I think society is coming to realize that dementia, elder related dementia—there is a variety of different types—is very common, and it is becoming part of the dialogue. LL: I think they are also seeing that it is not their image of elderly anymore. It is people who are still actively working, and now they are hearing about children every now and then with a diagnosis as well. It is kind of tipping the cards and making people look at things differently. WH: And dementia is a very broad word. Does dementia mean a cognitive declining cognitive function as you get older? Does it mean psychosis when you are younger? What does dementia really mean? I think the way we use it in this conversation is more associated with aging than it is with the more standard notions of psychosis. LL: Thanks for clarifying that. Now in your career, you have been at the forefront of medical research and application and you have had the opportunity to educate a generation of doctors at Harvard Medical School, which I just said just kind of like, wow. You were named by Time Magazine as one of the twenty five most influential global business executives, and today you are chair and president of ACCESS Health International, which is dedicated to ensuring quantum advances in medical technology translating into improved health outcomes just all around the world. I have to ask you, what got you interested specifically in Alzheimer's and dementia with this book, Voices in Dementia Care?
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WH: The foundation that I created about fifteen years ago looks at health systems as a whole, and I spent a lot of time looking around the world and writing books and writing about the best hospital systems in the world. As I did so, I began to recognize that no matter how good the system was—take Singapore or Sweden for example, I have written two books on both—they were not good at taking care of older people, and they were not good at all at taking care of people with Alzheimer's or age related dementia. Even in the best health care systems in the world, there are major gaps. When you are a person like me and you see a major gap, you say, okay, that is an opportunity. Let us see what we can do to address that issue. LL: That makes sense, and I think that that is a real important thing. You know, when you were talking about these other countries and that they are good, but not as good is what we would like them all to be. WH: Well, they are not very good at all. Let me take an example from another country, Japan. Every night in Japan, over a thousand people go wandering from their home and are hard to find because they have age-related dementia and some of them never come back every night. LL: Oh wow. WH: Some of them are lost. That just gives you a microcosm and they are looking at a problem that is going to be far greater than that as the population continues to age and they are not the only ones with those problems. Are there technical solutions? Are there social solutions? How do you deal with a problem like that? Those are things that kind of hit you when you say, let us think about what we can do. LL: Boy, that just really hit me when you said a thousand people a night. That is just unbelievable. Who knows how many here in the United States because so many people will not even talk about it. WH: We do not count. LL: Why is America so afraid to have this conversation? Did that come up in your book at all in terms of that being something that gets in the way of us being able to provide good care, or is that just a sideline? WH: It did not come up directly. What we did is we looked at people who are doing it well to help serve as examples. It is a 1555
profound question. One of the reasons is that we, as a country, do a poor job of providing social care. In fact, there is a good chunk of our country that does not think we should provide social care at all. If you do not think we should provide social care at all—and that is a big part of the population, a big political constituency—it is quite diverse. People who should be in favor of social care are not. That is people at the bottom of the pyramid. Many of those people are not for social care, and people at the top of the pyramid who are enjoying a great lifestyle do not think we should be helping those people. We are a country that is mixed. We have great people with big hearts, open wallets. Many people want to do the right things. And we are a country that has the opposite. Those are big tensions in society that are reflected in politics, and that reflect how we deal with these programs altogether. The problem of how you take care of older people and how you in particular take care of people who have lost cognitive function. It affects Republicans, Democrats, libertarians, communists, you name it. Everybody has this problem. I do not know of a single friend who is not dealing with this issue in one way or another. LL: Yeah. I know when I go out and speak, I can ask a crowd of a thousand people, have them all stand up, and I will have six questions. If it is a parent, grandparent, aunt, uncle, whatever, and go through and say, you know, sit down if they have dementia and at the end there might be anywhere from three to six people standing out of a thousand and that is even on the high side. That happens rarely. WH: I agree. It touches everybody. LL: People are just shocked. WH: One of the reasons that we do not deal with this issue is we do not deal with a lot of issues. It is not just this issue. It is the way we are as a country. By the way, it is not all bad. That same tendency, do it yourself, be independent, do not depend on the government is great in many ways. It just is not great for this. LL: It really does take a village because the ripple effect is so huge, not just a physical aspect but an emotional, a financial one. There are so many things that we have to consider. Now I want to ask you with your book again, Voices in Dementia Care: Reimagining Our Care Culture, what can people expect to find in your book?
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WH: I think what they will see is what they were hoping for: that some people somewhere have figured out what to do—that is humane, affordable, and kind—to help people with various kinds of mental dysfunction do the best they can do. One thing that I can tell you as being part of the medical world is we really are in the best part of humanity, where highly educated, dedicated people do their best to take care of the people amongst us who are doing most poorly. It is a wonderful part of humanity and I think that is one thing they can learn. Secondly, there are places they should be looking for that are like this. What we tried to do in this, after listening to all these people in Northern Europe and the United States, is abstract what are some general lessons. At our best here in the United States, we are as good or better than anybody. There is nothing that they are doing in Europe that we are not doing here too. We are doing the same kinds of things. They are just doing more of it than we are. But we have people here who are doing wonderful work. That is what I hope to do with this book, to show by example what can be done when it is done best. I can give you a series of things that we found. We can go right through them from person centered care to creating caring environments that encourage autonomy, making use of new technologies. There are a lot of things—integrated care, all of these things that are lessons that we learned from talking to all of these people. I can tell you it was a wonderful experience because the people we interviewed have dedicated their lives to this. Deeply thoughtful, wonderful people have dedicated their entire lives to making other people's lives better. LL: What I like about the book is, you know, when you were talking about being humane, making it affordable and kind, I mean, you are really talking about giving people hope. I think for so long that dementia has been sold as doom and gloom. There is nothing that we can do. This is the end of the road, and there is so much life that can be lived and still lived well. WH: One of the things people kept saying is to remember the person you are dealing with that has dementia is the person you love. It is still that person. It is another aspect of that person, but it is that person. It is not a new human being. It is not a stranger. It is that person. As you well know, many of the characteristics, the likes, the dislikes, the phobias, the passions of people who have lost a lot of 1557
their cognitive function—they still have that personality there. They still enjoy things. They still have their desires, not different from what they had before. LL: That is very true. I saw that with my mom repeatedly, that there would be moments where she would have kind of that blank stare, and then all of a sudden these beautiful moments of clarity and her humor would come out. It would just touch my heart on such a deep level because you realize how much you missed it, and it was just so much more profound. To realize that the soul is still there, the personalities are still in there. But I think so often we have been told that it is just going to be this progression. We have been told that they are not there, and so we do not look for those signs. We do not engage in normal communication. Most of our communication is nonverbal. WH: There are lots of things left that people should pay attention to, like a schedule. There are people who like to sleep in in the morning and stay up late at night. There are people who pop up in the morning and are done by early afternoon. That does not always change when you get older, and when you may not have all your faculties. You have to respect that. Many of these institutions put everybody on exactly the same schedule. There are places like Vermilion Cliffs that focus on letting people have their own daily rhythms. The same thing with autonomy. Do we keep people confined to their room or to a recreation facility, or like some places in Holland, do we create an environment where they can walk around? Can they get out into streets that are protected within a local environment, but it is like a village? They can go from place to place. They can go to shops. They can do a lot of different things. You know, I remember very distinctly when I was at a farm in Vietnam. They were teaching us how to make those delicious vegetable wraps. My wife and I were learning and eating and having a good time, but there was an old woman wandering around. I finally asked, who is that? That is our grandmother, they said, and she is really not all here. But she was all there. She was right there. She was interacting as she could. Who was this old woman? She was a Vietcong commander. She did a lot, that lady. The whole family just included her. She was there unconstrained, wandering around, interacting as she could. I mean, that is a wonderful example of how
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you can treat people. And there are institutions or places like this group in Holland who do that for all of the people who live there. LL: It is incredible. And it is so important, like you said, to allow people to have their own daily rhythm. I do not know if you are familiar with Harry Urban, but he lives with dementia as well. And one of the things that I love that he said is he is like, everybody likes routines. And he is like, but you know, sometimes you want your routine, and it is really our routine. If you want things to go smooth, you need to adjust to our routine because we cannot adjust to yours anymore. We do not remember, we do not have that capability. He kind of laughed because he says so often care partners will say, routine is good. But we have to look at whose routine it is, and why it is. WH: Exactly. I think that is part of person centered care— understanding who the person is, remembering that a person has their likes and dislikes. One of the oddest, if not the most, a little bit humorous places that I learned about was one that recreates the environment of East Germany in the fifties where refrigerators do not work and radios have one channel. People are happy there. The people who grew up in that period are happy there. That is taking into consideration what people like. This is what we think we can teach in a modern world, this is what we see you like. LL: Because we always think bigger and better and fancier, even myself. I am sixty now, and I could go without the upgrades. This is functioning just fine for me. I do not need to learn another process again. Dialing it down sometimes is really helpful and comforting in a lot of ways because people feel more in control than what they are used to. You have referred to a person WH: I like rock music from the fifties. I get very happy when I hear that. LL: Each genre is a little bit different over the eras there. One thing I want to ask you about is person centered care because, one, I want you to define that for our audience and two, personally, I do not like that term because I personally think it is overused and under delivered, but I would like you to explain what it is to our audience and your thoughts are on the term itself. WH: There are two versions of the term. Person centered care is what we were just now talking about. Understanding the individual and their likes, dislikes, lifestyle, where they have been 1559
and working with a person that is still there even though they do not have all the faculties they had before. It is still a human being with likes and dislikes. That is one aspect of person centered care, and many institutions do not respect that. Everybody is supposed to get up at the same time, eat at the same time, go to bed at the same time, do their exercise the same way. And that is just not who we are unless we happen to be in the United States military. It is not how we are. We are all different. That is one definition. But there is another definition to me of person centered care because when I look at what we need to do as a society, I see we have to pay attention just like we are talking about to the very individual things. We have to build systems that are person centered as well. What I mean by that is for older people, hospitals are not the best place to be. First of all, they are dangerous. Second of all, they are expensive, either for the individual or for society, whoever happens to pay. The best place for somebody to be is in their home. Next place is in the community, then outpatient care and, if necessary, hospital. That has to be integrated. Integrated care that allows you to deliver the detail of care you would in a hospital room at home or community is the ideal. Add to that social care, where all of the social services are integrated into medical care as well. So medical care just becomes essentially another social service. And it may not be the doctor who is in charge. It may be the social worker who really knows that person who may be in charge, or it may be mixed responsibilities depending on the particular situation. To me that is a system of a person centered care, and that I think is a positive definition. One that is workable, because it tells you there is a policy that you have to adopt. You cannot have social care entirely different from medical care, and you cannot have mental care, whether for a younger and old person, divorced from home care and social care. There's a group out of Monaco, or a hospital in New York, that has specialized in integrating mental care into home care, whether it is for an older adult or whether it is for an adult with a younger adult with mental issues. That kind of integration to me is the best kind of person centered care, and add to that the individual care for who that person is and you have a good recipe for how societies as a whole can begin to deal with these enormous issues. LL: I like the breakdown of the two different types there. When I go out and speak, I encourage people to kind of kick person 1560
centered care to the curb—because, again, I for the most part think it is overused and under delivered—and start using the term relationship based care because I think that gets to the core. WH: That is one side of it, but that is not getting at the other big issue, which is how a society can, and I can tell you through my work at ACCESS Health, we focus on what government policies can be, because if the government policies aren’t there, it is not going to happen on a major scale. This is huge. We are talking about millions and millions of people. You are going to have many individuals doing what you just said. But if they are not embedded in a system that makes it possible, you get frustration after frustration. You want to read about frustration, read our book about the Swedish healthcare system, which is great if you are young and sick but not good if you are old and ill because their social care and their medical care just are not integrated and it is deeply, deeply frustrating. You could hear it in the voices of the people we talked to that frustration day after day of trying to get those two things to work together. One is municipal, one is county, two different administrations, two different bureaucracies. No way to integrate the payment structures, those things. If you are going to change dementia care on a broad scale, you have got to involve government policy. And that is why I think person centered care or whatever you decide to call it, integrated care, is vital to achieving the goals that you and I care about. LL: It really is about getting everybody on board. Like you said, it goes across the board and can be delivered because all these little pockets are nice and they are helpful, but we have so many different levels of care and so many different kinds of care. You are right. We do need to integrate that big time, so I am totally with you there. WH: What is the whole person, what is their social environment, what is their dietary habits, what kind of families do they live in, what kind of personal support they have—all that is part of taking care of people. You can do it on an individual level, but it is going to be ever more powerful. Finland is currently in the process of integrating all social and medical records so that providers actually know the patient or the person. Whether you are a social worker or the doctor or the nurse practitioner, you know that person. Now there is a big term out there called social determinants of health, as if social determinants of health are different from medical 1561
determinants of health. They are all integrated. You cannot separate a human being from their environment. To me, person centered care means taking in the environment and developing systems of payment, integration, and information that capture all that and make it possible for the people that you and I know to do their work more easily. LL: That makes sense. I think exactly what you are talking about is what we are lacking right now, that information, the delivery, and the payment systems to meld together so they work easily, and so we really can care in the best fashion. WH: As much as we may not like it, that is the government, that is what government policy does. In particular, it is what Medicaid/Medicare does, because they are the ones who pay most of the costs for elder care. LL: That makes sense. Now, when you did your interviews for this book, was there anything that really surprised you when you were talking with people? WH: I was surprised by the degree of frustration. Most people created islands of excellence in the sea of mediocrity, and they were frustrated. That was surprising. They dedicated their whole lives to creating a system that works. Many of these systems are quite different, but they were all working in one way or another. There are commonalities to all of them, but all of them expressed the same problem. These people we can take care of. But what about all the others? LL: I have found, and I do not know if you have found this, but when I travel, and I do not go around the world just in the United States here, but the level of people talking about toxic environment in our healthcare system is it has just kind of blown me away, and the exhaustion of people working. WH: I will tell you about another surprise since you asked about surprises. My previous book is called World Class, and it is a deep study of an academic medical center here in New York. I looked around the world before I settled on this one. What I learned there was they asked themselves a question. First of all, they set the parameters. We cannot influence the government, you know, whether it is Obamacare or whether it is Trumpcare. No matter how big we are, we have a voice, but it is just one voice out of a thousand. We cannot change New York state, and we certainly cannot even 1562
change New York City, but we can be the best we can be. We will do everything to achieve world class status in patient care, in medical education, and in biomedical research. They went from mediocre to the best in the world. They are right up there with the best by any measure. They have been number one in quality and safety. They have the number three medical school. They have the highest per capita research dollars per scientist of any institution in the United States from a bad position fifteen years ago. In ten years they turned the place around by saying, what can we do? Not what the government is going to do. What can we do? There are two parts of the equation. You have to work with the government and you have to get policies right, but you also have to hold people accountable for the quality, the cost, the safety, and the patient satisfaction of what they deliver. You have to hold yourself accountable, and other people have to hold you accountable. The payers. That is a big issue in elder care and in dementia care. You and I know that there is almost no way of holding people accountable for substandard care. They do not get their institution closed. They do not get their money cut off. They are not sent to remedial school. Nothing happens. The next person who comes in gets the same mediocre care as the last person that left. That is not the way it should be. It was a big surprise to see how institutions that decide to be better can do that. We just hope that more and more people do that. LL: To me, what you are saying is it turns into that whole shift in culture of believing that you can be better and empowering employees to try. I think that is one of the downfalls I see in some companies is they have taken out the creativity and the ownership and everything has gotten so task oriented and so driven by not wanting a red flag that there are these huge gaps in how they care in terms of knowing the person. They are doing the tasks and they are checking those off, but there is no twinkle in the eye for the person with dementia, for the family, and for the staff. WH: They do not ask the family, is this person really being cared for? They do not even ask the person. I think that those are important things. I will tell you something else that surprised me. The same people who are doing a mediocre job, when allowed to do a better job and encouraged to a better job and given the resources to do a better job, perform magnificently. NYU Langone 1563
did not change the people. They changed the culture, and they changed the desire basically. Let us have a culture of excellence. Not a question of let us get along. It is a matter of leadership, it is a matter of the board's leadership, it is a matter of the people there. The people who spend their lives in healthcare want to do good. You are dealing with the best kind of people. I have been in an academic medical center. I have been in businesses big and small. And I can tell you there is a big difference. If you are in an academic medical center, a hospital, everybody there wants to do a good job. In a business, most of the people are doing something quite honorable, feeding their family, but they really do not care if they do A, B, or C. When you deal in the health sector, almost everybody is on board. They want to do a good job. You are dealing with the best motivation in the world. You just have to unleash it. LL: You have to give them permission to care. Some of the policies have turned around where you cannot give somebody a hug, you cannot touch them, because of a few bad apples, we have forgotten about the moments of joy or how to communicate or even with families. I mentioned I am doing one on why families act the way they do. We only call when there is a problem. We are not saying that we get that person, that we enjoy their presence, that they are engaged. We are saying we screwed up on a med, they fell down, there is a bruise you know, something is missing. Those are not trust builders. I think we have to realize what everybody is looking for and be respectful of that. Those can be tasks, too, when you make a call or send a picture of those moments of joy. I have talked with a lot of companies, and they are like, oh, well, you know, we will do this every Thursday. I say, no, no, you have made it into a task. It is not authentic now. There is a difference. WH: You are right. I can truly see the many years you have spent thinking about these issues. There is not a single topic we have touched on that you do not have personal experience with. LL: It is interesting, and I believe that any person can make a huge difference. I have been shocked because I was told with everything I have done that it was not possible. It could not happen. For me, I would feel bad not trying. I would be ashamed of myself not trying. I think a lot of people have that in them, but their fear of failure is so much greater. That is another word I have kind of kicked to the curb. I have kicked perfection to the curb. I have 1564
kicked failure to the curb. To me, progress is better than perfection. It is just moving forward. Failure is the opportunity to learn, and it is a gift. It is a gift to make it better. We do not look at it like that. We look at it and we shame it and we guilt it and we throw it in the corner, we toss it out. WH: The one thing we did not talk about is the burden that places on a person. If you are trying to do it as an individual, it is a killing task. When you measure the stress levels of people who are caring for an Alzheimer’s spouse, it is about the same as a soldier in battle, not the soldier resting between fights, but actually in battle. That is for day in, day out, day in, day out. Even soldiers do not fight every day. But somebody caring for somebody with advanced Alzheimer's is, and we need to give everybody support. It is not something that any single person should have to bear themselves. It is too great a burden. I think that is another thing we need to talk about as a society. How do we help primary caregivers if they are a relative with their job? There are so many ways we help children. We send them to school. We have teachers. We have whole institutions for this. Well, guess what? We have more older people than we have children. Should we have institutions like schools that help you as a parent, as a spouse, deal with these issues? You do not ask society. Society did not say educate your kid yourself. Teach your kid how to play football or tennis yourself. Teach him how to play the piano yourself. But when it comes to an old person, do everything yourself for this person. It is not reasonable. LL: Yeah. WH: The burden it puts on somebody is unbearable. It can be born, but it is born with a task, there is stress. We do not think of things that way. LL: It is very important. You want to do the right thing, and you also feel the societal pressure of doing it on your own. I have heard a lot of people say the same thing after I have mentioned this, but it was really interesting. One of the things I found was there were two different kinds of people in the world and one would ask, how is your mom doing because they really wanted to know. And the other set asked because they wanted to give me permission to never go back and see her because they were so uncomfortable not knowing what to do or how to help that they just wanted it to stop.
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When I realized that it was like, oh my gosh, this is really a huge problem that there is this much discomfort in hearing about this. What other things have we not talked about that you just really feel are dire, that people need to understand about our healthcare system and our care cultures and you know, dementia as a whole? WH: Let me just be a little more optimistic than we have been talking. We have been talking about a lot of needs, but technology is going to be a big help. You can now essentially take care of people at home as well as if they were in a hospital. You can do all the monitoring, all the checking, most of the medication delivery, almost everything you could do in a hospital room, you can now do at home, and you can monitor exactly what is happening on a minute to minute, day to day basis. Increasingly we have artificial intelligence services that help you. You might not notice that somebody is not talking or that their speech pattern has been slightly altered, but AI might and will give you a prompt. It will not tell you what to do, but it will say, have you considered that this patient may have a physical, not a medical, problem. They are not moving around as much as they used to, or their speech pattern suggests that they are in pain and they may not want to tell you that. Those are the kinds of things that we can look forward to that can have everybody do a better job. That is a positive story. I do not think, and I am pretty sure we are not going to replace personal care. No robot is going to replace personal care. It just is not going to happen. But technology will make the job of the caretaker easier. Just take something like scheduling. Having a scheduling app is going to make somebody's life a lot easier. All the contacts are there. All the numbers are there. All the things that are supposed to happen when all the addresses are there. If you have a single app like that, it is going to make somebody's life easier. You can understand what is happening with your loved one when you are not always there. You know, in this world of ours, we travel around a lot, even if we have primary responsibility for someone else's care. Technology makes it possible to be a lot closer. There are many things. Those are all positive. We do not rely on technology to do the job, but we allow technology to help us do a job. LL: I like that. I get people reaching out to me all the time in terms of new things that are coming out. It is so important, especially when it comes to dementia in terms of having a pilot base, to really 1566
get their feedback—those actually diagnosed, those caring for them, and thinking about the progression as well, because there are a lot of things that can help them be more independent, as well as just monitoring and supervising them. WH: That is also true. LL: We have so many people who live alone who do not have somebody to help them either. Those technologies can come into play. What do you think of, I know in other countries they have, I cannot even think of the word now, but you know, social workers and nurses come out to the house versus going into the clinic and they are just set up by neighborhoods? WH: I think those are some great ideas. The more you can get people to where they live, as long as people can get out and about, that is fine. When they cannot, it is much better to have people come to their home than have them be shepherded to some other place. People are much happier in their own environments. LL: I think you can get the true scoop on things that maybe you are missing, that are not being told, when you see the environment and things as well. WH: That is right. There are places where a handyman is part of the team. They go in and fix up the house. Part of the problem that a lot of people have is they are dealing with substandard living conditions that sometimes the fixes are pretty simple. Fix the refrigerator door. Make sure that the temperature gauge is working and not broken. That window ought to be able to open. Simple things like that. LL: And the stress that those things cause, too. When I was in residential real estate for twenty five years, I saw that all the time and people would shut down half of their house, sometimes even more, because they were not using it. They did not want to heat it. They did, nor they did not feel safe, doing those steps or the lighting or whatever it might be. WH: Right, the step was loose. It could be fixed. LL: Things were deteriorating, but they did not know who to approach or how they would get funded. WH: Right. There are places we have come across where handymen are part of the team. LL: Yeah. I love that idea. I love that holistic approach. WH: That is tapping into your real estate background. 1567
LL: Yeah. It is very interesting, but it is just one of those things where I think we have to look bigger and broader, and we have to get people past the stigmas and the fears. WH: Those are either called person centered care or social determinants of health, or a lot of different names, but I think we are talking about the same kind of thing. LL: To get people to realize that dementia is just another thing in life we have to adjust to. We have adjusted to cancer. We have adjusted to heart disease. We have adjusted to aging. All of those things. Life is all about adjustments, and it is never going to change. It is always going to be there. It is just how graciously are we going to approach this? How are we going to work as a team to provide the best care and the best lifestyle for everybody? How do we lend a hand up, and how do we ask for help? I think there is such embarrassment here in the United States with asking for help. Who do you go to, and how do you ask and not feel ashamed that you need it? WH: Part of that is you do not feel you are going to get it when you ask. I think in situations where people truly believe they are going to receive care when they ask, they are less reticent to ask. LL: That makes sense, too. A lot of sense. How do you see insurance companies and managed healthcare systems? Is this something that they are really pushing for as well? WH: The answer is yes and no. Those that already have good businesses are reluctant to change. That is normal. But there is a whole financial sector that is quite interested in this, in long term care insurance. We are underserving long term care insurance and there are many, many opportunities, and thoughtful businesspeople are looking at this, certainly in countries like China or India that do not have the Medicare/Medicaid systems that we might. Even here we are looking, there are a lot of people who are looking at long term care insurance. I would say that is one of the big things you look at. Another whole thing is fintech for health. We focus on issues like, how do you pay for cancer care? How do you pay for care of rare disease, but it is a big issue of how do you pay for dementia care? You may have a good insurance policy, yet if either you or your loved one has a serious medical condition, you can end up either in a mental institution or in a living condition where because you are so fragile, you need months of reintegration. Nobody pays 1568
for that. They do not even pay for psychiatric care. Huge gaps in our insurance policies. Medicare will not pay for that. Medicaid does not pay for that. Insurance companies do not pay for that. What are people to do? It is an enormous unfulfilled need. LL: You cover some of that in Aging Well, too, the solutions to the most pressing global challenges of aging. You talk in there about how 4.4 billion Medicare dollars were wasted annually in unnecessary emergency care, and how do we prevent avoidable hospitalizations? There are so many, so many different things. WH: That is one issue, but the other issue is just getting people to pay for psychiatric care, getting people to pay other than you yourself and who can afford it. Some of these places are $40,000 a month. Who can afford that? The one percent. That is the answer. The ninety nine percent cannot. Yet it is needed for a lot of people. LL: Exactly. We are seeing that more and more, every day on the news. The whole mental health of society has just changed so significantly and elevated in terms of kind of the dysfunction and the frustration they are going through and the unmet needs are bubbling to the top, and we cannot ignore them anymore. WH: My hope is the people who listen to you, your audience, will translate what we are talking about into pressure on their city counselor, their mayor, their Congressman, their Senator. Do something about this and find a common voice. We are the biggest voting bloc, and we are getting bigger. We older people are a voting bloc and we should exercise our political power to make sure we get what we need for ourselves and our loved ones, and I would urge your listeners to move from understanding to action, because it is action in the political sphere that will get results. We can see, by looking at the impeachment hearings or whatever else you want to look at, that people are sensitive to what most people in their voting area want. You may agree with it, you may not, but politicians are sensitive. They are listening, and even if it goes against the grain of what they believe, they will do it if they want to get reelected, or they will do it to get reelected, because they want to be reelected and we have to collectively exert our power. If we do not, we will not get what we need. If we do and we do it thoughtfully, we may have a much better world for everyone. So again, I would urge your listeners to figure out what they need from their politicians and put pressure on them until they get it. 1569
LL: We cannot expect them to know if we do not tell them. They need to know the numbers. Well thank you so much for your time today. People can go to your website, which is willliamhaseltine.com or ACCESS Health at www.accessh.org. Again, I thank you so much for your work and taking this time to share it with us. WH: Thank you for all your great work, and taking personal experience and making it general and helpful to many. It is a wonderful thing to have done. LL: Well, thank you. Again, go out there and purchase this book, Voices in Dementia Care: Reimagining the Culture of Care. Thank you all and have a wonderful week. Bye now. WH: Thank you very much.
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March 2020
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Interview With Bloomberg Asia March 4, 2020 | Interview
Female Reporter 1: Let us start with the US. We have already seen eleven deaths out of only a confirmed 120 plus cases or so. Does that make sense to you? William Haseltine (WH): It makes sense in the sense that we can find those people who are sick. We are actually not finding people who are not sick. We are only finding the sick ones and we are finding them in nursing homes and other places where the death rate is likely to be higher. So I think the enrichment for death over infection is artificial. There are many, many people who are infected who are not detecting, and that is a direct result of us not having tests available. Even today as we speak, those tests are widely available all throughout China, many millions of them have been tested, but we just do not it have yet. Female Reporter 1: Now we are getting more and more news of the virus spreading in the US, or at least more confirmations of the spread. Facebook is now coming out and saying that an employee in Seattle has been diagnosed with the coronavirus. We have seen this type of virus before. Why don't we have a solution to this? WH: It has to do with human nature. We respond to crisis and then we forget and we are absorbed by the next crisis that comes along. I am not the only one who has been warning that nature is there ready to pounce. We know about volcanoes, we know about earthquakes. If you live in an earthquake zone, you make preparations to make buildings earthquake proof. We live in a world where the natural world, the viruses, will continually assault us. We know that. Yet, we have not taken the most fundamental precautions. And in particular for this type of virus, nature has warned us twice with the SARS epidemic and the MERS epidemic that these are dangerous viruses. And if you think a little bit beyond that, we have known that these viruses are around for a long time. Every season there is another coronavirus that comes through and 1572
gives us a cold. Polio was a cold virus with an unfortunate habit of paralyzing about one out of a hundred people who got it. It is very similar to the coronavirus, which may kill one out of a hundred people who have it. The symptoms are a little bit worse than a cold for about fifteen percent of the people, but that is the natural world. And we know and we have the tools to prevent it. We can develop drugs that could be stockpiled and available to prevent transmission, just like we know how to prevent AIDS transmission now. We could prevent flu transmission, coronavirus transmission and others. And we should have done it, but we did not. Hopefully we will do it now, although I am not at all sure that we will. Female Reporter 2: With HIV infection, obviously huge strides have been made since the introduction of prep. Could something similar be done for various strains of coronavirus? WH: What is great about it is if we find the right combination of drugs, and it usually takes a combination of drugs, it should work on most, if not all, coronaviruses. The combination of drugs we use to treat HIV work on almost all strains of HIV. So the techniques the virus has to evade our immune system do not work so well to evade our drugs because we work on the inside and the inside stays much more constant than the outside which changes to thwart our immune system. Female Reporter 2: Let me go back a step. You were talking earlier about the very limited nature of testing that's taking place in the US. We know that is why there are differences between the confirmed cases we see in South Korea for example, versus Japan; because of the huge gap in how much each of these countries is capable of testing. If you do not test broadly, how much of a risk is that when it comes to community transmission? WH: It is enormous. The way we know in public health how to handle these kinds of things, you find one case, you test all of their contacts. If there is one case on a plane, you test everybody on the plane, and you test everybody who is in the family and has been in contact with that person. It is called contact tracing. To do that, you need to have the test widely available and you need to have a lot of them available. You do not want people to slip through your cracks. Female Reporter 1: How do you feel about Congress approving that $7.8 billion in order to deal with this outbreak? WH: It is a good start. 1573
Female Reporter 1: Where should it be used? WH: It should be used, first of all, for tests. It should be used for providing ventilators to hospitals. It should be used for making whatever medical supplies we need, and there are a lot of disposable supplies. If you go into a hospital today, you go into an isolation ward, everything you touch is disposable. Well, you run very short of those supplies very quickly in a crisis. So, we need to prepare for that as well. Then, there are longer range things we should do. We should begin to activate; we have legislation dating back to the anthrax attack where people got really worried. We passed some very interesting laws and rules and regulations, and we follow those up with something called BARDA. There is BioShield and BARDA, which give our government the authority to fund and test and approve, on a vastly accelerated rate, new vaccines and new drugs. And so, we need to include the coronavirus in the BARDA/BioShield legislation. I developed a drug from idea to approval and stockpiling within two years and two months. That sounds like a long time, but it is a lot shorter than twenty years, which is what it usually takes. And that is thanks to the fact that as a biotech company, we knew that the government would buy our product and stockpile it. And in fact, over the years they spent $500 million stockpiling this particular way to protect against anthrax. So, should there be another anthrax attack, our government has the drugs at its disposal to protect people exposed from getting sick, and those who are infected from dying. That is what we should have had for the coronavirus and that is what we should also have for flu. So I would think at least part of that money should go to that kind of development program because this will not be the last round of virus we get. Female Reporter 2: Bill, how do you write the Chinese response in terms of the lockdown and containment measures? And is it fair that there is criticism that other countries around the world have wasted that window of opportunity that was given by China to get their own houses sorted? WH: I do not want to make any judgment about another country. I am comfortable talking about my own. And in that respect, I am unhappy that we have not taken full use of the time we have had between the time we knew this was likely to be a threat 1574
and the time we have finally begun to mobilize some sort of response. But even now, our response is disjointed, it is not well coordinated, and it is not what it should be. I was watching a program just yesterday and there was a doctor from the hospital just down the street who was basically tearing his hair out because he could not get access to tests for the people who came in to see him who were ill. And he certainly did not have access to test any of their contacts. So, it really was moving to hear this doctor sort of screaming in agony because he could not do his job because we hadn't given him the tools needed to do his job. But he kept saying, “we have known about this thing since December, and what do I have in my hands today? Nothing.” It was really a moving performance.
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Fireside Chat on COVID-19 at the SwedishAmerican Chamber of Commerce March 11, 2020 | Interview
Barbro Ehnbom (BE): I have the privilege to welcome you all on behalf of the Board of the Swedish-American Chamber and on behalf of the Swedish American Life Science Summit. It is my delight tonight to be able to welcome such a fantastic guest, one of the world's foremost scientists, particularly on viruses. We are lucky that Dr. Haseltine lives here in New York City as he is here tonight to tell us a little bit more about the coronavirus. We will also have a chance to ask a few questions. Thank you so much for being here. William Haseltine (WH): Thank you for the generous introduction. You are lucky to have Barbro as a representative of Sweden. I have worked with Barbro and the Swedish American Life Science Summit from the beginning. It has been a wonderful experience. Not only do you get to go to Stockholm at the best time of the year, which is mid August, but you are there with a wonderful group of scientists from all over the world enjoying the summer crayfish and a cruise through the archipelago. First, a bit about my background. I am a scientist working on applications of molecular biology for medicine. Early in my career I decided viruses would be a way to understand what was happening with human biology. My entry into virology was through studying mouse and chicken cancer causing retroviruses. I had the intuition that this family of viruses would cause human disease. Then HTLV followed by HIV were discovered. I was one of the only people in the world actually working on human retroviruses at the time. I was in the right place at the right time. Let me remind you a little bit of what it was like in the early days of the AIDS epidemic. It reminds me of what is happening now with COVID-19. All of a sudden there was a new disease that was, people were dying. In this city, our artists were dying, our theater actors were dying, our designers were dying. Really the flower of creativity 1576
in New York was devastated. People would lose one, two, or three friends a week. It was a horrible time, and nobody knew what it was. Then it was discovered the disease was caused by a human retrovirus. Still, most people preferred to ignore or minimize the danger as did Reagan, our president at the time. He did not want to say a word about it, even though his friends from Hollywood were dying. In 1985, well after the virus had been isolated, Discover Magazine published a story in which they said not to worry. It is only going to affect homosexuals and drug users. It is not a heterosexual problem. Then a book was published attacking me and Bob Redfield. Today Bob is the director of the CDC. Bob and I were personally attacked in a two hundred fifty-page book called the Myth of Heterosexual AIDS. People did not want to believe what it was. It was hard to get the money to do the research. What has happened since? Forty million people have died of AIDS. About two million people every year are infected and about a million and a half people die each year, even now. The good news is we have a way to control HIV and AIDS. The first way is information, safe sex, a clean blood supply. We have diagnostic tests. All over the world, people know what AIDS is and they know how to protect themselves from it. We now have drugs to prevent infection of those exposed and to save the lives of those infected. We now have a new equation: U=U., undetectable means untransmissable. What are the lessons for today? Well, today we have a new epidemic COVID-19. It is a new coronavirus, a member of a family of viruses discovered in the 1950s. One third of all the colds you and I get are coronaviruses. Everybody in this room has had coronaviruses, everybody. Three of ten of your colds are due to coronaviruses. Coronaviruses generally do not cause too much trouble. They cause a cold. And we know how colds are transmitted. So, if you want to know how this COVID-19 is transmitted, think about what you know about cold viruses. Now there is another example that goes back in history a little bit that most of you know about: polio. Most of you have not had direct experience with polio because the vaccine has been really effective. When I was a kid, we knew about polio because every summer we could not go swimming. We had to be in groups of three, not four. We could not go to the movies. What we did not know about polio is that it was also a cold virus. Only one out of a 1577
hundred people who contracted the virus were paralyzed. Does that sound familiar? Does that sound like this COVID-19? It does! What we are going through right now is familiar to those of us sixty five and older because this is exactly what happened during the polio epidemics. It is nothing new for us. It is new for most of you. Can we control the epidemic? If you do not know who is infected, you cannot control it. That is a major lesson. So, if you do not have a test and if a test is not widely available, you cannot control the infection. What country in the world today has the tests they need? China, South Korea, Taiwan, Singapore. What country is not testing? The US! Why the hell not? Why are we so behind in testing? You talk to anybody in public health and they will tell you if you are going to control an infectious disease and you are fortunate enough to have a test for it, you test and you do contact tracing. If somebody has a symptom, you test them. If they are positive, you test everybody they have been in contact with, and if need be you test everybody they have been in contact with, and you isolate them or you treat them. We do not do that even today, after the virus has been around for three months. What is wrong with the United States? I do not know what is happening in Europe. The promise is in two days we will have the test. Will we? NO way. It is a huge public health failure. Our political leaders are denying that this is a serious problem. Think back to what was happening with HIV. People denied it was a problem until it was unavoidable. What finally did it for HIV/AIDS in the United States was a very famous movie star got infected. It was not just that he was infected. He went to France to get treated and came back almost dead, both from the infection and the treatment. People began to ask, “Why does a famous American have to go to France to be poisoned? Why can't we do something here?” Now there is another aspect that really bothers me about this epidemic, and that is that we should have been prepared but were not. Predictive protection against a tourist attack with anthrax is the model we should have followed for coronavirus threats. Envelopes filled with powdered anthrax were sent to politicians and journalists. Some got infected and died. The attack came on the heels of 9/11. Our government swung into action. We decided that we needed to protect ourselves from terrorists that could use 1578
bioweapons against us. Enabling legislation was passed lickety split. What was that legislation? It was called BioShield followed up by something called BARDA, legislation that allows rapid development, stockpiling and deployment of anti-bioweapons vaccines, drugs, and diagnostic tests. That legislation is meant to protect us from manmade bioweapons. What about those diseases that nature itself produces? In the recent past we have experienced epidemics and some pandemics. AIDS, swine flu, Ebola, Zika, and many more. We are not protected against the worst terrorist of all, nature. Think of nature as the ultimate artificial intelligence machine. Evolution produces billions of random changes in viruses every day in an attempt to find chinks in our armor. It is not surprising nature succeeds. There’s a whole world out there in nature that is after us. That we are not prepared is evident from the COVID-19 pandemic. Could we have anticipated this event? Nature gave us two warnings. Yes. Our situation is like living on a volcano and hearing terrible rumblings. We had SARS, we had MERS, and we knew you could get lethal viruses. So, what happened with SARS and MERS? After the first and second lethal coronavirus attack, scientists around the world took the lead and began developing drugs both to treat and to prevent infections. And guess what? They came up with many drug candidates. The drugs showed they worked in the test tube. They showed they worked against the virus, and some even worked against animals infected by SARS and MERS. Those drug candidates are still around. I will give you a graphic example. My daughter is a sculptor. She works on biological themes. She competed in Singapore for a big sculpture in the middle of their Biopolis and she won. She asked the Biopolis scientists what they were most proud of and they said it was their creation of a SARS protease inhibitor. We can stop the SARS virus. She made a sculpture based on their work. It is a walk-in sculpture. When you walk through the active part of the SARS protease, you become a drug that stops the SARS epidemic, and by the way, you are walking on a pavement built in the form of the drug they discovered that stops the SARS and MERS proteases. Why can’t we take that drug today? Because it was not economically feasible for big pharma companies to spend the money to take the drug through the human trials necessary for FDA 1579
approval. The financial incentive was not sufficiently attractive. There is no regular market. There is no predictable market. No government was willing to step in to stockpile the drugs. That is why we do not have it. You can go to the literature and find twenty compounds that, if you manufactured today, would prevent you from getting infected if you were exposed and would cure you if you got infected. There is one drug approved in China and the NIH is testing another that may work. That is really good news. My prediction is that within a matter of months we are going to have prophylactic drugs and we are going to have curative drugs available. It is going to happen. Most of the work is already done. It is now just a question of turning the crank. Following BioShield rules, a company need only show the drug works in animal models of human disease and one safety trial. It can then either be sold or stockpiled. Let us take a broader perspective. What does nature hold in store for us? There will be another lethal coronavirus epidemic. When? Five years, ten years from now. There have been three in twenty years. Why should there not be another? Let’s be prepared. Let us stockpile the drugs. Most antiviral drugs work on the inside of the virus. Unlike the outer shell of the virus, the inner working changes very little from strain to strain. Combinations of two or more antiviral drugs also defeat virus resistance. We need a set of anticoronavirus drugs that act on different viral proteins to use in combination, just like we do for HIV. What else is out there that is going to get us? A terrible new strain of influenza, that is for certain. The last time a brand new flu came around, it killed between 50 and 90 million people. That was 1918-1920. The next one could kill a billion people or more. How did the 1918 flu kill? It triggered an immune reaction called cytokine storm. Well in the morning, dead by evening. Are we protected? No, we do not have the prophylactic or curative drugs for flu. Why? Because it is a hard virus to work with? Not at all. I look at that virus and see at least ten different ways you can make prophylactic and curative drugs for the flu. Let’s learn our lesson and bring new anti-flu drugs to FDA approval and stockpile them for what we know is to come. What else is on the horizon? As we are sitting here, 500,000 Indians are going to die of tuberculosis and one third of those are 1580
going to die of antibiotic resistant, multidrug resistant tuberculosis. You talk about something you can catch on a plane just by breathing. You do not want to be on a plane anywhere near somebody with antibiotic resistant tuberculosis. That is much more dangerous than the flu or anything else that you are likely to encounter. Over half a million Indians a year have it. Are we prepared for it? We are not. Nor are we prepared for a wave of antibiotic resistant bacteria that exist and are spreading around the world and in our hospitals. There is a big dearth of research in antibiotics. Such research is perfectly suited for national governments to create markets that do not naturally exist. COVID-19 is yet another lesson from the natural world, one we have ignored in the past and ignore in the future at our peril. If you live in an earthquake zone, you build earthquake proof houses. If you live near a volcano, you pay close attention to the local seismometer and clear out when it goes off. Yes, we are on the alert today. But will we forget again tomorrow? It is up to us to work to convince those in government meant to protect us now and in the future. I am happy to answer some questions. Questioner 1: The World Health Organization has declared COVID-19 a pandemic. How will that impact our everyday lives? Should we participate in social distancing or should we continue with life as normal? WH: You should not continue with life as normal. You should avoid big crowds. Do not go to political rallies. Do not go to sports events. Do not go to the opera. Stay away from all big crowds. If you take public transportation, wear gloves. Wash your hands, take it seriously. If you are going to be in a public space for a long time, a taxi or an airplane, wipe down your seating area. Questioner 2: You did not mention malaria. Malaria is another big problem too. WH: Yes, exactly. Malaria is on my list too. Drug resistant malaria is a growing problem. Questioner 3: Will a vaccine against COVID-19 protect against the next coronavirus infection? WH: Probably not. Coronaviruses are what I call hit-and-run. They must change their coat every year to avoid our natural
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immunity. Like the flu, a vaccine against last year’s coronavirus most likely will be weakly effective at best Questioner 4: Do you think drugs effective against one type of flu or coronavirus would be effective against all strains. WH: Very likely. Combinations of drugs that prevent and cure one strain of influenza and one strain of coronavirus are very likely to be highly effective against all strains. Viruses vary the outer shell much more readily than they do the key enzymes they need to reproduce. Questioner 5: How many people die a year from influenza infection. WH: In the US between 20 and 60 thousand people die per year from influenza. On average about 400,000 people die each year from the flu. Questioner 5: What would be the advice from an expert like yourself to chiropractors? Mine is worried sick. WH: Anybody who is in a service industry should be worried right now because we do not know how many people are infected. That is a huge problem. The United States is a service economy, not a manufacturing economy. So, we are going to get hit hard. Questioner 6: Will the infection disappear in the summer with the heat and spare the tropics? WH: I would not count on that. Singapore lies just above the equator. It is moist and warm all year round. Singapore has a problem with COVID19 and had a problem with SARS. Questioner 7: What do you expect from Trump's task force? WH: Not much. So far the administration's response to COVID-19 has been pathetic and dangerous. Denial, deferral and prevarication coupled to inaction. We have every right to be ashamed of our leaders. Not so our professional public health officials who have been muzzled. I hope for better. Our local officials are doing what they can, but they need federal help and guidance. BE: Thanks Bill for an excellent discussion.
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Interview With MSNBC The Beat With Ari Melber March 18, 2020 | Interview
Ari Melber (AM): We turn now, as we have been doing on so many of these nights, to experts involved in all of this. We are joined by Maryland governor Larry Hogan, who has declared a state of emergency, closed schools, bars, and restaurants, and activated the state’s National Guard. We are also joined by William Haseltine, an infectious disease expert and former Harvard professor, who has done extensive work in HIV and AIDS. He was also in Wuhan this past Fall. New York Times columnist Michelle Goldberg is also here today. Her writing has been about how she is grieving for the way life in New York has already changed. Thanks to everyone for coming. Governor Hogan, what are you telling your citizens? Governor Larry Hogan (LH): This is an unprecedented worldwide pandemic, and none of us have imagined something like this could ever happen. We have been taking unprecedented actions almost every day. This virus is rapidly changing. But we have been taking actions as fast as we possibly can and trying to get the federal, state, and local leaders together with all of the smartest experts in the medical profession, in hopes of saving hundreds of thousands of lives in America. I am the chairman of the National Governors Association. We had our fourth call today with all of the governors. We have another one with the President and Vice President tomorrow. Every level of government is trying to do everything possible to address this pandemic, but it is pretty overwhelming. AM: Governor, take a listen to what one of the fellow governors you mentioned you work with, Governor Cuomo, recently said. Governor Andrew Cuomo (AC): “Today we are announcing a mandatory statewide requirement that no business can have more than fifty percent of their workforce report to work outside of their home.” AM: What do you see as the most important measures and how much of them need to be uniform? You mentioned your role 1583
leading the Governor’s Association. You are talking to the President tomorrow. You are in the thick of this for your state and across the country. How much of it should be synced and how much of it needs to be tailored to the given situation in each state? LH: Governor Cuomo is actually my vice-chairman of the NGA. He was on the call with us today and will be on the call tomorrow. What has been happening is each governor has been making decisions on their own in their states based on the situation on the ground, but we have also been sharing information on an ongoing basis back and forth. However, some of these decisions could be made and perhaps should be made at the federal level, but we are also not waiting for those decisions. We are taking those actions. We are one of the first states in the country to declare a state of emergency, one of the first ones to close all of the schools, and one of the first ones to close all the bars and restaurants. Governor Cuomo’s action today is really cutting edge. Some of the things we are talking about in California with shelter in place, there are numerous actions being taken by governors across the country. People are being as aggressive as possible because every day that we wait, we are putting more people’s lives in danger. AM: I hear you on all of that. I want to bring in Professor Haseltine. There are many clichés that get kicked around, and we want to be vigilant and clear, not panicky. This is an important time for people to understand, whether you are watching the news or talking to your friends who do not watch the news, that what you do not know can kill someone. I want you to listen to some of the reporting we have seen in places where as much as this pandemic is being talked about, some of the information clearly has not reached everyone. Professor, I ask you in all seriousness, what do you say with the national mega phone we are handing you tonight to people who think that if they are not seeing it in their lives, it feels like “an overreaction?” William Haseltine (WH): Even if you are young, a millennial, middle aged, or old, no one is immune from this virus. We know that everyone who is exposed can get sick, and in some cases very sick. Even people in their middle age can get sick and die. Look what happened to the young 33-year-old doctor in China. This is a very serious infection. It causes mild symptoms in many people, but a very large number of people contract serious symptoms, up to 1584
fifteen and sometimes twenty percent, enough to send them to the hospital and maybe even the ICU. This is not an infection to take lightly. AM: What did you learn from your time studying and dealing with the situation in China that may be relevant here? WH: The first thing to say is China is extremely well-organized and very disciplined. The other thing to say is Wuhan is a very beautiful city with a very capable research center as well. Two million students or more graduate every year from their universities. It is a very important city for China. I have an operation in China and many of my friends are from Wuhan and other major cities there. To watch what they are doing is really incredible. They are monitoring each and every person. If you live in an apartment building, they know if you go out. If you go to get food, you will be stopped three times on the way. What is the result? Today, they are getting back to normal. Singapore is also very well controlled and are getting back to normal. There are pictures of filled streets in Singapore because they have controlled the infection. This is an infection that can be controlled. However, to control the infection, we have to control ourselves. AM: When you put it like that, of course, everyone is well aware of the differences between our country and some of these other states that have different systems of government. We might not like their approach to liberty and human rights, which are very serious things to counterbalance, but from an infectious disease perspective, you see some upside. This is a time to be aware of all of the tradeoffs. I want all of you to stay with me, as I turn to Michelle. Let’s hear your view of understanding what is happening in America, Michelle. Michelle Goldberg (MG): None of this should be a surprise. People have told us that this was coming for weeks or even months, so there was time to prepare. I think it was inevitable that it was going to hit us. It was not inevitable that it was going to hit us this hard, though. It was not inevitable that we would have the shortages of ventilators and ICU beds. Now, people are living in extreme distress. You don’t just have people who have had their lives upended by illness. You have people whose jobs have been lost. Every single empty restaurant is many, many people who will not work again. A lot of these businesses are never going to come back. Our cities are not going to look the same when this is all over. 1585
However, we could not have been spared. No amount of preparation could have spared us for what is going on right now. If you look at those boys on the beach, on the one hand, they sound very irresponsible, but on the other hand, they sound like people who might have simply taken what the president was saying a few days ago to heart. People are just now beginning to wake up to the gravity of this situation. It is at least in part because our political leadership is only now beginning to wake up to the gravity of the situation. AM: I think that is an important point. We have been careful to let the evidence lead here. But governor Hogan, I would give you a chance to address that in all seriousness and not as a “political observation.” Did the President and other leaders make a mistake by saying as recently as two to three weeks ago that everyone needs to “relax” and that this would basically go away by itself seasonally? LH: There is no question that was a mistake, but I do not think we should waste a lot of time finger-pointing and talking about what mistakes the President or anybody made in Washington D.C. Let us talk about what we can do right now. But this discussion is exactly right. I have been talking about this for more than a month. We declared a state of emergency about sixteen days ago. We have had press conferences every day, but nobody was really taking it seriously. Last Thursday, we put an order in place across the state about limiting the social contact in bars and restaurants and limiting the number of people. Everybody completely ignored it. St. Patrick’s Day weekend, they were jam-packed. Then we had to actually shut them all down, because people were not paying attention. AM: Walk us through that, because you are one of the people that has to make these hard calls. Give us a little more color and detail on what you are saying. You basically were trying to initially work through more voluntary methods and you felt in your own state that your constituents did not “get it,” so you had to get more drastic. LH: Well, I have had press conferences almost every single day for the past two weeks and said things are going to get worse. These numbers are going to ramp up. We have to address these things. And everybody said “oh, that is interesting.” We have messaged and taken actions every day, but just in the past few days, a lot of people said this is not a big deal. It was not just the President saying that. 1586
There were people on the streets. Kids partying in bars did not think it was a big deal. Now everybody is home, watching your show and watching other networks that are saying, “oh my gosh, look at these numbers and look at what is happening in Europe.” They are looking at us closing the border, shutting down Visas, and putting shelter in place. Now people are paying attention, but it is almost too late. Every day we do not take action is causing more damage. Yes, we are behind the eight ball. Yes, mistakes were made at every level, but let us talk about what we are going to do today and right now and what we can do together at the state, federal, and local level, as well as with the private sector and the smart doctors. Every single American is in this together. It is not Republicans and Democrats. It is everyone. It is the citizens who have to join us in this, because no matter what we are doing in the elective office and what the smart doctors are doing, if the citizens are paying attention, they are the ones that can stop this from spreading. They all have to be a part of this. Everybody is in this together. AM: Governor, I appreciate the point you are making. You mention the numbers sinking in to people watching. We have some of the numbers approaching 8,000 cases. The Dow down six percent, wiping out years of gains because of the reaction, and then thirty eight states with school closures. Michelle, I give you the final word here. MG: I am one of the people whose children are at home, and I have very abruptly been turned into a home schooler with no experience, but nothing could have prepared us for what is happening right now. Nobody who is alive right now has ever experienced anything like this, but there is still no excuse to the extent to which we have all been cast at sea. I should say, though, some very competent governors are really taking charge of the situation. AM: Right. That is why these conversations are important. We lose the governor who is going to be busy, so I appreciate you making time for us in the broadcast, Governor Hogan and Michelle Goldberg. We keep Professor Haseltine. I have some other questions for you, sir.. The risk of the coronavirus that is also specifically facing nurses, doctors, and healthcare workers, is coming into view. According to the previous reports, two E.R. Doctors are in critical condition 1587
because while they were doing their job, they themselves contracted the virus. Meanwhile, the head of America’s largest union for nurses warns that many nurses are still lacking the protective equipment, gowns, and coverings for the head, legs, and feet that are needed to fight the virus. Here is what the head of the Minnesota Nurses Association stated. Female Speaker: “Minnesota nurses from many different hospitals believe their respective hospitals are unprepared and unequipped to protect nurses. I have witnessed this mad scramble for people to get the PPE that you only have one or two masks left on the floor. That is up at the desk, in the drawer, or it is locked up.” AM: That brings us to Lisa Merck, a Colorado nurse practitioner who started feeling sick after returning home from a trip to Hawaii. She was feeling ill for weeks but was initially denied a test. When she did get one, it came back positive. Lisa Merck is here and joins me along with Professor Haseltine, infectious diseases expert. Thank you so much for agreeing to talk to us. Walk us through what you felt and how you were delayed in getting the test. Lisa Merck (LM): My symptoms actually started around February 19th. I just had a slight runny nose. Then my body started aching, but I thought it was because we were traveling and carrying backpacks. We had been gone for about three weeks, and then we came back. I went and got a massage. I just thought that would help out. Then my symptoms waxed and waned. I felt good. I went and volunteered for a race and watched my little nephew. Then on March 1, 2 and 3, I started getting a fever. My husband also had a fever. We laid in bed and just kind of laid low. I went to my clinic and got an influenza A and B test because I thought we had the flu. They tested us for influenza, but that was negative. Then the 2nd of March, I called the CDC and I called our local public health department and just told them about all of the travel that we did. I told them what my symptoms were -- that I had a fever, but no cough or anything like that. They said that I did not meet the criteria for any type of testing, so I went back to my clinic and worked. I was feeling a little bit better. AM: Let me pause there, Lisa, just for our reporting purposes. You made an effort to take precautions, but in this world we are 1588
living in and with the shortages, you were basically told that you could not be tested, but you could still go back to work? LM: I never really asked if I could go back to work. I just assumed it was okay because nobody seemed on high alert that I would have the coronavirus, so I did not either. I went back to work for a couple of days. Then on the 5th, 6th, 7th, and 8th of March, I started feeling really ill. I started getting very nauseous. My joints were hurting much worse. I felt like every time I would sit up I wanted to collapse, and I was having shortness of breath. I finally asked my husband to take me to the emergency room on March 8th, where he took me in there and they did a full workup on me. They did a chest x-ray and found out I had viral pneumonia. My white blood count was low. They did a CMP, which was fine. Then they did the COVID-19 test, which was positive. They then sent me home and told me to wait. That was on March 8th. I did not get my results back until four days later on March 11th, so I have been in isolation since March 8th. AM: What is your take away from this? Do you look at this like it could have gone better? LM: I think it could have gone better. I think we can test more people, and we can get the tests out much faster. Right now I have some friends and family that are still waiting for their tests. They were tested on Friday and are still waiting for test results today, so I think rapid testing is going to be key right now. AM: It is very striking to hear your story. Professor, I want to bring you in and ask a new question, because everyone can understand if you say the system is stretched and working as best as it can with the priority matrix. I think most people can accept that. Yet as with so many things in America, it is not a uniform priority matrix. There have been reports of other people who may not really meet the criteria somehow as VIPs still getting tested before a nurse, for example. WH: That is the worst type of public health. What you should have with a disease like this is contact tracing. Anybody with symptoms that fall within a very broad category should be tested. You should test everybody who has been in contact with those people and trace all of their contacts, followed by mandatory quarantine. Everybody who has symptoms that are broadly defined 1589
should be tested. It is not a question of how many tests you have. If you do not have the test, you can’t do it, but now that we are about to have the test in a few days, it is how you use those tests that are going to be really important. Italy had a lot of tests and has had a big problem. They did not do rigorous contact tracing and mandatory isolation. That is what needs to be done now. AM: Let me take a final question, Lisa. What do you say to other nurses and doctors who look at this and their families and are thinking about the risk exposure? What do you say to them because clearly you seem to believe in your profession and this is hard on everyone? LM: I have a lot of friends in the nursing field and the healthcare field, and they are just really worried. “Is this worth it to my family? Am I bringing stuff home to my family?” For me as a nurse and to my fellow nurses and healthcare providers, am I going to get reinfected again? The other thing is how long am I a carrier for? Right now I have been told you need to have two negative corona tests 24 hours apart. Then I was told the other day that I only need isolation for ten days, and now I was told I do not need any other testing. I am very worried about going back in the public sector and practicing. AM: Professor, can you briefly resolve that for us? WH: I wish I could. There is no answer to that question. The only answer to that question is to make sure testing is done frequently. Not just every so often. Every day is the best way to do testing. Certainly, she needs to be tested many times, at least twice before she goes back to work. Part of the problem is the tests are not available yet to do that. AM: Right. First of all, I appreciate both of your candors in walking us through what we know and do not know, and acknowledging what we do not know is part of this. Second, we do have reports of the federal government and the Congress drastically increasing the funding and the support for testing. That part of the help is on the way. I want to thank Professor Haseltine who was with us for multiple parts of the show, and Lisa Merck, I want to wish you a continued speedy recovery. Thank you and all the nurses like you doing your work. Thank you. LM: Thank you. 1590
WH: Thank you.
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Interview With MSNBC Stephanie Ruhle March 23, 2020 | Interview
No transcript is available. The original piece is available here: https://www.msnbc.com/stephanie-ruhle/watch/nyt-scientistsidentify-69-drugs-to-test-against-virus-81103941523
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Interview With MSNBC Morning Joe March 26, 2020 | Interview
No transcript is available. The original piece is available here: https://www.msnbc.com/morning-joe/watch/doctorrecommends-strict-measures-to-curb-coronavirus-in-u-s81229893860
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Interview With China Global Television Network March 30, 2020 | Interview
No transcript is available. The original piece is available here: https://america.cgtn.com/2020/03/31/the-heat-covid-19-impacton-spain-and-u-s
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April 2020
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Interview With Houston Matters: Special Edition April 1, 2020 | Interview
William Haseltine (WH): It is a pleasure to be here. Ernie Manouse (EM): It is sad that it is under these circumstances, but I am thrilled you accepted our invitation and can join us to talk about this. You have had a lot of experience in what goes on in these global pandemics and understand the way to treat it, the way to look at vaccines and medications. At this point, do you have hope? WH: We always have hope, and in this case, I have got a lot of hope. This is not a hard problem to solve from a drug point of view. This is a virus. It is not cancer. It is different from your body. It is a foreign invader. Not only that, there are many, many points of vulnerability. We have very powerful tools to find new drugs that target these specifically. We have a lot of drugs that we know work against viruses, not this one, but we are confident that because we have been able to find drug cocktails for HIV, we are able to cure hepatitis B, there are great drugs for herpes virus infections. This is a problem that can be solved. It will not be solved immediately, but I guarantee you we will solve this problem. As for vaccines. We are hopeful. Vaccines are more complicated. These viruses have developed ways to evade our immune systems in one way or another. That is why they are successful. We certainly will have vaccines. Vaccines will raise immunity, whether it is a perfect shield or not, we do not know yet. And for how long if you are vaccinated, whether protection be long lasting or not, we do not know yet. I am reasonably confident we will also have effective vaccines and that if they do not stop the disease will certainly weaken its impact on the human population. EM: The problem with vaccines, though, it is going to be a wait before we get them. No matter what we want to do, no matter what we hope for, there is a little lag time there.
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WH: There is going to be a lag time for truly effective drugs and there is going to be a lag time for the vaccines. EM: I was going to say, early on, the President was talking about different drugs we could use and it felt as though they were talking about it like no matter what your illness, just go into a drug store and just pick something up. There has to be more thought when people say what kind of drug can actually show potential to help with this particular virus. This is a little bit in the weeds of a question, I know, but how do you go about deciding where you should even look in the world of drugs that currently exist or even in vaccines that were started to know that they might show hope in this battle? WH: Let me answer that question in a couple of ways. First of all, I want to make sure whoever is listening knows there are no drugs that we are currently certain will work to treat this disease. No drugs. You may have heard about of a whole series of drugs. We do not know that any of them work for sure because they have not been done and tested under the proper conditions. The first place to look for drugs that we might already have approved that could be useful are drugs that are useful for cancer, as well as those that are useful for other viruses. So far those have not proved to work. That does not mean that they will not. It just means it has not been proven yet. The next place you look for drugs is all of those chemical compounds, drug candidates that were produced to fight SARS and MERS. There were many, as many as twenty possibly thirty, that were shown to be potent in their ability to stop the virus growing in the laboratory. That is different from showing that it is safe in humans and that it will stop it in humans, but at least it is a good start. Why, you might ask, don't we have those available today? Because we stopped all research when we thought SARS or MERS would go away, despite the fact that I, and many, many people who understood how dangerous these viruses were, urged that we bring those to completion. We did not. The third place to look: We know what this virus needs to grow. There are at least four or five absolutely critical parts the virus cannot do without. I have great confidence that we can find new compounds not yet discovered that will work to stop each one of those. So, we are very confident in the long run. The short run, I would say is still very much open. 1597
EM: When we talk about coronaviruses, we tend to use the term coronavirus to mean what we are talking about today, but as we know it is a whole family of viruses. Are there other drugs out there that are effective against other coronaviruses. Is that somewhere we might look? WH: There are a lot of coronaviruses. There are eighty eight different families of coronaviruses and within each family there are many, many variants. There are no known drugs that are shown to stop coronaviruses. There is a short term potential treatment and a way you might even prevent these infections and that is being tested right now, passive immunotherapy. Passive immunotherapy initially uses convalescent sera. That sera can be used to treat those that are most critically ill. That is being done today. The next step for passive immunotherapy is to prepare hyperimmune IgG from convalescent plasma. Hyperimmune IgG is purified from large pools of convalescent blood. If there is a large enough supply, hyperimmune IgG can be used to treat those who are critical and to protect healthcare workers. I am pretty sure that will work. I think hyperimmune IgG should be available sometime this summer. EM: Why would people consider chloroquine related drugs for treatment of COVID? WH: The answer is a little bit technical. When the virus enters your cell, it goes into a little compartment within the cell. The virus needs special conditions in that compartment to initiate infection. The chloroquine family of drugs has the potential to change those conditions so that they are unfavorable for the virus. There is some evidence in the laboratory that that happens. Now the problem. This approach has never worked well for other viruses that rely on a similar strategy to initiate infection. What works in the lab does not always work in real life. The issue may be the amount of the drug needed to change the conditions enough. That level of drug may be toxic. We already know enough to know that, at best, the chloroquine family of drugs may have only a weak effect. They might be mildly effective, but they will not cure all. It simply will not be. What will eventually be the cure is either the hyperimmune IgG or very specific combinations of antiviral drugs.
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What is happening now reminds me of the early days of HIV/AIDS when people were desperate to try any kind of drug. We learned a very powerful lesson. Be careful of what you try. Suramin as a treatment for HIV was tried in France and other countries. It did not work and was toxic. Curiously the enthusiasm for chloroquine drugs also started in France, by a doctor with a controversial reputation. There was Compound Q, a drug from the traditional Chinese pharmacopeia. A community of gay activists tested Compound Q outside of government control. A lot of people ended up dying sooner than they had to. After that failure I was part of a dialogue with the leaders of that community. They learned an important lesson and became partners rather than critics in drug testing by the NIH. Curiously, I was working very closely with Tony Fauci in those days, the same Tony Fauci, and this is thirty years later, who is leading the fight against COVID-19. When Tony issues cautious statements about the drugs some are touting, be sure that he has very good reasons to urge caution. EM: Wendy, one of our listeners asked, “Why weren’t vaccine and antiviral drug efforts continued after the SARS and MERS epidemic waned?" WH: The belief that disaster won’t strike again seems to be an integral part of human nature. People put out the fires of today but generally not those of tomorrow. One lesson we should all take away from the COVID pandemic is that nature is mounting a sustained attack on human beings. Each organism is in a fight for its own survival. Each must adapt to its immediate ecosystem. For many viruses, we humans are part of their ecosystems. Each day, nature throws up trillions of random mutations in viruses that may infect us. Usually they don’t help the virus. Sometimes they do. The viruses, by massive parallel mutation, are out there trying to crack your protective code, whether it is our immune system, our healthcare systems, our social systems. Nature is experimenting with ways to find the chinks in our armor and no matter what we do nature will succeed. Nature is a far more dangerous and persistent foe than any ideological terrorist. Think of all of the living world as a giant AI machine capable of learning. What is it learning? How to replicate in this delicious environment of billions of humans closely networked and closely interacting.
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The lesson? Know that we are and always will be under assault and prepared to defend ourselves for the inevitable. EM: How do we know where to put our resources? WH: We’ve known for at least seventeen years that coronaviruses are dangerous. Nature warned us once with SARS. Nature reminded us once again with MERS. It seems we did not heed the lesson. Now that we are in the midst of the third assault we rue the day we dropped our shield. But will we remember tomorrow? What else is coming our way. We know antibiotic resistant TB is out there and coming to get us. We know that antibiotic resistant microbes, specifically flesh eating staphylococcus, are out there and are coming to get us. We know that global warming is changing the environment, so tropical diseases like malaria, dengue, zika, and yellow fever are coming our way. We know a new, highly transmissible and deadly influenza strain, one far more deadly the SARS-CoV-2, is on its way. We just do not know when, but we are certain it will come. Up to one billion people or more may die if we are not prepared. Can we protect ourselves? Forewarned should be forearmed. Just after 9/11 and the anthrax attacks that followed closely on the heels of that tragedy, we ramped up our defense against bioterrorism. The Department of Homeland Security working with the Defense Department, the Centers for Disease Control and the National Institutes of Health created a matrix. Down one axis were potential organisms that might be weaponized. On the other axis were extant defenses. Where there was a match, the box was checked. Where there was an open square, the government promised to buy and stockpile vaccines, drugs and other effective countermeasures should some company develop one. I know the process well because at the time I was CEO of a company that filled in one of the boxes. We were in fact awarded a contract to supply a strategic stockpile. We need to be far more prepared for what we know is coming our way. That means research. It means development, and if a drug company will not pay for it, the government should pay for it just as we do to protect ourselves from bioterrorists. When I worked with Tony Fauci on that legislation, we made sure that the wording covered "new and emerging infectious disease of man made or natural
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origin." We have the legislation, we have the tools, we just did not use them. Frustrating then and even more so now. You bet! EM: One listener asked us to discuss testing people for antibodies to the virus. They are beginning to do that in England. WH: There are two types of tests. One measures the presence of the virus itself. I call this genomic tests. They detect the actual virus. The early versions were slow and cumbersome. After a swab was taken, it was sent to a specialized lab for analysis. The results are slow, many hours at best, many days at worst. Recently a new type of genomic test has been developed and approved for use. This test also measures the presence of the virus itself. The test is called a point of care test. A positive answer shows up within 5 minutes, negative in 15 minutes. That will be a game changer. But the supplies of this test are very, very limited. There is a different type of test altogether. These tests determine whether or not you were infected by the virus. They measure the immune response to the virus. Within the first two weeks of infection the body makes an initial antibody response. These are called IgM antibodies. Several weeks later the body begins to make more effective and longer lasting antibodies called IgG antibodies. Tests for such antibodies are fast and cheap. I recently described, in the New England Journal of Medicine, the use of one such rapid test to screen the entire population 12 and over for evidence of infection with hepatitis C. It required one drop of blood from a finger stick and took five minutes to get the answer, and cost 50 cents each!! The test is made by a US company. We can do the same for SARSCoV-2, and we should. Serologic tests that cost $1 or less are available from China, Singapore and an increasing number of sources. I just learned that Andorra is going to test everybody, all 70,000 people. EM: We have been very fortunate here in Texas. Our numbers are still relatively small. Can you actually control this virus, this outbreak, by opening some areas and closing others? Keeping some people on stay at home orders and other areas can be open and relaxed? WH: You probably cannot do that in the United States. In China they were relatively successful with a modified version. It is important to understand exactly what they did. In China, if somebody is infected, they contact the trace. They do a very rigorous 1601
interrogation to make sure they know all the people that person has been in contact with. Each and every contact is put in what they called controlled quarantine for fourteen day post exposure. Controlled quarantine is isolation in a single occupancy hotel room. Leaving the room is not allowed. I emphasize everyone no matter their test result. That is how China controlled the infection. That is how Singapore is controlling the infection. That is how South Korea is controlling the infection. It is not what we are doing. I am sitting here in the middle of New York, in the middle of our rampant epidemic. We are not doing contact tracing to any extent. We are not putting people in mandatory isolation as single individuals. We know this virus can be controlled without any medical intervention. You can stop this epidemic. We are not doing what is needed to stop it. We are doing what is needed to slow it. I have a thought experiment for you. All of us know by now what flattening the curve looks like. That means reducing the number of new cases at the peak and stretching out the timeline of the epidemic. I am interested in the area under the curve. That tells us how many people will be infected in total. Flattening the curve helps prevent hospital overload. As the curve moves down, flattening the curve does not mean reducing the total number of people infected. It could mean that, that might be the case for South Korea, Singapore, Hong Kong and Taiwan, but it does not necessarily mean that. A word of advice from Houston. Don’t believe you will be spared. It is simply a dangerous assumption. EM: What can an individual do to protect themselves and their family? WH: The most important thing to do is to remain at home and as isolated as you can be. And when you leave the house for needed supplies, leave for the shortest time possible. Only have one person go. Wear gloves. Wear a mask that protects others if you happen to be infected. Limit your exposure to as short a time as possible. Wash your hands when returning home. I wear gloves when I go out and wash my hands when I return. Be careful of how you handle the gloves as you do not want to touch what those gloves have touched. Do not go out and mix with other people. Do not have friends over. Do not take any public transportation unless absolutely necessary. If you must be in public, wear a mask and cover your hands. Be aware. Be vigilant. Be in the moment and do not let your mind wander. 1602
EM: Will the virus mutate to become airborne? WH: It does not have to mutate. It is already airborne. Maybe not as airborne as some other viruses, but it is also airborne. EM: What does that mean so people understand? WH: It means that you can get it from breathing the air that somebody exhaled. SARS-CoV-2 is not as infectious as tuberculosis, for example. It seems to be airborne to some limited extent. EM: What should we do with the cruise ship in the Caribbean now looking to dock? WH: Well, you are getting beyond my area of expertise. That is a very tricky question. I just feel for all of those people who are on those ships. I do have a word of advice. Stay off cruise ships for a long time to come. EM: If tomorrow you were handed the keys to the kingdom, what would you do? How would you start to fix this problem? WH: The first thing I would do is institute mandatory contact tracing and fourteen day isolation for all those in contact with a person known to be infected. I would do population based genome and serology screening. I would do everything in my power to make sure healthcare workers had the equipment they needed to keep themselves safe. We only have so many healthcare workers and we are losing them. In other countries they are losing them pretty fast. It’s a real tragedy. Every life is a tragedy, but a life that can save other lives is a special kind of tragedy. In the United States I would activate all of our research efforts. I would order the pharmaceutical companies to drop almost all other projects to concentrate their full power to finding drugs, vaccines and monoclonal antibodies to prevent and cure this infection. I would put a full court press on our efforts to create protective hyperimmune IgG so that we can protect our healthcare workers. That is off the top of my head but give me more time and there is much more I would do. EM: Thank you for your time. WH: You are welcome. Fare thee well Houston! END Note: This transcript has been lightly edited
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Interview With Michael Davidson, CEO Of Gen Next, Inc. April 2, 2020 | Interview
Michael Davidson (MD): So doctor, really, really appreciate it. I will jump right into the sort of mechanics and nuts and bolts of the science. There is a discussion about the mysterious COVID-19 denominator. Do you think we will ever understand the global scale of an infection? And can you even just elaborate on what it means to have, you know, what a denominator is. William Haseltine (WH): Well, thank you. Thanks for your question and thanks for the opportunity to speak to this very interesting group. Let me just begin by responding to something you said early on, which is what is going to be the new normal. Each of us looks at our own lives, our own cares, our own focus for what the new normal might be. For me, since I began working on pandemics in 19, early 1980s with the AIDS pandemic, which by the way has killed about 40 million people just to give you some perspective on the size of various pandemics. I, and many of my friends and people that I know in this community had been warning this was going to happen. We are still warning it is going to happen and it is going to happen again and again. The way I think of nature today is a giant AI machine. It is trying to crack our code, our healthcare code, our immunological code, our social code. And there are trillions of experiments, random changes in viruses and bacteria happening every day in which some of those are trying to find a way to grow in this new environment, which we have been kind enough to give them, seven billion of us packed into cities, traveling all over the place, and that is nature. It is there. It is going to stay there. It is going to be continuing to crack our code, and we have been warning this is going to happen. It has been extremely frustrating that after every epidemic, the interest flows away, the money flows away and we are sort of left high and dry and nobody will listen.
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I learned something about a Greek myth that you may find interesting. You might, some of you may know the myth of Cassandra. Cassandra was cursed. I forgot, I actually looked up why she was cursed, but she was cursed with a curse that she could see the future, but nobody would believe her. Now, I used to think it meant that nobody would listen. The curse was more subtle. People did listen to Cassandra. They just did not believe her. The most famous case is she goes to Priam and she says there are Trojans in that horse. He listens to her and said, I hear what you are saying. I do not believe you. Okay. That is how we all felt. Some of us were privileged to be listened to by people who had authority in various countries to do things, but we just were not being believed. My hope is the new normal we will be believed. And I think there is a chance of that not because of the people who are going to die. Already forty million people died of HIV/AIDS and that was not enough to warn us. It is because of the economic impact. American society did not begin to react until the stock market crashed. That is when the administration got into action. If you actually want to put a date is that very first day we saw that dramatic drop. That is when our government, federal government swung into action. Local governments knew there was a problem before. I think because the economic devastation is so severe and by the way is going to be persistent for a lot longer than people think. People may remember, and my hope is our new normal will be, we will put the effort in a fraction of that, my guess is $50 trillion, $60 trillion to get this globe back in functioning order. A tiny, tiny fraction of that could have stopped this. So that is, I would like to begin by saying what I hope we learn from this. We may learn it, we may not, but it is something we should all encourage additional research and initial preparation. And by the way, we know what is coming. We know there is going to be another flu. We know there is going to be another coronavirus. We know there is going to be antibiotic resistant bacteria. We know antibiotic resistant TB is coming. We know these things are there. We cannot tell you exactly when, but it is 100% certain it is going to happen. And so I hope we get prepared. The good news is we know what to do. Will people listen and if they listen will they believe? And then will they translate that belief into action? So that is not the question you asked me. And now I am prepared to, if you 1605
want to re ask the question, I will answer your question. That is a per oration, I guess they call it. MD: I appreciate it. I want to go back to some of those ideas, I do. I like them. Can you talk about the COVID-19 denominator on the global scale. WH: Well the denominator is how many people in the world are infected. And we can know that pretty quickly and pretty cheaply. And the way you do that is with a, what is called a serological test. You measure the level of antibodies. You do not wait for people to get sick. Some people never get sick. So I give you an idea how cheap and fast it is. Abbott developed a fingerstick for hepatitis B, excuse me, Hepatitis C. Egypt tested 65 million people at 50 cents a pop in five minutes, you get the antibody results. That is what you can do. They organized the test for the whole country. Now they tied that to free treatment and they eliminated hepatitis C from their population. They treated 4 million people with the drugs that eliminated. And by the way, $35 a person and it cost us $80,000 a person for the selfsame drugs. But just to give you an idea how quickly and easily it can be done, and those tests are on the way. The Chinese make them, the Singaporeans make them, we can make them. A lot of people can make those tests and they can be made very cheaply, very fast. That will give you an idea of how many people have been infected. It takes about two weeks, maybe a month before you show up, but if you have been infected, we will know what the denominator is. We do not know it now, but we will know it. But to me, when I listen to Fox News and other places like that and they talk about, oh, we really do not know the denominator, it is only one percent lethal or 0.5% lethal. It is bad enough. Look at our hospitals. We know a lot of people are infected. I do not know what the fascination with what the hit rate is. And by the way, that depends very much on the health of the population. What the real question people ask when they say, what is the denominator is if I catch this virus, how sick am I going to get and or how big a problem will it be for my country if you are a leader and that depends on your healthcare system. I have seen places where the hit rate, at least as far as I know, is about five percent and other places where it is below one percent. To me that is a question of measurement. It is also a question of how healthy the people are and it is very important 1606
how good the healthcare system is to take care of you because it can make a huge difference when you go to the hospital and you are critically ill, what hospital you go to and how you are treated and it is not really, we have drugs do treat you yet. It is just supportive care. I will give you one small example. Normally if you have terrible respiratory problems, which just gives you so you really cannot breathe it and you are going to die because you cannot get enough oxygen into your body. They stick a tube down your throat. To do that, they got to put you on Curare so your muscles relax so you do not gag. And so they basically paralyze you. And that is what happens. If you are lucky enough to recover, you are basically paralyzed and totally weak and takes you a long time to get out of there. There is a hospital here in New York that has figured out a new way to do that. They do a little tracheotomy. Put a tube down there, they use far less Curare or other measures and people recover much faster and you will get a much better airway access. So there are little things like that that are going to make a huge difference in that numerator, denominator that people are so concerned about. But the answer is we will know from serological tests. We do not know now, but we will know. MD: So the question is, it sort of speaks to your point that it has a ripple effect. You know tracheotomy, other treatments that are needed to stabilize in the moment. And that creates a burden on the system at large. And so you start to know how large that systemic effect is going to be. It seems like somehow we have to have an idea of how widespread and how fast it is going to go. You know, even I think China, watching their reporting, they were saying X amount dead, but they were, you know, multiples of that of urns distributed. Is that true and is, what is the likeliest scenario, you know, say for the next month to three months of how infectious it is going to be? Or do you think that we will have a sense of the containment from understanding the test and the innovations like you mentioned like in the hospital in New York. WH: First thing to say, this is a highly infectious virus. We know that. People can go to church and another group can come in and if they sit where the other people sat who happened to be infected but asymptomatic, they can get infected and they can die. Whether and how long it works for an aerosol, let may tell you an experiment I 1607
remember that was done with a cold virus. I do not think it was a coronavirus, but it might have been some time ago. They took soldiers and they put them in a tent, thirty of them in two tents. One of them they divided with a screen, which air can freely pass. They put somebody with a cold into both tents. Everybody in the open tent got infected. And only those guys on one half of the tent where the guy was introduced with the cold got infected. So that tells you what some colds do. You have to have some kind of touch. It was not just through the air. Now this virus may be somewhat like that, but it may be a little different. I am asking my friends right now who may have a long memory to go back to find exactly how that was done. But I do not think we can do that experiment today, but we did do it back in the fifties and sixties. So this is a virus. It is contagious. You have to worry about it. It is spread around. And so what is the most likely scenario? In the US what is going to happen and what we are seeing happen is we see what happened in New York and it is, we do not know where on that curve we are. We know where the ascending part of the infection. There is a hope, the containment, the way we are doing it here in New York will slow the spread and eventually the number of infected people will go down. We are not sure the kind of measures we are putting in place in New York are good enough yet. They are not what the Chinese did and they are not what the South Koreans did and they are not those methods that are shown to work for this virus. We are a lot looser than they are in the way we are doing self isolation. For example, the Chinese had three levels. If anybody wants you can go to my website and you can see an interview I did with several people actually who have gone through this process. But for example, there is self isolation, which is what we do. There is home quarantine, which means you cannot open your door. You are there, and you cannot open your door and it is very carefully policed. And then there is controlled quarantine where if you have been known to be exposed to somebody, you are put in an isolated hotel room and you cannot open your door for the full fourteen days. That is just if you happen to be on the same plane that somebody who was exposed. Everybody in the plane goes into an isolated hotel room. That is how they controlled it. Today, anybody who comes in from outside of China is in controlled quarantine. They are home, they cannot open their door. They can open it to get the food and that is it. 1608
Somebody from their apartment building puts the food in front, runs away, you open the door and that is how you get your food. Are we doing that? No. So are we sure that we are going to bend the curve? We hope we are, but we are not doing what we know works. If you do not do that, there is another way to do it, which is what the South Koreans and the Singaporeans do. And that is very rigorous contact tracing. If somebody is infected, they sit them down and they go through a very long detailed interview. All the people since you could have been infected, that you were enacted and all of those people as a minimum are put into home quarantine where they cannot leave their apartment and some of them are put into hotel rooms. So that is how you control it. And it is not a matter of testing. It is contact that matters because the Chinese knew that some of their tests were false negatives. So they did not even bother with a test. If you are on that plane, you went into the hotel room and anybody wants to read that story. I think my website is www.accessh.org. It is the organization that I a chair. So we do not know. And the next thing that is going to happen is you are going to see this infection roll out across the country. If we are lucky enough to begin to control it in New York, it will be still on the rise elsewhere. The implication in the country. The implication of that is that we have got to control for the last big epidemic in the country, not the first one because those people can come and re-infect the uninfected population. So we are in a situation that is going to be much longer than people are thinking about today because we are not, and then we are going to have to wait until the last country is clear because this virus is going to spread all over South America, all over Africa, all over the Middle East. It is spreading everywhere and until that has burned itself out in the world or until we have an effective vaccine or effective prevention and treatment, we are going to have to be shut down. It is something that people have not actually thought through. I do not think you have heard this argument before because you have to think through what is likely to happen. And if you look at China today, China is coming back, they say, but if you fly in from outside of China, you are quarantined for fourteen days. That is it. You have to do home quarantine for fourteen days and in some cases in Singapore you might have to do controlled quarantine, be stuck in a hotel room for fourteen days. 1609
And if you go from one city in China to another, you have to do self isolation for fourteen days. That is how they are trying to control the virus. What is that going to do to the global economy in China? And how fast does that mean they can come back? Yeah, they can come back partially. They tried opening theaters and closed them back down again. MD: Can you talk, I know we are going to probably have quite a bit of questions on China. I want to get some time for the science of it. Can you talk about the race for the therapeutic antiviral drugs, your expert perspective? So one, a bit about the race for the vaccine. How is that unfolding and two, the symptom fighting kind of therapeutics? WH: Okay. So let me say, first of all, despite what you may have heard, there is no real way to treat yourself if you are sick or no proven antiviral therapy. You may have read that there is things like chloroquine or remdesivir or one thing or another. I can tell you as we speak today, there is no clear controlled trial that shows what works. Will there be? Absolutely, there will be but there is not yet. So how is that going to roll out? The first thing that is happening, and it is happening now, is convalescent plasma. When you recover from the virus, and we have studied this in other coronaviruses, you make antibodies and those antibodies help shut down the infection. Taking sera from those people and giving it to somebody who is critically ill can sometimes prevent that disease from progressing. The earlier you do it the better because this virus causes some damage which is irreversible, but if you catch it early enough, convalescent serum may save lives and we are now doing that and it has a good probability of success. I think the success in some cases is very high, but it depends when you use it. The next step we are also gearing up to do and that is to make what is called hyperimmune gamma globulin. What you do is you identify people who have recovered, and we have over three hundred centers around the country to do this. You collect their blood, prepare the plasma, measure the ability of that plasma to knock out this particular virus, the ones that are best you pool, purify, that is called the IgG antibody and that makes a safe and effective way to treat the virus. You treat people who are again critically ill as early as you can, but there is another very important 1610
use for that IgG, the hyperimmune IgG and that is to protect healthcare workers because if you give them those antibodies, they are going to be protected from up to three weeks from infection. Maybe not all of them, but it is a pretty good way to protect. So within the next by summer for sure and maybe before, we are going to have preparations of hyperimmune anti-COVID gamma globulins to use for those who are critically ill and for healthcare worker protection. That is good news. The next step, and I know a lot of people around the world and some of my former students and professors that were in my department are very actively engaged in this, is taking the next step and making human monoclonal antibodies that will do the same thing and then you just manufacture them. So you make monoclonal antibodies. Probably you need a cocktail of two because this virus can mutate and get around one. We already know that from its sister viruses, MERS and SARS, they can mutate. You probably use a cocktail of two, both of which neutralize and then you just manufacture that. Those antibodies are being produced as we speak. They have to be scaled up. It is a big process. They have to be proved, they have to be shown to work. But I developed one such antibody when we were subject to anthrax attack and we developed an antibody in a really short period of time, a monoclonal antibody, which would both treat you and save you if you were infected and almost dead actually. It brought the animals back from the dead just about. It was protective for up to two months if we gave animals the vaccine, I mean the monoclonal antibody, and that is what we are looking forward to. So I would say we are going to have that certainly this year and hopefully within months rather than towards the end of the year. So those are the three things we can do right now. If there is any questions I am happy to answer before I go into drug development and then vaccine development, those are three different pathways, but the most immediate thing is sera from convalescence, hyperimmune gamma globulin and monoclonal antibodies. MD: Two other questions. What was it about Wuhan in your opinion why it originated there, why it spread so quickly there? WH: First of all, I had never heard of Wuhan and when I was there I thought, how dumb am I not to know about this big huge city. It is a major transportation. It is the Chicago of China. And 1611
nobody had ever heard of it. I knew about it because the man who runs my foundation in China is from Wuhan and he had always been telling me how wonderful it was and when I was there it was fantastic. Sometimes there is an image that everybody maybe people my age have in their head, and that is swimming in the Yangtze River, a little round head bobbing in the river that we used to see every year. Well, that is where he went swimming. The Yangtze River runs right through there. It is a beautiful city. It is like a park city. It is got enormous hills that are green. It is got very big parks. It has got one of the biggest biotech parks and high-tech parks I have ever seen in my life. They graduate two million students a year and they absorb many of those in their high-tech businesses. Almost every LED comes from Wuhan and in fact if you go down in the city and the river Yangtze at night, the whole city is lit up, every building around you, in a coordinated LED display. I found it a little bit garish, but it certainly is impressive. If you see every building with a ripple going around for maybe a mile on each side and through the middle and the bridges all coordinated. Every building is lit up with LEDs. So it is a very interesting city and it is a major transportation hub, a major research center. So a lot of people. Wuhan is also the city where the Sun Yat San Revolution took place that created a democracy in China before it was subject to all the troubles that went through with the Japanese invasion and WWII. And then the revolution. So it is a very rich history. It is a beautiful city. It is a very high-tech city. It is a highly educated city. And it is famous for street food. I went to a morning street food and it was fantastic. Actually, I took pictures for my grandkids. There were some unusual things like scorpions on sticks and grasshoppers and little grubs the kids found kind of fascinating, but the street food is, they are famous for their street food. One thing is they send all over China is a spicy duck neck that might not what you want to chew on for your midday snack. It is what a lot of Chinese chew on that for midday snacks. So Wuhan is a great city and it is a shame that it happened there. Now why did it happen there? It could happen anywhere. Coronaviruses are all over the place. Every year we have a coronavirus cold that goes through. It is one third of all colds are caused by coronaviruses. They live in bats and bats live everywhere. One thing that most people do not realize is one quarter of all the 1612
mammalian species are bats. They are extremely successful. There is1400 different types of bats and they all can harbor the viruses and also some very interesting biology. They are resistant to most viruses and cancer and the reason I think they are is because they have to use so much energy to fly that that gives them inflammation and they can have to evolve to control that inflammation and in so evolving they control cancer and they control viruses. We can learn something from them. It is actually our immune system is generally killing us with this virus. You get a hyper immune reaction. It infiltrates your lungs and kills you. Your immune system is working too hard. Well, the bats immune system is tapped down so the virus lives in them but does not kill it and it is all over the place. The previous big coronavirus infection, actually it was from a tune bat in Egypt infecting a camel exported to Saudi. China is not the only source of these viruses and is not the source of these viruses every year. So we get these every year. It is just this one happens to be lethal. Now most people do not realize that polio was a virus like this. It was a cold virus that one out of a thousand people got paralyzed. We know the numerator and denominator is there and there would be a whole chain of transmission paralyzed, whole chain of transmission, paralyzed. And until we had the serologic tests, we did not even know how it was transmitted. When I was a kid, we thought it was in the water. Stay away from swimming pools in the summer. We knew it was human transmitted too, do not go out with more than groups of three. That is what we all lived through. People my age. But these cold viruses come from everywhere. So to call it a Chinese virus is not exactly right. These viruses are everywhere, bats are everywhere and they harbor lots of different viruses and they continue to come out. That is what I was saying earlier when I was talking about nature as a giant AI machine trying to crack our code. That is what it is doing and it is everywhere. Do not be paranoid. Just be prepared. MD: Now my last question and then we will open it up to the members in the chat and then just for members to please. We will try something new. If you are on by video, you will get preferred treatment when it comes to question time. So love to see the faces. All about the community. It helps me hug you appropriately. So my question is about the measures that China has taken specifically and then the comparison between authoritarian countries and free 1613
societies in general. And at what point do our values play into dealing with a pandemic? And I want to give a personal story that informs my point of view. When I was 19, I did some volunteer work in Fort Worth, Texas working with individuals with HIV and AIDS. And one of the things that always broke my heart was how they talked about how utterly stigmatized they were and that oftentimes that was worse than the disease itself. And so that informs to me how a free society treats this. And so I have this sort of shutter a little bit when I hear, let us track everybody. China is using an app, they are heat seeking everybody and I understand the public health implications, but how do we balance those two when you have totally different ways of living? WH: I would say that there is no real difference between an authoritarian government and a democracy in times of plague. If you look around the world, there is not a real difference. There is a real difference in other aspects, but it is not got to do with democracy. It is got to do with the efficiency of government, the responsibility that leaders take and the preparations that they do. South Korea is a democracy. Singapore is a democracy. Those are real democracies. Taiwan is a democracy and they have done at least as good a job as China has done. Democracies can cope with this. It is not a matter of democracy. It may be a matter, at least at the beginning of how people define their personal freedom and their parameters. But the Romans came up with a formulation a long time ago and I suspect other societies before that, which is when it comes to governance, the public health is the greatest good and public health exigencies trump any other legal framework. They trump any other personal because we all recognize that we live in a collective society and our freedoms are constrained. We cannot go out and kill the people we are angry at. We cannot go in and take their money because we want it, even though we would like to have some money that other people have. We have constraints. And in an epidemic where your behavior can kill, not one, but hundreds of other people, our world, our governance systems have learned to constrain your behavior. And if that behavior means locking you up in a hotel room, if that behavior means tracking where you go, that is permissible and it should be permissible because the greater good is the survival of the rest of humanity, not your individual freedom.
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Now will those apps, will those techniques extend beyond the epidemic? Well, we already know they extended, they were there before the epidemic. You know, people using facial recognition. They are using, yeah, and it is not only the government. Who actually knows where your cell phone has been. I have seen these demonstrations where they can track you every single minute even when your phone's off. They know exactly where you have been minute by minute. And companies have that capability. They are using that to predict where deals are going down in New York City by looking at where the phone usage is. It is amazing what you can do. And as private companies, it is not just the government that has that. Those are broader questions that are beyond disease control. But we should be grateful we have those tools to help us identify. I have interviewed somebody in great detail about the WeChat app and how it works in China and that you can go onto your WeChat and find out is there somebody near you infected? And if there is, how near they are, just like we have, is there somebody you want to date near you? Is that person a block away, five blocks away? We have that technology and we have had it for dating. Now we have it for this. So I am not worried about that. I think it is perfectly appropriate to put in the most stringent personal controls if you are in danger by your behavior of killing other people, which is really the way you should look at it. MD: All right. Let us open it up for questions. WH: Pretty serious stuff, but that is, you know, this is serious times. MD: It is a free society that is your point of view so we can engage it. I like a place to talk about big and grand rough ideas, so appreciate you bringing it in. I am going to start going to some of the members here. Hang on. Matthew, I am hoping, hang on here, Matthew, I am hoping to see you on video, but I am still going to let you have the first question. You put it here in the chat box, please take it away. Question: Thanks Michael. And apologies for not participating with the video. So Dr. Haseltine, thanks for being here. You have kind of touched on this a little bit, but I wanted to double down on it. There has been reports that China is suppressing its data to the world and not sharing the true amount of people infected or killed in their country by this virus. Some reports I have seen have been 1615
speculated be over 200,000 deaths and while alone, meanwhile, we have been hearing reports that their financial centers are back online and people are still back to work and that there is no new cases found in recent days. Can you speak to these reports and their numbers? WH: I would say as far as I know, the Chinese are being accurate and transparent in reporting their data. And what I hear from my people on the ground corresponds to what you are hearing from their government. I think at this point there was a period at the very beginning, and I actually tracked day by day in great detail what happened about the first ten days. There was some reason to believe they were not totally transparent. After that, I think we have had total transparency from the Chinese government. I cannot prove that, but I can tell you everything I hear is consistent. So I think that is an unpleasant rumor that should be put to rest. I think we should move on to the next question because I think that is all I want to say on that. MD: Brian Vulwinkle, I am going to you next. Thank you for visiting with us Dr. Haseltine. A quick anecdote, then some macro data and a question for you to respond to. My neighbor 42 just recovered from confirmed case of COVID-19. He said it was like a flu and like previous years he did not go to see any doctors. His wife insisted and sure enough test came back positive and he did not take any radical experimental drug therapies, not even a prescription. He just overcame it like flu in previous occasions he had. With a doctor at Stanford and Dr. Katz at Yale discussing the idea of herd immunity that we may have been exposed to this since January and cycle through millions of folks and perhaps with respiratory diseases or respiratory issues result in the morbidity of 168,000 each year from data from the CDC, about 438 per day on average. Could this have been out there and herd immunity and happening and that is when COVID-19 been lost in the big data. WH: The answer to that is I do not think so. The way, the reason that I do not think so is you track hospital admissions. I have been in touch with a number of hospitals and people working there at the heads of hospitals and doctors working there. They have a, they are the people who actually see the most dire effectiveness and it is a dramatic and major change. What they will tell you is this is not the flu, this is not the flu. You talk to somebody who is really ill or getting ill and this is not the flu. This is extremely serious and you 1616
can go from being well to being extremely ill in a short period of time. And so the way you look at what this infection is doing is what the hospital admissions for this are, and that is brand new. Secondly, herd immunity. What does that mean? That means that about 150 Americans, million Americans would have to be infected at a, let us take a conservative death rate of one percent. You figure out how many million Americans that is. One percent of 150 million is a lot of Americans. And that is what herd immunity would mean. It is heartless and thoughtless to think that herd immunity is going to protect us. So the answer is we are going to have better data as we talked at the top of this hour when we have the serology test, we are going to see how, as the very first question is what is the denominator. But the numerator we are getting very clearly and it is new, it is on the upswing. And you have seen that in China and other places. They just did not have these admissions, then they got them. Now they do not have as many. So they have very few now. So, I hope that has help answers your question. And congratulations for learning how to use the video. Take care. And good for your neighbor. MD: Greg Schoenberg. I am going to go to you next. I saw you on video. It looks like you went off video. Sneaky. I am going to unmute you. Greg. Question: Hi doctor. Thank you so much. Yeah, here I am. So my question relates to the spread of the virus into different parts of America, specifically rural parts of America. And you know, I am wondering if you could speak to whether or not the virus will ultimately spread out in a different manner or it might be less lethal or it will just take more time. WH: I think the last question is, it is going to be haphazard how it gets into rural communities. You have seen rural communities in Georgia that all got completely wiped out as somebody got in there and it just spread around. And that was a chance that somebody happened to end up in that city. Well that chance could happen anywhere because there we know there is asymptomatic transmission so you can feel perfectly well. You could never feel that you have been infected or you can feel you have had a mild cold and you can be spreading it and some fraction of those people who get it are going to get very seriously ill and show up as a COVID epidemic. And that can happen anywhere. Look at Idaho, the ski 1617
resorts in Idaho. People would say, oh this is the best place. Clean air, mountain air. Some people who are infected ended up in that community and it is a hotspot of people who are really seriously ill. So it can happen anywhere. Now to your question, will this mutate in a way that changes the way it transmits or it changes its fundamental lethality? We already have one piece of evidence. It is not as lethal as it was originally in Wuhan and that is, there were actually two strains that you can see. The very first epidemic was more lethal than the second. That is not to say the second one we are experiencing now is not lethal. The first one, and they can actually measure changes in the genome to show that there are two slight changes. There is some slight changes that led to a slightly less infectious form, pathogenic form of this. There is speculation that the reason for that is those people who got sick very quickly were controlled more tightly than those who got sick more loosely and so one virus was controlled by our action, human action and the selective pressure was human action against those who got quickly sick to give a strain that took longer and was not as lethal. That is a speculation but it does show that in real time the virulent properties of this virus can evolve and that is not unusual for these kinds of diseases. It would be unusual, this virus is a little bit different from some others because, for example, from HIV and some other viruses and that it actually has the ability to proofread itself when it copies itself. It is got a whole proofread. It is a pretty big impressive virus actually for an RNA virus, it is the biggest of its class and it can be that because it is making fewer mistakes when it copies. If you think about something that has to reproduce itself and it has an intrinsic error rate, many of those errors are going to be lethal to the virus. So there is a limit, if you do not proofread about how big you could be. That may be 15,000 units long. This one is 30 to 35,000 units long and it is got a proofreading activity. That means it does not change so fast. Does not mean it cannot change, but it does not mean it does not change so fast. So I do not think in the near term we are going to see major changes in the way it is either transmitted or whether it is increased or decreased lethality. I hope that helps. MD: I am going to go to a Lee Mark and then Dr. Dundat. Lee, you are, I will let you go.
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Question: Hey doctor, thank you for sharing your knowledge with us today. My question is this, so far stay in place orders are being put in place at the state level or regional level. But the timing and the ground rules are not necessarily consistent. Some kind of curious at this point with the spread we have had, what would the effect of a more nationally coordinated timing around stay in place order do to slow the spread of the virus and how long if it were successful, how long would it need to be for? And I have the same question for the effect of us wearing surgical masks if and when in public. What effect might that have? WH: Okay, let me answer them separately. It would have been very beneficial had there been a federal order to stay in place. It would have minimized the impact around the country dramatically in my opinion and the opinion of many public health experts as well. I am not alone in that opinion. We did not do it. We still have not done it. And we do not have a uniform measure. For example, I understood, although I have not actually read the order that it is still possible in Florida to have major evangelical Christian meetings, even now, even though there was a lockdown. There are some exceptions. It would be enormously helpful to have the same standard and a strict standard around the country promulgated by the federal authorities. And it is just human nature that you need protection. You need political cover to take such a dramatic action. And governors as you have seen, have waited till they get what they think is political cover. They are worried about their constituents for exactly the reasons we were talking about. Americans do not want to feel constrained in any way. We are used to not being constrained. And there is a lot of, I think that is it is in some cases it is a great thing. In this particular case, not so great. In terms of masks, masks are of three or four functions. The first is it prevents you from spraying out fomites. And those we know can contain infectious virus. And because we do not know if we are infected and we can infect somebody else because you can be asymptomatic and not even feel bad. You do not know if you are spreading around the virus, so it makes sense to put a mask to stop that kind of fomite and to wear gloves when you go out. Secondly, I think has a major psychological impact. If you are taking trouble to put a mask on yourself, you are going to be much more aware of your own situation, much more aware of your effect on others. And 1619
you can see in Italy where people thought they were nuts to wear masks to now they think you are antisocial if you are not wearing a mask when you go out. That is going to happen here too. Especially in areas like New York where people are infected. You see people really giving you a dirty look if you do not wear a mask today and that is going to happen more and more. So masks do have a beneficial effect. Now they are not going to protect you from breathing in because the virus could go right through that mask. So I hope that answers your question. Thanks. Question: I just was wondering how long, if, if people were staying in place right now, how long would someone like you recommend that in a coordinated way they do it? WH: You know, it as long as there is a high incidence and rising incidence and as long until we get to a lower level of infection and spread of infection in a city, I think it is a good idea to wear a mask and it is a good idea to stay in home quarantine and as I mentioned earlier, it is going to be a lot longer than we think because we have to protect ourselves from internal migration. And as long as there is a major focus in this country, we are going to have to protect ourselves in our cities by very careful measures. We can be freer. If you are in Singapore for example, people go out, they go even to theaters, they go to restaurants, but they know their government has done everything it can to isolate every contact that might be infected. We could get there, but it unlikely we are to get there soon. And the trade-off is that kind of strictness versus how long you are going to have to be in home quarantine. The people in Singapore were never home quarantined like we are or self-isolated like we are. They just never were. They never shut things down like we did because e they took a different, more strict measure. So it is really a balance for when we can be released from home quarantine. It is going to be longer than we think. MD: Dr. Dundat and then I am going to go to-WH: Let me say one other thing that I like to make sure that I mention. People talk about flattening the curve. I think this group is sophisticated enough to know it is the area under the curve that matters as much as the timing of that curve. When people talk about flattening the curve, I want you to look at the area under the curve. How many total people are going to get infected. People are not 1620
talking about reducing the number of people when they talk about flattening the curve, they are talking about not overstressing the healthcare system, not saving lives. Okay. It is a different or not saving people from infection. The area under a flattened curve could even be bigger than an unflattened curve. We have to do both. We have to not only flatten the curve, we have to reduce the area under the curve and I do not hear that conversation. MD: Dr. Dundat and then Brad. Question: Hey doctor. It has been very enlightening and I appreciate all the information you are giving us. I do not know if I understood you correctly because I had not heard this before. Did you mention that there has been mutation in COVID going on that you guys have seen? If that is true, how do you think that that might impact the development of the vaccine and the monoclonal antibodies? WH: That is a very good question. Let me take monocle antibodies first. Monoclonal antibodies work by a very precise fit, atom to atom on the surface of two molecules, an antibody and the target spike protein. We know from other studies that the SARS and MERS virus can escape from a single monoclonal antibody by making one or two extra bumps so the fit isn't good anymore. We know that. That is why I think a monoclonal antibody therapy is going to need at least two to make it harder. That is what happened with HIV/AIDS. You may remember AZT, it worked for many people for one year and then they died. It took a protease inhibitor plus a reverse transcriptase inhibitor to get to the state where people could begin to live a normal life and now we have thirty different drugs that work on different parts of the virus. It is one of the things I helped to pioneer, that whole theory of how he needed to do combination chemotherapy. That is what we have to do with monoclonal antibodies. Now a different question is vaccines. Vaccines usually produce a very broad array. Now I have just written a piece which I am going to post shortly on will we have a vaccine? And my answer to that is almost certainly we will, but it is not a hundred percent sure. One of the tricks of this virus, which is a little bit disturbing, is that it, a lot of the antibodies you make are decoys and do not actually neutralize, and they are short-lived. Coronaviruses that neutralizing antibody responses generally no longer live than a year and you can 1621
be reinfected with the alpha and beta coronaviruses after one year with a selfsame strain. Now how do we know that? We in the late fifties and sixties did exactly those experiments. We infected volunteers, waited different times and reinfected with a selfsame strain and they were reinfected. So there is a vaccine, it may not work for very long. So there are some real questions. I am totally in favor of a massive efforts to make vaccines, but a vaccine may not be the one and only answer to this problem. We have to be prepared to do many things. And when we are developing vaccines, I am recommending that we do at least ten different ones simultaneously. And I agree with Bill Gates that we have to immediately ramp up the manufacturing for any one of those ten in case one works better than the other. And I can think of at least ten or more ways to make vaccines. I have been involved in making vaccines for thirty, forty years now. So there are a lot of great ways to do it, but we have to try them all because we simply do not know which ones will work and even the ones that work best may have their limitations. That is pretty sobering, but I think it is, it is accurate. MD: I am going to Brad and then I am going to Nia Stefani. Question: Thanks so much doctor. Hello from sunny Phoenix, Arizona. My question originally was about the antibodies, but I think your response really helped me understand the kind of the recurring, the chances of when it immediately developed on them that they could still get infected within, after a year period. So really like my concern right now is I think about it is people who are symptomatic in some way may get tested. Generally in my observations are it seems like people who are asymptomatic are not being tested, so even determining who may have antibodies presently available through plasma or otherwise seems to be like a structural or institutional problem in a sense. What are your predictions on that and how that could play out over the next couple of months? WH: Yeah. Even before this became a big problem in the US, long before actually, I have been following what they have been doing in Egypt. I just published that article in the March 12th issue of the New England Journal of Medicine and in Egypt they have a program called 100 Million Healthy Lives and a friend of mine runs that and they created a nationwide program. Their country's about 90 million people, but it is got about 65 million, 70 million people 1622
over the age of 12. They created a nationwide program to test everybody in the country for hepatitis C antibodies and viremia, everybody in the country for hypertension, for diabetes and obesity. They set up 10,000 testing centers and they work with companies to get the Abbott test down to 50 cents and the Roche PCR down to $5 and they tested within a year, everybody in the whole country. That is what we should do for a number of chronic and infectious diseases including the coronavirus. We should do it. If Egypt can do it, why can't we? That is how you really get information and if you look at the health problems in America, hypertension is a major cause of death. That is avoidable. Diabetes is a major cause of death, which can be managed. Obesity, huge costs as can be counseled and hepatitis C and pretty soon COVID and other viruses are going to be treatable. We can do that if the Egyptians could do that and it didn't cost them all that much. Now part of the reason they were able to treat everybody is they got the cost down to $35. Here it costs $80,000 okay. That is another issue that we have to address, but we could do much, much more and we should learn to do much more. Hopefully we will put in place a population based, COVID screening serology test, finger stick five minutes, you know the answer and you record that answer on a tablet which is distributed and it does not take a huge amount of training to administer those tests. I was watching massive training programs with about forty, fifty people at a time, average housewives, painters, average guys off the street who decided they wanted earn a little extra money by participating is one of these trainings at these testing centers. There were supervised by doctors. They were not done by doctors. And it is an amazing program. If you want to read about it, it is in that March 12th issue of the New England Journal of Medicine. So the answer is we can do it, we should do it. Will we do it? It depends on people like you putting pressure on your congressman, your senators and other people you know, to get this kind of reasonable program done. And it could be useful for lots of our health issues. MD: I am going to ask Nia’s question for her. She has some little ones running around. The question is, you know in terms of day to day routines and even everything from ordering food from restaurants and Amazon orders, there is this sense that the virus could be everywhere and you need abundance of preparation. How much 1623
should we just cut off all interaction even with ordering food from restaurants. WH: You cannot, you cannot do that. You go to eat right? You got to get your medicines. There are certain things you have to do. Can you take extra precautions? You can wipe down packages. You could do things like that, but who knows if you have ordered out, somebody sneezed on it. Who knows if you pick up an apple from a grocery store, if somebody sneezed on it or touched it. The other day I watched somebody with their bare hands feeling the avocados. Okay? I said, well, can you do, when you take those avocados home, you make sure you wash them, right? I do not know how many people wash avocados before they peel them. I never did, but I sure as heck I do now. So you take the precautions you can. We have to live. We live with humans. We are, you know, a collective species. But you take the precautions you can and that is the best you can do. You know, the way, again, going back to my friend who was on that airplane, he was in a hotel room for eleven days, not because they did not want him to be infected, but they put it him there and somebody with a hazmat outfit would bring us food, put it in the door, ring the bell and run like hell. And he was told not to open that door for thirty seconds to a minute to let them get clear. That is how they handle it. And I think you got to, we have to live, we have to eat. We have to do what we can to protect ourselves and those we love. MD: All right, the last question and I am going to share with you all are our lineup. Anjolie, you were a flipping rock star yesterday. Thank you so much. Go ahead and ask your question. Question: Yeah, I wanted to ask, so in terms of what is the best way to get the economy back up online, would you recommend us doing large scale health monitoring in the interim future with, you know, like everyone taking their temperature every day, having temperature screenings in tall buildings, getting them at schools? Or would you recommend we just stay on a complete shutdown order and try to contain the virus more quickly that way? WH: I think the quickest way to get back to work is to test everybody, everybody and the ones that are, you know, the ones that are positive, you isolate and treat if they need it. And the ones that are negative you allow out. For example, you have heard about 1624
the color-coded app or the color-coded QR code on people's phones in China. It is green, red or yellow. And if it is green, you can go into shops, you can go into a lot of places, but they ask you, they show you and before you go in, they take your temperature, even if you have got a green indicator on your phone. So they are actually very careful now and I think that is the quickest way. Want to see what can be done, you follow what China, Singapore, and South Korea are doing. The thing that you know that always bothers me with, and it bothered me in other previous infections and diseases is we know what can be done. We know it because we have seen it work. Why do not we do that? Right? That is a really serious question. What stops us from doing what we know works? And your question is in that line, we know how you can get people back to work, but we are not doing it and that means the economic harm we are doing ourselves far exceeds, and you think of what it means for people to be out of work. They are now what, ten million people that are looking for jobs that are unemployed and there are going to be twenty million maybe or more. What does that mean? Who is going to pay that? Where does that money come from? You think science is arcane. Try to figure out where $10 trillion is going to come from, right? It comes out of thin air. Where does it come from? I'm trying to learn and getting my economist friends to teach me where that money comes from. But it is kind of mysterious. And so those are the kinds of issues that we are going to be facing. You asked a really good question. And let us hope we learn from others. MD: Thank you so much doctor. Really appreciate it. You are bold in your convictions and your experience and I appreciate it. Thank you for joining us and thank you to all of our members for being on the call. I love that there is an array of points of view. I think it is really important to lean in whether it is provocative or uncomfortable that we lean into these conversations and these ideas. Study any period of time in crisis and wandering and history and it is always the times that we do not lean into the ideas when we get the most lost. So it is critical to get in there and get the best information and perspectives that we can have. It is obvious that the world is deeply interconnected right now. So we owe it to ourselves to draw in as much information as we can and you are helping us with that doctor. So I really, really do appreciate it.
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Interview with Asia Pacific Biotech News April 4, 2020 | Article
Based on a situation report by the World Health Organization (WHO) on 29 March 2020, the number of confirmed cases has reached a staggering 634,835, globally. With the death rate soaring to reach above 30,000 it is no wonder that the WHO risk assessment ranks the COVID-19 outbreak at very high.<1 As countries scramble to contain the spread with lockdowns and stricter social distancing measures, the scientific community is also doing its part to search for a vaccine or treatment for the fatal disease. A quick search on www.clincialtrials.gov displays 192 clinical trials currently focusing on studying the effectiveness of various therapeutic options against COVID-19.a Some of these trials include studying the use of patient plasma, traditional Chinese medicine, or even repurposing of previously approved drugs for other viruses. To help us consolidate the current lessons and priorities of the scientific community as well as governments of countries both affected and unaffected is Dr William A. Haseltine. He has granted APBN his exclusive comment on the matter and provided insight to better prepare for future infectious disease outbreaks. 1. With COVID-19 now spread to over 100 countries, what in your opinion should governments and healthcare organizations prioritize to contain the disease? Universal testing should be their first and foremost priority. Everybody who has either been exposed or exhibits symptoms must be tested. Everybody administering the tests must be protected with adequate training and gear. Contract tracing, both primary and secondary, must be implemented. All who test positive must be quarantined. The second priority is to ramp up emergency preparedness in hospitals. We need extensive isolation wards staffed by trained personnel and stocked with equipment. If and when drugs are brought to market, our hospitals must have them immediately. In
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the meantime, healthcare workers must be prepped to administer the prophylactic and therapeutic drugs to come. Last but not least, clear public health communications and public awareness. Most governments need a single authoritative voice -- a trusted channel of communication -- that can guide the actions and fend off the fears of a listening public. 2. What three lessons in relation to the response by the scientific community towards the COVID-19 outbreak can be applied to preventing or handling future outbreaks? The first lesson is that the coronavirus will return, again and again. We cannot repeat the mistakes we made this time around -waiting to act until it’s too late. We need to be prepared. That brings us to the second lesson: only combination antiviral drugs can beat back the incoming tide of coronaviruses. A COVID19 vaccine may or may not be effective against future strains. Just like we did for HIV, we need to develop broad-spectrum drugs that will treat and prevent against the coronavirus family, not just one strain. The third lesson is to keep watch for other viruses, as well as changes in our capacity to resist infection, that may cause even more deaths in the future. One danger we’re all familiar with is the flu. Another is the possibility of antimicrobial resistance. Current trends prevailing, two million people are expected to die due to antimicrobial resistance in India by 2050. Drug resistant tuberculosis is yet another danger in many parts of the world. In 2017, India had 2.8 million cases of tuberculosis and 423,000 deaths. Nearly one third of the cases were drug resistant tuberculosis. 3. In finding a “quick-fix” to treating COVID-19 currently approved drugs are tested for treating the novel coronavirus, in comparison to developing a drug from scratch which would be the more sustainable approach and why? The most efficient approach would be to repurpose drugs that are already approved, since it is the approval process that prolongs the drug development pipeline. Another way to circumvent the many months – typically years – needed to develop a drug and bring it to market is to use federal agencies like the Biomedical Advanced Research and Development Authority (BARDA) and emergency funding mechanisms like Project BioShield to fast track clinical safety 1627
trials. The advantage of this approach is that the drugs would be more numerous, more specific, and more likely to be effective at lower doses. Either way, we need combinations of drugs to avoid problems with resistance, which we know occur. My recommendation is a broad spectrum, anti-coronavirus drug. In fact, we should be doing the same thing to treat and prevent the flu, which is already alarming enough to be on the BioShield list. 4. What can be done to ensure that there is a business incentive for pharmaceutical and biotechnology companies to continue to develop drugs and vaccines against viruses to prevent future outbreaks? What’s the difference between an antiviral drug for coronaviruses and antiviral drugs for measles and chickenpox? Predictability and seasonality. If you are dealing with a virus like measles, which has a character that is predictable and relatively static and unchanging, then it makes economic sense to combat it with a vaccine. Coronaviruses, on the other hand, attack us in the form of specific strains that appear almost erratically – and, unfortunately for vaccine developers, on a timescale unbeholden to market forces. That’s why the search for a coronavirus vaccine has, despite the two major outbreaks (SARS and MERS) that preceded COVID-19, proven futile until now. Any money invested in drug development simply dries up once the worst of the outbreak is over. Hence the need for a broad-spectrum anti-coronavirus drug that never goes out of fashion – a major investment in the short term, but the most economically viable option in the long term. Absent a normal market incentive, you will need a government incentive for a drug to be produced at a large scale – which is precisely what BioShield and BARDA create. They provide money not only for buying up mass quantities of the drug, but also for much of the research and development it takes to get there. Suddenly, a market is guaranteed. 5. In relation to healthcare system preparedness, what more could have been done to minimize the spread and number of deaths from COVID-19? Testing, testing, testing. Look at what happened in the United States. Shortly after the outbreak began, the World Health Organization produced a diagnostic testing kit that most countries 1628
have since replicated. Our Centers for Disease Control and Prevention decided to deviate from established guidelines and produce their own. Weeks passed before they reached a handful of designated labs -- who promptly discovered that the kits were flawed. No surprise is it then that even today, when cases are approaching the thousands, the United States remains an untested nation. If a reliable, standardized test had been made immediately available to all, that would have slowed the spread of the disease considerably. So, would stockpiles of emergency equipment and procedural training for the medical personnel we lean on for protection in these kinds of emergencies. The COVID-19 pandemic has shown us that health systems worldwide aren’t equipped to handle a global health crisis of this magnitude. So long as our health systems remain hospital centric, and so long as our hospitals remain overburdened even on an average day, they will be unable to mount an adequate defence against the disease. We must forge a new path toward a health system of integrated and distributed care, where patients receive care where they need it most — in the home and community. Footnotes Search term used was COVID-19 and included all completed and active clinical trials that were either recruiting or not yet recruiting. Search was done on 29th March 2020. References World Health Organization, (2020, March 29). Coronavirus disease 2019 (COVID-19) Situation Report – 69. Retrieved from: https://www.who.int/docs/default-source/coronaviruse/situationreports/20200329-sitrep-69-covid-19.pdf?sfvrsn=8d6620fa_2
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Interview With Fox News Daily Briefing With Dana Perino April 6, 2020 | Interview
No transcript is available for this interview. The original version is available here: https://video.foxnews.com/v/6147481787001#sp=show-clips
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Interview With Chicago's Morning Answer April 9, 2020 | Interview
No transcript is available for this interview. The original version is available here: https://www.youtube.com/watch?v=0Gld-Mw7760
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Interview With Olivia Messer, Daily Beast April 9, 2020 | Interview
Olivia Messer (OM): Let us start with just kind of the basics. Could you go over what blood antibody testing is? William Haseltine (WH): Okay. Did you see the piece that I on serological testing which I will get to you. It is probably in Forbes. When you are infected, your body makes what is called an adaptive immune response. That means your body is learning how to fight it. We actually have three lines of defense. The first line of defense we have is skin. The second line of defense is called innate immunity where if anything looks strange, you have cells that attack it. You have cells that release things called defenses that are toxic and that kill. Then, you have an adaptive immune response that says,” I see something weird and I am going to do everything I can to get rid of it.” And the adaptive response has two pieces. One is a cellular response where the cells learn to see it and to either engulf it or destroy it. The two cells are killer T cells and macrophages. Macrophages, which means big eater, will gobble it up and T-cells will kill it. On the other hand, you have the B-cell part of your immune system which makes antibodies and those antibodies are proteins which are adapted to the very specific foreign substance. So, if it is a virus, your body is always experimenting, sending out, making all these different combinations. It is like a key that is looking for a lock. The moment the new lock shows up, i.e. this foreign structure, it says, “okay, let us go.” And it amplifies, and while it is amplifying, it starts changing and fits better and better. It is like a rough cut in Haute couture. First is the rough cut of the dress and it gets finer and finer and over time you get a perfect fit. It refines, and as it does that, it starts out with something called IgM, then it switches to IgG, and eventually IgGs improve. The IgM is more transient, and the IgG is much longer lived. In some cases, it lasts your entire life, in other cases, you have to get a vaccine every ten years, and in others it may
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only last a year. So, it depends on how your body is stimulated and on how it reacts. So, if you are going to get an antibody test, what you want to measure are those antibodies. You want to measure the fact that you have got IgMs and IgGs. The test consists of taking a drop of blood, putting it on a little channel which it separates out the red cell. When that is filtered out you have the serum which then flows through little tubes or down paper or various strips. And the first thing it looks for is if it is going to react to blood, meaning if it is going to read it. And if it can, the test will show one line, like for a pregnancy test. The next line, if it is a good test, checks for the presence of IgM. If there is IgM, the next line appears if there is IgG. So, the test result will show any combination of the three strips. OM: Got it. WH: And what do you do to put in the test? Well you can put in various things but usually people put in a piece of the virus, which is in the interior of the virus and does not change very much from virus to virus. It is one of the things that wraps up the center. This virus has got a core and it has got a membrane with spikes that stick off it. For testing, they usually take a piece of the core. You can grow it up in large amounts and that is what the antibodies are recognizing. That is reliable if it is done properly. But the catch is it will not tell you if you have got this virus or a cold. And if you look at the current tests that are approved, they are not specific for SARSCOV2 but rather coronavirus specific. And about one third of colds are coronaviruses. So many people are likely to be positive by the serology test that never had the virus. Now is it possible to make tests that are even more specific? Yes, but it is much harder to do. And as far as I know, nobody is coming up with the test to do that. There are people trying to make more specific antigens or more specific tests and I believe it will be possible. But as far as I know, those are not yet available. OM: So, when Fauci this morning said on the Today Show that we are going to have a blood antibody test available within days to weeks, he does not mean ones that are specific to COVID-19. WH: I believe that is the case. The current test which is approved by the FDA, will tell you that you have got a coronavirus, but it will not tell you if it is necessarily the COVID coronavirus. It
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is not that it is impossible to make such a test. I do not believe that the current tests that are being made do that. OM: How much harder would it be to make such a test? WH: It will take some more time. I think you can make those tests. But it is going to take a lot more time to validate, to make sure it picks up that virus. First of all, you have got to make sure you have somebody who has never seen a coronavirus. About one third of all colds you get are coronaviruses. Now the loophole there is that coronaviruses do not make IgG reactions that last very long. So, after a year or two, even though you have had a coronavirus, it will not show up anymore. So, it is a little complicated to do that because you have got to get the people who do not have active coronavirus IgG, but have had this virus. And the way you would run this test, is you take a swab of that genomic positive person and now we know he has got coronavirus antibodies and he has got IgGs which are going to last awhile, maybe a year or two. So he might be protected against that virus. But if you just do a random population, you are going to get all sorts of people who have never even had the coronavirus show up. Now there is another wrinkle that just appeared. A Chinese paper just came out. They said we looked at 170 people; 75 people with mild disease. These were hospitalized but not ICU patients.. We looked at the antibody levels and their ability to knock out the virus. And what we found is the following. All our old patients made great antibodies and those antibodies knocked out the virus. But as many as one third of the total patients did not make very many antibodies, even though they were positive for the virus and they were ill enough to be put in a hospital. When we went back and we looked at their antibody levels, the young people did not make very good antibodies and we could not find them. And some of these antibodies do not even neutralize the virus. So, about a third of the people that they found did not make neutralizing antibodies and made very low or undetectable levels of antibodies altogether. This is not going to be a foolproof test because here are these people who are genomic test positive, put into a hospital, released from the hospital, and you cannot find the antibodies in one third of them. When I wrote my piece, I did not know about this wrinkle.
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OM: If those loopholes were not there, if we had a test that could detect COVID-19 specifically, would something like an antibody test be the key to turning things around more quickly? WH: What you are going to have is a test that is going to be useful for saying people may be protected from reinfection for some time with a caveat that maybe we are measuring the wrong virus, but as long as you knew that they were really infected and you got a positive strong reaction, the chances are pretty good that that person is going to be protected at least for a while. And I think the really operational question is if you have high level IgG, can you go back to work? If you have been infected and you do not have high levels of IgGcan you go back to work? That is another question. Maybe yes, maybe no. Maybe you will be one of these people who get reinfected. OM: Yes, I’ve seen that. WH: And whether that is the original virus or a new virus could be told by sequencing, but I have not seen the results yet because each virus has got its own distinctive fingerprint. So the simple use of this test is to detect people who are protected who then can go back out into society. But there will be the loophole that maybe it is a person that was infected, did not make antibodies to the virus so they are not protected against this virus, but had a cold four months ago that you are picking up now. OM: Right. You do not really want to send them back to work. WH: Well, you would not know whether to send them back to work. You probably would take the chance. OM: So if we had a more specific antibody test, we could be using it to say anyone who has high level IgG can probably go back to work. And that would probably be the safest way to sort of end this? WH: Probably yes. It is not foolproof, but it is better than other things. OM: What would having a specific COVID-19 test allow people to do? WH: I think it would give you confidence that they could go back to work and not infect their fellow workers nor be infected by their fellow workers. And they are going to say that whether it is specific or not. If you just take the simplest use of the current tests, 1635
if you have been COVID positive and you have strong antibody reaction in this antibody test, you are going to be cleared. There will be a little bit of loophole, but people are going to have to live with that. I think for a practical matter it is certainly livable. If I were advising government, I would say to go with the idea that you have to warn people that the test is not 100% reliable but rather 90% to 95%. Does that make sense to you? OM: Yes. So in those terms, do we have any issue with production of those tests? WH: No, not with those tests. We do now because they are not available widely. But you know the Egyptians just used the Abbott finger stick on 65 million people. If you want to read how to do it, I just published a paper in the March 12th issue of the New England Journal of Medicine. It was the front story and I have been to Egypt three times last year to look at what they were doing and they used the hepatitis C test made by Abbott to test 65 million Egyptians twelve and over. Now, I just published another article in Forbes, which basically says not to profiteer. What should the costs be? The cost of the Abbott finger stick, foran American company was 50 cents a finger stick. The cost of a PCR was $5. I have seen finger stick tests go for anywhere from $10 to a hundred dollars. I have seen PCR go anywhere from $150 to $2,000, not to mention the treatment which the Egyptians gave for $45 which we charge $80,000 for. This is not a time to profiteer. The real cost for a massive use of a finger stick tests should be 50 cents a test. Abbott did it for Egypt. They can do it for America. A PCR test should be five dollars. That is the end use cost. OM: So, this would potentially be the key to getting people back to work. WH: And what you have to do is you have to do massive testing for the virus and serology. Anybody who is positive for the virus, you have got to do extensive contact tracing and mandatory isolation for fourteen days of everybody who has tested positive and you have to have detailed surveillance of everybody you have identified as a contact whether or not they are positive, so that they do not leave a confined space. You verify that by either putting a bracelet on them, or by tracing their cell phone. Someone I work with flew from Shanghai to Singapore, and he gets the request on his cell phone to say where he is, what his temperature is, and maybe one out of four 1636
of those times the request is to take a picture of his surroundings to verify where he is. That is what we have to do to get back to work. OM: For the antibody testing to make sense for us to use, we still have to implement massive genome testing and diagnostic testing. WH: Absolutely. I am giving you examples from what is happening in Wuhan today. They are getting back to work, but they are getting back to work really carefully and for anybody who is positive, they contact trace, isolate and if the person is sick, take care of them. They are really on top of it because they do not want the virus to come back. OM: I have not left my apartment for very long, but in order for me to get on the subway and get back to my office, ideally I would be tested to see if I had it. And if I ended up being given an antibody test, one that is specific enough… WH: Yes. Well the antibody tests would say that you’ve had it and so that you are safe. What they have in Wuhan is on their cell phone, a QR code that they are required to show when they go into restaurants or shops or back to work. It is a certified QR code that says they are okay. For example, you can fly out of Wuhan; the first plane left yesterday. They could not get into the airport, they could not get onto their plane and they could not get off their plane unless they show their green QR code that says, “I am okay.” The government says “I am okay.” OM: Well, what happens is if we test people to see and they have never had it? Do we not send them back to work? WH: No, you send them back to work, but you be careful of anybody. The first thing is the first people can go back to work, maybe they have recovered, but that is not really what you want to concentrate on. Once the level of infection drops to very low for four weeks, you can send people back to work, but you are going to really screen a lot of people for a virus. The moment a virus is detected, you are going to protect everyone by having anyone who was exposed to it isolating themselves. You get back to work, but you get back with extreme caution knowing at any moment, one person could start the whole thing over again. That is why it is going to be a very long time before we get back to normal. OM: How long will it be until we have a test that would allow us to do that? 1637
WH: The one thing that we are going to have over time is we are going to have point of care, five-to-ten-minute tests, for our genome positivity. So that is a big step forward. The White House has that right now; Mr. Trump is not allowing anybody who comes to see him unless they have passed that test. OM: Sure. WH: So that will make it easier. Instead of waiting seven days, there will be a five-to-ten-minute test. OM: This is really interesting because my next story is actually about the process of pulling us out of the lockdown, which is what we have been talking about, and how complicated that can be. I think there are people who really believe that one Saturday, everyone is just going to be allowed to go back to brunches and bars. WH: Well, if you want to get the infection rolling again, that is a good way to do it. OM: Right. But the alternative is to release people carefully and in sections and monitor everyone. WH: Very, very carefully. That is exactly right. But who do you get back to work first? Who do you let go second? It is going to be a long time before we have sports events and theaters. Let me give you an example. If you are in Beijing right now, you can go out to a restaurant, but before you enter the restaurant, they take your temperature and you show your QR code and you are allowed to sit at a maximum of four per table at a predefined distance from one another. And if you come in with a group of more than four, you are put at different tables. That is what we are going to be looking at. OM: Are we ever going to be at the level where we are that sophisticated and though in our response? WH: If we are not, we are going to suffer. OM: It just seems like they are itching to reopen things in a way that might be dangerous. WH: Yes. The danger that we are going to run out of patience, run out of political will. However, whoever makes the decision to reopen things will be held responsible. And the next thing that happens, is the hospitals get flooded again and your neighbor starts to die. In our case, we will hold the president responsible. You can already see him getting more careful. I heard him talk about clinical trials the other day. 1638
OM: That is a big deal. WH: That is a big deal. I praised him for that when they asked me what I think about hydroxychloroquine. OM: He is taking it one step at a time. WH: He also refused to give a date to end the lockdown. He said that last time he gave a date, he got in big trouble and he just gave my feeling of what a date might be. OM: What are the hurdles? WH: There are a couple of practical hurdles. First hurdle is making the rapid genome test widely available and making it affordable. That is going to take time and effort. That could be done by the end of summer. That is the first thing. The second thing is dramatically strengthening our public health services at the federal, state, and more importantly, local level so that we have the cadre of people who could do the contact tracing and the compliance with the necessary quarantine of those exposed. That is hard but it is all doable. India is doing it. I listened to Tony Fauci’s interview with the head of the New England Journal last night and he said, that in a way we have been so successful at treating infectious disease, we have forgotten the most basic part of it: public health service. We do not have the people that know how to do contact tracing at the federal level and we have dramatically weakened our public health service at the state and especially the local level. Most of these hurdles are manpower hurdles, training people. OM: So, having a rapid genome test widely available is necessary. What about a blood antibody test? WH: That is important, but it is not as important. What would be very important with an antibody test is to show that most people were infected, because nobody knows how many people have been infected really. And the only way to know that is with this anti antibody test. It would be helpful if it was specific, but even a nonspecific test would be a big help. There are some suspicions that in a very short time, half the citizens of New York will have been infected. OM: Right. WH: And if that is true, then most people can go back to work because the virus will not have very much room to go anywhere. That is called herd immunity. Maybe that has happened, but we do not know.With HIV, nobody knew how big the problem was until 1639
we had a serology test. Once you realized the problem was about a hundred times bigger than the number of people that were sick, you knew you had a problem. It would be the reverse in this case. Once you knew that most people were infected, you know you did not have a problem. OM: So, say in New York, if we were able to make all of these things happen by November while releasing people in chunks to go back to work; is there any model for how that has been done in the past? WH: I do not think so. OM: The idea is that first you send people back to work carefully and contact trace. Then at some point after that, once you are certain that things are back under control, you can start opening mass gathering areas. WH: I would not say mass gathering. You can get people back to work with distance, with real discipline of hygiene, and it is only after a long time that you can open up theaters, maybe a year. These viruses do not care about us, they care about themselves. I think it is part of the reality that we have to put into our minds. Things are going to open up, but they are going to open up slowly and carefully if we do not want to get this whole thing rolling again. And you could look at Singapore today. Singapore today had more cases than it has had for a very long time. It has had 270 cases, 74 cases today. Now they have locked everybody back up. OM: The idea is, instead of having waves like that, to try to be so careful that new infections do not become waves and clusters and hotspots again, right? WH: Yes, that is the point. You do not want that to happen. OM: Thank you so much for your time. I really appreciate it. WH: Thank you Olivia. Keep up your spirits and keep up your writing.
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Interview With The Heat April 10, 2020 | Interview
The original piece is available here: https://america.cgtn.com/2020/04/10/the-heat-covid-19-andthe-race-for-a-vaccine Anand Naidoo (AN): For more on the impact of the coronavirus in the United States we turn to Dr. William Haseltine in New York. He is the chair and president of ACCESS Health International and is best known for his groundbreaking work in HIV and AIDS. Dr. Haseltine, thanks so much for joining us. William Haseltine (WH): Pleasure to be here. AN: We have just been reporting those very grim figures coming from New York State. 799 deaths on Wednesday, April 8 alone in the state itself. 7,000 people have died across New York state. What is your assessment of what is happening in that state right now? WH: Well, we are definitely in the midst of a tragic epidemic. I live here in the middle of Manhattan. The city looks like it is deserted. People are quite worried. I know people, many people who are infected, some who have died. And it is a pretty serious situation here. AN: Dr. Anthony Fauci with the National Institutes of Health has expressed cautious optimism. He says that the spread may be slowing in New York State. What do you make of that? WH: I certainly hope it is true. I observe people staying inside, shops closed, every museum closed. The city has really closed down. That is hopefully a very positive sign to reduce person to person contact, which is how this virus spreads. However, we are not doing what has been done in East Asia, identifying people who are infected through testing, doing rigorous contact tracing and mandatory isolation of those people exposed regardless of their test result. Rigorous containment means isolation in a room by yourself and you do not step out of the door. That is not what we are doing, and I think that is worrisome. It means if anything, we can perhaps 1641
reduce the spread, but we are not going to eliminate it at nearly the rate which was done in East Asia. AN: Why is that not happening in the United States? Is it logistics? Is it a lack of equipment? What is it? WH: Lack of leadership, lack of preparation. A public health service which has been allowed to fall into rack and ruin and tatters. It is sort of paradoxical. We have such a great health system in many of our cities that we have controlled infectious diseases pretty well until now. People forgot about how important the fundamentals, the blocking and tackling of public health is, i.e. the ability to identify those infected, the ability to contact trace, the necessity for isolation in case of transmissible diseases. We are not good at it. Hopefully we will learn our lesson and will get good and remain good, but right now we are not. I think East Asia had what you might call it an advantage. They had the SARS and MERS epidemics, so they understood what this could do, not just for the health of people, but to economies. If I analyze why East Asia has done so well, it is that they understood what pandemics can do to economies and therefore they were willing to take really drastic action and they were willing to prepare. You know, South Korea has done reasonably well in this epidemic. One reason is that in early December 2019 South Korea ran a simulation of what a new SARS like epidemic would look like before they knew it was coming. AN: In fact, you wrote about that in the article in Forbes Magazine in which you said that the pandemic is a big one in terms of lives lost and economies destroyed, but you point out that it is a big one, not because this is an especially powerful virus, but because of the human reaction to it. WH: That is entirely correct. COVID-19 is a tragedy that did not need to happen. The United States right now is leading the world in terms of the epidemic. For me, as an American, as a scientist who has built his whole life fighting infectious diseases and other diseases, it is an unnecessary tragedy. Had we heeded the warnings out of China, which were clearly given—they were not, as our President claims, obscure in January—we would have been in much better shape. Had we taken to heart the lessons of SARS and MERS, that coronaviruses that cause colds could cause serious problems, we would have a drug available which would have stopped this 1642
epidemic before it had a chance to get off the ground. Those drugs could have been available. We knew we needed them. This virus is a cold virus with a nasty, nasty habit. But I remember back to the days when there was another cold virus, it is called the polio virus. Most people do not realize that that was a member of a broad family of cold viruses that also had a very nasty habit. I think we should get our act together and take cold viruses much more seriously now and in the future. AN: Dr. Haseltine, I am wondering how seriously these guidelines that have been put out by the White House are being taken because the Centers for Disease Control has said that essential workers in healthcare and food supply who have been exposed to the virus but who recovered, they can now return to work if they are not showing any symptoms. Is that advisable? WH: You know, if they are antibody positive, and ideally you would want them to be neutralizing antibody positive, I think that is possible. We do not quite know enough about the virus. There was a recent report out of China that suggested that some people who recover from the virus do not have protective antibodies and that fraction was rather large for people who are mildly ill and discharged from hospitals. They were ill enough to be in the hospital, but it was about a third of the people that were discharged after having been ill and in hospital that did not seem to be able to protect themselves. I do not think they are necessarily going to be a source of infection, but they might be re-infected. AN: If we look at China, over to the city of Wuhan, which is where this started, there was a 76 day lockdown there. Now that city has been reopened, people are allowed to move out of the city and move into the city. It is gradually returning to normal. What is the lesson from that city? WH: Well, there are a couple of lessons. First of all, to say the lockdown is over is a little bit of an exaggeration. The extreme aspects of the lockdown are over. But I have friends and people I am in touch with in Wuhan and it is by no means back to normal. For example, if you are going to leave the city, you have to prove with your QR code that you are free of infection. To enter a restaurant, your temperature must be taken, and you cannot sit very close to one another. You cannot have groups together. It is hardly back to normal. 1643
What is the lesson from that? The lesson from that is if you want to not just flatten but crush the curve, you have got to be stricter than we are. If you want to end it so you can get back to work, the tougher you are in the early phases and the mid phases of this epidemic, the faster you are going to get back to work. We in the United States are not on track to get back to work in a normal way in any foreseeable future given the way we are handling this infection. AN: What are your thoughts on the likelihood of a viable treatment coming to market very soon? WH: I do not know about what is coming to market, but there are viable treatments right now which are protective antisera. A convalescent sera from a person who has a powerful neutralizing antibody response to this virus so you can knock it out, can be used to treat somebody terminally ill. There are right now people in the process of pooling those sera. They should be testing them for their ability to knock out the virus so you then have a highly concentrated preparation called IgG. That could be used to treat patients and to protect workers for a period of three to four weeks. Those are not commercial products. Those are things that the public health service will do. We have, for example, in the US over 300 plasma collection services and many of those have been activated. I think within the next month or two, already we have the beginnings of that. The next month or two, it may be even sooner, we will have some effective ways to protect healthcare workers and to treat those and save the lives of many. Let me also say that saving the lives of people who are critically ill is an art form. And that the results can vary from twelve percent fatality when people are intubated to greater than eighty five percent fatality depending on where you are treated. We should up our game so that most people have access to the best treatments that result in fewer fatalities once you are critically ill, that is with good medical practice. AN: Could you tell us would the United States be prepared for the next pandemic? You said this is the big one, but perhaps the one positive thing that might come out of it is that we would be prepared for the next one. WH: Well, we certainly are not and no country is. We can tell you in advance what is going to happen. We know sometime, could 1644
be tomorrow, it could be twenty years from now, there will be another influenza epidemic which is equivalent to the 1918 flu. And if we do not improve our game, it could kill one to two billion people. That is not an exaggeration, one to two billion. We must take this lesson seriously. I think we will because this is getting too many people in the pocketbook. AN: Dr. Haseltine, I have to go and we have run out of time. Dr. William Haseltine, thank you so much for joining us. WH: You are welcome.
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Interview With Jared Hopkins, Wall Street Journal April 20, 2020 | Interview
Jared Hopkins (JH): How do you sort of design and prepare a trial for this and what are the challenges? William Haseltine (WH): I am happy to help. Give you a little bit of my background in this field so you have an understanding and the perspective from which I speak. I was one of the very first AIDS researchers and we did the first sequence of the HIV genome and identified about eight targets for drug development, proposed the theory for combination chemotherapy, and was a participant in the development of the first protease inhibitor which made all the difference. And in fact there are now a number of drugs that are based on discoveries we made. One of them is the integrase. We developed assays for the integrase. In addition to that I have been a biotech executive and I have brought eight drugs to FDA approval through companies that I have founded. The one that is most relevant to this is a drug that we developed for anthrax. It so happened that I was living between DC and New York at the time. And our post office on P Street was the one that was attacked. I got a team together and from the moment of conception, the actual desire to do something, to FDA approval was two years and six weeks. It was extremely fast as you know, covering the pharmaceutical industry. And it was a monoclonal antibody that not only serves as a temporary prophylactic, i.e. if you are injected with it, you are immune from four to eight weeks from infection. And it is curative in the sense that the animals that we tried it on, even if they were hours from death, we can save them. It was a very successful program, and the Department of Homeland Security has today purchased about $500 million worth of that drug for our stockpile. JH: Which one is that called, sorry? WH: It is called Abthrax. It was the very first drug developed under BioShield. In addition to that, I have paid a lot of attention to 1646
the field. Anyway, so that is some very specific experience that I have got. The first thing I would say is that the problem of developing drugs for the coronaviruses has been solved. It is an easy problem. We know what to do. We have chemicals that are going to work. And so it is a question of doing the clinical trials, and they can go reasonably fast. Now why do I say that? In 2003, the SARS virus came up. The community responded. A number of drugs were developed. The crystal structure of the protease, actually there are three great targets in this virus, the polymerase, a protease and helicase. We know how to make drugs that are active against all three, in particular the protease because that is a great target as we know from hepatitis B. That is what inhibits hepatitis B. Two different protease drugs used in combination are curative. Protease drugs were developed. They were shown to protect animals when exposed to SARS. Same drug was shown to protect animals when exposed to MERS. The same drug, one in particular, but more than one, were shown to be active against other known coronaviruses and are now known to be active against SARS2, this particular coronavirus. And the reason that they are is that most viruses are pretty conservative on their inner workings, whereas they change their outer shell to the immune systems, but the immune systems are not primarily reactive against their inner workings and it is harder for them to change. HIV was an anti-protease, hepatitis B is an antiprotease and these drugs are anti-proteases. In fact, my daughter happens to be a sculpture. She is inspired by some of the work that I have done. She built a sculpture for Biopolis. Is this a little too detailed for you or is this helpful? JH: No, yeah, go ahead. WH: Okay. She built a sculpture in the middle of Biopolis in Singapore to celebrate their development, along with a German scientist, of a drug that inhibits the protease and it is a three dimensional twelve foot sculpture showing the backbone of the active side of the protease. The pavement is the drug of which I just spoke. And if you walk through you become symbolically the inhibitor to stop SARS. That drug will work and does work against the SARS2 virus. And there are several others. JH: Which drug is that?
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WH: It is a drug that was developed by a German scientist together with the Singaporeans. His name is Rolf Hilgenfeld. For transparency, I am now working with him to get that drug developed. But there are other drugs. There are drugs against helicases. There are other drugs against the polymerases and those drugs are certainly going to work in combination. We are going to need a combination because these viruses mutate. Just like we do with HIV/AIDS, we are going to use two or three different drugs against this. And the clinical trials are not that difficult. What you do is you find people who are virus positive. You treat them with increasing, well, first of all, you do a safety trial, but these things are likely to be safe. But you do a safety trial. That is about twenty or thirty people. It will take maybe a month or two months at most to do. Then you take a group of people that have been shown to be virus positive and you administer the drug to them. Hopefully they are reasonably healthy. You measure how fast the virus load drops. We have already got surrogate markers. The idea of parallel track that was developed for HIV by the FDA which allows you to use surrogate markers. You do not even have to wait until people are cured. You can just watch the virus load drop and if the virus load drops quickly, it should drop within a day or two, you should be able to get a readout. The next step would be to take people who are mildly ill, not yet in the intensive care unit, but perhaps hospitalized and treat them. Following that, you would treat people who are in the intensive care unit. And I think that I see no barrier to that process. I am sure that major companies are, Pfizer is certainly doing it. Glaxo is doing it. There are a number of companies that are moving along this path. All you have to do is look at the literature and you will see that by 2012, 13, there were nice reviews where people would outline all the various targets, what the chemical structures were that were likely to be active. And basically at the end of these articles they say why haven't they been developed? Well, it is because the pharmaceutical industry has no financial incentive. Now, the one thing that they all forgot, and this is something I think nobody has made the point, that if we had a drug that worked against this virus, which we will have shortly, that very same drug would be able to treat one third of the common colds. Now, my mother always told me when I was a kid, sonny when you grow up, find a cure for the 1648
common cold. You will become a millionaire and very famous. And it turns out that since one third of the colds are caused by coronaviruses and these drugs are very likely to go work against them, pharmaceutical companies probably made a mistake. They thought of it only as SARS and not as a drug to treat one third of the common colds. At any one time, about five percent of the population in the US has an active coronavirus infection. A drug against this coronavirus would probably stop most if not all of those. JH: I mean, when do you think the earliest that a treatment might be available, like widely available? WH: Well, I think remde sivir looks like it might be at least partially active. It is not an ideal drug. It is not developed specifically for this coronavirus. It is meant to inhibit RNA dependent RNA polymerases. From what I see and what I have heard more or less through the grapevine is that it seems to work reasonably well in monkeys. And it has, you have seen some very preliminary suggestions that it might work in critically ill patients. I am hopeful that it will work. At least it will be partially effective in slowing the progress in improving the outcome for people who are critically ill. So that could happen very soon. I think that Gilead has already ramping up production of that. Insofar as these new drugs go, I would guess that because of the major effort that the pharmaceutical companies have got to be putting in that we should see in the next two or three months at most some positive results from the phase one and phase or phase one, phase one B, early phase two clinical trials of these drugs. Widely available, probably no later than the fall for some of the drugs. JH: And is that because basically these, the outcomes are sort of the end points that you are measuring are, you know, it is within a week, two weeks, three weeks. It is a relatively short period. WH: Yeah. This is not cancer. This is not lupus. This is not some long-term disease. This is an infectious disease. You know, why we could develop the HIV drug so rapidly is because the FDA allowed a surrogate marker. All you had to do is measure virus drop. By the way, we have all of the legislation in place that we need for super fast approval. It is exactly the protocols that I used to develop Anthrax, BioShield and BARDA. Under BioShield for a list of compounds. What the Homeland Security and Defense Department 1649
did is they made a matrix. On one axis, they had biological threats that a terrorist might cook up. On the next axis they put countermeasures and they had boxes empty and boxes filled. Where there was an empty box, they sought solutions. In particular, the empty box that I responded to was the possible attack of a population with an anthrax made deliberately resistant to antibiotics of an uninfected population. There was an empty box, nothing to be done. I came up with an antibody to the toxin, a monoclonal antibody to the toxin, which solved that problem and in negotiations was the DOD, I said, you set the criteria for activity. If I meet those, you have to promise me that you will buy it. They said we will. And they wrote down a very specific list of criteria that the drug had to meet. As a result, all I had to do was show that it was active in two animal models of a human disease and one safety trial. That was it. JH: But isn't anthrax a different sort of analysis comparison only because, I do not mean this with the process, the regulatory process here, but in terms of developing a medicine only because, it is not a virus, right? WH: You know, it is not a virus. It is a bacteria. But what is the difference? The difference is it will kill you quickly, just like this virus. And let me just say that we could do the same for, this is not a complicated problem. We know exactly where the virus’ weak points are. We know that drugs have already been developed that work. What is the problem? No problem. JH: Well, so then why prior to COVID, if we have a drug developed that worked, then why? WH: Because they were never tested in humans. They were left on the shelf by the United States. JH: No, no, no, no, no. What I am saying is like, why is everyone, why is every drug company and everyone and their mother is basically trying to get their treatment tested and approved? WH: That is what they are doing. Well, but you know, what they are trying to do now is a little bit different. They are trying to see if drugs that are already approved will work. That is what is going on right now. And at first I was very hopeful that that would work. But as time goes on, I think the best hope that we are going to have from drugs that are already approved for a different virus or a different disease will be modestly effective, not zero. I think that the remdesivir has some hope. The hope that the HIV protease 1650
inhibitors would work turned out not to be the case. They do not, but that is not surprising. They were not developed to fit into this molecule. So what is being developed is people have gone right back to all that work that was done up to seventeen, eighteen years ago, and in some cases ten years ago for MERS and are hauling out those drugs and getting them ready for their clinical trials. I would be very surprised if we are not seeing the first safety trials of some of those drugs very soon, if they are not already done. It is not rocket science. It is pretty easy. JH: So my question was kind of like, one of my questions, you know, sort of designing trials in this environment— WH: There are plenty of people, not a problem. Design trial, simple. JH: Because in China now there have been reports that they cannot enroll patients for remdesivir because they do not have enough. WH: Well, we got plenty. JH: You think that there is plenty? WH: We have more than enough patients here. There are what, 800,000 Americans infected by now, and another 800,000 coming in the next few weeks. Of course we have enough patients. That is, from a drug development point of view. That means an embarrassment of riches. We have plenty of patients, more than enough. For these trials, the first phase you do a safety trial. That is thirty people. That is normal people. That is not a problem. For phase one B, phase two, say you need fifty people, a hundred people. That is all you would need. We have a tiny amount of people to get these answers. Let me give you a number to think about. Let me give you some real data. AZT, the first trial that showed that the drug worked, was thirty six people—eighteen on the drug and eighteen untreated. We knew within two weeks that that drug worked. And from then on it was a very rapid development pathway. Now turned out it worked, but the virus in a person developed resistance within about a year and most of those early survivors then died. And it was not until we were able to add a protease inhibitor, and now as total of about seven different kinds of inhibitors, that we were able to get long term survival. It does not take a lot of people, it does not take a lot of time to do these trials.
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JH: So similar to that example, let us say remdesivir or any of these drugs within the next couple of months shows efficacy, you know, maybe more than a handful that they show efficacy, don't companies that are developing drugs then come into a situation where every patient is going to want to just get on remde sivir, instead of enrolling in a clinical trial and testing a new drug? WH: You know, that certainly was not a problem with HIV/AIDS. Never was a problem. I do not think it will be a problem. It tells people look, you know what you do is you will say, look, we will give you remdesivir and we will give you B. We will give you A and B. It is like cancer today. You give the best standard of care, plus. That is what you do. If everybody is on remde sivir, fine. They are not going to solve the problem completely. If it does, God bless them. If it does not, people are going to be willing to try remde sivir plus X. Why not? JH: I just got one last question on the anthrax thing. How were you able to make the drug so quickly? WH: Well, we already had a relationship with a company called Cambridge Antibody Technology. We had already made a drug which eventually became the first drug for Lupus called Benlysta. So we already had that relationship. We just said, okay, now we want to make another antibody. We did. We were successful. We already had the facilities that we needed to make the drug under GLP conditions. We made that. And then it was easy. You just showed that it was safe. You showed that it worked in animal models, which it worked extremely well. And then you showed it was safe in a trial of about, my memory is only about thirty people and it was approved. JH: You make drug development sounds so easy. WH: In this case it is dead simple. This is a very easy medical problem. What I tell people is science will save us. It is going to save us from this disease. In fact, I will tell you the irony, the thing that is deeply, deeply frustrating for me. We already had the drug that is going to save us, and had we been a little more pressured, like many people pleaded for, we could have stopped this disease with maybe ten or fifteen people in China dying and that would have been it. If the drug were on the shelf, if it had been stockpiled, nobody more than the first five, ten people would have had to die. JH: Which drugs are you referring to? 1652
WH: Any one of the drugs that were shown to be worked against the protease of the SARS and MERS coronavirus. And I can tell you the people that developed that drug really are unhappy and now they are working their very hardest to try to get those drugs. JH: Are you referring to a specific one? I just thought like, I cover Pfizer, their antiviral is… WH: I want you to go back and look at Larry Altman. He was the great reporter for the New York Times. He, and Brody, another great New York Times reporter, in 2003 wrote a New York Times story about how the drug I am discussing was going to be developed by Pfizer. It never was. And had it been, it would have worked against MERS and it would have worked against this virus. They had the rights to develop it and never pushed it forward. Read that story. It is a great story. If you want, I can send it to you. I have got it. I will have to do a little digging, but it's a 2003 story about this drug and how Pfizer's going to develop it and stop SARS. Well, it would have stopped COVID-19. Talk about frustration when you know, that something is going to work and because neither, and so it is a double failure. It is a failure of the pharmaceutical companies to do their job just because they are not going to make money. You can understand that, but still, they should have done it for the good of humanity. And it is a failure of the government that had a program. Now the way I look at biological agents, we are willing to do a lot to protect ourselves from manmade terror. But when it comes to the greatest terrorist of all, i.e. nature, we were not willing to do what we knew we should. Now, who is we? It is me and a bunch of virologists and other people who understand the nature of these viruses. And the irony is, had they developed that drug, as I said, they would have had a drug for the common cold because one third of the common colds are these viruses. JH: Can I ask you about, the original reason that I reached out initially was on hydroxychloroquine. Yeah. And the reason why I reached out is because if it is history, I guess in testing other viruses, I am trying to get up to speed on that. I understand that it has been tested on a bunch of viruses. It has never really worked. WH: Look, it is a complete zero. We know that for sure now. And not only is it a zero, it is dangerous because we know that patients, many people are having heart complications. People who have got serious infections have heart complications, kidney 1653
complications, and this virus is lethal for those people, this drug is lethal for those people. It is not only ineffective, it can kill them. There was recently just today a whole new study by people who work with rheumatoid arthritis and a number of people with lupus and rheumatoid arthritis take for inflammation, hydroxychloroquine or chloroquine. They get COVID just like everybody else does and they are on it permanently. JH: Yeah. I actually read a story on that yesterday. WH: Yeah, I saw the story. Not only does the drug not work, it is dangerous. JH: Going back and, and I do not mean… WH: Well, you know, let me just say, I am going to take you back to the AIDS situation again because every time there is a new disease, it is the same story over again with slightly different players. There were plenty of drugs that people tried when there was nothing around. And you can understand that. The French had a drug called Suramin, which is the one Rock Hudson took. It did not do him any good and might have done him considerable harm. This is what happens in epidemics. People struggle and you could understand it. They want something. Give me something doctor, and doctors are going to give what they can, but once you know that a drug does not work and can be dangerous, you should stop. JH: But isn't what happened here is that we did not know that it did not work right or that it was not effective? WH: No, we knew it was not going to work. There is no reason to believe that. Any good virologist would tell you the chance of that working is close to zero. JH: Can you take me back to you either in the eighties or the nineties and was hydroxychloroquine or chloroquine, I heard anecdotally that it was tested on AIDS and HIV back then. Is that true? WH: I do not remember that. No, I do not remember. I would not be surprised, but I cannot tell you for sure because I do not know. JH: Okay. But you do not remember like a formal study or anything like that being done? WH: No, I do not. I know that people tried a drug called Suramin. I know there are a number of drugs that were tried. You know, the Chinese are doing something crazy and they are treating 1654
a lot of people with traditional medicines. And that is because people are hopeful. I mean, people will take what doctors give them, but that does not mean it is going to work. JH: Okay. all right, Well I appreciate you taking some time here and explaining. Is there anything I did not ask? WH: Well, yeah, you did not ask about vaccines. JH: Oh, I am sorry. WH: I think the best solution is drugs. Why? They are oral, not intravenous. The problem with ramdev sivir is that it is intravenous. That is a problem. It means that it cannot be widely used. You want a drug that is both prophylactic. There is another major point here. You want a drug that is prophylactic and therapeutic, right? That is what you want. That is what Anthrax is. That is what many of these HIV drugs are now. The drugs that we now have can prevent you from being infected when exposed. For this, you want a drug that is safe enough for many unexposed people to take, especially for healthcare workers. And you do not want it to be intravenous. You want it to be oral, especially for protecting healthcare workers and for people who are mildly ill, and you do not want them to progress. So, and that monoclonal antibodies that people are developing, and I think probably we are going to have effective monoclonal antibodies. There are several issues with those. First, they are intravenous. Secondly, they are very expensive. They are hard to make. And the third is that this virus already is mutating in precisely those areas. JH: Say that again. WH: This virus is already mutating in precisely those areas where the monoclonal antibodies are likely to bind, and from work on SARS and MERS we know that the spike protein will vary in response to pressure from a monoclonal antibody. So although everybody is excited, Regeneron has done some very nice work with MERS on monoclonal antibodies. They will work, but they are awkward for the reasons I just mentioned. Expensive to make, intravenous in their form of administration, and the virus is certain to escape. So that is why you want these drugs. You want combinations of drugs that are orally available, that are easy to administer, that are hard for the virus to get out of, and you want to use two or more in combination. So that is where the other kind of
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drug we did not discuss is the monoclonal antibody, which is moving along. Next issue is a vaccine. These viruses as a whole are trickier than polio, for example. The reason for that is that they do not seem to raise the same kind of protective immunity that other viruses do or the viruses like polio do. If you look at the history, and I have recently reviewed what we know about the cold virus, within a year of infection, it is possible to be re-infected with precisely the same cold virus. And that is from volunteer studies where you took a bunch of volunteers, you infected them with the cold virus, they got a cold. A year later you tried to re-infect them and in many cases, you were able to do so. Second thing is, if you look at the antibody responses in people who have survived the infection, in some reports up to one third of people who survived, do not make protective antibodies. That fits with the earlier information that these viruses are not good or actually one of their survival techniques. And there is a major observation about the coronaviruses in general and that is the same four viruses have been causing colds in human beings for at least since the 1990s and even earlier in 1960s when they were originally isolated. For some reason they can, and they do not change that much on their exterior. They are not like HIV completely changing all the time. They just do not raise very good protective immunity. That means, it does not mean it is impossible. It means it is harder. There is another issue, which is that the antibodies that are raised actually exacerbate the disease. You may have followed the dengue situation. Have you followed that at all, the dengue vaccine? JH: Yeah, where the vaccine actually made people worse. WH: That may happen with these viruses. There is evidence that these viruses may fall into that trap, that a vaccine may not protect and it may actually exacerbate. That is one of the reasons vaccine development has to go more slowly. You have got to test it very carefully to make sure that that is not going to happen. And there is some indication that it might. And that is not even getting into all the different kinds of vaccines that people are trying to raise. There are many, many different ideas, you know, delivery. Basically, some people are going after a killed virus, some people are going after various forms of the spike protein, whether it is delivered as RNA, a gene, as a protein, as a piece of a protein. They are all worth 1656
exploring. But you have got to be very careful in the development. Suppose you have got a vaccine that works. It seems to work, protects. You have got to test it in a lot of people. And the reason for that is a vaccine is being used to treat healthy people. In this case, hundreds of millions of healthy people, maybe even billions of healthy people. And if there is a one in a thousand side effect multiplied times a billion people, that is a lot of people, a lot of side effects. You have got to be very careful with that. Second of all, something people have not thought about. I do not think I have seen nobody write about it. Think about your own experience with a vaccine. You get a jab, you wait two months, you get another one, you wait another three or four months, and you get a third one, right? Why? Because your body needs to see it several times to develop immunity. Let us say it takes a year to develop a vaccine. Well, the population may not even begin to get resistant to it for another six to nine months. That is a big, long gap. The vaccines may seem simple but are not so simple. And with HIV, we have managed to turn it from a terrible pandemic into a manageable pandemic through drugs alone and behavior. JH: Is what you are describing also the reason why so many, talk about vaccines, why so many companies and researchers and universities are trying the vaccine? So many unknowns, potent issues and you know, maybe you can get one that you do not have to go three times. You want to get one you go one time. The mRNA, the new technology, has not been proven. WH: People are talking about the different vaccines they are developing. But if you would look under the covers, you would see they are developing more drugs than they are vaccines. I mean everybody remembers polio and polio was solved by vaccines. They are hopeful that will work, but it is on the surface a more complicated problem than polio turned out to be. Actually parenthetically when I was a young professor, I was given the laboratory space in which the polio virus was first isolated and I sat at the desk of the man who did it and used the containment facility that he had used to first capture the polio virus. JH: What is the most important thing to know about this vaccine development process that is going on right now in the industry? They sort of ramped up manufacturing and everything.
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WH: From the layman's point of view, it is going to take more time than they think, and it is not a straight path to a win. There are major unknowns that may derail it. It is nothing to count on with certainty. Whereas with drugs it is a certainty that we will have them. JH: But on that point, and then when you are saying there are major unknowns that might include mutation, that might include how often you need to get a vaccine, even if it works, side effects that sort of stuff? WH: Well I am not so worried about mutation in this case. I am more worried about will the vaccines raise in most people the immunization that is needed, will it raise it for long enough and will the vaccine actually exacerbate the infection? Those are the three major worries. JH: Will it raise it, and then will it raise it long enough and then that will it exacerbate the infection. WH: Exactly. Those are the issues. JH: Okay. Is there more, because I do not want to keep you much longer. I really appreciate this. WH: Listen, you are a major voice to the public. JH: What is your view on mRNA? WH: It is an unproven technology that is unlikely to work. JH: Why do you think it is unlikely to work? WH: Well, because what you need with a vaccine is, you need a lot of antigen and you need it to be delivered in a way which the body recognizes. And nobody, as far as I know, and I think it is true, nobody has ever demonstrated an effective RNA vaccine and precedent to RNA was DNA vaccines. No DNA vaccine has ever been approved and people have been trying to use DNA as a vaccine for thirty years and it has not worked. In theory it should work. You stick the DNA in and out pops the protein, the body should see the protein. What is the difference between, you put the protein in and the body sees it or whether you make it and the body sees it. So in theory, it is reasonable to try but to pin your hopes on a technology, i.e. RNA vaccines that have never been used before, when you know that thirty years of research shows that DNA vaccines have not worked, is not the best bet. Does not mean it will not work. Nobody in their right mind would say it could not work. But if I
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were handicapping it, I would not handicap, I would give it a, I would give it a pretty big handicap. JH: Just to play devil's advocate here, you know, most people who get this recover, right, and then additionally, you know, most people have mild to moderate symptoms. WH: Yeah. But 40,000 Americans who are dead would not particularly agree with that. JH: That I understand. I understand that, but I mean if you have a treatment you know, based on our conversation, treatment is expected before next year, or in the next few months and be widely available by the fall. WH: If we are lucky. Yes. It could be maybe six months more, but not much longer. JH: Well, is a vaccine sort of less a priority then? WH: You want a vaccine because the things that have worked to control major epidemics and diseases are vaccines that if you can get a vaccine is the best way. It is the best means to do it because you go around, you can do it anywhere in the world. We have eradicated smallpox. We were close to eradicating polio right on the edge, right on the edge of eradicating polio. We know that they are the cheapest, best things to do if you can get one. But there are viruses like dengue for which it has not been possible. Herpes has not been possible. It may be possible soon, but it is not yet. Cytomegalo affects kids. We do not have a vaccine yet and it is not for want of trying. You know, there have been thirty or forty years of effort. Now again, just for disclosure, I am working with a company that I think finally solved the herpes problem, but it is going to be a number of years before that is approved, if it ever is approved. It is not straightforward that you can vaccinate against every virus. And with HIV, you know, I predicted in 1986 we would not have a vaccine and it was the first time that they had to make it, they started throwing things at me and I had hit the second international AIDS meeting and they had to pull me off the stage. But that was in 1986 and we still do not have a vaccine. JH: Yeah, I mean, you know, I am not a scientist. I do not have a science background education wise. But I am very skeptical of a vaccine coming in the next twelve to eighteen months as some have predicted.
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WH: But I can tell you with near certainty we will have the drugs. These drugs will work. JH: Yeah. Even if you look at remdesivir and some of these other ones, I know they have not been read out yet, but the anecdotes, information that has come out for remdesivir is that it appears to have some level of efficacy and we just do not really know. WH: The only thing you can say about it is it was developed for Ebola and it failed for Ebola. But Ebola could have failed because Ebola developed so quickly. And the conditions for IV administration of a drug where Ebola broke out might not be ideal, but it is not going to be the drug you want because of its delivery. You are not going to want to IV all your hospital staff every other day. You would much rather pop a pill every day. You know, something like 50,000 American healthcare workers were infected as of last week, and seventy five percent of those are women, probably mostly nurses and support staff. That is a pretty big number. How many more thousands can we take and still have a competent healthcare service? Really, the first people to get these drugs besides the patients that are critically ill should be the healthcare workers. JH: Right, I think that is probably, yeah. What is interesting too is that when you talk about hydroxychloroquine, all these trials are enlisting healthcare workers, right. And so you know, does that exclude them from being in other trials? WH: No, just as I said, it does not. You could keep them on hydroxychloroquine if you wanted and add A, B and C to it. You know, we have very good ways of doing that with, that is how we develop all the cancer drugs now. You never do not treat somebody for cancer. You always add, you give them the best standard of care, plus your goodie. It is more complicated for you to do it that way, but that is how it is done. What it does is it in cancer weakens your signal because some of the best standards of care are going to be good for your patients. If you are a good for your patients you have to be even much, much better to show up against that background. But that is how we do it. We are never going to let anybody go untreated for lethal disease if there was any kind of treatment around. JH: Right. Right. No, I understand. Okay. Dr. Haseltine, I appreciate you taking a few minutes. Is there anything else I did not ask you that is good to know at this point? 1660
WH: Yeah, the diagnostics. I have just written an op-ed that I am circulating around, but basically my calculation is we need two billion tests and people are just not thinking the right magnitude. We need a Manhattan like project that the federal government does. It is a very, again, simple engineering problem. We know what to do. It is as simple as developing one little component for the Saturn Five rocket. It did not complicate it. It is already done. Model systems are done. You just have to do it at a higher scale. What I would propose the federal government do is a crash program to develop the instrumentation that allows you to do five minute point of care tests for, in the next two years, for two billion tests. That is what we are going to need. Everybody who goes to work should be tested. Everybody who goes to school should be tested. Everybody who is a healthcare worker should be tested and they have to be tested multiple times. You know, I was just looking at the CMS document, just wrote a little piece on this. I write mostly for Forbes on the blog and what this says. Basically, what I said is, look, it basically says, how are we going to get the hospitals, you know, nobody is going to the hospital anymore. Well, that is not good. People are dying because they are not going to the hospital. I myself am a cancer survivor. They have canceled all my appointments for follow-up. Is that good? No, that is not good. Now fortunately my risk is quite low, but some people's risk is not so low of heart disease, kidney failure. And they cannot go to the hospital either. And telemedicine is only going to go part way. What do you have to do? The recommendation CMS just issued a document for phase one is to segregate COVID from nonCOVID patients. To do that, you have to test every single one of them. Anybody who goes to hospital has to be immediately tested. You get the results. JH: This is what they have done in China, right? WH: Well not really. They are trying but everybody goes to the hospital and gets a test and they either go through route A or they go through route B and there are separate entrances. There are separate waiting rooms. There are separate examination rooms. And every healthcare worker gets tested repeatedly. That is a lot of tests and we are not even beginning to think about it. You know, you talk about a million tests a day, that is not enough. You need a huge number of tests. 1661
I will give you a story. I recently wrote a piece for the New England Journal of Medicine where I analyzed what they have just done in Egypt to screen the entire population for hepatitis C, hypertension and diabetes and offer free treatment. They tested 65 million people. What is the cost in Egypt? Fifty cents for Abbott's finger stick for an antibody. If you are antibody positive, which about four or five million people were, they get a PCR test. Five bucks for the PCR test. Now, if it's five bucks for four million people, you can get that down to a matter of 50 cents per PCR for a billion people easily. The machinery should be developed and the test should be made and the materials should be provided to everybody for free. I was very heartened to see that is what the Democrats are calling for right now. I did not know that until I had written this piece. They came to very similar conclusions, the guys in DC, that everybody should be given the opportunity to be tested. If you are going back to work, you have got to be tested more than once. If you are going to school, you should be tested more than once. If you are a healthcare worker, you should be tested repeatedly. If you are a patient, you should be tested. It should be everywhere and easy. It is doable and not a problem, and if we are going to really open up and get our economy humming again, who is going to want to work in a factory where you do not know if your neighbor is infected? Who is going to want to send their kids to school? Who is going to want to go to a ballgame? JH: No, these are good points. I do not know. WH: Okay, well you do have the answers. The answer is you got to do it and it is not hard. Again, it is not hard to do is now. It should not even be hard politically to do. JH: Well, that is another thing. WH: It is a big mistake. It is a big mistake to politicize it. JH: What is the best way to identify you or quote you in a story? WH: I am the chair and president of ACCESS Health International. That is a not for profit that I created. We work around the world on health system strengthening. JH: Great. Okay. If there are any other questions, I will follow up.
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Interview With Houston Matters: Special Edition April 24, 2020 | Interview
No transcript is available for this interview. The original version is available here: https://www.houstonpublicmedia.org/articles/shows/houstonmatters/2020/04/24/368009/special-edition-dr-william-haseltineapril-24-2020/ Ernie Manous (EM): Today we have got a very exciting show. We are thrilled to have with us a return guest, a global health expert. He is a scientist and pioneer in the realm of the human genome and now entrepreneur chair and president of ACCESS Health International, a global think tank, chair of US-China Health Summit, former professor at Harvard Medical School, regular contributor to Forbes. Of course we like to call him Dr. William Haseltine. Dr. Haseltine, welcome back to the program. William Haseltine (WH): It is a pleasure to be here. Thank you. EM: A very impressive resume, but with that impressive resume comes years and years of knowledge and understanding about all sorts of things when it comes to health in our globe. Correct? WH: That is for you to say, not me. EM: Well, I think it is safe on this point for me to say, yes, it is true. I am curious, before we get into all of the medical aspects and the science that is going on now, I am curious about your thoughts of what we started with across this country. Different states are deciding to try and reopen their economies. From a scientific point of view, from an understanding of viruses and global pandemics, is our approach correct? Is it too soon? What are your thoughts on this? WH: I think the future for us on the course that we are on, the future for the United States, is to have a very prolonged epidemic where we seem to control it in one place and it springs up in another, and that is because we have not ever fully controlled it. You know, 1663
if you look at some other countries in East Asia that have taken very strict quarantine, what they call controlled quarantine, testing, contact tracing, controlled quarantine, they have gone up a mountain slope and climbed right back down. So they are beginning to reopen and that makes some sense, but they are re-opening extremely carefully and we can discuss that. We on the other hand are not in the process of controlling it. We do not have anything approaching controlled quarantine. So we are climbing up a mesa tabletop and we cannot see the downslope. It is going to be a long, long, long down slope with a very bumpy terrain where we go up and down on the course that we are on. That has a very negative long-term effect on the economy because nobody is going to be sure when or how or if they can reopen. And if they do reopen, well, they just have to close right back up again. That is what we are looking at very clearly as our future. EM: Is there a way to start to reopen that would be safe or at this point, with everything you have just said, this needs to be stalled. What is your point of view? WH: There is a way to open up, but there are a couple of criteria that everybody would agree on I believe. One is that the rate of infection in the overall population has to be low in the local population wherever you are. It has got to be low. And when I mean low, it means barely detectable, just a case here or a case there. Then you can begin to think that, well, okay, if I go out, I am not going to bump into somebody who is infected. The next thing you have to do is very careful identification of anybody who is infected. That means lots and lots of tests. We will need billions, not millions of tests per year until this is medically controlled. I said billions of tests. The only way we can get billions of tests is for the federal government to launch a crash moonshot Manhattan like program. We can do it. It is not tough. It is technically feasible, but we need to do it. So identification. Second contact tracing. We need to know everybody an infected person has been in contact with for the previous ten days at least and maybe a little longer, and that means everybody. We need an army of about 300,000 to 500,000 contact tracers to find all those contacts. Each person is going to have many, many contacts in ten days. There may be twenty, there may be a hundred.
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The third and everybody would talk about that. If you listen to Brian Williams last night, everybody was talking about testing, contact tracing. Nobody was talking about what you do with the people you have identified. So you identify somebody who is exposed. What do you do? The answer to that is controlled quarantine. That is something that is not even in our lexicon. What does controlled quarantine mean? In East Asia, which has climbed off their mountain peak, it means isolation in a room by yourself, without family members and in contact only with hazmat clad people for fourteen days from exposure. In East Asia, they have just extended it to twenty one days because after people come out after fourteen days, some of them have started new little infections. They should be in the US in all our empty hotel rooms, but they have to be supervised. They have to be carefully supervised so people do not come out of their rooms and the people who are feeding them and cleaning the rooms need to be completely outfitted in hazmat outfits. That is part of the lexicon which is not even in the imagination of most people. Now you could ask, would Americans do that? Americans will do what is necessary if they are given the proper leadership and they understand the cost of not doing it. The cost might be to their life, the life of their loved ones, and if that is not enough, it will be continued loss of jobs, economic hardship, unemployment that lasts for a very long time. We have to get moving again, but the only way we can get moving is to control this disease and without the kinds of measures, the three steps, people talk about the first two, they don't talk about the third, without those three steps, very hard to imagine. EM: A question I have for you, and I am looking for an answer that may be reflected in what you have seen with other pandemics, other cases of viruses out of control. The argument we start to hear a lot of is, but now that they have tested so many people in New York, we are starting to think that the death rate might be much, much less than what we thought. So why are we reacting so strongly to this? Isn't what they are saying the cure is worse than the virus? WH: Well, you know, I live in New York. I am speaking to you from New York and I will give you a reality check. I live in one of the poshest places in the city, right opposite the Met Museum. 1665
Six blocks down and two blocks over, there is a morgue on the street. A friend of mine went in there with a camera and there were forty body bags on the pavement. Some of those might have been my friends because I have had friends who died. Go to any New York hospital, and there are people waiting to get in and they are completely chock-a-block full with people who are dying. So if people want to have a picture of what could happen to their community, they should just look at what is happening here. We are Americans just like the rest of the country. That is what people should have in their mind. You know, you can say it is only one percent of the population that dies. Well, one percent of the population is a lot of people. S it is indisputable that people are dying and they are not dying like they died from the flu. We are already way past what has happened this year, the whole year for the flu. And we are not anywhere near the end. We just passed 60,000 people died in America from this disease in a matter of three weeks. How many more people do they want to die? Do they want their kids to die? Do they want to die? Do they want their parents to die? Ask the people that want to open up so much and even those people that want to open so much are doing something that is counterproductive because opening up too soon will just prolong the epidemic and it will prolong the economic hardship. EM: We were talking earlier today in our offices about this very point and what we were talking about is that some of the people that are needing to reopen shops feel that they have been without pay for a number of weeks. They are without support. They have a family to raise. They look at the numbers and they say, this is a risk I am willing to take. If it's one percent, if it is ten percent, is it worth it to me to get back to business to help save my family, and we look at this every day from a very scientific point of view and medical point of view about what it is doing and what happens in people that die. How do you talk to people where they see their livelihoods are going to be gone? Their families are going to crumble. They are not going to be able to provide when at the same time we know the answer is to confinement and to hold off on this opening. How do you balance that? WH: Let me say first of all, we do not know what the ratio of infected to serious disease and death is. Some would put it at one to 1666
one hundred, which you just did, and some would put it at five percent or higher. Okay. That is the first thing. Second thing to say is America is unhealthy. Something like seventy percent of the Midwest is overweight, obese, in fact. That is a predisposing condition, a serious predisposing condition, and it could be ten or fifteen percent mortality with that condition that so many of our fellow Americans experience. So who knows what the actual number is. That is the first thing I would say, but there is a deeper underlying social reality, which is everybody has to sympathize with people who do not have a job and have to support their family that might not have food to eat. That is a social problem and is something that our government should do to help us. We do not have a social safety net in this country that gives people a security so that they have to ask themselves that horrible question. Am I going to risk my children's life by getting infected and my own life because I cannot feed them? Am I going to go out and risk my life so I can feed them? And even then will there be a job. Who is the say that job, that shop that opens up, will still be allowed to open up once the infection takes off again. Or if you are in a community that has not been infected, it takes one person coming in. Think of this, there is about three million people in the world infected today. It all started with one person infected, just one, only one. And that is what has happened to the rest of the world today. If one person can infect the whole globe, somebody better think that one person could infect their town or their even village. It is a terrible conundrum. And the answer to that is the government should be giving people the food and the economic support they need, everybody in this country, until they are safe to go back to work. EM: Sorry about cutting you off while you were speaking there. We are going to take a quick break right now. When we get back, we are going to dig deeper into the science of all of this. Talk about the new things we have heard about on the horizon. Some are promising, some not so much. We are talking with Dr. William Haseltine, global health expert, here on Houston Matters Special Edition. I am Ernie Manous. We will be right back. This is Houston Matters Special Edition. I am Ernie Manous. We are talking with Dr. William Haseltine, former professor at Harvard Medical School talking about the impact and the future of the coronavirus and a Fall surge. Other people talk about a second 1667
wave, other people talk about a spike coming. The way I look at it is that this is just dependent on how we deal with it right now and how quickly it comes back again. Are those different things? The same thing? What are we talking about? WH: I think that the notion of big waves, let us say big, big waves, think of them as super waves, the type that people ride off the coast of Hawaii, come from our observation of both influenza and coronaviruses in general, and they have a seasonality to them. Let us take the coronaviruses. Let us say a background level in the summer might be one. And by the time January, December, January rolls around, it might be up to four, three and a half to four, the wave. And then during the summer it will come back down to one and then it will go back up to four again the next year. And we have actually tracked that for these coronaviruses, these four that I mentioned. We have tracked it by region of the country. We have tracked it by country. We have tracked it all over the world. And that is basically the pattern in the Northern hemisphere. They never go away. People are getting these colds all the time. And this virus is now so widespread, we believe it will be endemic, whether it is your local cat that gets it and gives it to you, whether it is in some people at some level they give it to you, whether it is some other reservoir. These cold viruses keep coming back and back again. And we think the same thing is almost certain to happen with this now. Why people are more susceptible to the influenza and to coronaviruses in the winter months, nobody knows. It is not the heat or the humidity that is changing the virus because there are plenty of people like in Singapore that have epidemics where it is always hot and it is always humid. So, you cannot count on heat and humidity. It is something else. Maybe it is we do not aggregate as much. That might not be the case. Maybe it is the fragility of our mucus membranes when it gets cold. There is something that gives this pattern. Other viruses have completely different patterns. Polio for example, and I remember as a kid, is a summer virus. It is also a cold virus. So does that say it is going to be for fragility of your mucus membrane? No. So it is a mystery. But what is clear is that the two epidemics that we see coming again next November, December, January, February, are influenza and another resurgence of this virus. That would happen naturally if we don't have a medical way to control it or a social way to control it. 1668
And I think what we are talking about is how big will those waves be. What we can do, what we do right now today, each and every one of us is help make that wave smaller, that second wave smaller. We want to make it small enough so it does not overwhelm our hospitals. We want to make it small enough so people who become ill with flu can get the care that they need. But the fear that you heard Bob Redfield, a good friend of mine for many, many years, we worked hand in glove together for years on HIV/AIDS. You heard him voice that these two things are going to come together and if they do, the hospitals that we know get overcrowded with the coronavirus patients will be doubly crowded by having to take care of influenza patients at the same time. So we hope our actions right now can suppress that so it is a rather small wave underneath the wave of what we get every year with influenza. EM: Since I have you on the line, maybe you can help me understand something I heard in the White House briefing yesterday, which I have not heard expressed in the way that they said it from the podium. I am trying to understand what the half-life of the virus means. I always assumed that meant the power is cut in half, the ability to do the damage is cut in half, but they were talking about viral load cut in half. What is the actual scientific definition of a half-life of the virus? WH: It depends in what context. Let us say the half-life of the virus as it is in a droplet that you expel when you cough and it lands on the surface is the time in which half the viruses that landed there are dead. And so if the half-life is an hour and half of them are gone in an hour, seventy five percent of them are gone in two hours, et cetera. So that is related to how likely you are to get infected, which is how much virus it takes to infect you. What is the dose it takes? With most viruses, there is a dose response so you can tolerate a few viruses, but as you go up in concentration you can tolerate fewer. So the half-life of a virus outside of the body determines the dose that you are going to get if you are exposed to that surface and therefore, whether you get infected or not. EM: Do we know the dose size of virus to infect us with this coronavirus or we do not know that yet? WH: I do not know it. I can tell you with many viruses there is a sort of a step function. So below a third threshold you get very
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little infection. And then once you reach that threshold, almost any person or animal exposed will get infected. EM: When we were talking a moment ago, you mentioned getting it from your cat or something. And I am curious, what do we know about transfer from animals to humans or humans to animals, especially when it comes to household pets at this point? WH: Well, this virus came from bats originally, so we know that happened. Did it go through another species like a pangolin? Maybe. It did not have to. It just takes a little bit of bat poop into the water and this virus is transmitted oral fecally. So that could happen. We know that cats, but not dogs have a high affinity receptor for this virus. The first time most people heard about it was the tiger in the Bronx Zoo. It is not the first time I heard about it because I knew the cats had a receptor that was compatible for this virus. Does that mean they can give it to you? Probably it does. If the cat gets infected and does have symptoms which cats get, they have sort of the sniffles and stuff, it could well give you the infection. They are zoonotic viruses, that is viruses that jump from animals to people. For example, right now there is an infection going on where people are being continually infected by camels. Camels are the reservoir of the MERS virus and every year people get infected, not from other people but from camels. So it is not outlandish to think that cats could become a reservoir from which people can get infected. EM: Another term that if somebody asked me about WH: I am going to be hated by cat lovers for that. But that is I think the facts. EM: Well that is what we turn to you for. The actual information unbiased and accurate. Somebody asked me today and I thought I would let you address it, the difference between antigens and antibodies. A lot of people have had no science training and they hear these terms thrown around and they get confused. WH: That is the difference between a key and a lock. People understand that. There are two halves that are both needed to function. So an antigen is a foreign substance that causes an antibody reaction. An antibody is a molecule your body makes that recognizes that foreign substance. So right now in New York, all the trees are flowering and they are producing pollen. Those are antigens and your body is reacting to them and your eyes are watering and your nose is running. So the antigen is eliciting a reaction. So the antibody 1670
is the molecule your body makes that will see a very specific hand in glove like fit. And when I say lock and key, it is a very good analogy because the intricate shape where all the atoms are placed on the surface of the antibody have to match perfectly with where all the atoms are placed on the antigen, has to be a very, very tight fit for it to work. So it is a lock and key kind of thing. I hope that helps. EM: It does. In this area, I know a lot of people are concerned with we are played with natural disasters here. We get bad weather, we have flooding, we have problems here. From other outbreaks you have seen in other parts of the world, could we, should we expect major flooding, hurricane hitting Houston to exacerbate this or are they in different realms at this point that we would not have to worry? WH: You know, I grew up in a place called China Lake, which is near Ridgecrest where the huge earthquake just happened. And I had been, while I was in China Lake, in several earthquakes. I once had the pleasure of being with a seismologist during an earthquake. I can tell you what makes a seismologist happy is an earthquake. You never saw a happier guy. But in direct answer to your question, they are unrelated. They can work on each other and make things worse. And that is always the case. For example, if you look at the regions of America where we have unserved populations, where we have a lot of migrants, where we have a lot of poor people, we have a lot of poorly served communities. The virus is wreaking havoc there, not because they are more susceptible, but because the conditions they live in are worse, because their underlying health situation is worse, and because their medical care is worse. And if you look at our cities, the ratio of those underserved populations is maybe a five times amplification in terms of the effect on those communities as to the effects on more affluent communities, a five to one ratio, and it is not a matter of race. It is a matter of opportunity and the conditions under which you live. Those are called the social determinants of health. They determine, unfortunately, the outcome of this epidemic, and it falls very, very heavily on those unserved populations or underserved populations regardless of race. EM: One thing I want to get into before we go to our next break is how different treatment is by which hospital you end up with. In a sense, it is almost, I believe, the luck of the draw as to where you go to the care you receive. What is your thoughts? 1671
WH: It makes a really big difference. If you are on a ventilator in most places in the United States today and around the world, your chance of living is about ten percent. If you go to the best medical care, the chance maybe fifty percent or sixty percent once you have been ventilated, once you are intubated and ventilated. In some cases, it can be even lower than that where there is super experts. So it does matter where you go to be treated. Ventilation and treatment of patients that are undergoing this new and very complicated disease is an art form. There is no recipe book for it. It depends upon absolute training, highly specialized training of the people who are doing it. It depends on knowing in real time exactly what has happened to each of your patients and then being able to correlate that through a data system that gives you the information you need in real time and then it takes a dedicated organization to say we are going to do everything we can possibly do to save our patients. Unfortunately, there are too few systems like that in our country. I will give you another statistic. Even in the best hospitals, the death rate is probably twice what it has to be. There are some hospital systems like in Chicago, in Philadelphia and one or two in here in New York where the death rate in hospital death rate, despite what kind of patients you have is half of what it is in other hospitals. That is because those hospitals focus on it. I will do a little selfpromotion here. I wrote a book called World Class, which tells you how a hospital can achieve those kinds of results. It is not easy. It is like going beyond six Sigma to no fault. That is what it is like if you around, if anybody is listening who is into manufacturing, everybody knows about six Sigma, but there is another level beyond that which is called no fault, which is how nuclear reactors operate and how airlines have to operate. It is beyond six Sigma and those hospitals that are pushing beyond six Sigma are the ones that have the best results. EM: We are, on that note, going to take a quick break. We will be back with the last chunk of our show today where I think I am going to take Dr. Haseltine a little globe-trotting to see how other parts of the globe are handling this pandemic. This is Houston Matters Special Edition. I am Ernie Manous. We will be right back after this break.
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Dr Haseltine, before I get back into my side, when we talk about flattening the curve, from a biological point of view, from a global pandemic point of view, is that important and why? WH: Squashing and crushing the curve is better because that means fewer people get infected. Flattening the curve just means you stretch out the infection. There is the total number of people, same number people get infected. Same, same number of people, but instead of all at once, they get infected over a much longer period. That is good for the healthcare system so it gives the hospitals time to prepare and to treat the people as they should and not be overloaded. What we really want to do is squash the curve. We want to come down so that there are not many people infected at all. And that is possible as has been shown in a number of East Asian countries. But at this point, the way we are behaving in most of our regions, we are flattening the curve and it will be a very, very slow comedown from those curves. That is what is happening in Europe as well. By and large, US is behaving a little bit, the epidemic is behaving like it does in Italy and in Spain where you have a sharp uptick, it then gets to a plateau and it is very, very slow to come down. So that flattens the curve. That is not what you really want. You want to squish the curve. EM: I did say before we went to our break that we were going to do a little globe-trotting and I am curious, what are we learning about the way they handled things in Italy and Spain? WH: They did not do what they should. That is why they have an epidemic which looks just about like ours. First of all, they were very slow off the mark, just as we had all the controversy about who knew what when and did or did not do something. They are having the same conversation and in fact they have carried it to the next stage which is a legal stage where they are taking to court their political leaders for inaction. So their situation is pretty much like ours. They have asked everybody to self-isolate, but they have not instituted quarantine. They have been better at testing than we have. But that still has not made a huge difference because without quarantine, testing does not have the teeth that it really needs. If you have somebody who is known to be infected and then go down to their basement, well the chances are their family is going to get infected and their family is going to go out and infect other people. That is the reality. So if somebody is infected or been exposed, they 1673
should be isolated. That is why Europe as a whole has the kind of problem we have here in America. Now, if you go to East Asia, they have been much more strict and the reason for that is they knew the economic harm this would inflict. It had closed down their economies before and they were not going to do it. They had practice. They knew what to do, and they put in very, very strict control measures, controlled quarantine. And that has not just flattened the curve, it has obliterated the curve. But a bad lesson from Singapore is if you do not obliterate everywhere, it's going to come back to bite you because they did not treat their worker population, their foreign worker population, the way they treated the rest of Singaporeans and the infection just came roaring right back. So they have had to close down their economy again. So, and we do not know. And I think in many parts of the world like Africa, Sub-Saharan Africa, almost all of South America, very little insight. We get some horror stories like out of Guayaquil, Ecuador. But the information is so sparse. Or Russia, I mean Russia, there has to be a rampant infection. Forty people came in on one plane from Russia to China. Chinese being repatriated. Forty to fifty people on that plane were infected. So what does that say about the infection in Russia? So there is major epidemics raging in parts of the world which we do not hear anything about. But ultimately it's going to be our problem because as I said at the beginning, one person infected started this whole thing, one infected person. That is all it takes. So as long as there is one infected person somewhere in the world and we do not have a medical way to stop it, social measures are the only way to control it. EM: In the one minute that we have left, I wanted to hit this topic and I am sorry for shortchanging it, but the talk of indirect deaths from this pandemic, can you address that for us. WH: Yeah, it is a really big problem and there are probably just as many or more indirect deaths. When an indirect death means you cannot get, you do not see your doctor when you need to. You have a heart attack, you do not go to see the doctor. You have a heart attack and the ER guys do not come. You have a diabetic crisis and you do not go to the hospital because they will not take you. There are many, many reasons people who are diagnosed with cancer can't get care. People who are in the middle of cancer therapy, get it interrupted. There is a lot of death there and I should also add to 1674
that suicide. The rate of suicide is skyrocketed because this is a very stressful situation and people who are fragile will crack. So there is many reasons for it and it is a double tragedy. EM: So note in there too, if you are suffering from anything, contact your doctor. I know a lot of people have fear of going to the doctors and checking in with hospitals, but they should still behave like they did before because we need to take care of everyone in our community. Dr. Haseltine, thank you so much for bringing that flashlight and shining it into those dark corners we do not often talk about when we talk about this pandemic. Always a pleasure to talk with you. I learn so much from you each time. Thank you for joining us. WH: My pleasure. Thank you very much for your interest.
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Interview With Dana Perino, FOX News April 24, 2020 | Interview
Dana Perino (DP): Thank you for joining us today. William Haseltine (WH): My pleasure. DP: We have a reporter before you and then we will bring you in on what you think are promising new treatments. WH: Okay, good. DP: It may take more than a year to find a vaccine, but breakthrough research is being done on other solutions. Mike Tobin is in Chicago. Mike, one university is fast tracking a coronavirus drug. Mike Tobin (MT): They are certainly hoping to fast track. They have what could be a breakthrough and the reason these doctors at University of Louisville think that they can fast track this drug is because it has been in existence for years. It is a synthetic DNA and it was developed for the treatment of cancer patients. It has already been through clinical trials on a hundred different patients, so you have a rough idea of what the side effects would be. Professors at the University of Louisville say it binds with the proteins in our cells. These are proteins that a virus would use to live, replicate and thrive. DP: The protein that is targeted by a drug is the one that helps viruses. So, you use synthetic DNA to block the ability of the virus to synthesize protein and therefore block its replication and infection in cells. MT: However, this would not take the place of a vaccine. Professor Bates described it as a “stop gap measure for someone who is already sick.” You use the synthetic DNA to stop the virus from growing and getting worse while the body's natural defenses kicked the virus out. The FDA is overseeing some 72 different clinical trials of treatments ranging from antivirals to drugs that stop the body's defenses from overreacting. Things like swelling to what you have already heard about with plasma and antibody treatments. And
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professor Bates says in this current environment, in this current crisis, things are moving very fast through the testing phase. DP: There is hope. Thank you so much Mike. And there is another promising new weapon in the fight against coronavirus. It is an antibody research being done in China. Here to tell us about it is Dr. William Haseltine, chair and president of ACCESS International Health and also a former Harvard Medical School professor. While I know that this is a little bit technical to explain, I also know you are very good at explaining things to people like me. What would this do to the virus to help us? WH: The first thing to know is that this is an experiment. It has not been tried in people yet, but it is very promising. We know that the sera, the plasma from somebody who is recovered, has a possibility of stopping the virus. That is because they have substances in that plasma called antibodies. What the Chinese have done is actually pulled out of those individual cells the active part, the antibody, made of what is called monoclonal antibody. As a result, we should have the effect of plasma, but more potent and more reliable. It should be able to treat people who are infected and prevent people for at least a limited period of time from becoming infected. DP: This is being done in China, but people are quite skeptical of China at the moment. Is this a type of treatment that US scientists could do as well? WH: Absolutely it is. In fact, I know of labs both in the US and in England that are currently conducting similar experiments. People may be skeptical about China, but they should ask themselves who controlled the infection, China or the United States? DP: So, in terms of this type of treatment, how soon could somebody benefit from something like it? WH: When we were hit with anthrax, I developed a very, very similar drug. The process from the very idea to the time it was approved took two years. That was superfast then; twenty years ago. We are better now than we were then. And we have full government support and world support behind this. I believe we can fast track this so we can get to approval within about four months and it may be available shortly thereafter to some, and then to increasingly larger numbers of people. The bottleneck eventually will be manufacture. 1677
DP: So, this is something that, before we get to a vaccine, could actually have a lot of promise. I do not want to get ahead of ourselves because we have to let the science work itself out. But you are hopeful about it and I know you are a cautious guy. WH: I want people to understand in the midst of this epidemic that science will save us, and this is one very bright spot and you are about to hear many, many more. There is going to be a flood of very exciting new drugs to treat those who are ill and to prevent those who were exposed from becoming ill. DP: All right. Dr. Haseltine, pleasure to have you. Thank you so much. WH: You are welcome. DP: And you actually have an article on Foxnews.com that everybody should check out about the different ways that the governors are treating this.
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Interview With The Heat April 30, 2020 | Interview
No transcript is available for this interview. The original version is available here: The Heat: COVID-19 research and medical response
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May 2020
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Interview With Bloomberg News May 18, 2020 | Interview
No transcript is available for this interview. The original version is available here: https://www.bloomberg.com/news/audio/2020-0518/fighting-coronavirus-conspiracy-theories-podcast
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Interview With Thomson Reuters May 19, 2020 | Interview
No transcript is available for this interview. The original version is available here: https://www.reuters.com/livevideo?id=Paj8
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Interview With CNBC May 20, 2020 | Interview
No transcript is available for this interview. The original version is available here: https://www.cnbc.com/video/2020/05/20/fmr-harvard-profsays-modernas-vaccine-trial-publication-by-press-release.html
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Interview With NBC Nightly News May 20, 2020 | Interview
No transcript is available for this interview. The original version is available here: https://www.nbcnews.com/nightly-news/video/u-s-gives-1billion-boost-to-oxford-coronavirus-vaccine-effort-83761221840
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Interview With The Intercept May 21, 2020 | Interview
This is a lightly edited transcript of the conversation between Sharon Lerner, investigative reporter and William A. Haseltine, Chair and President, ACCESS Health International. Sharon Lerner (SL): I was looking at a CNBC piece today that was saying that health regulators have fast track approvals for coronavirus research and development, allowing scientists to skip through months of red tape. They were talking about this as a good thing. I wanted to speak to you more broadly about the dangers of skipping through red tape. Are there public health dangers in this area? WH: What some people call red tape, other people call responsible regulation. I have had years of experience in working with the US Food and Drug Administration and other regulatory agencies and I would not say it is uniform. However, it is my most common experience that they have been extremely helpful. I always felt that as long as you approach them in a straightforward manner, they will be more than helpful. They gave me clear advice and facilitated development. They also helped streamline the process. Their interest is getting drugs that work onto the market that improve people's health. The times that they warned me or gave me advice to stop or slow the development of a product, in the long run, it always turned out that they knew more than I did and that they had very good reason for doing so, often because they were in possession of information from other experiments that had failed or other trials that had failed or other drugs that had elicited adverse reactions. I never found their objections frivolous. In fact, I found them profound. Thus, the regulations that are in place are there for a very good reason; not to impede development, but to make sure that drugs that are approved are safe and effective. Is there a danger of skipping over? Now I have to say, I probably hold the record for going from idea to approval and purchase of any drug. I may be wrong, but AZT may be a close second, if it didn’t 1685
already beat it, but the drug was approved by the FDA under a special exemption through BioShield. BioShield created a mechanism whereby for drugs that were a threat to national security, no matter the nature of the infection, if there weren’t any people being actively infected by the agent, which is not the case for this disease, except in China… SL: What do you mean? WH: Let us take anthrax as an example. While it is very hard to find people infected by anthrax today in the United States, or anywhere, there was a worry that anthrax would be an infection that would be launched by a terrorist. So, there was a need to find a drug that would prepare people who were not vaccinated because we had no effective vaccine. W still do not, from a deliberately constructed strain of anthrax that was antibiotic resistant and released against the public. So, we had to ask what the threats and countermeasures are. I thus developed my company, Human Genome Sciences, and developed an antibody that works against the toxin, which both prevents anthrax infections for up to four or five weeks, and them, whether they are antibiotic resistant or not. Now all we had to do under those circumstances was show that it worked in two animal models of human disease and have one safety trial. So, if there is no natural infection in progress and if it is deemed to be a threat, we have legislation on the books which allows rapid development and stock piling. Now, it is not approved for market, but the US government stockpiled it. And there are now a number of such drugs. So, we have the legislation in place. That is justified under the circumstance that there are no natural infections. I do not believe it is justified under the current situation, where the virus should be tested in people who are likely to be infected. And there are plenty of those people all over the world. Also, there are grave dangers in skipping over. For example, I do not believe that Moderna tested their vaccine in monkeys. Every other company is testing it in monkeys and reporting that data while Moderna does not mention any data. Did they go to humans? SL: Did you ask them for it? WH: No, I have not. I just look at whether or not they have tested it in monkeys. They say that it worked a certain way in mice, but we did not see the data. That is dangerous because all the other companies, with one exception, have done monkey experiments and 1686
this is what they found: none of them, with one exception, reported that the animals were protected. They all were infected and had nasal infections. So, it lessens the impact of the virus on the body at best. For most vaccines, you want them to protect from infection and stop the infection in the population. People talk about herd immunity; a vaccine is going to create that. These vaccines, as far as we can tell, would not give you herd immunity. What they would do is maybe give many people who are vaccinated a nasty cold that they could give to unvaccinated people and kill them. The problem is that it would be counterproductive. The second problem is one that people are not addressing. We know that the older you get, the weaker your adaptive immune response is. You lose memory of recent immune exposures just as you lose your cognitive memory. And so, we are in a catch 22. The people who need it the most are those who have the toughest time making immune responses. The third very serious issue is that I do not believe a vaccine exists which protects a human being from an infection through the nasal mucosa. People have tried for years to do it and have always failed. When you look at the history of the MERS and the SARS viruses in primates, they got great immune responses and never were able to prevent mucosal infection just like most of the vaccine reports that we see. Yes, they make neutralizing antibodies. Sometimes they make very high titers of neutralizing antibodies. If you look at the literature, they tried whole and killed virus, attenuated virus, DNA vaccines, protein vaccines and even subunits. SL: When you say they tried, are you talking about in the past or are you talking about the coronavirus? , WH: I am talking about SARS and MERS. We have fifteen years of literature on trying to make vaccines, and people before that tried to make vaccines against cold viruses. All of them ran into the exact same problem. They could protect animals and make all these antibodies, but they could not protect them from primary infection. SL: Interesting. And why do you think people are glossing over this point? WH: I think that this is one of those unfortunate situations where scientific endeavor meets policy and political realities. And under those circumstances, it is ever so much more important for 1687
medical researchers and scientists to observe utmost clarity, responsibility and ethics in their communication. People could have a commercial motive, a reputational motive, a nationalistic motive or even a political motive. All of those are recognized motives. I taught a course for twenty years at Harvard called biology and social issues, and the point of that course was to help nonscientist undergraduates understand how to interpret scientific argument that involved a political issue, nuclear power, nuclear and biological weapons. And it is a very big issue. When I was being interviewed last night by Brian Williams, he said, “what are we going to do? You know, an educated consumer is what you want, but what are we going to do?” I answered that scientific truth is not a matter of majority opinion. You cannot find it by asking a bunch of experts. When Discover Magazine did that thirty-five years ago about HIV/AIDS, they asked twenty experts and concluded that HIV/AIDS would never be a big problem; which is wrong. Scientific truth is not a matter of majority opinion. It is a matter of fact, but that fact has to be verified and it is our responsibility as scientists to be absolutely clear and transparent. If we make a statement, we have to show the data that supports that and we cannot make these nebulous press releases. If you look at the May 19th issue of New England Journal of Medicine, you can see how upset the biomedical community is about what is going on. There was an article by Andre Taleo, Why You Have to Follow the Controlled Clinical Trial Route, and in simple terms: if you do not, you are going to mess up like people have messed up in the past. There are other articles like, Finding the Treatments by Jesse Goldman, Finding Effective Treatments for COVID, Scientific Integrity and the Public Confidence at a Time of Crisis. They show that I am not the only one who is upset by this. Here you have the Journal of American Medical Society deeply upset at what is going on. And they are not just upset at companies but also at universities and at the federal government. One of these young reporters said to me in the CNBC interview, “oh, you are questioning Tony Fauci, but he is the best expert we have. He is the number one.” And while he is under a lot of pressure, he did say that Remdesivir is very, very modest in its effect. Very, very modest might mean Tamiflu-like or worse. SL: Is it comparable to Tamiflu? 1688
WH: Perhaps not even that because the Chinese published a story that says it does not reduce viral load. While the Chinese tried to look for the antiviral effect of the antiviral drug, it was not there. It had no effect on viral load. Now the people have come back to me and said that it is hard to measure viruses. However, the Chinese measured it in Hong Kong with a Hong Kong cocktail. SL: Let me ask about the specifics on Remdesivir. So, as you know, it is now not only being widely distributed in the US, they are talking about distributing it in 127 countries. And they are probably going to start charging for it in the summer. But I was looking at some of the emerging evidence that the drug seems to create problems with the kidneys as well as with the liver enzymes. How do we weigh the potential adverse effects against the benefits if we do not fully understand what the benefits are? WH:. I think it has no benefits. I have not seen the data, but if I hear Tony Fauci say that it has very, very mild effects at best and it has any side effects at all, it should not be used. And if you look at how it was pushed through, there was something suspicious about it. The weakest end point you can possibly imagine in a clinical trial is getting out of the hospital early; and the FDA would never approve a drug on that basis because they want real evidence. Did it shorten the disease symptoms? Did it reduce the virus load? These are the questions that need to be answered for antiviral drugs. When people measure the virus load, they do not find any difference. For side effects, it is bad to have money made and lives damaged by drugs that do not work. That is why you cannot short circuit these processes. You can speed them up, if you speed up transparency. So most, not all, journals are allowing their authors to publish online preprints before they are even reviewed, and then allow those papers later to be published. That is good because we can see the data, but people started misrepresenting what is actually in print, saying they protected animals when in fact they did not. A responsible statement would have been that the animals were vaccinated and while virus load was reduced, they all still had a nasal infection. We believe that might mean if we extrapolate that to a human being, they might have a cold, but not pneumonia. But we cannot be sure of that until we check it in humans.
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SL: You were talking about people who can publish their preprints and that is good because we can see the data, but for people to start giving inaccurate descriptions… WH: The example I would give is Adrian Hill talking on CNBC saying something like “it worked”. The vaccine worked because it reduced the viral load of the lung. Most people would mean it did not infect the animals. A more accurate description would be the animals were infected, but the virus load was dramatically reduced to the lung. SL: Right, right. WH: There is a very good STAT article on the Moderna issue where they go through what other scientists say and every part of that is accurate. We do not know what normal neutralization is. We know they give some measure that says that it made the same number of antibodies as convalescence. We know that many convalescences make no neutralizing antibodies. And some of them make a lot of antibodies that are not neutralizing. And some make really low levels of neutralizing antibodies. Some make none and some make low. So, what does it mean? SL: Right. WH: There is a broader issue that you are approaching, which I think is the right thing to do. And please, do look at JAMA because you can see the community's upset. I just saw today an article or a quote where Tony is saying that he did not say we could go full speed ahead. I do not like the name warp speed. I would say there are two meanings for warp and that is what I worry about. This is my actual worry. We think it means going very fast but it actually means distorting. That is what it means. And I fear that that warp speed is going to distort our regulatory process. That the administration will put its thumb on the scale as it does in so many other cases to favor its cronies and to favor a political outcome regardless of the cost of human life. I see that happening. I see the FDA being compromised the same way that inspector generals are compromised. And in this case, we are talking about hundreds of thousands if not millions of lives. SL: Yes. So very specifically. What do you make of US President Donald Trump holding on to his various financial holdings and dates and various companies? Do you think that is a concern or not an issue? What do you think of that? 1690
WH: Anybody who works for the government has a responsibility to make sure that their decisions have no financial benefit to themselves. That is an absolute rock-solid principle of government employment. And therefore, if he holds shares in a beneficial way, if anybody holds shares in a beneficial way over an area in which he has decision making power, it is a serious issue. SL: I wanted to also ask you about some of the allegations that Rick Bryce made in his whistleblower complaint. He lays out some very specific descriptions of pressures he said he experienced to go around the scientific processes to make sure things get approved right way. Did you find any of that surprising, or concerning? WH: It is all concerning. Any time you try to warp science and the scientific process for political purpose, it is dangerous. We, as scientists and doctors, have a moral responsibility to be exceptionally clear because the stakes are so high; because billions of people may be exposed to a drug like Remdesivir, maybe even exposed to a vaccine, we have to be especially conscientious and regulators also have to be. That does not mean we cannot do everything that is necessary to make things happen quickly, but you cannot cut regulatory corners and you cannot overstate or misrepresent what is actually being done. The only way to do that is to make sure that when you make a statement, the data is clear for everyone to see. Why can we say something about the Oxford study? Because they made the data clear and wrote right on their website, do not believe any rumors you hear unless you see it here. It is like saying, do not listen to what we say, look at what we write. That is what I mean by being responsible. SL: Bill, about the list of drugs being considered, we have talked about Remdesivir… WH: I think that it looks like Remdesivir does not work at all as far as I can tell. If it does, it has such a minor effect that there should not be a mad rush to get it. The one cocktail that does look like it helps people with moderate to serious disease is what I call the Hong Kong cocktail. It is four drugs which have been shown in the published literature to reduce viral load and to save lives; to actually reduce death. Remdesivir has never been shown to reduce death, but this cocktail of generic drugs has. The biggest downside of Remdesivir is that it is not an easy drug to deliver as you have to be in a hospital and have an IV line. It is also not easy to make. On the 1691
other hand, this cocktail of drugs, which is lopinavir, ritonavir, ribavirin and interferon beta can be taken either orally, intramuscularly or subcutaneously. This is much easier to administer, even to administer for people who are not hospitalized. But nobody's rushing to get that drug. They are all generic drugs. SL: Is it because they are all generic? WH: I do not know if that is the answer, but I can tell you that makes it easier. It is a wonder drug regimen which has shown to have some effect. SL: And could you send me any of these studies you have that shows that effect WH: It was published not long ago SL: Just to go back to finish that last question. Are there other drugs you put in the category with the Moderna vaccine and Remdesivir that you think has been their… WH: Remdesivir. When I look at the data, I see all the animals which have been infected. Again, they found that the amount of virus in bronchial lavage was less, but nonetheless, they looked to me like infection from their own charts and I think their idea that it worked was overstated. The natural interpretation the virus worked is that the animal was protected entirely from infection. Anything less than that needs a lot more explanation than simply saying that it worked. SL: Thank you. WH: You are welcome. Thank you. Bye.
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Interview With Bloomberg News May 22, 2020 | Interview
Bob Langreth (BL): I wanted to ask if you know the names of the other people that you know of who were calling for stockpiling coronavirus drugs? Any figures you can think of? I am talking to Dr. Hotez later next week. William Haseltine (WH): There are a number of people who developed all sorts of things for this. My former associate Wayne Marasco at Harvard is pretty busy and you may have a hard time reaching him. There is Michael Farzan at Scripps in Florida and many other people who were working on these issues. There is a review by Roper and Rehm in 2009 on the topic of vaccines. If you go to Google, and search reviews for anti-coronavirus drugs, you’ll find it. Another person that I am doing some work with is Rolf Hilgenfeld. He is in Germany. I was interested in this topic because of my daughter—she is a sculptor who combines art and science. She won a commission in Singapore and built a sculpture of the active site of the SARS protease based on Rolf Hilgenfeld’s research. He did the crystal structure and worked with a group in Singaporeans to find a drug. That sculpture is the active site of the protease, which are the paving stones, and is about a twelve-foothigh sculpture in the middle of their biomedical research facility called Biopolis, the bio city. And when you walk on these paving stones it is a structure of a drug that stops the protease from working. Figuratively you go through the jaws of that enzyme and you stop SARS. That gives you an idea of how far people had gone in their research, that was done in 2006. It turns out that same compound also stops SARS-2 and MERS. It’s a good example of a drug that was never stockpiled. And it is not that we do not have the authority, Bioshield gave us the authority to do it. BARDA is now being used to pump all these crazy billions into vaccine flyers—a billion dollars just yesterday to the earliest stage, partially active British vaccine— or a half a billion dollars into a technology that has never been shown to work. 1693
BL: Yes. We have been hearing a lot about them. WH: Yes. But if you actually look at their history, they have a spotty history to say the least. BL: Yes, you do not have to be a specialist to look at a partial data release and wonder at a study of eight people. WH: Yes. A study of eight people and a billion and a half dollars, 1.7 billion-dollar offering the next afternoon. BL: Yes. That has been interesting to watch for sure. WH: But it will not be the last time we see something like this happen. All we can hope for is that the investment pays off and the vaccine works, but I think we know it is going to work partially at best, and maybe not at all. BL: When you talked about the drug candidates that were being developed back in 2006 and earlier, what did you mean when you said that they neutralize or even stop the SARS? WH: They do not neutralize it; they prevent replication of the RNA. If you take that same drug and apply it to cultures in which you have SARS-CoV-2— which has same chemical compound,— it stops the virus from growing. It essentially kills it. It is a good antiviral drug as opposed to a drug like Remdesivir, which does not do that. The one study that is published in a proper peer reviewed journal shows that Remdesivir, which is widely touted and now sought-after, does not work at all. In particular, it says it does not reduce viral load. It also has no effect on any clinically measurable variable. It is an antiviral drug that does not have an antiviral effect. So, at best, and in the words of the head of NIH, “it has a very modest effect.” BL: Why are we hearing about it so much? WH: I think that there is a major effort to distort our regulatory apparatus to make sure that there is an appearance of progress when there may not be real progress. This is a big worry of mine. We may have drugs and vaccines that have the appearance of effectiveness in the public mind, but which have no real effect on patients. That is a tragedy in the making. If we warp our regulatory apparatus, as we have warped our oversight of so many other parts of government, we will be making an error of monumental significance. And I believe there is a real danger that that is in progress. Tony Fauci, to his credit, gave a red flag about warp. He said, “I do not like the name warp speed.” Take a look at what he said recently. I would 1694
take it further than he did and say there is a real danger that we will warp, i.e. distort, our regulatory apparatus to speed drugs to patients which are either ineffective or even possibly dangerous. You have already seen it with Remdesivir, a drug with little to no effect, being sent all over the world. And I fear we may see the same with vaccines. It sure looks that way right now. BL: I am just digesting that. That is really important. WH: That is extremely important. It is an enormous red flag. The way Remdesivir was handled where emergency approval was given, which was then mistakenly described as FDA approval. I was on CNBC, and a young reporter said. “But you are saying that Remdesivir may not work, but it has been FDA approved.” I said, “It has not been FDA approved. It is given emergency authorization, yes, but we do not know the data. A doctor does not know the data, so that is a distortion of the process.” If you have a drug and a paper comes out that says it does not work, what is the doctor going to do? Is he going to give it to his patient? There are negative effects of that drug. First of all, it is a hard drug to give. It has to be given by somebody in the hospital with an open IV line. You are not going to walk around with that. And there is a rush around the world to get it. Why? If it works as well as Tamiflu, we will be lucky. And you know how well Tamiflu works. Is it a coincidence that the same company that pumps out Tamiflu pumps out this thing? No. BL: When you say that, does Tamiflu not work particularly well? WH: It does not work very well at all. Well, at best it may knock one day. BL: No, the only thing I have read about Tamiflu is that it is all made in a single factory in Switzerland. So, if anything happens to Switzerland… WH: It will not be any great tragedy because it does not work anyway. They do not actually claim it works very much because they cannot. The one thing they can say is it does not seem to kill you, which is not very much. People are trying it for all sorts of things, but it does not have much effect. And I am afraid that Remdesivir may be worse because of its side effects. Yet it is getting the same kind of distorted distribution. If that were not enough, there also is hydroxychloroquine, which is dangerous because it does kill people, and which has been widely touted despite FDA. That is 1695
putting a thumb on the regulatory and distribution apparatus. What is true if a drug is approved for one indication, a doctor can prescribe it for anything. However, whether they should or not is another question, and whether patients will demand it is also another question. So, we are seeing distortions already of one sort or another. And the fact that there is no data publicly available for Remdesivir even now, twenty-five days after the announcement, is surprising to say the least. BL: And yet it is STAT news; which has been garnering tons of coverage. WH: That is right. I was asked by Brian Williams, “well what should the press do?” The press should realize, this is what I told him privately, that at this moment you should analyze any announcement about a drug or a vaccine as part of a political campaign. That is a scrutiny you should give it for veracity and rigor. Reporters know how to do that. This is no different. I see science and medicine being used as part of a political campaign; praised when it helps and excoriated when it detracts. BL: I totally agree. You have to keep an eye on the political context, which is somewhat all encompassing right now. I also wonder about the economic side of it. WH: If you look at an issue like this, there are political consequences. There are commercial consequences, that means making money for individuals. There are economic consequences, major economic consequences. There are reputations at stake. There are nationalistic interests at stake. You have a very potent brew of issues around this. It is extraordinary. The heat around this process for science is extremely unusual as it had political, commercial, economic, reputational, and nationalistic pressure. BL: I am not sure if we have ever had something that has focused the minds of everybody and the interest of society in such an extraordinary way. WH: No, I do not think we’ve had it. And I’ve been through the AIDS days and the polio days. I have spent a lot of time looking back at history, reading the history of epidemics and disease and reading the impact on our cultural and emotional life through the imaginative literature. This is unique. To look at a comparable effect of an epidemic you would have to go to the 1350s with the great bubonic plague. Not only did it devastate the economy and 1696
population of Europe for about fifty years, the effects of that epidemic are felt even today. An example of this is the prominence of Basque names in Southern Spain. While the Basque country is in the North, so many people died in that great plague that they had to import people from there to have a viable city. And that imprint is still there in the family names of that city. It just gives you an idea of the magnitude and the very, very long impact that events like these can have. BL: This is all really fascinating. I want to ask you about something in your project syndicate pieces. Again, sort of looking at the pharmaceutical industry specifically and looking at the sort of commercial interests that are in this sort of mix. You said that they have been surprisingly silent. Can you tell me what you mean by that? WH: You hear a little bit about what they are doing, but all the big pharmaceutical companies are in high gear. As part of the United States constitution, we have the right to patent. Benjamin Franklin probably had the best phrase to explain what he was doing when he said, “Patents add the fuel of economic interest to the fire of invention.” I think that is positive. I think denying people medical care because of cost and price is wrong, but that does not mean that you should take away economic incentive because it does indeed add the fuel of self-interest to the fire of invention. But the pharmaceutical industry is working overtime to find drugs and they will find some that are able to save those who are infected. Will those drugs be prophylactic? Some of them will be just like the antibodies will be prophylactic. Hopefully, the healthcare workers will get them first and then it will be spread widely. Remember the second use for AZT was for doctors and nurses that have needle sticks. And today, I have pioneered the use of drugs to prevent maternal child transmission, but we recommended to show it worked in monkeys first, then people picked it up in humans, and it was able to reduce maternal transmission from thirty to five percent. It is now down to zero if you do it properly. There are no treatments now, but there are cocktails of drugs that, if exposed, prevent you from getting HIV preexposure prophylaxis. That is what everybody does when they go into malaria belts, preexposure prophylaxis. Eventually we get drugs that do that.
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First-Generation will be IgG. Second generation will be monoclonal antibodies. Third and fourth generations, maybe in combination, will be single drugs and then cocktail drugs. It takes a long time, however. Once you begin to treat healthy people with long term drugs or vaccines, you have got to be very careful because it might make them sick. The same applies to prophylactic drugs. You are giving those drugs to healthy people, which is very different from trying to save somebody's life who is sick because a very different side of the profile is required. And that is why it took thirtyfive years to develop good cocktails, to do preventive prophylaxis for HIV. You had to make sure the cocktail did not make anybody sick because you are treating healthy people. And now we have run out of time. But it has been a pleasure talking to you. You are a very well-informed young man. BL: Oh, that is wonderful to hear. And I thank you very much.
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Interview With Chinese TV May 27, 2020 | Interview
Male Speaker: Working together to find the origin of this coronavirus. What is the chance of us finding the origin? WH: My understanding is that half of it is almost identical to a bat virus and a little bit is quite similar to a pangolin virus. There are some peculiar features of this virus that we have not quite seen before, but it looks like a new virus that entered somewhere in China with one person, and then spread all around the world. I don’t know how and from what animal, but these viruses jump frequently from animals to people. It is something that is expected. It is not surprising. Male Speaker: You think it is very important to find origin? Is it possible we can find origin? WH: I think that we know enough. We know that it comes from bats via animals, that is a danger and that it can happen again, so we have to be prepared. The only thing I would say is my country, your country and other countries that knew this was coming did not take adequate precautions. We did not develop the drugs that we should have. I hope once we are done with this epidemic we will have learned more. These viruses cause human and economic devastation. I think most of the eastern countries were better prepared because they had already suffered economic devastation from the SARS virus. Thus, they immediately understood how damaging this could be and took very rigorous methods to contain it. Other countries who have not experienced it were not quite so sure. They are now. Male Speaker: About the virus, has there been some mutation in this coronavirus? Will this lead to a worsening of the symptoms or in your analysis, is it more infective? WH: I have seen some evidence in two different parts of this virus, the spike protein and one of the open reading frame proteins, that suggest that this virus has the capacity to be more transmissible and more lethal than the standard strains. These viruses do change, 1699
even if they do so slowly, and it looks like this one has already begun to do so in a way that allows it to spread more and to kill more. It has got to be pinned down a little bit more, but it definitely is possible and I think it is very likely it is happening. Male Speaker: I want to do a fact check. Are men more likely to be infected with COVID-19? WH: No, there is no evidence that there is a difference in infection of men and women. There is a difference in how sick people get. While infection rates in men and women are almost equal, there are somehow more men than women who are sick in some countries; but in other countries there are more women sick than men. It is not necessarily a property of the virus but rather a property of how people live in different countries. Male Speaker: In many places, we’ve seen that people who have recovered can still test positive for the virus. What is the reason? Is it possible that these people could still be infectious? WH: People who are infected by coronaviruses in general can probably be reinfected by the same virus even after they recover, after some time at least. We have been studying these viruses for fifty or sixty years and the same cold viruses come back over and over again. They go into a population, they decrease, and then they come right back and reinfect people. People in the seventies did experiments where they infected a group of people, waited a year and reinfected them with the same virus with pretty much the same symptoms. Thus, it is very unlikely to get long lasting immunity from natural infections. But you know, if you look at China it was a relatively small fraction of people that were infected anyway. This virus can infect all the rest. You gotta be very careful. Male Speaker: Well, if COVID-19 recovered patients develop an antibody themselves after they are cured, can they be prevented from being infected again? WH: The answer is probably not. They could be protected for a while, but we know that you do not get protected from these viruses forever. Male Speaker: Why does the US CDC say antibody tests for COVID-19 are wrong half the time. What is your take of this? WH: That is only true for some lousy tests. There are some tests that are right, 99.9% of the time. So, it depends on the test you use.
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Male Speaker: What do you think of the vaccine competition between various countries? Can a competition accelerate the development of vaccines? WH: Let me start by saying it is good that many, many people are trying to develop a vaccine because it is a very hard problem and I do not see it as a competition. In my opinion, it is not about when we will have a vaccine or who will win. The question is if anybody will win. We do not know if we can make a vaccine yet. And if we do make a vaccine and we do not know how many people it will protect, how well it will protect and how long it will protect. There are huge questions that remain unanswered. So, I would not focus on who is ahead. I would focus on trying to solve the problem. Male Speaker: If China has it and the United States has it at the same time, do you think they should collaborate and cooperate to go global? WH: You know, it is so speculative whether we are even going to have a vaccine. So why speculate? As a scientist, you do not know what you are going to find. So let us focus on trying to get the best data we can and on having as many people as possible work on it. Male Speaker: Well, some experts believe that genetic differences may be related to the differences in the mortality. Is there any evidence on that ? WH: There is no evidence at all of that. I think this virus affects most people pretty equally. It is mostly dependent on their lifestyle rather than on their genetics. Male Speaker: What needs to be done with the COVID-19 as of now? WH: We know that without a drug or a vaccine, this virus infection can be controlled. China has done it reasonably well. South Korea, Taiwan, Australia and New Zealand have all done it well. Denmark is doing it reasonably well. Most European countries are doing better now. You do not need a vaccine or a drug to stop this infection. All you need is clear messaging from political leaders. If somebody is sick, do contact tracing and do mandatory controlled isolation for the incubation period. You do those things and we know that you can eliminate the virus from your population. There may be sporadic cases but you go through the same measures. We know how to control it. Some countries do it a lot better than others. 1701
Male Speaker: I remember you always emphasize that this is a global pandemic. No one country can solve it and we cannot put borders around any one country. You say that we should focus on communication and cooperation between the US CDC and the Chinese CDC. Any suggestions? WH: In this case it is more important for the scientist and the doctors to speak to each other. The Chinese scientists are great and we have very great communication. The moment there is a meaningful result, everybody in the world can see it because the journals have said to publish you papers online immediately. I am reading what the Chinese scientists, the British scientists, the French scientists, the Indian scientists, the American scientists are doing almost as soon as they do; which is fantastic. Now, whether our governments or CDCs can talk is unknown to me. But I have to say I have been very impressed by the clarity in the communication and writings of the Chinese doctors on how they are controlling this infection and on the way their patients are responding. Same with the people in South Korea and New Zealand. A lot of information is being shared and that is good. You know, if this had happened thirty years ago, we would not have this internet so we could not get the information so fast. And by now Americans have a lot more experience in treating this disease than anybody in the world. We understand this disease in a way that Chinese never did because we have had so many more patients for such longer time. We are learning about the vascular disease, the kidney disease, the brain disease. We are really getting a very detailed picture and I think we are helping the whole world understand what this disease really is. By now, there is almost no disease in China for doctors to study. What are they going to do? They are reading our literature and that's good because this is not the last time we are going to have a coronavirus epidemic. Another one is coming in the near future. Male Speaker: If you were top advisor to president Xi Jinping or President Trump, what would your advice be? WH: It is difficult to give advice that does not include staying home, but there are very interesting things governments should do. They should communicate clearly that this is a big danger and show by example. They should embolden and strengthen the regulatory agencies, the CDC and others. But they should not try to put their thumb on regulatory scales to accelerate the development of drugs 1702
and vaccines faster than scientists think they should go. There are very good reason we have all of these rules in place about how you test drugs and how you test vaccines. Let me just mention something very obvious that most people wonder about. Why might a drug development go faster than a vaccine? The answer is when you are using a drug, you are treating a sick person and you are willing to take chances because that person is already sick. But for a vaccine, you are injecting healthy people. You may take a few thousand people with a drug, but with a vaccine, you may be treating hundreds of millions of people. You have got to be very careful because you are treating healthy people and you do not want to make them sick. So, my advice to people in government is to give people the resources, but not to warp or distort the regulatory process. You have to be very precise and very careful because you are putting healthy people's life at risk by giving them a drug or a vaccine. I see people all over the world trying to distort the regulatory process for speed and what you may get is more death, which will destroy trust in government, in science and in medicine. That is what is happening right now. Companies are behaving improperly by communicating results with no data. If you are going to talk about your data and you are a accompany, it is essential to share that data. Some companies claim to have found a good vaccine, but when you actually look at the data, it does not look so good. Now, over time we will learn and get better. But I think there are some problematic things going on both at the government level and the private level and the research level. There is no reason to distort the regulatory and scientific process. There is every reason to do it with full resources, to do it with your best people, your best companies, and to do it responsibly. That is the way to solve the problem, especially since we already know how to control this epidemic without a vaccine or without a drug. China is in no rush to develop some dangerous vaccine because you have such few cases. I wish I could say the same for my own country or other countries, but I cannot. That is where you want to be giving yourself the luxury of time to do it right. I am absolutely certain that we will have drugs and ways to cure us and to save us and to protect our healthcare workers. When it comes to a vaccine, we may or may not find one. Let us be careful and do it right. 1703
Male Speaker: In the last twenty years we have lived with Ebola, SARS and we overcame those viruses. WH: You know, with SARS, what happened is everybody gave up. We had good drug candidates, which are the same ones that are going to work against COVID. So, the SARS drugs that were given up on, the countries should have stockpiled them. If we had had the SARS drugs approved and stockpiled for emergency, no more than ten or twenty people would’ve had to die in the whole world. There is a sculpture of an active site of the SARS protease sitting in Biopolis in Singapore , and in the middle of it is a model of the compound which stops it. That very same compound, if it had been stockpiled, could have stopped COVID before it spread. The same is true for flu and for Ebola. Because there is no company that can make money off developing a drug, governments should do it as they have the resources. That is a lesson that I hope we take into the future. Let us not forget the greatest terrorist is not a human being. It is nature. Male Speaker: What is your most important message about COVID-19 during this pandemic? WH: My most important message is that we have the tools in our hands right now to stop the epidemic. Do not wait for a vaccine which may never come. Do not wait for a drug that will cure you. Use methods of public health and government and governance to control the epidemic. That comes from a scientist who spent his whole life developing drugs and vaccines. I would much rather see us use tools that we have in hand to stop it. Male Speaker: Thank you, Dr. Haseltine, for joining us and for sharing your wisdom and thoughts.
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Interview With German TV May 29, 2020 | Interview
This is a lightly edited transcript of the conversation between William A. Haseltine and Petra Patz, German television reporter. Petra Patz (PP): So we are doing a story on Moderna trying to explain to Germans what this company does, what has happened recently, et cetera. William Haseltine (WH): I am happy to make comments on Moderna but I think it is essential to also talk about companies like Merck, AstraZeneca, Johnson and Johnson and three of the biggest Chinese companies, Sinopharm, Sinovac. There are a lot of big, big players You get Merck that has made the most vaccines of any company in the world and saved literally hundreds of millions of lives and their CEO says, “we are committed to doing this and we are going to put our full resources behind it”, which is reassuring. However, he is also very straightforward and claims that we cannot have a vaccine by the end of this year. And not only that, if we make a vaccine we are going to be giving it to hundreds of millions, if not billions of people. So if one out of a thousand people have a nasty side effect, that is three million people. Are you going to give three million perfectly healthy people a nasty side effect? That is the question you have to ask yourself about these vaccines. Let's take a drug like Vioxx. Vioxx had a heart effect in people who were already at difficulty in something, like one out of 10,000, and they pulled it off the market. Such a ratio is not that unlikely for a vaccine, especially for a new vaccine with a technology you have never used before that has no proof of concept in any approved drug. So, when Merk tells you it is going to take a while, he means three years at best. But you still gotta be careful. And when you are looking for a side effect, you are not looking for a side effect that is going to appear in a month. These people are going to be vaccinated for life. How many people and how long is it going to take you to make sure you are safe? 1705
Now what I personally worry about is politicians all over the world who are going to put their thumb on the regulatory scale and change the way vaccines are approved for political expediency and because of public demand. That is a terrible mistake. We know that what happened with the swine flu was a mistake, and this could damage biomedical research for generations. You make a vaccine that harms millions of human beings and you bring in the threat that there will be no vaccines for the entire generation to come. Already half the people in the US say that if there were a vaccine, they would not take it. There is a big anti-vax movement that says vaccines are a plot. In fact, the leader of our country believed it too. So that is an issue. And your story pertains to Moderna, but it is a story much greater than one about a little biotech company with an unproven technology trying to make its way in the world. It is a very big issue. The other thing is: who is watching who gets the money? How come they get the money? How come AstraZeneca gets the money? How come Novavax gets the money? Who is deciding? Is there a group of objective decision makers? If there is, I have not seen it. Right. And you know, there is a very good CNN story, if you have not read it on Moderna. PP: I have seen it. WH: Yes, it has been around for a while. I think it came out two weeks ago. I think you just saw the one about their money. Look at a much deeper story about who they are which came out a couple of weeks ago. It is a very good story on them. PP: On Moderna? WH: On Moderna specifically. CNN wrote a very long story on Moderna, one of the longer pieces. It is a very good piece of journalism. That would give you a lot of background. Now it turns out one of my very good friends, a scientist I respect very well and who I created a company with is one of the founders. He has confidence in it. He is one of our best scientists in this country, but it does not mean it is going work. PP: Is Moderna a typical biotech company? In what way isn't it? WH: It has never got a drug approved and has new technology, which is pretty typical. They are extremely well financed for a company at their stage. That does not mean there has never been a precedent, but they are very, very well financed. I would say their 1706
press release prompted me to write an op-ed called Publication by Press Release, which I put into the Washington Post. It is a dangerous precedent because it is the same as the CFO saying, “I had a great year, I made a lot of money, but I am not going to show you my books.” As a shareholder, you would not be pleased. As a regulator, you would not be pleased either. So there is no reason for us to be pleased about a company who does not give us their data. And there is one thing that is true in life that our president Reagan said about almost everything: “trust but verify.” Some people would not even trust, especially if there is a political motive, a financial motive or a reputational motive. I do not pretend to know what Moderna’s was, but we still have not seen the data and I think it is unlikely that we will see it. And even what they said was extremely vague, with no completed trial. Now, if you want to see a serious critique of that read STAT. They have done a very good job of deconstructing a lot of those arguments on why you cannot understand what it was that they did. Now if you look at a lot of the other vaccines, you can see what kind of problems they may have encountered. There is another story that came out maybe in STAT again, which said, “I am one of the three guys who dropped out. They gave me a shot and it knocked me out for three days.” And one of the reasons why is an adjuvant I helped to invent. An adjuvant is a substance that makes the vaccine more potent. They are putting in a substance which is likely to be very weakly antigenic, not very potent by itself. So, they have got to put it in a dose of a foreign substance that triggers your immune system to help. They did not have to put in an ordinary adjuvant, they had to put in extraordinary adjuvant. One of my friends who got that said that he couldn’t talk for three hours. It was such a shock to his system, he could not talk for three hours. That is not something you want to give to 3 billion people. Okay, and what is that adjuvant? The most potent part of that is called Quil-A and comes from a Peruvian tree bark. The company I created in 1981 is the first one ever to invent that. It was a refined product from a saponin which is a tree in Peru. Those poor trees in Peru are now getting stripped of all their bark to make that. But it is really, really potent; almost like getting kicked by a horse. That is what they have to do to even begin to get some responses. And even then, they had a very nebulous response. The said that maybe they made a response 1707
which is as good as zero to low, but did that protect the animals? We do not know because they did not challenge animals. There is another big problem with Moderna. As far as I know, they have conducted no studies on monkeys. Everybody else shows you their monkey data, which is not very impressive. It may prevent the disease in the lungs, but it does not protect the nasal passage. We do not even know if Moderna ever went to monkeys, but I don’t think they have. That is an example of putting somebody's thumb on the regulatory scale. So, I think they went right to humans without going through monkeys, which is another issue which I do not think people have identified. So there are a whole lot of issues involved in this particular company, and you have got big companies with huge reputations and enormous technologies and experience in the same field. There are also other small players like Novavax, which has a similar kind of issue. You do not know what they are really doing. They are using some adjuvant and then the little particles. If they are announcing they are going to human trials, what does their monkey data look like? We do not know. Who did publish their data nicely was a Chinese group, Sinovac. You got to see what their data was. Eventually you also got to see Oxford data, but it was not all that strong. And by the way, that fits with fifteen years of experience with SARS and MERS vaccines. People have tried virus killed, they tried attenuated live virus, they tried DNA vectors for various and many different viral proteins including the spike proteins. They tried purified proteins and virus like particles. And pretty much the story is of the ones that worked at all were able to raise some neutralizing antibody, but none of them protected the monkeys’ nasal mucosa. So that is pretty much standard no matter which way you do it. A lot of times you do not even get any protection. But if you do get protection it is only partial, then there is a real question. If you are only going to get partial protection, what will that do to a population? Will that mean people who are running around with a cold will infect people who do not have the vaccine and kill them? It is very possible. You vaccinate people and now you have turned the virus into a cold except for those who do not make a good response to your vaccine, who you kill because now the virus is everywhere. I mean, there are some real concerns on what
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encompasses partial vaccination that I do not think people have thought about. So, I would say with cautious optimism that I hope there is a vaccine. You get the best players in the world using their best technology with their enormous resources. And you do not see Merck asking for a government handout. You just do not see them saying, “I need a billion dollars from the government to do this” because they are going to do it. You know, looking at their bottom line, the profit on an ethical drug is eighty percent. Ethical pharmaceuticals are extremely valuable. They are like an Haute couture dress without all the Haute couture. PP: What about the vaccines? WH: Some of the vaccines have a very high margin. Some of them are very cheap like tetanus, typhoid, those ones. But you look at the new vaccines, some of these new vaccines are very expensive. Shingrix would be a good example. PP: If Moderna calls you today and says we want to regain your trust, how could they do that? WH: I have had calls from Moderna associated people and have asked them to show me the data, to show everybody the data. I asked them to put the data out there for everybody to see, especially for experts. Show me the data so I can make a decision, or not. So ,I can understand what you are trying to say and we have not seen it. The other thing I would say, I have watched an interview with their CEO. Okay. It was a masterful lesson in how to evade a question. PP: Was that the Maria Bartiromo or whatever? WH: No. I do not know who did it, but it was not Maria Bartiromo. It was somebody else. He answered a bunch of questions and he gave almost perfect non-answer answers. And I think that is not encouraging either. Go find it. I think, it was on CNN or MSNBC. Find that interview and see if you conclude that those answers were answers to the question. PP: If you were their CEO, all of the sudden, what would you do? WH: Let us say if I were their chairman, I would do a very thorough vet of who was my CEO and who were the executives and who is responsible for all those public statements and then consider with my board what should be done to right the ship. PP: Why? 1709
WH: Because it is not a clear story. It is a story that, in my opinion is a discredit to the whole field. They are discrediting the whole vaccine. At least if you look carefully at what the Oxford group did, at first it looked like they did the same thing, but they actually did not. It was not the Oxford group and it was not a company that made an announcement. It was a single scientist giving an interview to the New York Times. Now was he vetted, did Oxford University say it is okay to do that? I cannot answer that question. When Adrian Hill spoke in public about it, I believe he was misleading because he said it worked. What he meant wass that it cleared the lungs, but it did not stop the animals from being infected. A vaccinologist would say it did not work because these animals were infected. He has since clarified that and said the animals were infected, but only in the nose. Maybe it was only the nose and maybe it was only seven days. But because monkeys are very different from people, you do not know what is going to happen in a person. Maybe he is right, maybe he is not right. But to say it worked was misleading. Okay. And then later he said that they put so much virus into the nose that of course the monkeys were going to get infected. But what about that huge literature of SARS and MERS that says they are always going to get infected in the nose no matter how much you put in? So you could evaluate the data and see that what they did is very interesting. The day before the guy’s New York Times editorial came out, they posted on their website that there would be a lot of rumors about their vaccine. That people should not believe them unless it was on their website. Well, that might have applied to Adrian Hills interviews too because the data was not there until a paper was published. Eventually they published a paper a couple of weeks later. On the other hand, Sinovac did not say anything. They just published their paper and you got to see it. So, you got to see the data and looked at least as good, if not better than any other one I have seen. PP: So, is there no agency or anything that is looking into these people and saying they got to publish the data? WH: Well, you know, maybe your country will have it. We are much laxer in some respects for policing public behavior than some other countries. I would not look to the US regulatory authorities necessarily to enforce this. If you look at the literature, there is a long 1710
history of the FDA trying to exert its authority over public companies that make press releases that in some way may enhance their value that may or may not be supported by published data to police for the public. I looked at that literature and there is literature going back at least fifteen, twenty years,. I do not think the FDA has managed to assert its authority, but it certainly has tried. So that is a direct answer to your question. Is there a way to police it? Yes. The FDA has on the books some authorities to do that. Whether they can actually use those authorities, I do not know. So far, I have not seen it work, but that is one way of doing it. If it is a publicly traded company, the Securities Exchange Commission (SEC) have every right to ask if the company has a misleading or forward leading statement. So two regulatory agencies should be involved with public companies. One is the SEC and the other is the FDA, both protecting consumers. I am not an expert to know whether this was a violation, but I would recommend for both agencies to look at it. PP: In the next month, how should we watch Moderna? What are they doing, what they are not doing? I am asking this in terms of the warp speed. WH: The other night a journalist asked me what warp means. Well, warp means to distort. It is like taking a board and bending it. That is warped. They are going to warp our regulatory processes for what they believe is expediency and put people and a whole field of biomedical research and biomedical products at risk through hasty unconsidered action. Not too different from hydroxychloroquine which put people at risk. Europe has now taken a stand on not using it and America has not. Right. Given the data, that is what it looks like. WHO has come out and said that this is not to be used. Okay. And so, when you see scientific and medical advances getting warped for advantage of one sort or another, it is disturbing. And even if the goal is to get a product to the market sooner, there are good reasons. You know, all of us who have gone through the HIV/AIDS time know what the public pressure is. During the early days, activists thought we were hiding things from them. The way they described the first clinical trial is the following: there were 36 people given the first drug AZT, 18 given it and 18 not given it. That was described as 18 people deliberately left untreated. It is a very accurate description and because there was such a big difference in the two, 1711
that drug was immediately accepted as a very likely candidate and zipped. We zipped right through to approval and all subsequent antiHIV drugs did the same with a surrogate marker. They came to understand that, but when they decided to do their own trial of a drug called compound Q, a Chinese drug from the Chinese traditional medical pharmacopeia, they did it with no controls and in the end a lot of people died earlier than they had. After that they worked very closely with NIAID and all the AIDS trials to make sure everything was done properly. Then there were proper controls. We learned. People learn, communities learn over time how to do it right. The biomedical community has learned to be careful. There is an opinion piece that was publiches in the New England Journal a few weeks ago. It said that just because there is urgency does not mean you throw out the regulatory processes. If anything, because of the magnitude of the problem, you tighten them up. You do everything you can to speed it up within what we know gives us good answers for safety and efficacy. And the more people are going to get it, the better your data on safety has to be. Do not warp our regulatory process. And so, I am afraid that is what might be in the works, and will cause the countries who are doing it to suffer. PP: You think that the pharmaceutical community goes along with that? WH: I think the responsible pharmaceutical companies do not. You heard Ken Fraser not going along with that. That is why he was not willing to say that they are not going to have a vaccine by the end of the year. Just not going to happen. So, I think the big companies are not going to go along with that, at least I hope they do not. So this is a serious issue for all of us who have spent our lifetime developing drugs, discovering the underlying science, developing drugs, getting them into patients. I have eight drugs that are approved by the FDA for various indications, cancer, lupus anthrax, all sorts of diseases; even diabetes. I have learned that when the FDA recommends us to be careful, you should follow that because they have more information than we do. And in every single case, when they have asked me to go slow over time, I have learned exactly why. They want drugs to be approved, but they want them to be safe and they want them to be effective.
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You know, there is a counter argument that says, “who is to tell me what I should take?” That is fine if you are highly educated. What if you are a three year old kid? What if you do not speak the language? What if your hopes exceed your reason? You know, human beings are complex. We have two sides, faith and hope, and rationality. I think time and time again, we have shown that faith and hope is stronger than rationality and that is what you play on when you are dealing with these kinds of drugs. You have to be very careful not to take advantage of people. PP: Another question, may I ask you what you are working on right now? WH: I am helping a lot of people who are my former students. I am old enough to have grandparents and great grandparents as students. That means third generation students. They are all active because they were all of the HIV business and drug development business. I have started all of these companies. I have people who are in those companies all out there. They come to me for advice. I am happy to give them advice and it has been fun. It is a wonderful field because it is something that science can really get its teeth into. I will give you just one example. This virus has a lot of tricks up its sleeve and we only know a few of them. One of its tricks is that it goes in and turns off your ability to see it. It cloaks itself almost in an invisible cloak because it turns off exactly those genes you need to start making antibodies inside of toxic T-cells. It turns them off. Now it does not turn them completely off, but it turns them pretty far down. And the difference is that SARS-2 turns it off more than SARS-1. So what does that mean? It means the virus gets an extra chance to grow because it does not have so much opposition and your secondary immune system is not affected by the interferons. That makes all these cytokines that go crazy and that is what you see in many SARS patients. You see a lot of virus and you see a lot of this effect but with a weak immune response. Now we know there is one tiny gene in SARS-2, 22 amino acids long, which is much more potent than SARS-1 and that has all been worked out recently. That is really interesting data and it tells you, that if it is turning off interferons, maybe we should turn them back on. Maybe we should give people some interferons. In the one trial that really showed virus load reduction in Hong Kong, I call it the Hong Kong cocktail, one of the things that made it work was interferon beta, 1713
exactly what this virus turns off, and they show good improvement in terms of number of viruses that go down into people. The time spent in the hospital also got shorter. It is the only one that I have seen right now in humans that actually lowers the amount of virus. The other drug people are touting, which is Remdesivir, does not do that as far as I can tell. If you actually look at the published study, the amount of virus does not decrease. If you look at the NIH study that just came out, there is no study of the virus. How could you possibly test an antiviral drug and not measure the amount of virus? They took the weakest possible end point for Remdesivir, which is the number of days to leave the hospital and that was it. That is all they showed. They did not show it caused survival. So it is an antiviral drug that has no antiviral effect that anybody measured in a human being. Maybe somebody will, but so far, they have not and when they tried, they did not see it. It does not take a huge study. Everybody criticizes the Chinese study because it ended early. Go back to the AIDS trial. Eighteen patients were all it took to show it knocked down the virus. You do not need a hundred patients. Maybe for a good endpoint for mortality or getting out of the hospital sooner you need more patients. But to know whether it is lowering virus concentration, you do not. I think the Chinese used 36 patients and they saw it. So why not measure the virus load in your 500 patients? They did not or if they did, they did not report it. PP: Anything else that I should ask you about Moderna that I did not ask that Germans should know? WH: I would not say about Moderna in general. I would say the very good news is just, as in the case of HIV, the entire scientific community has been activated. People all over the world are working like crazy. That is really good news. We are working in a coordinated fashion like never before. People are allowed to put up their raw data instantly and the paper can appear a month or two later in the published journal. That allows us to see right away what is happening. A very good progress is being made just on the clinical front. You know, if you are a doctor, you must use the tools you have. I think one of our defense secretaries has had a very good summary. You go to war with what you have, not with what you would like to have, right? We are in a war. Our doctors are on the wards. They are getting better and better at using what they have. 1714
Anticoagulants are saving a lot of people. But you still have to be careful. You do not want to cause bleeding in somebody that might bleed. But anticoagulants are working very, very well. This Hong Kong cocktail looks good. We can combine it with anticoagulants. Just simple procedures like flipping people over on their stomach for a while help. So, mortality in good hospitals of those people who are in intensive care has dropped from ninety percent, in some cases, to twenty percent in a matter of weeks. That is fantastic news. You are using the tools you have to solve the problem in front of you and you are hoping that better tools will come along. And so, if you only consider this disease based on the number of people dying, it is getting better pretty fast. How about measuring it by the number of people getting infected? You know, I just tried to find that number. I have asked my friends who run big hospitals. We cannot find that number. How many people in Germany went to the hospital for this disease? You think it'd be easy, right? We can't get that number. Nobody has it. CDC does not have it. Doctors do not have it. You do not have it. It is a very important question. So, we should be measuring how many people have been going to the hospital, not necessarily how many people die because we are getting better at saving them. Hope this has been useful. PP: I hope that I may talk to you again. WH: Okay, good. Thanks.
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Interview With NTV Wie Ticket Amerika May 29, 2020 | Interview
The transcript of this interview isn’t yet available. Listen to the full English-language interview here: https://www.youtube.com/watch?v=_VgVj85eMiI
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June 2020
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Interview With HBO Sports June 2, 2020 | Interview
Josh Fine (JF): Some schools brought students back yesterday, and other students are going back over the next week or two. And we could use your guidance or thoughts on what to make of this. Is this a good thing? Is this a bad thing? I have some specific questions, but before I jump in, I am just wondering what you make of that? William Haseltine (WH): Look up COVID cases US online. And you should see that yesterday, we had 16,000 people who were infected. JF: Yes, I see that. WH: And you can see that on March 25th, we had 12,000 people and on March 26th, we had 16,000 people. So we have just as many people infected today as were infected March 26th. JF: I see that. WH: And on March 26, we did not think it was safe to play football. And we certainly did not think it was safe on May 11th when we were shut down. So why do we think it is safe when there were 16,000 people infected yesterday, and who knows how many today? I will tell you, these low points are Mondays and Tuesdays because they are counting people from the weekend and then it usually goes up again. But we will see, maybe it is going down, but there are still a lot of people infected and they are infected all over the country. Let us look at COVID cases in Alabama. Now let us take Wisconsin. That is looking a little better, but we still have plenty of cases. Now take a look at the US in general. Let us look at the world because we are not completely isolated here. Worldwide, 220,000 people, almost 223,000 people were infected yesterday. Not good. I want to show you something else here. Go back on this world chart to February 4th or 5th. February 5th was 3,400 people. They were all Chinese. After that, it is about zero Chinese. Let us go to China right now. You will see a few, but not many. Single digits for a very long time and even zero for some days. Yesterday 1718
was zero. If we had controlled the infection like that, there would not be a question about football players playing. But when infections are high, you cannot risk infection spreading among everybody coming to the stadium. The Chinese would not allow that when there is a peak in infections. Their high number, when they were going bananas shutting down everything, was about 3,800. They are a country of about 1.4 billion. We are a country of about 340 million. And we have roughly four times that number total and, in per capita numbers, 16 times that. That tells you that we are taking a risk with those players infecting each other. We know that sports guys infect each other, especially in basketball. A lot of famous basketball players got infected. So they are taking a risk. Now, those kids are on scholarship and it is their only chance to get an education. Some kids may also be from some low-income area where their parents cannot afford to send them to a good school. I think if you looked at the economic income of a college football player, it would be substantially lower than the economic income of the class as a whole. I do not know if that data is published, but I think it is true. Therefore it is in that particular group where infection rates are about four times higher than they are in the rest of the population. Because we know that this virus is disproportionately affecting people from poor communities regardless of race, all the players on those teams are at an even higher risk. I do not think that the schools have taken all of those considerations into account. If they did, I think they might reach a different decision. Now it may vary by region. But one thing about football is you play people from different regions. So let us take a look in Chicago. Let us just look at COVID cases Illinois. That is going down too, but it is still pretty high. It is about a thousand people there that got infected yesterday. What is happening is that if one school plays another school, this virus really gets around because people move around. You are not going to have a football team that only plays with themselves. They are going to be playing with people from other states. So if one person on that team, one coach that travels with the team, one of the support staff, assistant coaches, junior staff, the guy who takes care and gives guys massages after the games, about120 people are going from state to state. If one person in the
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country in your division gets infected, probably many people will. Remember when there was a herpes outbreak in wrestlers? JF: Yes. WH: Well, this is a lot more infectious than herpes. You do not need to have skin to skin contact. All you have to do is breathe. And one thing that football players do is breathe a lot. I mean, those guys are out there really working. You know, if you are on the line, it is like you are wrestling. You have like fifty to a hundred wrestling matches all at once. You know, all in an hour and a half, two hours, three hours, right? You are wrestling, you are sweating, you are exerting maximum. Your lungs are pumping as hard as they can. I cannot think of a better way to infect somebody for the guys on the field. So you are taking a big risk. And the risk is pretty serious because we know that this virus infects people who are in college. We know that there is a borderline between, let us say under twenty and over twenty, but the real number for this childhood COVID is pretty horrible. If you actually read what happens to childhood COVID, you find out that if you get infected, you may feel bad or have a little cold, or you may not feel anything. Then two to four weeks later, when the virus has gone, you are testing negative most of the time. So you do a virus swab and you test negative. You may have antibodies, but you are negative. And you may even be negative for antibodies. All of a sudden, you get hit and you could have myocarditis, an aneurysm, or kidney failure. You could even go into toxic shock. It can go into your brain or wipe out your liver. It is a bad, bad disease. It is called MIS-C. They say it is for kids younger than twenty. But actually, I know people who are thirty who have it. So they are taking a very serious risk with these kids. Very serious. And what is the benefit? Is it an educational benefit? I doubt it. Are all the fellow students going back into class? No, not yet. And even if they were going back to class, they would be saying, “stay six feet away and wear a mask.” You are not going to do that on a football field. Can you imagine every football player wearing a mask and staying six feet from the other guy? How are you going to tackle anybody? How are you going to be a lineman, staring each other in the eyes or getting ready to fight? If you cover football, you know exactly what football is like. Have you been in the locker rooms after a football game? 1720
JF: Yes. WH: Well, you know what it is like. Is that possible to avoid contact and breathing in a tight space like those steamy stinky locker rooms? If I could imagine one place where you are going to get COVID, it is in a locker room after a football game, and you and I know exactly what that is like. I think that is the perspective that this story needs. JF: The perspective of… WH: Of what it is really like to play football, to breathe on each other, to be close in those really steamy, closed quarters with a bunch of guys puffing away at each other. JF: And if they say, well, this is outside, so we are not going to have it. WH: Yes, but that is not the locker room. And outside it is still a matter of distance. When you are wrestling with somebody on the line, you are not outside anymore. You are right in their face. And that is what your coach tells you. Get in their face. That is exactly the words that coaches use. “Hey, right guard, get in that guy's face.” And he does it, he gets right in his face. Being on the line is like hand to hand combat. It is the closest thing there is to hand to hand combat, except for maybe wrestling, which is literally hand to hand combat. JF: You know, there are some people in college sports, like the head of one conference who says, “the kids are safer here than they would be at home.” WH: That is a lie, a straight out lie. JF: I want to ask a few obvious questions, but I want to hear how you describe them. Let’s take an offensive lineman for the University of Alabama who lives in Seattle as an example. He is flying across the country to be back for practice that is starting in two days. Is he going to be more at risk now than he was previously when he was at home? WH: Absolutely. And by the way, airplanes are a terrible place to be. I will give you one specific case with SARS, which is not as transmissible as this. One guy on a plane infected about twenty-one people on that plane who were not even close to him. About four of them died, and it is not because they do not filter the air. It is that not all the air gets filtered and the guy might walk up and back to the bathroom. And that was with SARS, not even as transmissible as 1721
this. And he does not even have to be a player. He has to be one of the support guys. It could be one of the crew on the plane. It could be anybody. JF: So in your view, the schools are not only putting their own people at risk, but they are putting others at risk as well. They are failing to do their public health duty. WH: That is right. Yes. I believe that is true. JF: That is very interesting. And you think that, but even just looking at the health risk for the kids themselves, are they at as bad of a risk? WH: They are at a much, much higher risk. Look, you have a bunch of kids in close quarters, breathing like crazy on each other in small and closed spaces, mixing with kids from all over the country. As I say, how many people did it take? It took one guy with herpes to infect the whole league. JF: I am just going to play a little devil's advocate. But if they say, “We are creating a bubble, Dr. Haseltine. We are going to test the kids when they arrive and quarantine them for a week. And then they are going to be within our little bubble for the next six weeks. They are not going to interact.” WH: Okay. Have you ever tried to keep a football player in the bubble? Not so easy to do. First of all, the tests are not always positive. A lot of people do not test virus positive for quite awhile. And after, if they have been positive, they might have suddenly felt a cold and then they’re no longer virus positive, but they still may be able to spread the virus. The tests are not perfect. You just saw that at the White House, right? If they cannot protect the White House, how can they protect the football team? Is there any bubble tighter than the White House? You are telling me that these football players are going to be more careful than our germophobic president? And yet people right around him, his valet, the guy who dresses him and the guy who serves him food got infected, and the spokesperson. One of the team’s spokespeople got infected. JF: The NCAA says death rates for young, healthy Americans is similar to the flu. WH: Let me ask you a question. You want to take a one in a hundred or one in a thousand chance of dying, if you were going out and doing something you did not actually have to do? That is a hell of a lot more than driving a car or taking a bus ride. And the 1722
fact is we do not know. Another fact that people do not think about. Death is not the only thing that happens to you with this disease. In fact, it is the minor thing that happens. I mean, you are gone, but this disease can maim you for life. It can wipe out your kidney. So you need dialysis. It can cause myocarditis. This virus actually has the receptor in the heart. It can give you an aneurysm. It can give you blood clots. It will stroke you out, give you a heart attack, or give you a fatal pulmonary embolism. You are putting people who might be infected at extraordinary stress. And we have not talked about what extraordinary stress might do to somebody who would otherwise survive or have no symptoms. We do not know because we have not done it. These guys, when they are out on the field, they are under maximum physical stress. You cannot get higher stress than a lineman in a big ten confrontation. It just does not happen. These are the best-conditioned guys in the world and they are completely wiped out. They have used every bit of energy they have, and it is a huge stress on the system. And we know that stress wipes out the immune system. That kind of stress is very bad for your immune system that should be fighting the virus. That is not a good thing to happen either. So yes, maybe it's true for a normal teenage kid that they rarely die. Some of them get terrible diseases, but we do not put them under maximum stress like this. We just do not do it. JF: So you are taking someone who is more exposed to people so they have a greater chance of getting the disease. You are putting them under stress, so that makes them either more susceptible to getting a disease or having a more severe symptom. WH: We do not know that. But they are not taking that into consideration. I think the people that want those kids to play, want them to play for the economic benefit, not for educational benefit. Pure and simple. It is no mystery. It is not the glory of the game. It is not the value to those kids' careers. It is bottom line income to those universities. That is what this is about. And they are putting those kids at risk for the economic benefit of the school and of the league itself. And they do not know that they are taking a lot of risks with these kids' lives and they are moving into the unknown because we do not know if somebody is infected due to the superhuman stress. You and I could not begin to do what these guys do. Not even for five minutes. They are physically amazing human beings. 1723
JF: What you are describing sounds unconscionable. WH: I think it is a mistake. JF: Okay. Well, that is fair enough. I did notice that, using your example of the big ten schools, I think University of Iowa and University of Nebraska started practice yesterday. And if I am not mistaken, those schools are literally closed both for other students and just for staff or faculty. I do not know how closely you follow these matters, but the pro sports have gone back and what some advocates for college athletes will say is that the pro leagues at least have players unions that can advocate for their rights, whereas the college athletes basically are completely at the mercy of the schools. And that explains why college football came back before any other sport. WH: I do not know that for a fact. I think that is a good hypothesis because the money in professional sports is bigger than it is, but you really have to look at what fraction of income these guys are going to forego. Especially in big ten football, a lot of the alumni are motivated to give back to the football program. Now I was just looking up Ohio and Nebraska. And by the way, those states are not controlling their infection for beans. Go look at COVID cases in Ohio; they are not doing great. It has been constant for over a month. JF: Yes, and the football team went back yesterday. So they flew in a hundred guys from all over the country and they started them on weightlifting and wind sprints. WH: Look in Nebraska. Nebraska is not doing so great either in controlling their infection. JF: What they say is, “hey, we got to start somewhere. This is a good place to start.” WH: I think it is probably the worst place to start. It is probably the highest risk these students will ever have. What other students travel around the country, bang into each other, and are in close quarters all the time? You are going to have many students. Even if they go back, you are going to wear masks and stay away. They are going to have classrooms. I tell you, take a look at what it is going to do if they go back to class. I know because I have very detailed plans of what you do in a classroom. You seat people far apart. You do not let them get close together. You test them when they come in for temperature. You do all sorts of things to keep these kids apart. 1724
You know, there are a number of schools in Scandinavia and in China that are open. I have friends who are running schools in different places. And you have a whole series of very strict rules that you follow. Not too many people can be in the room. I mean, there are all sorts of rules that people should follow, and they are not going to do this for these football players. If you want a good picture, go watch a practice and see how many are wearing masks. JF: If you want to do a test case on campus, bring back your chess team and your debate team. WH: Exactly, bring back the mathletes. JF: Right. But do you think these guys are at heightened risk because of their socioeconomic issues and race? What about these linemen with obesity, hypertension, or those kinds of things? WH: We know that if you have got hypertension, you are in trouble. If you are overweight, you are in trouble. Now, I do not know how you tell a guy who can run a fifty meter race faster than you can even imagine that he is obese. I do not know how that figures with a disease. I do not think anybody has really studied that particularly. I do not know if you are in super shape and you happen to weigh 350 pounds. Some of these young guys weigh over 300 pounds. That is why they are the big ten linemen. You are a center. You are a guard. You are easily going to weigh over 250 pounds. Even if you are around 6’ 2”, you are going to be up there. And that is a big predisposing factor as is hypertension. JF: Right. The schools in their defense will say, “We are being very careful. We are testing them. We quarantine them when they arrive. We are keeping them in small groups. They have a group of seven people who are together, and they go to the weight room and do wind sprints together. And we do not mix and match.” WH: And when they do a scrimmage, how many people are on the field? JF: Well, they will say they have not started scrimmaging there. WH: Yes, but will they scrimmage? Of course they will. And when they are playing a real game, are they going to play with little squads of six? What is this, the X league? I do not think so. JF: But are you concerned even already, like, even before you get to, I think they do not start like that level of practice, whether it is scrimmaging and all that until July. But right now already, they
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are doing more of the sprints. But you are already concerned just with that. WH: I would say in the famous words of president Reagan trust, but verify. If they say they are going to do those things, are they really? I do not believe that they really will. I think they say they will, but when push comes to shove, how are you going to keep these guys in groups of six? How are you going to keep the locker rooms rotated? It is not going to happen. I think there is going to be a lot of stuff on paper that is not observed in fact. In my city, New York, everybody is supposed to wear a mask. Well, go look on the TV at these demonstrations, how many people are wearing masks, go out to the parks, or go out to the beach. Now you cannot go into a pharmacy or some shops without a mask. There are plenty of people without masks. So even though that is the rule and it is supposed to be followed, people do not do it. JF: Right. WH: And I do not think football players are famous for being the best at following the rules. I was a professor. And I taught a general education course, with a lot of different athletes. Often they were all sitting in the back of the room, especially the ice hockey players. They are rougher than football players, believe it or not. JF: Right. I am a Harvard hockey player. Those guys go on to the NHL or something. WH: That is right. And they really thought it was a gut course, I got the hockey players. JF: Yeah. This is all interesting. It does sound like potentially quite abusive. I do not know how much of this applies, but since they are not employees, I do not think they have the benefits of sort of labor law or OSHA or really any of those things. WH: That is a good point which I had not considered. Thanks for bringing that up. That is a very, very good point that they are not protected. And you know, the other thing is most of these guys, as we said earlier, could not afford to be where they are. And many of the stars get a huge number of perks, even though they are technically not supposed to. They get cars and lots of money from their family. They sort of become the number one economic support for a whole extended family system, not just their immediate family system. And they are very proud of that. And they have a whole lot
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of family pressure. Even if the family realizes they may be putting this kid at risk, their benefit is huge. And let us talk about something else most people never talk about, which is sex. I do not think you can stop a whole team of footballers from having sex. And one thing about COVID that nobody ever says is that it is a sexually transmitted disease because you exchange saliva, you breathe in each other's mouth, you get as close as you possibly imagine, even closer. You literally get under somebody's skin. That is sex. You are not going to stop these guys from having sex. JF: Right, which of course would bring a lie to this whole notion of a bubble. WH: Exactly. You are going to keep a whole football team in a bubble where they do not have sex with the people around. No way on earth.. JF: Right, which sounds like a strong argument not to bring college back in the fall. WH: That is for sure. Bill has a recipe. It is safe to bring pay people back when there's very low community transmission. And I mean in the single digits, in a whole city. Then you are pretty much okay. And you have got to have a good system to identify the people sick, contact trace, and isolate those people. When you are able to get the infection rate so it is in the single digits for a couple of weeks, then that is fine. Then have your football practice, et cetera. But do not play with a team from a city that does not have the same low community transmission that you have. If you are in Alabama and you are about to play the guys in Wisconsin and the communities in Wisconsin still have a high rate of infection, do not go there. And so what is the point of bringing the guys back if you are not going to play? So you have got to look at just not what is in your community. You have to look at the communities of everybody you are playing with. JF: It sounds like there are two issues here, both important. One is the health and safety of the individual athletes, individual students. And the other is the public health responsibility of the schools. These are the kind of potential for increasing the spread of the virus. And sounds like you think both. WH: They are both risky. Yes. They are doing both. I hope this has been helpful. 1727
JF: Okay. Thanks. WH: Thanks.
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Interview With Bud Mishra, Hightech COVID Group, and Charles Cantor June 6, 2020 | Interview
Bud Mishra (BM): Today we have a self-assembled group of people from different backgrounds, covering epidemiology, immunology, computer science, math, finance, and economics. First, we have William A. Haseltine who has been good at bringing people together both in academia, in industry, and in governance. He is going to be a very good advisor and has worked on the virology of Leukemia and HIV. Bill Haseltine is a scientist, businessman, author, and philanthropist. He was a professor at Harvard Medical School and Harvard School of Public Health from 1976 to 1993, where he was founder and chair of two academic research departments. His work has been driven by his deep appreciation of the human condition and he draws his inspiration from the great works of art, architecture, music, and literature. Today, we will read and ask questions, and have discussions instead of presenting papers. William Haseltine (WH): What I would like to do is primarily take questions about the current epidemic. My view is quite a broad one of this, and I am prepared to talk about many topics. I think about this from the public policy perspective. My current foundation has a focus as a think tank of about 120 people spread all over the world. We have offices in Beijing, Delhi, Singapore, New York, Manila, Scandinavia and a few other places. We are advisors to the government on health system strengthening. I am very interested in the medical aspect of it. What are we doing for treatment? My most recent book is a book on healthcare systems here in the US. What do you actually do to treat people and how do you do it with the tools you have on hand? I am interested in the drug development and vaccine development process, which I am observing pretty closely. I have also taken a great interest now in understanding these unusual viruses – the coronaviruses – and I am working with 1729
multiple scientists, some of which I met in Alex Rich's lab at MIT. Thus, I would consider myself to have an unusually broad perspective on what is currently happening. For those who are interested, I have a blog on Forbes on which I write a piece almost every day. I write op-eds. I am active on social media and I am trying to communicate my understanding of what is going on to others. My most recent effort is a new concept – a book – , which I am about to publish. It is going to be called a living book, and the title is A Family Guide to COVID: Question and Answers for Parents, Grandparents, and Children. The book is going to live on the web and on our website. It will be continually updated as we learn new information. If you buy a copy, you can print it on demand and you will get a subscription which will allow you to see the most recent copy on the web. The inspiration behind this book are my grandchildren, who regularly ask me questions, as well as friends who like to refer to me because of my background. Allow me to give a very quick overview of how I see this. In thinking about these viruses and this epidemic, I have come up with a new way that I think is going to help us all explain evolution to our friends. One of the big problems with evolution, is that it is an abstract concept that escapes almost everybody. You can understand adaptation is survival of the fittest, but exactly how is that happening? Think of a virus as an artificial intelligent agent. Think of it as machine learning that you throw a bunch of solutions at and the one that fits the problem is a success. That is evolution. And it is a way of understanding these viruses. Every day there are trillions of experiments going on in the natural world, trying to crack our code. They are trying to use us as their ecosystem, and because of our number, our proximity to each other, and our travelling, we are making it easier for viruses to thrive. And the impact is devastating on those treated unequally. One of the really interesting things to think about is the very first antibodies you make to these viruses are germline antibodies. That means somewhere in our evolutionary history, we have seen these often enough that we have built a germline response. Over time it improves, but the first antibodies are ready to go. We are ready to see coronaviruses. And the coronavirus has been very successful in our human species. Ever since we were first able to find the first human coronaviruses in the 1960s, there are four cold viruses that 1730
have been circulating for as long as we have observed, which is at least 50 years. Thus, when thinking about what is going to happen with this one going forward, you have to think that these viruses do not go away. The very same virus that infected you one year can infect you the next year. This was proven in the 70s when people took two of these cold viruses and gave it to volunteers that got colds. A year later, they gave them the same virus and they got colds again. So, one of the strategies that these viruses have is not to invade the immune system completely, but they do affect it. Thus, you make an immune response, but it is not a very good one and it is not very durable. These viruses essentially survive by using one gene that turns down our whole ability to make antibodies and cytotoxic T cells. The current virus is really subtle because most of the people that it infects do not get very sick, making them great agents – children especially. However, this virus kills people while the other four viruses do not do that anymore as have been around a very, very long time. SARS and MERS killed too many people and got stamped out right away. It is in the virus’ interest if you could get around, like these cold viruses. This virus did something that is probably evolutionarily. It crashed our economies. It is bad for the virus to crash an economy, because if you are going to spend, like we in America are going to spend $10 trillion cleaning up the damage that this virus does, we are going to spend hundreds of billions if we need to eliminate it. We are going to spend what it takes to close it down eventually, because the damage it causes is too great. So that way, this virus has not exactly adapted well, but if we were not so good at our science, it would be really a good adaptation. What are we going to do to fight back? The biggest lesson that I have learned from this epidemic is that you do not need a drug nor a vaccine nor a test to control this disease. All you need is efficient governance, good leadership and good public health. Now why do people not behave that way? Let me take you back to the early days of AIDS. The moment we had isolated the AIDS virus and knew for sure how it was transmitted, the problem was solved: do not have unprotected sex. Human beings had the knowledge to solve it, but we did not because we could not adjust our behavior. Redfield and I helped design a program the US military. Everybody was tested. 1731
All the positives – heir discordant couples – were brought in and counseled twice. Thirty percent of people complied, seventy five percent did not. In five years, ninety percent of those who did not comply were infected. So it is human behavior that can control these epidemics, but human behavior is not controllable. If you look at New Zealand, Australia, Thailand, South Korea, Japan and of course a great example is China, you can see that they controlled the epidemic. For example, China’s new daily infections are in the single digits, sometimes even zero. Thus, it is possible to reduce infections to zero. However, other countries did not follow China’s lead, which is a huge failure on their part. There are a variety of responses, some of which are really bad like Brasil’s, some of which are bad like that of the US, and some of which are sloppy like England’s. Nonetheless, eventually you get the message and you get better, reducing the number of cases. You can also be like India or Brazil where the number of cases is just skyrocketing. This variation in responses has wrongly put people’s hope in science to fix the problem. So where are we with vaccines? There are about 120 candidates that we know about. There are also a lot of people working on this, and there is a huge amount of money being spent. We in the US have probably committed about five billion dollars right now, and we are willing to commit more if we can get a vaccine, especially if we can get a vaccine fast. But what are we going to get for all this money and effort? What we are doing in the US is that we are going to pick five, six, seven candidates and we are going to distort our regulatory process. We are telescope testing. So, we are going to just allow you to do a few animal trials for safety. The most important animal trial is the one in monkeys, which some of the vaccines have not gone through. The results need to at least show that an antibody has been raised. Even better would be if the vaccine is slightly neutralizing, if not fully. Then, we are going to do a short safety trial in humans of maybe one-to-two hundred people. Once that is done we are going to skip the phase two and efficacy trial and are going to go straight to a phase three trial, and we are going to do it on, let’s say, 2,000 number of people. So, there is a huge drum beat right now going on we should be aware of. 1732
I have written a piece that is called Challenge Trials are Unnecessary, Uninformative and Unethical, but we are about to do them. And if we do not do them, someone else will. We are talking about giving a healthy person, who may or may not be protected, a dose of a lethal virus, which makes 20 percent of people it infects seriously ill. Most people do not die because we have pretty good medical supportive care, which is improving daily. So, you are going to see the death rate go down as the number of people infected goes up. Before, eighty percent of people who were intubated died, and now it has gone down to about twenty percent in most hospitals. We learned how to give people blood thinners. We learned to flip them over. We learned to use tools at hand. Another thing the virus does is that it latches onto the ACE-2 receptor, which is all over your body; it is on your kidney, it is in your heart, it is on your blood vessels. It even gets into your brain up through your nose. This virus gives you huge blood clots that go into your lungs, your brain, your heart, directly wipes out your kidney. And there are a lot of other more subtle things it does which are not good for you, which means that if you get it, you are sick for a long time, maybe even for the rest of your life. About half the people that were in hospitals a month ago are still in the hospital today. They are over the first viremia, but they have huge sequela, and that is going to be a huge problem for our medical system. That is not a virus you want to give to volunteers. In addition, it is my belief that we are rushing for a vaccine for economic reasons; countries will not tolerate the economic disasters. And in fact, I think the reasons the Asians responded so well is because they knew this would shut down their economy, not that it would kill a few people. It was really about the economy. That is why we are spending all this money. So, what are we going to get? We know that these viruses are tricky to vaccinate against because we have already tried for SARS and MERS. We tried everything we knew at the time: whole killed virus, live attenuated virus, sub viral particles, DNA vaccines, virus vector vaccines, and they all gave us the same picture. Either they failed, or the ones that seemed to work on monkeys gave them antibody protection, but none of them protected from infection. All the monkeys got infected through in their nasal passages. That is because it is really hard to protect primary infections through the 1733
nasal mucosa. Viruses have these little things called M cells. They are a little particle that gets on and goes just shooting right across in its own little spaceship, across transcytosis, and waits on the other side in a nice little patch of immune cells. But what is not so good about the nose is you do not produce all the IgA like in the gut. Every day you are producing about five grams of IgA in your gut. You are not doing that in your nose. And if that were not enough, there are cells that go back and forth called dendritic macrophages that these viruses can ride in. We never have been able to stop those infections. And even with flu vaccines, you do not stop that. You just get a good reaction, meaning you do not get as sick. So the main problem is that we can neither stop primary infection nor the spread of the virus. The other problem is that we do not know what kind of immunity we are going to get. These viruses naturally only give you a transient immunity. We do that with the flu, so the vaccine is going to ameliorate the lung damage. However, that does not mean that it will prevent the virus from getting in your brain or in your blood cells from your nose. Thus, there is an uncertainty as to what is going to happen with the vaccine due to the lack of tests. Another issue is that the people who need the vaccine most are old because their immune system cannot remember diseases they’ve had and thus they have reduced immunity. Your immune system starts to decline quite rapidly from the age of twenty five on. So, you have got to produce superhuman efforts, like an adjuvant which can activate a whole immune system. If you give an adjuvant to a young, healthy person, he feels like he will go faint. Some cannot talk for hours. These are not easy things to give for really strong, healthy people, but they are more than necessary to get the old people protected. For the safety profile, one out of a thousand side effects is easy to imagine with a vaccine with a potent adjuvant, even one out of a thousand lethal events. Are we going to make five, six million people sick with this vaccine because we rushed it forward? It looks like that is what we are going to do. It looks like we are developing a vaccine that is partially effective for some people, hard to get it to others, and of unknown side effects. If you are going to give a drug, the way you do it is you test it on a minimum of one hundred thousand people, if you are giving it to a broad population. And after you have tested one 1734
hundred thousand people, then you will have a continued period of observation in order to make sure that it is safe. We are not doing that for this vaccine. So, what we are looking at are the benefits and the risks. Let me ask you if there are any questions about that. If so, I will answer them before I start talking about drugs. BM: Are innate immune systems playing a role in deciding who is asymptomatic and symptomatic? Are any genetics HLA, TLR, and if so, can we classify people? WH: There are some hints, not in the HLA realm, but in the blood type, that there may be associated genes. I think the safest way to think of it, from a public health point of view, is that everybody is at risk of infection. And by far the dominating effect of how sick you get are underlying conditions and age. So, any genetic effect is minor secondary to that. I have just looked at allelic variation of the ACE-2 receptor and there are studies now of that receptor. There may be two nulls on the X chromosome out of three million nulls, which could be a mistake. That is pretty unusual to find only two nulls for any gene you look at. One of my students discovered ACE2, so I am talking to him all the time about what he knows. I just sent him the complete list of allele variations and there are already people who have already made a collection of those proteins and done binding profiles. And there are a couple that may make a difference. So, there may be a few people around, not many that are less sensitive to this virus because of the ACE-2 variation. Other questions? Charles Cantor (CC): Yes. I like your outline with what you described on the vaccines. There is possibly an alternative approach that is applied in some European countries, essentially stating to let those that are at a low risk of major health effects be non-socially isolated, and let thereby the virus into that community and protect those that are at a high risk and keep them isolated. And then you rapidly come to a point where you have hopefully established a form of herd immunity, slowing down the rate of transmission. But this is something that the US has not done because we have tried to save the healthcare infrastructure, slowing it down significantly, but thereby blasting the economy to pieces. What are your thoughts on that?
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WH: I do not think there is herd immunity for these viruses at all.
CC: You think there is no protection out of the natural infection? WH: I think this virus is designed to evade herd immunity because that is what most coronaviruses do. So, it only induces temporary immunity, which is why I said that these cold viruses come back every year, meaning you do not get herd immunity. That is the first response. The second response is that we are now recognizing there is a late syndrome. It is not frequent, but it is horrifying and occurs in children and people up to thirty years of age. They may get a light cold or nothing at all, and then late they have already made IgG, so it is two or three weeks later. Toward the end of a six-week period, they go into toxic shock and they get myocarditis, they get aneurysms, they get lung disease, they get all sorts of things. If they do not get emergency care, they can die right away. It is called MISC, Multi-system Inflammatory Syndrome- Children. There are maybe three hundred fifty to four hundred people who have been diagnosed with that. And it is hard to say, but I reckon a handful have died from it. If you actually look at who gets really sick from this, people in their twenties, thirties, forties, fifties, sixties get really sick. And about fifteen, twenty percent of people infected get really sick, which may mean lifelong illness. The thing to watch is morbidity, not just death. I cannot find, the number of hospitalizations from COVID in the US. Neither can I find how many people have been in the hospital for how many weeks. What are the long-term consequences of this? You cannot find it. The world is blind in terms of the really longterm human impact of this virus. If twenty percent of people are going to suffer serious disease that may be prolonged, we have to really understand what we are talking about. Male Speaker: If people are not socially isolating and you think the rapid vaccine development is going to be a mistake, what is your strategy? WH: Let me answer this by going to the next part of the discussion, which is what works for HIV, for malaria: prophylactic chemotherapy. And there is a real breakthrough that has just occurred in HIV, which has taken us thirty-five years. I predicted 1736
we could do it and actually did the first kind of preventive work. I was able to show that you could prevent mothers from transmitting the virus to their infants by treating the mother with antiretrovirals, AZT. And over time, we have gotten better and better. I was able to reduce the maternal transmission in monkeys to about five percent of normal and in humans about the same; actually from thirty percent to five percent. There is now a single shot that will protect you from getting HIV for two months. That is almost like an annual vaccine, and we will probably find a better vaccine. So, what you can see is chemoprophylaxis. When I look at that virus, there already are so many targets and some have not even been fully explored yet. It is one of the things I am diving into and trying to understand the molecular biology. There are plenty of targets; with AIDS we found about ten good targets. Interestingly, the targets which is working now is one that I pushed for a long time that nobody seemed to pick up. Finally, Merck licensed the assay from us, it is from integrase, the ability of the virus to integrate it in the cell. They have made a really good drug, a second-generation drug that is very long lasting. And the drug itself you give in a formulation that is a slow release and it protects people. A single drug is protecting people for up to two months, as long as they have tried it. So, I think that the progression is going to be the following. You already see people being treated with convalescent serum. Those are the antibodies. And there is some data, which says it is slightly working. The next step is to make concentrated IgG. That is, you take the people who have the best neutralizing antibodies, you concentrate that, and you use it. There are tons of people all over the world making monoclonal antibodies. We know enough to know we need a cocktail because this virus will mutate against one. As a matter of fact, several of my students have independently made great monoclonal antibodies. Those clinical trials are just getting underway, and those are going to be very effective at treating people who come into a hospital and it is going to keep them out of the ICU. It is also going to give prophylactic protection for highly exposed people like healthcare workers. And behind, is a whole set of drugs that were developed for SARS and for MERS such as protease inhibitors and helicase inhibitors. What is interesting is that the same compounds that 1737
stopped SARS and MERS, also stop this virus in animals. And we are going to have, as we have with HIV, a group of forty, fifty drugs that we use in various combinations, and then over time, we will get better and better at using those drugs. We can take all the learning we have had from HIV and drug development there and apply it here, especially the long acting drugs, the formulations that we have done. Vaccines are a hope, and I did not quite finish the story in vaccines because what you are likely to get at the end of 2020 is a vaccine which may work, may not, or may be partially effective; but will not stop infection. And we cannot have any idea of long-term consequences of infection because we will not have the time to learn about them. It will be of dubious safety and we have no idea of how long it will last because we have not had the time to test. And that is the vaccine that you are likely to get if you are brave enough to take it. On the other hand, the drugs are not so easy to give because you have got to give them continually. And if you are looking for a mass solution for the rest of the world, it is going to be tough. It is a good way to protect healthcare workers, a good way to protect people who are exposed, but it took about twenty five years to get drugs that could be tolerated by fully healthy people. And that is really where you are talking about prevention, which are things with very low risk, just like the vaccines. It cannot have a substantial risk in a population because it is not ethical to do that, which is why it is taking so long to get the right cocktail of drugs that you can give to healthy people. I think another way to answer your question is if you talk to historians and you read the history of disease, cultures eventually adapt to the presence of a deadly disease. We bear it in some ways or another. So, what can we do if we have no other solution? We will change our cultural behavior to adapt. That can be a slow process, but it is already in motion. Let us tolerate people dying as long as it is not too many. That is what we are doing right now. We are going through a cultural adaptation to a lethal disease in our midst. We are going out and trying to be a little careful, with some people being a little bit more careful than others. We have reached a plateau. And that is how we are dealing with it. So. we will have
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a cultural adaptation, which includes accepting a certain amount of death and accepting some behavior changes. BM: Some of the people in the group are exploring using technology, mainly the cell phones and data and badges to monitor infected people. With that, we would be able to diffuse the virus and keep vulnerable people far apart from those infected. What are your thoughts on this? WH: You know, there are limits to digital solutions, but they can help in some ways. I think that the best way they can help is to make contact tracing efficient. But the contact tracing without mandatory isolation is not a solution. So, what it looks like to me is we have reached a plateau and we are willing to accept 20,000 people a day being infected. We are getting better at saving people's lives. We do not care about the wounded. We do not even mention them. The number of deaths is going down. This approach is only effective if implemented correctly, like in China where your phone is either green, yellow or red. If it less then green, you are sunk. If it is yellow or red, you better stay home. And if it is red you are risking other people’s lives as well as your own. So that would be an efficient way to do it. BM: When you say cultural adaptation, do you mean that we might become more like China or Korea? I have a student from Hong Kong who went to Australia and she said, when she went there that she was the only person wearing a mask. So, there is a cultural difference. Should we become more like that? WH: I think each culture finds its own way to accommodate. We will see what the tolerable level of this infection is about 200 in Spain, for example. In Britain it is a couple of thousand. As I say, our tolerable level seems to be 20,000 a day. So, I do not think we are going to be like China or Australia but we may not have big football games for a long time. That will be an internal response because people will simply not want to go to football games. That is by far stronger than any external thing. So that is the cultural adaptation that I am talking about. Behavioral, individual behavior. Female Speaker 1: What is your opinion on the fact that the virus is believed to be getting weaker? WH: The answer is, if anything, I see it getting stronger. I know of two mutations that improve the transmissibility and lethality of this virus. One of them is an envelope gene that makes it better able 1739
to infect and that one is spread all over Europe. And secondly there are two actually that have been seen in a couple of places that tamp down the primary immune response even more strongly. What is happening is we are getting better at treating people. We understand this is a multisystem disease. It is not only a lung disease and we are able to handle the lung disease better. We are also able to handle the clotting better. We are able to handle the kidney disease better. We are on the lookout for heart disease. So, we are getting a lot better at treating people who are seriously ill. I want to thank you for the opportunity. I hope this has been useful. It has been fun for me. All: Thank you. WH: Thank you very much. Good luck to everybody.
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Interview With University Of Miami Business School June 10, 2020 | Interview
John Quelch (JQ): Good evening everybody from Miami. I am John Quelch, the Dean of the University of Miami Patti and Allan Herbert Business School. Welcome to another Southern Glazer’s Distinguished Leader event. Tonight, our special guest is Dr. William Haseltine. We are going to hand it over to him shortly but to introduce Dr. Haseltine, we are privileged this evening to have our president Dr. Julio Frenk, who is a good friend of William's. I am going to hand it over to President Frenk for the introduction of our distinguished guest. Julio Frenk (JF): Thank you John, and good afternoon everyone. I am truly delighted to join in for what I am sure is going to be a very insightful lecture. Although we cannot be together in person right now, I am very glad to see that the Miami Herbert Business School continues to complete these necessary conversations around important issues. It is my pleasure to introduce today's speaker, who, as you just heard, I have had the privilege of knowing for many years dating back to my time at Harvard University. If I had to describe Bill Haseltine in one word, the word that comes to mind is multifaceted. He is a renowned HIV/AIDS and cancer researcher, and he is also an innovator and a writer. He is a gifted scientist and his interests have evolved from the micro level of groundbreaking work in HIV/AIDS and the human genome to the macro level of complex health systems. In recent months as the world has grappled with the COVID-19 pandemic, he has become a prolific commentator who really offers clear-headed analysis in the uncertainty of the pandemic. Whenever I get his emails describing some of his latest contributions, I immediately empower him, because I have found him to be one of the clearest thinkers to make sense of this very complex challenge we are all facing, and I immediately forward it to all my friends and contacts. Bill really understands, unlike many others, the complexities of the challenges 1741
before us and we are really fortunate to have him with us this afternoon. Please join me in welcoming Dr. Bill Haseltine to the University of Miami in this virtual forum. JQ: Thank you very much President Frenk and joining me on the fireside chat this evening is one of our distinguished faculty members, professor Karoline Mortensen, who is a professor in the Department of Health Management and Policy, and the co-director of our Center on Health Management Policy. Karoline will be alternating with me in terms of fireside chat questions to Bill. For a couple of minutes, I am going to start talking about topics other than the immediate coronavirus. Bill, you are the Founder and President of ACCESS Health International. Before the coronavirus, I think that is how you would have been primarily introduced. What is ACCESS Health, why did you found it, and how are you measuring its success? William Haseltine (WH): ACCESS Health is a not-for-profit think tank consulting group. Our mission is to make sure everyone, no matter where they live and what their age, has access to high quality affordable health. After a career, both as a scientist and a businessman, I came to realize that no matter what science can create and understand and no matter what products businesses can produce, if health systems are not designed and funded properly, it really is all for nothing. In the end, it is about the delivery of health services and products, which the industry makes, to people in a way that makes a difference to their life. I also came to it with the understanding, as a scientist deeply interested and aware of the enormous progress that is being made, that unless people see the tangible benefits in their lives as these scientific advances are made, they are unlikely to keep funding it at the level that they are. The problems in the United States are really acute. Our healthcare costs are very high, yet our quality is extremely poor compared to the amount of money we spend. Even on an international scale, we, in the United States, have health outcomes that are well below the OECD level, almost a standard deviation and a half below. We are ranked number thirtyfour in health outcomes despite all of our knowledge and expertise. How long will our American people continue to support the engine that drives the future of everyone's health? Solving these problems of health equity, which we see acutely in COVID and in the social determinants of health, are extremely 1742
important. We should be asking ourselves the fundamental questions about what the health system can do to contribute, other than providing the goods and services that we do. We work around the world. Our belief is we do not have all the answers. It is clear if we had all the answers, we would be doing better. There may be good answers from India, China, Japan, or other places. We have offices around the world. As we have developed over the last few years, we have been fortunate to have very close relationships with government officials and people who advise the government. I am the chair of the US China Healthcare Summit. I have just been asked to be an outside advisor to the Indian government to help them fight COVID. But before that, the foundation, ACCESS Health, played a major role in drafting their health reform package that the prime minister had instituted. Those are successes that make me extremely happy because fifteen years ago when I created the foundation, that was what I helped to do. Now, interestingly, we have had less success in the United States. We are a big country with a lot of experts, yet a unique voice is hard to find. I wish we had made progress here, but I think at least with COVID, we have a chance to make a unique contribution to the way we are dealing with this problem. JQ: Bill, could I ask you to briefly comment on your business initiatives and perhaps one or two of the companies that did exceptionally well? You also mentioned that the United States has this wonderful scientific engine. Why is it that the scientific engine is not dedicating more of its resources towards solving some of these equity issues that you refer to? WH: With respect to business, I have created and am still creating a number of companies. I am happy to say that for my first ten companies, all the initial investors made a lot of money. That is not to say that all investors greatly profited, because stocks go up and down if they are public, but many investors had a healthy return. We have had eight products approved by the FDA or other agencies that attack such diseases as cancer, lupus, diabetes and some infectious diseases. Some of these drugs are for AIDS, in order to protect against bioterrorism with anthrax. It has been fascinating. I come from a background where my dad was a civil servant as a scientist and I had no concept of business, but when I really began to learn about medicine, I understood how important businesses are for translating scientific discoveries to products that people use. Once 1743
I made that discovery, I was fortunate to have good friends and be able to create a number of companies. Human Genome Sciences was the biggest and most successful. I was the founder and CEO of that company for twelve years. We started with $15 million and we sold it for $3.6 billion. That was a pretty good return on the original $15 million dollars. Beyond that, it really changed the paradigm for how you do research. People used to go from phenomenon to gene. Now you go from gene to phenomenon and it saves about twenty years of research. Wanwag actually called it clone by phone when he was asking for a solution. He called me up and said, “Do you have a gene that does this?” I said, yes, we do. Within two or three weeks, he had a scientific publication. We really sped up the process. That is what I wanted to do. Let me take you back to my very first company. The idea is much more relevant today than people thought it was then, which is to create animal vaccines using new technologies. We invented a very commonly used adjuvant now called Quil-A. I had a Peruvian scientist who knew about a tree that created inflammatory reactions and thought this would be a good thing to use for an adjuvant. As a result, our company created Quil-A, which is now a hot commodity in the COVID vaccine market. That has been a lot of fun. The first vaccine we created was a peptide vaccine with a new adjuvant for cat leukemia. It works and is still used. JQ: That enables me to pivot to our COVID discussion. You have spanned three very important pandemics: the polio pandemic, the AIDS pandemic, and now the COVID pandemic. If we look at the first two pandemics, what lessons were learned that proved to be useful then, or perhaps are useful today as we face the latest pandemic? WH: For me, who was a kid during the tail end of the polio epidemic, what I see around me is very common, but it is very familiar. As a kid, I was told that you cannot go to a swimming pool in the summer. You cannot be associated with more than three people in the same time. Movie theaters are out. There is polio around. I remember tangible fear. We were afraid, and we did not know of exactly what, but we were afraid and we knew our parents were afraid. As a kid, it is an indelible impression. I remember the very first vaccines. First you get a jab and then they give you a sugar cube to swallow. After that, no more polio. 1744
What are some lessons looking back? Many years later when I got my very first laboratory at Dana Farber Cancer Institute, I was amazed to discover it was Ender's laboratory where he had isolated the original polio virus. That was my lab. I decided that I was going to learn a lot about polio. What I learned really surprised me: polio is kind of like a cold virus. It is actually an enteric virus. It is waterborne mostly. Out of every two hundred people it infects, one gets paralyzed, and one in every 2000 people who are infected will die as a result. That sounds pretty familiar. There is a lot of familiarity in this. However, there is also a difference. There was great confidence that we would get a vaccine knowing what our immune reactions are. Once you are hit with polio, you never get infected again. There is a difference with this disease. There are good experiments to show that if you take a coronavirus and you infect a human being with a cold coronavirus, you can come back a year later and re-infect them. That means this virus has a different strategy from polio. Immunity for polio is very, very long lasting, but immunity for these viruses is probably not. As a virologist, when I looked deeply into that virus, I see that there are at least twenty tricks we know of now, and we are still counting, that this virus uses to mess with our immune system. This is not just a simple virus that goes in and replicates. It is really big. It is three times bigger than the AIDS virus. What is it doing with all those extra parts? It is subtly altering us so it can come back again and again, like the colds do. We are dealing with a virus that has learned to counter our immune defenses as AIDS does extremely well, yet we still do not have a vaccine and we have doubts about how easy it is to get a vaccine. It does not mean we cannot, but it means we have to be very cautious with what we are going to get when we get one. First of all, of course, safety is important. The vaccine has to be safe, but then its effectiveness is what matters next. If the virus is going to come back every year, will the vaccine stop all of its manifestations? There is another feature that we have to think about. How does this virus get into us? It gets in through our nasal passages, for the most part. You can swallow dirty water and you will get it too. But mostly, it gets in through our nasal passages, and vaccinologists had a very difficult time stopping that kind of infection. There is something else that is very specific. When SARS and MERS came along, we were not idle. Scientists got their full operation going to 1745
make drugs and vaccines. Every kind of vaccine you can think of was tried and they all had the same effect. Yes, they raised immunity in the animals. No, they did not stop nasal infection. None of them did so. That is true of the data we have seen for the SARS vaccines. They may reduce the total amount of virus in the body, but not in the nasal passages. What does that mean for disease? Does it mean we are only going to get diseases in the nose and maybe the brain, because there is a route from the nose to the brain and nowhere else? There is no animal model that we can follow because there is no animal that gets heart disease, kidney disease, and blood clots like we do. We do not really know and are waiting to see. These are some lessons that you learn when you look at a lot of different viruses. Each one has its own strategy, and this one has a tricky one. I would say it is halfway between polio and HIV in terms of certainty for finding a vaccine that is going to solve our problems. JQ: Thank you, Karoline, over to you. Karoline Mortensen (KM): Thank you for joining us, Dr. Haseltine, to have a conversation about COVID. We are really pleased that you are here. I just want to set the context. New numbers came out today; there have been 8,500 new cases in Florida just this week. Miami Dade County, where University of Miami is, has 20,000 cases and up to 784 deaths. But we are reopening our economies full steam ahead. You have a new book out, A Family Guide for COVID-19. What is your advice for consumer health and consumer behavior? You had some news about a vaccine that did not sound promising. What do we do in the meantime? WH: There is a Swedish thinker who has written a very interesting essay. I am about to share it with my group. It is called The Hammer and the Dance And Where are we in Sweden? What he means by the hammer and the dance is you do what China does and shut things down really tight. Then you are free to behave more freely as long as you are careful versus what Sweden has done, which is only taking partial measures, asking people to behave, closing colleges and not having big openings or meetings, but not being too strict. They decided to let businesses go along. Well, the consequences have been disastrous for Sweden. They have more deaths per capita than anybody by far in Scandinavia and even Europe. They have had a disaster and now they realize it. They realize they made a huge mistake. What was the mistake? It was not 1746
to close up tight, like their neighbors did. It was to close partially. It is very familiar to me looking at the United States. What we did in New York was tighter than most places in the country. What do we get when we do that? In the United States, for the last two and a half months, we have had about 20,000 people a day infected. That is what happens when you do not close up tight. Now we are opened up and we have 20,000 people a day getting infected. We seem to want to tolerate that. What is our tolerance level? We know some of those people are going to die and many of those who do not die are going to be severely injured for the rest of their life. They are going to have fibrous lungs. They will have hearts that do not function well. They will have lost their kidneys altogether. Some of them have brains that have suffered serious ischemic strokes. We are not counting those people. We count the dead, but we are not counting the wounded. What is the price we are going to pay for what we are doing? I do not think we have calculated it. We are also about to reopen. That feels good. Let us get out. This week, it feels different. At least to me, I see people getting worried again. I hear Tony Fauci reminding that it’s not over. I see numbers, like you mentioned, going up in Texas, Utah, and some parts of Florida. We in New York are now more careful. Once you go through that, you are more careful. It is going to be a long time before New Yorkers are comfortable getting together in groups again. I do not know if that is true for other parts of the country that did not go through it as severely. Yesterday, when I was walking into my apartment building here in Manhattan, they were carrying out a body from my own building; somebody who had died of COVID. That is a reminder it is not over in New York either. I am worried about what is happening. I don’t think I am the only one that is worried. You have to remember today, there are about seven million people in the world who are infected. Six months ago, there was one. Now we have 20,000 people a day. What is going to happen? I do not think it is predictable, but any prediction we make does not look so good. KM: You have been outspoken about Moderna, their vaccine development process, and the data surrounding that. What are the dangers of what you are calling publication by peer review? WH: The analogy I have given is what would you think of a CFO of a major company that said we had great results, but never 1747
showed you their numbers? I would not be confident. In fact, it would be a violation of the SEC. What do you think of a company that says we have a great vaccine, but I am not going to show you my data? It is transparency that I am calling for, but the transparency is a much broader issue. Let us talk about the Warp Speed vaccine effort. We hear about it, but do we really know what it is? Has anybody laid it out and said, “This is how we are planning to do everything?” I am beginning to get some ideas of what we are going to do. Some of those ideas seem somewhat worrisome for me, but I cannot tell you because we do not know. Also, transparency of regulation is an issue. What will the FDA require for safety and what will they require for efficacy? Do we know? I do not know. I think the public knows that is not right. We are the ones at risk. We should know how our money is being spent. We should know what the plans are, at least in some detail. How many people are going to be tested? Will they do a challenge study with a live deadly virus? What are their plans? How are they going to judge safety? What are their own internal standards? The government and NIH are helping, and some companies are involved, but we need to know more information. We especially need to know what the FDA is doing. The transparency is not just with Moderna; the transparency is written large. There seems to be a cloak of opacity around this massive effort. The United States and Europe, specifically England, are not the only other countries doing this. Who knows what the Russians are doing? We know some things the Chinese are doing because they are publishing it. Who knows what the Indians are doing? A lot of people are doing this. If we are not transparent, why should they be transparent? We, as a human species, are all involved and should know what is happening. KM: We are seeing that the coronavirus seems to be disproportionately affecting communities of color. We are also learning from some of your work at ACCESS Health International that there may be some relationship to blood type. What are you learning now about blood type and COVID-19? WH: The first thing to know about this disease is everybody is susceptible. There may be a tiny fraction that isn't, but we have not found it yet. I was looking for people who do not have the receptor. Of the millions of people that have been sequenced, they found two 1748
that may not have it, but that could also be an error. It seems to be a requirement. Everybody seems to need that protein to be functional and alive. I think you are going to find that everybody is susceptible, so everybody can be infected. Then the question is, “Are some people with certain blood types or genetic backgrounds slightly more susceptible?” Yes. It seems that there is a ten percent greater chance you will be infected. It is a little harder because the blood type is A and there are more A's than anybody else around. However, even with those statistics, it looks like O is slightly less susceptible to infection and A is slightly more, but the overriding feature is people of all blood types could get sick, infected, and die. It is not a blanket protection by any means. The questions regarding health disparities and why more people of color in the United States are getting infected and dying are related. The simple answer is they have to go to work in order to live. Many of them are undocumented or if they are not undocumented, they do not have the luxury of unemployment insurance or social benefits if they fall unemployed. They have to work. Some of them are required to work if they want to actually work, which is all the people involved in the infrastructure of our cities and our life. Making sure we have police, making sure the water works, and ensuring the lights are on are some of the things that people have to do. Most of those people are minorities and they are minorities that are disadvantaged across the board in health. I do not know who created the term social determinants of health, but it is a very potent term. You find that, on average, delivering healthcare is about twenty percent of the jobs. Where you live and how you live is eighty percent of your life's health history. The most startling example I know of is Chicago, where you go twenty blocks away, three or four subway stops, and you have a twenty year less life expectancy and you are three or four subway stops away from some of the best medical care in the world. There are many disparities and this virus is just now revealing them as disparities, which we have known to exist in our community. They are revealing things that we know, but they are highlighting it for us. I do not think that if you are in poor health, which many people are because of their lifestyle, you are more susceptible to dying from this virus. You can be rich and in poor health and die too. It is a matter of underlying health rather than race, blood type, or anything else. 1749
KM: Let us be optimistic and assume that I am one of these pharmaceutical companies working on a vaccine, and I am able to get something out. Now we have a 2020 vaccine that we can mass produce. How do you ethically allocate a vaccine like that? Does the federal government have any role in pricing something like that? How would pricing work? WH: You are getting beyond my expertise. Those are very interesting questions. Many of the vaccines that are being made are being manufactured abroad. Some of the major manufacturing facilities are in India. Many of these countries are developing their own vaccines. But I know from my work in ACCESS, and as we all know, that medicines are not equally distributed around the world. Let me just give you an example that I wrote about recently. Egypt, the country that we know about, is a middle income country. They recently did something remarkable. They screened everybody over the age of 12 and over for diabetes, hypertension, hepatitis C, and obesity. The whole country, with 65 million people, was screened. They did it in about nine months. They did a PCR test on the four million people with hepatitis C viremia, and they all received free treatment that costs the government $34. That is the price. Here, it is $80,000. In a country as diverse and complex as Egypt, you can run these major health programs and solve big health problems. Many people may not realize that Egypt was the center for hepatitis C infection. It is eliminated today from that country. Everybody who is hypertensive has access to free medication. It is an amazing story about what you can do today. That was not a country that had particularly equitable distribution of drugs, but now they are moving in that direction. It can be done. You would say that India has huge social discrepancy and it does. There is no doubt about that. Some populations get a lot better care than others. However, the price of medications there is something that almost everybody can afford and the Indian government is keeping it that way. It is a requirement that the price is affordable for most people. Governments can intervene in very powerful ways. Companies, in some cases, are cooperating. Some are forced to cooperate, but it is something that can be done. China also has lowered its drug prices so that it can be affordable for almost everyone. It is still more complicated than it might sound, but these
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are things that the two biggest countries in the world are doing pretty effectively. KM: Are there other things that the United States could model off of as we reopen? What have other countries, such as Singapore, done well that we could try to emulate as we reopen our economy? WH: Singapore was doing some things well, but they forgot about their guest workers. They experienced a tremendous infection rate in their healthcare workers, which is just now getting under control. It is obvious to anybody who has been in the healthcare business, but the first thing you need to do is find the person that is infected, isolate that person so they cannot infect anybody else, and you put them under controlled isolation. If they're sick, you put them in a controlled space where they are not going to infect many people. The second thing you do is contact trace. You go back two weeks, or however long you have to go, and you find everybody that has been in contact with the infected person. You do that rigorously. We have talked about this, but then most people do not talk about the next step. Once you have found somebody exposed, whether they are testing positive or negative, you do mandatory controlled isolation in a facility where they are all by themselves in a hotel room. This is because they were exposed, not because they tested positive. If you do that, you can drive the infection rate down and you will have a strict stay at home order. You can drive the infection rate even in a city like Wuhan down to zero. The last week or so, there have been zero infections in that city that had over a thousand people a day at one point infected. Thus, we know this can be done, and we know it is effective. This virus is exploiting, not just our immune systems, but our sociopolitical systems as well. It is very interesting that viruses adapt. They mutate and try to find the best way to solve their problem, which is growing. Our sociopolitical systems, as you look around the world, especially where the virus is not successful, get exterminated. For example, Sweden, which would seem to be a country very different from Brazil, seems to be doing the same thing. There are subtle differences in sociopolitical makeup, which make a big difference. I think that is not something that most healthcare theorists have thought about: how a natural organism interacts with our political systems. We are seeing a very dramatic example here in the United States. What New York does is not what Texas does, for 1751
example. Same country, but different region, with a very, very different response based on people's feelings about the way they should live and the way government should work. I think another lesson is that in times of crisis, you need excellent governance. You need leaders who are clear, consistent, believable, truthful, and compassionate. Those are all things you need from leadership. Then, you need a public health service that can integrate and function over the entire area that you need to work. It is up to the governors. The governors will say it is up to the city. The city will say it is up to the county. The county will say it is up to the municipalities. The municipalities will say it is up to the individual health care providers. Try to get numbers for something as simple as how many people have been hospitalized. We cannot do it in the US. How many people are still in the hospital? We cannot find it. These are really important things to know. We do not have a healthcare system. We have fantastic research and the CDC is basically an intelligence organization. Overseas, maybe it has a functional arm, but not here. It can give advice because they like our intelligence unit, but it is not a really integrated public health service for our nation. That is a mistake. We should fix it. JQ: I have three questions from our listeners. Number one, what are the prospects for therapies as opposed to vaccines as in the case of AIDS? Secondly, is there any role that vitamin D plays in the equation? Lastly, if we all keep social isolating for long enough, does the vaccine go away or is it back to square one immediately when we leave our homes? WH: HIV is a disease for which there is not a vaccine today, and there may not be one tomorrow. How do we control it? Well, we give public health measures, messages about safe sex, and we have programs for needle exchange. But now we have drugs that if you are diagnosed as being infected, they give you a good prospect for living a good long life, as long as you take your drugs and you are monitored. Drug resistance does not come up, but we have 30 or 40 drugs. You can mix and match and pretty much give people a normal life span, and we are getting better and better at that. Will we do that for COVID? I think the answer is absolutely. I can tell you as somebody who helped design those drug development programs for HIV and found some of the drugs, we can do that and should have done that for this virus. In fact, some of the very same 1752
drugs that work well against MERS and SARS that we brought right through animal tests, you will see them entering. For the next three or four months, you are going to see a whole bunch of conflicting reports of drugs, or they are really off the shelf that people are putting into people. You are not going to see much from those, in my opinion. You are going to get a lot of noise and very little real action. There will be monoclonal antibodies and cocktails that are effective cures, or for somebody infected, prevent them from getting sick. They could speed the process of becoming healthy and will be very effective in protecting those exposed from being infected, at least for a period of two or three months after infusion. That is on the horizon. There is a whole series of really potent antiviral drugs. I am not talking about remdesivir, which is called an antiviral drug. When you measure it, it does not drop the viral load in a human being in a noticeable way. Thus, it is not an antiviral drug. It is something else. In culture, it is not an antiviral drug that you can measure in people infected with COVID. When it has been measured, it has not worked. There will be really effective antiviral drugs that target the protease, helicases, and polymerases. We will have those drugs. They will stop people who are infected from falling ill. They will speed the recovery of those who have fallen ill, and they can be used prophylactically in healthy people. The challenge is that the bar is a little higher because your safety profile has to be better if somebody is already healthy. If the chance that they are going to get infected is really high, you are going to give them those drugs anyway. I am certain we are going to have that. What we are going to have, even if we never have a vaccine, is a way to protect people who are exposed. Let us say you are a family member and you have exposed every member in your family. The drug will then be used to treat every one of those members, so it stops infection. In the case that they get infected, they will never get sick, and by extension, all those who have been in contact will also not get sick. All of a sudden, if we have those, which we will, we will be able to get people who have been exposed flocking to us for the drug. Right now, nobody wants to be identified as a contact, especially if they think they are going to be put in an isolated hotel room for two weeks. But once there is a drug that says, “You have been exposed, but we can save you from getting sick and dying”, there is going to be a different 1753
reaction. We saw that with HIV/AIDS. Before there was a drug, nobody wanted to get tested. Once there was a drug, lots of people were happy to be tested. There are drugs that can be used for curative purposes and prophylactic purposes. Very often, the same drugs do both. As I say, the risk profile for the prophylactic drugs has to be better than for the therapeutic drugs, but we will solve that problem. I am sure of that. We are going to get vaccines eventually, which will be partially protective for parts of the population for some period of time. Now, on to the second question: the role of vitamin D. I would not bet on it. There are a lot of things that you are going to hear about. That always happens at this phase of an epidemic, where people are really anxious and there are a lot of people hawking A, B, C and D. Will it have any effect? It might make you a little bit healthier, but it is not going to be a cure all, I will tell you for sure. JQ: There is a question about cross corona immunities. The notion coming out of Europe is that between forty and seventy percent of us were already immune because of these cross corona immunities, particularly those of us who have children in the household. WH: If you are not immune from reinfection from the selfsame coronavirus that gives you a cold, why on Earth do you think you would be immune from a different coronavirus? I think that is not out of the question that some people may have residual antibodies to conserve regions that are conserved across the coronaviruses, but I would not count on that to protect very many people. If you are looking for a reason why some people get sick and others do not when they are infected, or some people who are exposed or infected and others not, that may be a small factor if you have been recently infected with a cold. I do not think, from first principles, it is likely to be a robust factor. JQ: In addition to the head of the Sylvester Cancer Center, Steve Naima, and Cindy Monroe, our Dean of Nursing, who are both on the call, we also have a special guest from the West Coast. Stanford professor Carlos Bustamente is joining us. Many of us will remember that Carlos was here at the University of Miami as a presidential distinguished scholar a couple of years ago. Carlos, do you have a question that you would like to ask Bill?
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Carlos Bustamente (CB): Thank you, Dean Quelch. It is a privilege and a pleasure to be here. I am curious about your thoughts on how COVID changes in the short and the long term and how we will go about delivering care and doing research. One of the things that I have observed is we are all hands on deck, and the research that is going on at the medical school must be COVID research. How do we do a better job in organizing those data and making them available? How do we shift to more telemedicine and other ways of delivering care to improve outcomes and to really deliver primary care? WH: Carlos, thank you for those questions. In the middle of this, there are some very bright spots. One of the bright spots is how the world's medical system and the world's caregivers are responding. When people first came in and thought it was a lung disease, all of a sudden they are seeing all these clots. The solution was to treat some people with anticoagulants. It makes an enormous difference. Everybody is being treated appropriately, hopefully with anticoagulants. It is saving a lot of lives. Some people said, “I am going to put people on their stomach, and they are doing better.” Guess what? Everybody's getting prone now. This is good news. This is what should happen. We are sending those messages around at lightning speed. Also, there are some things that are not so good. People will say that hydroxychloroquine may work. Everybody tries that. They are discovering it does not work so well. But on the other hand, there is a report out of Hong Kong that there is a cocktail that does work and people have not paid attention to it. It is not uniform and there are some distortions, but it is a lot better. That is good news. On the scientific front, I have never seen such a flood of exciting new work visible before review. You cannot even talk about your paper before we have accepted it. Now it is there to see. That is fantastic. It is from all over the world, too. I just wrote a little essay on this variant virus. There is a variant that seems to be spreading throughout Europe, faster than anything else. A computer scientist, who is trained on looking at AIDS variants and understands how to decipher what it means, said it looked like this virus mutated and became more transmissible. A pushback. How do you resolve that? First of all, how do they make that discovery? About 30,000 sequences from around the world are in a common data bank, and 1755
they will let you see in real time what is happening. That is amazing. It could not have happened before. Then the biochemists got a hold of it and now it turns out that sure enough, this makes a real difference to how it is ten times more infectable. It has this single mutation. The virus is changing; it is adapting. I do not necessarily think it is killing you faster, but it is great for the virus. It can get around more. Those are the kinds of scientific collaborations that are fantastic. On the other hand, there is a lack of transparency on what we are doing for vaccine development and what the regulators are going to approve or not approve. We need to be a lot more transparent at the other end of that. For example, do we know what the FDA's requirements will be for approval of a COVID vaccine? What are the safety parameters and what are the efficacy parameters? I think you are going to find them distorted almost beyond recognition. You cannot do a yearlong study. You cannot do it in six months. A 2020 COVID vaccine is not going to have a known safety profile. It cannot. No matter how many people, you are still not going to have a long term. Can you really give a vaccine to two billion people, where one in a hundred thousand side-effects is going to show up in a nasty way and maybe undermine all the good efforts we have made to give people confidence in vaccines? We have to be careful here. Transparency is important. The same thing is true with transparency and public announcements for corporations. If you are going to announce you have something that works, please show us the data so that it can sustain critical analysis by knowledgeable people and not some unsubstantiated press release. You are getting CEOs, not CFOs, saying they have great results, but we cannot see them and they are going ahead with their trials anyway. That is not good. There are a lot of positives and some negatives here. JQ: Profiting handsomely on the press release is another problem, as well. President Frenk, do you have a question or a comment to make here? JF: I have been fascinated. Bill sends me a lot of what he has been publishing, and it is an amazing treasure trove of insights as we have heard some today. You made a very interesting point about the adaptability to different political realities, but there is the question of how those political realities also shape human behavior. As we 1756
reopen the economy, what can we expect in terms of the dual purpose of protecting people's health and reactivating the economy? How are those going to interact? Is the solution a drug as you were talking about, even if we do not have a vaccine? What is the other set of interventions that we might have to persuade people to do, such as wearing face masks and keeping distance? How do you bring that part of a puzzle into your thinking? WH: Julio, you are asking really interesting questions that are real time experiences for many people. The first thing to realize is that collective action is a result of individual actions. Each person makes their own decision and that leads to some collective response and the personal decision is going to be based on what they believe in general, specifically, and based on experience. My experience of seeing a body pulled out of my own building yesterday is one person's. A guy on a horse ranch in Wyoming is going to have a very different personal experience, and he is going to behave differently because of that. That is going to affect collective responses. I think our country is so complicated, so we have to have a single response. If we are not lucky enough to have a good vaccine and the drugs do not come along quickly enough, I think the country will really suffer enough to begin to get a collective sense of what we have to do, but we may never get there. Certainly, with polio, that is what happened. As a kid, there was a collective sense throughout the whole country that we were at risk. I was on a military base in the middle of the Mojave Desert and my experience was not too different from a kid playing stickball in Harlem. It was the same kind of experience because we had years of experience in polio coming back and back. That can happen to societies, but it takes a long time. I hope we never have to get there. I hope that we do get vaccines or drugs. But at this point, we are reaching for a solution that does not exist. We are taking a chance on not changing our behavior really significantly, or at least changing our behavior really significantly for a short period of time so we have driven this down to zero, like a number of countries have done. We are going about our business for the last two and a half months with 20,000 people a day being infected that we count. That is how we decided to do things. Now, the consequences could be pretty disastrous. You are hearing people begin to get worried about that again. But Julio, I have a question for you. You were the Mexican 1757
Minister of Health. What do you think is happening south of our border? JF: What you are seeing is that variation in regimes and it is really not a good response. My observation, and this is totally speculative, is that there are two patterns that stand out to me when you look at the effectiveness of political leadership. The countries that have done the best have an over representation of women as Presidents or Prime Ministers, such as Taiwan, New Zealand, Norway, Denmark, and Germany. The countries that have done worse had populace men as their leaders. I am not talking about a cause and effect relationship. I am just saying that there are mindsets that are converging to that differential political reaction. It is in the mindset of populace leaders to distrust science and minimize technical expertise. This is what we have seen. It goes all the way from Russia to Turkey to Italy. Britain is not a populace government, but they have a populace Prime Minister. It is here in the States, it is in Mexico, and it is in Brazil. It is a consistent pattern now, regarding the value of science as the key ingredient for policy-making. Somehow, women get it better. WH: Maybe you are right, Julio, but every time I think of women leaders, I think of Margaret Thatcher, Catherine the Great, or Indira Gandhi. I can think of women leaders that are no different from men. I think you are right in the sense that political leadership makes a big difference. Is it the underlying population that gets you those leaders? Or is it the leader that is making the difference? We are not going to resolve that here. JQ: We have one woman leader who is really exceptional. The Dean of Nursing, Cindy Monroe, asked a question, which is related to what you were just speculating about, and that is European countries with strong public health systems and universal healthcare. England, Spain, Italy, and France, for example, still could not control COVID any better than systems that are not like ours, a universal healthcare system. How would you respond to that? WH: I would say the difference in control of this infection is not controlled by the healthcare system. This infection is cared for by the healthcare system. The control is a matter of individual behavior. As I look at many of the countries you mentioned, the one country that performs poorly is Great Britain. All the others, after a really terrible experience, shut themselves down and are driving the 1758
infection to very low rates. That is the reaction of a lot of people following instructions and driving it down. Britain looks a lot like the U.S. It is only partially controlled, and the people are only partially behaving. JQ: Well, every good European would always say that the British only partially behave. Let me ask Karoline if she would like to pose a final question before we complete the hour. KM: I would like to ask a question for President Frenk on his behalf. Earlier, you mentioned the importance of a strong leader and President Frenk has been fearlessly leading our healthcare system through this enormous change. Do you have tips or advice on how healthcare delivery will change in the coming months? WH: That was an earlier question that I did not pick up on. One of the things that I have been working on and writing about when I studied at the NYU Langone medical system is the focus on the importance that technology allows you to distribute healthcare to outpatients, communities, and even to homes. You'll link that through telemedicine. That is a big trend. It is one that, if you have the right information system, can give you very high quality health that is convenient, safe, and cost effective. It can really make a big difference to all of those features that we need for healthcare. On the other hand, what this epidemic shows is the need for big hospitals capable of dealing with complex cases that have flex capability. Now I would say that there's an answer there relating to how many people have forgone healthcare in this epidemic. I am an oncology survivor myself. I had head and neck cancer. I have missed my appointments for the last six months because they are not available. I am not alone. People with heart disease, kidney disease, and a lot of the excess deaths we are seeing are not COVID related, but rather due to their lack of medical care. There is a way to do this. We have the hospitals take care of the acute COVID patients, but really build an existing outpatient service, which COVID patients do not go to on the whole. There is a way to do it, but it is not there. I would say the answer is pretty complicated: build a distributed healthcare center, which has a tertiary or a multi-specialist academic center at the center, that has big flex capability. One that is like that is Rush. Rush actually was built to handle bio-terrorism. Every unit can be converted instantly, and even the lobby can be converted to an isolation ward. It is an amazing place. 1759
Build these facilities, but at the same time, make sure that if there is a crisis going on, you do not neglect the health of your population, which everybody has done. It is very bad for health and it is terrible for the economics of the healthcare system. You look at the holes in the budget of the healthcare systems now, and they are enormous. Some of them are over a hundred million dollars a month. It is not good. That is because people are not going to get their checkups. They are not going for their healthcare. They are dying because they are not getting the care they need. That is a part of it. Telehealth is the answer that most people want to hear. That is not the only answer. It is a much bigger question than telehealth. JQ: Bill, thank you so much for an enormous number of insights packed into the last sixty minutes. On behalf of the University of Miami, we truly appreciate that you joined us. I want to thank President Frenk professor Bustamente, Steve Naimus, and Cindy Monroe for being with us today. Thanks again to Karoline Mortenson, one of our outstanding professors in our health management and policy area, for also joining me for the fireside chat. Thanks for all you are doing Bill, and good luck. WH: Thank you very much.
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Interview With VuMedi June 11, 2020 | Interview
Anja Celio-Cega (ACC): Could you tell us something about the COVID-19 vaccine tests that are now done on animals? I have seen your report that they would decrease the viral load in organs, but the infection would still be there. If results were the same on humans, what would this mean? William Haseltine (WH): We have some information about the activity of vaccines currently under investigation for prevention of COVID-19. The information we have comes from animal studies that have been published by a number of different groups. We also have a wealth of information about vaccines that have been tried for the SARS virus and the MERS virus, which are in a way cousins of this virus. SARS-1 is the virus that caused SARS and is much more closely related to this virus than MERS. With the vaccine data that we have seen, the vaccines raise antibodies in the animals. That is not surprising. You put a foreign substance into an animal, and it is very likely to raise antibodies against it. Some of those antibodies seem to have activity. They do have activity in tests to inactivate virus in tissue culture. And that is how you measure the effect. Hopefully, you are able to demonstrate that an animal that is infectable and gets a disease similar to the one the humans get would be able to resist infection. That is how you know that you have an effective vaccine. Not only does the virus not grow, but the disease does not appear. Unfortunately, we do not have animal models of the COVID disease that mimic humans. At best, you can give a very high dose of the COVID virus to nonhuman primates, monkeys, and they will have very mild symptoms. If you are just examining them as a doctor would a person, they breathe a little bit faster. That is about it. If you actually look at what has happened to some of them, they have some damage to their lungs. If you look at what is happening in their bodies, they have very high concentrations of virus in the nasal passages and very high concentrations of virus in the lungs. But 1761
despite that, they do not seem to have many of the other symptoms that humans do. When you vaccinate with a couple of the vaccines that have been tested and you look to see whether you stop infection, the answer is definitely not. You do not stop infection. One study that I am thinking of in particular from the Oxford group reported on six vaccinated monkeys and all six of the vaccinated monkeys had the same level, presumably a high level, of virus in their nasal passages. They had a much lower level in their lungs. And some of the minor lung damage that is seen in monkeys was not evident. In addition, they made antibodies to those viruses. What would that translate to in a human? Well, we do not really know. We know that it would not stop the infection. You would still have the virus in the nasal passages. It would be presumably transmitted because that is the major role of way the virus is transmitted from person to person, from virus coming out of the nose. It might protect from lung disease, but since the animals do not have as serious lung disease as humans do, we do not know that. And then humans have a whole series of other events that occur. You trigger a cytokine storm, which monkeys do not get. You trigger kidney damage, heart damage, damage to the veins and the arteries. You trigger a whole clotting phenomenon, which causes trouble in the brain. And there is some suspicion that the virus travels from the nasal passages into the brain. I would say it is that ladder that you would be most concerned about because the virus is still there and in high quantities in the nasal passages right next to the brain. It can travel up the optic nerve. It can travel up the olfactory nerve, and the brain is immunologically privileged. So, it is very hard to vaccinate what happens inside the brain. So, you do not know what it is going to do if you extrapolate that to humans. There is another concern which is not tested for under these circumstances which happens with older people. The people who need the vaccine most are over sixty. And in fact, most of them are over seventy. And people over seventy respond very poorly to vaccines. So, we do not know if the studies in healthy young monkeys are going to translate to unhealthy old people. I think it is unlikely that they will. In addition to that, there are safety concerns that appear. And in one of the vaccines, the Moderna vaccine, there were several that are called class three adverse events. Those are 1762
serious. And at the high dose, there are some serious adverse events. We only know that from anecdotal presentations from the company, but nonetheless, they were mentioned. And they were mentioned also by some of the NIH scientists who are participating in those trials. So, we are left with an idea that we may have partial protection. We are left with the idea that it will still be transmitted, and that older people may not respond well, if they do react at all. And there is some question about the safety of some of these vaccines. I would add that when vaccinating older people, the way it has worked in the past is to give them repeated doses, and then give them frequent doses thereafter. People are talking about potential yearly doses. Well, for the vaccine to work on an older person, you need a powerful stimulant and adjuvant which are harmful and can be very damaging. For the other types of vaccine that use viral vectors, particularly adenovirus vectors, no matter the virus, you make antibodies the first time you see it, which makes it very hard to come back a second, third and fourth time. So, these animal studies give us a picture, not that it will not work, but that it will have a limited use. Also, it may be suitable for a limited number of people, maybe not the group that needs it most. ACC: Excellent. Thank you. How relevant are antibody tests and when will we know if these antibodies actually give us immunity? How relevant is that to developing and distributing a vaccine? WH: The level of naturally produced antibodies is a very good indication of how easy it is to create a vaccine. If the body responds, and almost everybody responds by making a high level of antibodies, the virus is immediately cleared, and the people are not subject to reinfection for many years, sometimes decades. You have a good indication that you can make a vaccine. On the other hand, if it is like HIV, the virus goes in your body, makes a tremendously good B cell and T cell, and it does not clear the virus, then your chances are very low. This virus is kind of in the middle. We know that the immune response to this virus varies between people. We are slowly beginning to get an idea of the nature of it. And there are conflicting reports and that is normal for an early stage. Some people respond one way. Some people say there are very few people making neutralizing antibodies. Some people say many make neutralizing 1763
antibodies. Some people say most people make a small amount of neutralizing antibody, and that is all it takes. It is not clear at this point, but what is clear is that this is not simple. We know that because the immune responses are complex, which we have established from the sisters of these viruses. The sisters are those that cause our colds. They are also coronaviruses. Some even come from bats. Some even use the same receptor. Those viruses are very peculiar because you are infected, you clear the infection, and a year later you are re-infectable by the selfsame virus. That means immunity does not last very long. Now, unfortunately for SARS and MERS, we did not really study them long enough. Certainly not for MERS. And for SARS, there are still questions. What kind of immunity do we have? So, we are sort of in the dark here as to whether people make protective immunity. And I would say, if you were to ask me now, I would say some people do for some period of time, but most people do not for very long. That is how it looks to me now, although that picture is evolving, and we have to look at it more critically with much more detail, and that is in the works. We will know those answers in a few months. The first main group of people were infected in March. So, a year from March, two years from March, three years from March, we will have a better fix on it; but that is not the kind of answer people want now. ACC: Exactly. Thank you. I am getting the impression that you think it is unlikely that we will have a vaccine… WH: No, that is not correct. It is clearly possible to have a vaccine. We are going to have a vaccine due to the huge push from industry, from government, and from people like you and me that want a vaccine; whether that happens by the end of the year or soon thereafter. We are going to have something that we call a vaccine. My questions are different. How well will it work? Will it protect everybody? Will it stop disease as we hope? And how long will it last? And will it protect the people who need it most? There is a lot of effort on this from multiple governments, and we are going to get something. I am just not sure what we are going to get. What I would argue is that what we need to answer that question is transparency. We, professionals and the people who are going to receive these vaccines, need to know what is happening. How are you testing these? How do you really know that these are effective? 1764
How do you know these are safe? How do you know how long it lasts? Give us your protocols. And we need transparency from our regulatory agencies, both the ones in Europe and the ones in America that everybody looks at. But there are other regulatory agencies too, the Chinese, the Russians. What are the rules that they are going to put in place? How effective does it have to be? How safe does it have to be? You know, the thing that is different about vaccines from all other drugs is that you give it to healthy people. And we might be giving it to billions of healthy people. If you have one in a thousand adverse event, and you give it to a billion people, you have a million people with an adverse event. Some of them may be dead, and they were healthy before you did it. The first rule of medicine is do no harm. We need to know what the regulatory agencies are going to allow. And we still do not know that from any of them. That is not acceptable. ACC: Excellent. Thank you. I think this is something that our physician community will definitely listen to. Is there something else you would like to share? WH: I hope we have a vaccine that is safe, first of all. That is effective in not only preventing infection but preventing disease. And that is safe enough to use repeated times in our older population that needs protection very badly. I would add that there are alternatives. There are very good alternatives. Let us talk about the medical alternatives first. The medical alternatives are to develop really effective antiviral drugs, which we are in the process of developing. These will be monoclonal antibodies. And there will be antiviral drugs, not like remdesivir which does not work very well, but real drugs. And I do not see any of them in clinical trials right now, but they are about to enter clinical trials. These drugs will stop the virus in its tracks. That is what we did with HIV. You will be able to take anybody who we know is exposed, treat them with the drugs at the early stage before the damage is done, and prevent the damage. You will be able to take people who are known to be exposed, treat them, and they will not get sick. You can use these as chemo prophylaxis. There is a way of doing it. And you can make some of the antibodies. I have made an antibody that protects people from anthrax for two months. The same could be said of respiratory syncytial virus. There is a monoclonal antibody that protects people for four months. You can 1765
give that to people who are known to be exposed and who are at high risk, like healthcare workers. So, you do contact tracing and give these people the drugs. Meanwhile, you take the time to know the characteristics, particularly the safety characteristics. My biggest worry is not that this vaccine will not protect people, but that it will harm people. That is what we have to worry about, because if it harms people, you are not just harming the fight against COVID, you are harming the fight against all infectious diseases. We already have a problem with credibility. There were two surveys done. If there were a vaccine, would you take it? One survey, forty nine percent of the people said no. Another survey about forty percent said yes, and about thirty percent said maybe. Why? It was going to protect you. People have in their minds that vaccines may not be safe for their children and for themselves. And if we make a mistake with this one, the whole vaccine system can crash. And that would be a tragedy beyond measure for our children, our grandchildren, and our future generations. That is what is at risk here. It is not just COVID. We have two good methods. The first one I just described, prophylaxis with drugs that are shown to be potently antiviral, and we will have those. That I am certain of. The other thing we should remember is that it’s been proven to be within human capacity to stop this infection without a vaccine, without a drug. That is what China has done. That is what South Korea has done. That is what Australia and New Zealand and Thailand, and a number of countries have done. And you can see, even in Europe, they are pushing it down. It is behavioral change. You can stop with behavioral change. You can have a temporary vaccine. In HIV, there is now a shot once every two months, that is as good as any vaccine. You could not hope for a vaccine that does better. A shot every two months for healthcare workers. One shot for people who have been exposed. I will tell you something else that has got to happen. The moment those drugs come on the market, the moment they are available to people, there is going to be a rush to get tested. Right now, people are hiding. Why? They do not want to be shoved in isolation for two weeks. I think they ought to be, but they choose not to be mostly. The moment we can say that you will never get sick if you take this shot, it is going to change the picture. So, what we are looking at today is not what we are going to be looking at 1766
five, six months from now, when we are thinking about whether or not we should start vaccinating people. The equation is going to change really fast. And so, I think that is something that people have to have in mind. What is the rush if we are going to have other methods? ACC: It is such an interesting perspective. I think I have recorded about twenty COVID vaccine videos, and this is the first time that I have heard this perspective. I love it. So, I am promising you this is the last question before I let you go, because I am sure you have other places to get to. How likely do you think is it that SARS-CoV-2 will disappear the same way SARS did? WH: It is not going to happen. SARS was particular in a couple of ways. One, it was not particularly transmissible like this was. And I must say, there is good evidence right now that this virus has gotten more transmissible since its arrival in China. I have just written a little piece on that. There is one particular mutation in the spike protein that has taken over most of Europe and the West, and even China. It is actually displaced the virus that was there. And there is a lot of really interesting experiments now that show why. It is not just that it is a founder effect. It actually displaced viruses that were already established. But we know the biochemical mechanism. The outside of the virus that attaches the cell to start the infection has two parts. And those two parts are loosely associated once the virus leaves its mother cell. And for the first generation of the virus, it fell off pretty fast. So, the viruses that were left were diminished for the total amount of active attachment sites. They could not attach as well. They were mostly bare. What this mutation does is that it increases the infectivity of this virus by a factor of ten. You need ten times less virus. And the reason for that is it does not fall off so fast. You can actually measure the virus of this particular strain, and see that has taken over almost all of the Western world and a good part of China now, too. So, this is not going away. It is going to be like the cold viruses. It is going to be around, and we are going to have to be careful with this virus for a very, very long time. It is not going to go away like SARS. ACC: Thank you so much. I actually think that social isolation really works. I am based in Croatia. We have fourteen active cases at the moment.
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WH: It does work. It is a whole other discussion of where social isolation works and rigorous public health. But it is really a question of leadership, governance, and government capabilities. And I can say in many countries, if you have a failure of any one of those three, you are going to have a permanent problem. We have, in the United States, a failure in all three. Just take the public health service. It is devolved right down to the municipal and town level and sometimes to even smaller units. And there is no overarching way you can give a command and have it executed. The CDC is an intelligence service. The NIH is a research service. The public health service is devolved. So, the president says it is the governors. The governor says it is the counties and the cities. The cities say it is a smaller unit. So, you do not have the kind of effective response that you need. In addition to that, there is a real debate over the effect on the economy. What is happening in our country and around the world now is running back to the middle ages. We are going back to a time when we were saying we have to live with death at our side. During those times, children died at birth. They died before one, they died at age five. You could have a fully healthy twenty-year-old dead the next week. Just look at the literature and look at the history. That happened. Well, in the United States, we are willing to live with twenty thousand people a day infected and to go on about our day. It affects me personally. I came to my apartment building a couple of days ago and they were carrying out a body of my own building right before my eyes. We live with that. How long are we going to live with it? In 1950 we said we did not have to live with that. In the thirties and earlier we did live with it. Now we do not. We are going back to the days earlier and maybe back to medieval days where death walks beside each one of us. ACC: Interesting, distressing. Thank you so much for this. I really appreciate it. It was really my pleasure and a very big privilege to interview you. WH: It was my pleasure. Thank you for your time.
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Interview with Bloomberg Businessweek (Podcast) June 16, 2020 | Interview
Carol Massar (CM): If we are looking at some of the virus headlines, we see Florida reporting new cases rising to the highest level since the pandemic began. Texas saw hospitalizations surge to more signs that the virus outbreak is worsening in some US states. In the meantime, you have Beijing shutting down its schools, concerned about new infections as China started testing all shipments of imported meat. They had a fresh outbreak that was linked to another wholesale seafood and meat market in the capital. Back with us to talk about where we are, what we need to do, and how we deal with what is going on, especially when you come at it from different angles when it comes to the virus, is Dr. William Haseltine. He is Chairman and President of ACCESS Health International, and he joins us on the phone from Connecticut. Dr. Haseltine, it is great to have you back with us. What do you make of the most recent virus headlines? William Haseltine (WH): Right now, I am looking at what has happened in Florida. In many ways, it was predictable. It was averaging about five hundred, previously four and six hundred, and even up to eight hundred cases sometimes for about a month and a half. Then, starting at the end of May, early June, it just started to rise. A couple of days ago there were two thousand five hundred new cases and now maybe another two thousand new cases. It is pretty serious. What it means is that the precautions that people were taking were eased off about two weeks ago and we are now seeing that as spikes in newly diagnosed infections, mostly because people are getting mildly ill or seriously ill. That is happening in many parts of the country. Some other parts like New York City is still relatively calm. People in New York got really scared, and they know it is important to keep social distance. However, even in New York, people are beginning to forget.
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Jason Kelly (JK): Dr. Haseltine, what have we learned about our initial response that we can put into practice now, because there is this strong resistance on the part of both government leaders and just everyday people to go back to a full on shutdown? WH: I understand that. It is fully understandable. The way I look at it is the following. We paid a price, but we did not get the benefit. That is because we did not do it right. We did not really enforce contact tracing and mandatory isolation. Additionally, all the people were not observant about the precautions they were urged to take. We never cleared the infection, like a number of other countries did, or reduced it down to a very manageable level of a few dozen in the whole country. We just did not do that, so we paid a price without getting a benefit. The net result is we are now going to end up in a different situation, which is what I call back to the future. When I was born seventy-five years ago, it was right on the cusp of the vaccine and the antibiotic miracles. Before that time, people lived with the understanding that death could strike at any moment. I remember polio. I remember being terrified of rheumatic fever. Those are things we could not control. In fact, we built the world in a world without vaccines and in a world without antibiotics, but you pay a price, which is what we are beginning to understand. The price is that death is at your shoulder at all moments. It seems we are willing to adapt to that. We have adapted in the past. We will adapt again. We are exiting the time, at least for now, where we have a free ride and do not have to worry about dying of an infectious disease tomorrow. CM: Wow. How do we do this? We are kind of in this interesting situation and yes, history has shown us we can forge ahead and we can build society, but there is a cost to it. As we reopen, do we do it, or do we pay the price? WH: We do it. I happen to agree that we do not have any choice, because Americans seem to be undisciplined and we do not have neither the leadership, the government nor the government apparatus that we need. We need leaders that are clear, consistent, credible, and compassionate. We need governance that works, and we need a public health service very much like an army that has unitary command from the top to the bottom. When the President says it is up to the governors, he is right. He does not have a tool he can use like he can use the military abroad. We do not have that 1770
tool. When the governors say it is up to the municipalities and the cities, I live in New York and you can see the tension between the governor and the mayor. In some places, the mayor or the county leader may even say it is up to the local authorities. We do not have unitary command in public health service. If there is a lesson we learn from this, it is that we need unitary command to protect us internally as we do externally. Our biggest threats in my lifetime have not come from abroad. They have come from diseases within our own country, whether it was HIV/AIDS or whether it was a number of other diseases, such as polio. Those are the big threats. We are not prepared for those like we are prepared for external threats. JK: Let us get back to our conversation with Dr. William Haseltine, Chair and President of ACCESS Health International, joining us on the phone from Connecticut. He also has written a new book. It is called A Family Guide to COVID. One of the things I love about this, Dr. Haseltine, is that it is a book that lives right now, but this is a fast moving story. You give people access to your website because you are going to keep updating this. Tell us what led you to write this. WH: During the early days of HIV/AIDS, I remember so many people had questions, and there was no place they could go for answers. This is even more serious than that, because kids are affected as well. If you are a parent, you have kids that are asking questions all the time. I am a grandparent and I have a lot of grandchildren and their parents asking me questions. So I decided I would write a book to answer questions in a very simple way, the kind of questions that kids are going to ask or parents will ask themselves and each other. They ask questions like, “What has happened mom? Why can’t I go play with my friends?” or “How long is this going to go on?” or “Will science save us?” Adults are going to say stuff like, “Should I really put masks on my kids when they go to play with their friends? Should they play with any friends? What is the situation today?” This is an ever changing situation, so this is what I call a living book in the sense that the book will change along with our knowledge. Questions will disappear. Answers will change. There is no set of answers yet, so it is a living document. It has been a lot of fun to do and I hope it is helpful.
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CM: I have to say, we just went through a conversation with my daughter last night. She is seventeen and getting ready to be a senior in high school. Jason also has a teenager the same age and two other children. My daughter was saying, “I just miss my friends mom.” They have done the Zoom thing, but we do not know what school is going to be like in the fall. Her world is being turned upside down. We are so happy we are healthy, but you do realize the mark this is having on a younger generation. WH: Absolutely, you do. It is at a time when young people have to get out. This is what young people have to do, whether they are children or teenagers. To do this book, I talked to a lot of kids. I rounded up every grandchild and child I could find and a lot of teenagers. I talked to a teenage boy who said, “This whole thing is a plot to keep me from my girlfriend.” That is life. That is what parents are dealing with. JK: They are, and I think we do think a lot about, as Carol mentioned, kids going off to college and being deprived of that experience. However, I think you provided some really good historical perspective in that regard, Dr. Haseltine, that this is new to all of us in many ways. Yet, as a society, this is something we have dealt with before and we just have to learn to adapt in many ways. WH: We do, but it is not going to be easy. CM: Earlier, I was listening to a conversation on Bloomberg Radio about a vaccine, and I know there are some folks that are saying we could get it later this year. What is the reality, and until we have a vaccine, will life not be normal? WH: We lived, as I said, for centuries without vaccines, so you can live. Secondly, there are things you can do, since other countries have shut this virus down almost completely, even though it will not be gone completely. We are going to have drugs that are temporary vaccines for anybody who is exposed. We will have drugs within a year that will prevent anybody from being exposed from falling ill. I am virtually certain of that. For vaccines, I give them a fifty, fifty shot. JK: Wow. As always, we really appreciate your time, Dr. William Haseltine. The new book is called A Family Guide to COVID, and when you pick it up, you should note that it is a living book. You will be able to get into a website that will be constantly updated, because the questions are changing and as you said, the 1772
answers are changing. I think about the conversations we have now, Carol, versus what we were having a month ago or six weeks ago. We are in our fourteenth week of doing this broadcast this way. CM: I know. What is also interesting and crazy is that there are still so many questions about getting our heads around it and getting back to normal. I think what Dr. Haseltine says is that at some point, you are going to have to get out there and there will be a price to pay for it. JK: There will definitely be consequences, and we will all have to adjust. That was Dr. William Haseltine, Chair and President of ACCESS Health International. Check out his new book, A Family Guide to COVID.
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Interview With Bloomberg Markets: The Close June 16, 2020 | Interview
Taylor Riggs (TR): I am curious what your thoughts are as we have all been looking for new vaccines and new medicines. Today, it looks like a study showing that an old generic 60-year-old drug could be promising from early results. Does that give you some comfort? William Haseltine (WH): It surely does. If you are a doctor on the frontlines, you have to work with the tools you have, not with the tools you wish you had, and not with a vaccine or drug that may or may not appear. What is happening that is very encouraging to see around the world is that there are a number of advances that have dramatically reduced death. I count the fourth in a series. The first one is really simple. You flip people over on their stomach instead of keeping them on their back all the time. It turns out that doing this allows the deep lungs to get more air, which saves a lot of lives. Second, people found that if you use anticoagulants -- one of the really amazing discoveries of this infection is late in the disease course -- it inflames your blood vessels, which can trigger massive blood clots all over your body. Judicious use of blood clots has had a very dramatic effect on reducing death. There was a drug cocktail that was put together in Hong Kong based on their experience with SARS and MERS using off the shelf drugs. Anticoagulants are off the shelf. These drugs that were used in Hong Kong, interferon beta and ribavirin, are also unpatented. They have been used for a long time and make a big difference. The drug that does it, and now beclomethasone added to all of that. The drug that does not make a difference to survival is the one that everybody is running around about, remdesivir. Studies show it makes absolutely no difference to your outcome if you are really sick. However, it is really encouraging that we have tools at hand that make a big difference. I will tell you how big a difference. If you went into an ICU unit and needed breathing support through intubation, at the beginning of the epidemic you had about an eighty to ninety percent chance of 1774
dying. Today, you have an eighty percent chance of living. It is a big advance. Caroline Hyde (CH): Wow. That just really puts into context of how important generic drugs under our noses can perform. But doctor, what about the hope for some sort of silver bullet, some sort of vaccine that might not only prevent the disease ripening within people, but also hopefully stop the spread? Are you hopeful for that in the next twelve to eighteen months as it stands? WH: We are like the handicap thing. I would say I am pretty sure, based on my own work and what I see around, that I would give it a ninety percent chance that we are going to have drugs that will prevent people who are infected from getting sick, and those selfsame drugs will prevent those who are exposed from being infected. I give that a ninety percent chance within a year, year and a half at most. For vaccines, it is like judging a horse race when the gates have just opened. I give them a fifty, fifty chance. We do not know enough yet. We know enough to be worried but we have some encouraging results, so we are in an intermediate phase. It is a little too early to call, but as far as the drugs that are going to be able to really treat this disease, these will not be off the shelf drugs. These will be brand new drugs directed specifically for the virus. Over time, we can look forward to a single shot that will prevent you from being infected for months. That has just happened for HIV/AIDS, and I am sure we can do it for this virus too. Romaine Bostick (RB): Doctor, if or when we do get to that stage, is this the type of vaccine or drug that would have to be revisited or updated on a yearly basis like other types of vaccines, such as the annual flu shots? Or is this just going to be a one shot deal? No pun intended. WH: At this point, it does not look like it will be a one shot deal. It looks like a vaccine. I am going to make a distinction between two kinds of drugs. There are vaccines that your body makes an immune reaction to. Therefore, you have some degree of protection. At this early stage, it does not look like it is going to last very long. You probably need boosters or you will need another shot. The drugs, on the other hand, by their very nature, will only last a certain amount of time. Now if they are easy to take, like a pill, you could take those for a very long time. If you are in an endemic malaria area, you can take those pills pretty often and you 1775
can take them for a long time. You can take them if you are just a tourist or you can take them if you live there. That is the kind of thing we are talking about. Or if we have a long acting shot, you just have one shot that lasts two or three months. I developed an antibody for anthrax. You give it to people and they are protected for one to two months from anthrax infections. Those are the kinds of things that we are developing. As I say, I am pretty sure we are going to have the drug half of that, and I am fifty percent sure we are going to have the vaccine part of that. TR: Doctor, we were getting some headlines out today that Beijing has closed its schools as they are now seeing a second wave of infections. I am curious about what your thoughts are on a second wave. I am also wondering that maybe with some of these vaccines, if it gives us the disease, our bodies can learn to fight it. As long as it prevents the most severe symptoms, that helps herd immunity and helps us to recover from this faster. What were you thinking about a second wave, schools reopening, and herd immunity? WH: Those are a bunch of questions all rolled into one. I will try to take them apart. First of all, what is happening in China, specifically in Beijing? For the last six weeks, they have had no cases. All of a sudden, a few cases popped up. That is what we can expect in the most successful public health measures to contain this disease. No cases for a long time with the exception of some sporadic cases. You have to do everything you can to control it before it spreads. I am pretty sure they are going to do that. That is what you can do without a vaccine or without a drug, and not only are they doing it, but they are doing so effectively. We should be lucky to get there. Rather than zero cases for six weeks, we have had over twenty thousand cases a day for more than two and a half months. We still have twenty thousand cases a day for two and a half months, so we are very far from where we would like to be. Now, the next question you asked is whether there is such a thing as herd immunity. I do not think it exists for coronaviruses. The way we reason and the reason we think that is that a long time ago, coronaviruses got into the human population and every year, those selfsame viruses come back again and again and again, infecting the very same people and giving them the very same thing. When I look deep into this virus, I am learning more about it each time. This is a very complex virus, and it has at least twenty tools at its 1776
disposal to change our immune system in its favor. Part of that change is that it says, “ok get rid of me today, but I am going to come back tomorrow.” That is how it evolved. It is cracking our immune system’s code. It cracked it a long time ago, so it knows how to do that. These viruses are very likely to come back, so that is why it is going to be harder to develop a vaccine. It is also the reason why this is going to be around for a long time. There is no herd immunity for the current generations of cold viruses that infected us for decades and longer.
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Interview With Dong Lyu June 18, 2020 | Interview
Dong Lyu (DL): What do you think about CanSino in relation to the other companies like Moderna and the Oxford vaccine? William Haseltine (WH): I have read the Lancet paper that was published by CanSino and I have read most, if not all, of the other papers that have been published as well as many of their public announcements. There was a recent public announcement by Sinovac describing their work in humans, but not providing us with the actual data. I commented on their absence of transparency, which I think is egregious. I think if you are going to talk about it, you have to have data. Now, CanSino has the advantage of having published their work in Lancet on May 22nd, so it is available to be looked at. In my opinion, it is equal in merit to the work that has been done by all of the other vaccine companies of which you have heard a lot. I do not see any real distinction between the work that they are doing and the work that is being done by Oxford and AstraZeneca. They are basically using the same kind of vector and the same kind of antigens. I would say that there is a difference in that CanSino is using one type of adenovirus, a human type, whereas the Oxford group is using another, a chimpanzee. However, both of them have the disadvantage that if you are going to repeat vaccination, neither one is a vaccine of choice because you make antibodies to the vector itself, whether it is a chimp or a human adenovirus. I would say that those two seem quasi equivalent, about the same quality, to me. You can expect very similar results from these studies. It is far too early to know whether any of the preliminary data that has been released by any of the groups, whether it is in primates or humans, is likely to be effectively preventive. I will give you a case in point. In regards to HIV, you find the highest T cell immune responses and the highest C cell immune responses. They are off the charts, yet the virus is resistant to inactivation. Now you could say that few, if any, of the antibodies that are made in HIV are neutralizing. On the other hand, you can 1778
say there is not always a good correlation between neutralization and protection. You can also note that in many coronavirus infections, even though the immune response can temporarily clear the virus, for the most part, it does not give lasting immunity. So there are serious questions about whether a vaccine can do better than natural immunity does. Those are questions we do not know. I would say what is also clear from almost all the work on coronavirus vaccines of humans, whether it is SARS, MERS, or COVID, is that people have failed to protect the nasal mucosa. When they tried it in monkeys, they failed. We do not know in humans, but every vaccine that has been tried does not protect against infection of the nasal mucosa. Will it protect from all aspects of the disease? Will it speed up the infection by creating more people who are infected and can shed the virus through their nasal passages to others? Will the virus travel from the nose to the brain as we predict? We do not know the answers to these questions. I would say that CanSino is in the game. It is about where the other so-called leaders are. Whether anybody will cross the finish line with efficacy and safety data is unknown. In particular, I have written and commented on the fact that in the six months that are left before the end of the year, you cannot do a year safety trial. Under any circumstances, you are not going to know the long term effect of these vaccines. It is impossible to know. Unless you test a hundred or two hundred thousand people with your vaccine, you are not going to have an adequate idea of what the safety profile is for a vaccine that is intended for billions of people to use. One out of ten thousand effects for a billion people is a hundred thousand very ill or dead people. You have to be extraordinarily careful. In addition, we know that some coronavirus vaccines for other strains elicit negative effects. If you have been vaccinated and then become infected, you have a negative effect. It worsens the disease and it can worsen it in several ways. It could either worsen it as a general increase of infection, or it can cause lung diseases. We know vaccines have done that. Does that mean it is impossible? No. Does it mean that this company has an advantage over the other companies that are using adenovirus? No. But does it mean that they are in the game? Yes.
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DL: What do you think about the viral vector technology? What do you think about its chances of developing a viable shot for the coronavirus? WH: While viral vectors have a reasonable shot, the problem is that they are limited in the number of antigens they carry. Typically the ones that are being used carry the S protein. Some carry the N protein. Some carry the S, the N, and the M, while some carry the S, the N, and maybe the E. At this point, we do not know what the correlation, if any, is for protection. There are recent studies on the natural T cell responses that show that both M and N seem to be important for T cell responses. Are those important for protection? We simply do not know the answer. The limitation for most of the viral vectors that are being used is that they use only a limited range of the viral proteins. That is not true of the killed vaccine, and it would not be true of an attenuated vaccine, but it is true of the adenovirus vaccines. DL: When you look at the data in the Lancet paper, what worries you the most? What do you think the biggest challenge for CanSino is? WH: If they really want to have a safe and effective vaccine, the biggest challenge is to line up two or three thousand volunteers. That is the biggest challenge for any of these groups. A hundred people is a tiny group. It is a drop in the bucket, and it does not give you an idea of how safe this is. The primary concern with vaccines is not that it is going to work, but rather that it is going to injure a lot of otherwise healthy people. The difference between a drug and a vaccine is you give a vaccine to healthy people, and your risk tolerance is enormously smaller. The risk profile is what takes most vaccines years and years to develop. You have to minimize the risk. That takes time and a lot of people. The more people you are going to be testing, the longer the time you have to take and the more people you have to use. There is no way to do the proper tests for anybody in six months. It cannot be done. If something is approved though, it will be an exception to what the normal practice is for vaccine approval, which is probably not a good idea. DL: So you think the story is still out on safety, even if they have done phase one. WH: Phase one just says the vaccine is not going to kill people right away. To do a real safety trial for a vaccine that is to be used 1780
by three billion people, you have to test hundreds of thousands of people. If you do not, you are running a risk. DL: So until the completion of phase three. WH: No, nobody is talking about more than a hundred thousand people. Oxford and AstraZeneca may be talking about thirty thousand people, but that is still too small of a group. Even then, they are not talking about treating them for very long. It really depends on what the risk tolerances of people are. People are not particularly tolerant of risk for vaccines anywhere in the world today. A COVID vaccine that has unpleasant side effects will set back vaccination around the world in a very serious way and will threaten many poor people all over the globe. COVID is already disrupting childhood vaccination programs. DL: I just wanted to know your take on the existing immunity. How do you think it will affect how successful the final vaccine will be? WH: There is nothing particularly unique about the CanSino vaccine.We are still learning the rudiments of the human immune reaction to this virus. They have only had six months to study it, which is a short time. We are learning more and more about it as we go. Some of the things we are learning are not reassuring, while others seem to be more reassuring. The answer is we simply do not know. Until we can follow those first people infected for a year or two years, we are not going to know how long immunity lasts. Wuhan is a great case. They had it first and had about two months before other people had it. Follow those people's immune reactions over a one to two year period and we are going to get some idea. We already know that the immune responses are very complex. They are not simple like they are for some other viruses. The virus has about twenty different ways to alter our immune response. This is not a passive virus. It goes in, and it is very active in derailing our immune response. It may even be mutating to get better at that. There is an indication that some strains of this virus are more efficient than the first ones that appeared in down-regulating the primary immune response, the adaptive immune response. And there may be more. We have to wait and see how this virus adapts even further. Now, there are mutations that allow it to be transmitted ten times better. The strain that was originally in China is now mostly replaced 1781
by a different strain that seems to be better, more readily transmitted. We understand that in some detail, so we are shooting at a moving target. You asked me about the CanSino vaccine. Nothing special at all that distinguishes it from other attempts, other than that they published the first data of human trials, which means they are in the game. However, it does not mean they are ahead, it does not mean they are behind, and it does not mean they will win. It also does not mean that any vaccine will be okay. It is like you are calling a horse race as the gate just opened. You cannot tell. DL: What about the preexisting immunity to adenovirus? How is that going to render the final vaccine? WH: It may limit it, but it limits the other adeno vaccine as well if you want to go back and re vaccinate. Now, they are saying that the first round will not do very well. We are going to have to go back with a booster. Then, every year, we are going to have to go back again and all the adenovirus vectors will fail at that point. They have to do something else, so it is not particularly bad. DL: Would this be the same challenge for the Oxford vaccine as well? WH: Second time around it is going to be the same challenge. If they are planning on two doses, are they planning to use the same vector to give us a booster? They are going to have the same problem. You have to use it once and that is it. DL: That is exactly what they are going to do in their upcoming trial in Canada. I was just looking at their posts on clinicaltrials.gov, where they posted the details of their phase one and two clinical trials in Canada. In addition to testing the two doses that they have already done in China, they are also going to have a group that will be administered with the shot twice with the interval. WH: It is not going to work as well the second time around. That is the way it is with these, but do me a favor and send me that report you have about their description of their Canadian clinical trial. I have not seen that. DL: Sure, I will send it to you. Actually, another question I wanted to ask you is that it also means that the bar is very low for a vaccine. You touched upon this. If you look at the vaccine developed by Oxford when they do the challenge trial for animals, it does not even prevent those animals against infection. 1782
WH: I would be surprised if the CanSino vaccine did as well. I do not think it does. DL: In the Lancet, CanSino mentioned their animal challenge trial, but they did not do it on primates. They did it on ferrets. WH: That does not count. Ferrets do not count. DL: Why do you think they only did it on ferrets? We do not know what other animals they have done challenge trials against. Why do you think they have not published the data for animal trials? WH: I am not a mind reader. I cannot tell you. That is asking an intent question, and I try to never judge people's intent. I just judge what I see. DL: What about the challenges of late stage phase three trials for China's vaccine, given the infection is so low? WH: They would have to do them elsewhere. There is not enough infection in China to do the studies today, but there are 120,000 people a day infected. There is no shortage of people. DL: We are seeing the political environment becoming increasingly hostile towards Chinese vaccine developers. The US and a lot of Western countries are blaming China for covering up the epidemic in the early days. That does not do good for a lot of Chinese companies wanting to test their vaccines overseas. We do have a lot of people infected in the US, but I am just not sure how likely it is that a Chinese company would be able to test their vaccine there. WH: There are plenty of other places to test it. I would recommend South America. China has good relationships with many South American countries. There are many places and Africans, so there are going to be more people to test it on than you can imagine. It is not going to be a shortage. DL: One last thing I wanted to ask you about is how has CanSino’s track record been with developing vaccines? WH: I have no idea. DL: They claim they have developed an adenovirus vaccine for Ebola. WH: A lot of people did that. Most of the people who developed these have used the adenovirus vectors for Ebola and some for other diseases as well. However, I am not familiar with that work, so I cannot comment.
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DL: The success in those vaccines won't say much about their chances of success with this vaccine, right? WH: Merck has vaccines against twenty-five different organisms, but it has not developed neither an HIV vaccine nor a herpes vaccine. It has not effectively developed a malaria or TB vaccine. Some organisms are easy to protect with vaccines and some are difficult. I have to go, but thank you for your time. I hope it has been helpful. Please do send me that article. DL: Thank you for taking the time to do this. I will send you the details of their clinical trials in Canada.
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Interview With Bloomberg News June 22, 2020 | Interview
On "What'd You Miss This Week," Bill Bratton, the former police commissioner for Boston, Los Angeles and New York City, who now serves as senior managing director at Teneo, joined to discuss the federal efforts to reform police. James Norman, CEO and co-founder of Pilot.ly and partner at Transparent Collective, came on to talk about his experience as a black executive and founder in Silicon Valley and how the technology industry needs to change to achieve greater racial equity. Dr. William Haseltine, who pioneered the first HIV/AIDS treatment and developed the first drugs based on the human genome while at Harvard Medical School and now serves as the president of ACCESS Health International, explained the cheap, widely available drug showing major promise to treat COVID-19 patients in the U.K. Then United Airlines Chief Communications Officer and former White House press secretary Josh Earnest came on to talk about the airline's efforts to revive the summer travel season and how the private sector can enact policies to fight racial inequality.
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Interview With FOX News Dana Perino June 22, 2020 | Interview
There is no transcript for this interview but the link is available here: As US coronavirus cases continue to spike, when will it be safe to see high-risk loved ones?
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Interview With CNN Anderson Cooper June 30, 2020 | Interview
COOPER: He sprays a mask on his face every day for vanity, but an actual mask that would protect other people that -- that he just can't do. Joining us now, CNN chief medical correspondent, Dr. Sanjay Gupta; also Michael Haseltine, a preeminent researcher formerly at Harvard University and the recent author of "A Family Guide to COVID." Sanjay, Dr. Fauci is warning today that if -- I mean, if basically, we don't do something, if we don't turn this around, if people don't start wearing their mask, the United States could see 100,000 new cases a day. DR. SANJAY GUPTA, CNN CHIEF MEDICAL CORRESPONDENT Yes, you know, I mean, it's mind numbing to hear a number like that, right? It's really -- it's really frightening. I was not surprised at the number. I mean, we're seeing what the growth of these cases. It's like a big, you know, freight ship in the middle of the ocean. It's gaining a lot of steam and it's going to be hard to slow down. I think that's what he was referring to. What I was surprised a little bit, Anderson was that he even gave a number. I mean, he's always so careful with these things. He typically doesn't give a number because he doesn't want to be pinned down to it. And if he does give a number, it's usually a conservative estimate, you know. Anderson, you'll remember, it was just a couple of months ago, and we were hearing that 60,000 people were likely to die by August 4th, according to one of the models that you and I were talking about, and that was horrifying. Right? And now we're here at the end of June, and it's double that. So, I don't know. These models, you know, it's tough to make anything of them, but I think there's no question the numbers are going in the wrong direction. Absolutely.
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COOPER: Yes. Professor Haseltine, first of all, I apologize. I think I called you Michael to begin with. It's William -- William Haseltine, Professor, what's your reaction to the testimony on Capitol Hill today and the spike in cases in large parts of the U.S.? DR. WILLIAM HASELTINE, CHAIR AND PRESIDENT, ACCESS HEALTH INTERNATIONAL: Well, we're now reaping what we've sown over the past months. That is we failed to control this epidemic in a number of our southern, western and the south part of California. We just didn't do what we needed to do. And the moment we relaxed, there was a big base of infection that just exploded. And so those places like New York City that took it seriously, we've gone from 10,000, 11,000 people down to 500 to 600 a day. We're not where we need to be, but we're doing a lot better. But the whole rest of the country didn't pay attention, didn't believe what everybody was telling them, and this is the result. And now, we hope people will start behaving more responsibly. We hope that leadership will behave more responsibly, and we can begin to put this genie back in the bottle. COOPER: Professor, do you really think that's going to happen, though? I mean, it seems like you know, the President made a decision early on, just to wash his hands of this and to, for reasons that are pretty obvious, just get people trying to reopen stuff so the economy picks up, so it reflects well on him. I mean, it takes political courage and will to really make a change -- and do you believe it's possible to put the genie back in the bottle? HASELTINE: I think it's maybe not possible to put our President back in a bottle, but it is possible for the American people. We're a smart people. I have great confidence in my fellow Americans, and I believe that this situation is now so grim and is getting worse by the day that everybody is going to begin to understand, it is their responsibility. And we don't have a national leadership. We're going to have local leadership. You can already see that happening. The local leadership in this country is saying, wait a minute, this is my state. This is my city. I've got to protect it. I don't care what the national government is telling me. I've got to protect my people. And I'm seeing that response and I'm very heartened by that response. And I think you're going to see the mayors and the 1788
governors singing a very different tune from now on. They know it's in their backyard and it's their job to take care of it if no one else does. COOPER: Sanjay, I mean, is it too late for contact tracing in some of these places? GUPTA: I think it'd be very hard to do contact tracing right now. I mean, these numbers are just too big. I mean, you know, you think about contact tracing 40,000 people every day. That's an entire sector of our society that would need to be devoted to that. You're calling people, you're trying to find all of these contacts. People don't answer the phone. You've got to go to their house or their apartment, knock on the door. I mean, it's a lot of work. That's why you want it to see the numbers come down to a manageable level. And again, Anderson, you remember that even a couple of months ago, people like Dr. Tom Frieden were saying, we would need 300,000 contact tracers in order to do this right -- Tom Frieden, former head of the C.D.C. That was back then. That was when the numbers were what they were back then. So, I think now would be really hard. That's why we've got to bring these numbers down. I should say as well, I agree with Professor Haseltine. You know, I think that one thing we did see in some of these places around the country, even when places started to reopen even where I live, and things were reopening, there were groups of people who just immediately took advantage of that. But for the most part, things -- people still stayed home for a period of time. They still wore masks in certain areas. So, if not the policies, then the people, may help lead us out of this. COOPER: Yes, we've got to take a quick break. When I come back, we're going to talk more with both Sanjay and Professor Haseltine. I want to ask about this new strain of the flu that's been uncovered and what that may add to the mix this fall. We've also been trying to track down Florida Governor, Ron DeSantis for days to ask him about the rising number of cases in his state and whether he regrets opening so early. He's been difficult to find, put it mildly. Randi Kaye got to him today. We'll show you how that went -- ahead. 1789
COOPER: We're back with Professor William Haseltine and Sanjay Gupta. We've been talking about testimony today from Anthony Fauci and others pointing to the outbreak in this country getting almost unimaginably worse in the months ahead, but if that's not enough, there could be more -- another virus that could turn ugly. Sanjay, what are you learning about the new swine flu that the Chinese researchers discovered? GUPTA: Well, you know, this is a part of a surveillance program where they've been looking at these pigs, swine in China and for the last several years, they basically looked to see if there's any viruses that are of concern, and mostly there haven't been there. There may be a virus one year, it disappears the next year; but one virus sort of stayed constant over several years, they are calling it G4, that's the name of the virus, and they also found it then in the workers who are handling these pigs, about 10 percent of the workers who handle these pigs. So this was a zoonotic virus and made the jump from animals to humans. So that was the first point of concern. What it does not appear to do and this is significant is actually move them from human to human. That's when you know, obviously as we saw with this coronavirus, things get really concerning. But this is what you know virus hunters do, Anderson. You and I spent time with them in various parts of the world. This is the type of surveillance. Right now, this is something they're keeping an eye on, but the quote that I heard was, you know, not something to get freaked out about right now. COOPER: Professor, in terms of what Dr. Fauci said about, you know, possibly getting up to 100,000 new cases every single day. How do we avoid that? I mean, what is -- is it just the things we now know, which is, you know, social distancing, staying at home as much as possible, mask wearing -- all the rest that we know or is there something more and new that has to be done? HASELTINE: There is not going to be time for very much new. Time will bring drugs to bring this under control. Time may bring vaccines that will bring this under control. But for now, there are new studies that show that what we're talking about -- wearing masks, social distancing, staying home, only doing what you really have to do can reduce transmission by twenty1790
fold. It can change it from a curve that goes up to a curve that goes down. That is a big change. And I think that's what every American needs to hear. Their individual actions are going to determine what happens to this infection going forward. If that number is going to be 100,000, and then 200,000 a day, that's because we made it so. If that number goes from 100,000 to a thousand a day, it's because we made it so by our own actions. It is time for us to understand that each action contributes to what this virus will do. We can't control it, but we have to take what people are telling us seriously. COOPER: Yes, I mean, Professor, has there ever been, you know, a virus or disease that's been brought under control without you know, firm leadership from the place where it's in? HASELTINE: You know, I can't answer that question. But I can tell you, I grew up during polio days, and everybody knew how to behave. We couldn't go in more than groups of three boys at a time. We couldn't go to the swimming pool. We couldn't go to theaters, and everybody did it, because everybody knew what would happen if they didn't. And so, it wasn't so much at that time that our leaders told us. We had a cultural understanding. We have forgotten, because we've been so lucky since the war to have antibiotics and vaccines that we think we're privileged not to have disease. Well, this is a reminder. We have to go back to some of those older patterns. It isn't that we didn't have them. It is that societies can't behave that way. So, we've forgotten how to do it. And it's time to remember. COOPER: Sanjay, I think it's such an interesting point. I mean, you know, the idea of citizenship, of you know, being part of a community, and that is not just, you know, me it's we, and the emphasis, you know that you have to think about the we in all of this. GUPTA: Yes. HASELTINE: And there's no government there. COOPER: Sorry. Go ahead. HASELTINE: There is no government that can do this. No government can control a whole people. We have to do it ourselves. We have to internalize it. 1791
COOPER: Sanjay? GUPTA: They can't control -- I think that's true. But I will say, I think that we have suffered a little bit from the mixed messaging in this country. I mean, I think that if people were certainly clear to gradually -COOPER: The President of the United States leading the way on example, at the very least. GUPTA: Yes, and also just like basic things where there was these criteria that were released from the White House, you know, in terms of when state should reopen. Pretty simple criteria to follow. I mean, you know, that's what needed to be done. And then, you know, the next day it was like, yes, but we're going to go ahead and open anyway. I wasn't sure at the time whether any state really followed the criteria. Had we done that, we'd be in a much different position now. And it was enabled -- these criteria. I mean, there was no law enforcing it, but it was enabled to not follow the criteria. So, the question about leadership is a good question. But I think part of the problem is that we have suffered from mixed messages. There are people who still believe this is not a problem right now, and it is. COOPER: Yes. And frankly, with the President announcing if the Virus Taskforce policy recommendation on wearing masks at the very same moment, he does that, you know, not even out of, you know, with a silent voice, he says out loud, you know, it's only voluntary, you don't have to do it and he's not going to do it. Sanjay, Professor Haseltine, thank you so much. Appreciate it. More now in Florida, which reopened early and enthusiastically because as Governor Ron De Santis said at the time, Florida is not New York.
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Interview With MSNBC Stephanie Ruhle June 30, 2020 | Interview
Perry Alexander (PR): Dr. William Haseltine, an infectious disease expert and president of ACCESS Health International. His new book is A Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children. We got several of them to start with. Doctor, we appreciate your time. We have seen the states reversing their reopenings or putting things on hold. A lot of this likely the result of what happened over the Memorial Day weekend. Now we are heading into the 4th of July weekend. What is your primary concern that things are only going to get worse as we head into another holiday break? William Haseltine (WH): Well, I think we are all concerned about what has happened. And the issue is not so much that you are opening too soon in all these states, it is you never did what you should have done in the first place to control the infection. Many of these governors were lax in following the recommendations of the CDC and the government which were very clear. Make sure people wear masks, keep social distance, wash their hands and stay home as much as possible. They just did not follow what was clear advice. They had an underlying problem and the moment they loosened it up, it just exploded. The only way to control it again is to make sure that everybody exerts their own personal responsibility. This is a virus that is transmitted from person to person. It depends on individual action to protect yourself, your family, and everybody around you. PR: Doctor, the simple truth is that Americans have seen a lot of doctors like yourself. At this point, their eyes kind of blur hearing this sort of similar message, but in a sentence or two, to people who are waking up right now and seeing these stunning figures, what do you say to them as we head into the summer? WH: You know, what I would say is it is clear that this virus can be defeated without a vaccine or without a drug. All people have to do is follow the rules. Look around the world. You look at Asia. 1793
You look at Europe. You even look at New York City. We are not famous for being ruly. We are famous for being unruly. At least, we were able through our own individual actions to stay home, wear masks, keep social distance and drop the infection level tenfold. That is what we have done in New York. That is what we have done in New Jersey. That is what we have done in Boston. PR: Let me ask you about the article you just put out in Forbes basically saying that our best hope for relief from the virus may not ultimately be a vaccine and may be these antiviral treatments. Tell us sort of what they are and how soon they could be widely available. WH: Well, there are two types of antiviral treatment. Those that use antibodies. Those are purified antibodies not from your blood but you make in the laboratory. Those can be essentially the mini vaccines. You can give the people and they will be immune from infection for a couple of months. They cannot only treat the disease, they can make you immune from infection. Those are being developed. And then there is another class of drugs called the protease inhibitors. Those stop a key part of the virus. Many people may know that hepatitis C is curable. That is because there is a drug that stops the protease. HIV, drugs that stop the protease. We can use those drugs. How soon will be available? I think by the end of the year and I think what they can do is give us the space to make sure we have a safe and effective vaccine. If we get these drugs approved, we do not have to PR: So doctor, WH: Go ahead. PR: No, I am sorry to interrupt. As we heard as it relates to a vaccine, Dr. Fauci has said he thinks it possible to get a vaccine perhaps by the end of this year. I guess the questions now are will it work and will it be safe and what is the risk to this expedited effort? WH: I think you have mentioned both of them. We may have a vaccine. It may be approved, or at least Emergency Use Authorization by the FDA, but I can guarantee you we will not know how effective it is and we will not know how safe it is. We may have one. That is why I am pushing the idea that drugs are the way to go in the short term to give us space to know whether a vaccine is safe or effective. So, yes we are likely to have one, but we do not know whether it is going to be safe or effective. And the other thing I would say about Dr. Fauci, if you listen closely, he says 1794
if everything goes perfectly. If everything goes perfectly and then he adds, it almost never does. So that is what it is going to take and even then we are not going to know how safe and effective it is whereas we know with viruses very much like this, respiratory syncytial virus for children, we can treat them and we can prevent it with antibody drugs. PR: Right. Dr. William Haseltine, we appreciate your expertise and your time. Obviously, a message a lot of Americans need to hear right now. We thank you.
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Interview With Caixin Chinese News Service June 30, 2020 | Interview
Female Speaker: There are forty kinds of vaccine tests in developments around the world and there are five kinds of vaccine platforms, including viral vector vaccines, RNA and DNA vaccines, and live attenuated vaccines. I know you have expertise in public health, especially HIV. In your opinion, what is the difference between these vaccine platforms and what are their advantages and disadvantages? William Haseltine (WH): There are many different vaccines under development for COVID around the world. I know of six that are in human trials today. Those fall into three general categories. First is using whole killed virus. That is very similar to the Salk vaccine polio virus. Second, there are viruses that are carried in by another virus that does not itself cause too much trouble because it is an adenovirus. It is a defused virus and it carries it in and there are several attempts to do that. Lastly, there are RNA vaccines that have never been tried before. I would say the highest risk and perhaps the most dangerous ones are the RNA viruses. Not because they are inherently dangerous, but because you have to put them in with very strong adjuvants to make them active. The adjuvants themselves can cause trouble. It is an unproven technology with serious adjuvants, so I would say that is the highest risk. The adenovirus and the kill vaccines are in different proportions. People have successfully made killed vaccines. I would say that is probably the highest probability for success because we know that it has worked. Nobody has really made an effective adenovirus vaccine yet that is approved for use, so it is somewhat uncertain. Although there is some evidence that shows it will work, we do not know how well it will work. Let me tell you a more general problem. If you look at the natural history of viruses, they tell you a story about how easy a vaccine is going to be. Like polio, the story was that the virus comes in, you get it once in your lifetime and you are immune the rest of 1796
your life. That is a story that tells you it should be okay. HIV, on the other hand, is a different story. You get it once and it stays for life. No matter what you do, you cannot get rid of it. That is a different story. Thus, it is not going to be easy to make a vaccine. SARS-CoV-2 is an in between story. I call it a get it and forget it virus. The reason for that is if the virus comes in, you handle it if you are successful. Then, it goes away and the same virus comes right back and gets you again. Your body forgets it. That means it is going to be more difficult. We cannot be sure. There is much uncertainty around this vaccine. Female Speaker: The problem is that we do not know about the antibodies? WH: We do not know how long they last, and we do not know if they will be protective for everybody. I will tell you one thing we do know. We know that none of the vaccines that are currently being tested prevent infection. A vaccine should stop infection, but these do not. In all the animal studies that have been done for this virus, MERS, and SARS, they do not stop nasal infection. They may stop the virus from growing in other parts of your body, but they do not stop it from getting into you and growing in your nose so you can spread the virus. If they do not stop that, the question is, what else don’t they stop? A vaccine is not a shield. Rather, a vaccine is an early warning that says, “We have seen it before.” Let me just give you something to think about it. Most people do not realize our nose is right next to the brain, but it is. Your nose goes right back behind your eyes. That is a thin bone from your brain, and the nerves go right through that. This virus goes right through that and can get into your brain. Thus, if it is in your nose, it can be in your brain. I am worried about these vaccines. That is why I am thinking more and more about our success with drugs. Another virus, respiratory syncytial virus, affects children, specifically babies. It goes in through the nose, and we can solve that problem. Do we have a vaccine? No, but we have monoclonal antibodies that if you give them to babies in the susceptible period, it protects them for up to four months. It is like a mini vaccine. It protects them from just the period that they need it. That is a monoclonal antibody. That is not a vaccine. After four or five months, it goes away, but you need it for that period. We can do the same. There are many groups 1797
around the world and some in China. One Chinese group just published a very important paper in Nature, one of our best journals, showing that they have two monoclonal antibodies that do exactly what you would want them to do. They did beautiful work. They showed exactly how the monoclonal antibody touched the receptor. It was exemplary work. They are one of many groups doing this. We are going to have these antibodies, likely RSV antibody soon, which will be the equivalent of a treatment and a mini vaccine. This means that if you are exposed, you are going to be protected. Let us just take an example. Suppose somebody in a family is infected, a mom or a dad in family. Then, everybody in that family could get these monoclonal antibodies, and will not get the virus and get sick. Is that not what we want? I would give that a ninety eight percent chance of success. I would give a vaccine a fifty percent chance of success. The vaccine also has unknown risks, so it can be dangerous. On the other hand, we pretty much know the risks for the antibodies. There are a hundred antibodies already approved for human use. That does not mean they are totally harmless. You have to check them for safety, but a hundred different ones are already approved, especially for viruses that get in through the nose and for babies. I think we will be in good shape soon. I would hope we get these drugs used and make sure we do all the tests necessary to know how safe and effective these vaccines are. Let me mention one other thing about vaccines. With a vaccine, you give it to a fully healthy person. You something to three billion people, it better be safe. Suppose you have a one in 10,000 adverse effect. For giving it to three billion people, that is 300,000 bad events. What do I mean by a bad event? Lifetime trouble, death, and other terrible things. That is a lot of people. You better be sure it is safe, but it is hard to know if something is safe. Female Speaker: It is very appropriate to let the vaccines be applied to the general public? WH: Exactly. Drugs are different. If you give drugs to people you know are likely to be infected because they are exposed, such as healthcare workers that are taking care of these people who are sick, you give it to them, which is reasonable. However, to give something to everybody that you do not know, what is going to happen? I would say there are questions with vaccines. Drugs are far
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more certain, and they are coming along pretty fast around the world. I am happy to say that China is doing a fantastic job in developing these drugs. There is another beautiful paper from a Chinese laboratory showing inhibitors of the protease, which is another very good target for these viruses. These are two beautiful pieces of work on drug development published in the leading international journals. Female Speaker: What do you suggest? I just want to understand your perspective. What you were describing, is it the same as the concept of herd immunity? WH: Not at all. Personally, I do not think herd immunity exists. This is, as I said, a get it and forget it virus. Coronaviruses fool your immune system. After a year, you do not even know you have had it, and the same virus can come back and get you again. We know that for sixty years of watching coronavirus cold viruses, every year they come back. You make antibodies, they go away, and the virus comes back and gets you again. We think that is likely to happen in this case. There is even evidence now that immunity begins to fade. Again, a wonderful Chinese paper showed this in a series of studies, and they are the only ones that have had the infection long enough to know you can watch the antibodies fade over time. Over a couple of months, they start to go away. Female Speaker: In two to three months? WH: Yes, so that is telling you that it is not going to be an easy job to make a vaccine. Drugs are different, though. I do not think there is herd immunity. I do not think that will ever happen. If it could happen, it would have happened for these cold viruses a long time ago. We have been dealing with this for probably thousands of years, but at least we have watched it for the last sixty years and it has not happened. When these cold viruses go through the population, they infect a lot of people, sometimes thirty percent. If you look at most people, they have antibodies; at least half the people or more have active antibodies to these viruses. If there was going to be herd immunity, you would see it, but you do not. Not only do they have active antibodies, they also have T cells. That is the other part of the immune system. They have T cells, and they have B cells that are working. It does not protect after a year. I am not hopeless. I am very positive. We are going to get through it with science. Our drugs are going to do it and eventually, our vaccines may, but our 1799
drugs are definitely going to get it. We are going to knock it out, and we are going to be able to cure people. We are going to be able to treat, cure, and prevent this infection through drugs, if not through vaccines. Female Speaker: Why are all the governments around the world just investing tremendously in the vaccines? WH: Governments are investing in vaccines, but they are doing it more for the economy and for political purposes rather than health. I will predict that two months from now, you are all going to be talking about antiviral drugs, and maybe even vaccines too. They are the most immediate treatment we can get. As I said, I give them a ninety-eight percent chance of success, while I give vaccines a fifty percent chance of success. You are going to see people start talking about the tangible hope and it is on the horizon. You can see it coming with these beautiful pieces of work published in the international journals. Female Speaker: I have also read those journals and they are talking about where the antiviral drugs can target. WH: It’s not so much targeting the cell, but rather targetting the virus. The great thing about viruses is they are not us. They have pieces, which are shaped differently. It is all about shape. Their shapes are different from our shapes, so you can find things that bind and stop their shapes from working that do not touch us. That is what you want, and those are what are being developed. The antibodies touch their shapes and stop them. The small molecule drugs get into their little crevices and stop them from working, and it does not bother us because we do not have those shapes. That is why I do not favor treating the targets that are our own targets, but treat what the virus brings in with it. That has been very successful for HIV, for example. We have no vaccine, but you can cure and now prevent it. A wonderful paper on HIV has just been published explaining that you can give one shot and it protects people for two months. It is like a mini vaccine. I think the concept people should have is drugs can be mini vaccines. Female Speaker: So the drugs kind of assist the immune system? WH: Not at all. They work differently. They stop the virus so the immune system does not even need to work. They just stop the virus. 1800
Female Speaker: People talked about lots of drugs before, including antiviral drugs. But right now, in the U.S. only remdesivir is mentioned. WH: Remdesivir is not even an antiviral drug. There is another beautiful paper from China that shows that the drug does not prevent people from dying, and it does not even change the amount of virus that people have. I do not know why they call it an antiviral drug. Maybe it is in a test tube. It surely is not in people. We are at a stage where we do not quite yet have the tools we need, but those tools are coming. Of course, you have to treat people as best you can. You use the tools at hand and doctors are getting better. For example, if somebody is critically ill, we now give them anticoagulants, so the blood clots do not form. You give them dexamethasone to calm down the immune system if they are very late in disease. Let me just say, do not use dexamethasone early because it accelerates the disease. It is a fine use of that drug. Putting people on their stomach, not on their back, is another way to treat people. All these things are keeping people alive. You use the tools you have and you use whatever drugs you have. Pretty soon, better drugs are coming, real drugs that do not act around the problem but act at the very core of the problem to stop the virus. That is what you need to do. Female Speaker: You think new drugs will come out? WH: Absolutely. Female Speaker: But after the clinical trials, people are kind of disappointed. WH: No. Nobody has done that. You are absolutely incorrect. People have not done the clinical trials yet with these drugs. They did not exist. Now they do, and now we can try them. I am pretty sure they are going to work. People tried with a kitchen sink of things that existed. There are lots of things. Chinese traditional medicines, Indian traditional medicines, hydroxychloroquine, you name it. None of them worked very well. The drugs I am talking about are new compounds specifically designed to stop the virus from growing and they will work. Female Speaker: Sometimes the virus would change its RNA, but that is the problem for both vaccines and antivirals, right? WH: It is.
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Female Speaker: Can we develop the antiviral drugs to be effective? WH: Let me talk about virus variation. The first thing that is interesting about variation is sometime around February, the virus in Europe changed to become more infectious. It became ten times more infectious, so you needed ten times less virus. That virus has spread all over the world now, even in China. A virus that was not so infectious got to Europe, it changed, and it became more infectious. It came to the US, it spread all through the US, and it spread all through South America. That virus changed and changed to be more infectious. Viruses can also change to be resistant to drugs. HIV is a master of change. How do you cope with that? Use two or three drugs in combination with antibodies. You do not use one antibody, but rather two antibodies. It is harder for a virus to change two things simultaneously. What you do is you use combination treatment. For HIV, you use two or three different drugs. If somebody becomes resistant, there are now about thirtyfive drugs approved for HIV. You have other combinations, so you can keep people alive for most of a normal lifetime. That is eventually what we are going to get for this too. There will be resistance to one, two, or three different drugs, but there are going to be many targets and many different kinds of drugs, just like there are for HIV. With HIV, I helped define the targets, and we found six or seven really good targets. Those turned out to be good targets. You can use them in combination. This is an even bigger virus. There are going to be more targets. I can count about five or six great targets right now that you could make drugs against. As we learn more about the virus, there will be more. This is a target rich environment for drug developers. I am happy to say that drug developers around the world, in China, the United States, Japan, Korea, India, and Europe, people are working like crazy on trying to make new drugs against these targets. It is a wonderful time, and we will succeed. Female Speaker: Right now, lots of vaccines are about to enter phase three. I am just a bit confused why the antivirals fell behind at this stage. WH: They did not fall behind. They only fell behind in rhetoric. They fell behind in the human consciousness, but not in reality. People want simple answers. It is simple to say vaccine because 1802
everybody knows about it. It is harder to say antiviral drug because people say, “Antiviral drug, what is that?” But tell mothers about respiratory syncytial virus, and they know it. Young mothers know that their babies could get this terrible respiratory disease, and that they can be prevented with an antibody cocktail that works perfectly well, so they use it to treat and prevent the virus. I think the word mini vaccine is probably a good way to describe it. I just came up with the idea to call it that this morning. Female Speaker: I think vaccines are more expected because people believe that once they get a dose, they can be prevented from re-infection for a long time. WH: Let me ask you a question. Is that what you think about the flu vaccine? If you get it one year, does it protect you forever? Female Speaker: No. WH: You know sometimes that is not true then. Female Speaker: For the antiviral drugs, such as the cocktail drugs, does it also mean that we need to take it once a day? WH: I think what is going to happen is you take it once you fear you have been exposed. For example, you are a healthcare worker and you are working in an ICU unit. You are breathing in viruses all around you. You want to take it every day, but suppose you are in a family and somebody in your family gets it. You only want to take it for about two weeks. Suppose you have been contact traced. The government calls you up and says, “You have been on the same airplane as somebody who was infected. We are tracing 278 people, and you are one of them.” What do you do? Stay home or take the drug. If you take the drug, you do not get infected. You do not have to stay at home or in controlled isolation for two weeks. You just take the drug and it is okay. At that point, everybody is going to want to know that they have been contact tracing because they can take the drug and be protected. That is going to be very good news, especially in a place like China right now, which has pockets of infection. They have to close down whole cities. Why close down the whole city when you can just give the people who have been contact traced the drug? Then, there would be no more problem. Female Speaker: Another question is regarding how people worry about the cost. Yesterday, the deal was set for the price of remdesivir at 520 dollars? 1803
WH: No, $3000 for the treatment. I was a pharmaceutical executive. Drug companies charge what they could get away with. It is as simple as that. Let me give you an example. The same company, Gilead, gets away with charging $80,000 for curing Hepatitis C in the United States for treatments, but in India, it costs $35 and in Egypt, it costs $45. Because it was so cheap, Egypt was able to treat everybody in their country of 4 million people who had Hepatitis C and cured them. There is no more Hepatitis C. We have not done that in the United States because we are looking at the cost per person of $80,000 and saying that we cannot pay that. Drug companies charge what they can get away with, and that is what Gilead is doing. The funny thing is most drug companies are screaming, “Gilead, you gave away this drug too cheaply. You are going to ruin all our prices. How are we ever going to charge a hundred thousand dollars for a drug again?” I say that they are charging way too much. It is going to cost you $10 to make this, and you are going to charge $3,000 for something that costs you $10 to make. There is some problem here, especially since they did not even discover the drug and it does not work very well. Female Speaker: There are lots of clinical trials and there are lots of them that have entered phrase three. We want to know when we interpret clinical trials data, what kind of data can convince the public and the government that a vaccine or antiviral drugs is safe and effective enough? WH: Let us take two different cases. There is a difference between drugs and vaccines. Drugs are used for people who are exposed or sick and you have a different risk profile. When you are going to use a vaccine for billions of people, you want the side effects to be very, very manageable. Therefore, you have to test it on a lot of people for a long time. That is why vaccines take so long to develop because you are treating healthy people. The first rule in medicine is do no harm. Here are healthy people and you are going to give them something that could harm them. If you are going to give it to billions of people, you better test it in hundreds of thousands of people, right? Because a one in a hundred thousand mistake that causes death is going to be 10,000 dead people per billion. That is the reality. Are you willing to pay that price? Maybe it was going to kill 10 million people. You have to know that, and the only way to know that is to do the test. Some of these effects last 1804
over a year. You are going to have to test it for a year or two. You cannot know it in six months. That is why when people ask me about when we are going to get it, while a government will approve a vaccine in six months, I guarantee you that you will not know how effective and safe it is. I would be extremely unhappy if people took a vaccine that they did not know if it was safe or not and gave it to 3 billion people. It could harm people, and it could harm the whole concept of vaccination. Female Speaker: We also noticed that because to them it is too serious and every country in the world is speeding up their vaccine clinical trials. In some countries, they may even skip the animal trials. We are very worried we are speeding up these clinical trials. It definitely means we are taking more risks. WH: We are taking much more risk. It is not just a financial risk. If we approve it, we are taking risks with people's lives. You risk people’s lives when there is a good reason to it. We are not averse to putting young men and women on the frontline and having them killed to defend ourselves. We understand that there are some things you risk life for, but do not risk life unnecessarily. If the drugs are going to form a stop gap, a wall to protect us while we develop the vaccines, use them. Do not do things that are unnecessary. Do not risk human life unnecessarily. Human life is the most precious thing we have. It is the jewel of everything. Thus, we should not risk that if we do not have to. I understand doing it if you have to, but not if you do not. Female Speaker: What is the difference for the clinical trials for antiviral drugs? WH: It is much faster. You give somebody an antiviral drug that works, and you will know in one to three days whether the virus has gone away. If the virus has gone away, you know you have won. Then, you only have to look at safety. Different from vaccines, drugs react in animals like they do in people. That is why it is much faster. You find a drug that is going to drop, because you are fighting not the animal, but rather the virus. If that drug gets in and stops the virus from growing in an animal, the chances are extremely good it will work in a person. The only difference is going to be if it is fully safe or not, but it is going to work. It is going to work in the human if it works in an animal. Thus, the trials are really fast. When we had the first drug for AZT, eighteen people were treated and eighteen 1805
people were not. All of the virus dropped. That drug was approved in months. All you have to do is show it is safe in people and not all that many people, because you are not going to give it to anybody who is healthy. All you have to do is show that it is safe and within two or three days, you know whether the virus has gone away. We approved HIV drugs just because the virus had gone away. Same thing with Hepatitis B. If the virus goes away, it goes on to approval. It can be very fast, and it will be fast. Female Speaker: Could you name some names of the antiviral drugs that you think are very promising? WH: They have very technical names now. It would not make any sense to anybody. FC483B or 11A seem promising. Does that help you? Female Speaker: Yes, thank you so much. Also, I know that you pay lots of attention to Chinese clinical trials. Do you notice any differences between the processing or anything between the clinical trials between U.S. and China? WH: I think it used to be that they were very different. There is now convergence. China is now working at world standards, but since you raised the issue, there is one thing that concerns me. That is the recent announcement that they are going to be approving an early stage vaccine for your military. I do not understand that. First of all, you do not have a big problem in your country. Why are you planning to send your military to some country that has the virus like India? What is going on? Why do you need to protect the whole military when you are not protecting the rest of the population? I do not get it. There is some issue and I think it is unwise, premature, and not needed. Other than that, China has been exemplary in its development of drugs and its transparency in the whole process. We are learning a lot about this virus from Chinese scientists and doctors because they have seen it first. Your pharmaceutical industry and your scientists are doing a superb job. They could not do better. They are as good as anybody else in the world. I am very, very pleased with that. I am not happy, but then who am I? I am an American sitting in a different continent, and I am not judging. I do not think it is the right thing for me to do, but since you asked that question, I will tell you I am concerned about the young people in your military.
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Female Speaker: Actually, your concern is also much of the public's concerns. In addition to the military, some state owned companies also give their staff some vaccines if they are sent overseas, but these kinds of regulations are less transparent. WH: It is up to countries to decide. They have the authority to do it. It is their people, and it is the people in the country who decide whether they want to have it done or not. It is really not for me to say. Female Speaker: We have one final question. You talk about a lot of concerns on the clinical trials, which is actually very helpful for us. However, we still want to know what the milestones and tipping points are that tell us that the vaccine or drug can work after achieving them. WH: For the drugs and the antibodies, it is very clear. The virus disappears from the body. For a vaccine, you will see protection; the virus does not grow in the body. That is not true for any of the vaccines today, though. In animal studies, all of them fail on that criteria. That means you have to back up and say, “Well, the virus is growing, but let us hope it does not cause a disease.” That is a big worry. There is no clear point. The point is the people who get infected do not get the disease. That is much harder to follow. First of all, you have to know who is infected and you know that not all of them get the disease. Only a small fraction need to be seriously ill. You have to look at that fraction and say, “They are vaccinated. Ninety-five percent of the people are getting infected and they are not getting sick, so my vaccine is going to be on the other five percent of the people. Some will get sick and some will not.” It is going to be very murky. That is another reason for caution. How are you really going to know? Suppose it causes a brain disease in two months. You are not going to see that, and all of a sudden, their brain falls apart. That is not good. There are things to worry about with how you are going to measure vaccines that I do not think most people have thought through. They think it is going to stop the infection and everybody is fine. These vaccines do not stop the infection. They may stop some parts of the disease, but maybe not all parts of the disease. Ninety-five percent of people do not get those diseases anyway, so it is hard. It is not easy. Female Speaker: Is that true for all kinds of vaccines?
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WH: The answer is yes for polio. Polio only paralyzes one out of two hundred people. It was more difficult, but people took their time. They did not rush it. They did those studies and they did them properly. Female Speaker: I get it. Female Speaker 2: I have one question. So far, researchers have published some data of animal experiments and phase one and two clinical trials. What do you think of this data? How can we assess if the vaccine is potent or safe when we are looking at the data that has been published so far? WH: The animal data is limited, but it shows that all the vaccines that have been demonstrated do not prevent infection. Because the animals do not get the disease, you cannot say anything about disease. You can say they do not have as much virus in their lungs, but because the animals do not get very sick, you really do not know what that means. We have to wait to see what happens with people. We know it does not stop infection and is unlikely to stop infection in people, but it might stop some diseases and not others. We just have to wait for the human data. You cannot tell from the animals. There is a saying that goes, “Mice deceive in vaccine trials and monkeys lie.” The lore in the vaccine world is that many things work in mice. Some things work in monkeys, but if it worked in a monkey, you cannot really tell if it is going to work in a human. Female Speaker 2: I noticed that some phase one and two data says that the vaccine can make the antibody positive right inside the human body, almost one hundred percent. How should we interpret this data? WH: With caution, because you do not know that those antibodies are protective and you do not know how long they are. You know that there is a high degree of variability in the amount of antibodies to make, what kinds they make, and if they protect. We do not know all of those things. We also have almost no data about the T-cell arm of the immune response. If that were not enough, we know that some antibodies for some viruses make things worse. There are a couple of examples of that, even for coronaviruses in cats. So far, we have not seen that in people. That is good, but we do not know. At least we have not seen it in animals. There are a lot of unknowns still.
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Female Speaker: I have another question. Right now, although the COVID-19 outbreak in Beijing is on a small scale, it still worries lots of people in China, because about one month ago, we believed it was all gone, but it came back anyway. How can we deal with that? Does it mean that we have to be used to it once it comes back, and we take drugs? I think that is why people are tired of it. WH: The virus does not care if you are tired of it or not. The virus is doing its best to survive. I lived at a time when we did not have many vaccines. I lived at a time when we did not have many antibiotics. My lifetime has seen most of the vaccines developed, and most of the antibiotics developed. In fact, I was the very first person in the United States who was not in the army to get penicillin when I was an infant. People live with disease. You have to be more careful. We used to be much more careful. People watched their food more carefully. They took hygiene really seriously. If you had a sore throat, you were kept home longer there. You could live with these things. Now, you, as people in China are doing, are going to be wearing masks and keeping social distance, but it will come back. It will keep popping up. Right now, there are over ten million people in the world infected. One person started the whole thing. Now, there is ten million of that one person running around the world. This virus is here to stay and it is going to keep coming back. There will be drugs. Eventually, there will be some vaccines. There will be strict public health measures that say, “It has popped up here, so let us be careful. It is okay to be over here, but over here, you have to be careful. It is going to be with us. It is not going to go away. Not quickly. We have to learn to live as we learned before. We built a whole world. Imperial China was built without a drug or a vaccine. It worked, so we can do it. We just have to do it differently. Thanks a lot. Take care. Female Speaker: Thank you. Bye.
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July 2020
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Interview with CNN Chris Cuomo Prime Time July 1, 2020 | Interview
Chris Cuomo (CC): Let us bring in doctor William Haseltine. Good to have you on “Prime Time.” The idea of the pandemic disappearing. What does that mean through a medical lens? William Haseltine (WH): This pandemic is not disappearing, but this pandemic has to disappear. It can be without a drug or without a vaccine if you have leadership, governance, and individual responsibility. It can be reduced to zero or very low levels as we have seen in a number of countries. CC: Now, if the response from the White House with the president is disappearing, that is what I am saying. Hopefully, we will make it disappear. What is missing in terms of the message? WH: You need to have clear, consistent, credible, and compassionate leadership. You need governance that has the right tools. You need a Surgeon General that has troops. You need people because every individual has to take it upon themselves to be responsible for playing their part in ending this pandemic. You need all three layers to work together. One without the other will not work. CC: The idea that America is unfixable. We are always going to be here. It is inevitable. This is how it works. It is not about how we reacted to it. What is your sense? WH: All you have to do is look at America county by county, state by state. You can see that leadership, organization, and individual [00:01:45, the feed was temporarily lost] CC: We lost Haseltine. Thank God not to Coronavirus. He was making the point that the idea that we had to wind up here and it was inevitable is not true on two levels. One, if you look at other countries, you will see how they handled it more quickly than we did. Even Italy wound up getting through it with an economy that we did not, in terms of time. We will see how they come out of it, though, because they did not go into it with the economic assets we did. Why is it still taking us so long? If you look state by state and 1811
county by county, you will see the areas that treated it most seriously and worked the hardest on preventing the virus from spread are reopening the best. We had it backwards in some places. We should not have reopened and then take care of the virus. We needed to take care of the virus and then reopen. That was the way it was going to be. Places that did not do that have paid the price. We will try to get Haseltine back but, even in little doses, he is a lot of medicine and we appreciate it. Let us get a better sense of the reality of where we are and where we are headed. From Nick Watt right now. Nick Watt (NW): Every state beach parking lot in southern California and the Bay area will now be closed for the fourth of July weekend. Governor Gavin Newsom (GN): A weekend that has raised a lot of concern. NW: Bars, dine in restaurants, and movie theaters will also now close again in nineteen California counties for at least three weeks. Today, the daily death toll in the state is higher than we’ve seen since April. GN: Do not take your guard down. Please do not believe those that somehow want to manipulate the reality. NW: Record numbers are now hospitalized in Arizona. Mayor John Giles (JG): I’m not sure what more we can do short of a total shut down. NW: Record high hospitalizations also in Texas and long lines to be tested. Mayor Steve Adler (SA): While we opened in phases, we went from one phase to the next phase too quickly, so we were not able to see the data. NW: He is echoing Dr. Fauci, one of the most respected voices on this virus, but no longer respected by all. Male Speaker: He does not know what he is talking about. We have not skipped over anything. The only thing I am skipping over is listening to him. NW: Thirty-seven states are seeing case counts climb. Twentytwo now pausing or rolling back reopening. New York City was due to open indoor dining Monday. Not anymore. There is now a new warning from the federal official in charge of testing. Those under 35 are driving out breaks right now and testing alone will not be enough to stop them. 1812
Male Speaker: Testing is critical. We cannot test our way out of the current outbreak. We must be disciplined about our own personal behavior, especially around the July 4th holiday and among the young adults. NW: Vaccine would of course be the game changer. Some promising data from Pfizer today. Robert Wachter (RW): We have an effective vaccine that is proven on January 1. This doesn’t end on January 2. It is going to be another six months, nine months, could be a year before we get it distributed enough to make a meaningful difference. NW: CNN. Los Angeles. CC: All right. That is the straight take. Let us bring back Dr. William Haseltine. We got him back. I want to get you one more question. This has been politicized. That is not debatable. You just heard that yahoo from Texas, the lieutenant governor, saying he is not listening to Dr. Fauci. It is the same guy who said it’s worth dying in order to get the economy reopened. The idea of heading into July 4th weekend and the message the president may send by going to South Dakota to be in the presence of Rushmore and people not socially distance and mask optional at an event like that. How powerful is this message? WH: Let me give you an idea of how I give my friends advice who ask about a barbecue, something very simple. I say fine, have a barbecue outside. It is much safer to be outside. Do not go inside. If it rains, do not go inside. Go home. Magnify that small piece of advice by a huge crowd of 30,000 people or more. Gathering on the fourth of July with or without mask. It is a very dangerous situation. If you are worried about a barbecue at home with friends, and you do not go inside because you might infect one another, you should certainly worry about a very big crowd. CC: The argument of it is my right to assemble. You did not care like this about the protest. You cannot protest without a mask. What do you make of that argument? WH: I am a big proponent of individual freedom. But when somebody else’s freedom impinges on mine, we all know and learn it in high school and civic class. There is a border to personal freedom. You can have all the freedom you want as long as it harms no one else. The moment it harms someone else, society has a right to say be careful. Change your behavior. We do it all the time. For 1813
example, take a speed limit. You can go as fast as you want, but if you are endangering other people, you can get a ticket, pulled over, and even tossed in jail. You have to be careful. You cannot just go around recklessly driving. That is essentially what it is like. You do not know if you are infected. You might be infected, not know it, and then harm other people. A simple mask is not a great thing to ask. CC: It is only when you cannot socially distance. You are not asking them to wear it all the time everywhere they go inside and outside, no matter what the situation is. Just when you can’t socially distance and around people that you haven’t been around, you should wear a mask. Thank you very much. Sorry for the hiccup. Even in small doses you are great medicine. I appreciate it. WH: Thank you.
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Interview with CNN Anderson Cooper July 6, 2020 | Interview
ANDERSON COOPER: Perspective now from two leading public health experts Dr. Peter Hotez, Dean of the National School of Tropical Medicine at Houston's Baylor College of Medicine. Also, William Haseltine, a preeminent researcher, formerly at Harvard University and the author of a "Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children." Dr. Hotez, you're in one of epicenters of the virus right now in Houston. I am wondering when you hear the President saying that 99 percent of cases are harmless, I mean, as a scientist, what do you think? DR. PETER HOTEZ, DEAN OF THE SCHOOL OF TROPICAL MEDICINE, BAYLOR COLLEGE OF MEDICINE: Well, Anderson, what I think about are the 2,000 COVID-19 patients right now we have in our Texas Medical Center in Houston including 600 in the ICU, almost 600 in the ICU. You can't hide ICU admissions. You can't hide hospitalizations. And I think about a lot of my former students and residents, doctors, nurses who are taking care -- technicians who are taking care of those patients tonight. So, this is a catastrophe for our city and the State of Texas. The numbers are accelerating precipitously. Around 7,000 to 8,000 cases a day. We're seeing this in Florida. We're seeing this in Arizona. The cases are rising so rapidly that we cannot even do contact tracing anymore, I don't think -- I don't see how it's possible to even do that. So, essentially, even our limited means of public health control are not possible. So this dramatic acceleration, the epidemic is out of control in the southern part of the United States. Now we're seeing the numbers rise in Tennessee and the northern part of the Midwest. HOTEZ: You know, last week there were 40,000 in new cases a day. Earlier -- then, later in the week there were 50,000. Now it's 1815
getting 60,000. Dr. Fauci predicted 100,000 new cases a day and we're rapidly approaching that. This is a public health crisis for our nation. COOPER: Professor Haseltine, I mean, when the White House says that the rest of the world looks to the U.S. regarding its coronavirus response, the place with the most cases and most deaths, as a leader on COVID-19, how do you wrap your head around that? I mean, what needs to be done now if Dr. Hotez is right in some of the states, there is no point in doing contact tracing because there are too many cases and it's just not possible. DR. WILLIAM HASELTINE, CHAIR AND PRESIDENT, ACCESS HEALTH INTERNATIONAL: Well, first overall, this is -- I agree entirely, this is a terrible tragedy for our country, and it is a preventable tragedy. At this point, what we have to do is people have to exert their own individual responsibility. It's clear we don't have national leadership to do that. The leadership in our Governor's Mansions is erratic, sometimes it's good, sometimes it is not. And then it changes. Some of our mayors are great and some aren't. It's unfortunately up to each individual to be responsible for themselves, their family and all of those around them. And it's a very difficult thing to ask people who really are getting mixed messages. But I'm afraid at this point, we've passed the point of no return in many of our states. Not all. In New York, New Jersey, Northern California, people are responsible, but at this point, it's up to us and that is a very sad thing to say about your country. COOPER: Dr. Hotez, Dr. Fauci said something today that I want to read to our viewers. He said, "Rather than looking at the public health effort versus economic opening as if they were opposing forces, they are not. We should use the public health effort as a vehicle and a pathway to get to safe reopening. It's not an obstacle, it's a pathway to do that." That is just logical and makes sense and frankly, that's nothing new. That is the argument he and health professionals have been making all along, but the administration has created this either you're for opening or you're for everybody staying at home rather than it being a pathway one to the other. HOTEZ: Anderson, what they can't figure out is this. As the numbers approach that 100,000 mark per day, and it is going to be 1816
pretty quick, we're soon going to get to the point where everybody in the United States knows someone personally who is very sick with COVID-19. That is going to have an incredibly destabilizing effect on the country. That and -- we might as well come close to collapsing the economy. COOPER: We are going to take a quick break. There is more I want to talk about. When we come back, we will play you Dr. Anthony Fauci's grim assessment of where we are right now and talk about ways forward, you know, through treatments, vaccines, changing the way we live. Later on, more why the President is wrapping himself in the losing flag of a failed racist past. COOPER: We are talking tonight about the reality everyone now seems to be facing or just starting to come to grips with, except that is, the President and many of the people around him. You cannot say however he hasn't had some of the brightest minds at his disposal or that he has not been warned. We alluded to it at the top. Today, Dr. Anthony Fauci in a livestream with his boss, N.I.H. Director, Dr. Francis Collins pulled no punches. COOPER: Back now with Dr. Peter Hotez and Professor William Haseltine. Professor Haseltine, is it becoming more and more evident that at least, in the United States, the only way we are going to go back to any semblance of pre-COVID life is for a vaccine to come along? Is that the only hope? HASELTINE: Well, I hope it's not the only hope. I think behavior change by most people is the actual answer. But there are two solutions from the medical world. One is a vaccine that everybody is talking about. In my opinion, it's going to come, but it will be partially effective and we don't know for how long it will last. There is another solution which is coming very quickly, which is a bridge to an effective vaccine and that is the use of combinations of antiviral drugs to suppress the virus and to protect people from being infected in the first place.
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We know that works for something called respiratory syncytial virus. Another virus that affects in this case instance, children. We know that it works for malaria and so, we are very hopeful. We actually know and have the drugs and the model for this is HIV. We've developed drugs and there are some spectacular new drugs on the near horizon for controlling HIV. We can do this. So that is a double strategy from the medical world providing drugs to prevent infection for those who are exposed, which would be a bridge to a safe and effective vaccine for which we will have time to test to make sure it's both safe and effective. COOPER: But Professor Haseltine, I mean, if states now aren't able to do contact tracing because there are simply too many cases, I mean that's, you know, in a war movie, this is where you call an air strike on your positions because the enemy is in the wire. It would seem to be a huge concern just from a social distancing standpoint. You would still argue that people as you said people need to kind of take control of this themselves and do social distancing, wearing masks. It's up to each of us now. HASELTINE: That is unfortunately about where we are now. However, what you'll see is the moment there is a way to prevent infection for those who are exposed, with drug treatment, which there will be. People will flock to be tested if they've been exposed. Once there is a way to prevent you from being infected, the complete mind changes. We have seen that with a number of diseases, and again, HIV for example. Once we had drugs to treat people with HIV, people wanted to be tested. Before, there was no incentive to be tested. Now, if you're tested and exposed, you might have to be quarantined for two or three weeks. That, instead of taking a couple of pills every day is going to be your alternative and I think you're going to see a mind change. So, this isn't forever. It is for a while. COOPER: Dr. Hotez, I mean, what do you -- in terms of where you are in Houston, what needs to happen? What are the steps? HOTEZ: Well, let me just follow on what Dr. Haseltine, and I absolutely agree. We will have partially protective vaccines and we will have various forms of prophylaxis and monoclonal antibodies,
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but it's not going to happen for several months, at the very earliest, maybe six months, maybe a year. And during that period, a lot of damage will happen. The rate of acceleration we're seeing, we will have catastrophic numbers of deaths. So, we still need that national road map and plan. We can do this. We can stop this virus if there is the political will and leadership and we can discuss how that could be done. COOPER: Yes. Dr. Peter Hotez and Professor William Haseltine, as always, thank you so much. I really appreciate it.
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Interview With CNN Poppy Harlow July 8, 2020 | Interview
POPPY HARLOW: Ryan Young, thank you for that reporting. All of this and yet the president's words last night, we are in a, quote, good place with respect to COVID. Let me bring in Dr. William Haseltine, Chair and President of ACCESS Health International and former Professor at Harvard Medical School. Good morning, professor. If I can just get your big, 30,000-foot view on where we are in this country in terms of fighting COVID, because you've got this in Arizona, you've got it in Texas, you've got it in California, you've got it in Florida in terms of seeing records, where will we be two weeks from now if hospital stays are a lagging indicator? DR. WILLIAM HASELTINE, CHAIRMAN AND PRESIDENT, ACCESS HEALTH INTERNATIONAL: Well, there are a couple of things to think about, first of all, that this epidemic in our south and our southwest is out of control. PH: Yes. WH: It's a dire situation. And if people don't observe very careful social distancing, it will get even worse. This virus has no reason to stop. It's highly transmissible. When people get together, it will be transmitted. And the only thing we can do now is urge people to be as careful as possible. It is out of control. Second thing that's happening now is with the hospitals. You asked me about them. PH: Yes. WH: And there's something called crisis standards of care that is about to be -- it's already implemented in Arizona and it may be in a number of these other states. What does that actually mean? It means that if you're old, you get sent home without care and you die. That's what it means.
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We are on the brink of not treating people. There's a whole equation that you're going to put into effect, which says, are you worth treating or not. And one of the biggest factors -PH: You think that will happen? You think older people, let's say, in Florida, where you have older people in retirement communities, that come in with COVID, the hospitals will be at the brink within a few weeks where they will turn them away and they will have to go die at home? WH: It's already official in Arizona that that has been authorized, crisis standards of care. It is about to be, I believe, implemented in the other states as capacity. We need federal help to these states in a massive way to avoid sending people home to die. And as I said again, if you look at -- I've looked carefully at those standards of care. What it means is if you are old, they ask do you have one year to live if you survive, five years to live, how long are you going to live if you survive? If that, they think, is too short, you get sent home without care. It is pretty serious to think that we, in the United States, are at the brink of that. And the only way to avoid that in these states as the infections climb and hospitals fill up is to have massive, federal intervention, as we were having in New York when we thought it would happen here. HARLOW: Right. And we had the USS Comfort and Mercy and these hospital ships that it sounds like they need to go, you're saying, to places -WH: And we had the National Guards setting up hospitals in -we had hospitals in Central Park. We have them (INAUDIBLE). We have to begin to get massive intervention to save the people who are already getting ill. We know there is an even bigger wave on its way. PH: So you have, as we wait, all wait for a vaccine, you have said repeatedly there's a reason for hope that medical solution to this crisis will soon be at hand. Are you talking about therapeutics, like a remdesivir or the news we had yesterday out of Regeneron, which seem to help in terms of lessening the severity for the length of time that it had lasted or are you talking about something else? WH: No, no. I'm definitely not talking about remdesivir. I'm not a fan of that drug. I think it is way oversold. However, there are drugs like the ones that Regeneron and other companies are developing, monoclonal antibodies that can be used not only treat 1821
in the early stages of infection but very likely will provide a shield for those who are exposed, like healthcare workers or a family member of someone who is infected. The use of these would be to administer it for high-risk individuals, people like emergency care workers, healthcare workers that are very high risk and people who know that they have been exposed. And it can serve as a bridge to a time when we can have a safe vaccine. I'm mostly concerned, not about the efficacy of the vaccines, but the safety of the vaccine. So this is very positive news, and it's not just one drug. There are many drugs in the pipeline. This virus is -- yes, go ahead. PH: Doctor, I was just going to say, the president said last night, and I'm quoting him here, we're going to be -- in two to three to four weeks, I think we are going to be in very good shape. Is there any scenario in which that is the case? WH: No, there is not. I'm sad to say there is no scenario in which we are going to be in good shape in three or four weeks. Three or four months, if we do things right, possibly, but three or four weeks, no. And the other issue is school openings. I have so many people - you know, I've written this book, A Family Guide for COVID for questions and answers, and what everybody is asking me now is about schools. We can reopen schools in areas that have relatively low disease burden. But even there, we're going to need massive federal assistance. The local people cannot afford to implement anything that's needed and the state has to help and the federal government has to help. It's okay to say, yes, open schools, but open schools without additional support, they're going to need just the kind of support you need in factories and companies are going to need a lot of extra money to put in all those safeguards and nobody is talking about that, open schools. And the teachers and the teachers' unions have got to become flexible because this is not going to be a normal school. There are going to be all sorts of safeguards for the teachers, for the students. There will be kids in pods. It's a very complicated situation and it's one that cannot be addressed without massive new funding.
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If you want to have students even in safe districts, you've got to get more money for public schools. PH: We have the head of one of the biggest teachers' unions in Florida joining us ahead this hour, so we'll address much of that. We appreciate your time. WH: Well, ask him about the flexibility, how these teachers are going to -- I have a lot of friends who say only one out of six teachers are going to help with virtual education. The other ones don't like it. PH: I will be -- I'll ask her that and we'll have you back, Dr. Haseltine. I'm sorry, we're out of time. I appreciate you. Thank you very much. WH: My pleasure. Thank you.
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Interview with Don Lemon
CNN Tonight | July 8, 2020 | Interview
Don Lemon (DL): I want to bring in William Haseltine, former professor at Harvard Medical School. Thank you for joining us. I appreciate it. We are hearing two very different messages from President Trump and Dr. Fauci. Listen to this please. Donald Trump (DT): “I think we are in a good place.” Tony Fauci (TF): “We are facing a serious problem now.” DT: “We are almost up to forty million in testing and forty million people, which is unheard of.” TF: “This is the thing that is a little bit concerning. While we now have 37 million tests have been performed. The question is when you get on the phone and talk to the people in the community there are still lapses there where the dots are not connected.” DT: “If you look at the chart of deaths, deaths are way down.” TF: “It is a false narrative to take comfort in a lower rate of death.” DL: My question is, how worried are you that Dr. Fauci, the expert, was not at today’s briefing and the president is openly disagreeing with him? WH: I have worked with Dr. Fauci for thirty years. During the AIDS epidemic, I worked with him closely. We all are worried. It is not just Dr. Fauci that is worried. Every American is worried about what is happening, whether they are voicing that worry or not. You cannot look at three million infected people and sixty thousand new infections detected yesterday. That means there are probably 20,000 new people and twelve thousand new people going into the hospital. Of that, there will be at least 1,500 people dead. Just because they were diagnosed today. We know that our states are going to something called crisis standards of care, where they will be turning away people because they do not think they have a chance to live. They will be turning away people because they are old and do not think it is worth saving. They just do not have the facility. We should not be talking about restricting things. We should be talking 1824
about how we get more aid to our southern states that are in desperate need. DL: Southern and western states. We have that map, and you can put it up, with the red and orange. If you listen to the president and many in the administration or his apologists, there is a map. Plus, fifty percent with the red and the orange is plus ten to fifty percent in the country. New cases in the past week versus the previous week. That is just extraordinary. It is astounding. WH: I want people to think about something else. We have seen this CDC guidance reversed once before. Remember, when it had to do with reopening, the CDC had one set of guidelines and were asked to rewrite the guidelines by the White House. They did. Look at what has happened. The CDC is now being asked to rewrite the guidelines for school opening. What do you think could happen then? DL: That is what I want to talk to you about. Let me ask you, the president is really pushing hard to send students back to school. There are so many considerations here: students, teachers, siblings, parents at home, school bus drivers, all the workers, lunchroom, and on and on. How do parents know if it is safe to send kids back to school and teachers actually know it is safe to hold a class? Go on, please. WH: First thing I would say is everybody wants the kids to go back to school. We know we need it for the future of the nation and for the sanity of children and parents. It is a very difficult situation. We all want to do it, and we want to do it safely. Our children are the most important precious things we have. Dr. Redfield, my good friend, was quoted out of context when he said it is difficult for children to get sick. That is not true. Children get infected and infect each other. They infect parents. When they do get sick, it is catastrophic. I have a friend with a child who got sick, and he barely made it out alive. We now know there is long term damage to his brain. Four out of four children in one study had brain damage that may last a lifetime. This is not something to fool around with. DL: You were being, I think, sarcastic when you were saying you hope Dr. Redfield was taken out of context because I am not so sure that he was.
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WH: I was not being sarcastic. He is a wonderful man with a great history of fighting AIDS his entire life. He is in a difficult position. I hope it was not an accurate quote because it is not true. DL: I hope you are right. I hope that was not accurate as well. But in this environment, well, I won’t go on. Thank you, sir. I appreciate it. Thank you for appearing on the show.
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Interview With CNN Don Lemon July 9, 2020 | Interview
Don Lemon (DL): Here is our breaking news. The U.S. sees a record number of new coronavirus cases in a single day today, with more than 60,000 new cases reported. The virus is surging in at least 33 states, more than 3.1 million confirmed cases in the U.S. since the pandemic took hold and more than 133,000 Americans have died. Here is what Dr. Anthony Fauci was saying, that some states reopened too soon, including Florida and Arizona, two states where this virus is raging. I want to bring in now CNN medical analyst, Dr. Larry Brilliant, who is an epidemiologist, and William Haseltine, a former professor at Harvard Medical School. So good to have you on. Let us see, professor, why don’t we start with you. Let us talk about California, Florida, and Texas. They all reported a record single-day number of coronavirus deaths. How did the U.S. fail so badly at the coronavirus response, even when the president says we are doing great? William Haseltine (WH): We have missed three of the milestones that it takes to control an epidemic like this. You need leadership, which is clear, consistent, credible, and compassionate, which we are lacking. We need a national public health service that is capable of executing from a central organization in the federal government, through the states, to the local communities, and we do not have that. Finally, as you have heard, we have a divided polity, with a divided people, and we do not have a sense of solidarity that we take care of one another. Some countries can get by with two out of those three. We do not have any of the three. We have not controlled the infection, and now it is out of control because we opened too early. DL: Dr. Brilliant, President Trump plans to visit Walter Reed. He said that tonight. He is going to do it on Saturday. He also said that he plans to wear a mask. He says he has no problem with masks. I quote here, “it is up to you.” My question is, when projections
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show universal mask-wearing could save 45,000 lives, should it be mandated? Larry Brilliant (LB): That is a good question. If we had a vaccine that would save 45,000 lives, we would certainly put a lot of social bumpers in to incentivize people to use it. We should find a way to incentivize mask-wearing. I think one way would be to make people who do not want to have a mask unable to go to certain places. It is like having a license. You do not want somebody to come in your business place, your school, or your church if they are bringing the virus in. That is an unwanted visitor. DL: But, you see people around the country fighting that. You see all the videos online, even when stores or places of business have those policies, people still do not follow the rules, and there aren’t any real consequences to it, doctor. LB: It is insane that we have made a mask, which should be a symbol of public health and liberation from this pandemic, into a political symbol. It does not make any sense except that we seem to be living, Don, in a topsy-turvy world where up is down. DL: I want to ask you, professor Haseltine, that the president is pushing for schools across this country to reopen, despite the virus surging in 33 states. The question every parent and educator is asking: is it safe? Are these decisions being made with public health and not politics in mind? William Haseltine (WH): We have had a recommendation from the CDC about what we should do if we are going to open the schools. That recommendation has been withdrawn. New recommendations are being drawn up. It is almost like the opening redux. We had a recommendation from the CDC. It was buried and altered. Now, we are living with the consequence. This consequence may affect our children. We have to remember that everyone says young children aren’t so susceptible, but they do get infected and some get desperately ill. I have a friend who has a child who is desperately ill from this disease, so it does affect children. We have to remember that half the schoolchildren from seventh grade to 12th grade have the same susceptibility as you or I. It is a serious problem. We are not only dealing with young kids when we are talking about schools. We are talking about high schools, which have the same susceptibility. They get sick. We are also then talking about colleges. When we’re talking about schools, we are talking about a 1828
third of our population, and are we going to put them at the same kind of risk? The other thing is risk varies by geographical area. Some places may be okay under careful circumstances to open schools, and other places, like Houston, Miami, and parts of Los Angeles, you would not dream of doing that. You would not dream of sending your precious child to a school in those cities today. DL: Thank you both. I appreciate it. By the way, the CDC said earlier they are competent in these guidelines despite what the president says, and they have no plans of changing it.
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Interview With CNN Anderson Cooper July 10, 2020 | Interview
Anderson Cooper (AC): We need to hear from our medical experts of the lack, more than four months into the pandemic, of any coordinated federal response to it and the ongoing clash between the president and the facts as well as the people bringing him those facts. Joining us is William Haseltine, a preeminent researcher formerly at Harvard University, the recent author of A Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children. Also, Dr. Peter Hotez, Dean of the National School of Tropical Medicine at Houston’s Baylor College of Medicine. Professor Haseltine, you know Dr. Fauci. You worked very closely with him on HIV/AIDS. When he tells the Financial Times he last saw the president June 2nd and has not personally briefed him in two months, what does that signal to you about what is going on and where things are headed? William Haseltine (WH): It is not a good sign. The chief infectious disease officer for the United States who really understands this disease is Dr. Fauci, and Dr. Redfield also. They are extremely well versed in what to do, and without them, for the president, it is like flying blind. It is like turning off your radar in the middle of a storm if you are not talking to those people. They are the people that are necessary to guide you through this storm. AC: Professor, do you worry that the CDC, which is the traditionally preeminent scientific organization around the world that people turn to, has it been severely weakened under this administration because it does seem like there have been a number of instances, with the most recent one just yesterday or two days ago when the president and Vice President Pence saying that the guidelines on schools by the CDC are too tough and expensive. They will get new guidelines next week, and there is going to be something coming out next week. WH: The CDC is the organization that we Americans trust to give us policy guidance on how to behave and what rules to follow 1830
for our cities and states reopening and sending our kids back to school, dictating the safety of our most precious possession: our children. It is critical we listen to the best advice. They are the best in the world. They are still the best in the world. It does not help if no one listens or if they change the rules for whatever purpose. It is a very dangerous situation for individuals and our children. AC: Dr. Hotez, every day goes by without a national plan or leadership on a federal level. The fact that PPE is now back in the headlines with questions about how much PPE is available. Dr. Hotez, does that make sense given how far we are into this pandemic? Peter Hotez (PH): If this continues at this rate, we are headed towards something unprecedented and catastrophic. Let us look at what the country is going to look like, say, six weeks from now— by September 1—if we continue along this trajectory. We will easily exceed 100,000 new cases per day, Dr. Fauci’s apocalyptic prediction. We will have hospitals overwhelmed, not only in terms of ICU beds and hospital beds, but exhausted hospital staff and hospital staff that are getting ill themselves. So, we will not have enough manpower and human power to manage all of this. The consequence of that will be when we see mortality rates going up. That is what we saw in Italy and in the early stages of the epidemic in New York. We already have deaths now starting to increase. They said there were no deaths. We knew there was a lag, and now the deaths are starting to increase. It will accelerate as hospital ICUs become overwhelmed. We will have students in schools where the teachers are now getting sick and the school staff will start to abandon the schools. We are looking at what I think is going to be one of the most unstable times in the history of our country unless we figure out a way to do something and implement a federal plan. We still can do this, but we need a president and White House engaged. AC: So, professor Haseltine, let’s assume a potential future in which the president won’t shift strategies, which there is no sign he is. Let us talk about what the rest of us can do, governors, Congress, and others, what can be done to not have us have 100,000 per day? WH: First of all, let me reinforce what Peter said. All people who study these viruses think that the summer is the quiet time. I want you to think about that. This is the quiet time for 1831
coronaviruses. That is what you were hearing. That is what we believe. If this is the quiet time, I hate to think what winter is going to be like this year. That is the first thing to say. Second thing to say is it feels a little bit like you are on a ship where the captain said, we are sinking, so every man for himself. If it is every man for himself, we better pay attention and do what we can to help ourselves. We have to make sure we wear masks, social distance, and be aware of our environment, like everybody says. What is the infection rate in our immediate environment, so we can analyze how much risk we are taking when we go out? All of these things are left to individuals, which is a very sad state of affairs. We need the government right now to send the needed people, equipment, and supplies to our southern and western states. We need our government to start an education bailout program to help our schools prepare. We are not prepared at the federal level, and the local level cannot afford the changes that are needed. AC: Dr. Hotez, what do you see as a path forward? PH: The path forward is there is no choice. We need a federal plan and road map. We know the states cannot do this in the lead, and we have seen what happens. It just does not work. So now we have to look around at who is going to step up to take control of our COVID response. If the White House won’t do it, we will look to the CDC. The CDC seems to have trouble with taking leadership. They seem to want to have the states lead with CDC advising. Maybe they can turn it around. That would be the best thing that could happen. If not, I think we are going to have to look at other levers. Can Congress take control and mandate that if the CDC won’t do it? We have other options. We have the U.S. military, Walter Reed, the energy labs, and contractors, but someone is going to have to step up. There is no other way around it. AC: Dr. Peter Hotez, Professor William Haseltine, thank you so much. I really appreciate it.
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Interview With KNX News Radio July 10, 2020 | Interview
There is no transcript for this interview but the link is available here: KNX In Depth: Coronavirus on frozen shrimp now?! -- Youth sports won't be playing ball anytime soon -- Taking you inside the ER of one of California's biggest medical centers
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Interview With Houston Matters Ernie Manouse July 13, 2020 | Interview
Ernie Manouse (EM): Good afternoon and welcome to Houston Matters Special Edition. I am Ernie Manouse. On today’s show, we are very excited to have back with us Dr. William Haseltine. He is the president of Haseltine Foundation for Science and the Arts and president of ACCESS Health International. In addition to all of that and all the work he is doing, he has had time to write a new book, A Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children. It is an honor to welcome back Dr. William Haseltine. Hello Dr. Haseltine. William Haseltine (WH): It is a pleasure to be here. Thank you. EM: I guess the place to start with is with all the work you are doing, all the things that are so important, all the information you are sharing, how and why did you find the time to write a book about parents, grandparents? WH: Thanks for asking that. I am a grandfather and I have three lovely grandsons, three, six and eight. It is hard to keep track because they keep changing how old they are. They ask me a lot of questions. In fact, one of my nicknames is Willipedia. They ask me a lot of questions and their parents ask me questions and because of my background, a lot of my friends and other grandparents and friends and children all ask questions. I decided that this is such a complex and deep issue that touches all aspects of our lives that it would be important to give some very simple answers to people’s most common questions that I got. That is how I started, to help other people understand what is going on. As this progressed, as I got deeper into it, we decided to write a multi-level book. So one level looked really simple. 1834
So one level it looks really simple. Mom, why can't I go out? Mom, why can't I go see grandpa? Dad, why can't I play sports? All these kinds of questions. Things that parents need, but there is a lot of references there. So because it is an ebook, you can click on it and go deeper and deeper right down to the scientific data if you want. They are real answers. They are not all in the book, but it points you exactly how to find the information. Now, the other thing I decided to do, which was a lot of fun is because things change, COVID is a rapidly changing problem. What we know today is not what we will know tomorrow, and it is an ebook and that allows us to change it. Right now, we are right in the middle of the second edition. So when you get the book as an ebook, you have a free sign in to all the subsequent changes. What is really interesting is both the questions and the answers change. I will give you an example of how that might change. Am I at a higher risk if I am pregnant? It is an important question a lot of women are asking and the first answer to that was no. That is not the answer today. Now we know more. The answer today is yes, you are at higher risk of getting infection and therefore you have to be very careful, super careful. There is an infection, a chance that you could infect your fetus and have a miscarriage. You have to be very careful. And if you should get sick, there is a higher chance that you are going to have a serious consequence of being sick. That is pretty serious information. And then we can give you the data that supports that if you want to have that data. And there are many examples like that, that just in the last month since we have written it have changed. EM: Do you find it is challenging to explain to people, because we get this all the time. We are on every day talking about this topic. And as you said, the answers change. We learn more. People misinterpret that as you do not know what is going on. They are giving out fake news. It keeps changing. Nobody knows what they are talking about. Does that frustrate you as much as it does me and trying to explain this is a moving target and we are sharing what we know as we know it? WH: I think that is what you have to say. And if you do not know the answer, I am not afraid in this book to say, I do not know the answer. There are some questions where I say in the book, we 1835
do not know the answer yet. And so I think as long as you are clear, you know, in a crisis, and I have been thinking about what we need to do to control the epidemic in the United States. You need leadership. Leadership, first of all, has to be clear. That means what you know and what you do not know. If you look at what our governor Cuomo did, he told you he did not know things. He was very clear about that. I do not know what is going to happen next. I do not know about this. I do not know about that. You have to be clear. You have to be consistent. That does not mean you have to always give the same answer, but you have to be consistent in the way you speak to people. You have to be credible. You have to be believed. You have to keep to the facts and you have to be compassionate. You have to understand that the information you are giving people can feel like a physical blow to them. It can hurt them. That information is a psychic hurt. Like the one I just gave you about pregnancy. That is hurtful information. So you have to deliver it with compassion. Knowing that mothers are worried, pregnant women are worried. And so you have to give that answer with compassion. If you have that way of communicating, you can get yourself through this and you should not be surprised that people are confused because the situation is confusing. It does not help that we do not have a clear spokesperson to look to. Our president is not the right person for this job. Maybe he was okay for some other jobs, but as a leader in this kind of crisis, he does not have the skills of communication. He communicates for his private purpose, not for all of us. And that is really confusing. I think that more than anything else is a problem for listeners. If he says this and the other people say that, who am I going to believe? That is really confusing and is dangerous. And we can see the consequences of that danger. Let us just take two recent examples. The CDC came out with some guidelines that says what you need to do before you reopen. Those were never allowed to be published by the White House and they were altered. Many people opened against the guidelines that actually were crafted and put out. And even those were not fully obeyed and led to a terrible situation. Right now, we are in exactly the same situation with schools. I can tell you the questions I am getting right now are about schools. CDC put out some guidelines. The White House said we do not like your guidelines, rewrite them 1836
please. Well, what kind of a message is that giving to people and I am afraid that what has happened with this tremendous wave of new infections might happen with our youth as a consequence of not being prepared. So communication is what you are doing Ernie, what I am trying to do is a little bit like howling on a hurricane, because there is so much pressure being put against clear messaging. It is tough, but all you can do is keep on slogging and try to get the message out as best you can. And you guys are doing a good job. EM: Before we move into getting into your career and all of the work that you have done and how it benefits us today, I want to ask a little bit more about the book and then we will take a break. But I am curious, the questions that you get from children are they really that different from the questions you get from adults? And I know in the technicality of them, they may be different, but in the general themes, are we all curious about the same things? WH: We are, but children understand things differently. And for part of that, I go back to my own life and remember what it was like when polio was around. I actually remember that. I remember something that adults won't necessarily remember, which is how much I was worried that my parents were worried. What really scared me was how scared my parents were. I did not know enough to be scared about polio, but I really knew enough to be scared about my parents. And that is what upset me most. I knew that they were worried and they would say, you know, I lived in a desert. You go out and go lizard hunting, but you can only be with three people. If you get bit by a snake, somebody stays with you and somebody runs for help. Four people, no. No swimming pool in the desert, 118 degrees, no swimming pool. Now an adult might understand that and a kid has a hard time. Why can't I go see Hopalong Cassidy in the school movie theatre in the summer? Well you can't, it is too dangerous. It is too dangerous? Yes. It is too dangerous. Somebody is getting hit over here and over there. So I remember that. And so they are many of the same questions, but they come with a different kind of feeling. An adult, you think you should know. Children, you pick up more emotion than you do fact. EM: What do you find hardest to explain to children today? WH: I think the hardest thing is to know that people they love may die. That is really hard. You know, I will give you sort of a sad story from my grandson. One of them, he is five years old. We love 1837
each other and we have a lot of fun doing all sorts of things. And he is in the Dominican Republic right now. And he knows he cannot fly. He said, but grandpa, I cannot fly to see you, but can I dig a tunnel? Okay. So it is hard to explain to him why I cannot necessarily dig a tunnel or you cannot fly. Those are the hardest things. When you see it really tugs at your heartstrings, because you want to see them, they want to see you and you have to explain to them why it cannot be done right now. Then the questions that are really struggling with right now is people going back to private school and to public schools. What are we going to do? How are they going to keep my children safe? I am going to put them into an environment and the teachers. Some people I know are teachers. Please tell me how I am going to stay safe. I know that this is like a cold virus and kids giving me colds all the time. You are telling me that they are not going to give me this? And then I go home and give that to my family. Those are really tough, tough questions. EM: We are going to talk about more of those tough questions in just a moment. You are listening to Houston Matter's Special Edition. I am Ernie Manouse. My guest is Dr. William Haseltine, founder, chairman, and president of ACCESS Health international, and the author of the book, A Family Guide to COVID. We are going to take a quick break. When we come back more with Dr. Haseltine. You are listening to Houston Matter's Special Edition. I am Ernie Manouse. My guest today is Dr. William Haseltine, the president of Haseltine Foundation for Science and the Arts and the author of the new book, A Family Guide to COVID: Questions and Answers for Parents, Grandparents, and Children. Dr. Haseltine, before we took our last break, we were talking a little bit about school and going back to school, and I am curious your feelings on what we should be doing as a nation or individual communities to get schools up and going again. We talk about how important it is to have students in the classroom, but it is also very important to keep them safe. So how do we make this decision? WH: We all want our children to go back to school and the grandchildren and children want to go to school. And we have to think about school as K through postgraduate education, not just K through six. It is a whole generation that is being put at risk at this point. And our future, our technological future, our industrial future 1838
is at risk, our psychological future, because it is very damaging because not to go to school. So they have to get back to school, but they have to do it safely. And we know that this virus is transmitted from child to child, that some children get desperately ill. And the belief is that children are resistant to infection. And that is only partially true. They are about one third less infectable, below the age of ten, but above the age of ten, they are fully infectable. That is dangerous and all the way through age thirty, they can be infected. So think about the kids in junior high and high school, as well as the kids K through six. They are just like adults. And they get sick too. Actually about half of the people in hospitals are under the age of sixty. And many of those are under the age of forty. And a lot of those are college age and teenage kids. And when they get sick, they can get desperately ill. So we really have to figure out how to protect those children. Now, let me just say public schools do not really have the knowledge or the tools or the resources to do the job. I am right now writing an editorial, which is calling for an educational bailout. Public schools are supported by local communities, by local taxes. They are not supported by federal tax. There is very little federal support for education. We need to help our schools learn what to do, buy the equipment and hire extra people. We need the same thing we needed for our businesses. It is even more important because it is all our future. The businesses are current, but our future is our children. And these schools simply cannot do it. I cannot tell you how many parents are getting messages that are very mixed. You know, we are not going to do anything, or we are going to have your kids in different pods, or we are going to have you go to school one week and not another week, or we are going to have some teachers teach in real time in the morning and all afternoon virtually. Well, how do teachers know how to teach virtually? I have a friend of mine who says only one out of six of my children's teachers knows how to teach virtually. The rest either refuse to do it or do it really badly. We need big programs in place. It is true we have to get them back to school, but we have to give our public education system help. We need a big bailout and we need to start right now if we are going to open it up for the fall. These kids have been out of school far too long. And if we do not have that, you are going to have a horrible mess. And if you think the current mess is bad, think about 1839
every parent's screaming their heads off about the risks their child is taking. The other thing I would call upon is flexibility in the teachers unions. Teachers unions are powerful and conservative and protective. All of that is good in some circumstances, but in other circumstances, you need to add flexibility. Teacher unions have to be willing to now entertain something they never would before, a whole set of new part time people to help them out and they will need salaries to help support those people. Those are just a few of the top line things that we have to think about. We need our best minds thinking about how to keep our kids protected in schools. And that is particularly true. You know, if I were giving you this story a month ago, I would be more hopeful. But now that we know the epidemic has ballooned out of control, 60,000 people a day being infected, which means walking around 600,000 people because people were infectious for about ten days. There's really 600,000 people in our country spreading this virus around. We have to be really, really careful. So that is some of my thoughts on this topic. And I do not hear a national dialogue. I hear pressure. Get the schools open. I do not hear people saying how we are going to get them open. EM: In addition, though, to money and staffing, when you look at it, what could be done in the classroom that keeps our students more safe? We talk about the distancing and the mass squaring. Are there other precautions they should be taking and are these even realistic precautions when you are dealing with the space and class size or you are dealing with the behavioral issues that come with children trying to get them to conform? WH: Those are all issues and it depends on the age of the kid. What you do with a five-year-old is not what you are going to do with an eleven-year-old or a fifteen-year-old or a twenty-five year old. All of these things we have to think about because education does not stop at sixth grade or twelfth grade. It continues on. So each one has its own special considerations. Let us take kids in elementary school sitting at desks. If you look at what some people are doing there, some countries are doing, they are putting plexiglass shields around each desk and the kids are wearing face masks, not face mask. A better word is face shield. They are wearing face shields which protect their eyes and their mouth. And it is easier for the kids 1840
as well. So those are things that you can do. You can do scheduling. You can do alternate weeks where the kids are in school and in virtual. So you get a mix. You can say, let us restrict sports. Do sports where you do not share equipment and you do not come in contact with each other. Ping pong, for example. Now there is a ball that goes back and forth and you made sure the kids wash their hands right before they play piing pong. But there are some games you can play and kids need sports just like they need everything else. A lot of outdoor track sports. You know, the other thing, if the weather is okay, have your classes outside, because we know that there is a far less chance of being infected when you are outside than inside. You know, another question that has changed is how dangerous is it to be inside? We used to think about little spit droplets. Look at your computer screen sometime, and you will see what I am talking to you about. Right? I look at mine every day. I have to clean it off again. But it is also things that hang in the air, they just hang in the air and that can be four or five hours. And the more you are in that space, the more they are going to hang around. And when you are in the open air, it is completely different. So the chances is much less, less than ten fold the chance you will get infected if you are in the open air. So if you can, do it in open air. Now in New York, you could do that some parts of the year, but not most of the year. So you have got to be careful. There is a whole other thing about school plan. What are you going to do with the air handling systems? You colder it gets, the more internal air you use versus external air. And you want to use as much external air as possible. That means you have to have a bigger energy bill. You have to have bigger kinds of filters, better filters. These are building considerations. So as you start to drill down, there are many, many things we can do that most people are not thinking about. EM: Should we have been better prepared for all of this? With all the knowledge we have, the viruses and the years of work that you have done in this field and others, should we have not been better prepared? WH: You know, we should have been. And there are two or three things that really upset me deeply about this. Many of us had warned that this was coming and many of us had been really specific, there is another coronavirus coming to get us. And the academic community had done a splendid job of finding new drugs that even 1841
those drugs that were developed for SARS and MERS would have stopped this epidemic. They actually got them right through the point of animal testing and then stopped because they said no more interest. It is not the pharmaceutical industry's fault entirely. They could have done it, but we have special programs in the United States that I helped to design with the National Institutes of Health to protect us and stockpile drugs in just this kind of emergency. And our focus was so much on terrorists and not on nature as a terrorist that we did not develop those drugs, even though we were clearly warned. Let me give you another warning. It is clear as anything, clear as the desk I am sitting at, a new flu is going to come along and be worse than this, worse than this. And we could have class specific drugs that would stop all flus just as we are getting class specific coronavirus drugs that could have stopped this. If we had those stockpiles, nobody had to die. Nobody, zero people had to die in China or the United States. It is not just United States. Korea, South Korea, China, Hong Kong, Singapore, all of these people knew that SARS and viruses like that were coming at them, yet they did not develop the drugs nor did we. So there are things we could have done. In addition, once it hit, there were so many clear warnings about what to do. People say the Chinese did not tell us, but you did not have to only listen to the Chinese. You could have listened to the South Koreans, the Taiwanese, the people in Hong Kong, in Australia and New Zealand that had been through this. They knew the toll in life and economies that these viruses cost. And we did not listen. We were very, very well warned about what was coming and we just did not pay attention. And those two failures have led to a disaster today. And you can only just describe what has happened in the US today is a disaster. Sixty thousand people a day and climbing. It is not in control and we do not know where it is going to end. EM: To flip this a little bit and wrap up our talking about schools and education, are there positive examples on the globe somewhere where people are doing schooling correctly now? WH: There are. Taiwan, South Korea, but they depend on something that we have not done, which is control of the epidemic. So there is a very low level. Instead of tens of thousands of people a day, there may be tens of people a day in their country getting infected. When you are in that situation, which we could have been 1842
if we had done things right, that is a completely different conversation. The conversation in Houston, where there are 10,000 people, or in the state of Texas, 10,000 people getting a day, a hundred thousand people walking around, spreading the infection. That is a very different conversation. So the answer is yes. If you handle the infection, you get kids back to school safely. If you do not handle the infection, you have all the questions we are struggling with. EM: So in a very brief answer on this before we go to our next break. Is the talk of opening schools a little premature considering where we are with the spread right now? WH: It depends where you are in the country. If the level of infection is low in your community, by low I mean less than ten a day, you should consider opening your schools with care. If the level is as high as it is in most of the South today, in most of the Southern cities in California, and in some other hotspots, the answer is I think it would be foolish to do so. We have to wait until we reduce the total level of infection. EM: We are talking with Dr. William Haseltine who has written a new book, A Family Guide to COVID: Questions and Answers for Parents, Grandparents, and Children. He has also had the unique opportunity to be in the rooms where it happened in government. We will delve into that a little bit more right after we take a quick break. This is Houston Matters Special Edition. I am Ernie Manouse. My guest today is Dr. William Haseltine, founder, chairman, and president of ACCESS Health International. He is joining us right now to share his views on the state of the world in the time of coronavirus. And my next question for Dr. Haseltine would be, you have been, as I said at the end of the last segment, in the rooms where it happened. You have been at the highest echelons of government advising on medical science, the different issues that are affecting us today. I am curious how difficult is that position to be in, to be talking to elected officials who feel torn loyalties to what things they may feel they should be doing, what they may feel their constituents want, what they think is politically advantageous. How do those conversations go down? WH: That depends who you are talking to. I have had the privilege of talking to leaders who are very willing to listen and to 1843
understand. I will give you a very specific example. During the early days of AIDS, the French were famous for making great advances, but they had also made enormous mistakes. And prime minister Mitterand knew they had made mistakes and had chosen the wrong courses, that is a wrong scientist to bet on. And they brought me over to France every six weeks for about five days to be an advisor, a private advisor, never to talk about it. Now it is like thirty years later, I can talk about it. To help give them direction. And that was pleasant because they were really interested in really listening and they knew they had messed it up. They infected all of their hemophiliacs by taking bad advice from their top scientists, and they did not want that to happen. It almost caused their government to collapse. It was horrible, it was terrible. And that was pleasant and there are a number of leaders around the world that were really interested, and I was asked to help a number of leaders. That is not true of all leaders. And I will tell you a good friend of mine who routinely goes into the White House and has for many, many years has said to me, my mentor told me, when you go into the White House, you are walking into a lion’s den and never go into it with the attitude that you are going to have your job when you get out. Walk in that door and every time you walk in the door and know, when you give your advice, you may be out of a job the next day. You still give the advice you think is right. That is what it feels like. The people who are currently at the top of the US in the fight against COVID are very good friends of mine. And my heart breaks for those people because they are in an enormously difficult situation. They have to speak truth to power, and that can end their career and their usefulness at any moment. And you see it almost happening in real time. They know what is happening. They have all the information. They are doing their very best from years and years of work to try to protect us. And they are in an extremely difficult situation. EM: Isn't there a point where truth to power is one thing, but they have to have truth to the people. And how do you balance that? How do you, if, because I hear this conversation all the time. It is that the people that surround the highest folks in government, I do not want to give names right now, but they are changing the message they are giving to the people to appease the leader. But isn't there a moral obligation to say enough of that and speak what they know 1844
directly to the people, or is it the worry that once they do, then they do not have a platform to speak from anymore? WH: But I think you are seeing that, you are seeing some of our leaders or our healthcare leaders speak very directly and some other speaking perhaps too indirectly. And I think it is my job and people like me job to call them out and help them steer a little more close to what their moral obligation is. You are right. You have put your finger exactly on it. At the same time, you may be replaced by somebody who is a political hack rather than somebody who knows what to do. It is a very, very difficult position to be in. Have I been in that position? I have not been in the positions of holding that kind of government power and government responsibility and being at the mercy of a political leader saying you are out today. So I have managed to avoid that, deliberately, I might say. I like to be in a position where I am relatively independent. Now, have I ever been attacked? I of course have been attacked. I remember in the early days of AIDS, there was a book written that attacked me and the current director of the Centers for Disease Control. The title of that book you are going to find a little amusing, The Myth of Heterosexual AIDS. Okay. That is a book that you can buy today. When you read that book and when I actually looked into it, I came to understand that it was actually the government in power that encouraged that writer to write that book to shut me up. Okay. EM: And for people who do not know, because you were saying AIDS was something that was going to step outside of the gay community. WH: Yes. They did not want to hear the message that AIDS was a problem for the whole community, not just the gay or Haitians, as it were. Government is a very powerful institution. It has many arms to control messages and if there is somebody giving a message you do not like, they can try to shut it down, whether you are in government or out of government. Nobody who has been in my position has not received the dings of the public forum. It just goes with the turf, but you asked a very specific question about what it is like to give advice to people in power. In some cases, it is a very pleasant experience. In some cases, it is one that you have your heart in your mouth all the time. And you know, and my friends know they may be out of a job tomorrow and yet they continue on. 1845
EM: Let me take you all the way back. If I know your story correctly, when you graduated college, you had the epiphany that you wanted to treat and cure disease. That became your life goal. If that is accurate, where did that belief come from? What made you decide this should be your life's work? WH: Well, it actually happened earlier than that. Actually, my life actually coincides this span of now 75 years with the beginning and the end of health security. Why I say that is I was one of the very first civilians treated with penicillin when I was four months old. My mother fought like a tiger to get the army base to give her rare penicillin to save my life when I was four months old. That was the beginning of the antibiotic era. In my young days, there was polio all around and then there was a polio vaccine. And when I think back now, there have been AIDS, there have been other issues, but there has not been anything like this since polio. There has not been a great flu pandemic. So that is part of it, but there was much more specific to my family. My mother had terrible diseases. She had septicemia. She had a neurosis, psoriasis, and she would get septicemia. And as a four year old kid, I would stay by her bedside and watch that poison go up her arm. It is a red line, and knowing if it went up too far, she would die. I remember that feeling. I remember when she had detached retinas and they had to cut your eye out and sandbag you in place for six weeks and then give you pinhole glasses. She had two of those operations. She had psychological problems. She was bipolar and eventually died from that. And I was surrounded by that kind of disease pressure. I myself had a pericarditis where I was confined to home and could not go out and play. And I decided it was not fair that people had disease, not to the people I loved and not myself. And when I grew up, I would do everything I could to try to make sure that people were free of disease. And I had to decide at one point, should I be a scientist? Should I be a doctor? And I got very good advice that if you do not really want to put your hands on a sick person and heal them and you are good at science, it is better to be a science scientist. You can do more for humanity that way. And that was a decision to whether I should be, I was admitted to both Harvard Graduate School and Harvard Medical School and I chose the graduate education and science. And then I was fortunate to have the world's best mentors. I had James D. Watson a Nobel prize 1846
winner. I had Walter Gilbert, a Nobel prize winner, David Baltimore a Nobel prize winner, Baruch Benacerraf a Nobel prize winner. I had the best mentors. That was like a wind in my back. The other thing to say about that time, which it is really sad when I look at our times today, scientists were heroes. We had leadership in the White House that said go. They put money out there for us. Every door just opened for me. There were scholarships, there were special summer programs. There was an idea that science will save us from the Russians. Science will save us from disease. It was just a wonderful time to be a scientist. And all through my early career doors were just opened by these wonderful government programs. And I just wish that were the case today. I wish that rather than going into finance, people would say, hey, yeah, you can make money, but you can make a real difference to people's lives. And you should use your brains for that. Maybe this epidemic will change people's orientation. I hope it does. I am actually writing an autobiography now and it has got points. The first point is it is meant to encourage young people. My career has been fantastic. Not only have I been privileged to make major discoveries that have changed people's lives, but I have created businesses and have made a lot of money. I have been hobnobbing with Elizabeth Taylor and Princess Diana. Maybe those does not resonate so much with the younger generation. In my generation, that was hot stuff. EM: Yeah. That resonates with me. That is great. WH: And you know, I have a great lifestyle. I have friends all over the world. I have colleagues and friends that go back many years. I have had a very rich life, traveled all over the world. It has just been a fantastic life and it is a life that just continues to open up to new chapters. And it has fulfilled what I wanted to do, which is to make a difference to human health. I have been extremely fortunate, but I know enough to know it was not all through my efforts. It was because our country kept opening up the doors that made it possible for me to do that. EM: It is part of your story. And in there is the fact that you kept pushing, even when there were time, when people were saying, let's move on. If you believed in something, you stayed with it and pushed through it, retroviruses, for example, leading to then help for leukemia and things that the community had said, ah, maybe this 1847
isn't working, let's look somewhere else. There were opportunities for you to continue your work and make great advances. WH: Well let me give you a story about that. Discover Magazine did a look back of possible mistakes they had made. And one of the mistakes they made is that AIDS would never be a heterosexual disease and would not be a major problem for the world. Twenty years, twenty five years later, they did a look back and said, have we ever made mistakes? And they said, that was a mistake. How did we make it? We interviewed twenty people and nineteen of them told us that it was not going to be a heterosexual problem and it was not going to be a big problem. One of them, Dr. Haseltine got it exactly right. So I wrote back and I said, I want all young people to benefit from this story. If you have your facts to support you, scientific or medical truth is not a matter of majority opinion. It is a matter of nature. It is like trying to argue with a volcano. You cannot do it, right. It is what it is. And if you understand things, stick to your guns no matter what other people are saying. And I think with a case of retroviruses you mentioned, I had the intuition based on something that most people did not understand at the time. Now I would say, as a scientist, my fundamental goal was to cure people and to keep people safe. Most of the people who were my scientific colleagues were doing science for science. It was an interesting problem. And that is very valuable. I do not want to say it is not valuable. I did science for health. So when I looked at viruses, I was looking for what might be important to human health, not necessarily only how they work, which I was interested in. So I looked at not just the animal models. I looked out at nature and I saw that cattle got disease. I saw that sheep got disease. It was not at all like our laboratory animals. The virus would go in and disappear. And the disease would appear years later. I said gee, that looks to me like what could happen in cancer? Let us keep plugging. And I tell you a story about how hard that was. There was retrovirus meetings at Cold Spring Harbor. They lasted a week and there was a blowout party on Saturday nights. And there was a rump session Sunday morning when everybody was hung over. That is when they looked at human retroviruses, right? That is it. So nobody showed up. Nobody wanted to listen to us. Nobody would fund us. But a few of us kept plugging. First HTLV, the leukemia virus came along and then of course, AIDS came along. And a few of us who were in the 1848
right place, who kept at this, in the belief that these would be important, were in the right place at the right time to make a big difference. And that is another lesson for people. It depends on what your interests are. My interest was human health, science for human health, not science for science. I respect those people. And many of them are mentors who taught me how to do things. You have to have your own purpose in life, figure out what your purpose is, and then go forward. That is one of the reasons I am writing this book. I want people to understand that their life can be in their own hands and you can do many, many things in science with what you have learned if you have your own purpose. Use the tools that society gives us, the institutions and the tools to have your purpose and you can do wonders. EM: We are listening right now and talking with Dr. William Haseltine. This is Houston Matters Special Edition. I am Ernie Manouse. We are going to take a quick break. When we come back, we are going to move to the future. We are going to look at what we need to do now with COVID-19 and the coronavirus. We all talk about vaccines, but are there other things, other steps along that path. We will find out in just a moment. You are listening to Houston Matters Special Edition. I am Ernie Manouse. We will be right back. This is Houston Matters Special Edition. I am Ernie Manouse. My guest today has been Dr. William Haseltine, scientist, author and philanthropist, and author of the book A Family Guide to COVID: Questions and Answers for Parents, Grandparents, and Children. Dr. Haseltine, we have talked a lot about mistakes that are being made, things that have happened in the past, looked back at your career a bit. Now let us shift the focus to moving forward. Big question a lot of people have is what is happening with vaccines and all of that, but I have heard you talk about steps between having a vaccine and just having the rampant spread that we are in right now, things that can address the higher risk population in healthcare workers. Want to talk a little about that? WH: Yes, thank you. This comes directly from my experience with HIV/AIDS, and that is when you are dealing with a virus which you may or may not be able to make an effective vaccine or one that is partially effective and may last for a short time, which 1849
looks like this one is headed for, and may have some safety issues as well. You think about alternatives. What can we do while we get it right on the vaccine? What is a bridge to a vaccine and the answer is antiviral drugs. And there are a lot of ways we can make drugs and combinations of drugs which can stop viral infection and can protect us. And what we have done with HIV is exactly that. We have controlled the epidemic through the use of antiviral drugs. If you are infected, you can lead almost a full length, maybe in many cases, full length life now thanks to combinations of antiviral drugs. These are chemicals, pills you take or shots you get, and over time we have gotten better and better at that. So good at that that not only if you are infected, will it save your life, but it can protect you from getting infected in the first place, prophylactic drugs, preexposure prophylaxis, or even post exposure prophylaxis. First, we were able to help doctors who had stuck themselves with a needle. Then we were able to give mothers who are about to give birth the drugs that prevented them from infecting their children. We can now do that a hundred percent, protect the children, very close to a hundred . So low that you cannot measure the number of infected infants. And we can now begin to do it in such a way that one shot can protect you for two months or eight months. There is a new drug that has just come out, one of the most beautiful pieces of science I have ever seen, that there is one drug which works in a tiny, tiny amount, the most potent drug ever found, has a longest, half-life, tremendously safe, a million fold difference between the amount that is toxic and the amount that works against the virus. One shot looks like it is going to protect you for eight months. Let us translate that to COVID. COVID has a lot of great targets. There were already drugs on the shelf, never developed, being developed now to do that. Monoclonal antibodies, chemicals to stop various things that the virus needs to do. Those drugs can be very effective at helping people or say healthcare workers who are regularly exposed, or suppose you are a family member of somebody who's caught it. You know you are exposed. You could take these drugs and never get infected. Or if you had been infected, you could take these drugs and never get sick. That is coming. That I am certain we are going to have. And pretty quickly, those drugs are moving along quickly. It is pretty easy to develop those drugs because you do not have to take a huge population. You have to take a few 1850
people and show that the concentration of viruses drop. And if they drop, you know, if the drug is relatively safe, you know you are in good territory. So there will be prophylactic drugs. First of all, treatment drugs, curative drugs, and drugs that prevent you from getting infected. That is on the way. EM: So how does that differ? People keep talking about vaccines as opposed to these prophylactic drugs. Why is it thought that way? Why has all of our focus been on vaccines? Because when you even look at, like you mentioned, AIDS/HIV for all these years, we have been trying to come up with a vaccine for it and it does not exist. But they have been able, as you said, to control the spread, or at least control the behavior within people with these drugs that exist. Why has our focus been so on a vaccine as opposed to prophylactic? WH: I think a vaccine is what we are hoping for political and economic purpose. People understand the vaccine. People do not have that necessary same familiarity with prophylactic products. Those people who travel to malaria zones do. And there is a really good example that mothers should have. And that is very often, especially at the right season, infants are given a treatment that prevents them from getting respiratory syncytial virus, RSV. So that is something that happens today. Those are preventive drugs that you do not wait until you get the disease. You use a drug before. And I think it has to do with the idea that you want to protect everybody blanket. The problem with that is, is that this is a very tricky virus. This is not like polio or measles or mumps where your body clears it. This is a virus that goes in. You get it. Most people get over it, but you forget you ever had it. The same people could get reinfected with the same kinds of viruses. And we know that for sixty years of watching coronaviruses that cause us Coles, you get you yourself can get a coronavirus cold with one virus and the next year get exactly the same one. The virus doesn't even have to disguise itself like polio does. Polio kind of gets you and then comes back with a hat and dark glasses and a raincoat to get you again. Right? But this virus fools you even before that. We now know that if we watch people, they get infected, they make antibodies and very quickly, in a matter of a few months, their antibody levels are dropping, dropping, dropping, which means the virus can come right back. So it is going to be hard to make a vaccine.
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And whether it is going to be safe is another issue, especially for the most people at highest risks which are old people, people like me who are older than 70. It is hard for us to make vaccines. So you got to really jazz up, boost it up, and that can be tough on the body. So I think we are going to hear about it. The effort is, there is a massive effort to develop these drugs. You are just not hearing about it. I predict in about two months, the news is going to be about these drugs. It will take about two months. That is how long it is taking. A number of these are just about coming out. You are hearing about monoclonal antibodies. You are going to be starting hear about other drugs. You are going to hear about this, and it is going to be a great bridge to a safe and effective vaccine if we can make one. EM: Let me ask this. We talked about this awhile ago, the idea of the quarantine and the isolation and all of that because if you stop where the virus can spread, it dies out in the community. If you have these drugs and you did a mass distribution of them to the community, to the populace, would that work to starve off the virus and it would drop in numbers? WH: The answer is yes, but there is a big if. The if is a big difference from treating people who are not exposed and have no risk as you would with a vaccine. See with a vaccine you are treating fully healthy people. And in this case, you may be treating billions. So your side effect profile has to be amazing. One in a hundred thousand bad events, like a death, is going to kill tens of thousands of people. That is why vaccines are so tricky. And that is why you have to be so very careful of their side effects. With these drugs, you treat people who are, first of all, you know, they are going to be regularly exposed healthcare workers, right? You will treat people who know they have been exposed and that will make contact tracing all the more attractive. Let me take you again back to the early days of AIDS, before there were drugs to treat AIDS, everybody avoided who could avoid getting tested because the test result was not a positive diagnosis. It meant you were going to die. Once we had drugs, people wanted to be tested. The same thing will be for contact tracing. The moment we have these drugs, people are going to want to know that they were exposed because there is something they can do about it. That is a much narrower group of people that you would use if you were using a vaccine to protect everybody. The use does not have to be so widespread. It can be 1852
done through contact tracing and everybody who knows they have been exposed. If you have a friend that is infected, a family member that is infected, you have somebody in a workplace that is infected, then you can treat everybody. And I think that is, for example, let's take these meat packing plants. What you would do is you treat everybody in the meat packing plant and that would help them. They would not get infected. They would not transmit it to other people. You could stop that local transmission. Same in a school. If three or four kids got infected, you could treat everybody in the school and it would stop it. So that is the kind of use I foresee, not a mass use across everybody who is healthy because it is going to be a long time. It has taken us twenty years to get the side effect profile of these things down low enough for many people who might be exposed to be used. I think we can speed that up a lot, but not infinitely. EM: Dr. Haseltine as we slowly tick out of time. We have only got about fifteen seconds left. Is there hope? WH: There is, of course, hope. We have survived a lot worse than this. We have survived a hundred years of bubonic plague. We have survived smallpox. Human beings survive. We may be damaged in our survival, but we survive and we will survive this. EM: And with that, I want to say thank you very much to Dr. William Haseltine, scientist, author and philanthropist. He is the founder, chairman and president of ACCESS Health International, and president of the Haseltine Foundation for Science and the Arts. And how can we forget? He is got a new book out, A Family Guide to COVID: Questions and Answers for Parents, Grandparents, and Children. Dr. Haseltine, thank you again for joining us. It is always a pleasure to talk to you. WH: My pleasure. Thank you very much.
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Interview With CNN Erin Burnett July 13, 2020 | Interview
Erin Burnett (EB): Up front now, William Haseltine. He is a former professor at Harvard Medical School and The School of Public Health and author of A Family Guide to COVID. Professor, I really appreciate your time tonight. You have been looking at studies like these. How significant are these sorts of conclusions? William Haseltine (WH): These are very significant for the future of this epidemic. What they show is something we had suspected but not really known until now. This is, like its sister coronaviruses, the ones that give us colds, very different from the childhood viruses. With viruses such as Measles and mumps, if you get them once, then you are protected for life. With the cold viruses, it is really different. You get them and forget them. Your body forgets they were ever infected, and they come back and get you again every year. You can be re-infected by the same cold virus and get the same cold every year. We did not know that was happening with this virus, but there was an early study from China, and now two other studies from Spain and the UK, that actually measure the virus and antibodies in people and watch the immunity decline. That is what we were afraid of. EB: Obviously the time frames they are talking about are pretty incredible. A few weeks, twenty to thirty days. We have all been told you may only get a few years of immunity. It was assumed you would have some. This is really quite different than what people had been hearing. Professor, one clinic in New York City was particularly hard hit by the virus and had sixty-eight percent of its antibody tests come back positive. Obviously, those are people who actually went in and got the tests. It would not be sixty-eight percent of the whole community having had it, but it was enough to have people talking about herd immunity. Once you get to herd immunity, so many people have had it, it is essentially the same as 1854
vaccinating everybody. This idea is gone. You say herd immunity will never likely be achieved for this coronavirus. How come? WH: First of all, herd immunity depends on long lasting immunity. If it does not exist, you cannot get herd immunity. So, we do not have herd immunity for the cold viruses, such as coronaviruses. This looks just like its brothers and sisters except a lot nastier. It does not look as if it is different in the sense it makes your immune system react any more strongly. It just does not seem to. Your immunity seems to fade away. In fact, we knew from the very beginning that immunity was odd with this virus because some people get over it, and you cannot find any antibodies. So, it is a very strange virus that is messing with our immune system in very interesting and unusual ways, but ways that are very concerning for anybody who thinks that herd immunity is a good idea. It will not happen. Individually, that means if you had it, you have to be just as careful as if you did not have it because you might get it again, causing exactly the same disease, or even worse, as it did the first time. EB: This is all really sobering. You are left with therapies that may work, but also this concept of a vaccine. So many people are now just betting on a vaccine as a sure thing and a matter of time. Even in this country, there will be hundreds of millions of doses ready by the end of the year even before they find out if the vaccines actually work because they want to make sure they are ready if they do work. Do you think a vaccine will work? Obviously, we don’t have one for the other coronaviruses. They are not as deadly. We never felt the need to. Do you think a vaccine is a sure thing or not? WH: It is definitely not a sure thing, but it is also not a sure thing that it won’t work. It gets a little complicated when a virus is messing with your immune system. It has its own tools. It goes in and changes your immune system. When it leaves, it doesn’t leave much of a trace. A vaccine does not have all of those tools. A vaccine is just a tiny part of the virus most of the time, so it might not do that. On the other hand, if you have some lasting immunity and the virus comes in and uses its tools to make you forget you ever saw the virus, it could be a different situation. We are left again with an 1855
uncertainty, and one thing we all hate is uncertainty. However, that is our life today. EB: All right. Professor Haseltine I appreciate your time. Thank you. WH: You are welcome. EB: A sobering but important one.
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Interview With Thrive Global July 15, 2020 | Interview
Lauren Clark (LC): If you were to imagine the significance of childhood's imagination, during this particular time, how would you articulate it? How is it useful for adults in mental navigation and maneuvering through this extensive time of quarantine? William Haseltine (WH): I just recall my own feelings and thoughts during the time of polio. I did not know exactly what was out there, but I knew there was something dreadful that my parents were afraid of for themselves and for me. It was a feeling of real discomfort that manifested in, “you can only play with three friends,” “you can't go to the swimming pool,” “you can't go to the movie theaters,” and “you have to stay inside.” It was a time of deep unease and anxiety, not because I knew what was happening, but rather because I knew my parents were worried. That is how children perceive this. LC: According to your perspective, if children were to articulate, or draw out their understanding of COVID-19, what would this drawing look like? WH: It would look like a very fearful monster outside their door. LC: Based on your understanding, what has made COVID-19 the most challenging thing to deal with? Why is it different than anything we have ever experienced before? WH: It is not different from anything we have ever experienced before. People have experienced the bubonic plague, smallpox, and polio. We have just forgotten what dealing with something like this is like. LC: In your latest book, A Family's Guide To COVID, you focus on the dilemma of parents, grandparents, and other familial figures to protect their children. What is the phenomenon of using fantasy's ability to educate children in a way, where they feel they have some level of agency and control within this particular epidemic?
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WH: I think it is very important not to broadly say that children are this way or children are that way. Children are just as individual as adults, so for each child, you have to pay attention, even within a family, to the differences in their reactions. What will work to give agency to one child will not work for another. We have to understand what each child’s interests are and amplify their experiences with what actually interests them. It is extremely important that children feel that they have some degree of control. One way to do that, for example, is to customize their protective equipment. You could give them face shields covered in Star Wars, Paw Patrol, Hello Kitty, or other characters and images they like. You could also focus on their ability to do creative things. From my own experience, I can tell you that one of my grandchildren loves virtual education, while the other hates it. Different children have different abilities to respond to various pressures and finding unique ways to support them in their response to what is going on today is critical. LC: You recently returned from Wuhan, China, where you served as the Chair of the 9th US- China Health Summit. Have you observed a different way, in which COVID-19 is being explained to Chinese children? Kindly elaborate, and how has differentiation of culture and methodologies of containment contributed to this? WH: In general, the Chinese are very child-focused. From the very beginning, there were tremendous numbers of books and videos to explain what was happening to children in ways that I just simply have not seen in the U.S. I have surveyed many of the books and some of the films that are out. In terms of the emphasis that our society is placing on children's understanding of COVID, I would say that the United States is doing 1/20th of what the Chinese are doing. The Chinese have made an enormous effort to explain and have children understand COVID. LC: In writing your recent book, even with all of your expertise, how have you had to return to your own inner child, in order to understand the virus, through the eyes of children? WH: My experience with polio was extremely helpful. I had recalled it for many years, but this brought it all back. In addition to that, I had pericarditis when I was 7 years old. That meant I was confined to my home for about 6 months and couldn't go outside. I can recall my feelings during that time as well. They have helped me 1858
with understanding what children and my grandchildren are going through right now, so I have recalled my own personal experiences with a pandemic and with a disease that I myself suffered. LC: Has your recent book forced you to re-examine your own research, as it relates to possible drug vaccinations for COVID-19? What have been the challenges in telling a hard truth to parents about the aura of uncertainty? WH: Writing the book reinforced my belief in science as a factbased part of human culture and the importance of dealing with the world as it is, rather than the world as we wish it to be. As a scientist, you do not have the luxury to wish the world to be one way or another. Your job is to find out what it is, regardless of what you think. The way most scientific mistakes are made is to believe you understand nature when your job is not to predict, but rather to observe and interpret. I would say the same applies when you look at an epidemic. There is a great desire to transform the world into something that is suitable for you and your individual life when it is not. This epidemic makes that abundantly clear. LC: As a scientist how would you differentiate the level of uncertainty during the initial AIDS epidemic versus COVID-19? Is the general public experiencing a greater level of intensity than we had during the AIDS epidemic? WH: Absolutely. The amount of information about this epidemic is far greater than what we had about HIV/AIDS. That is because it affects everyone, not just limited populations as was believed to be the case for HIV. LC: You developed the first strategy in creating a drug for HIV. Do you see a similar methodology, which can be used for COVID19? What more is required in developing a suitable vaccination for the coronavirus? What more is needed? WH: Fortunately, there is tremendous interest all over the world in developing drugs that will help us against COVID-19. This was not the case with HIV for many years. There has also been an enormous global effort, which is very powerful and has resulted in very rapid engagement across the world. We also now have many global centers of excellence that can address these issues. When HIV came along, only the United States and some parts of Europe were engaged. Now, the United States, Europe, China, Japan, Korea, all of Southeast Asia, India, and everyone else has the capabilities that 1859
we had then. I would say that at least a hundred times more effort has been put toward developing COVID remedies and vaccines than there was to developing the same for HIV. That, of course, is wonderfully encouraging. LC: What challenges have you experienced in securing your own mental wellness, during this quarantine era? Has quarantine allowed you to discover creative skills about yourself? Do you see these skills being used in developing a treatment for the coronavirus? WH: As a scientist and public health advocate, I've had an intense focus on understanding the virus, the disease, the social impact, and the message to control the pandemic through medical, government, and social methods. This has allowed me to use my many years of experience in all aspects of health, and I believe it has been very beneficial to my mental health. Additionally, I have very strong family support by my wife, grown children, and grandchildren. I believe there is no better guarantee for mental health than productive work and a strong family life. The quarantine has allowed me to deploy my many skills and understanding of science, public health, and medicine. It has also allowed me to use my skills in public communication to help others achieve a level of comfort and understanding with what is happening in this current pandemic. As part of the quarantine process, I have acquired a country home and rediscovered my love of gardening and taking care of our natural surroundings, a skill that I had not practiced since my early youth. LC: Let's pretend you are on another island with very few people. You are sitting back and are observing the current situation. What do you see as it pertains to US citizens and our mental wellness? In protecting our mental health, what are we doing wrong? What are we getting right? WH: In any crisis, we need three fundamental elements. The first is leadership, which is capable of clear, consistent, credible, and compassionate communication to the people of a nation. The absence of such communication by our political leaders in the United States is cause for great anxiety throughout the country. The second requirement is strong and effective governance. In this crisis, that means a public health service that is not only capable of formulating policy, but also executing it at the national, state, 1860
county, municipal, and local level. We are absent in such effective and organized public health implementation, which leaves people confused. The results of such an absence of a public service in the United States leads to a patchwork of widely differing approaches. It may vary from community to community and even in some cases, from block to block within a city. That creates substantial uncertainty and anxiety. The final need for coping with a crisis is social solidarity. This is the feeling that everyone is in this together as equals, both in their risk and their opportunity to access medical care, and is responsible for themselves, their families, and others in modifying their behavior. In the United States, this sense of social solidarity varies regionally, but in general, it is weaker than it is in many other countries. Again, this produces anxiety and uncertainty over whether our neighbor will protect us as we will protect them. LC: If you could paint the current aura of the world with 4 colors, what would you select. What is your reason for choosing these four? WH: None of the colors would be bright, but rather muted. I would paint much of Asia in a dusky rose and the United States in dark gray. Actually, I would paint all of North and South America, with the exception of Canada, in dark gray. India would also be in dark gray, most of Europe would be fuchsia, Russia would be painted in dark gray, and Australia and New Zealand would be a dusky rose. Dusky rose means the infection is under control, except for sporadic outbreaks that are contained. Fuchsia means that the infection is not under control, but is not out of control either, and dark gray represents a situation that is disastrous in the number of infections, is rampant, and is out of control. LC: How do you envision American families taking advantage of this time to strengthen familial bonds with their children and loved ones? WH: In reflecting on the social and cultural impact of COVID19, I have come to the conclusion that one of the fundamental reasons for family structure is protection in times of crisis. Almost all families reconnect and rebond to protect one another. In my view, it has been an extremely positive time for reinforcing the need for family values and the protective power of families. By families, I am not only referring to the traditional family of husband, wife, and children, but also the more complicated families, such as LGBTQ+ 1861
couples and the families with unrelated members and older people in the family circle. There has been a renewed emphasis on the importance of tight familial relationships. LC: If you could draw out a safer re-opening of public, and private, spaces in the United States, what would that look like? How would it be more effective in contributing to containing the virus? WH: We have excellent examples around the world of how to contain the infection, without a vaccine or with a defective treatment or vaccine. Many countries, such as our European neighbors and the Canadians, have done it, while we have not. We do not need to look any further than these examples in Asia, Australia, New Zealand, and Europe to understand what needs to be done. Unfortunately we are not doing it. If we are specifically talking about a safer re-opening of schools, it is important to note that when people discuss this matter, they focus on K-6 and they say that the children are resistant to infection, which is only partially true. They are resistant, but they are also about two-thirds as infectable. In many cases, they can transmit the virus more effectively than adults. If they do get sick, they often get some very serious life-threatening illness. The big gap in the discussion of schools is high school. Kids in high school, ages 14 and above, are as equally infectable as adults. There is no privilege of infection, and in some cases, they can transmit the virus more effectively. People between the ages of 15-50 make up half of the people who are in the hospital. Thus, in order to contain the virus more effectively, I plead with educators and policymakers not to base decisions on school reopening only on K-6, but on grades 7-12 as well.
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Interview With CNN Anderson Cooper July 15, 2020 | Interview
Anderson Cooper (AC): Joining us, CNN chief medical correspondent, Dr. Sanjay Gupta. Also, William Haseltine, former Harvard researcher and recent author of A Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children. Sanjay, another day goes by, America is dying. Still no plan from President Trump and the federal government. We had this conversation over and over again and with the good professor Haseltine as well, but without federal engagement, professor Haseltine said in the past the answer is each of us doing all we can, citizens and everybody else, stakeholders being involved but without the federal government, does this get better? Sanjay Gupta (SG): I think it is very hard for it to get better. Clearly, the status quo is not working, Anderson. The numbers continue to get worse. What we are seeing now is a pattern. The reason that the federal guidance is so important is because what happens in so many communities and states is that things get into a real crisis situation before action is taken. People know what to do. The public health strategies are actually not that complicated here. We have seen it work in certain states in this country for periods of time and in countries around the world. We do not have to remind people that there are countries around the world who have had fewer infected people throughout this entire pandemic than has happened in just one day in certain states in this country. So, the public health strategy is obvious. What is happening is the states are red lining and the virus makes a decision for them. They have to go into some sort of shutdown mode because the hospitals are becoming overly full, or they have to have these terrible situations where people cannot get care when they need it. AC: Professor Haseltine, has there been a country in the industrialized world that has ever responded to a pandemic or national health emergency as badly as we are right now? I am trying to think of other examples. I can understand the countries that lack 1863
resources or have totally corrupt leadership not responding. However, it is hard to imagine anyone else handling this the way the United States has. WH: We are in a small select unfortunate group of countries that includes Brazil, Russia, and India. Those are different kinds of countries, but certainly some of them have well developed economies, and are a mix of developed and developing nations. So, we are doing extremely poorly. It is a very dangerous situation, and it is getting worse. We desperately need guidance and the southern states, as we discussed before, need federal help. They are running out of resources and are shipping people to hospitals that aren’t well prepared to deal with them. They will be shortly turning away people for lack of facilities. It is a dire situation in some parts of our country, and it is crying out for federal intervention. AC: Sanjay, part of what Dr. Fauci told the Atlantic Magazine today, he said “We got to almost reset this and say let’s stop this nonsense and figure out how to get our control over this now.” That makes sense, but without the president and all the people around him buying in, I am not sure how any of that changes. SG: I think the guidelines were straightforward and easy to understand. If you want to do a reset, it does not mean you have to shut down the whole country again, although some parts of the country would likely need to be shut down. If you live in a community where the case numbers have gone up five days in a row, you have to go back a phase, which might mean shutting down. You need to get the numbers down fourteen days in a row. If you start to do that, there is a path out of this. This is not an inevitable situation that is unfolding now. Create a tsunami of activity around testing. It was 2.5 months ago that Ambassador Birx said we need a breakthrough on testing. We still do not have it. People in nursing homes often cannot get tested. In Arizona, it might take eleven days to get the test results back. We are in the middle of July now. The reset involves basically doing all the things we know how to do, said we were going to do, and people promised we would do. We just need to actually do them at this point. I don’t know what else it takes, Anderson. We come on every night and talk about this. My parents live in Florida. People are really frightened down there because of what Dr. Haseltine is saying. They are worried somebody is going to have shortness of breath. They are going to call for an 1864
ambulance and be told, look, we would love to come get you, but we do not know where to take you because there are so many ICU beds that are full. You are going to have to ride it out at home. It is unbelievable. We just keep saying the same thing, and I do not know what else to say at this point. AC: It is so strange, professor. I remember you talking on this program in the past about when you were a kid, and Polio was a concern. People just knew how to behave, and young kids would not go out in groups of more than three. You knew not to go to community activities. You think back to WWII when there was this national effort to fight the war and beat back fascism which was an extraordinary nationwide effort, not even talking about globally but in terms of this country alone. Mask wearing could be a patriotic thing. It is protecting our country. Social distancing could be sold as a patriotic effort to get our country back on track and yet, all of that has just been squandered. WH: I think what may happen is over the school reopenings. I’m working on understanding this movement more, but I can tell you everybody who listens will hear a scream of anguished parents. They do not know what is going to happen to their children and themselves, and parents are vocal. They have a real passion for protection of their children, and I think they may be the tipping point that convinces even the most recalcitrant amongst administration and Congress that it is really time to get serious. When the average mother is terrified for her child, to send that child to school, you have a political forest of significant magnitude. If the politicians are listening to what I am hearing, they will pay attention. It is what we need now. AC: Sanjay, Dr. Fauci made a comparison this week to the influenza pandemic of 1918. I know you talked to him about that. What did he say? SG: He was very worried that there was a lot of similarities between what was happening now and 1918. The comment was perceived as this could have the same impact and magnitude of that pandemic 100 years ago. When we talked today, he wanted to make it clear he is obviously very worried about that pandemic as we all are. However, the idea that you had anywhere between 50 and 100 million people died during that pandemic, and if you do the math now and account for the change in population, that could mean 200 1865
to 250 million people would die from this pandemic. He did not want to suggest that. As bad as this is, as gloomy as these numbers and the entire situation is, we are still a different world than we were 100 years ago. This is a contagious virus. It is circumnavigating the globe. It is far more lethal than the seasonal flu, but we do know how to take care of people in hospitals if they get there. Intensive care is much better. We possibly have therapeutics coming along and maybe a vaccine. He wanted to be careful. In terms of how bad this is, we still need to not over-state how bad this could be. AC: Yeah. Certainly, I agree with that. Thank you. I appreciate it.
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Interview With CNN John Berman July 15, 2020 | Interview
John Berman (JB): This morning, promising news about a potential coronavirus vaccine. Biotech company Moderna has published its phase I results, which show that the vaccine did induce an immune response against coronavirus, with only mild side effects. The final phase of Moderna’s study begins later this month. This is the first vaccine candidate to publish results in a peer-reviewed medical journal. Joining us now is William Haseltine. He is a former professor at Harvard Medical School and Harvard School of Public Health. Professor, we are thrilled to have you on this morning to talk to you about this because this is really right in your wheelhouse. I think you have been appropriately skeptical, as always, about development over time. When you see the results, the peerreviewed data now, which is wonderful to get, what is your reaction? William Haseltine (WH): Firstly, it is good to see that a new technology is having the desired effect, which is inducing antibodies to the antigen, which is COVID. Secondly, there were some elicited neutralizing antibodies, which is good as well. However, we will have to see whether those were protective or not. I have to challenge your comment about the side effects. There were some very severe side effects at the high dose, enough to send one young man to the hospital. There were three out of fifteen in the high dose that received severe adverse events. That caused them to reduce the dose of the vaccine in the second bigger trial. So, they are not out of the woods on the safety issue. JB: That is a great point, and I am glad you brought that up. The side effects were mild enough to continue with the trials. They were not so severe that they had to halt the trials. That is an important distinction. But I have listened to you also explain why making sure there are no side effects is so important, because you are talking about administering this on an enormous scale. Maybe over a billion people will get this. 1867
WH: That is right. Vaccines are different from drugs, where you can tolerate some effect if you are already sick. Healthy people are receiving the vaccine. In America, we are talking about vaccinating 300 million people. In the world, perhaps three to five billion people will be vaccinated. A small side effect shows up as an enormous number of people injured. That is why we have to be so careful. Most people are most concerned about the safety of a vaccine and are willing to put up with some weakness on the efficacy side. I think in this case we have to be very careful to look at safety and then efficacy because this is a tricky virus. You get the virus, your body begins to clear it, and then forgets it ever had it. The virus can sneak back in, apparently, year after year, with these kinds of viruses. It is a trickier thing than the other viruses we have been successful with, like Polio, Measles, mumps, et cetera. But that does not mean it is not going to work. I think this is a good and hopeful sign, and it is great to see it in the literature. Alisyn Camerota (AC): But professor Haseltine, everywhere I go, people say what is the latest with the vaccine? What is happening with the vaccine? What do we need to know? And so, this morning, I mean scale of one to ten, how optimistic should we be about this one as it heads into phase 3? WH: Five. About a fifty-fifty chance. The good thing is that there are many other vaccines as well. This is one of a whole bunch. We have our entire medical community. We have the National Institutes of Health. We have everybody pushing the pharmaceutical industry as hard as they can, not only in this country, but around the world. I look all around the world to look at the vaccines. The Chinese are doing a good job. The Indians are doing an interesting job. French. All sorts of people. In Singapore, they are doing a good job. We are going to have a vaccine eventually. JB: When we say there is evidence that it has produced neutralizing antibodies, what exactly does that mean? How much do we know about whether this vaccine can prevent people from getting the virus? WH: The answer to the last question is that we do not know that yet. You have to wait until you actually see people who are getting infected and look at the difference between those that have the vaccine and those that do not. Neutralizing antibodies means if you take a little bit of the blood from these patients and purify it 1868
away from the cells, it can stop the virus from infecting another cell. You put the virus in with cells, you put some of the serum in and it stops it at some dilution. What they found is the ratio between antibodies that stick to the virus and antibodies that stop the virus is about a thousand to one. That itself is a little bit worrying, but not enough to stop any trial. There are a lot of binding antibodies and a few neutralizing antibodies, about a ratio of 1,000 to 1. I know we are getting into the weeds a little bit, but it is important when you are trying to see if you can stop the virus with those neutralizing antibodies and not cause some other effect with all the binding antibodies. It is an interesting positive development. I am very encouraged by the fact that this is a brand-new technology for vaccines. It seems to do what other older technologies do. That is good news. AC: Professor, you have an op-ed on CNN that says we are wasting time talking about herd immunity. Why is that? WH: There are two reasons. First of all, herd immunity in the United States, if we were ever to go for it, would cost about five million lives, five million dead people. Not five million infected, five million dead. That is because you would have to infect sixty percent of the population. We know what the death rate is from this virus. Nobody wants to do that. Secondly, coronaviruses I referred to a little while ago are more complicated. These viruses have the habit of going in and your body forgetting it. We were not quite sure that was true of this coronavirus until three different studies in China, England, and Spain, which showed that over time, antibodies begin to fade in people who are infected. If that were not enough, when this virus goes in, it has a way of turning off exactly the response you need. The vaccine is not a shield. A vaccine is an early warning system that allows your body to react in days, not weeks to what you have been infected, and the virus can turn that down. This is a sneaky virus that can get back in after you have cleared it. There is no such thing as herd immunity. JB: Professor William Haseltine, thank you so much for being on. WH: Thank you for letting me talk about details. JB: It’s important. WH: It is.
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Interview With CNN Don Lemon July 16, 2020 | Interview
Don Lemon (DL): Let us bring in now William Haseltine, former professor at Harvard Medical School, and Ron Klain, who coordinated the Ebola response in the Obama White House. So good to have both of you on. Thank you so much. Professor Haseltine, let me start with you. Highest single day yet again today. Cases are rising in 39 states. You say the United States could end up going beyond Dr. Fauci’s warning of 100,000 cases in a day. Tell us why you say that. Why do you believe that? William Haseltine (WH): If you look, you see an epidemic out of control. We thought we might have reached a plateau, but now we are climbing a very steep mountain at a rate which is frightening to all of us. We do not know where that will end. We know these viruses have the capability to infect most of the population. Even under the worst scenario that you can imagine, you could have 200,000 a day. You could have 500,000 a day. There is no real limit until you hit about half of our population or more. That means if we really let it go and do what they say, “just ride that sucker through,” we are talking about five million dead Americans and ten to twenty million permanently injured Americans. That is what we are talking about. We need to stop it now. We know how to stop it. We know what we should do. However, we need the leadership at the federal and state level. It is shocking to me that those states that thought that they were most protected because of their philosophy seem to be the most affected today: Florida, Georgia, Texas, and others. Anybody in epidemiology, and anybody who understands these viruses, can see this is an uncontrolled and upsetting situation to find ourselves in. DL: Those states were also bragging about it. We figured out how to do it, Florida said, and look at Florida now, Ron. What can be done when the president’s focus is elsewhere? He was talking about home appliances and showerheads today. He’s promoting
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Goya beans. What does the country do when the president pretends that there is no crisis or that the crisis is over? What are we to do? Ron Klain (RK): Sadly, what we are to do, Don, is get sick in record numbers and go to the hospital to die in record numbers. Whether or not it ultimately gets to the kind of numbers Dr. Haseltine is talking about, even frankly, if it just stays at 70,000 a day, we are in one of the worst epidemics in the world right now. Wherever it winds up is because of a lack of leadership from the president. We still do not have testing widespread, available, and accessible. We do not have contact tracing, so we cannot run down and isolate chains of transmission. We do not have adequate protective gear. How can we be in a position as a country that the president won’t use his power to order the manufacture of masks, gloves, face shields, gowns for our doctors, nurses, and our front line workers? We are seeing shortages of these again at the crest of the disease. How can we be in a place where the president is saying anything other than every American should wear a mask when they are around other people? Of all the things we could do, wearing a mask is the simplest to reduce transmission of the disease. We need to do everything I said, but masking is very inexpensive and easy to implement, and it is inexcusable that the president isn’t going all-out for it. DL: Do not get me started on the whole mask situation. We have had times in this country where we have had to make incredible sacrifices. We made a sacrifice. We sat on our couches or whatever. However, this isn’t as if someone is drafting you into a war like they did with our relatives in years and decades past. This isn’t Vietnam or World War II, where people are going off to war. They are asking you to wear a mask. That is what I don’t understand, Ron. Before we go to the break, this has been weighing on me here because I want to talk about this. Ron, there is another study about hydroxychloroquine that said it does not work, this time for patients who are not hospitalized. Another piece of evidence from something the president touted as a quick fix. Ron? RK: The president has been selling these false solutions throughout. He has been promising people silver bullets and magic cures. The only way we are going to fight this virus right now for the time being before a vaccine is by using the basic tools of public health. Testing, tracing, isolation, gear, protective gear, masking, and 1871
all these things that are in our reach that exist. Those are the things that are going to bend the curve and help reduce the number of cases we are seeing. DL: Yeah, our time is short. Thank you. I apologize for the shortness of time. You can blame Chris Cuomo for that. Thank you both.
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Interview with CNN Don Lemon July 20, 2020 | Interview
DON LEMON, CNN HOST: Florida teachers, suing to overturn Governor Ron DeSantis' emergency order forcing schools in that state to reopen. That as we learn more about what role kids play in the spread of the coronavirus. Let's discuss now, from former Harvard Medical School Professor, William Haseltine. He is the author of the new e-book. It's called "A Family Guide to COVID." And it is much needed so, doctor, thank you. Professor, I should say, thank you so much for joining. You talked in the e-book about how virus transmits in children. The virus transmit in children, now researchers in South Korea have found that children between the ages of 10 and 19 can transmit the virus just as much as adults and that children nine and under transmit the virus at a lower rate. What does that mean though for reopening schools? DR. WILLIAM HASELTINE, CHAIR AND PRESIDENT ACCESS HEALTH INTERNATIONAL: Well, I think that every parent knows about cold viruses. And this is a cold virus for the very bad habit. We know, if you send your kids to school, they come back with colds and they give those colds to you? That is exactly what happens with this virus too. And what the Korean study shows, is yes, kids nine to 19, spread the virus like adults, but kids a little bit younger, don't spread it so rapidly, but the catch there is they have three times as many contacts as the older people. So it averages out the spread about the same. And as you've heard earlier in your program today and reread across the country, young children are getting severely ill and unfortunately some are dying. LEMON: I want to play this for you. This is Missouri's governor, what he said today about the kids going back to school. Watch this. (BEGIN VIDEO CLIP)
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GOV. MIKE PARSON (R-MO): These kids have got to get back to school, they are at the lowest risk possible. And if they do get COVID-19, which they will, and they will when they go to school. They are not going to the hospitals. They are not going to have to sit in doctor offices. They are going to go home and they are going to get over it. (END VIDEO CLIP) LEMON: What do you think of that, is that message dangerousHASELTINE: I think he should talk to the mother who just lost her children. I have friends whose son, grandson barely made it. Just barely made it. They rushed him to the hospital, he needed six people to attend him, to get him back alive. And he was in the hospital for weeks and he will have heart damage for the rest of his life. This is not a joke. So, let me say, there's a very thorough study that everybody should take a look at. Our national academy of sciences which includes medicine, science and engineering put out a detailed report on the question of should kids go back to school? And I have to say, the most unsettling part of that is it admits outright, we don't know the answers. And therefore, if you don't know the answers you don't proceed blindly. There's something else I would like to say that I talked about in the book a lot. And that is a hierarchy of risk. People when they consider sending their kids back to school should think, first of all, what is the risk? How many people around me are infected? You can find that out by looking at your zip code or your county? How many people are there, if it's more than one or two per zip code, you could be in trouble? The second thing is, do I have a risk? Am I sick? Are my kids sick? Does he have diabetes? Is he over weight, does he have asthma or does anybody in my family have that that is at higher risk? Then you start to look at the schools. And I can tell you, that there is no guidance and the national academy of reports said the same thing. There is no federal guidance. There are very vague rules and some very vague questions. And it's driving teachers and parents completely nuts. They don't know, we have some answers in our book. And I'm writing a new book on the topic of how you decide what to do for 1874
your kids in school. For both your k-6 and your k-12, which are two different kinds of problems. But it is a huge problem that I think this is going to be the tipping point where people don't think mostly about politics, they think about their kids. Is this world safe for my kids and who has made it safe and who has made it more dangerous? LEMON: Professor, thank you for your time, I appreciate it. HASELTINE: Thank you.
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Interview With CNN Jake Tapper July 20, 2020 | Interview
Jake Tapper (JT): Right now, I want to bring in William Haseltine. He is a former professor at Harvard Medical School and author of the new book A Family Guide to COVID. Thank you so much for joining us. I appreciate it. Just minutes ago, President Trump tweeted this photo of himself, seemingly encouraging mask wearing and calling it patriotic. What did you make of it? William Haseltine (WH): I am very happy to see that. It is about time that happened. We are in a pretty desperate situation right now with the virus raging across the country. More than one to two people are dying every minute today and will be tomorrow as well. It is welcomed to see the president finally doing what health experts say. I hope he and our administration are beginning to follow many of the other recommendations as well. We need leadership desperately. It is not just enough for states and local communities to take action. We need leadership. JT: Absolutely. I want to talk about some of the areas where leadership has been sorely lacking. But I also want to talk about this encouraging news in the search for a vaccine. How significant do you think the early results from these trials are? WH: They are early results but can only be described as encouraging. Many of the vaccines, about five or six, show immune and neutralizing responses, which is what you want. They have varying degrees of safety, which is not good. Some of the them are not particularly safe. They have caused seriously adverse reactions. However, many of them seem to be fully tolerable. Almost all of them seem to need more than one dose, which is not optimal. But I would say these are encouraging, yet early, results. We need to wait to see whether or not they are going to prevent infection. If they prevent infection, will they prevent disease, or if they do not prevent infection, will they prevent disease? That is up in the air. But, this is nothing but encouraging at this point.
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JT: What are the next steps for the trials? How soon theoretically might the general public get one of these vaccines should everything go well from here on out? WH: I think that the general public at first will not be the first to receive the vaccine. At first, emergency health care workers and hospital workers that are exposed to the virus everyday will get the vaccine. Then it might be people who are known to be exposed to this virus. The general public will get the vaccine only after we have much more experience with the safety profile, particularly for people who are older, weaker, have fragile immune systems, and children. It is going to take some time. I wouldn’t be surprised if something were approved this year given the effort right now. That something may be effective and safe, but we won’t be absolutely sure on either score. So, I think it is going to be some time before there is a vaccine. I think we do not have that time right now. That’s four, five, six months away. With over one person dying per minute every day, we have to do something more than just waiting. We have to control how we mingle, wear masks, and distance. We need leadership and organization. It is not enough to have leadership. You have to have the tools to implement as well. We need the full force of the federal government coming in and helping the places that need help. JT: I want to play for you something that Missouri governor Mike Parson told a radio show about children and coronavirus, something fairly shocking. Take a listen. Mike Parson (MP): “These kids have got to get back to school. They’re at the lowest risk possible. If they do get COVID-19, which they will, and they will when they go to school, they are not going to the hospitals. They are not going to have to sit in doctor’s offices. They are going to go home, and they are going to get over it.” JT: “They are going to go home, and they are going to get over it.” Now, it seems true that children under the age of 9 have the least adverse reaction. But there was so much there that was ignorant; I did not even know how to react. What do you make of it? WH: Firstly, when we talk about schools, we are talking about k-12. Those people over ten have the same kind of risk profile you or I do and can get sick. Secondly, we know when kids do get sick, it is truly horrendous. They get the very late stage of the disease with heart disease, brain disease, and kidney disease. I have a friend whose 1877
son went through that. It is terrible. He will be damaged probably for the rest of his life, even with contracting the virus at this young age. So, if they do get it, it is a very bad experience. Not only that, but they do spread the virus. This is a cold virus in its essence, with a very unpleasant effect that it kills people as well. But it is fundamentally transmitted like cold viruses. Everybody knows how you get a cold virus. You send your kid to school, and they come back and give you a cold. I am a grandfather, and when I get a cold, it is because my grandson has gone to school and come back. Old people get viruses from their grandchildren. What he said is misinformed. JT: He is also a governor. William Haseltine, thank you for your time and your expertise.
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Interview With MSNBC Stephanie Ruhle July 20, 2020 | Interview
Stephanie Ruhle (SR): Right now we are joined by Dr. William Haseltine. He is the president of ACCESS Health International and wrote A Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children. Dr. Haseltine, we need all of those answers. Firstly, the White House is now trying to block more money from the CDC for funding testing and contact tracing. Why would they do that? William Haseltine (WH): It is totally baffling. I have been looking through history to find out if there’s a government that has done so badly in an epidemic. The only thing that comes to mind is Nero watching while Rome burned. This is an international disgrace. Our government seems to be doing not what it can to prevent the disease but to accelerate the disease. It is absolutely horrifying to anybody in public health and this is just the latest. To think that people are dying, rushing to hospitals, and our hospitals are full because we are doing more testing is absurd. I think it is time for we the people to send messages to our elected officials who will listen and tell them, enough is enough SR: Let’s talk about school because we are one week closer to the start of school. We know we have not gotten official CDC guidance. Do you think school districts, cities, and localities have the resources and guidance they need to safely reopen? WH: The answer is clearly no. There is some very rough guidance. A matter of fact, I am writing a new book to help people understand the risk of themselves and their children with school reopening. We first discuss the importance of being aware of how many people in your community are infected. Secondly, one needs to be aware of their own personal risk and the risk to your child. Do they have predisposing factors? The third is to understand what your school’s plan to avoid risks and backup plans. As we look across the country and I hear people who are speaking to me, there is deep confusion. If there is going to be a tipping point where the people 1879
of this country say, enough is enough, I believe it will be over the issue of their children. They may be a Republican, Democrat, or libertarian, but everybody wants to protect their child. When it comes to this issue, we just do not have the federal or state guidance, and the local communities don’t have the resources to train, to add the extra people, and to put in the protections. We are going into a crisis that is a dinner table conversation every night with concerned parents. SR: I am a parent. The administration keeps telling us that kids cannot spread this disease, but there is a new study out of South Korea that says middle and high school students are just as likely to spread the virus as adults. WH: In fact, even younger children are able to spread the virus. Anybody over 10 or 11 is essentially equal to an adult in their ability to get sick and spread the virus. Now it seems as if young children, at least some young children, are about one-third more resistant to getting the virus. That says nothing about their ability to spread. This is a cold virus. Everybody knows how you get a cold: you send your kid to school, and they come back and give you a cold. This is a cold virus with a very unpleasant additive of killing people. If you look at the number of young children, infants under the age of 1 and a number of children under the age of 10 getting this terrible multisystem inflammatory syndrome, it is unpleasant and very dangerous. I think any parent that thinks they should send their kid back to school while an epidemic is in their community really ought to think again. SR: Dr. Haseltine, thank you for joining me. Every time you’re with us, you make us better, you make us smarter.
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Interview With CNN John Berman July 22, 2020 | Interview
John Berman (JB): Joining us now, CNN political analyst, David Gregory and William Haseltine. He is the chair and president of ACCESS Health International and a former Harvard Medical School professor. Professor Haseltine, I want to start with you. Yes, the president used different words than he has before on the status of the pandemic, saying it is going to get worse before it gets better. Yes, he used his least ambiguous language yet on masks, and that is a good thing. But, the admission you just heard there that the administration is in the process of formulating a strategy, and it is going to be great, why the wait? William Haseltine (WH): We know what the strategy has been. It has been to, in his own words, ride the sucker through. It is a dramatic underestimate of the power of this virus. Part of the strategy is also to wait for a vaccine and drug. However, we know that is not going to come soon enough for schools opening and mass distribution. We have heard a lot of the vaccine experts talk about it maybe being ready in September. Ken Fraser, the head of Merck, has called that irresponsible. The vaccine is not what people should be talking about because they are underestimating, in my opinion, this virus. We cannot underestimate it. There are other strategies that people have done all over the world, and even in New York, to control this infection. We have strategies that work. We are not yet implementing them here. Actually, almost to the contrary. Alisyn Camerota (AC): I do want to get to those strategies in a second. But first, David, let’s talk a little bit more about this White House briefing because it is so striking to see such a different President Trump. Here is somebody who is sober. He is reading off notes. He is staying on message. He is not veering off into strange lands of suggesting that people inject themselves with detergent or disinfectant. So, what do you think of the effect? I mean, obviously, Dr. Fauci, Dr. Birx, and Dr. Redfield were not there. What do you think the effect of these new White House briefings will be? 1881
David Gregory (DG): Well, I think, unfortunately, in the president’s mind, and so often in our evaluation of it, it is performance art. How did he do? How did he seem? What was his tone like? The bar is so low. He speaks a little bit more forcefully about wearing masks, and we say that is a good thing. That is a real sign of progress. I think it is an admission of the White House and the federal government led by the president that, indeed, things will get worse before they get better. Why they will get worse is what we have been scrutinizing over the many weeks now. I would love to see the public health experts out in front, without the president calling Dr. Fauci an alarmist, because we know what the remedies are. We know what the strategy should be. It takes collective action. I still think it is striking that there is so much we do not know or cannot get our arms around with regard to the virus. I think the president has got to be the one to lead that. He cannot leave it to the states where there is a patchwork. He has still got to lead. JB: That is right. It is not about tone; it is about results. It is about plans. It is about what you are doing. To that end, Professor Haseltine, after I spoke to you last night, I spoke to an emergency room doctor in Arizona who told me they are rationing tests in emergency rooms in Arizona. They do not have enough tests to give to everybody, so they have to pick and choose who gets the tests. People who are dying who almost definitely have coronavirus are never being tested. There are billions of dollars in unspent funds, already appropriated for testing, that have not been used yet. So, what does that tell you? WH: Well, it tells you that we are not coordinated, and we have not been from the very beginning. In any epidemic, you need leadership, governance, and social solidarity. The U.S. has been sorely lacking on all three. I hope what is happening now is a clarion call to repair the damage. It is not going to be soon enough to save these lives, but it could be soon enough to save another hundred thousand or several hundred thousand lives. We need to start acting now. AC: On that note, professor Haseltine, since President Trump says they are now working on a strategy, can you just give us the top three things that they could do today to turn this around? WH: The first thing that they can do is have a leadership that talks about this in realistic terms, showing that each person has to do 1882
their own part. The second is a centralized federal program to provide the assistance, education, money, and tools necessary to the local public health services to make sure that this happens. That is really what we need. It has been clear all along that is what we need. All the while, supporting research to make sure that if there is a chance for great drugs and vaccines, we are making the best use of that chance. JB: David, you had something you wanted to say? DG: It just seems so obvious, that, as a country, we have to be wearing masks. We have to find a way to live with this virus at a time when we are balancing reopening carefully, and much more carefully than we have done in certain parts of the country that are seeing this resurgence. Also, what was lacking yesterday was a kind of centralized federal plan to assist states who are going to make local decisions about how and when to reopen schools. This is coming up for families, very quickly, within weeks, and there is no plan. Coercion is not a plan. Forcing schools to reopen is not a plan. I encourage pushing schools to try to reopen in as safe a way as possible because the need is so great. But, there are not the resources or coordination there as the professor says. That is what is vitally necessary right now. JB: So David, there was a stunning moment that had nothing to do with the pandemic at this news conference yesterday when the president was asked about the case involving Ghislaine Maxwell, the friend of Jeffrey Epstein, who is charged with assisting his sex trafficking ring. I want to listen to what the president said about this accused felon. President Trump (DT): I want to wish her well, frankly. I have met her numerous times over the years, especially since I lived in Palm Beach and I guess they lived in Palm Beach, but I wish her well, whatever it is. JB: “I wish her well.” Wow, David. DG: How many times would it be a much better idea not to comment. We have covered presidents who have said really inappropriate things for me to comment on a case that is being investigated, a lurid, disgusting set of crimes that she is accused of. She is entitled to a fair process. But for the president of the United States to comment at all, including wish her well, I am sure his advisers wish he had not. There are so many areas where a president 1883
should say, just not appropriate for me to weigh in and cause news on this. I do not think the president has ever grasped or cared to grasp that what the president of the United States says reverberates much more widely than average people. JB: It has legal implications. Will she take it as a message from the president of the United States, who has pardon power, among other things. DG: And who has a track record now of intervening in cases where he has personal favor. JB: David Gregory, professor William Haseltine, thanks so much for being with us this morning. WH: You are welcome. Thank you.
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Back To School? July 27, 2020 | Podcast
It’s back to school time – or is it? Coronavirus has the start of this school year up in the air. As COVID-19 cases rise in most of the country, administrators, teachers, parents and kids are being forced to make tough decisions. We’d like to help as you and your family consider this upcoming school year. We’re kicking off this series with a conversation with Dr. William Haseltine. He’s written the book A Family Guide to COVID and believes kids in most areas should stay home right now. He also says there are specific questions parents should ask schools before sending kids back. There is no transcript for this interview, at this time, but the link is available here: https://positivelydad.com/podcast/back-to-school/
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Interview With CNN Erin Burnett July 28, 2020 | Interview
Erin Burnett (EB): New tonight, a CNN special report. Russia claiming a “Sputnik moment.” Officials there say they intend to approve a coronavirus vaccine in less than two weeks. And that means not just in trials, right? This means approve people getting the shot. They say they are going to inject frontline healthcare workers first and then potentially millions of citizens. This is just two weeks away, right? So, this is either a complete and utter game changer or something quite scary. Out front now, Dr. William Haseltine. He has studied vaccines throughout his career. He is also a preeminent researcher who has done groundbreaking work on HIV/AIDS and former professor at Harvard Medical School and the School of Public Health. I appreciate your time as always. In the story from Russia, they are going to be approving this vaccine in the next couple of weeks, giving it as an injection to frontline healthcare workers. They have not put out any scientific data to back up why they are doing this. What is your reaction to this? William Haseltine (WH): It is unwise. It is actually the second vaccine in the world that has been approved for wide scale use. The first was by the Chinese a couple of weeks ago for their military and civil servants who requested it. They cannot know if it is effective or how safe it is. Therefore, they are taking a risk with their people. They had said a couple weeks ago that they were taking a risk with some of their high officials and top businessmen, but those people were taking it at their own risk, as are the people now in China and Russia. EB: Now they are saying they are going to be giving it to doctors on the frontlines. I think it is safe to say it would be much worse to have a vaccine that is not safe than to wait a little longer for one that is safe and effective. As this happens, doctor, we hear countries all the time that broke the curve, and we show the U.S. curve going up, yet all these other curves are going down. We are now seeing major outbreaks in countries that really had this under control, such 1886
as Australia, Hong Kong, Japan. You see the curves go down and then surge in the summer. It is the spring where you see it come down, and then in the summer, it surges. Hong Kong now has over 100 cases for six days running, and they were basically free of the virus before. Now, even Germany sees what they call a very disturbing rise in cases. Sixty percent increase last week, albeit from low levels. Is this a warning of what may lie ahead: that this is just going to be a curve that just goes up and down? WH: I think it is a warning for those countries. You should also add Israel to that list because it exceeds all of them in its bounce back. What it tells us is something we knew. We were at a very high plateau at about 20,000 cases. We opened up, and now it’s 60,000 cases a day more or less. If we continue this way, it may increase to 120,000 cases a day. If you are not careful and do not observe the recommended rules, such as wearing face masks, avoiding crowds, not going to bars, and not intensely socializing, this virus will continue. You have to remember, Erin, this started with one person, and all of these infections started in our cities and countries with a very small number of people. Then it spread. This virus will do that if we are not constantly vigilant until we have some other ways to control it, hopefully a vaccine or prophylactic drugs. EB: It is a very simple thing you just said but a powerful one, if people realize. It did start with one person and now here we are. If you start to think, it cannot spread more, of course it can. You have an op-ed in Forbes arguing that a game changer for getting a handle on the virus quickly in the United States and around the world is through rapid antigen testing. I know Dr. Birx has brought this up. Explain it and why you think it could be such a game changer. WH: There are two ways to tell whether a person is infected. The most sensitive way is through PCR, how we are currently testing. However, we approved another way for emergency use, which is to measure the viral protein, not the RNA. Now, it is not as sensitive, and the tests that we recently approved in India and here do not catch all people. But the Indians have come up with a clever solution to that. They are used to dealing with not the best technologies when addressing problems. So, they decided to screen everybody with the antigen test. That catches about half of the people. The other half they say may be infected. They give them the PCR test, but they already caught the first half within 30 minutes 1887
and have them in their hands, so they can begin to control half of the infection immediately. We can do the same thing here since that test is approved. We should have a two-tiered testing system, one to catch half the people or more, because some people say its eighty percent effective, right away and put them in control. We can stop those infections right away and reduce what is happening very quickly. So, I would recommend a very quick rethink in how we do our testing. EB: It would be incredible if we could. To your point, it’s not 100% but even getting half right now when you’re getting zero will be helpful. These ten day wait periods are obviously toxic. I thank you very much as always. WH: You are welcome. Thank you.
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Interview With CNN Anderson Cooper July 28, 2020 | Interview
Anderson Cooper (AC): Let’s get some political and medical perspective right now from New York Times White House correspondent and CNN political analyst, Maggie Haberman. Also, former Harvard Medical School professor William Haseltine, author of A Family Guide to COVID: Questions and Answers for Parents, Grandparents, and Children. Maggie, there has certainly been a shift in how the president’s approaching the pandemic, or at least, there has been lately. Today, instead of talking about the almost 150,000 dead in this country or outlining a strategy to fight, he boasts about the number of tests as usual and encouraged governors to open up their states. Is there going to be a new plan, differing from president’s current plan going forward: just continue, everything’s going great while so many people continue to die? Maggie Haberman (MH): Anderson, I think you have hit on what the issue: the White House, in many respects, is treating this, at least in terms of how the president approaches it, as a messaging challenge, not as a public health challenge and something that needs to be addressed specifically. They are treating him like a spokesman. He goes out and tries to sell a more positive case by talking about the positive news. Part of that is a reflection, Anderson, of the fact that the president’s advisers, political and within the White House, recognize that if he does not turn around the perception of him regarding coronavirus with voters, then he is very likely to lose the election. So that is a shift. But, A, how long he can sustain it and, B, how honest he is actually being with people I think are the two open questions. AC: Right. Clearly, that is why he has started briefing people about the coronavirus again. The scientists are not briefing. He is the face of this which, given the fact that he is not going to briefings, is just stunning to me that the scientists are still silenced on this. Maggie, The Washington Post reported the reason the president has not been unable to rise to the challenge of dealing with this is 1889
because of a “almost pathological unwillingness” to admit error, combined with a positive feedback loop of overly rosy assessments and data from advisors in Fox News and a pension for magical thinking that prevented him from fully engaging with the pandemic. None of that is really new. It is stuff we have obviously known before, but it is remarkable, and you have reported on numerous times, that nothing has changed in this pandemic. You would think if anything could lodge the president from those patterns, it would be this. MH: Anderson, I think it is missing and that was a really welldone story by Ashley Parker and Phil Rucker. One ingredient in that paragraph that is missing is the president’s inability to see anything other than whether it impacts him or not. It started impacting him in his mind when his supporters started seeing COVID cases spreading in red states. Before that, the White House had been basically limiting this to a blue state problem. I think the president does have more agency than some of that might suggest. He tries to see if he can convince people of his version of reality. It is not just that he honestly believes he can. I think he wants to see if he can do it, in most of these cases. But I do think they are absolutely right. All of these factors, together, is why he has been uniquely unable to meet this moment. AC: Professor Haseltine, when it comes to testing, the president’s continuing to brag about the number of tests the U.S. has done. If it takes two weeks to get a test or even a week to get a test, does that not basically render those tests meaningless? William Haseltine (WH): There are a lot of issues with testing. First of all, in the United States today, only the worried are tested. We know that we are missing about ninety percent. Ten times as many people are actually infected as there are being tested. The reason we know that is because we have done serological tests and the numbers are ten times more than recorded. So, let us just do a little math here. 60,000 people a day are reported as infected. That means 600,000 a day are actually infected. If you are infectious for five to ten days, that means, every day, three to six million people are walking around, possibly, infecting you in this country. That is an epidemic out of control. I am not surprised that the president’s security adviser was infected if there are three to six million people walking around, breathing out this virus, every day. We have got to 1890
get this under the control. Testing is one part of it. But testing has to be actionable. You pointed out that, if you get a test result, you have to wait five, ten, or even two or three days, but that is not really actionable. You cannot take the action you need, which is isolate that infected person. We do not have the mechanisms to isolate those infected people even if we do find them. We certainly do not have an effective way to contact trace those people who have been infected. So testing, as faulty as it is, even if it were perfect, would be a problem. Being as imperfect as it is, it just magnifies the problem. No matter how many tests you say you are doing, if you look at the number of people being infected today, it has obviously not worked. AC: Maggie, do you know if anybody who comes into contact with the president in the White House has to be tested every time, every day, before they come in contact with the president? MH: People who are going to be in close contact with the president are tested before they are around him, which, I assume, but again we don’t know, is how they found that Robert O’Brien tested positive. Obviously, nobody wants anybody to be sick, but I will say that the White House made it a real concerted effort to keep that quiet. We had been chasing it this weekend as well as other reporters, and they did not go public with it until today. Contrast that with how they treated the vice president’s spokeswoman being tested positive, and they released that pretty quickly. It is important to actually let people know what is happening to allow people to have confidence in their government. That is not going to add to it when you have people getting sick and the White House is trying to do damage control. AC: Professor Haseltine, just in terms of testing, we talked to Bill Gates on the Town hall last week. He said he was a little bit more optimistic about better therapeutics, diagnostics, and testing by the end of the year, and then, ultimately, in the new year, waves of vaccines and in various stages. I am wondering if you share that slight optimism. I think he was saying he was more optimistic compared to what he was a month ago. Do you see improvements in testing actually possible by then? WH: Yes. In fact, let me first make a comment about the White House. Remember, this virus is not just droplets; it is aerosols. There are aerosols in the White House. You and I have been in the White 1891
House, and it is not very big. It is actually a small house with small spaces. That is exactly what you do not want, somebody breathing out this virus in that space. So that is something to think about. Now, with respect to optimism, I just wrote a story today about a new test that has been approved in India. It is a test for the virus that takes about thirty minutes to do. It is very cheap. Perhaps, less than five cents to produce. It is about fifty percent accurate in thirty minutes. They do not assume if you are negative, you are negative. They then do a PCR test on everybody else. But it identifies half the population right away, while they are present, and then can put those people under control. We have a test that has got emergencyuse authorization like that in the U.S. which I wish we would use the same way the Indians use it as a prescreen. At least, find the people with that test, and then look for the others. So that is something we could do tomorrow if we wanted. We have the approval for those tests. We have got the tests. We can find half the people right away. I do not know why we are not doing it. AC: Professor Haseltine, appreciate it. More on that to come, no doubt. Maggie Haberman, thank you as we...
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Interview With CNN John Berman and Alisyn Camerota July 29, 2020 | Interview
John Berman (JB): Joining us now is Dr. William Haseltine. He is the chair and president of ACCESS Health International and former professor at Harvard Medical School. Professor Haseltine, always a pleasure to have you with us. What will it take to keep those yellow states and cities, big cities such as Columbus, Ohio, whose mayor will be on soon, from getting to red to prevent from entering a crisis situation? William Haseltine (WH): If you look at the numbers, which I check regularly, you can see, those cities are approaching a crisis regardless. For example, two months ago in Tennessee, there were about 400 people infected on a daily basis. A month ago, it was about 1,400. Currently in this month, it is about 2,500 and continuing to rise. That is emblematic of what is happening in that region. What can we do? The first thing leadership in that state can do right away is insist on mask wearing, closing bars, and enforcing regulation preventing people from congregating in large numbers. The second thing that they can do is use the new options of speed testing, which use antigen tests in conjunction with PCR tests. That can identify almost all or half of the people who are infected right away and help them to stop spreading the virus by recommending, and in some cases, enforcing self-isolation. Those are things that can be done right now to help control what could get very, very serious. Alisyn Camerota (AC): But, professor, some of those states in yellow on that map are states in the northeast and the tristate area, such as Connecticut, New York, are already doing the things that you are talking about. Only Vermont is spared. So, why are their numbers going back up? WH: One of the reasons that numbers are going up is people are not following all of this advice. If you look around at beaches and events in the evening, people are still getting together. There are multiple types of epidemics. There is the epidemic of young people. 1893
They get together and are not taking precautions. It is willful neglect of precaution, so they can change that behavior. On the other hand, there are people who must go to work to keep their families fed, which is a very different group. That requires government intervention, such as economic support, to help those people keep themselves and their families safe. So, there is at least two different kinds of epidemics going on all over the country. It is not just Connecticut or New York or Tennessee. There are different kinds. Of course, there are institutions including our eldercare facilities, correctional facilities, and all of those in need of special attention. We need to understand that the virus is not a simple infection. It does not have the same effect on everybody. It is the aggregation that is most serious at this point. JB: Professor Haseltine, you heard the president once again leaning into the idea of hydroxychloroquine as a treatment for coronavirus. Yesterday, Dr. Anthony Fauci made clear that the overwhelming clinical evidence concludes that it is not an effective treatment for COVID-19. What is your view? WH: It is not a question of view; it is a question of facts. Dr. Fauci is correct. In any study that has been done, and they are carefully controlled studies, it shows that hydroxychloroquine has no effect on people at the early stage, middle stage, or late stage of contracting the virus. In fact, it can be harmful, especially to those in the late stage of the disease. Therefore, in my opinion, we are responsible to push away that drug. There are other ways to treat people at late stage which are now effective. There are drugs that are coming, I would say, relatively soon, that will treat people in the earlier stages. Those are the monoclonal antibodies and new antiviral drugs making their way forward. Those will make a difference but are not quite here yet. JB: Professor Haseltine, thanks so much for getting up for us this morning. Really appreciate it. WH: It is my pleasure. Thank you.
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Interview With CNN Jake Tapper July 29, 2020 | Interview
Jake Tapper (JT): Joining me now is Dr. William Haseltine, former Harvard Medical School professor and author of the book A Family Guide to COVID. Thank you so much for joining us. You say there are two different kinds of epidemics going on in the United States. Explain what you mean by that. William Haseltine (WH): Well, one of the epidemics is what you were just speaking of: young people going out, having a good time. We all understand that. They then come back and infect the people who they live with. Many of those are old and elderly. That is one epidemic, which is very worrying because their demographic, people in their 20s and 30s, is no different from the adolescent to teenagers who are about to go back to school. The students may not have the effects of this virus as badly, but they can infect the older generation, and we will see that if they go back to school. The second epidemic is in the minority communities, such as Latinos and blacks. Many of them do not have any choice but to keep going to work. They are either in essential services or do not have any other means of support than working. They live in crowded conditions and take public transportation, so they are exposed to one another. There are also institutions such as our correctional facilities, mental institutions, and elder care homes, which is a different category. We have to treat those a little bit differently. The way you treat and try to prevent the epidemic in those minority communities is different from the way you try to educate people who have the choice not to go out and gather. JT: All right. So, yeah, let us talk about that. Obviously, the educational component is important, and if not, laws and restrictions will be necessary when it comes to people in their 20s and 30s who are spreading this virus because of optional behaviors, parties, and going to bars and other gatherings. What about the people who are minority communities in less wealthy communities that have to go
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to work, take public transportation, or go to places where they get exposed? How do we solve that problem of getting infected? WH: There are two problems there. One is those that are in essential services doing the things that keep our cities running and keep us all safe, so we have to do everything possible to keep them safe. We have to reinforce the type of personal protection equipment we give them and be very careful with the way they work. Then there is the other group of those who are mostly in-service jobs that are not really essential, but they need the money. We have helped a lot of companies stay in business, but we are not going to get this epidemic under control until we help those people who are working only to feed their families and keep themselves afloat. If we can support our businesses, we need to support them too. JT: CDC director Robert Redfield acknowledged that the U.S. was too slow in responding to the virus coming from Europe, which impacted the ability of the U.S. to fight the pandemic. This is an argument that Governor Cuomo has been making as well about how New York was disadvantaged because the shutdown on travel from Europe came later than the shutdown on travel from China. When I say shutdown, I mean restrictions. Obviously there continued to be some travel. What is your big takeaway from Redfield’s admission today? WH: It is not a surprise, but I would rather focus on what happened a little bit later. The reason we are in the trouble we are now isn’t because the virus came here. It is because of what we did once the virus got here and what we are still doing now that the virus is here affecting so many people. We have not done what many countries did to control this virus. There are very fundamental questions about why and how. I think what we have to do now is focus on what we need to do. We know the very simple public health measures that we need to take, so I think it is time for us to wake up, put all of that in the past, and focus on saving the next 150,000 American lives and the next 300,000 lives that are going to be blighted as they are the wounded. JT: So, let us talk about that. In addition to obviously masks, distancing, washing our hands, avoiding indoor situations in parts of the country where it is dangerous, and closing down bars and places where it is dangerous to go inside, what else do we need to be doing?
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What does President Trump, Governor Cuomo, or our other leaders need to be doing? WH: We have a federal system, and in a federal system, a lot of the authority rests with the governors of the states and, in some cases, even the mayors of our cities. In that situation, you need a leader of a country that speaks in a way that people understand and are persuaded to behave correctly. You cannot order all the things in a federal system the way we are set up. We are not like many of the European countries. We count on a responsible leader protecting us. That is the responsibility. Even if they don’t have the tools to do it, they have the voice to lead, and that voice has been missing. We have a voice at the center of our government which is accelerating the epidemic, not controlling the epidemic. It is time for that to change. JT: Beyond that, what about more aggressive testing? What about using the Defense Production Act to force labs to hire more workers and buy more equipment? What about contact tracing? What does the government need to be doing there? WH: Those are all the things we really need to do if we are going to drive this not just to a low level, but to a point where our schools can reopen and we can go back to work. We need to contact-trace, but it is not enough to test and contact trace. We need programs in place to ensure people can safely isolate once they have been identified so they do not contact and infect others. Something I think is now newly possible is to set up a two-tiered testing system where the first test you do is a test for the antigen, the proteins of the virus. That can reliably capture half of the infected people and can do so within thirty minutes. The others you test anyway and get the results back as fast as you can. But once you have half of the people or more identified, you can then institute programs to allow them to safely and conveniently isolate for a two-week period. That is what is required to drive this infection down, and we are not doing that. We need the federal aid and states to put in the programs to do that. JT: William Haseltine, thank you so much. I appreciate it.
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August 2020
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‘Second Opinion,’ Episode 1: COVID-19’s resurgence L.A. Times | August 2, 2020| Video Commentary
Los Angeles Times Executive Chairman Dr. Patrick Soon-Shiong, a surgeon and scientist, is joined by renowned biologist William Haseltine for a discussion about COVID-19 and the public health implications of its recent resurgence. The discussion is moderated by Eli Stokols of The Times’ Washington bureau. Dr. Patrick Soon-Shiong, executive chairman of the Los Angeles Times, is a surgeon and scientist who has spent his career studying the human immune system to fight cancer and infectious diseases. He is the chairman and chief executive of NantWorks, and the owner of or investor in a number of companies, including ImmunityBio and NantKwest, which are currently researching immunotherapies for COVID-19. William Haseltine is a former professor at Harvard’s medical and public health schools, where he performed groundbreaking research on cancer and HIV/AIDS. Haseltine is also the founder and CEO of biotechnology companies responsible for drugs treating HIV/AIDS, cancer, diabetes and autoimmune disease. He is chair and president of the nonprofit think tank and advisory group Access Health International and is the author of seven books on health systems around the world. His most recent book is “A Family Guide to COVID: Questions and Answers for Parents, Grandparents, and Children.” To watch the full video, click here: https://youtu.be/0r45HiHYNNM
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An Interview With Thrive Global August 6, 2020 | Interview
Lauren K. Clark: If you were to imagine the significance of childhood’s imagination, during this particular time, how would you articulate it? How is it useful for adults in mental navigation and maneuvering through this extensive time of quarantine? Dr. William Haseltine: I just recall my own feelings and thoughts during the time of polio. I did not know exactly what was out there, but I knew there was something dreadful that my parents were afraid of for themselves and for me. It was a feeling of real discomfort that manifested in, “you can only play with three friends,” “you can’t go to the swimming pool,” “you can’t go to the movie theaters,” and “you have to stay inside.” It was a time of deep unease and anxiety, not because I knew what was happening, but rather because I knew my parents were worried. That is how children perceive this. “Different children have different abilities to respond to various pressures and finding unique ways to support them in their response to what is going on today is critical.”-Dr. William Haseltine Lauren K. Clark: According to your perspective, if children were to articulate, or draw out their understanding of COVID-19, what would this drawing look like? Dr. William Haseltine: It would look like a very fearful monster outside their door. Lauren K. Clark: Based on your understanding, what has made COVID-19 the most challenging thing to deal with? Why is it different than anything we have ever experienced before? Dr. William Haseltine: It is not different from anything we have ever experienced before. People have experienced the bubonic plague, smallpox, and polio. We have just forgotten what dealing with something like this is like. Lauren K. Clark: In your latest book, A Family’s Guide To COVID, you focus on the dilemma of parents, grandparents, and other familial figures to protect their children. What is the 1900
phenomenon of using fantasy’s ability to educate children in a way, where they feel they have some level of agency and control within this particular epidemic? Dr. William Haseltine: I think it is very important not to broadly say that children are this way or children are that way. Children are just as individual as adults, so for each child, you have to pay attention, even within a family, to the differences in their reactions. What will work to give agency to one child will not work for another. We have to understand what each child’s interests are and amplify their experiences with what actually interests them. It is extremely important that children feel that they have some degree of control. One way to do that, for example, is to customize their protective equipment. You could give them face shields covered in Star Wars, Paw Patrol, Hello Kitty, or other characters and images they like. You could also focus on their ability to do creative things. From my own experience, I can tell you that one of my grandchildren loves virtual education, while the other hates it. Different children have different abilities to respond to various pressures and finding unique ways to support them in their response to what is going on today is critical. Lauren K. Clark: You recently returned from Wuhan, China, where you served as the Chair of the 9th US- China Health Summit. Have you observed a different way, in which COVID-19 is being explained to Chinese children? Kindly elaborate, and how has differentiation of culture and methodologies of containment contributed to this? Dr. William Haseltine: In general, the Chinese are very childfocused. From the very beginning, there were tremendous numbers of books and videos to explain what was happening to children in ways that I just simply have not seen in the U.S. I have surveyed many of the books and some of the films that are out. In terms of the emphasis that our society is placing on children’s understanding of COVID, I would say that the United States is doing 1/20th of what the Chinese are doing. The Chinese have made an enormous effort to explain and have children understand COVID. Lauren K. Clark: In writing your recent book, even with all of your expertise, how have you had to return to your own inner child, in order to understand the virus, through the eyes of children?
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Dr. William Haseltine: My experience with polio was extremely helpful. I had recalled it for many years, but this brought it all back. In addition to that, I had pericarditis when I was 7 years old. That meant I was confined to my home for about 6 months and couldn’t go outside. I can recall my feelings during that time as well. They have helped me with understanding what children and my grandchildren are going through right now, so I have recalled my own personal experiences with a pandemic and with a disease that I myself suffered. Lauren K. Clark: Has your recent book forced you to reexamine your own research, as it relates to possible drug vaccinations for COVID-19? What have been the challenges in telling a hard truth to parents about the aura of uncertainty? Dr. William Haseltine: Writing the book reinforced my belief in science as a fact-based part of human culture and the importance of dealing with the world as it is, rather than the world as we wish it to be. As a scientist, you do not have the luxury to wish the world to be one way or another. Your job is to find out what it is, regardless of what you think. The way most scientific mistakes are made is to believe you understand nature when your job is not to predict, but rather to observe and interpret. I would say the same applies when you look at an epidemic. There is a great desire to transform the world into something that is suitable for you and your individual life when it is not. This epidemic makes that abundantly clear. Lauren K. Clark: As a scientist how would you differentiate the level of uncertainty during the initial AIDS epidemic versus COVID-19? Is the general public experiencing a greater level of intensity than we had during the AIDS epidemic? Dr. William Haseltine: Absolutely. The amount of information about this epidemic is far greater than what we had about HIV/AIDS. That is because it affects everyone, not just limited populations as was believed to be the case for HIV. Lauren K. Clark: You developed the first strategy in creating a drug for HIV. Do you see a similar methodology, which can be used for COVID-19? What more is required in developing a suitable vaccination for the coronavirus? What more is needed? Dr. William Haseltine: Fortunately, there is tremendous interest all over the world in developing drugs that will help us against COVID-19. This was not the case with HIV for many years. 1902
There has also been an enormous global effort, which is very powerful and has resulted in very rapid engagement across the world. We also now have many global centers of excellence that can address these issues. When HIV came along, only the United States and some parts of Europe were engaged. Now, the United States, Europe, China, Japan, Korea, all of Southeast Asia, India, and everyone else has the capabilities that we had then. I would say that at least a hundred times more effort has been put toward developing COVID remedies and vaccines than there was to developing the same for HIV. That, of course, is wonderfully encouraging. “I believe there is no better guarantee for mental health than productive work and a strong family life.”-Dr. William Haseltine Lauren K. Clark: What challenges have you experienced in securing your own mental wellness, during this quarantine era? Has quarantine allowed you to discover creative skills about yourself? Do you see these skills being used in developing a treatment for the coronavirus? Dr. William Haseltine: As a scientist and public health advocate, I’ve had an intense focus on understanding the virus, the disease, the social impact, and the message to control the pandemic through medical, government, and social methods. This has allowed me to use my many years of experience in all aspects of health, and I believe it has been very beneficial to my mental health. Additionally, I have very strong family support by my wife, grown children, and grandchildren. I believe there is no better guarantee for mental health than productive work and a strong family life. The quarantine has allowed me to deploy my many skills and understanding of science, public health, and medicine. It has also allowed me to use my skills in public communication to help others achieve a level of comfort and understanding with what is happening in this current pandemic. As part of the quarantine process, I have acquired a country home and rediscovered my love of gardening and taking care of our natural surroundings, a skill that I had not practiced since my early youth. Lauren K. Clark: Let’s pretend you are on another island with very few people. You are sitting back and observing the current situation. What do you see as it pertains to US citizens and our
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mental wellness? In protecting our mental health, what are we doing wrong? What are we getting right? Dr. William Haseltine: In any crisis, we need three fundamental elements. The first is leadership, which is capable of clear, consistent, credible, and compassionate communication to the people of a nation. The absence of such communication by our political leaders in the United States is cause for great anxiety throughout the country. The second requirement is strong and effective governance. In this crisis, that means a public health service that is not only capable of formulating policy, but also executing it at the national, state, county, municipal, and local level. We are absent in such effective and organized public health implementation, which leaves people confused. The results of such an absence of a public service in the United States leads to a patchwork of widely differing approaches. It may vary from community to community and even in some cases, from block to block within a city. That creates substantial uncertainty and anxiety. The final need for coping with a crisis is social solidarity. This is the feeling that everyone is in this together as equals, both in their risk and their opportunity to access medical care, and is responsible for themselves, their families, and others in modifying their behavior. In the United States, this sense of social solidarity varies regionally, but in general, it is weaker than it is in many other countries. Again, this produces anxiety and uncertainty over whether our neighbor will protect us as we will protect them. Lauren K. Clark: If you could paint the current aura of the world with 4 colors, what would you select. What is your reason for choosing these four? Dr. William Haseltine: None of the colors would be bright, but rather muted. I would paint much of Asia in a dusky rose and the United States in dark gray. Actually, I would paint all of North and South America, with the exception of Canada, in dark gray. India would also be in dark gray, most of Europe would be fuchsia, Russia would be painted in dark gray, and Australia and New Zealand would be a dusky rose. Dusky rose means the infection is under control, except for sporadic outbreaks that are contained. Fuchsia means that the infection is not under control, but is not out of control either, and dark gray represents a situation that is disastrous in the number of infections, is rampant, and is out of control. 1904
Lauren K. Clark: How do you envision American families taking advantage of this time to strengthen familial bonds with their children and loved ones? Dr. William Haseltine: In reflecting on the social and cultural impact of COVID-19, I have come to the conclusion that one of the fundamental reasons for family structure is protection in times of crisis. Almost all families reconnect and rebond to protect one another. In my view, it has been an extremely positive time for reinforcing the need for family values and the protective power of families. By families, I am not only referring to the traditional family of husband, wife, and children, but also the more complicated families, such as LGBTQ+ couples and the families with unrelated members and older people in the family circle. There has been a renewed emphasis on the importance of tight familial relationships. Lauren K. Clark: If you could draw out a safer re-opening of public, and private, spaces in the United States, what would that look like? How would it be more effective in contributing to containing the virus? Dr. Wiliam Haseltine: We have excellent examples around the world of how to contain the infection, without a vaccine or with a defective treatment or vaccine. Many countries, such as our European neighbors and the Canadians, have done it, while we have not. We do not need to look any further than these examples in Asia, Australia, New Zealand, and Europe to understand what needs to be done. Unfortunately we are not doing it. If we are specifically talking about a safer re-opening of schools, it is important to note that when people discuss this matter, they focus on K-6 and they say that the children are resistant to infection, which is only partially true. They are resistant, but they are also about two-thirds as infectable. In many cases, they can transmit the virus more effectively than adults. If they do get sick, they often get some very serious life-threatening illness. The big gap in the discussion of schools is high school. Kids in high school, ages 14 and above, are as equally infectable as adults. There is no privilege of infection, and in some cases, they can transmit the virus more effectively. People between the ages of 15-50 make up half of the people who are in the hospital. Thus, in order to contain the virus more effectively, I plead with educators and policymakers not to base decisions on school reopening only on K-6, but on grades 7-12 as well. 1905
Interview With Bloomberg Radio Carol Massar August 6, 2020 | Interview
Carol Massar (CM): Jason and I always look forward to this next guest when it comes to talking about COVID-19. Back with us is Dr. William Haseltine. He is chairman and president of ACCESS Health International. It is a non-profit think tank that works on improving access to high quality and affordable healthcare for people everywhere. He also has a great living eBook that came out this year. It is written with questions about the virus from the perspective of different age groups and living because it is constantly updated with new information. It is called A Family Guide to COVID. William Haseltine is joining us again on the phone. Bill, nice to have you back with us. Where should we start? Tell me what you think is most important when we look at what is going on with the virus in the US, globally and also regarding the race to find treatments and a vaccine. William Haseltine (WH): Thank you very much. Also, a new living eBook has just arrived. It will be up later today. It is A COVID Guide to Back to School. I mention it because that is the topic on Americans minds. Every parent and grandparent, such as myself, are absolutely upset, concerned, and worried about what to do with their children going back to school. The preschoolers, the k through six, and the six through twelve. The age groups are very difficult and confront different issues, not to mention college aged students as well. Shockingly, we do not have consistent national guidance. So, I am trying to give people the basics for how to make a decision since we just do not have the guidance. It is really shocking. The CDC does not give any good guidance. Additionally, the National Academy of Scientists which is a National Academy of Medicine, Engineering, and every academy that we have, put together a panel. Most surprisingly, the report said that we just do not know or have guidance about what to do. That was our national academy. It is really upsetting.
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Jason Kelly (JK): So, what is the first couple of questions we should be asking as parents Bill? WH: We should access our risks. The first stratification for risk is the amount of infection in your area, indicating how likely you are to run into somebody who is contagious. People say transmission, but contagious is the word you should use. How likely are you or your child going to run into someone contagious? We give a guideline whether you are in green, yellow, orange, or red by how many people per hundred thousand that are in your zip code and the zip code they come in from to work in your school. That gives you a guideline of whether you are in a hurricane and should stay home in the basement, a thunderstorm and you can stay home and not go out, a heavy rainstorm where you go out but heavily equipped, or a light rain and you have to know where you are going and how well you will be protected. Or if you are lucky enough, and there is nowhere in the country where we are lucky enough yet to be on a sunny day. That is the first thing. The second thing is, know your personal risk. Are there any health issues? Do you or your child have diabetes, serious asthma, obesity, or other conditions that put them at risk? Or anybody living with you like your parents, the child’s grandparents, that the child will bring home danger to them. Finally, and more difficult, we have to judge what that school is doing. For that, you as a parent have to take the initiative to look at what that school is doing. Do you really have confidence in the people there? What is the plant like? Is it an old broken-down facility? Is it a brand-new facility? What is the air handling like? What are they telling you? Are they dividing the kids up into small groups? Is facemask protection required? Do they separate the children adequately? Those are things you as a parent have the responsibility to do before sending your kid out there. No matter what you are hearing from national news, kids do get infected. There is something we have to demystify about the virus. This is a cold virus. It does a lot more damage than most cold viruses like those you get every season. One third of the colds you get are coronaviruses. We know how you get a cold. You send your kid to school, and they come back with a cold. That is not new. One of the three colds you get every year is a coronavirus cold. Essentially, the story of this book is to give people simple guidance on how to 1907
imagine what their risk is. If the risk is too high, you just do not send your kid to school. JK: You are listening to Bloomberg Businessweek, Jason Kelly and Carol Massar. Let us get back to our conversation. We are back with Dr. William Haseltine, president of ACCESS Health International, author of a couple of eBooks. They are out there and being updated practically hour by hour it feels like because that is how fast this is moving. To your point Carol, what is A Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children and newly released, as of today, A COVID Back to School Guide: Questions and Answers for Parents and Students. Bill, we can talk all day about back to school. I do want to ask you about, maybe back to work, if I can because these are intertwined subjects, of course. We need kids to go back to school and learning in some fashion. But what have you learned when talking to people about what it is going to take for people to feel good about going back to the office? WH: It should not be surprising that it is almost exactly the same questions that you would ask about sending your kid to school. You are more concerned about the kid because you think you yourself have more control, but in fact, when you really think about it, you really do not have control of who you meet. You have control of what you can do to protect yourself, but you do not know who that other person is. Therefore, the same kind of rules apply, which is how much infection is in your area, what is your personal risk and the risk of those you live with, and then how much is your business doing given the conditions that they are in. There is one area that is driving this epidemic. There are three or four total, but the one that I would like to focus on is there a lot of people who have to go to work. Either they are essential workers, or they cannot put food on the table if they do not go to work. They do not have that choice of making the decision that you or I might have about staying home or going back to work. It is so important to make sure their work environment is safe. The responsibility of the organization that they work for is to make sure that the people who have to work there are safe. That is enforced, irreproducible across the country. There are some places that are going to be good about safety and other places that are not. That is going to keep driving the infection. It is on all of us to put the pressure on our local governments to make sure that all workplaces are safe, especially 1908
those places where people have to go to work, like the fire department, despite the fact there is an epidemic raging. That is something we all have to work with: protecting ourselves and protecting them is protecting us. CM: I think we are all realizing the importance of community. It is not just about us as individuals, but it is about taking care of our community at large, and that is what we need to be thinking about. I have to ask you though. I am still struck by Governor Cuomo on Monday. I was away for a week, came back, and he was very strident and critical talking about the potential of basically the federal government coming out and saying we made a mistake, we need to do a redo, and we need to shut down again. Would you be in favor of shutting down the country as a whole like we saw in other countries where they have seemed to have get ahead of the virus better than the US? Would you be in favor of that? WH: I am not in favor of shutting the whole country, but I would be in favor of shutting a place like Houston, most of Texas, most of Florida, most of California, or at least the southern half of California down. You have to be aware of what is going on, and if you are not in control, which we are not, you have got to shut things down for five to six weeks. But that is not enough. You have to take a leaf out of what we learned from the Chinese. When there are sixty thousand people a day being infected in America, there are only fifty people a day being infected in China. Let me say that again. Sixty thousand Americans get infected when fifty people in China get infected. It can be done, and it is not just shutting everything down. It is making sure you contract trace, and then enforce mandatory isolation for all those exposed, not even infected, just exposed. That is how you do it. It is not magic. We do not do anything like that nor does any European country. That is why when you look at Europe, they have not controlled this. It can blow out of control just like it did here at any moment. JK: Always good to catch up with you. We are learning more, and there are some simpler solutions to this. A lot of it comes down to how we are interacting with each other and as a community, as you said Carol. Dr. William Haseltine, chair and president of ACCESS Health International. Check out his books A COVID Back to School Guide: Questions and Answers for Parents and Students.
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The Randy Tobler Show August 8, 2020 | Interview
Dr William Haseltine: 'You'd like to hear a consistent voice that says, this is what you should do' Legendary public health expert Dr William Haseltine tells Randy Tobler, "My heart really goes out to those parents who want to do what's best for their kids, they know education is crucial." (KFTK) – Dr William Haseltine, a former Harvard Medical School Professor, known for his work on HIV/AIDS and the human genome, joined Dr Randy Tovbler to discuss the COVID-19 pandemic as well as his A COVID Back to School Guide. Dr Haseltine agrees with the premise that education is crucial for kids, "but at the same time, nobody wants to risk their child for this disease." "Some people say they there's no risk at all to children, that's false. It's simply not true. Some people say they're very hard to infect, and they almost can't get infected. That's not true either. Others say if they go to school and get infected, they won't bring the infection back. That's not true either," says Dr Haseltine on possible infections of children. Haseltine says he wrote the book, a followup to A Family Guide to COVID, to give parents a good set of "very simple rules to follow," when dealing with COVID. How many people in your area are infected, "that's the most important thing, because people who are infected are contagious and can infect you, can infect your child." How vulnerable are my children and myself, "if a child has asthma, if a child has had some immunological difficulty," says Haseltine you don't send your kid to a school that might infect them." Figure out how your school is dealing with the pandemic, "that's the hardest, because how are you as a person, going to know if they're really going to protect your child."
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There is no transcript for this interview, at this time, but the link is available here: The Randy Tobler Show Podcast
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Interview With Abi Millar August 21, 2020 | Interview
Abi Millar (AM): How will these new tests improve COVID19 testing and increase capacity? William Hazeltine (WH): Any test that makes testing simpler for the patient and the user is an advantage over the current PCR testing methods. The three new methods that they are supposed to use based on advances in genome testing technology should all help simplify and speed protection of SARS-CoV-2 positive individuals. The PCR tests and the new tests all detect viral infections using very different technologies. The PCR test is the most sensitive test, but it is slower, most expensive and requires more highly trained personal. The two new tests detect viral RNA are simpler to use, use less expensive methods and produce answers more quickly AM: What's the importance of rapid diagnosis when it comes to COVID-19? WH: Containment of the epidemic depends primarily on identifying those people who are contagious and isolating them from people who they might infect. Convenience, speed, and price of a test are critical to move from testing of those who believe they may be ill or have been exposed, to testing the general population. Because the great majority of people infected by SARS-CoV-2 don’t know it, because the virus has no discernable symptoms in up to 90% of all people infected, testing the worried or the ill misses I estimate up to 90% of people who are actually contagious. These tests are a first good step to identifying those who are contagious. I look forward to further improvements that make it even easier and less expensive then this current generation. That being said, this is a good next step in the ability of tests to help control the pandemic. AM: There is no publicly available data about these tests' performance. To what extent is this a cause for concern? WH: It is a great cause for concern. These tests should not be generally used without information available to the public regarding the sensitivity and specificity as well as the cost and speed of the test. 1912
It is irresponsible to introduce these tests without release of underlying data that supports their use.
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Interview With Nik Zecevic August 26, 2020 | Interview
Is Convalescent Plasma Therapy Effective Against Fighting COVID-19? Convalescent plasma therapy is being used to treat COVID-19 patients, but is it safe and successful? Dr. William A. Haseltine, the chair and president of Access Health International and Robert Segal, president of LabFinder are providing answers. Here is the link for the video interview
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Interview With CGTN Mike Walter August 28, 2020 | Interview
With about a thousand people dying from COVID-19 every day, the U.S. still has the worst outbreak in the world with nearly a quarter of all coronavirus cases. But the number is on the decline. And that could be welcome news for President Trump who has come under fire for his handling of the pandemic. To discuss: ● William Haseltine is the chair and president of ACCESS Health International and the author of “A Family Guide to COVID.” ● Stanley Perlman is a professor of microbiology and immunology at the University of Iowa. ● Georges Benjamin heads the American Public Health Association. ● Joseph Williams is senior news editor at U.S. News and World Report. Here is the link for the video interview
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September 2020
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20% of Coronavirus Infections Are Asymptomatic But Still Contagious September 22, 2020 | Interview
COVID-19 can have ‘hidden’ symptoms Experts say some people may actually have symptoms but not realize they are signs of COVID-19. “There is some indication that many asymptomatic people actually suffer occult [hidden] disease, which affects their actual physical abilities during the infection and for some time thereafter,” William A. Haseltine, PhD, a former professor at Harvard Medical School and Harvard School of Public Health and the founder and chair of the division of biochemical pharmacology and the division of human retrovirology, told Healthline. Haseltine, who’s not associated with the study, emphasizes that a definitive answer to the question is still under investigation and will require long-term follow-up. “The findings of this systematic review of publications early in the pandemic suggests that most SARS-CoV-2 infections are not asymptomatic throughout the course of infection,” the study authors concluded. The researchers emphasized that these “presymptomatic” cases and the risk of disease spread from those infections means that a combination of preventive measures, including “enhanced hand and respiratory hygiene, testing and tracing, and isolation strategies and social distancing,” will remain critical. Click here to read the entire article
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Interview With Houston Public Media Ernie Manouse September 29, 2020 | Interview Town Square with Ernie Manouse is a gathering space for the community to come together and discuss the day’s most important and pressing issues. In the first segment, Ernie is joined by Dr. William Haseltine, a renowned scientist, biotech entrepreneur, chair and president of ACCESS Health International (a global think tank), chair of the US/China Health Summit, and a former professor at Harvard Medical School. They discuss how the current Covid vaccines in phase-three trials are designed to merely lessen the severity of Covid symptoms, not prevent infection or spread. Dr. Haseltine also reacts to the global milestone in coronavirus deaths–more than one million people worldwide have died in the pandemic. Click Here for to listen to the interview
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Interview With TRT World and Ghida Fakhry September 30, 2020 | Interview
As the global death toll from COVID 19 reached a tragic milestone, with over 1 million deaths worldwide, the US alone recorded more than 205,000 deaths and over 7 million active coronavirus cases. The rising number of deaths and infections brings a renewed sense of urgency for a cure. But also, a growing weariness among Americans that politics rather than science is driving the process for vaccine development and approval. With federal public health officials being openly contradicted and rebuked by President Donald Trump, and the White House accused of interfering in the vaccine process for political gain ahead of the November 3rd election, trust in the safety of a vaccine is waning. Guests: Dr. William Haseltine- Chair and President of ACCESS Health International, a nonprofit dedicated to improving global access to healthcare, and a former professor at Harvard Medical School where he founded two research departments on cancer and HIV/AIDS Dr. Gregory Glenn- President of Research and Development at Novavax, a Maryland-based pharmaceutical company awarded $1.6 billion by the US government to support development and manufacturing of a coronavirus vaccine Dr. Joycelyn Elders- Former Surgeon General of the United States under President Bill Clinton Watch the interview on YouTube
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Interview With Mark Masselli And Margaret Flinter HealthcareNOW Radio | September 2, 2020 | Interview
This week Mark Masselli and Margaret Flinter welcome Dr. William A Haseltine, President of ACCESS Health International, a global health think tank. He is also a renowned scientist, entrepreneur, philanthropist and founder of Harvard Medical School’s HIV/AIDS and cancer research centers. He discusses his two new books: A Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children, and A COVID Back To School Guide which are continually-updating ‘living ebooks’ offering answers to the many questions families have about how to navigate their way through the pandemic. Here is the link for the interview
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Interview With Hedy Phillips September 7, 2020 | Interview
Hedy Phillips: Can you wear a disposable mask more than once? Or is this a bad idea? William Haseltine: Yes you can wear a face mask more than once, especially if it’s a surgical mask. You can’t wash these masks, but you can put the mask on in the morning and take it on and off as needed during the day. However, I do not recommend using the masks for a second day. Hedy Phillips: if you're stuck in a situation where all you have is a disposable mask that you've already worn once, what are you recommended to do? William Haseltine: Wearing a disposable mask that you have already previously worn is better than wearing no mask at all, but you should do your best to change your disposable face mask every day. It is unadvisable to wear a disposable face mask for multiple days for several reasons: For one, the mask gets dirty and bacteria can get inside and secondly, the mask can get contaminated externally as well. This means there can be a bunch of bacteria growing inside and outside the mask so it is unsanitary to wear the mask for more than a day, both for you because of the contaminated inside of the mask, or for others because of the particles that may adhere to the outside.
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Interview On CGTN America September 10, 2020 | Interview
Another grim milestone is at hand for the United States as it crosses 190,000 coronavirus deaths. President Trump has been criticized for not doing enough, but the White House is pushing back, saying the administration has done everything to protect the American people. Now Trump’s response to the coronavirus is again being called into question, with the release of audiotapes of interviews he did with renowned journalist Bob Woodward for his latest book, “Rage.” Obtained by CNN and other news outlets, President Trump goes on the record back in early February describing the virus as highly contagious and deadly. Joining the panel: ● Dr. William Haseltine is Chair and President of ACCESS Health International. ● Dr. Stanley Perlman is a Professor of Microbiology, Immunology, and Pediatrics at the University of Iowa. ● John Tamny is Editor of Real Clear Markets. ● Joseph Williams is a Senior News Editor at U.S. News & World Report. Here is the link for the interview
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Interview With Reuters Marilynn Larkin September 10, 2020 | Interview
Marilynn Larkin: Have you had any clinical experience with such children? William Haseltine: No. Marilynn Larkin: Does the use of convalescent plasma seem like an option that could/should be tried in such cases? William Haseltine: Absolutely not. The convalescent plasma is not proven to be effective even for adults. The trials were not conducted properly, and the results were equivocal. The NIH (National Institute of Health) has recommended against the routine use of convalescent plasma. The hyperinflammatory disease in children known as multi system inflammatory syndrome (MIS-C) is a late consequence of infection occurring two to three weeks after the initial virus infection. At that time there is no active virus detected. The theoretical purpose of convalescent plasma is to prevent virus replication, which is no longer an issue when MIS-C appears. Therefore, there is no rational for the use of convalescent serum to treat children with MIS-C. Marilynn Larkin: Any caveats/concerns? Anything else clinicians should be aware of? William Hazeltine: There are always risks of adverse reactions with infusions of human serum. There being no benefit, the risks, any possible risks are an unnecessary danger.
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Interview With Equal Parts September 11, 2020 | Interview
Here is the link to the interview audio Intro: Welcome to the Equal Parts Podcast, brought to you by Care Work. Emily Paisner: Being a working parent is hard. This year we're facing a lot of unanswered questions about the health and safety of our families. Professor William Haseltine is a renowned scientist who's well known for his pioneering work on HIV AIDS, cancer, and genomics. He was a professor at Harvard Medical School and Harvard School of Public Health and is now the President and Chair of ACCESS Health International, a think tank focused on improving access to high-quality affordable health care for people all over the world. Professor Haseltine has written two important resources for families trying to navigate life in the middle of a global pandemic: A Family Guide to COVID, and A COVID Back To School Guide. These are living ebooks meaning they're constantly being updated as new facts and information about the virus become available. He also has a new autobiography coming out this October, My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19. In this episode, Professor Haseltine answers the questions that we all face every day when it comes to COVID and our kids. He offers clarity on making decisions that are best for our families as we all continue to navigate this pandemic together. Have a listen. Professor Haseltine, thank you so much for being here today. We really appreciate it. William Haseltine: It's my pleasure. Thank you. Emily Paisner: In both of your ebooks, you write about the importance of having situational awareness about the coronavirus. You point out that one of the first things we need to know is the risk of infection in our community, and that we should be checking
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it often almost as much as we check the weather. Can you tell us a little bit more about that? William Haseltine: Yes. It is pretty much like the weather. When you go outside, you want to know if it's sunny, a light rain, a heavy rain. If it's a terrible thunderstorm or a hurricane, you stay inside. If it's a tornado, you go to the basement. That's pretty much like COVID. If there's nobody infected in your community, you don't have to worry. If there are some, but not many, that's between those numbers that you can tell how many people for a hundred thousand, then you've got to take precautions. That's a yellow sign. If it's more people infected, and you're likely to encounter somebody who's infected, highly likely that's orange. If it's really dangerous, that's red. If you take a look at the map of the country, they often display it in terms of no color, yellow, orange, and red. You can find that kind of information out by zip code and by county. I urge every parent to do that because the chance of meeting somebody who's contagious is directly related to that color coder. Emily Paisner: You also write about gauging our own personal risk. Of course, this is going to vary from person and family to family. Overall, what are the questions you recommend we should be asking ourselves and things that we should be keeping in mind to determine that level of risk for ourselves and our families? William Haseltine: We're talking about the hierarchy of risks. The first is to know if you're likely to bump into somebody who's contagious and that's what we've just talked about. The second is if you bump into somebody who's contagious, how risky is it for you? There are a number of factors that determine risk. The major factor is age. The older you are, the more likely you are to get infected, and the more likely you are to suffer the serious consequences. That's because your immune system doesn't work so well, and the virus can really attack you much more readily. Then if you're younger, there's a number of other considerations, which added to age makes it even more dangerous. Those include being obese. Obese doesn't mean you're hugely fat. It means body mass index over 30. Most people we think of is really heavy, our body mass index over 40. That's really dangerous. Then there's underlying conditions like asthma, being under cancer 1926
treatment, cardiovascular disease. Those are all predisposing conditions, whether you're young or old. All of those are important to understand. If you're a family unit, it's important to consider everyone in the family. If you're living with your parents, for example, you're living with or having in your house a cousin come to visit who has serious asthma, or maybe overweight, those are all serious considerations for evaluating your risk and the risk of others. Another risk is pregnancy. Pregnancy not only predisposes women to infection. If they are affected, the course of the disease is likely to be more severe than if they're not pregnant. Emily Paisner: We know that half of a million US children have been diagnosed with COVID 19 according to the American Academy of Pediatrics and the Children's Hospital Association. What do we know about children and the risk of contracting and spreading COVID? William Haseltine: It really depends on the age of the child. We call it children, people who are 18 and younger and you really have to stratify what you mean by children. If the child is under the age of five, they can be infected, they can produce enormous amounts of virus, they can spread the virus to other people, but it's unlikely that they'll fall ill themselves. We actually have a good understanding of why that is; the viruses that latch on to a certain component on yourself. Young people don't have much of that component in their lungs, they have it in their upper respiratory tract, their nose. They don't have it in their lungs. Although they get infected, they generally don't get the worst consequences of this disease. Then there are children from five to let's say adolescents, 12, they can be infected, they don't get most of the symptoms but if they do get one of the delayed symptoms which is called multi-system inflammatory syndrome, it is very, very serious. They can appear to be perfectly healthy three weeks after infection and then fall really seriously ill. They can be treated with high dose of corticosteroids and recover pretty well. Most of them recover. Unfortunately, a few you die, but most out if they're treated properly. Then there are the teenagers and above and those are just like adults. You get infected, some people get really ill, it depends on your underlying conditions; is there a heart condition, is their asthma, are they overweight? 1927
Increasingly, because of the way this virus is now being spread through social interactions over the summer, a very large portion of people who are being infected are young people. Now, I'm not so young, so I consider young people anybody under 50. Anywhere in the age of 20 to 50 is a major demographic being affected. Because it's such a major group being affected, many of those people fall ill. The majority don't fall ill but a large number because the number is so large of people being infected up to 50,000 per day, 40 to 50,000 per day in the US that we know about. The number could be 5 to 10 times higher than that that we don't know about. A number of those are falling ill and filling up hospital beds. Just because you're 20 to 50 doesn't mean you're out of the woods when you are infected, especially if you have any other associated condition that might be a risk. Emily Paisner: Yes, we're seeing a lot of that in colleges right now and seeing how quickly it can spread and get out of hand. Talking about schools, and it's fall, it's traditionally back to school season where everyone's gearing up and excited, but this year is very different than anything we've ever seen before. Many schools are using a hybrid learning model, a mix of inperson and remote instruction. They're dividing, my school is doing this, dividing kids into cohorts to lower the risk and minimize the number of kids that are in school at a given time. Do you think that this is a good middle ground in terms of giving kids the in-person learning that they need while also keeping our teachers safe? William Haseltine: It could possibly work in a green and yellow zone. It cannot work in an orange or red zone. A lot of our experiments are now being done in orange and red zones. We are going to see a lot of infections and some disease, especially amongst the older teachers and amongst children with high-risk profiles, that is virtually inevitable. One of the reasons for that is that to manage that kind of system, you need real experts. Many of our public schools are underresourced. The teachers are stressed. They don't have the training that you would need to enforce these disciplines. What we're finding in colleges and universities is that the students are disobeying what they have been told to do. They're having parties, they're getting together when they shouldn't, they're breaking their pod restrictions and we can't be 1928
surprised by that. Until you're about 25, your brain hasn't really fully matured into understanding how to evaluate risk. There's good evolutionary reasons for that, but it's something that we have to understand. What has been happening around the country as we are in the early stages of this massive social experiment is there are a lot of new infections taking place. Now, fortunately, most young people don't fall ill, but the people they can come in contact with may fall Hill and some of them may die. It's pretty serious what's going on now in our educational institutions. I take that K through 12 right on through graduate education is a really serious problem. The reason let me point out is serious is because we have such a high level of infection. Let me put it in a different way. How many people walking around in the United States at this very moment are likely to be contagious. That number is between a million and a million and a half. That is a lot of contagious people. You can calculate that number in some very simple ways. If there are 40,000 people a day being infected, they might be infectious for about 10 days. That's 400,000 people right there, but we know we're not catching all of them. We're catching between, let's say, 1 in 5 and 1 in 10. That puts the number much, much higher of people walking around with the infection who are potentially contagious. Emily Paisner: What I find really interesting is that at the beginning of our conversation, you talked about how we should be checking the levels of cases in our communities on a regular basis. The school system is asking parents to make decisions about what type of learning environment they want their kids to be in for several months, certain quarters. You have to lock in your decision in order to save your child's spot in that whatever cohort you've decided to put your kids in, whether that's fully remote or hybrid or fully in person. That really does put parents in a really challenging situation. William Haseltine: Yes. My advice would be pretty simple. If you're in an orange or red zone, do everything virtually. If you're in a yellow zone, consider your family risks and consider how competent you believe your school authorities are. Competence in schools, as you well know and we know, is not equally distributed across all the public schools. Many public schools are in very poor 1929
facilities. The classes are overcrowded and the general condition of the public school and its operations are poor. That would be an indication to keep your child at home. If you can, there are serious issues because many times when you have that profile of a public school, you are in a community where most of the people have to go to work to survive. They can't afford to do remote work. They can't afford to stay home. Those are really difficult situations or situations that we as a nation have to confront if we want to protect our young people. Emily Paisner: What sort of questions should we be asking of our schools that they're doing to keep our kids safe? What should we be asking them to do? William Haseltine: We should be asking them to test themselves frequently, do spot tests of classes. There is a new method, which is-- not a new method, but an interesting method, which is to check the sewage effluent from individual schools that will tell you if there's COVID in this school and that's being done now, as some basically testing the sewage for virus. Most people don't realize that this virus is not only breezed out, it is excreted in the faeces and it's transmissible that way as a matter of fact. You can tell whether there's virus in the school by testing the school affluent every day, and that would be a very good indication. Are the schools having large classrooms or small classrooms? Are there children in pods? Are the pods really enforced? To enforce a pod is not just the school. The schools that do that demand that the parents provide information about what extracurricular activities the child may be in. Is there a social activity that the child may engage with or the family may engage in? The pods are rather inclusive and intrusive into your personal life. If you're really going to have a pod in a school, that pod includes everybody that child will encounter. They can't have afterschool friends that aren't in their pod. The family can't socialize. The parents cannot travel outside of the state. Those are all restrictions that most people aren't aware of when they're thinking about what a pod might be. Pods are really serious, self-isolating groups. If a school isn't insisting on that degree of integrity of the pod, there is no point in having the pod. I would guess that most schools are not doing that. Some are, most are not.
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Emily Paisner: I would agree with you. [chuckle] At the time of this recording and our conversation, there are more than 6.3 million confirmed cases of COVID in the US and more than 190,000 deaths, which is just shocking. Sadly, we are leading the world in both metrics, not ones that we want to be leading in. These numbers are far exceeding those of other nations and other nations have been successful in stopping the spread of this. What can we learn from some of these other countries in containing the virus and reopening the schools? William Haseltine: The major lesson is to isolate those people who might be contagious, and not focus on those people who are what's called PCR positive or viral RNA positive, which is what we've done. We've basically had a program where we're trying to identify those who are worried and those who are ill with COVID by testing. That isn't a public health strategy. That is a medical strategy. A public health strategy is what the successful other countries have done. What they do is they focus on who might be spreading a virus, who might be contagious, and making sure that those people are isolated from others. What would that look like in the United States? With over a million people at any one time in the US being contagious, contact tracing is extremely difficult. The way it was done in those countries is a few people were identified, all of their contacts were identified, and isolated regardless of test status. That's how they did it. They isolated everybody who could possibly be contagious, and that stopped the epidemic, even lowering the epidemic in Wuhan within two months, brought it down to zero. That's how you do it from public health perspective. Now, because we have so many people infected, we could do that with new technologies that are basically a saliva-based home test, that should cost about 50 cents to $1. If we did that every three days for everybody, we would be able to identify those who are contagious. If we then did the next step, which is support people in family isolation for 10 to 15 days, give them the support they need, supplement their income if they need it, provide medical assistance if they need it, we could stop this infection like they have done in many other countries. Within about two to three months, it would no longer be a problem. Even if a vaccine is improved by the end of the year, it will 1931
be at least a year before it has taken its full effect. That's the most optimistic prediction. We need to do something in the meantime and I think that's what we'll do. If we do that, we can go back to school without worry. I have offices in Shanghai and Beijing and Singapore, and those places these kids are back in school. No problems. We could do the same. Now in India, they're back in school, but they have a problem that's at least as big as ours, or even worse. It really depends how you take care of your entire country. We in India are doing very badly. Other countries are doing better because they've taken a very different approach. They've taken the approach of containing those people who are likely to be contagious. Emily Paisner: Knowing that we are not doing everything we can or should be doing here, what is your view on when you think we will safely be able to have our kids back in school? As parents, what should we be realistically setting our expectations for? William Haseltine: Let's hope by the time we're talking next year this time, we have a program in place to identify those contagious, we have a way of preventing transmission through vaccines are other methods, and we've driven every part of the country to very light yellow to green. I think it's going to take at least another full year. This year is going to be difficult. Emily Paisner: I just think that's helpful for parents as they're mentally trying to prepare for the year ahead. We've covered a lot today. I truly appreciate your expertise here. As we wrap up, can you just share the one most important piece of advice you would want to leave our listeners who are primarily working parents with? William Haseltine: It's your responsibility to take care of yourself and your kids by understanding that the weather out there can be inclement, and you've got to take and rigorously take the necessary precautions to protect yourself and your family. Take this seriously. Emily Paisner: Professor Haseltine, thank you so much for your time today. We really appreciate it. William Haseltine: My pleasure. Thank you for the opportunity. Outro: Thanks for listening to this episode of Equal Parts. See you next time. 1932
Emily Paisner: Wait, before you go, I just want to tell you a little bit about Care Work by care.com. They work with some of the world's largest companies to offer family care benefits to their employees. If you're one of the lucky ones who already has care benefits at work, use them. If you don't, ask for them. It's a real lifesaver. To learn more, visit care.com/careatwork. Again, that's care.com/careatwork.
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Interview With Houston Public Media Ernie Manouse September 14, 2020 | Interview
Town Square with Ernie Manouse is a gathering space for the community to come together and discuss the day's most important and pressing issues. In the first segment, Ernie is joined by Dr. William Haseltine, a renowned scientist, biotech entrepreneur, chair and president of ACCESS Health International (a global think tank), chair of the US/China Health Summit, and a former professor at Harvard Medical School. They discuss the realistic expectations for an effective COVID vaccine, how the U.S. can put COVID in the rear-view mirror (even without a vaccine), and what to expect on a global scale as we enter flu season. Here is the link to the interview.
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Interview With George Citroner September 18, 2020 | Article
George Citroner: What do we know about how infectious asymptomatic COVID cases can be? William Haseltine: They can be highly infectious. Asymptomatic people can be as infectious or more infectious than people with serious disease. The reason being the concentration of virus in oral nasal secretions peaks early in the infection process and can reach as many as a billion virus particles per milliliter. By the time people are seriously ill, the concentration of virus has dropped by many orders of magnitude and often infectious viruses are not detectable. Therefore, asymptomatic people or people in early stages of disease that may be unaware that they are infected are the most contagious. George Citroner: Of those people who are pre-symptomatic can they still spread the virus to others? William Haseltine: Absolutely yes. George Citroner: Are social distancing, mask use, and hygiene measures effective to prevent virus spread due to pre and asymptomatic individuals? William Haseltine: Yes. George Citroner: Do people who test positive for COVID asymptomatically still carry significant risk to their health? William Haseltine: This question is still being investigated. There is some indication that many asymptomatic people actually suffer occult disease which affects their actual physical abilities during the infection and for some time thereafter. However, a definitive answer to the question is still under investigation and will require long term follow up.
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Interview With Houston Public Media Ernie Manouse September 29, 2020 | Interview
Town Square with Ernie Manouse is a gathering space for the community to come together and discuss the day’s most important and pressing issues. In the first segment, Ernie is joined by Dr. William Haseltine, a renowned scientist, biotech entrepreneur, chair and president of ACCESS Health International (a global think tank), chair of the US/China Health Summit, and a former professor at Harvard Medical School. They discuss how the current Covid vaccines in phase-three trials are designed to merely lessen the severity of Covid symptoms, not prevent infection or spread. Dr. Haseltine also reacts to the global milestone in coronavirus deaths–more than one million people worldwide have died in the pandemic. Click Here for to listen to the interview
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Interview With TRT World and Ghida Fakhry September 30, 2020 | Interview
As the global death toll from COVID 19 reached a tragic milestone, with over 1 million deaths worldwide, the US alone recorded more than 205,000 deaths and over 7 million active coronavirus cases. The rising number of deaths and infections brings a renewed sense of urgency for a cure. But also, a growing weariness among Americans that politics rather than science is driving the process for vaccine development and approval. With federal public health officials being openly contradicted and rebuked by President Donald Trump, and the White House accused of interfering in the vaccine process for political gain ahead of the November 3rd election, trust in the safety of a vaccine is waning. Guests: Dr. William Haseltine- Chair and President of ACCESS Health International, a nonprofit dedicated to improving global access to healthcare, and a former professor at Harvard Medical School where he founded two research departments on cancer and HIV/AIDS Dr. Gregory Glenn- President of Research and Development at Novavax, a Maryland-based pharmaceutical company awarded $1.6 billion by the US government to support development and manufacturing of a coronavirus vaccine Dr. Joycelyn Elders- Former Surgeon General of the United States under President Bill Clinton Watch the interview on YouTube
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October 2020
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Interview with CNN Don Lemon October 9, 2020 | Interview
DON LEMON: To the president and his top aides don't seem to care that COVID-19 is surging across the country. Cases are spiking already today. And the day is not even over. More than 54,000 new cases reported. 54,000. The U.S. death toll more than 213,000 now. And yet the president battling the virus himself, inviting 2,000 supporters to the south lawn of the White House tomorrow for a campaign rally. Are they ignoring the real possibility of another super-spreader event? Let's bring in now Dr. -- Mr. William Haseltine, I should say, former professor at Harvard medical school. He's also the author of the COVID commentaries. Good to see you professor. Thank you so much. WILLIAM HASELTINE, CHAIR AND PRESIDENT ACCESS HEALTH INTERNATIONAL: Your welcome, thanks. You can call me doctor if you like, I'm Ph.D. LEMON: All right, thank you doctor. Doctor, professor. So listen, seriously though, the president says he has been re-tested. But the White House, or his doctors, they haven't released the results. So, let's say he still has the virus. OK? Should he be hosting a White House event tomorrow or a rally next week? Is that reckless? HASELTINE: Well, the first thing, I think, is not wise for him personally. I think almost any doctor would recommend rest, stay quiet, don't get out there. And if he's doing it, it's against any good doctor's advice. Good doctors would not do that. This second thing is, it really depends on the precautions that they are planning for the Rose Garden. If it was anything like the introduction of the Supreme Court nominee, it is definitely very dangerous thing to do. As you know, COVID is spreading. And it is spreading particularly at the White House. And it's likely to continue to do so. And in the United States, and people coming from all over the United States. We're in the midst of another major rise in COVID.
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As you mentioned, there were 54,000 people so far today that have been tested positive. That there were 56,000 yesterday and over 920 people died. This is not over, we are not out of the woods, and it's a very dangerous thing to do. LEMON: So, the White House couldn't keep the virus out of the Rose Garden nomination event a couple weeks ago. We just had it up on the screen. Doctor Fauci is calling that event a superspreader event. I want you to look at his rally. This is in Minnesota. Nine people ended up testing positive. Is he a walking superspreader? HASELTINE: You know, a super-spreader is somebody who themselves produces a lot of infectious virus and infects others. I can't tell you if he himself is a spreader. If Hope Hicks who was on that helicopter is a super-spreader. But what we can say is those events with a lot of people packed together, not doing social distancing and not wearing masks, is definitely a super-spreader event. And beyond that, those people fan out all over the country. You know, one of the big problems we had earlier was that motorcycle rally. Where everybody came together from around the country. And then spread out again. And there were many, many people who were contacted by who got infected there. Who got infected and started their own mini epidemics wherever they were. One thing people have to remember, the epidemic, the pandemic, which has circles the globe and killed over 210,000 Americans, started with one person. One person can start a global (inaudible) with this virus. And that is something that everybody should take to heart. Do you want to be next to that one person? LEMON: No, it's rhetorical but no. Doctor Haseltine, thank you. I appreciated it. HASELTINE: You're welcome. Thank you. Read transcript of interview here
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Interview with VuMedi October 16, 2020 | Interview
What Would COVID-19 Vaccine Do? What Are the Vaccine Trials Measuring? Which Requirements Need to Be Met for FDA Approval? Watch the interview here
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Interview with CNN Digital Holly Yan October 21, 2020 | Interview
Insufficient testing is holding the US back "Unfortunately, the US is not better at controlling Covid-19 than it has been since the beginning of the year," said Dr. William Haseltine, a former professor at Harvard Medical School and the author of "COVID Commentaries: A Chronicle of a Plague." "We have more people infected. We have more states, we have our rural areas affected. Once again, we have hospitals filling up -this time, not just in our major metropolitan areas, but in more rural areas. The death rates are going up," he said. Americans should have quick, easy access to testing, Haseltine said. But that's still not the case in many places. "One of my grandchildren had a cold. And we had to get tested. It was murderous. In New York City, there were two places that could do the rapid tests," he said. "Two places in Manhattan. That is unbelievable. And we had to wait hours -- six hours just to get tested." Health experts agree that testing is key to finding those infected with coronavirus -- especially nonsymptomatic carriers -- so they can isolate for 14 days and break the chain of infection. Since the beginning of the pandemic, "we are a little bit better at testing, (but) not much," Haseltine said. By this point in the pandemic, he said, Americans should have access to cheap, rapid 15-minute tests similar to the ones used by the NBA. Haseltine said tests have gotten more accurate in recent months, and some are more affordable -- as cheap as 50 cents. But even if all families had access to rapid tests, not everyone can afford to miss 14 days of work to isolate -- especially since many Americans don't have sick leave from work. "My recommendation is make (tests) universally available to every household, and if somebody in the household is positive ... we
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make it economically possible by paying them to stay home -- the whole family -- for 14 days," Haseltine said. "That could end this epidemic within three to four months." Haseltine said he has calculated the estimated costs for "a program to get everybody three or four months' worth of free tests -- they can test everybody in their family -- and pay everybody $500 to stay home for two weeks, for their entire family" if someone tests positive. "It would cost less than $200 billion. And we are already $16 trillion in the hole on this pandemic (projected through fall 2021). It's a fraction of what it would cost." This plan is "comparatively inexpensive, compared to what we are putting up with," Haseltine said. "If we decided to push the button now, go full-speed ahead, we could probably have this epidemic over and done with by March." So why don't we all have Covid-19 tests in our medicine cabinets yet? "From the President on down, most of the official leadership has been deeply misguided," Haseltine said. "They have focused first on treatment and not on prevention." In June, President Donald Trump famously said "slow the testing down, please." He has said increased testing can lead to higher numbers of reported Covid-19 cases. Adm. Brett Giroir, the White House testing czar, said Covid-19 testing has improved dramatically in the US. But Giroir has repeatedly said, "We can't test our way out of this" pandemic. "He's right in a limited way," Haseltine said. "He's right that testing isn't enough. Testing plus isolation is the way to drive this down to zero ... voluntary testing followed by paid isolation." As for the theory that Covid-19 cases are surging just because of increased testing, "that is absolutely not the case," Haseltine said. "That is not why hospitalizations are going up. That's not why deaths are going up." Read interview here
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White House Nearing Deadline for Fiscal Stimulus (Podcast) October 21, 2020 | Interview
Dr. William Haseltine, Chair and President of Access Health International, provides a coronavirus and vaccine update. Bloomberg News U.S. Health Care Reporter Cynthia Koons walks through the story “Covid Plus Decades of Pollution Are a Nasty Combo for Detroit.” Bloomberg News Congressional Reporter Erik Wasson talks about the White House nearing its goal of having a fiscal stimulus deal in 48 hours. And we Drive to the Close with Barry James, Portfolio Manager with James Investment Research. Hosts: Carol Massar and Paul Sweeney. Producer: Doni Holloway. Click Here for to listen to the interview
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Interview With KNX News Radio October 22, 2020 | Interview
Tonight represents the last chance President Trump will have to personally do damage on the campaign of his opponent, Joe Biden. The second and final debate of the presidential campaign comes a mere 12 days before the election, with polls showing the President trailing in the national race... falling behind in several key swing states. Will we see another angry, aggressive performance from the president..........will Biden be able to put to rest the questions about his own mental fitness? We'll go In Depth. Is the integrity of this election being threatened by foreign actors? That was kind of the indication given at a news conference by the directors of National Intelligence and the FBI, but it raised more questions than answers about the activities of Iran and Russia, so we'll take a closer look. Southwest becomes the latest airline to give up on blocking off middle seats as the industry grows more confident that their planes present low risks for COVID spread. Meanwhile, in most of the country, a surge of coronavirus infections is in full effect and doctors are increasingly worried that we're entering a dark period for this pandemic. But........at the same time......COVID-19 is becoming a less deadly virus. Both research and anecdotal evidence shows the mortality rate for patients is going down. Interview with William Haseltine is at the 20 minute mark. Click Here for to listen to the interview
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Interview with CNN New Day October 26, 2020 | Interview
BERMAN: So election day now just eight days away, which means nine days left to vote, including today. And this morning, the Trump administration is dealing with a new coronavirus outbreak in the White House. Look at the circle surrounding Vice President Mike Pence. At least five members of his inner circle have recently tested positive for coronavirus, including his body man and his chief of staff. And despite crystal-clear CDC guidance that he should quarantine for 14 days, the vice president not doing it. He is the leader of the coronavirus task force, and he's out on the trail, no mask, yesterday in Kingston, North Carolina. He's headed to Minnesota today. Joining us now, CNN senior political reporter, Nia-Malika Henderson. Also with us, William Haseltine. He is a former Harvard Medical School professor, and he is currently the chair and president of Access Health International. [06:15:10] Professor Haseltine, I want to start with you. Because to a certain extent, what's happening with the vice president is emblematic of where we are in this country. We just had our single worst week of the pandemic in terms of new cases. The White House chief of staff says we are no longer trying to control the pandemic. We can't control the spread of the virus anymore. And as if to prove it, the vice president, who should be in quarantine, is out on the campaign trail. Your reaction? WILLIAM HASELTINE, CHAIR/PRESIDENT, ACCESS HEALTH INTERNATIONAL: Well, this is a really dangerous and serious situation. I think we're looking forward to a number of record weeks in the very near future that will drive this daily rate above 100,000. And I can see, if I'm looking across the world, looking at Europe as a predictor of what will happen here, as it was in the spring, that 1946
there could be 200,000 cases. Which, if you project forward, could mean up to a million deaths a year from now. It is a really dangerous situation. But we're not hopeless. We do have hope. There are countries that have driven this infection close to zero. Ten, 20, one, two, three, zero cases. It's not impossible. It's not too late to do it, either. All we have to do is universal household testing and paid family home leave for two weeks for people who are infected. We can do it. CAMEROTA: Yes. But Professor Haseltine, the White House just admitted yesterday, they don't know how to do that, they don't want to do it, they can't figure out how to do that. I don't know what "We're not going to control the pandemic" means to Mark Meadows. I don't know why they've given up or feel so impotent to stop this. I don't -- I don't know what his thinking is, but they're not going to do any of that. It's true, they're not. And they haven't. And that's where we are where we are. But it isn't impossible. You shouldn't give up. I can't understand why a government would give up in the face of such a disaster. It is -- it's not rational. It's -- there are things to do. There are a lot of things to do. It's not just masks. Masks will help. But we can bring this close to zero with good government action. We have the tools. We have an emergency powers declaration. We have the Defense Production Act. We have tremendous expertise as to what to do. It's this administration is not following what other countries have successfully done, and it is a big puzzle why they haven't done it. BERMAN: Nia-Malika, what about the messaging? Because I don't know that it was a gaffe when Mark Meadows, the White House chief of staff, told Jake in this terrific interview that "We're not going to control the pandemic." That's nine days he said that before election day. NIA-MALIKA HENDERSON, CNN SENIOR POLITICAL CORRESPONDENT: Yes, it didn't sound very much like a gaffe. It sounded like a statement of what their policy is, what their approach is to the pandemic. Essentially, everyone is on their own. If they want to wear masks, fine. If they don't, fine, too. And we've obviously seen that in effect at these big rallies that Donald Trump has had. 1947
They seem to think that the sort of saving grace will be these vaccines, which we know won't be here for months and months and months and certainly not available to a wide swath of Americans for many, many months, deep into next year. So that is their stated approach to this. And listen, there is even some evidence that they think herd immunity is the way to go with this. Let as many people get infected as possible, and somehow there'll be this sort of immunity. Of course, what they leave out is the million or so people that would die as a result of that kind of approach. You know, this -- it isn't even that this administration has given up on fighting the coronavirus. They sort of never even really started, in many ways, and they've just sort of hoped that it would go away. Let's open up the schools without a plan. Let's open up businesses without a plan and hope everything goes well. And so that seems to be where they still are. CAMEROTA: Professor Haseltine, the only reason we know about this outbreak in Vice President Pence's orbit is because of reporting. They hadn't disclosed that. We think there's five people. We can't be certain, because they're not -- they're not being forthcoming. They're not voluntarily disclosing it until reporters call and say, You need to confirm this or not confirm this. We have sources saying that people around you are very sick. And -- and so when the head of the coronavirus task force, which is what Vice President Pence is, when he is flouting the CDC guidelines, he is not isolating and staying home for 14 days, which is what you're supposed to do when you come into very close contact, as he has, with his body man, you know, the guy who is with him during all waking hours, he's not doing it, because he says he's an essential employee, I guess, or an essential worker. How is campaigning -- I mean, I guess, does campaign fall into the "essential" category? [06:20:05] HASELTINE: You know, I'm not an expert on that, but I think it makes common sense. You see the other vice-presidential candidate isolating under much more, let's say, generous circumstances, that she has not been as exposed as the vice president has been.
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But this is emblematic of the whole attitude that this administration has not, as was pointed out earlier, taken this epidemic, this pandemic, nearly as seriously as they have. They're not using the powers that the federal government has. And the result of that is the U.S. is, by far, the world's leader. We're now at an average of 60,000 people. And that can quickly go up much higher. If we follow what Europe is doing, we're going to have four times as many people infected within a matter of weeks. And there's no end in sight following that through this winter. This is a tough time, and it's time to take tough actions. BERMAN: I want to read you something that former homeland security adviser Tom Bossert said over the weekend about these rallies, about the types of events that both the president and vice president are going to. He says, "Given the new case totals in the United States, if you have a gathering of a thousand people or more, the odds are almost 100 percent that at least one person in attendance is infectious," he says. Does that sound right to you, Professor Haseltine? And keep in mind, the president and vice president are both doing these giant rallies. Keep in mind, the president once again tonight is going to host an event at the White House to celebrate the confirmation of Judge Amy Coney Barrett. We know the last time they did that, it was a super- spreader event. HASELTINE: That's a conservative estimate. There are going to be, as we know, people who are infected, and people who will transmit that infection to others in these types of situations. It's a certainty. And Bossert's statement is -- is a very conservative reading of the facts. BERMAN: Professor Haseltine, thank you very much. Here is the link for the complete show transcript
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Interview BioInnovation Summit Fireside Chat With Yu GuoLiang October 28, 2020 | Interview
Yu GuoLiang (YG): Thank you Bill for joining me for this fireside chat with the BioInnovation forum. This is actually our second year. I certainly wish you could be here in person. It has been a really long time since we first met. I do not know if you remember it was exactly twenty eight years ago. You invited me to your house and you convinced me to join you to go from Boston to Maryland to work on the Human Genome project. You told me we were going to make history. You remember that? William Haseltine (WH): I remember that, Yu GuoLiang. It is a pleasure to see you. It is a pleasure to participate in this very exciting fireside chats that you have arranged. I think you are doing a great service to the biotech industry in both countries and beyond. I remember it very well. I remember all the excitement of our work at Human Genome Sciences and how you and a whole team of former Caspian Chinese postdoc to graduate students had really formed a really important part of Human Genome Sciences. In fact, if I remember correctly, it was members of your team, that whole group, that came down that made some discoveries that led to the first drugs that have really emerged from the genomics effort. One of the things I think we are proudest of at Human Genome Sciences is maybe the only company that not only discovered a new method to find drugs, that is genomics, but actually take a drug that we found using pure genomic techniques all the way to the market. Many of the biotech companies use new manufacturing techniques, found new ways to make drugs, took an older target and turned it into a drug. But we did something that was truly unique, discovered a new way to find drug targets and took it all the way to the market. I am very proud of what you did, what your team did and what we were able to accomplish. I think that set a marker for the entire drug development industry. It is what we wanted to do with Human Genome Sciences and we succeeded and I want to thank you and all 1950
your friends and the whole team for doing that. It was a wonderful event. YG: Thank you for the kind words. Actually, I think I really want to take this opportunity to thank you for giving me and our team this opportunity to work in Human Genome Sciences and be able to discover something that we are really proud of and be able to make a contribution to the society to bring real drugs into the market and to benefit the patients. The truth is, you have changed my life and changed our life, my family as well. As you know my wife is also very proud to be a member of the Human Genome Science project. WH: I got a two for when you joined us. I got you and your very productive wife and it was wonderful. I remember those days as really as we were pioneers out there on the forefront. We were taking a lot of arrows in our back and some in the front, but we persevered and did well. I am just happy to see the influence that all you who returned to China have brought with you in helping electrify the Chinese biotechnology industry to make it what it is today, which I think is a power, one of the two or three great biotech powers of the world today. YG: Yes, exactly. We will go back to that in talking about what we should do and what we are facing in China right now. I tell you there are nine of us who are former colleagues from HGS, you would be so proud. They are all coming together now after so many years and they work in many different places. Now they are coming to Hangzhou and work together with me on another journey that is so exciting. WH: Well I look forward to the time I can come back to Hangzhou. I remember visiting with my wife and having a wonderful time. We stayed at a beautiful inn, the Aman Resorts right outside the city on a tea plantation. It was one of the best places I have ever been. Staying right in the middle of an old village turned into a hotel, in a tea plantation, fifteen minutes from downtown Hangzhou. What could be better. Right on a beautiful lake as well. I would be more than happy to come back to Hangzhou. It is a wonderful city. YG: So as soon as the pandemic is over, the travel is free, WH: Well it is over for you. It just is not over for the rest of the world. I keep telling people look, the rest of the world has to learn 1951
from China. You can control this pandemic without a vaccine and without a drug. Public health alone can do it. Why the heck don’t we do that? There is something that I think is really important about that. We need three things that work very well in China that do not seem to work in Europe and the United States and that is, you need leadership, leadership that tells it like it is. It is a serious problem. You know after the first problems, with Wuhan, the central government did a magnificent job of leadership. The second thing you need is you need governance. You need to have a system that works. You need to have a public health system or people make policy and everybody in the country follows it. That has been extremely difficult. Then you need a population that follows the rules, not only for themselves, but other sense of social responsibility. And there are a few countries, what I tell people is that a fifth of humanity, mostly Chinese, some New Zealanders, a few South Koreans, and some people in Taiwan and Southeast Asia mostly, with the exception of Malaysia, are virtually free. So you can control this, but we are not doing it. I tell you, it is a tremendous sadness to see what is happening right this moment in my own country, in Europe, in South America and India. Now South America and India you can say, well they are not well governed anyway. They are kind of a tumultuous society. But that is not true of Europe and the United States. It is real failure on all three scores and China is a shining example and because of geopolitical reasons, we are not able to even talk about it. People do not know that 650 million people traveled all over China over the golden week and nobody got infected. That is amazing. You should be very proud of your country and I just wish other people would take what you have done seriously and we can do the same thing. YG: Yeah, so you know, Cam is also in China. He is still in quarantine but we were talking about it feels so good to be free and to be able to travel all over the country in China without having to worry about being infected and without having to worry about safety issues and the people here live very, very normally. WH: Every country can do that if they took your example. And it is a tragedy to the world that is happening. Now the one freedom you do not have is to travel outside of China. Maybe you can travel to Singapore and Hong Kong, maybe. Pretty soon you will be able to go to New Zealand too. And of course you go back and forth to 1952
Taiwan. I have somebody in the office that works for us in Beijing and Shanghai who goes back and forth to Taiwan. Even then, of course, you got to quarantine. But I do not advise any Chinese to go traveling to Europe or the United States in the near future. This is not a safe place. YG: Yeah, this is really very unfortunate. So if we think ourselves as biotech professionals, scientists, do you think there is a near term solution, for example, a vaccine or certain medicine that would make the society feel that there is a way to deal with it? Now we have, at least in the United States, I am also a US citizen. It is kind of, as you said, very sad that WH: You know, the short answer to that question is no. We are not going to have either vaccines or drugs that do anything real, they may change the perception and I think that is even more dangerous because they are not going to change the reality. I have read the vaccine protocols really carefully, the ones the big companies in the US and Europe are pushing and all they are hoping for is a very weak flu vaccine. What do I mean by that? It does not stop infection, it is not meant to. That is not a hurdle. It does not stop serious disease. That is not a hurdle. And it does not stop death. If it does not stop infection, it is not going to stop transmission. If it does not stop serious disease. Who cares if you get a cold? We do not care about cold vaccine particularly. If it does not stop death, that is not good at all, or serious illness. That is not what it is expected to do. Then we look a little more carefully at something like the flu vaccine. Flu vaccine does not do those things very well, especially for older people. So, people are putting their hopes on a vaccine, but I do not think it is going to change the trajectory very much. In fact, if it is not really effective which it does not look it is going to be, we are going to have a new wave of infection because people are going to relax even more. So it could actually accelerate the pandemic, not decrease it. In terms of the antiviral drugs, we are going to have drugs that work very well to suppress the virus. That is not the issue. The issue is when to use those drugs. There is a very short window when antiviral drugs can work, we now know. That is during the incubation period and just before you get sick and just one or two days afterwards. Then the virus is gone. It is like getting hit by a car. Yeah, bang, you get into trouble and then all the long recovery and 1953
sequalae take place. Over time we are learning how bad this disease is. I will tell you something else I just learned. Forty percent of those people who recover from serious COVID have an autoimmune like disease. That is part of what is going on with the long haulers. I will tell you another thing we just discovered. If you have antibodies to interferon type 1, which many people do, you get infected by this virus, you are in deep trouble. Something like fourteen percent of people in the hospitals with serious COVID have interferon deficiencies for one reason or another. Well guess what, you recover from COVID, and you have an interferon deficiency. The other bad thing we have learned is that this virus can come back. There were earlier reports from China and from South Korea of reinfection. Now we know what really occurs. And it is like all the other coronaviruses. It comes right back. YG: Yeah. There are new strains of coronavirus will occur. WH: It is not even new strains, it is just the same guy. With a cold virus, it has been documented that the same person got infected four times in six years with exactly the same virus. It may even be that having antibodies makes it worse for you and makes it easier to get reinfected. So all this hope for a vaccine, I have modest hopes that it will have some effect for some people like the flu vaccine. But the way we are doing it so fast and the way you did it in China so fast is dangerous. Who knows how well it is manufactured? If you do not inspect the plants, which we are not doing, you do not know. Who knows how stable it is. And if you do not do long term safety studies, you do not know how safe it is. We know vaccines can mess you up. So, I worry about what is happening in Russia. I worry what is happening in China. And I worry what could happen in the United States if we rush these things forward. Putting our hopes on medicine rather then public health seems antithetical in this discussion of biotechnology, right? But it is the right thing to do. One thing that is good about this epidemic for biotech is everyone is looking to biotech and the big pharmas for answers. I like that. You like that. Some of the investors like that. It is maybe a long term solution as you and I know. It takes a long time to get drugs to market that are effective and safe. I am glad they are looking at us, but let’s first put our hopes in public health and then biotech and
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pharma to make sure the damn thing does not happen again and next time it comes around we are prepared. What I hope happens in China and US is that we are not as unprepared medically as we were this time. We had the possibility of developing drugs, like protease inhibitors, helicase inhibitors, and having them on the shelf like we have for BioShield. If we had done that, we would not have had almost anybody die of this disease, in China or the US or anywhere else. Let’s take the lesson. Let’s find those drugs, test them, and get them stockpiled so the next time a coronavirus comes along, a flu virus comes along, a really nasty variant of a picornavirus or adenovirus comes along, we are prepared. It is something we know how to do as an industry. I urge us to be prepared and stockpile those drugs and the only people that can stockpile those are governments. Your government, my government, European government should stockpile those because many of those drugs work against all coronaviruses or all human coronaviruses. That is what we as an industry can do. YG: We can learn from the lessons in fighting HIV. It used to be such a devastating disease, AIDS, but now all those antiviral cocktails can really take control of the situation and as you know we have a number of viral inhibitors that allow us to be prepared and when the next time coronavirus come back, we can deal with it. WH: And we have to develop them for prophylactic use. Rapid testing, we also have to really ramp up testing. Make up testing like it is a pregnancy test, something people can do at home, it should cost fifty cents, should be widely available. Then you can find people early enough to treat them with the antivirals. The problem with the antivirals is that they may work prophylactically, they will work early in disease but they are very unlikely to work after the first week. So you really got to be careful. We were lucky with HIV that the drugs will work for years. People get infected with HIV and you have many years. As soon as you treat people with the drugs, the virus levels drop. That is not the case in COVID. Virus levels peak and then almost disappear and then people get really sick. So trying to treat the really sick with antivirals. There is a whole new class of drugs we need. We have always known we needed toxic shock drugs, but we do not have them. Inhibitors are not working. We need toxic shock drugs. We need better drugs to control hyperinflammation, which we know is happening, so we are getting 1955
cytokine storms. We are getting hyperinflammation. We do not know how to control those and it is not with the antiviral drugs that are doing it. They are not working there. There is almost no virus left. There is some other dynamic that we need to understand and develop the drugs and that is something our industry can do and if we do do it, we will be doing something for a very big cause of disease which really does not have a treatment now. I am excited about the possibilities. I am depressed about what is happening in our country, Europe and South America. YG: Right, yeah, yeah. So lets look back in the history when you first invited us to join the Human Genome Sciences where, at the time you called it making history which I totally now believe is the case and its revolution, we call it genomic revolution. I think all the science and technology are related to where we start to build knowledge, start to generate all the information, gather the information process into the knowledge, allow us to come up with new ways of developing a treatment. If we look back, what do you view that the Human Genome project has impact the industry and how does that impact our lives, not just professional lives but really the lives of every individual in society. WH: Let us start at the beginning. I think that when we started Human Genome Sciences, one of the things I realized was that there were very few targets for drug development. In the whole industry there may have been two hundred. The reason for that is people would identify a disease, find the tissue, the cell, the protein and the gene to work on that was at the route of that disease. I just described twenty to thirty years of work. Twenty to thirty years of work. At Human Genome, we realized, once we have the gene, you can go forward and it can take you weeks. It may take you ten weeks and you have a target. Now that changed the way the whole industry works. We did that first with HIV. We were the first to sequence HIV and we did not know anything about the virus. We did not know its proteins. Once we had the genome, bam, we knew everything we needed to know for drug development. We had six or seven targets and many of them have worked actually, even the capsid. Even integrase are now good targets. So genomics changed. A lot has happened with COVID2. First thing we knew about COVID before we knew about everything else is its genomic sequence and what kind of targets we could get and that comes from 1956
our kind of thinking. Everybody hoped there would be a flood of new drugs instantly. That is not what we ever thought because we have changed the process of discovery of targets and the way to work on a problem. We did not change how fast you can get the drug. We learned, how long did it take us. It took us fifteen years from the time we started to the time we got a drug, and guess what I said at the very beginning. We are going to find new targets, but it will take us ten years or more before we have a drug on the market. There is a long time, to discover, develop, test, safety test, manufacture, scale up and sell. We did not change that, but we changed something fundamental, how you find the targets. And now there are more targets available for more diseases than the industry can absorb. It is a wonderful thing and that is what biotech does. That is what your groups in China and we in America and Europe are doing. We are taking these wonderful targets that now genomics has provided and moving them forward towards drugs. And there is great hope. I think you have it, I certainly have it. That most of diseases, if not in my generation, because I am getting a little bit old, but for our children and grandchildren, most diseases will have a good drug and a good means to prevent them. That does not mean we have to give up on public health as we are learning, but it is a great step forward and I think we were a part of that. YG: Yeah, well you certainly convinced me at the time, twenty eight years ago and you continue to convince me so that actually all my career has been devoted into going after the genes that we initially discovered. Then being able to understand the biology behind it, and not just at the single gene level, but the interactions of all the genes and the pathways and the signals, interactions, the communications of the cell. All those biology linked by the knowledge that initially having the gene presented and the ability to understand what they do in different temporal spacial situation and that is where all those targets come from. WH: The other thing I would say that makes me very happy is, I have seen in my lifetime. When I was a graduate student, I was the last of the graduate students who thought Europe was the mecca for biochemistry and molecular biology. All the students just before me went to Europe for their postdocs. I stayed in the US and the US had a great flowering of modern biology and then biotechnology. Then I have seen Europe come back and build a strong 1957
biotechnology presence, and I am really happy to see that happening in China. Scientists like you and me do not look at borders. The only borders we have is what is known and unknown and what we can do to push those borders out, so we know more, we can do more, and we can help more people. Those are the borders we recognize. So it is great for me to see enormous community, well supported, extremely well trained, producing really high quality work. It is like you are new members of a club. We have our friends, our colleagues who think like us, do what we do, and amplify. The thing about science is the more people who are doing it, the faster it goes and it is much more an additive. It is an exponential increase in your ability to solve complicated problems. I have just written an autobiography and I did it to try to encourage young people to become scientists, my lifelong fight against disease from polio to HIV/AIDS to COVID-19. But in that, what you see is the importance of communication amongst scientists and how one scientist can influence another scientist and speed the whole program along and I think it is just wonderful to see such a strong effort in China today. I view what is happening in China today equal to what we can do in the United States. You are a very powerful force in biotechnology and welcome to the club and lets get on with it and do even better things in the future. YG: I really liked what you said Bill. I think the notion of science without borders and medicine without borders, it is certainly true. We have a slogan here, that [00:26:21, ??] in China for the world. We are all trained in the United States, many of us, really most of us got really great training from our universities, pharma companies, organizations and now we are here in China and taking advantage of current support from the whole society, not just from the government but from the community. WH: I hope there is a day when you see Americans in China being trained coming back to America. It is time for that. We have some troubles right now but lets hope we get over those because I have been tremendously impressed not only by what you have done in science and technology, but what your country has done on the whole. I think people who do not travel widely in China do not get the picture. They just do not get it. You and I know what it is like, but most people do not understand it. They have images of China from thirty, forty years ago. It is like somebody coming to America 1958
and expecting there to be Dodge City with cowboys. It just ain’t so. So the images most people have of China just are not right. Especially when it comes to science and technology. I do not see it as a competition. I see it as a win-win, actually a double-win situation. YG: Certainly. It is unfortunate that the government and the administration right now taking the position as if these two countries are in competition and to discourage the healthy interactions between the scientific community and technology. As a scientist, what do you think we should do? WH: You know, lets just take a look at what we do as scientists and biotechnologists. We are competitive. We are not always friendly. We are competitive. But I am looking back over a career and I realized my competitors were also my assistants because by their very good work, they opened up new knowledge that allowed me to make even further advances. And yeah, I was competitive. I wanted to be first. I wanted my company to do better. I may have sometimes said things that I should not have said about my competitors. But that is life. That is how we are. And actually competition is what drives us. It is a driving force. You cannot, I think, be highly productive without also being highly competitive. And that is for nation’s too. In the end, the progress of many is the progress for the few as well. The progress for a few is a progress for the many. That is what we have to remember. The world is a better place because more countries are prosperous. We are a poorer place when countries stumble and fall. Right now China is a poorer place because America, Europe, South America and India are stumbling. We need to pick ourselves back up from this terrible pandemic. We need to learn what public health can do and long term, what science and medicine can do to get back in the game, to move the world back to a much more productive place. I certainly hope we will get there. YG: That certainly is true. We all try our best try to continue our tradition for scientific exchange and for collaboration and competition, of course, a part of it. I hope your vision for how the world should look like resonates among the younger scientists here because, after all, they were trained in the US, have a lot, myself included, have a somewhat Western thinking, but now we are trying to do something in China we think is for a good course. Any 1959
advice you think you would give to young people here for giving very interesting time we are having here? WH: Well, first advice I give to young people is that science and technology is a wonderful career. It is a career that can be deeply rewarding personally, even financially and socially. But more than that it is giving something back to society from what society gives you. It is a tremendous exciting life. If you really take it seriously, it just opens door after door. My own career, I was an academic scientist. I worked on really interesting diseases and helped make some difference, that I was then able to go into business and create new businesses that had an impact. I now have a foundation that works around the world on healthcare advising governments. That is really a tremendous career for people and I think that is something they should remember. The other thing that I think young people should realize is science is one area where one person can improve everybody’s life in the whole world. I know the people who discovered DNA. I knew them both. One was my mentor, the structure of DNA. I know the people who invented polio vaccine. I knew Janus Salk and I had the desk, the very desk, then Joh Enders who discovered the polio virus. I used his equipment. My first professors’ lab was John Enders the discoverer of the polio virus. I know the person who solved the question of how we smell, how we see colors. I know those people. One person in science can change everybody’s life. I cannot think of almost any other profession where that is true and that is something young people might aspire to. If you want to save the universe, being a scientist is a great place to be. You can make a difference. I contributed along with a few friends to stop HIV from killing hundreds of millions of people, possibly. I myself did that. I know and I did it with some friends and that changed the world for many, many people. So this can happen and it is something that young people should think about. It is why I wrote the book and now I am writing a new version. This work is for fifteen year olds plus, it is also, I am writing a book for ten to fifteen year olds. I am rewriting it, giving it a little more color. YG: I would love to read your book. When is the book coming out? WH: You can read it now. If you get Amazon, it is an eBook. It is print on demand. By February it will be a hard back. The 1960
chapters that we did on Human Genome Sciences, of course, that is a big part of the story. I think you will find it interesting. YG: So Bill, I get invited to talk about my career and share my stories. Many of the things you just said, all those wonderful scientists who made a huge contribution, made an impact into people’s lives. I get to talk about them too. One of the persons I talk about is you. WH: Thank you. That is very nice for you to say. YG: [00:35:03, ??] join the industry. Never regret it. WH: Do not forget the philanthropy part at the end. Now I advise governments. In fact, we have offices in Beijing and Shanghai right now. We have offices in Southeast Asia and in India, lots of places in India. We helped craft a plan for the Modi government. We put together all the people from around the world, worked on the whole India healthcare plans. We are now working on health systems, which is what we need to control COVID too. We need public health and health systems to control this terrible pandemic. YG: So don’t you feel that as a scientist, not only it is our passion, it is a career that is fun to have but also our responsibility to the society, to the entire human race to be able to use the science and technology to protect people and to make people’s lives better. You feel a sense of responsibility as supposed to be ok, it is a career or it is a life where you make a living. WH: From the very beginning as I pointed out in my autobiography, I had a good reason to think about health. My parents both, especially my mother, were really ill. Actually, I would not be here talking to you if I were not one of the very first people in the world to get penicillin that was not a soldier. I got it in 1945, January of 1945. I was dying of pneumonia at age four months and my mother persuaded the military doctors to give me penicillin. Thank God for Alexander Fleming and the prepared mind. I would not be talking to you. Then many times in my life I needed medicines to save me. I am now a cancer survivor. Thank God for those medicines and those treatments. I saw my mother suffer from terrible diseases and I thought, this is not right, what can I do. I think other young people, if they feel that way, could make a similar decision. It is a wonderful career. As I say, it keeps opening door after door. Here I am at the end of my career, enjoying my grandchildren, traveling around the world, and all of a sudden I have something more to contribute. All my knowledge of science, viruses, 1961
AIDS, biotech, health systems, government, public health, all come together. Who would guess that at the end of a long career there is a new chapter. But it is a chapter based on a lifetime commitment to fighting disease. So, all of a sudden I am like an old soldier strapping on my helmet, my Kevlar vest again and getting out there and trying to do something. It has been very rewarding. It is a sad time but I got, I think, something I can contribute. The other thing I am doing, which is really fun now, is I am helping my former postdocs and graduate students, people like you. I am helping their students, next generation and even their students, their grand students, their great grandchildren. I am actually in conversations with scientific great grandchildren about what they can do to help fight this pandemic. Some of them are in biotech. Some of them are in universities. Some of them are in government. Some of them are in very high positions in government. They have been head of the CDC. They have been head of the FDA. Former students have been everywhere. So we are having great conversations. As you now, science is like a family. You and I are like a family. We know each other. We lived together for quite awhile before we went our separate ways. We really worked hard on sperate stuff. This is really going back to family and working with your great grandchildren on a serious issue. That is something science can give you too most people do not talk about. There is a sense of community, a global community, of shared thinkers, shared doers, people of good intentions trying to do the best they can with their life’s energy for others. It is a wonderful family to be a part of and you develop, like we have, very close ties that even though we may have not seen each other for many years, we still have a good understanding of who we are. A cousin, for example, we know where they come from. YG: Yeah. This is so inspiring Bill. I think many of the things you just said are really reduced to practicing our day to day life. Many of us who are your followers, as a scientist. Now many of us are mentors to our younger students and even student’s students. We are doing many of those things following your footstep. It is not only something that we only feel we ought to do, but it is actually fun to doing it. As you said, science is so much fun. WH: Well it is not always fun. Let’s make it clear. I tell you what, a lot of times, what I describe to many people what science is 1962
like when they ask me, what I tell them. What it is like to be a scientist in the lab. The way I describe it is you are trying to find out something true about nature. And if you have not done it. You do not know how unknown the unknown is. I describe it as being a miner being down in a coal mine and a black face with no lights chipping away at a rock hoping there is diamonds behind it. But not knowing if there is nothing but black rock behind it. You are down there chipping away, sweating, working for sometimes a year or two without knowing and you will find something and hopefully it is a diamond, but it might just be another rock. So that is what science is actually like. YG: But we are one of the few lucky ones who are once in awhile finding the diamonds. WH: Exactly. YG: Is of course mundane and tiring and boring, but I think if we look back in our life, at least when I look back at my scientific career, even just during the period at Human Genome Sciences, I forgot all the frustrations, all the hard work. I only remember the good things. WH: That is a selective memory and that is a good thing to have. YG: Right, it is always wonderful. Another minor detail, I do not know if you remember. When you invited me to your house and tried to convince me to go with you to Maryland to join the company, you said you look like a productive graduate student postdoc, having one Cell or Nature paper a year. You said that is not good enough. What if you could publish four such papers a year taking advantage of the knowledge you just gained from being at Human Genome. Guess what, I was at HGS for a little over four years and I published sixteen papers. WH: Congratulations. That is great. Good tradition. YG: A lot of very important papers including discovery of [00:43:25,??] including finding a lot of death receptors. Those are still very proud to have the opportunity. I want to thank you for giving me this opportunity, giving many of us the opportunity to participate in this. WH: I think that is another thing that science does for you. If you become a mentor, one of the greatest things is to have brilliant students. Whether you are in business or whether you are in academia, it is a wonderful feeling to be able to work with some of 1963
the brightest minds, most energetic people. It is a great gift. I call it the fountain of youth because what happens is these brilliant young people keep coming. They are going to get older but there is a whole bunch of new young people to work with. It is a wonderful rejuvenating experience to be able to work with all these wonderful young minds. One of the things I would always tell people is just because you are young does not mean you are not smart. You are not going to get smarter as you get older. It is the opposite. You may know more but you are not going to be smarter or you are not going to have any more capabilities. The example I think of is Alexander the Great who conquered the world in his twenties. You have young people, that is something else we all have to recognize, young people have great capabilities. We do not give them necessarily the responsibility they deserve except in science. When I was in my early twenties and I went into the Watson Gilbert lab, they said to me, find a problem and solve it, and we hope it is a really important one. That is the instruction they gave me. They did not say work on this problem or that problem. They said find a problem and solve it. I think that is a wonderful feeling of freedom as a young person. As I write in my book the first three problems I found, I solved, it just did not give me a thesis because they disproved other people’s theories. Finally I found a problem, I solved it. It is a great feeling for young people, it is a great career for young people. It is a career in which you can be your own boss which is something else. A lot of people do not like bosses. I never liked bosses. So being a scientist you can be your own boss. It is a wonderful feeling. YG: It is the free mind, the free, you can come up with many different kinds of innovations, could be technological, could be scientific, and try to solve a problem and make an impact on a real issue on our day to day life. WH: That is true. YG: So, Bill I do not want to tie you up too much. It has been a great conversation with you. I wish we could talk more. And again, I would be the first one to invite you, come to China as soon as we are free to travel around and join us and listen to your inspiring speech. WH: Listen, I will come and give a talk to young people about my autobiography and other topics if you would like, but lets get
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this thing over with first. The other thing I would like if you could, can you send me a video transcript of this. Here is the link for the complete video interview
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Interview with CNN Don Lemon October 9, 2020 | Interview
DON LEMON: To the president and his top aides don't seem to care that COVID-19 is surging across the country. Cases are spiking already today. And the day is not even over. More than 54,000 new cases reported. 54,000. The U.S. death toll more than 213,000 now. And yet the president battling the virus himself, inviting 2,000 supporters to the south lawn of the White House tomorrow for a campaign rally. Are they ignoring the real possibility of another super-spreader event? Let's bring in now Dr. -- Mr. William Haseltine, I should say, former professor at Harvard medical school. He's also the author of the COVID commentaries. Good to see you professor. Thank you so much. WILLIAM HASELTINE, CHAIR AND PRESIDENT ACCESS HEALTH INTERNATIONAL: Your welcome, thanks. You can call me doctor if you like, I'm Ph.D. LEMON: All right, thank you doctor. Doctor, professor. So listen, seriously though, the president says he has been re-tested. But the White House, or his doctors, they haven't released the results. So, let's say he still has the virus. OK? Should he be hosting a White House event tomorrow or a rally next week? Is that reckless? HASELTINE: Well, the first thing, I think, is not wise for him personally. I think almost any doctor would recommend rest, stay quiet, don't get out there. And if he's doing it, it's against any good doctor's advice. Good doctors would not do that. This second thing is, it really depends on the precautions that they are planning for the Rose Garden. If it was anything like the introduction of the Supreme Court nominee, it is definitely very dangerous thing to do. As you know, COVID is spreading. And it is spreading particularly at the White House. And it's likely to continue to do so. And in the United States, and people coming from all over the United States. We're in the midst of another major rise in COVID.
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As you mentioned, there were 54,000 people so far today that have been tested positive. That there were 56,000 yesterday and over 920 people died. This is not over, we are not out of the woods, and it's a very dangerous thing to do. LEMON: So, the White House couldn't keep the virus out of the Rose Garden nomination event a couple weeks ago. We just had it up on the screen. Doctor Fauci is calling that event a superspreader event. I want you to look at his rally. This is in Minnesota. Nine people ended up testing positive. Is he a walking superspreader? HASELTINE: You know, a super-spreader is somebody who themselves produces a lot of infectious virus and infects others. I can't tell you if he himself is a spreader. If Hope Hicks who was on that helicopter is a super-spreader. But what we can say is those events with a lot of people packed together, not doing social distancing and not wearing masks, is definitely a super-spreader event. And beyond that, those people fan out all over the country. You know, one of the big problems we had earlier was that motorcycle rally. Where everybody came together from around the country. And then spread out again. And there were many, many people who were contacted by who got infected there. Who got infected and started their own mini epidemics wherever they were. One thing people have to remember, the epidemic, the pandemic, which has circles the globe and killed over 210,000 Americans, started with one person. One person can start a global (inaudible) with this virus. And that is something that everybody should take to heart. Do you want to be next to that one person? LEMON: No, it's rhetorical but no. Doctor Haseltine, thank you. I appreciated it. HASELTINE: You're welcome. Thank you. Read transcript of interview here
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Interview with VuMedi October 16, 2020 | Interview
What Would COVID-19 Vaccine Do? What Are the Vaccine Trials Measuring? Which Requirements Need to Be Met for FDA Approval? Watch the interview here
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Interview with CNN Digital Holly Yan October 21, 2020 | Interview
Insufficient testing is holding the US back "Unfortunately, the US is not better at controlling Covid-19 than it has been since the beginning of the year," said Dr. William Haseltine, a former professor at Harvard Medical School and the author of "COVID Commentaries: A Chronicle of a Plague." "We have more people infected. We have more states, we have our rural areas affected. Once again, we have hospitals filling up -this time, not just in our major metropolitan areas, but in more rural areas. The death rates are going up," he said. Americans should have quick, easy access to testing, Haseltine said. But that's still not the case in many places. "One of my grandchildren had a cold. And we had to get tested. It was murderous. In New York City, there were two places that could do the rapid tests," he said. "Two places in Manhattan. That is unbelievable. And we had to wait hours -- six hours just to get tested." Health experts agree that testing is key to finding those infected with coronavirus -- especially nonsymptomatic carriers -- so they can isolate for 14 days and break the chain of infection. Since the beginning of the pandemic, "we are a little bit better at testing, (but) not much," Haseltine said. By this point in the pandemic, he said, Americans should have access to cheap, rapid 15-minute tests similar to the ones used by the NBA. Haseltine said tests have gotten more accurate in recent months, and some are more affordable -- as cheap as 50 cents. But even if all families had access to rapid tests, not everyone can afford to miss 14 days of work to isolate -- especially since many Americans don't have sick leave from work. "My recommendation is make (tests) universally available to every household, and if somebody in the household is positive ... we
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make it economically possible by paying them to stay home -- the whole family -- for 14 days," Haseltine said. "That could end this epidemic within three to four months." Haseltine said he has calculated the estimated costs for "a program to get everybody three or four months' worth of free tests -- they can test everybody in their family -- and pay everybody $500 to stay home for two weeks, for their entire family" if someone tests positive. "It would cost less than $200 billion. And we are already $16 trillion in the hole on this pandemic (projected through fall 2021). It's a fraction of what it would cost." This plan is "comparatively inexpensive, compared to what we are putting up with," Haseltine said. "If we decided to push the button now, go full-speed ahead, we could probably have this epidemic over and done with by March." So why don't we all have Covid-19 tests in our medicine cabinets yet? "From the President on down, most of the official leadership has been deeply misguided," Haseltine said. "They have focused first on treatment and not on prevention." In June, President Donald Trump famously said "slow the testing down, please." He has said increased testing can lead to higher numbers of reported Covid-19 cases. Adm. Brett Giroir, the White House testing czar, said Covid-19 testing has improved dramatically in the US. But Giroir has repeatedly said, "We can't test our way out of this" pandemic. "He's right in a limited way," Haseltine said. "He's right that testing isn't enough. Testing plus isolation is the way to drive this down to zero ... voluntary testing followed by paid isolation." As for the theory that Covid-19 cases are surging just because of increased testing, "that is absolutely not the case," Haseltine said. "That is not why hospitalizations are going up. That's not why deaths are going up." Read interview here
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White House Nearing Deadline for Fiscal Stimulus (Podcast) October 21, 2020 | Interview
Dr. William Haseltine, Chair and President of Access Health International, provides a coronavirus and vaccine update. Bloomberg News U.S. Health Care Reporter Cynthia Koons walks through the story “Covid Plus Decades of Pollution Are a Nasty Combo for Detroit.” Bloomberg News Congressional Reporter Erik Wasson talks about the White House nearing its goal of having a fiscal stimulus deal in 48 hours. And we Drive to the Close with Barry James, Portfolio Manager with James Investment Research. Hosts: Carol Massar and Paul Sweeney. Producer: Doni Holloway. Click Here for to listen to the interview
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Interview With KNX News Radio October 22, 2020 | Interview
Tonight represents the last chance President Trump will have to personally do damage on the campaign of his opponent, Joe Biden. The second and final debate of the presidential campaign comes a mere 12 days before the election, with polls showing the President trailing in the national race... falling behind in several key swing states. Will we see another angry, aggressive performance from the president..........will Biden be able to put to rest the questions about his own mental fitness? We'll go In Depth. Is the integrity of this election being threatened by foreign actors? That was kind of the indication given at a news conference by the directors of National Intelligence and the FBI, but it raised more questions than answers about the activities of Iran and Russia, so we'll take a closer look. Southwest becomes the latest airline to give up on blocking off middle seats as the industry grows more confident that their planes present low risks for COVID spread. Meanwhile, in most of the country, a surge of coronavirus infections is in full effect and doctors are increasingly worried that we're entering a dark period for this pandemic. But........at the same time......COVID-19 is becoming a less deadly virus. Both research and anecdotal evidence shows the mortality rate for patients is going down. Interview with William Haseltine is at the 20 minute mark. Click Here for to listen to the interview
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Interview with CNN New Day October 26, 2020 | Interview
BERMAN: So election day now just eight days away, which means nine days left to vote, including today. And this morning, the Trump administration is dealing with a new coronavirus outbreak in the White House. Look at the circle surrounding Vice President Mike Pence. At least five members of his inner circle have recently tested positive for coronavirus, including his body man and his chief of staff. And despite crystal-clear CDC guidance that he should quarantine for 14 days, the vice president not doing it. He is the leader of the coronavirus task force, and he's out on the trail, no mask, yesterday in Kingston, North Carolina. He's headed to Minnesota today. Joining us now, CNN senior political reporter, Nia-Malika Henderson. Also with us, William Haseltine. He is a former Harvard Medical School professor, and he is currently the chair and president of Access Health International. [06:15:10] Professor Haseltine, I want to start with you. Because to a certain extent, what's happening with the vice president is emblematic of where we are in this country. We just had our single worst week of the pandemic in terms of new cases. The White House chief of staff says we are no longer trying to control the pandemic. We can't control the spread of the virus anymore. And as if to prove it, the vice president, who should be in quarantine, is out on the campaign trail. Your reaction? WILLIAM HASELTINE, CHAIR/PRESIDENT, ACCESS HEALTH INTERNATIONAL: Well, this is a really dangerous and serious situation. I think we're looking forward to a number of record weeks in the very near future that will drive this daily rate above 100,000. And I can see, if I'm looking across the world, looking at Europe as a predictor of what will happen here, as it was in the spring, that 1973
there could be 200,000 cases. Which, if you project forward, could mean up to a million deaths a year from now. It is a really dangerous situation. But we're not hopeless. We do have hope. There are countries that have driven this infection close to zero. Ten, 20, one, two, three, zero cases. It's not impossible. It's not too late to do it, either. All we have to do is universal household testing and paid family home leave for two weeks for people who are infected. We can do it. CAMEROTA: Yes. But Professor Haseltine, the White House just admitted yesterday, they don't know how to do that, they don't want to do it, they can't figure out how to do that. I don't know what "We're not going to control the pandemic" means to Mark Meadows. I don't know why they've given up or feel so impotent to stop this. I don't -- I don't know what his thinking is, but they're not going to do any of that. It's true, they're not. And they haven't. And that's where we are where we are. But it isn't impossible. You shouldn't give up. I can't understand why a government would give up in the face of such a disaster. It is -- it's not rational. It's -- there are things to do. There are a lot of things to do. It's not just masks. Masks will help. But we can bring this close to zero with good government action. We have the tools. We have an emergency powers declaration. We have the Defense Production Act. We have tremendous expertise as to what to do. It's this administration is not following what other countries have successfully done, and it is a big puzzle why they haven't done it. BERMAN: Nia-Malika, what about the messaging? Because I don't know that it was a gaffe when Mark Meadows, the White House chief of staff, told Jake in this terrific interview that "We're not going to control the pandemic." That's nine days he said that before election day. NIA-MALIKA HENDERSON, CNN SENIOR POLITICAL CORRESPONDENT: Yes, it didn't sound very much like a gaffe. It sounded like a statement of what their policy is, what their approach is to the pandemic. Essentially, everyone is on their own. If they want to wear masks, fine. If they don't, fine, too. And we've obviously seen that in effect at these big rallies that Donald Trump has had. 1974
They seem to think that the sort of saving grace will be these vaccines, which we know won't be here for months and months and months and certainly not available to a wide swath of Americans for many, many months, deep into next year. So that is their stated approach to this. And listen, there is even some evidence that they think herd immunity is the way to go with this. Let as many people get infected as possible, and somehow there'll be this sort of immunity. Of course, what they leave out is the million or so people that would die as a result of that kind of approach. You know, this -- it isn't even that this administration has given up on fighting the coronavirus. They sort of never even really started, in many ways, and they've just sort of hoped that it would go away. Let's open up the schools without a plan. Let's open up businesses without a plan and hope everything goes well. And so that seems to be where they still are. CAMEROTA: Professor Haseltine, the only reason we know about this outbreak in Vice President Pence's orbit is because of reporting. They hadn't disclosed that. We think there's five people. We can't be certain, because they're not -- they're not being forthcoming. They're not voluntarily disclosing it until reporters call and say, You need to confirm this or not confirm this. We have sources saying that people around you are very sick. And -- and so when the head of the coronavirus task force, which is what Vice President Pence is, when he is flouting the CDC guidelines, he is not isolating and staying home for 14 days, which is what you're supposed to do when you come into very close contact, as he has, with his body man, you know, the guy who is with him during all waking hours, he's not doing it, because he says he's an essential employee, I guess, or an essential worker. How is campaigning -- I mean, I guess, does campaign fall into the "essential" category? [06:20:05] HASELTINE: You know, I'm not an expert on that, but I think it makes common sense. You see the other vice-presidential candidate isolating under much more, let's say, generous circumstances, that she has not been as exposed as the vice president has been.
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But this is emblematic of the whole attitude that this administration has not, as was pointed out earlier, taken this epidemic, this pandemic, nearly as seriously as they have. They're not using the powers that the federal government has. And the result of that is the U.S. is, by far, the world's leader. We're now at an average of 60,000 people. And that can quickly go up much higher. If we follow what Europe is doing, we're going to have four times as many people infected within a matter of weeks. And there's no end in sight following that through this winter. This is a tough time, and it's time to take tough actions. BERMAN: I want to read you something that former homeland security adviser Tom Bossert said over the weekend about these rallies, about the types of events that both the president and vice president are going to. He says, "Given the new case totals in the United States, if you have a gathering of a thousand people or more, the odds are almost 100 percent that at least one person in attendance is infectious," he says. Does that sound right to you, Professor Haseltine? And keep in mind, the president and vice president are both doing these giant rallies. Keep in mind, the president once again tonight is going to host an event at the White House to celebrate the confirmation of Judge Amy Coney Barrett. We know the last time they did that, it was a super- spreader event. HASELTINE: That's a conservative estimate. There are going to be, as we know, people who are infected, and people who will transmit that infection to others in these types of situations. It's a certainty. And Bossert's statement is -- is a very conservative reading of the facts. BERMAN: Professor Haseltine, thank you very much. Here is the link for the complete show transcript
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Interview BioInnovation Summit Fireside Chat With Yu GuoLiang October 28, 2020 | Interview
Yu GuoLiang (YG): Thank you Bill for joining me for this fireside chat with the BioInnovation forum. This is actually our second year. I certainly wish you could be here in person. It has been a really long time since we first met. I do not know if you remember it was exactly twenty eight years ago. You invited me to your house and you convinced me to join you to go from Boston to Maryland to work on the Human Genome project. You told me we were going to make history. You remember that? William Haseltine (WH): I remember that, Yu GuoLiang. It is a pleasure to see you. It is a pleasure to participate in this very exciting fireside chats that you have arranged. I think you are doing a great service to the biotech industry in both countries and beyond. I remember it very well. I remember all the excitement of our work at Human Genome Sciences and how you and a whole team of former Caspian Chinese postdoc to graduate students had really formed a really important part of Human Genome Sciences. In fact, if I remember correctly, it was members of your team, that whole group, that came down that made some discoveries that led to the first drugs that have really emerged from the genomics effort. One of the things I think we are proudest of at Human Genome Sciences is maybe the only company that not only discovered a new method to find drugs, that is genomics, but actually take a drug that we found using pure genomic techniques all the way to the market. Many of the biotech companies use new manufacturing techniques, found new ways to make drugs, took an older target and turned it into a drug. But we did something that was truly unique, discovered a new way to find drug targets and took it all the way to the market. I am very proud of what you did, what your team did and what we were able to accomplish. I think that set a marker for the entire drug development industry. It is what we wanted to do with Human Genome Sciences and we succeeded and I want to thank you and all 1977
your friends and the whole team for doing that. It was a wonderful event. YG: Thank you for the kind words. Actually, I think I really want to take this opportunity to thank you for giving me and our team this opportunity to work in Human Genome Sciences and be able to discover something that we are really proud of and be able to make a contribution to the society to bring real drugs into the market and to benefit the patients. The truth is, you have changed my life and changed our life, my family as well. As you know my wife is also very proud to be a member of the Human Genome Science project. WH: I got a two for when you joined us. I got you and your very productive wife and it was wonderful. I remember those days as really as we were pioneers out there on the forefront. We were taking a lot of arrows in our back and some in the front, but we persevered and did well. I am just happy to see the influence that all you who returned to China have brought with you in helping electrify the Chinese biotechnology industry to make it what it is today, which I think is a power, one of the two or three great biotech powers of the world today. YG: Yes, exactly. We will go back to that in talking about what we should do and what we are facing in China right now. I tell you there are nine of us who are former colleagues from HGS, you would be so proud. They are all coming together now after so many years and they work in many different places. Now they are coming to Hangzhou and work together with me on another journey that is so exciting. WH: Well I look forward to the time I can come back to Hangzhou. I remember visiting with my wife and having a wonderful time. We stayed at a beautiful inn, the Aman Resorts right outside the city on a tea plantation. It was one of the best places I have ever been. Staying right in the middle of an old village turned into a hotel, in a tea plantation, fifteen minutes from downtown Hangzhou. What could be better. Right on a beautiful lake as well. I would be more than happy to come back to Hangzhou. It is a wonderful city. YG: So as soon as the pandemic is over, the travel is free, WH: Well it is over for you. It just is not over for the rest of the world. I keep telling people look, the rest of the world has to learn 1978
from China. You can control this pandemic without a vaccine and without a drug. Public health alone can do it. Why the heck don’t we do that? There is something that I think is really important about that. We need three things that work very well in China that do not seem to work in Europe and the United States and that is, you need leadership, leadership that tells it like it is. It is a serious problem. You know after the first problems, with Wuhan, the central government did a magnificent job of leadership. The second thing you need is you need governance. You need to have a system that works. You need to have a public health system or people make policy and everybody in the country follows it. That has been extremely difficult. Then you need a population that follows the rules, not only for themselves, but other sense of social responsibility. And there are a few countries, what I tell people is that a fifth of humanity, mostly Chinese, some New Zealanders, a few South Koreans, and some people in Taiwan and Southeast Asia mostly, with the exception of Malaysia, are virtually free. So you can control this, but we are not doing it. I tell you, it is a tremendous sadness to see what is happening right this moment in my own country, in Europe, in South America and India. Now South America and India you can say, well they are not well governed anyway. They are kind of a tumultuous society. But that is not true of Europe and the United States. It is real failure on all three scores and China is a shining example and because of geopolitical reasons, we are not able to even talk about it. People do not know that 650 million people traveled all over China over the golden week and nobody got infected. That is amazing. You should be very proud of your country and I just wish other people would take what you have done seriously and we can do the same thing. YG: Yeah, so you know, Cam is also in China. He is still in quarantine but we were talking about it feels so good to be free and to be able to travel all over the country in China without having to worry about being infected and without having to worry about safety issues and the people here live very, very normally. WH: Every country can do that if they took your example. And it is a tragedy to the world that is happening. Now the one freedom you do not have is to travel outside of China. Maybe you can travel to Singapore and Hong Kong, maybe. Pretty soon you will be able to go to New Zealand too. And of course you go back and forth to 1979
Taiwan. I have somebody in the office that works for us in Beijing and Shanghai who goes back and forth to Taiwan. Even then, of course, you got to quarantine. But I do not advise any Chinese to go traveling to Europe or the United States in the near future. This is not a safe place. YG: Yeah, this is really very unfortunate. So if we think ourselves as biotech professionals, scientists, do you think there is a near term solution, for example, a vaccine or certain medicine that would make the society feel that there is a way to deal with it? Now we have, at least in the United States, I am also a US citizen. It is kind of, as you said, very sad that WH: You know, the short answer to that question is no. We are not going to have either vaccines or drugs that do anything real, they may change the perception and I think that is even more dangerous because they are not going to change the reality. I have read the vaccine protocols really carefully, the ones the big companies in the US and Europe are pushing and all they are hoping for is a very weak flu vaccine. What do I mean by that? It does not stop infection, it is not meant to. That is not a hurdle. It does not stop serious disease. That is not a hurdle. And it does not stop death. If it does not stop infection, it is not going to stop transmission. If it does not stop serious disease. Who cares if you get a cold? We do not care about cold vaccine particularly. If it does not stop death, that is not good at all, or serious illness. That is not what it is expected to do. Then we look a little more carefully at something like the flu vaccine. Flu vaccine does not do those things very well, especially for older people. So, people are putting their hopes on a vaccine, but I do not think it is going to change the trajectory very much. In fact, if it is not really effective which it does not look it is going to be, we are going to have a new wave of infection because people are going to relax even more. So it could actually accelerate the pandemic, not decrease it. In terms of the antiviral drugs, we are going to have drugs that work very well to suppress the virus. That is not the issue. The issue is when to use those drugs. There is a very short window when antiviral drugs can work, we now know. That is during the incubation period and just before you get sick and just one or two days afterwards. Then the virus is gone. It is like getting hit by a car. Yeah, bang, you get into trouble and then all the long recovery and 1980
sequalae take place. Over time we are learning how bad this disease is. I will tell you something else I just learned. Forty percent of those people who recover from serious COVID have an autoimmune like disease. That is part of what is going on with the long haulers. I will tell you another thing we just discovered. If you have antibodies to interferon type 1, which many people do, you get infected by this virus, you are in deep trouble. Something like fourteen percent of people in the hospitals with serious COVID have interferon deficiencies for one reason or another. Well guess what, you recover from COVID, and you have an interferon deficiency. The other bad thing we have learned is that this virus can come back. There were earlier reports from China and from South Korea of reinfection. Now we know what really occurs. And it is like all the other coronaviruses. It comes right back. YG: Yeah. There are new strains of coronavirus will occur. WH: It is not even new strains, it is just the same guy. With a cold virus, it has been documented that the same person got infected four times in six years with exactly the same virus. It may even be that having antibodies makes it worse for you and makes it easier to get reinfected. So all this hope for a vaccine, I have modest hopes that it will have some effect for some people like the flu vaccine. But the way we are doing it so fast and the way you did it in China so fast is dangerous. Who knows how well it is manufactured? If you do not inspect the plants, which we are not doing, you do not know. Who knows how stable it is. And if you do not do long term safety studies, you do not know how safe it is. We know vaccines can mess you up. So, I worry about what is happening in Russia. I worry what is happening in China. And I worry what could happen in the United States if we rush these things forward. Putting our hopes on medicine rather then public health seems antithetical in this discussion of biotechnology, right? But it is the right thing to do. One thing that is good about this epidemic for biotech is everyone is looking to biotech and the big pharmas for answers. I like that. You like that. Some of the investors like that. It is maybe a long term solution as you and I know. It takes a long time to get drugs to market that are effective and safe. I am glad they are looking at us, but let’s first put our hopes in public health and then biotech and
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pharma to make sure the damn thing does not happen again and next time it comes around we are prepared. What I hope happens in China and US is that we are not as unprepared medically as we were this time. We had the possibility of developing drugs, like protease inhibitors, helicase inhibitors, and having them on the shelf like we have for BioShield. If we had done that, we would not have had almost anybody die of this disease, in China or the US or anywhere else. Let’s take the lesson. Let’s find those drugs, test them, and get them stockpiled so the next time a coronavirus comes along, a flu virus comes along, a really nasty variant of a picornavirus or adenovirus comes along, we are prepared. It is something we know how to do as an industry. I urge us to be prepared and stockpile those drugs and the only people that can stockpile those are governments. Your government, my government, European government should stockpile those because many of those drugs work against all coronaviruses or all human coronaviruses. That is what we as an industry can do. YG: We can learn from the lessons in fighting HIV. It used to be such a devastating disease, AIDS, but now all those antiviral cocktails can really take control of the situation and as you know we have a number of viral inhibitors that allow us to be prepared and when the next time coronavirus come back, we can deal with it. WH: And we have to develop them for prophylactic use. Rapid testing, we also have to really ramp up testing. Make up testing like it is a pregnancy test, something people can do at home, it should cost fifty cents, should be widely available. Then you can find people early enough to treat them with the antivirals. The problem with the antivirals is that they may work prophylactically, they will work early in disease but they are very unlikely to work after the first week. So you really got to be careful. We were lucky with HIV that the drugs will work for years. People get infected with HIV and you have many years. As soon as you treat people with the drugs, the virus levels drop. That is not the case in COVID. Virus levels peak and then almost disappear and then people get really sick. So trying to treat the really sick with antivirals. There is a whole new class of drugs we need. We have always known we needed toxic shock drugs, but we do not have them. Inhibitors are not working. We need toxic shock drugs. We need better drugs to control hyperinflammation, which we know is happening, so we are getting 1982
cytokine storms. We are getting hyperinflammation. We do not know how to control those and it is not with the antiviral drugs that are doing it. They are not working there. There is almost no virus left. There is some other dynamic that we need to understand and develop the drugs and that is something our industry can do and if we do do it, we will be doing something for a very big cause of disease which really does not have a treatment now. I am excited about the possibilities. I am depressed about what is happening in our country, Europe and South America. YG: Right, yeah, yeah. So lets look back in the history when you first invited us to join the Human Genome Sciences where, at the time you called it making history which I totally now believe is the case and its revolution, we call it genomic revolution. I think all the science and technology are related to where we start to build knowledge, start to generate all the information, gather the information process into the knowledge, allow us to come up with new ways of developing a treatment. If we look back, what do you view that the Human Genome project has impact the industry and how does that impact our lives, not just professional lives but really the lives of every individual in society. WH: Let us start at the beginning. I think that when we started Human Genome Sciences, one of the things I realized was that there were very few targets for drug development. In the whole industry there may have been two hundred. The reason for that is people would identify a disease, find the tissue, the cell, the protein and the gene to work on that was at the route of that disease. I just described twenty to thirty years of work. Twenty to thirty years of work. At Human Genome, we realized, once we have the gene, you can go forward and it can take you weeks. It may take you ten weeks and you have a target. Now that changed the way the whole industry works. We did that first with HIV. We were the first to sequence HIV and we did not know anything about the virus. We did not know its proteins. Once we had the genome, bam, we knew everything we needed to know for drug development. We had six or seven targets and many of them have worked actually, even the capsid. Even integrase are now good targets. So genomics changed. A lot has happened with COVID2. First thing we knew about COVID before we knew about everything else is its genomic sequence and what kind of targets we could get and that comes from 1983
our kind of thinking. Everybody hoped there would be a flood of new drugs instantly. That is not what we ever thought because we have changed the process of discovery of targets and the way to work on a problem. We did not change how fast you can get the drug. We learned, how long did it take us. It took us fifteen years from the time we started to the time we got a drug, and guess what I said at the very beginning. We are going to find new targets, but it will take us ten years or more before we have a drug on the market. There is a long time, to discover, develop, test, safety test, manufacture, scale up and sell. We did not change that, but we changed something fundamental, how you find the targets. And now there are more targets available for more diseases than the industry can absorb. It is a wonderful thing and that is what biotech does. That is what your groups in China and we in America and Europe are doing. We are taking these wonderful targets that now genomics has provided and moving them forward towards drugs. And there is great hope. I think you have it, I certainly have it. That most of diseases, if not in my generation, because I am getting a little bit old, but for our children and grandchildren, most diseases will have a good drug and a good means to prevent them. That does not mean we have to give up on public health as we are learning, but it is a great step forward and I think we were a part of that. YG: Yeah, well you certainly convinced me at the time, twenty eight years ago and you continue to convince me so that actually all my career has been devoted into going after the genes that we initially discovered. Then being able to understand the biology behind it, and not just at the single gene level, but the interactions of all the genes and the pathways and the signals, interactions, the communications of the cell. All those biology linked by the knowledge that initially having the gene presented and the ability to understand what they do in different temporal spacial situation and that is where all those targets come from. WH: The other thing I would say that makes me very happy is, I have seen in my lifetime. When I was a graduate student, I was the last of the graduate students who thought Europe was the mecca for biochemistry and molecular biology. All the students just before me went to Europe for their postdocs. I stayed in the US and the US had a great flowering of modern biology and then biotechnology. Then I have seen Europe come back and build a strong 1984
biotechnology presence, and I am really happy to see that happening in China. Scientists like you and me do not look at borders. The only borders we have is what is known and unknown and what we can do to push those borders out, so we know more, we can do more, and we can help more people. Those are the borders we recognize. So it is great for me to see enormous community, well supported, extremely well trained, producing really high quality work. It is like you are new members of a club. We have our friends, our colleagues who think like us, do what we do, and amplify. The thing about science is the more people who are doing it, the faster it goes and it is much more an additive. It is an exponential increase in your ability to solve complicated problems. I have just written an autobiography and I did it to try to encourage young people to become scientists, my lifelong fight against disease from polio to HIV/AIDS to COVID-19. But in that, what you see is the importance of communication amongst scientists and how one scientist can influence another scientist and speed the whole program along and I think it is just wonderful to see such a strong effort in China today. I view what is happening in China today equal to what we can do in the United States. You are a very powerful force in biotechnology and welcome to the club and lets get on with it and do even better things in the future. YG: I really liked what you said Bill. I think the notion of science without borders and medicine without borders, it is certainly true. We have a slogan here, that [00:26:21, ??] in China for the world. We are all trained in the United States, many of us, really most of us got really great training from our universities, pharma companies, organizations and now we are here in China and taking advantage of current support from the whole society, not just from the government but from the community. WH: I hope there is a day when you see Americans in China being trained coming back to America. It is time for that. We have some troubles right now but lets hope we get over those because I have been tremendously impressed not only by what you have done in science and technology, but what your country has done on the whole. I think people who do not travel widely in China do not get the picture. They just do not get it. You and I know what it is like, but most people do not understand it. They have images of China from thirty, forty years ago. It is like somebody coming to America 1985
and expecting there to be Dodge City with cowboys. It just ain’t so. So the images most people have of China just are not right. Especially when it comes to science and technology. I do not see it as a competition. I see it as a win-win, actually a double-win situation. YG: Certainly. It is unfortunate that the government and the administration right now taking the position as if these two countries are in competition and to discourage the healthy interactions between the scientific community and technology. As a scientist, what do you think we should do? WH: You know, lets just take a look at what we do as scientists and biotechnologists. We are competitive. We are not always friendly. We are competitive. But I am looking back over a career and I realized my competitors were also my assistants because by their very good work, they opened up new knowledge that allowed me to make even further advances. And yeah, I was competitive. I wanted to be first. I wanted my company to do better. I may have sometimes said things that I should not have said about my competitors. But that is life. That is how we are. And actually competition is what drives us. It is a driving force. You cannot, I think, be highly productive without also being highly competitive. And that is for nation’s too. In the end, the progress of many is the progress for the few as well. The progress for a few is a progress for the many. That is what we have to remember. The world is a better place because more countries are prosperous. We are a poorer place when countries stumble and fall. Right now China is a poorer place because America, Europe, South America and India are stumbling. We need to pick ourselves back up from this terrible pandemic. We need to learn what public health can do and long term, what science and medicine can do to get back in the game, to move the world back to a much more productive place. I certainly hope we will get there. YG: That certainly is true. We all try our best try to continue our tradition for scientific exchange and for collaboration and competition, of course, a part of it. I hope your vision for how the world should look like resonates among the younger scientists here because, after all, they were trained in the US, have a lot, myself included, have a somewhat Western thinking, but now we are trying to do something in China we think is for a good course. Any advice 1986
you think you would give to young people here for giving very interesting time we are having here? WH: Well, first advice I give to young people is that science and technology is a wonderful career. It is a career that can be deeply rewarding personally, even financially and socially. But more than that it is giving something back to society from what society gives you. It is a tremendous exciting life. If you really take it seriously, it just opens door after door. My own career, I was an academic scientist. I worked on really interesting diseases and helped make some difference, that I was then able to go into business and create new businesses that had an impact. I now have a foundation that works around the world on healthcare advising governments. That is really a tremendous career for people and I think that is something they should remember. The other thing that I think young people should realize is science is one area where one person can improve everybody’s life in the whole world. I know the people who discovered DNA. I knew them both. One was my mentor, the structure of DNA. I know the people who invented polio vaccine. I knew Janus Salk and I had the desk, the very desk, then Joh Enders who discovered the polio virus. I used his equipment. My first professors’ lab was John Enders the discoverer of the polio virus. I know the person who solved the question of how we smell, how we see colors. I know those people. One person in science can change everybody’s life. I cannot think of almost any other profession where that is true and that is something young people might aspire to. If you want to save the universe, being a scientist is a great place to be. You can make a difference. I contributed along with a few friends to stop HIV from killing hundreds of millions of people, possibly. I myself did that. I know and I did it with some friends and that changed the world for many, many people. So this can happen and it is something that young people should think about. It is why I wrote the book and now I am writing a new version. This work is for fifteen year olds plus, it is also, I am writing a book for ten to fifteen year olds. I am rewriting it, giving it a little more color. YG: I would love to read your book. When is the book coming out? WH: You can read it now. If you get Amazon, it is an eBook. It is print on demand. By February it will be a hard back. The 1987
chapters that we did on Human Genome Sciences, of course, that is a big part of the story. I think you will find it interesting. YG: So Bill, I get invited to talk about my career and share my stories. Many of the things you just said, all those wonderful scientists who made a huge contribution, made an impact into people’s lives. I get to talk about them too. One of the persons I talk about is you. WH: Thank you. That is very nice for you to say. YG: [00:35:03, ??] join the industry. Never regret it. WH: Do not forget the philanthropy part at the end. Now I advise governments. In fact, we have offices in Beijing and Shanghai right now. We have offices in Southeast Asia and in India, lots of places in India. We helped craft a plan for the Modi government. We put together all the people from around the world, worked on the whole India healthcare plans. We are now working on health systems, which is what we need to control COVID too. We need public health and health systems to control this terrible pandemic. YG: So don’t you feel that as a scientist, not only it is our passion, it is a career that is fun to have but also our responsibility to the society, to the entire human race to be able to use the science and technology to protect people and to make people’s lives better. You feel a sense of responsibility as supposed to be ok, it is a career or it is a life where you make a living. WH: From the very beginning as I pointed out in my autobiography, I had a good reason to think about health. My parents both, especially my mother, were really ill. Actually, I would not be here talking to you if I were not one of the very first people in the world to get penicillin that was not a soldier. I got it in 1945, January of 1945. I was dying of pneumonia at age four months and my mother persuaded the military doctors to give me penicillin. Thank God for Alexander Fleming and the prepared mind. I would not be talking to you. Then many times in my life I needed medicines to save me. I am now a cancer survivor. Thank God for those medicines and those treatments. I saw my mother suffer from terrible diseases and I thought, this is not right, what can I do. I think other young people, if they feel that way, could make a similar decision. It is a wonderful career. As I say, it keeps opening door after door. Here I am at the end of my career, enjoying my grandchildren, traveling around the world, and all of a sudden I have something more to contribute. All my knowledge of science, viruses, 1988
AIDS, biotech, health systems, government, public health, all come together. Who would guess that at the end of a long career there is a new chapter. But it is a chapter based on a lifetime commitment to fighting disease. So, all of a sudden I am like an old soldier strapping on my helmet, my Kevlar vest again and getting out there and trying to do something. It has been very rewarding. It is a sad time but I got, I think, something I can contribute. The other thing I am doing, which is really fun now, is I am helping my former postdocs and graduate students, people like you. I am helping their students, next generation and even their students, their grand students, their great grandchildren. I am actually in conversations with scientific great grandchildren about what they can do to help fight this pandemic. Some of them are in biotech. Some of them are in universities. Some of them are in government. Some of them are in very high positions in government. They have been head of the CDC. They have been head of the FDA. Former students have been everywhere. So we are having great conversations. As you now, science is like a family. You and I are like a family. We know each other. We lived together for quite awhile before we went our separate ways. We really worked hard on sperate stuff. This is really going back to family and working with your great grandchildren on a serious issue. That is something science can give you too most people do not talk about. There is a sense of community, a global community, of shared thinkers, shared doers, people of good intentions trying to do the best they can with their life’s energy for others. It is a wonderful family to be a part of and you develop, like we have, very close ties that even though we may have not seen each other for many years, we still have a good understanding of who we are. A cousin, for example, we know where they come from. YG: Yeah. This is so inspiring Bill. I think many of the things you just said are really reduced to practicing our day to day life. Many of us who are your followers, as a scientist. Now many of us are mentors to our younger students and even student’s students. We are doing many of those things following your footstep. It is not only something that we only feel we ought to do, but it is actually fun to doing it. As you said, science is so much fun. WH: Well it is not always fun. Let’s make it clear. I tell you what, a lot of times, what I describe to many people what science is 1989
like when they ask me, what I tell them. What it is like to be a scientist in the lab. The way I describe it is you are trying to find out something true about nature. And if you have not done it. You do not know how unknown the unknown is. I describe it as being a miner being down in a coal mine and a black face with no lights chipping away at a rock hoping there is diamonds behind it. But not knowing if there is nothing but black rock behind it. You are down there chipping away, sweating, working for sometimes a year or two without knowing and you will find something and hopefully it is a diamond, but it might just be another rock. So that is what science is actually like. YG: But we are one of the few lucky ones who are once in awhile finding the diamonds. WH: Exactly. YG: Is of course mundane and tiring and boring, but I think if we look back in our life, at least when I look back at my scientific career, even just during the period at Human Genome Sciences, I forgot all the frustrations, all the hard work. I only remember the good things. WH: That is a selective memory and that is a good thing to have. YG: Right, it is always wonderful. Another minor detail, I do not know if you remember. When you invited me to your house and tried to convince me to go with you to Maryland to join the company, you said you look like a productive graduate student postdoc, having one Cell or Nature paper a year. You said that is not good enough. What if you could publish four such papers a year taking advantage of the knowledge you just gained from being at Human Genome. Guess what, I was at HGS for a little over four years and I published sixteen papers. WH: Congratulations. That is great. Good tradition. YG: A lot of very important papers including discovery of [00:43:25,??] including finding a lot of death receptors. Those are still very proud to have the opportunity. I want to thank you for giving me this opportunity, giving many of us the opportunity to participate in this. WH: I think that is another thing that science does for you. If you become a mentor, one of the greatest things is to have brilliant students. Whether you are in business or whether you are in academia, it is a wonderful feeling to be able to work with some of 1990
the brightest minds, most energetic people. It is a great gift. I call it the fountain of youth because what happens is these brilliant young people keep coming. They are going to get older but there is a whole bunch of new young people to work with. It is a wonderful rejuvenating experience to be able to work with all these wonderful young minds. One of the things I would always tell people is just because you are young does not mean you are not smart. You are not going to get smarter as you get older. It is the opposite. You may know more but you are not going to be smarter or you are not going to have any more capabilities. The example I think of is Alexander the Great who conquered the world in his twenties. You have young people, that is something else we all have to recognize, young people have great capabilities. We do not give them necessarily the responsibility they deserve except in science. When I was in my early twenties and I went into the Watson Gilbert lab, they said to me, find a problem and solve it, and we hope it is a really important one. That is the instruction they gave me. They did not say work on this problem or that problem. They said find a problem and solve it. I think that is a wonderful feeling of freedom as a young person. As I write in my book the first three problems I found, I solved, it just did not give me a thesis because they disproved other people’s theories. Finally I found a problem, I solved it. It is a great feeling for young people, it is a great career for young people. It is a career in which you can be your own boss which is something else. A lot of people do not like bosses. I never liked bosses. So being a scientist you can be your own boss. It is a wonderful feeling. YG: It is the free mind, the free, you can come up with many different kinds of innovations, could be technological, could be scientific, and try to solve a problem and make an impact on a real issue on our day to day life. WH: That is true. YG: So, Bill I do not want to tie you up too much. It has been a great conversation with you. I wish we could talk more. And again, I would be the first one to invite you, come to China as soon as we are free to travel around and join us and listen to your inspiring speech. WH: Listen, I will come and give a talk to young people about my autobiography and other topics if you would like, but lets get
1991
this thing over with first. The other thing I would like if you could, can you send me a video transcript of this. Here is the link for the complete video interview
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November 2020
1993
Interview with KIRO Radio November 5, 2020 | Interview
How Will the Election Affect the Pandemic's Third Wave? The US is hitting a 3rd wave of coronavirus cases while we reconsider our nation's leadership. What would it take for either Biden or Trump to get life in the US "back to normal" again? KIRO Radio's Dave Ross interviews virologist Dr. William Haseltine, a former Harvard researcher with a focus on public health, about how we can banish the pandemic for good... even without a vaccine. Then, reporter Aaron Granillo joins to talk about what the exit polls suggest American voters prioritized this election: the economy, or the pandemic? Click Here for to listen to the interview
1994
Interview with Seattle Morning News November 6, 2020 | Interview
Interview with William Haseltine is at the 13:15 mark. Margaret Brennan on the president's claims of election fraud // Feliks Banel, All Over the Map -- Columbia, Cowlitz, and Douglas Counties // Hanna Scott on efforts to reopen WA schools // Dr. William Haseltine on the effectiveness of a COVID vaccine // Dose of Kindness -- Two Blind Brothers // Gee Scott on the Georgia vote // Feliks Banel marks 80 years since Galloping Gertie Click Here for to listen to the interview
1995
Interview with David Ross November 6, 2020 | Interview
Dr. William Haseltine, We Don't Need a Vaccine to End the Pandemic As cases of the novel coronavirus reach new heights, you might be pinning your hopes on finding a vaccine. Dr. William Haseltine is here to shatter that illusion: but luckily, he doesn't think we actually need a vaccine to start dining out, hooking up and dancing in clubs again. Dr. Haseltine is a former professor and researcher at Harvard Medical School and the Harvard School of Public Health, the founder and president of ACCESS Health International, and an esteemed virologist who may just make an appearance on the next coronavirus task force. He sits down with Dave Ross to explain why the current vaccines everyone is racing to develop aren't going to be a perfect protection from the virus. But at-home tests and earning $500 a day to stay quarantined might help us get this under control the way Wuhan, China has. Click Here for to listen to the interview
1996
Interview with Houston Public Media November 10, 2020 | Interview
A New Vaccine Against COVID And Health Experts Answer Your Questions Town Square with Ernie Manouse airs at 3 p.m. CT. Tune in on 88.7FM or listen online. Join the discussion at 888-486-9677, questions@townsquaretalk.org or @townsquaretalk. A new COVID-19 vaccine made by Pfizer, other new COVID research and developments as Texas becomes the first state to break past the million case mark over the weekend. Global health expert and chair and president of ACCESS Health International, Dr. William Haseltine, walks us through what this means for the oncoming winter season. Click Here for to listen to the interview
1997
Interview on Bloomberg.com November 16, 2020 | Interview
Vaccine To Reach Most People By Mid 2021, Says Access Health International President Access Health International Chair and President Dr. William Haseltine discusses the timeline and effectiveness of a Covid-19 vaccine. He speaks with Kathleen Hays and Haidi Stroud-Watts on "Bloomberg Daybreak: Australia." November 16, 2020 (Source: Bloomberg) Click Here for to listen to the interview
1998
Interview on Health Matters Radio November 20, 2020 | Interview
About A Family Guide To Covid In A Family Guide to Covid, William A. Haseltine answers tough questions about Covid-19 honestly, with equal measures of clarity and compassion. A new disease has spread across our world. Schools have shut down, people around the world have been asked to stay home, businesses are shuttered, economies are crashing. The sad state of affairs is not entirely new for Dr. Haseltine who remembers how polio overshadowed his young life. As he got older, he realized that diseases didn't just harm individuals, they crippled communities and devastated entire countries. He became a scientist, dedicating his life to understanding the diseases that threaten us most and figuring out ways to stop and prevent them. Today, Dr. Haseltine finds that his children, his grandchildren and many of his friends and extended family members are coming to him with question after question. Why have our lives changed? Are my children in danger? When will this be over? Will there be a vaccine or a cure and if so, when? When will our lives return to normal? This book attempts to answer those questions about COVID-19 honestly, with equal measures of clarity and compassion. It is written especially for those who are faced with the difficult task of not only protecting themselves, but of protecting their families, their children, their spouses, and their parents. Split into two sections, the first section seeks to give answers to questions that children and grandchildren may ask. Each question has in fact been asked by someone under twelve, some as young as four and five. The second section provides short answers to many of the difficult questions adults from ages eighteen to one hundred and ten ask themselves to understand this new reality. Again these are real questions people have asked.
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As our understanding of Covid-19 evolves, so too will this book. When a purchase is made, readers will be given entry to a password protected section of Dr. Haseltine's website. There, readers can download subsequent editions freely and have the most up to date answers to the most critical Covid questions of the day. As Dr. Haseltine sees it, "Our children and grandchildren will one day look back as I do and remember a time when disease stalked the streets and changed their life. My hope is that some of those children will be inspired to dedicate their lives to science and medicine so that their own children and grandchildren and for that matter no child anywhere should have to endure what they did." The Interview: Ned Hoke (NH): Welcome back to Health Matter. Dr. Ned Hoke today joined by Dr. Haseltine who has written a very interesting book called The Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children. So, may I call you Bill? William Haseltine (WH): Yes, you certainly may. NH: Okay, Bill, welcome to Health Matters radio. WH: I am happy to be here. NH: So, for our listeners who may not be familiar with your name, you are somebody who has done a lot of groundbreaking work in the world of human science and the human genome. Maybe you could just give us a page of your background so our listeners get a sense of how you have become such an authority that you have. WH: Well, thank you for the opportunity and thank you to your listeners for being interested. For me, the COVID epidemic is an apotheosis of my career in a very strange way. I would never have predicted that this time of my life, I just turned seventy-six, I would be pretty much at the center of a global pandemic and have something to offer. From the time I was very, I knew I wanted to make a difference in medicine. By the time I got to be a graduate student, I realized I was interested in science. So, my career first took me to fundamental science with great mentors. I had four Nobel prize winners who were mentors. I became a professor at Harvard working on fundamental aspects of cancer and virology, particularly if you are interested in viruses that cause cancer. But that led me to suspect that retroviruses might be involved in human disease and after a couple of years of working and creating departments of cancer 2000
research at Harvard, HIV came along and it turned out that I made a correct guess along with a few others that HIV would be a retrovirus and was really one of the only people in the world prepared really to work on it in the very early days. I did a lot of work and realized that AIDS was going to be a problem that would be with us a long time like cancer. We needed not just a sporadic response; we needed an institutional response. So in addition to doing research and understanding the virus, coming up with a theory of combination chemotherapy for treatment of AIDS and helping develop some of the first drugs, I worked with a lot of different people to help. For example, founded amfAR to get research started, lobbied Congress to get money for research, worked with Princess Diana to destigmatize the whole problem. In retrospect, there are a lot of similarities between our responses to HIV and COVID. It is like everything that happened with HIV happened with COVID, only in a collapsed timeframe. People denied the issues of HIV at our highest level, President Reagan, for about five years. Research took off very quickly, but people were not prepared to take that this was going to be a serious disease. In fact, in a book written by all people Bob Redfield, the head of our CDC now, called The Myth of Heterosexual AIDS to give you an idea of those times. We did a lot of work on that and a lot of that has really helped me understand people’s reactions, reluctance, political considerations, wanted to shove everything under the carpet, let the next guy take the burden. All those things were going on. HIV/AIDS was a little different because it was not everybody. St first it was gays and drug users, and it took a while for people to realize it was a lot more than that. But for all that, science has done a wonderful job from the very beginning, just like COVID. The one brilliant success with COVID is science. Whether it is Chinese science or US science. Chinese sequenced the virus lickety split, created vaccines, drugs are on the way, same in the West. It has just been an amazing scientific journey that is about to make a big difference and do it pretty quickly. But from the political and social point of view, it has been a total disaster where we are. From there, I went into biotech and I created a number of companies. I think seven drugs are on the market that I had a hand in creating. That has taught me a lot about drug development, visive COVID and I actually developed vaccines and I actually created a 2001
company with a guy who created Moderna to make vaccines more efficient. We were not successful, but eventually he has been successful. So, I have created new vaccines, new adjuvants, got them approved. That is relevant. For the last fifteen years, I have been advising governments around the world on health system reform. One thing that COVID has made clear is we in the United States need to reform our public health system. We know we needed to make our healthcare system more efficient, better for patients, more cost effective. We spend four times more than the rest of the world but do not get very good results. Somewhat a little bit better than the Dominican Republic if you believe it. That is sad to say we are two standard deviations below the OECD, yet we spend twice as much then the closest neighbor and four times as much as Singapore which gets a lot better results. So I wrote a book called Affordable Excellence saying we could get a lot better results for less money. I actually studied in another book called World Class how a US institution, teaching research and medical care, can reform itself from mediocre to being the best in the world. So it is not just about what government can do, it is what hospital systems, and medical school systems can do themselves. You know, you cannot rely on the government for everything. There has to be somethings. But we have to do, each individual, each institution, has to be the best they can be too. And all of that is very good preparation for trying to understand what COVID is, what can we do about it, what can we do to try to get the public to respond in a better way. I have been working like seventeen, eighteen hours a day on trying to communicate my understanding in a way that is helpful to policy makers, the average man in the street with these books, The Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children and then another book COVID Guide to Back to School, same kind of thing. So that is a brief, it is probably longer than you wanted. NH: No, no, that is okay. I very much appreciated all the detail because I think what it does is, well it is the very thing I was looking for actually because what I wanted to do was I wanted to start our conversation really saying, what made me happy looking at The Family Guide to COVID was the authority that came in the language that you speak in in the book. The leadership that you are showing in the text and the layout and the intention and so on, it is 2002
all the things that have been so missing on a national scene. So, you stepped in with this philanthropy project, it seems like. This is not a way to make Bill Haseltine any more money. WH: No, every penny goes into the foundation that I started. It is definitely not to make money. I will tell you the lesson from this. During HIV/AIDS I became a private advisor to [00:9:17,??] and helped them sort out some of their nasty policy issues and people issues. But in the course of that, I made friends with an artist with Niki de Saint Phalle. She is a French American artist. She died a few years ago. But she wrote a book called AIDS: You Can’t Catch a Cold Holding Hands which was a model for me. It was a model about speaking to kids and their parents. She wrote it for her grandchildren about AIDS and I really wrote this book for my grandchildren. She was a real inspiration for me, not only a great artist, but a great humanist. The way I got to meet her is a scientist friend of mine said look, I have an artist friend who is writing a book for kids about AIDS. You know a lot about AIDS, maybe you should get together. And we became like the best of friends and this has been a great inspiration for me. There is one other inspiration thing about the work I do. I am really interested and have written an autobiography, and the whole point of that is to encourage kids to have a life in science. I had two great mentors. First was an undergraduate mentor who was a fisherman of scientists and was just totally dedicated to educating people and trying to find people to be scientists. And I am very, very indebted and grateful to him. But there is another later in life a man that I met who was truly remarkable. He was president of India at the time, Abdul Kalam. Abdul Kalam came from the poorest of poor backgrounds. He was about five feet tall, a Muslim and gay, and president of India. He is the man who started the rocket program and aerosonic bomb program and he spent all of his time trying to get young Indians to be interested in science and technology. I cannot tell you ho many places he opened up and what a wonderful human being he was. He was just a terrific educator. He wrote about five or six books to inspire kids become scientists. So, I wrote my autobiography for college kids and adults, but I am also writing another one for ten to fifteen year old guys and girls encouraging them to be scientists too. I have had a lot of good mentors and I want to carry the torch as far as I can. 2003
NH: Well, you are succeeding with me anyway. I want to let the listeners know this book, The Family Guide to COVID, is available on a website. Tell us about what a living eBook is. You sort of started this genre, so help our listeners understand and also give us the website where they can actually go read this publication. WH: First, it is for free on the website. It is www.williamhaseltine.com. If you go on there, you get the book for free. If you go on Amazon, you can get it for like $1. But because of the power of the internet today and how fast COVID changes, our world changes, I came up with a new format I call a living eBook, which is you buy it once, you get a passcode and we update it. We are already in the process of doing edition three of the Family Guide. You got edition two which is How to Enjoy the Summer. We are now working on How to Enjoy the Winter and Be Safe. So, the idea that you can buy one book and have it continually update is what I think the internet allows. That is the concept I call the living eBook. We have now three versions of it. We have the first one which is The Family Guide to COVID. It is undergoing edition three, it is in edition two now. You get it for free and you get the password. By the way the password is askdrbill. Second book is also a living eBook. Then I write a lot of things about COVID. I write abut two, three, four pieces a day. I find all the interesting journal articles and newspaper articles. Those are all put together in something A COVID Commentary: A Chronicle of a Plague Year. It is also available on Amazon and it is a compendium of all the things I have written up until September, and at the end of the year, it is going to be all the things I have written since January to December. It is another living eBook and it just will keep on going as long as I am writing about COVID, which hopefully will be for maybe another year and hopefully will be on to some other topic. NH: So, of course, we are at a unique pregnant moment now for our listeners who have jut recently heard about the Pfizer and the Moderna vaccines coming alive. Give us your take on where things are and how do you feel like the public information that we are getting is reasonably accurate. Can you imagine that the vaccine will be available to people in the Spring? What do you have to say about the current situation vis a vi the vaccine? WH: Well, the first thing is, the situation with COVID in the United States is absolutely horrendous and it did not have to be. One 2004
of the things that bothers me the most is that the Chinese showed us how to control this epidemic very early on. They had an epidemic like we had in New York City and since April, there has been no COVID in China to speak of. All COVIDS come in from outside and they control absolutely. So human beings can control COVID without drugs or vaccines. The fact that Europe and the United States and South America and other parts of the world have not is a disgrace to the human race. It shows how fragile and disorganized we are. The fact that it can be controlled and is still being controlled in China despite the rest of the world having a raging pandemic to me is absolutely horrifying. It is understandable but it does not make it any less horrifying knowing what this does to people. Second of all, right now we are in a terrible moment because we are in an exponential growth phase and we do not know where it is going to end. My guess, we can have four hundred thousand people every day getting infected and four thousand people every day dying. That is where we are headed if you want to know what I think. We see no way, with the current government and the conundrum and the horrible things that are happening in our national government and some of our state governments still, to control it. It is just maddeningly out of control. Now is there anything we can do? Yes, there are some things we can do right away to put an end to this, to stop it. France is locked down and has stopped their trajectory cold. They were zooming up like we are and now they have leveled off, in one week, two weeks, leveled off. We can do the same and drop. I do not see that happening just yet. What is happening with the vaccines? Well, the vaccines are working better then we thought. We do not know a lot about them yet. They have been tested almost entirely on young people and this disease kills mostly old people and we do not know what it is going to do to old people because vaccines stop working at about age forty five. That surprises people but that is how early vaccines stop working and in order to protect yourself from flu, some people over forty-five need a quadruple dose for it to work at all. So, will this be like that, we do not know yet. Is it really safe? We do not really know that because we have not spent enough time. How long will it last? We do not know that yet? Nonetheless, the data that has come out looked pretty good and I think what is going to happen is the vaccine will be rolled out. But it is not going to save us until 2005
summer. You know, Tony Fauci said the calvary is coming and it is coming from science in a year or two. But in the meantime, the homestead may be burned down, the wagon trains may be in a trash, the fort may be overrun like the Alamo and everybody dead inside. It will look like a burned out world three or four months from now. The vaccine will slowly get rolled out. It takes awhile for these vaccines to get rolled out. We are so disorganized in America. Think of testing is how vaccines are going to get out there. When the central government says it is up to the states, well that is a recipe of disaster. Some of the states will say, yeah, it is up to me the governor where other states will say, oh no, it is up to the counties or it is up to the municipalities. It is not even up to me. What one municipality does for testing or vaccines, another one may be differently. It is going to be a, I will not use a swear word, it is going to be a disaster rolling out these vaccines. We have no confidence the way our leadership is going if people believe the leadership. Try to believe a guy who has lied twenty thousand times. NH: Well Donald Trump is no longer really relevant. WH: Believe me, he is relevant until the day he steps out of office and he may be relevant for a lot of people. Look, people believe celebrities. He is the ultimate celebrity. I understand that a lot of my fellow Americans have their faith and belief in him. You cannot deny that anymore than you can deny that seventy percent of people who were told they were going to die when their partner infected them with HIV did not use condoms, seventy percent. So you have to understand where people’s minds really are and half of the American people believe in this president and we have to take that seriously. He could make a big difference. I have heard people in an interview say, if Donald Trump told me to wear a mask, I would wear a mask. So, I was hoping that after the election was over he would wake up and say, hey, I really will try to help. But he has not. He has done everything opposite. NH: He has been playing golf. He has been busy, the golf is very trying, takes a lot of effort. So Bill, forgive me, we need to take a break. We are talking to Bill Haseltine. We are trying to get to talking about the book The Family Guide to COVID and we are also spending some time talking about many other things that Bill has to do, has shared with us. Please stay with us.
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So welcome back to Health Matters. Dr. Ned Hoke joined today by Dr. William Haseltine and we are talking about his book A Family Guide to COVID, but really we are talking about the whole situation. Bill has been very generous so far. Keep being generous with us Bill. You are really giving us the data that we are really hungry for. On this program we have been reviewing and looking at all the COVID literature we can get our hands on, we have been making a point to try to share with our listeners the best parts of everything we can find and so far you are the best we found in terms of the authority and the breadth of vision that you have for this topic. So please keep talking about the current status if you would and where you think things could go and what we the fellow citizens you feel what we should be doing in addition to reading your book. WH: Well, first of all, it is very, very generous of you. Any author loves to hear what you just said. So thank you, thank you very much for speaking about the book and understanding what we are trying to do with it. I was trying to carry on the tradition of my mentors and people I was really close to in trying to help people understand the current situation we are in and what they can do about it. Everybody knows the US is really going up in flames with COVID and we cannot see an end to it at present because we cannot see, half the country at least, understanding what is happening to them. Just take the Dakotas, the worst in the entire world. When did you think that North and South Dakota would be the world’s hotspots for an infectious disease? That is the reality. The world’s hotspot is right now, in terms of number of cases, number of hospitalizations and number of deaths. The world’s hotspot. So, when that is happening, it tells you that this disease is really serious. But what can you do? Thanksgiving is coming up and I just canceled Thanksgiving for most everybody who was going to come because I do not want them to take the risk. I want to see them. I want to see my children. I want to see my grandchildren. It is a really important time for everybody, but it is too dangerous. And that is in New York where the danger is less than almost any other place in the country, New York and Connecticut. But it is too dangerous. So that is what I want people to understand. This is not going to last forever. You know, if this were the weather, we would be in cyclone condition. What do you do with a cyclone? You go to the basement with your family and you protect them. You want 2007
everybody to listen. Say it is your job to protect your family. That is your job in life. That is a human being’s job, is to protect those they love. You protect those they love by wearing masks, social distancing, do not gather with other people no matter what your age. You may not think you are going to die. You may kill your grandpa, or you may kill your grandmother or your mom or your neighbor. That is who you might kill by your behavior of gong out and going out to a party or going to a bar or meeting with people you do not know right now. This is a really terrible time. You have to assume that everybody you meet is infected because a lot of them are ten times more. We are infecting about a, my guess conservatively is we are infecting about a million people a day in the United States and that means because you are infectious for about ten days, there are about ten million people in our country spreading this disease around right now. That means you are going to run into a lot of infected people, and you may be one of them. NH: In your book, you break it down in a very useful way. You start with the questions the kids ask, questions that we ask ourselves, then you get to situational awareness. Maybe you can start with, go ahead. WH: The way I think about it is like the weather. If it is a nice sunny day, you ask Alexa, you ask Siri, whoever you ask. Oh yeah, it is a sunny day, go out no problem. That is a green zone where less than one in a hundred thousand are infected. Then if there is a light rain, you put on some protective gear, you go out, you do not really bother. You may not do some things you may otherwise do, but that is sort of like five people per hundred thousand infected. New York is somewhere in that vicinity now. Other places are not. Then you get up to a heavy rainstorm where you are pretty careful where you go. Finally you are in a cyclone and a lot of parts of the United States are in a cyclone where you hunker down and you stay in your basement and you dramatically limit what you do. The way you know that is you look to see if you are in a green, yellow, orange or red zone which is by how many people per hundred thousand are diagnosed that day, that week of being infected and you multiply that number by five or ten to understand how many people in your area are likely to be carrying the virus. So that is the way to think about the first part.
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Second part is what is my susceptibility to disease. Somebody in my family, are they overweight, obesity. Half the people in the Midwest are obese or a body mass index of thirty. Twenty percent of the kids have a body mass index. So, when they say, oh, we should only let the virus roll and only protect those people who are especially sensitive, well that is about half of America. You look at the numbers thirty seven percent of Americans have a body mass index of over thirty. That is a huge jump. So, you cannot do, you cannot protect one part of, you cannot protect thirty percent of the population. It is not just old people we are talking about. Second of all, do you have asthma, does anybody have diabetes, are you living with someone who is old. Third, if I am going somewhere, sending my kid to school, going to work, going to a store. How careful are they? What is your situational awareness? And that is something that everybody should have deep in their mind. Let me say the other thing, the biggest thing to watch out for, is it took awhile for us to understand that this virus is transmitted not just by droplets, it can hang in the air for four or five hours in an unventilated space and can infect you. If people are breathing out, even with a mask. Most masks do not stop the virus. Those tiny particles stay in the air for four or five hours. The longer you are in a closed space with more people, the more dangerous it is. Stay out of closed spaces with people you do not know because you are going to be breathing in and it is getting into your nose, it is getting, it gets into your mouth and it gets into your eyes, and hangs in the air for a long time. There are a lot of people who won’t tell you that, but we know that for a fact for a long time for this virus. It is an aerosol and if you want to know who knew it, [00:28:13,??] knew it in January when he was talking to Bob Woodruff. He said this is spread through the air just by breathing. It is not only droplets. So those are things I want people to understand that if they go to places that are, if they have to for some reason, put on an N95 mask and wear a face shield. And if you are going to travel, put on a hazmat outfit and wear gloves. Bring a lot of gloves and change your gloves as often as you would wash your hands. You think that is [00:28:49,??] No. if you are flying anywhere in the east, toward China or any of those places, everybody on the plane is wearing a hazmat suit, everybody has got an N95 mask and half of them have face shields. That is how they fly in China. I have the pictures. We are not seeing that. We are not 2009
seeing how they are protecting themselves over there. But we should be doing the same thing. You go on public transportation you should be wearing an N95 mask, you should have face shield, you should be wearing a hazmat suit and you should have gloves. That is how bad it is. People are not doing that. They have no idea that is what they should be doing. NH: Exactly. One of our previous guests on this topic, a guy named Dr. Steven Quay wrote a book called COVID-19 Survival and one of the things he came up with or he revealed is the idea of putting salt on a mask and salt was one of the ways of making the mask more effective because when the viral particles touches the surface of the mask, if the salt is also got a little bit of soap in it, the viral particles will be broken down by the salt. Apparently, there was some studies about that. Are you familiar with that? WH: I would be suspicious of that, but I will look at the studies. NH: Well anyway. WH: It is like trying to catch a bird by putting salt on its tail. You get close enough to get salt on the bird’s tail, you got to have the bird. I would not go chasing that particular one. I put my face in an N95 mask more than putting salt on a paper. Maybe it would work. NH: Anyway, there is actually some science on it that you could look about, but we will not try to solve that now. But the thing is what you have done for us is you showed us and you revealed to us what, again, is one of the things that is completely missing in the public discussion which is the depth of care that is going to take to get through this horrible period that we are obviously just getting in the beginning of here in terms of this winter. WH: Let me make another point. There has been a study of doctors and hospitals and healthcare workers in hospitals when they are wearing a face shield or not wearing a face shield, wearing hazmat outfit, gloves and N95 masks. And that face shield reduces transmission from low to zero. The face shields, by the way, kids like face shields. It is easier than the mask. NH: I like it. You kind of want them to do both though is what you are saying? WH: You want them to do both. For kids, use a face shield. It is much easier for them.
2010
NH: We have been talking about situational awareness. Let us move on to protection and prevention. We talked some about that but let us say, ok, the family goes to the grocery store and they come back. They have worn their mask in the grocery store, they come back, they wash their hands when they come back from the grocery store. To you, I would almost believe you say well you should probably take off your clothes and then launder those clothes and then change clothes when you got to your home. WH: That is not practical. No, I would not say that. I do not think just going to a store is going to pick up enough virus. There is something I want people to hear though they will not hear elsewhere and that is the Chinese have discovered that the virus lives on the outside of frozen food packages. They had a new infection twice. It happened in Australia too, that infections happened when big stocks of frozen fish and other food are sent in from South America and Asia, COVID infected areas, and they infected the workers in the plants who handled it and then infected other people and it has caused them to shut down whole cities, doing millions of tests and shut down entire cities or big chunks of cities until they have it under control. Be careful of frozen food. I would wash it off when you get it, grab it with your gloves, wash it off with water and maybe a little soap before you handle the packages. Frozen food is not something people are thinking about, but the Chinese have issued directives about it. Now let’s be clear, the Chinese, it is not in a single package. It is a whole bulk order that they know about. But what could happen on a bulk order can happen on a shorter order. All somebody has to do is breathe on the frozen food package and that virus is going to live. Viruses can live in the cold for a long time frozen. NH: Just trying to move the book here a little bit. What is important about the getting sick chapter from your perspective? Obviously it is all important but is there something that stands out that the public isn’t likely to hear unless they hear it from you today? WH: The most important thing everybody should have at home, two things. Almost everybody has a thermometer, but my guess is that most people do not have a pulse oximeter. If you are starting to get sick and feeling sick, the most important criteria of whether you should go to a hospital or not is your blood oxygen level. And it is a very simple little device, it costs like $10. You put it on your index 2011
finger and it tells you, do I have ninety seven percent oxygen, ninety eight percent oxygen, or ninety two percent oxygen. Anything below about ninety-four, you call your doctor and say, I think I got to go to the hospital, my chest does not feel good and my pulse oximeter is reading ninety four or lower. That is a sign, get yourself to the hospital. Get a chest x-ray and see how serious your situation is because the moment your oxygen level saturation drops, you are in trouble and you may not actually feel it. The thing about COVID which is really weird from doctors’ point of view is a lot of people who have very low oxygen saturation feel fine. That is really anomalous. Normally if you have low oxygen you feel terrible. But for this disease for some very odd reason I do not think people have worked out, follow the pulse oximeter, not how you feel. I would say everyone, every household should have a pulse oximeter. NH: And those are available obviously online somewhere. WH: Yeah, online or every drug store. It is a little device. It is smaller than a pack of matches. You pick it up and put it on your finger. It operates with a AAA battery or smaller. NH: I will definitely go get one. WH: You have one? You have a pulse oximeter at home? NH: No so it is time to get one. WH: You will have one tomorrow. You know, this week I got a light cold and like everybody else, I worry. Hey, I got a cold, my goodness, what is going on here. So, wat I did is I put my pulse oximeter on, oh ninety eight percent saturated, no problem. Calm down, it is ok. You are going to be fine. It is good for the positive and it is good for the negative. If that had been ninety-two, I would have been in the hospital. I would have immediately gone to the hospital. NH: Looking out, we said it is horrible and so on. Of course, we all pretty much agree about that. In your chapter on public health measures, there is the issue about the home tests. Now one of the things you just talked about with the pulse oximeter. So, is there anything else in the home test area we should be discussing? WH: Yeah, there is. We are not set up like the Chinese to force everybody to stay at home in a whole city pr province. We are just not setup that way like the Chinese, we are not. There is something we can do that we have not done. That is we test [00:37:38,??], and the British just bought about two billion of them by the way, that 2012
allow somebody at home to test themselves like a pregnancy test. And you do not have to probe into your nose. You just rub the inside of your nose down where you can reach it easily and then put it into a little solution, put a little drop of a solution onto a little strip like a pregnancy test and fifteen minutes later you know if you are infectious or not. That exists. It just has not been licensed for home use yet. It costs abut fifty cents each. My strategy is to say step one, saturate the environment with this so that people can test themselves and their family every three days, twice a week. Then you know who is contagious. Then the government steps in is the second thing. Give you $500 a day to stay home with your family and will make it impossible for you to get fired if your wife or husband stayed home with you and you are not infected. You are still going to be treated as if you are exposed and have to stay home. If we did that, and of course you have to send double checks before you get your money. There will be cheaters. You give t to workplaces, you give it to schools. You double check people before you give them the money. We can stop this in two or three months without the vaccine. It is a good interim measure. It is a measure we can put in place between now and when the vaccines are going to come online, which maybe not until the summer or fall before they are generally available. And we still have some barriers. How long do they last and are they safe? It seems like they are going to be effective in stopping you from getting sick, but will they be tolerated by old people. Will they work for old people? Will they work for a long time? Are they really safe? What are the long-term side effects? All of those we do not know, but let’s assume they are coming, that they are ideal, that they are not really going to be fully around for until the late summer is my guess. People say spring, I do not think so. I know how hard it is to make these things. I have made vaccines and they are noy easy to make, especially these new ones. Then you have to have it distributed in a way that somehow looks fair. But the way we are planning to do it, it is going to be like testing. It is a mess. So we have to straighten out that mess. So, it may be sometime this time next year before we can have a good vaccine program. No matter what the Biden administration does, it is going to take a lot of work to get our house in order from the mess it is in. In the meantime, we have this other measure, which is kind of like what the Chinese have done. I call it COVID control American style. Americans 2013
might respond to incentives to stay home if you pay them. Rapid tests can identify people. And by the way, that is a second effect. Now the drugs are coming online they, are going to work only in the early phase of the disease. They are not going to work later when you are in the hospital, the different kind of drugs. The ones that are going to work like the new Lilly drugs, the new antibody drugs, they are only going to work very early in the disease and to make them work early in the disease you got to find people early in infection. We are finding people late in infection and by that time the drugs do not work anymore. So, they have a second benefit of opening up a whole window of preventative therapy, treating people so they never do get to the hospital. Eventually we will have vaccines so that we will not get sick enough to go to the hospital. But in the meantime, we have some method that if you are infected, we can stop you from getting sick with drugs. But you only know that if you test people early. NH: So how far away are we Bill from being able to have those home tests. What is your guess? WH: You know, Britain just started two billion. So, we are just a decision away from having those. NH: The could be here in a month. WH: Yeah, they could be. These companies can make a hundred million a day if you want them to. NH: So that is something to look forward to and also something for our listeners to sort of beat on the table in terms of anybody they can reach out to in terms of their political representatives or whatever. They can say this home testing thing could be like a whole cause celeb, I would think. WH: It should be. Home testing coupled with paid home stay. Not one without the other. You need both. NH: Those are our cries, home testing and home stay. I am looking for the lines to use as the language to work it out. WH: Sounds like advertising, you got the right line. NH: So Bill, we have got just a couple of more minutes here and I want to come back again to reminding our listeners that a lot of what you have put together in this philanthropy of yours is available online. So, let’s go back again and talk. What I have in your
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book it says accessh.org/covidfamilyguide. That is another place to get this book or is it WH: Yeah, there are two places. One is williamhaseltine.com or accessh.org. Those are two places to get the COVID Family Guide and any of the other books that I mentioned. Amazon is another place to go. Barnes and Noble is another site that would have them. So, these books are accessible. If you go on to the websites that are my websites, they are free. You got to Amazon I think A Family Guide is like $1. Maybe it is a little more expensive, but it is not much. NH: What I want my listeners to realize is and why I really want to beat the drum for this is given what we have been faced with in terms of this horrible political environment, this book is such a breathe of fresh air, really Bill, to have an authoritative guide. The other thing I thought was really well done in terms it was written in large print. What is fun the cover of the book shows people holding masks. It is the sort of book you can sit in your lap and you can have your children there and you can sort of show them the pictures. Beginning of the book has pictures for kids so they can have the facts but they can also have the, WH: If you know my grandkids you see their faces in the book. NH: Exactly. So, there is that part and then there is the part that has got all the details about how people should be behave and how they should imagine themselves participating effectively in a protected way in the world. So, this is an incredible gift to the world, Bill. Is there any governmental organization grabbing up this and hoping and passing it out through public health channels? Are you aware of anything of that type? WH: No, I am not. This book is on one level what you described, accessible, easy to read. But for those who want more detail, this is your guide to depth because for everything we describe, we give the references all the way down to what the scientists actually discovered and the medical evidence they actually found. As we update it, we keep it up to date. So it is really at one level, you can read it at multiple levels, as a kid, as an adult, or as a guide to really go right down to where the research is to understand how we know what we know. NH: In 1985, you testified before the United States Senate. You concluded your autobiography with this line which I want to read 2015
right now: “This may be the worst epidemic to emerge.” Now we are talking, this is 1985 so we are talking about AIDS. “This may be the worst epidemic to emerge from our ancestral past for many generations but is unlikely, given the current conditions that it will be the last.” So you have been prophetic, Bill, and we certainly appreciate all that you have done and I really deeply appreciate what you have done with this guide and also spending time with us today. So, thank you for joining us. WH: Thank you and I really appreciate your interest and your support for what we are trying to do. Thank you. NH: Be well. WH: You too. Click Here for to listen to the interview
2016
Interview with KIRO Radio November 5, 2020 | Interview
How Will the Election Affect the Pandemic's Third Wave? The US is hitting a 3rd wave of coronavirus cases while we reconsider our nation's leadership. What would it take for either Biden or Trump to get life in the US "back to normal" again? KIRO Radio's Dave Ross interviews virologist Dr. William Haseltine, a former Harvard researcher with a focus on public health, about how we can banish the pandemic for good... even without a vaccine. Then, reporter Aaron Granillo joins to talk about what the exit polls suggest American voters prioritized this election: the economy, or the pandemic? Click Here for to listen to the interview
2017
Interview with Seattle Morning News November 6, 2020 | Interview
Interview with William Haseltine is at the 13:15 mark. Margaret Brennan on the president's claims of election fraud // Feliks Banel, All Over the Map -- Columbia, Cowlitz, and Douglas Counties // Hanna Scott on efforts to reopen WA schools // Dr. William Haseltine on the effectiveness of a COVID vaccine // Dose of Kindness -- Two Blind Brothers // Gee Scott on the Georgia vote // Feliks Banel marks 80 years since Galloping Gertie Click Here for to listen to the interview
2018
Interview with David Ross November 6, 2020 | Interview
Dr. William Haseltine, We Don't Need a Vaccine to End the Pandemic As cases of the novel coronavirus reach new heights, you might be pinning your hopes on finding a vaccine. Dr. William Haseltine is here to shatter that illusion: but luckily, he doesn't think we actually need a vaccine to start dining out, hooking up and dancing in clubs again. Dr. Haseltine is a former professor and researcher at Harvard Medical School and the Harvard School of Public Health, the founder and president of ACCESS Health International, and an esteemed virologist who may just make an appearance on the next coronavirus task force. He sits down with Dave Ross to explain why the current vaccines everyone is racing to develop aren't going to be a perfect protection from the virus. But at-home tests and earning $500 a day to stay quarantined might help us get this under control the way Wuhan, China has. Click Here for to listen to the interview
2019
Interview with Houston Public Media November 10, 2020 | Interview
A New Vaccine Against COVID And Health Experts Answer Your Questions Town Square with Ernie Manouse airs at 3 p.m. CT. Tune in on 88.7FM or listen online. Join the discussion at 888-486-9677, questions@townsquaretalk.org or @townsquaretalk. A new COVID-19 vaccine made by Pfizer, other new COVID research and developments as Texas becomes the first state to break past the million case mark over the weekend. Global health expert and chair and president of ACCESS Health International, Dr. William Haseltine, walks us through what this means for the oncoming winter season. Click Here for to listen to the interview
2020
Interview on Bloomberg.com November 16, 2020 | Interview
Vaccine To Reach Most People By Mid 2021, Says Access Health International President Access Health International Chair and President Dr. William Haseltine discusses the timeline and effectiveness of a Covid-19 vaccine. He speaks with Kathleen Hays and Haidi Stroud-Watts on "Bloomberg Daybreak: Australia." November 16, 2020 (Source: Bloomberg) Click Here for to listen to the interview
2021
Interview on Health Matters Radio November 20, 2020 | Interview
About A Family Guide To Covid In A Family Guide to Covid, William A. Haseltine answers tough questions about Covid-19 honestly, with equal measures of clarity and compassion. A new disease has spread across our world. Schools have shut down, people around the world have been asked to stay home, businesses are shuttered, economies are crashing. The sad state of affairs is not entirely new for Dr. Haseltine who remembers how polio overshadowed his young life. As he got older, he realized that diseases didn't just harm individuals, they crippled communities and devastated entire countries. He became a scientist, dedicating his life to understanding the diseases that threaten us most and figuring out ways to stop and prevent them. Today, Dr. Haseltine finds that his children, his grandchildren and many of his friends and extended family members are coming to him with question after question. Why have our lives changed? Are my children in danger? When will this be over? Will there be a vaccine or a cure and if so, when? When will our lives return to normal? This book attempts to answer those questions about COVID-19 honestly, with equal measures of clarity and compassion. It is written especially for those who are faced with the difficult task of not only protecting themselves, but of protecting their families, their children, their spouses, and their parents. Split into two sections, the first section seeks to give answers to questions that children and grandchildren may ask. Each question has in fact been asked by someone under twelve, some as young as four and five. The second section provides short answers to many of the difficult questions adults from ages eighteen to one hundred and ten ask themselves to understand this new reality. Again these are real questions people have asked.
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As our understanding of Covid-19 evolves, so too will this book. When a purchase is made, readers will be given entry to a password protected section of Dr. Haseltine's website. There, readers can download subsequent editions freely and have the most up to date answers to the most critical Covid questions of the day. As Dr. Haseltine sees it, "Our children and grandchildren will one day look back as I do and remember a time when disease stalked the streets and changed their life. My hope is that some of those children will be inspired to dedicate their lives to science and medicine so that their own children and grandchildren and for that matter no child anywhere should have to endure what they did." The Interview: Ned Hoke (NH): Welcome back to Health Matter. Dr. Ned Hoke today joined by Dr. Haseltine who has written a very interesting book called The Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children. So, may I call you Bill? William Haseltine (WH): Yes, you certainly may. NH: Okay, Bill, welcome to Health Matters radio. WH: I am happy to be here. NH: So, for our listeners who may not be familiar with your name, you are somebody who has done a lot of groundbreaking work in the world of human science and the human genome. Maybe you could just give us a page of your background so our listeners get a sense of how you have become such an authority that you have. WH: Well, thank you for the opportunity and thank you to your listeners for being interested. For me, the COVID epidemic is an apotheosis of my career in a very strange way. I would never have predicted that this time of my life, I just turned seventy-six, I would be pretty much at the center of a global pandemic and have something to offer. From the time I was very, I knew I wanted to make a difference in medicine. By the time I got to be a graduate student, I realized I was interested in science. So, my career first took me to fundamental science with great mentors. I had four Nobel prize winners who were mentors. I became a professor at Harvard working on fundamental aspects of cancer and virology, particularly if you are interested in viruses that cause cancer. But that led me to suspect that retroviruses might be involved in human disease and after a couple of years of working and creating departments of cancer 2023
research at Harvard, HIV came along and it turned out that I made a correct guess along with a few others that HIV would be a retrovirus and was really one of the only people in the world prepared really to work on it in the very early days. I did a lot of work and realized that AIDS was going to be a problem that would be with us a long time like cancer. We needed not just a sporadic response; we needed an institutional response. So in addition to doing research and understanding the virus, coming up with a theory of combination chemotherapy for treatment of AIDS and helping develop some of the first drugs, I worked with a lot of different people to help. For example, founded amfAR to get research started, lobbied Congress to get money for research, worked with Princess Diana to destigmatize the whole problem. In retrospect, there are a lot of similarities between our responses to HIV and COVID. It is like everything that happened with HIV happened with COVID, only in a collapsed timeframe. People denied the issues of HIV at our highest level, President Reagan, for about five years. Research took off very quickly, but people were not prepared to take that this was going to be a serious disease. In fact, in a book written by all people Bob Redfield, the head of our CDC now, called The Myth of Heterosexual AIDS to give you an idea of those times. We did a lot of work on that and a lot of that has really helped me understand people’s reactions, reluctance, political considerations, wanted to shove everything under the carpet, let the next guy take the burden. All those things were going on. HIV/AIDS was a little different because it was not everybody. St first it was gays and drug users, and it took a while for people to realize it was a lot more than that. But for all that, science has done a wonderful job from the very beginning, just like COVID. The one brilliant success with COVID is science. Whether it is Chinese science or US science. Chinese sequenced the virus lickety split, created vaccines, drugs are on the way, same in the West. It has just been an amazing scientific journey that is about to make a big difference and do it pretty quickly. But from the political and social point of view, it has been a total disaster where we are. From there, I went into biotech and I created a number of companies. I think seven drugs are on the market that I had a hand in creating. That has taught me a lot about drug development, visive COVID and I actually developed vaccines and I actually created a 2024
company with a guy who created Moderna to make vaccines more efficient. We were not successful, but eventually he has been successful. So, I have created new vaccines, new adjuvants, got them approved. That is relevant. For the last fifteen years, I have been advising governments around the world on health system reform. One thing that COVID has made clear is we in the United States need to reform our public health system. We know we needed to make our healthcare system more efficient, better for patients, more cost effective. We spend four times more than the rest of the world but do not get very good results. Somewhat a little bit better than the Dominican Republic if you believe it. That is sad to say we are two standard deviations below the OECD, yet we spend twice as much then the closest neighbor and four times as much as Singapore which gets a lot better results. So I wrote a book called Affordable Excellence saying we could get a lot better results for less money. I actually studied in another book called World Class how a US institution, teaching research and medical care, can reform itself from mediocre to being the best in the world. So it is not just about what government can do, it is what hospital systems, and medical school systems can do themselves. You know, you cannot rely on the government for everything. There has to be somethings. But we have to do, each individual, each institution, has to be the best they can be too. And all of that is very good preparation for trying to understand what COVID is, what can we do about it, what can we do to try to get the public to respond in a better way. I have been working like seventeen, eighteen hours a day on trying to communicate my understanding in a way that is helpful to policy makers, the average man in the street with these books, The Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children and then another book COVID Guide to Back to School, same kind of thing. So that is a brief, it is probably longer than you wanted. NH: No, no, that is okay. I very much appreciated all the detail because I think what it does is, well it is the very thing I was looking for actually because what I wanted to do was I wanted to start our conversation really saying, what made me happy looking at The Family Guide to COVID was the authority that came in the language that you speak in in the book. The leadership that you are showing in the text and the layout and the intention and so on, it is 2025
all the things that have been so missing on a national scene. So, you stepped in with this philanthropy project, it seems like. This is not a way to make Bill Haseltine any more money. WH: No, every penny goes into the foundation that I started. It is definitely not to make money. I will tell you the lesson from this. During HIV/AIDS I became a private advisor to [00:9:17,??] and helped them sort out some of their nasty policy issues and people issues. But in the course of that, I made friends with an artist with Niki de Saint Phalle. She is a French American artist. She died a few years ago. But she wrote a book called AIDS: You Can’t Catch a Cold Holding Hands which was a model for me. It was a model about speaking to kids and their parents. She wrote it for her grandchildren about AIDS and I really wrote this book for my grandchildren. She was a real inspiration for me, not only a great artist, but a great humanist. The way I got to meet her is a scientist friend of mine said look, I have an artist friend who is writing a book for kids about AIDS. You know a lot about AIDS, maybe you should get together. And we became like the best of friends and this has been a great inspiration for me. There is one other inspiration thing about the work I do. I am really interested and have written an autobiography, and the whole point of that is to encourage kids to have a life in science. I had two great mentors. First was an undergraduate mentor who was a fisherman of scientists and was just totally dedicated to educating people and trying to find people to be scientists. And I am very, very indebted and grateful to him. But there is another later in life a man that I met who was truly remarkable. He was president of India at the time, Abdul Kalam. Abdul Kalam came from the poorest of poor backgrounds. He was about five feet tall, a Muslim and gay, and president of India. He is the man who started the rocket program and aerosonic bomb program and he spent all of his time trying to get young Indians to be interested in science and technology. I cannot tell you ho many places he opened up and what a wonderful human being he was. He was just a terrific educator. He wrote about five or six books to inspire kids become scientists. So, I wrote my autobiography for college kids and adults, but I am also writing another one for ten to fifteen year old guys and girls encouraging them to be scientists too. I have had a lot of good mentors and I want to carry the torch as far as I can. 2026
NH: Well, you are succeeding with me anyway. I want to let the listeners know this book, The Family Guide to COVID, is available on a website. Tell us about what a living eBook is. You sort of started this genre, so help our listeners understand and also give us the website where they can actually go read this publication. WH: First, it is for free on the website. It is www.williamhaseltine.com. If you go on there, you get the book for free. If you go on Amazon, you can get it for like $1. But because of the power of the internet today and how fast COVID changes, our world changes, I came up with a new format I call a living eBook, which is you buy it once, you get a passcode and we update it. We are already in the process of doing edition three of the Family Guide. You got edition two which is How to Enjoy the Summer. We are now working on How to Enjoy the Winter and Be Safe. So, the idea that you can buy one book and have it continually update is what I think the internet allows. That is the concept I call the living eBook. We have now three versions of it. We have the first one which is The Family Guide to COVID. It is undergoing edition three, it is in edition two now. You get it for free and you get the password. By the way the password is askdrbill. Second book is also a living eBook. Then I write a lot of things about COVID. I write abut two, three, four pieces a day. I find all the interesting journal articles and newspaper articles. Those are all put together in something A COVID Commentary: A Chronicle of a Plague Year. It is also available on Amazon and it is a compendium of all the things I have written up until September, and at the end of the year, it is going to be all the things I have written since January to December. It is another living eBook and it just will keep on going as long as I am writing about COVID, which hopefully will be for maybe another year and hopefully will be on to some other topic. NH: So, of course, we are at a unique pregnant moment now for our listeners who have jut recently heard about the Pfizer and the Moderna vaccines coming alive. Give us your take on where things are and how do you feel like the public information that we are getting is reasonably accurate. Can you imagine that the vaccine will be available to people in the Spring? What do you have to say about the current situation vis a vi the vaccine? WH: Well, the first thing is, the situation with COVID in the United States is absolutely horrendous and it did not have to be. One 2027
of the things that bothers me the most is that the Chinese showed us how to control this epidemic very early on. They had an epidemic like we had in New York City and since April, there has been no COVID in China to speak of. All COVIDS come in from outside and they control absolutely. So human beings can control COVID without drugs or vaccines. The fact that Europe and the United States and South America and other parts of the world have not is a disgrace to the human race. It shows how fragile and disorganized we are. The fact that it can be controlled and is still being controlled in China despite the rest of the world having a raging pandemic to me is absolutely horrifying. It is understandable but it does not make it any less horrifying knowing what this does to people. Second of all, right now we are in a terrible moment because we are in an exponential growth phase and we do not know where it is going to end. My guess, we can have four hundred thousand people every day getting infected and four thousand people every day dying. That is where we are headed if you want to know what I think. We see no way, with the current government and the conundrum and the horrible things that are happening in our national government and some of our state governments still, to control it. It is just maddeningly out of control. Now is there anything we can do? Yes, there are some things we can do right away to put an end to this, to stop it. France is locked down and has stopped their trajectory cold. They were zooming up like we are and now they have leveled off, in one week, two weeks, leveled off. We can do the same and drop. I do not see that happening just yet. What is happening with the vaccines? Well, the vaccines are working better then we thought. We do not know a lot about them yet. They have been tested almost entirely on young people and this disease kills mostly old people and we do not know what it is going to do to old people because vaccines stop working at about age forty five. That surprises people but that is how early vaccines stop working and in order to protect yourself from flu, some people over forty-five need a quadruple dose for it to work at all. So, will this be like that, we do not know yet. Is it really safe? We do not really know that because we have not spent enough time. How long will it last? We do not know that yet? Nonetheless, the data that has come out looked pretty good and I think what is going to happen is the vaccine will be rolled out. But it is not going to save us until 2028
summer. You know, Tony Fauci said the calvary is coming and it is coming from science in a year or two. But in the meantime, the homestead may be burned down, the wagon trains may be in a trash, the fort may be overrun like the Alamo and everybody dead inside. It will look like a burned out world three or four months from now. The vaccine will slowly get rolled out. It takes awhile for these vaccines to get rolled out. We are so disorganized in America. Think of testing is how vaccines are going to get out there. When the central government says it is up to the states, well that is a recipe of disaster. Some of the states will say, yeah, it is up to me the governor where other states will say, oh no, it is up to the counties or it is up to the municipalities. It is not even up to me. What one municipality does for testing or vaccines, another one may be differently. It is going to be a, I will not use a swear word, it is going to be a disaster rolling out these vaccines. We have no confidence the way our leadership is going if people believe the leadership. Try to believe a guy who has lied twenty thousand times. NH: Well Donald Trump is no longer really relevant. WH: Believe me, he is relevant until the day he steps out of office and he may be relevant for a lot of people. Look, people believe celebrities. He is the ultimate celebrity. I understand that a lot of my fellow Americans have their faith and belief in him. You cannot deny that anymore than you can deny that seventy percent of people who were told they were going to die when their partner infected them with HIV did not use condoms, seventy percent. So you have to understand where people’s minds really are and half of the American people believe in this president and we have to take that seriously. He could make a big difference. I have heard people in an interview say, if Donald Trump told me to wear a mask, I would wear a mask. So, I was hoping that after the election was over he would wake up and say, hey, I really will try to help. But he has not. He has done everything opposite. NH: He has been playing golf. He has been busy, the golf is very trying, takes a lot of effort. So Bill, forgive me, we need to take a break. We are talking to Bill Haseltine. We are trying to get to talking about the book The Family Guide to COVID and we are also spending some time talking about many other things that Bill has to do, has shared with us. Please stay with us.
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So welcome back to Health Matters. Dr. Ned Hoke joined today by Dr. William Haseltine and we are talking about his book A Family Guide to COVID, but really we are talking about the whole situation. Bill has been very generous so far. Keep being generous with us Bill. You are really giving us the data that we are really hungry for. On this program we have been reviewing and looking at all the COVID literature we can get our hands on, we have been making a point to try to share with our listeners the best parts of everything we can find and so far you are the best we found in terms of the authority and the breadth of vision that you have for this topic. So please keep talking about the current status if you would and where you think things could go and what we the fellow citizens you feel what we should be doing in addition to reading your book. WH: Well, first of all, it is very, very generous of you. Any author loves to hear what you just said. So thank you, thank you very much for speaking about the book and understanding what we are trying to do with it. I was trying to carry on the tradition of my mentors and people I was really close to in trying to help people understand the current situation we are in and what they can do about it. Everybody knows the US is really going up in flames with COVID and we cannot see an end to it at present because we cannot see, half the country at least, understanding what is happening to them. Just take the Dakotas, the worst in the entire world. When did you think that North and South Dakota would be the world’s hotspots for an infectious disease? That is the reality. The world’s hotspot is right now, in terms of number of cases, number of hospitalizations and number of deaths. The world’s hotspot. So, when that is happening, it tells you that this disease is really serious. But what can you do? Thanksgiving is coming up and I just canceled Thanksgiving for most everybody who was going to come because I do not want them to take the risk. I want to see them. I want to see my children. I want to see my grandchildren. It is a really important time for everybody, but it is too dangerous. And that is in New York where the danger is less than almost any other place in the country, New York and Connecticut. But it is too dangerous. So that is what I want people to understand. This is not going to last forever. You know, if this were the weather, we would be in cyclone condition. What do you do with a cyclone? You go to the basement with your family and you protect them. You want 2030
everybody to listen. Say it is your job to protect your family. That is your job in life. That is a human being’s job, is to protect those they love. You protect those they love by wearing masks, social distancing, do not gather with other people no matter what your age. You may not think you are going to die. You may kill your grandpa, or you may kill your grandmother or your mom or your neighbor. That is who you might kill by your behavior of gong out and going out to a party or going to a bar or meeting with people you do not know right now. This is a really terrible time. You have to assume that everybody you meet is infected because a lot of them are ten times more. We are infecting about a, my guess conservatively is we are infecting about a million people a day in the United States and that means because you are infectious for about ten days, there are about ten million people in our country spreading this disease around right now. That means you are going to run into a lot of infected people, and you may be one of them. NH: In your book, you break it down in a very useful way. You start with the questions the kids ask, questions that we ask ourselves, then you get to situational awareness. Maybe you can start with, go ahead. WH: The way I think about it is like the weather. If it is a nice sunny day, you ask Alexa, you ask Siri, whoever you ask. Oh yeah, it is a sunny day, go out no problem. That is a green zone where less than one in a hundred thousand are infected. Then if there is a light rain, you put on some protective gear, you go out, you do not really bother. You may not do some things you may otherwise do, but that is sort of like five people per hundred thousand infected. New York is somewhere in that vicinity now. Other places are not. Then you get up to a heavy rainstorm where you are pretty careful where you go. Finally you are in a cyclone and a lot of parts of the United States are in a cyclone where you hunker down and you stay in your basement and you dramatically limit what you do. The way you know that is you look to see if you are in a green, yellow, orange or red zone which is by how many people per hundred thousand are diagnosed that day, that week of being infected and you multiply that number by five or ten to understand how many people in your area are likely to be carrying the virus. So that is the way to think about the first part.
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Second part is what is my susceptibility to disease. Somebody in my family, are they overweight, obesity. Half the people in the Midwest are obese or a body mass index of thirty. Twenty percent of the kids have a body mass index. So, when they say, oh, we should only let the virus roll and only protect those people who are especially sensitive, well that is about half of America. You look at the numbers thirty seven percent of Americans have a body mass index of over thirty. That is a huge jump. So, you cannot do, you cannot protect one part of, you cannot protect thirty percent of the population. It is not just old people we are talking about. Second of all, do you have asthma, does anybody have diabetes, are you living with someone who is old. Third, if I am going somewhere, sending my kid to school, going to work, going to a store. How careful are they? What is your situational awareness? And that is something that everybody should have deep in their mind. Let me say the other thing, the biggest thing to watch out for, is it took awhile for us to understand that this virus is transmitted not just by droplets, it can hang in the air for four or five hours in an unventilated space and can infect you. If people are breathing out, even with a mask. Most masks do not stop the virus. Those tiny particles stay in the air for four or five hours. The longer you are in a closed space with more people, the more dangerous it is. Stay out of closed spaces with people you do not know because you are going to be breathing in and it is getting into your nose, it is getting, it gets into your mouth and it gets into your eyes, and hangs in the air for a long time. There are a lot of people who won’t tell you that, but we know that for a fact for a long time for this virus. It is an aerosol and if you want to know who knew it, [00:28:13,??] knew it in January when he was talking to Bob Woodruff. He said this is spread through the air just by breathing. It is not only droplets. So those are things I want people to understand that if they go to places that are, if they have to for some reason, put on an N95 mask and wear a face shield. And if you are going to travel, put on a hazmat outfit and wear gloves. Bring a lot of gloves and change your gloves as often as you would wash your hands. You think that is [00:28:49,??] No. if you are flying anywhere in the east, toward China or any of those places, everybody on the plane is wearing a hazmat suit, everybody has got an N95 mask and half of them have face shields. That is how they fly in China. I have the pictures. We are not seeing that. We are not 2032
seeing how they are protecting themselves over there. But we should be doing the same thing. You go on public transportation you should be wearing an N95 mask, you should have face shield, you should be wearing a hazmat suit and you should have gloves. That is how bad it is. People are not doing that. They have no idea that is what they should be doing. NH: Exactly. One of our previous guests on this topic, a guy named Dr. Steven Quay wrote a book called COVID-19 Survival and one of the things he came up with or he revealed is the idea of putting salt on a mask and salt was one of the ways of making the mask more effective because when the viral particles touches the surface of the mask, if the salt is also got a little bit of soap in it, the viral particles will be broken down by the salt. Apparently, there was some studies about that. Are you familiar with that? WH: I would be suspicious of that, but I will look at the studies. NH: Well anyway. WH: It is like trying to catch a bird by putting salt on its tail. You get close enough to get salt on the bird’s tail, you got to have the bird. I would not go chasing that particular one. I put my face in an N95 mask more than putting salt on a paper. Maybe it would work. NH: Anyway, there is actually some science on it that you could look about, but we will not try to solve that now. But the thing is what you have done for us is you showed us and you revealed to us what, again, is one of the things that is completely missing in the public discussion which is the depth of care that is going to take to get through this horrible period that we are obviously just getting in the beginning of here in terms of this winter. WH: Let me make another point. There has been a study of doctors and hospitals and healthcare workers in hospitals when they are wearing a face shield or not wearing a face shield, wearing hazmat outfit, gloves and N95 masks. And that face shield reduces transmission from low to zero. The face shields, by the way, kids like face shields. It is easier than the mask. NH: I like it. You kind of want them to do both though is what you are saying? WH: You want them to do both. For kids, use a face shield. It is much easier for them.
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NH: We have been talking about situational awareness. Let us move on to protection and prevention. We talked some about that but let us say, ok, the family goes to the grocery store and they come back. They have worn their mask in the grocery store, they come back, they wash their hands when they come back from the grocery store. To you, I would almost believe you say well you should probably take off your clothes and then launder those clothes and then change clothes when you got to your home. WH: That is not practical. No, I would not say that. I do not think just going to a store is going to pick up enough virus. There is something I want people to hear though they will not hear elsewhere and that is the Chinese have discovered that the virus lives on the outside of frozen food packages. They had a new infection twice. It happened in Australia too, that infections happened when big stocks of frozen fish and other food are sent in from South America and Asia, COVID infected areas, and they infected the workers in the plants who handled it and then infected other people and it has caused them to shut down whole cities, doing millions of tests and shut down entire cities or big chunks of cities until they have it under control. Be careful of frozen food. I would wash it off when you get it, grab it with your gloves, wash it off with water and maybe a little soap before you handle the packages. Frozen food is not something people are thinking about, but the Chinese have issued directives about it. Now let’s be clear, the Chinese, it is not in a single package. It is a whole bulk order that they know about. But what could happen on a bulk order can happen on a shorter order. All somebody has to do is breathe on the frozen food package and that virus is going to live. Viruses can live in the cold for a long time frozen. NH: Just trying to move the book here a little bit. What is important about the getting sick chapter from your perspective? Obviously it is all important but is there something that stands out that the public isn’t likely to hear unless they hear it from you today? WH: The most important thing everybody should have at home, two things. Almost everybody has a thermometer, but my guess is that most people do not have a pulse oximeter. If you are starting to get sick and feeling sick, the most important criteria of whether you should go to a hospital or not is your blood oxygen level. And it is a very simple little device, it costs like $10. You put it on your index 2034
finger and it tells you, do I have ninety seven percent oxygen, ninety eight percent oxygen, or ninety two percent oxygen. Anything below about ninety-four, you call your doctor and say, I think I got to go to the hospital, my chest does not feel good and my pulse oximeter is reading ninety four or lower. That is a sign, get yourself to the hospital. Get a chest x-ray and see how serious your situation is because the moment your oxygen level saturation drops, you are in trouble and you may not actually feel it. The thing about COVID which is really weird from doctors’ point of view is a lot of people who have very low oxygen saturation feel fine. That is really anomalous. Normally if you have low oxygen you feel terrible. But for this disease for some very odd reason I do not think people have worked out, follow the pulse oximeter, not how you feel. I would say everyone, every household should have a pulse oximeter. NH: And those are available obviously online somewhere. WH: Yeah, online or every drug store. It is a little device. It is smaller than a pack of matches. You pick it up and put it on your finger. It operates with a AAA battery or smaller. NH: I will definitely go get one. WH: You have one? You have a pulse oximeter at home? NH: No so it is time to get one. WH: You will have one tomorrow. You know, this week I got a light cold and like everybody else, I worry. Hey, I got a cold, my goodness, what is going on here. So, wat I did is I put my pulse oximeter on, oh ninety eight percent saturated, no problem. Calm down, it is ok. You are going to be fine. It is good for the positive and it is good for the negative. If that had been ninety-two, I would have been in the hospital. I would have immediately gone to the hospital. NH: Looking out, we said it is horrible and so on. Of course, we all pretty much agree about that. In your chapter on public health measures, there is the issue about the home tests. Now one of the things you just talked about with the pulse oximeter. So, is there anything else in the home test area we should be discussing? WH: Yeah, there is. We are not set up like the Chinese to force everybody to stay at home in a whole city pr province. We are just not setup that way like the Chinese, we are not. There is something we can do that we have not done. That is we test [00:37:38,??], and the British just bought about two billion of them by the way, that 2035
allow somebody at home to test themselves like a pregnancy test. And you do not have to probe into your nose. You just rub the inside of your nose down where you can reach it easily and then put it into a little solution, put a little drop of a solution onto a little strip like a pregnancy test and fifteen minutes later you know if you are infectious or not. That exists. It just has not been licensed for home use yet. It costs abut fifty cents each. My strategy is to say step one, saturate the environment with this so that people can test themselves and their family every three days, twice a week. Then you know who is contagious. Then the government steps in is the second thing. Give you $500 a day to stay home with your family and will make it impossible for you to get fired if your wife or husband stayed home with you and you are not infected. You are still going to be treated as if you are exposed and have to stay home. If we did that, and of course you have to send double checks before you get your money. There will be cheaters. You give t to workplaces, you give it to schools. You double check people before you give them the money. We can stop this in two or three months without the vaccine. It is a good interim measure. It is a measure we can put in place between now and when the vaccines are going to come online, which maybe not until the summer or fall before they are generally available. And we still have some barriers. How long do they last and are they safe? It seems like they are going to be effective in stopping you from getting sick, but will they be tolerated by old people. Will they work for old people? Will they work for a long time? Are they really safe? What are the long-term side effects? All of those we do not know, but let’s assume they are coming, that they are ideal, that they are not really going to be fully around for until the late summer is my guess. People say spring, I do not think so. I know how hard it is to make these things. I have made vaccines and they are noy easy to make, especially these new ones. Then you have to have it distributed in a way that somehow looks fair. But the way we are planning to do it, it is going to be like testing. It is a mess. So we have to straighten out that mess. So, it may be sometime this time next year before we can have a good vaccine program. No matter what the Biden administration does, it is going to take a lot of work to get our house in order from the mess it is in. In the meantime, we have this other measure, which is kind of like what the Chinese have done. I call it COVID control American style. Americans 2036
might respond to incentives to stay home if you pay them. Rapid tests can identify people. And by the way, that is a second effect. Now the drugs are coming online they, are going to work only in the early phase of the disease. They are not going to work later when you are in the hospital, the different kind of drugs. The ones that are going to work like the new Lilly drugs, the new antibody drugs, they are only going to work very early in the disease and to make them work early in the disease you got to find people early in infection. We are finding people late in infection and by that time the drugs do not work anymore. So, they have a second benefit of opening up a whole window of preventative therapy, treating people so they never do get to the hospital. Eventually we will have vaccines so that we will not get sick enough to go to the hospital. But in the meantime, we have some method that if you are infected, we can stop you from getting sick with drugs. But you only know that if you test people early. NH: So how far away are we Bill from being able to have those home tests. What is your guess? WH: You know, Britain just started two billion. So, we are just a decision away from having those. NH: The could be here in a month. WH: Yeah, they could be. These companies can make a hundred million a day if you want them to. NH: So that is something to look forward to and also something for our listeners to sort of beat on the table in terms of anybody they can reach out to in terms of their political representatives or whatever. They can say this home testing thing could be like a whole cause celeb, I would think. WH: It should be. Home testing coupled with paid home stay. Not one without the other. You need both. NH: Those are our cries, home testing and home stay. I am looking for the lines to use as the language to work it out. WH: Sounds like advertising, you got the right line. NH: So Bill, we have got just a couple of more minutes here and I want to come back again to reminding our listeners that a lot of what you have put together in this philanthropy of yours is available online. So, let’s go back again and talk. What I have in your
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book it says accessh.org/covidfamilyguide. That is another place to get this book or is it WH: Yeah, there are two places. One is williamhaseltine.com or accessh.org. Those are two places to get the COVID Family Guide and any of the other books that I mentioned. Amazon is another place to go. Barnes and Noble is another site that would have them. So, these books are accessible. If you go on to the websites that are my websites, they are free. You got to Amazon I think A Family Guide is like $1. Maybe it is a little more expensive, but it is not much. NH: What I want my listeners to realize is and why I really want to beat the drum for this is given what we have been faced with in terms of this horrible political environment, this book is such a breathe of fresh air, really Bill, to have an authoritative guide. The other thing I thought was really well done in terms it was written in large print. What is fun the cover of the book shows people holding masks. It is the sort of book you can sit in your lap and you can have your children there and you can sort of show them the pictures. Beginning of the book has pictures for kids so they can have the facts but they can also have the, WH: If you know my grandkids you see their faces in the book. NH: Exactly. So, there is that part and then there is the part that has got all the details about how people should be behave and how they should imagine themselves participating effectively in a protected way in the world. So, this is an incredible gift to the world, Bill. Is there any governmental organization grabbing up this and hoping and passing it out through public health channels? Are you aware of anything of that type? WH: No, I am not. This book is on one level what you described, accessible, easy to read. But for those who want more detail, this is your guide to depth because for everything we describe, we give the references all the way down to what the scientists actually discovered and the medical evidence they actually found. As we update it, we keep it up to date. So it is really at one level, you can read it at multiple levels, as a kid, as an adult, or as a guide to really go right down to where the research is to understand how we know what we know. NH: In 1985, you testified before the United States Senate. You concluded your autobiography with this line which I want to read 2038
right now: “This may be the worst epidemic to emerge.” Now we are talking, this is 1985 so we are talking about AIDS. “This may be the worst epidemic to emerge from our ancestral past for many generations but is unlikely, given the current conditions that it will be the last.” So you have been prophetic, Bill, and we certainly appreciate all that you have done and I really deeply appreciate what you have done with this guide and also spending time with us today. So, thank you for joining us. WH: Thank you and I really appreciate your interest and your support for what we are trying to do. Thank you. NH: Be well. WH: You too. Click Here for to listen to the interview
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Interview with Vera Scuderi, Consultant, Innovation & Technology Hub at The European House-Ambrosetti Part I November 27, 2020 | Interview
Vera Scuderi (VS): I am interested in understanding how we can treat this topic because it is not easy to treat. I mean, it is not only about vaccination as I correctly understood, but it is about a different kind of dynamic that we should consider. The first topic that we took into consideration is the vaccine. Can we expect a vaccine, or better, when can we expect a vaccine because it is very probable that we will have one, some people say by the end of the year? Do you think it could be effective for the population and what can we consider for Italy? WH: First, the question is, will we have a vaccine? And the answer is there will definitely be vaccines that are approved. In fact, the Chinese and the Russians have essentially approved the vaccine even before they have tested it; but it is in fact approved and people in China, depending upon who they are, can request and receive the vaccine. I have offices in China and my people in China who are Chinese can request and can receive the Chinese vaccine. There are foreigners who are in China who are working for international organizations that can request and receive the vaccine. The same, I believe, is true in Russia. So effectively, there are already vaccines approved by governments, even though the complete story of how they work is not out. In addition to that, it is very likely within a matter of days or weeks, the United States will approve two different vaccines under what is called Emergency Use Authorization. The question is, will it be expanded access or Emergency Use Authorization? Those are quite different. Emergency Use Authorization is essentially a green light to use the drug by many, many people and expanded access is to restrict that to special circumstances. So, what we are really going to do before the US trials are completed, because we only have the 2040
interim analysis. It is not public yet. They are very likely going to expand access and possibly give Emergency Use Authorization. That will be followed by a number of other vaccines. Those two are called the Moderna vaccine and the Pfizer vaccine. There is the Oxford vaccine, and there are three or four others that are rapidly making their way through. So, I think there will be a very large number of potential vaccines. Now what we have to date for all of these vaccines is what I call publication by proclamation. We do not even have publication by press release, which was a criticism I leveled earlier at remdesivir and other drugs. People are not showing us their data. A head of Pfizer is saying they have a vaccine that is marvelous, ninety five percent effective. The people at Moderna is making the same claims with no data, not even a press release. It is astounding. I ran a company and those announcements moved markets by trillions of dollars all over the world. If I made an announcement of my little company, the SEC would be all over my case. They would have given me a tremendous amount of trouble. Where is your data? How can you give this kind of information? It is astounding to me that responsible companies will make announcements about the efficacy of vaccine and nobody knows what the story is. Now, because Pfizer is a big and reputable company, you believe it must be true. But it is like listening to the Pope saying, God is coming tomorrow to Earth. Maybe he is, maybe he is not, who knows. You might believe the Pope because he is a Pope. But, you know, I believe in what our former president used to say – trust but verify. You need to have the data, and it is astounding that nobody in the public has the data. VS: How is it possible that the scientific world is not asking for this data? WH: It is not the scientific, it is the business and political world. There are huge amounts of money, trillions of dollars in the economy, when the stock market goes up like it does because now people have hope, whereas before they were the gloom. Well, hope in this case is people's lives. We need to know the data. So, I am very exercised, at the moment, about the lack of data. I think it will be coming. I trust that it will be what they say it is. Now, let us assume that they are correct. Where are we? I listened to some of our top experts in the US give private conversations. In December in the United States, the total number of people that will be able to 2041
be vaccinated is about four thousand. Now in China and Russia, that number is much higher. Now come January, February, March, the number will ramp up very rapidly. But the other thing I can tell you for sure is that the vaccine will not be generally available anywhere in the world, except Russia and China – and maybe not even there for most people – until summertime and maybe a little bit later. So, it is going to be slowly rolling out. That is the first thing. So, the first non-study person will probably get the vaccine in December, but that won’t include many. And in January it will not be many people either. And in February it will be still a drop in the bucket, but by March and April, more and more people can get it. The next question is, do they really work? Well, we hope they work to stop disease. Now they have only been tested not to stop infection, but to stop disease. Nobody is testing whether they stop transmission, and nobody is testing how long they work yet because you cannot do it. VS: And you do not have enough time to test it. WH: You have no time. This sort of sounds like a technical detail, but it is not. If I give you a bunch of antibodies against the virus and then try to infect you, you are not going to get infected. But essentially that is what we are doing with these vaccines, because the time is so compressed. You are only measuring the immediate effect of giving people the vaccine, not the memory of giving the vaccine, because it takes about five, six months for the first antibodies to disappear to see if you have protection that remains. For none of the vaccines do we know that memory remains. Now, why do I say that? Why is that particularly troubling? It is troubling because the same virus can come back and infect the very same person year after year after year?. There have been studies done where one person got infected four times with the same virus in six years. And many people got infected twice in the same year. And every year these viruses come back and back and back, despite the fact that we are immune. Now, some people say not to worry about that. In fact, there was a studies done a long time ago where people were infected. Volunteers were infected with one strain of cold virus, waited a year, got reinfected with the same virus and they all got sick again. So these viruses are tricky. They are kind of like the flu, but they do not need to change so much. They have a lot of tricks in their immune system.
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So, what is known about the vaccines, at least by proclamation, is that a big effect in reducing disease. Now how serious is that disease? We do not know that either. But it does seem to have a big difference right after you have given the vaccine. Will it be durable? We do not know. The other thing we do not know is that many safety signals do not come up until much later. They are not all the immediate effects. And let me say something else. These vaccines are difficult to take. If you in your life have had a vaccine, some of them may stick you and you hardly know what happens. And sometimes your arm is sore for a couple of days. This is worse. These vaccines are going to be like somebody hits you in the arm. And some people are going to faint. And some people might have gone to the hospital and the more and more people you give these two American vaccines to, the more you are going to see that happen. And you are going to see new stories. Some people took the vaccine and ended up in the hospital because of the early trials. It does not mean they are going to die. They are going to probably recover. But we do not know that on a big scale. These are unknown long-term safety because there has been no long-term study. That is going to put a question in people's minds. And there are already a lot of people who are nervous about vaccines. So, the vaccine is very hopeful if it is done properly, but a lot of things have already not been done properly. I and many of my colleagues have called for increased transparency. You cannot just believe what people say. You actually have to look at the data because a lot of people come to me and they say, “Bill, should I take the vaccine?” And I say, I cannot tell you, I have not seen the data. And that is true for almost any responsible expert. They have not seen the data. Nobody has seen it except a very tiny group of people. So that is the first thing. Next thing to say is, right now, there is a massive pandemic problem in Europe, in your country, in Italy, in the United States, and in many other countries. Just how everybody predicted. In the winter, when people come together, the virus is going to spread. And there is something we now know about this virus; it is much more infectious than influenza, much more infectious. How do we know that? Because in South America last winter, when people did very poor control of COVID, they absolutely controlled influenza. Influenza cases dropped ninety eight percent. Already, influenza is not nearly what it was before. So, the control measures work 2043
reasonably well, even if they are imperfect, some people wear a mask and some people do not, for influenza. It is obvious they are not working for this. Just look at the American numbers and look at the numbers around the world. So, we are in the middle of a pandemic. Vaccine is not going to come in time. And so, in the meantime, all we have is public health. I will say one more thing about that and then get onto your next question. The next thing I would say is something which bothers me personally and that should bother every human being on this planet. We as humans using our brains and our ability to organize can stop the infection without a vaccine, without a drug. How do we know that? Because another number of countries have done that. One fifth of humanity is COVID free and they happen to be Chinese. There are a few other smaller countries that have done it, but China, when there were 1.2 million cases in the United States last week, there were eighty-nine in China, 1.2 million versus 89. And they are a country four times our size. What is going on? How stupid can we be? How unorganized? How can our governments fail us this way? The purpose of government is to protect us. That is why we have governments. We have to give up a lot of our freedom. We have to give a lot of our money. Governments do a lot of things, but their fundamental job is to protect us and they failed. Your government failed. My government failed. Most governments around the world failed. The Chinese government did not fail. Yet in America if you say that people say you are a communist. You like totalitarianism. No, I like efficient government. I like a government that works to protect me. Your country appeared to be doing better. But then the people gave up and the government did not step in. And medicine cannot take over where people and governments fail. You know, I have created a foundation called ACCESS Health International. The whole purpose is to say, we have had a marvelous time since the end of World War II in medicine. There are so many cures available, but they are not available to most people. Why? Because the health systems are so messed up. It is the case in so many countries, that the medicines you need cannot get to the people who need them. And if they can get to them, the people cannot afford them. That is emblematic across the entire world. You know, the United States that has fabulous medicine at one point is two standards deviations below the mean in outcomes. We spend twice 2044
as much as Europe does and we get much worse outcomes. We can do better because we are disorganized. And it is a very complicated political issue in all countries. Let me give you a conversation I had with Julio Tremonti. This is when he was Deputy Prime Minister and Finance Minister, and I was starting ACCESS Health. I said, “look, all around the world, people are not organizing health care efficiently.” He said, “yes. I know that.” I said, “even in Italy, you could do much better.” He said, “I know that.” I said, “well, here is all the systems I am working on. And I can show you that you can do much more efficient, much better care at much lower costs.” He said “I know that too, but you know something, if I did that, I would be out of a job because the only source of job growth in Italy is healthcare. And you are telling me that we should throw people out of work and do better? Yeah. Maybe we can. But then where are we as a country?” Now think about that for a minute and think about how that overlays with what we are experiencing around the world today. You know, everybody would have thought that in Great Britain and in most European countries with government sponsored healthcare, good social network support, people would stay home. We do not have to, in America, if you do not go to work, you die. You do not have food. Nobody is going to pay you. We do not have your social network for most working people. You do. Why don't you stay home and take use of the social network? Government does not ask people to do that and they have not done that. And then when they do do that, there are huge fights. Look at Britain. People are refusing to do it. So, it is not just about vaccines. It is about public health, and this is the story going forward with vaccines. Why do we think there is going to be any difference where we have vaccines? Some people are going to take the vaccines. Some people are not. Some people are going to behave responsibly and some people are not. Governments are not going, in general, to do the right thing. That is the way you look at 2021. Underneath that is the virus. This is a virus that comes back every year like the flu, except we know it is more transmissible than the flu and it is more lethal than the flu. And there is no indication that it does anything else but learn how to transmit itself better. Somewhere in about March, this virus learned how to get around a little bit better, right? So, all the strains that are all over the world today are not the original ones from China. They 2045
have a key variable that makes it about ten times as easy to catch. And who knows what the next widespread change will be. You know, you have to think about life from the virus’s point of view. A virus is a living entity that changes and tries to adapt to its environment. We are its environment today, seven billion of us, great environment, packed together. We can organize to defeat it, but we don’t do it. So, this virus is trying to figure out what its next move is going to be. And you have to think of it like machine intelligence where you just throw lots and lots of combinations. And we know you can defeat our brain. A chess master can be defeated by artificial intelligence just throwing random combinations of things. A virus in one person makes trillions of combinations every day. Think of that, trillions of combinations every day, trying to get better at what it is doing. That means spreading more. And whether it kills a few people doesn’t matter, as long as there are still more people to infect. So that is what we are facing. We have a vaccine now that may stop the virus for some time, but this virus could figure out all its combinations. If you look forward to 2021, the responses are going to be nonhomogeneous. How do we know that? Because the world is not homogeneous. Look at America versus China. 1.2 million in a week versus 89 in a week. Do you think that is going to change just because we have a vaccine? Some countries will be able to vaccinate their people and some will not. And then we are going to be in a world where one person can start the whole thing over again. Why is China so absolutely focused on keeping people with COVID outside of China? Because they know one person could infect the whole country again. And so, what they do is they put even tighter restrictions. I have recently been writing about their demand that people who are IgM positive cannot enter the country. Not only do you need a negative test, not only do you have to stay two weeks in quarantine, but you cannot even come to China if you have an IgM positive. That takes about seven to nine weeks to disappear after infection. So, they are careful, but other countries are not. In other countries you can still move around, and other countries are not controlling the epidemic. And so there may be isolated areas where people are doing well, surrounded by a sea of disease that is trying to get in. And so people are going to be very suspicious of each other. What does China worry about? China is like the canary in the 2046
coal mine because they are free of it. So anytime they see it, they know it is something new. For example, they know that five percent of people do not recover in fourteen days. So now they are extending their period to at least twenty-one days after infection and maybe longer. That is what IgM is about too. So, they know what the exceptions are because they are so clean. They can look at the exceptions. They know that the virus comes in on the outside of frozen food packages sent from areas of the world where there is COVID. There are at least three cases, maybe four now that are documented where frozen food has infected the workers that handled them, and they infected the people around them. How do they know that? They traced the actual strain. They know that. We also know other things. One person who has tested negative on an airplane can infect others and they can infect others too. How do we know that? A flight from Dubai to New Zealand, a guy who was tested PCR negative got infected, infected other people on the plane. We know that because they control them for 14 days and they checked the sequence. They could tell who gave the virus to whom. So, we are learning things about the future of the world where there are some places that are relatively free and other places relatively unfree. What that means for a business environment is uncertainty. That is the bottom line of all the things I have said. If there is one word that comes out of what I have said, a vaccine does not give us certainty. A vaccine gives us hope, but hope could be an enemy. I have often said that the last evil out of Pandora's box is hope. Everybody says hope is the answer. I consider it a double edge sword. You need hope to keep going on. On the other hand, hope is not based on reality, it is dangerous. If people stopped behaving and say “I do not have to pay attention. I am going to go to a bar. I am going to go out and pick up some girls,. I am going to pick up some guys.” Or whatever kind of people you want to pick up. They are going to do it anyway. They think that because there is a vaccine coming out, they do not have to worry. They were going to do it anyway, but now they have a better reason to do it. And so that is the way people are. What does that mean? Uncertainty. So, the bottom line of my recommendation for businesses is to continue looking at all possible contingencies and planning for them. And
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those who plan for the downsides will do better than those who plan for the upsides. VS: So, it will be an emergency situation, even if we would have some new scientific discoveries. WH: At least for a long time, I would say for most of 2021. I think 2022, we have to wait and see. VS: Yes. Maybe we will have some more data from the scientific studies. WH: It is not only a matter of science. VS Government and science. WH: Science and medicine has done wonders for health. Most people do not experience that, even in the United States or even in Italy, but in other parts of world, it is ever so much worse. And it is not that they could not get them. It is that they are not organized to deliver them. You know, healthcare is a big part of the budget and therefore it is a big place for people to steal. The way I look at it in America, every country has its own form of stealing or corruption. Our major form in the United States of corruption is healthcare costs. That is our corruption. And why did I call it corruption? It is kind of official and legal because these very big, organized blocks that stand to make billions and billions of dollars influence our government through donations to political causes. They can either win or lose an election. And they changed the laws so that we are the exception in the world that pays huge amounts of money for medical care and get lousy results. We are, as I said before, slightly above the Dominican Republic in outcome. We are not like Italy. We are not like Sweden. We are not even like Taiwan and Singapore or South Korea. And so where is that money going? Thise are the kinds of things that are going to continue to happen. So, you say there is going to be science and medicine. I say, yes, science and medicine can solve the problems theoretically, but no solution is going to work unless it is politically, culturally, and socially accepted. VS: Yes. That is clear. So, you think that we should take China as a benchmark case? WH: You know, yes. I take China as proof of principle it can be controlled. VS: Okay. WH: And New Zealand. But then you have to adapt that to your own country and your own situation. I have created what I call 2048
a program that can put COVID-19 back in its bottle very quickly. I call it COVID control with American characteristics. In America I actually say COVID control American style. So what is that? Because we have so many people infected, right now, my guess is there are probably about ten million people walking around transmitting the virus to other people. Everybody is exposed. Chinese control it by controlling people that were exposed, tested or not. You were in a city that had COVID, you are in quarantine. You are on an airplane where somebody had it, you are quarantined. You are in a food processing plant; the whole quarter of the city is tested and quarantined. No bones about it. You would quarantine the entire America today under that condition. That is not possible. But now there are very fast tests that should cost fifty cents. The cheapest now cost maybe $10, $5. They should cost fifty cents. They are so simple, anybody can use them like a pregnancy test, a little bit of spit, a little bit of swabbing the nose. No problem. You can get results very quickly. I have a two-step problem, I call it home testing, assisted home isolation. Instead of focusing on the exposed, we can focus on the contagious. I want to see enough tests freely available so every business, every school and every home can test everybody at least twice a week. That catches most of the people who are contagious. And then I want a program that pays people a lot of money, like $500 a day, to stay home with their family. Why family? Because that is who gets mostly infected. There is very good evidence. Most people who transmit it, transmitted to their family. So if people stay home for two weeks, maybe a little longer, that does two things. One, identify the people who are infected and contagious and give them an incentive to stay home. Two, people will identify themselves. You get paid more than you earn. And even in a country like Italy, where you have a basic guaranteed income, extra money is always welcome. VS: You need incentives. WH: You need incentive. And then of course you have to have public health officials before they pay you to check if are you really infected, because there are cheaters everywhere. And you need a safety net in workplaces because people will not test themselves. And in schools because kids’ parents will not test them. That is the way humans are. You know, I learned a lesson from HIV which I will never, ever forget about human behavior. In the early days, when 2049
infection was a hundred percent lethal or ninety eight percent lethal, I worked with Robert Redfield who is currently an infamous character in America and worldwide on testing the entire US military and public service for HIV. And we did it. And then anybody who was in a relationship with a discordant couple – one where the man infected the woman, not the woman infected the man – was brought into a room and counseled. Your partner is infected with a lethal disease and is going to die. If you have unprotected sex, you will get infected and you will die. Thirty percent of people used condoms, seventy percent did not and eighty percent of those people got infected. Fortunately, for many of them, there were drugs. So, they did not die. But that tells you about human behavior. It is a very serious lesson. If I ask any doctor how many people use condoms? They will say, thirty percent. Why? Because thirty percent of people take their medicines that are prescribed. The rest do not do it. That is the way we are. So, you have to have checks and double checks. But I believe that you could take the Chinese lessons and tailor them to your situation. You know, Chinese did not have to do that because they have a more organized society, and they have a whole system of how to control people's behavior. We do not have that, but we have other ways to do the same thing. And we should be doing that even while we have vaccines, because vaccines are never going to be the panacea. The panacea is to stop one person with a virus being next to another person without a virus, not a virus. So that is really how you stop it. Stop people with the virus from meeting people without the virus. VS: But do you think that we could have this hope to see our governments implementing effective decision and measures? WH: I think it will be variable. You know, who would have guessed that Sweden would be so irresponsible, except some of the Swedes by the way. I wrote a book on the Swedish healthcare system and I pointed out that it is a great system except for old people. And if you really want to learn about what you are going to have to do for your own, even if you have a great health system, take a look at Sweden that fails its old people. There were signs that they could fail and any country that believes they are exceptional, it is hubris. The Greeks had a good word for it. Those who are prideful are the first ones to fall. VS: Yes. 2050
WH: You know, from your point of view, advising companies, the word should be uncertainty, caution, and careful planning for downside contingencies. That means all the things from supply chain, to personnel management, to markets, to transportation. The industry that I would say is going to suffer for a long time is travel, leisure, abd hospitality. VS: Do you think that the Chinese that are managing this situation better than us will be willing to travel to other countries? WH: They are not allowed. They have a very strict travel policy. Now you can travel to Singapore. Soon I think maybe you can travel to New Zealand, and of course to Taiwan. They are very, very careful in where you go. And when you come back, no matter who you are, you have to be at least two weeks in isolation, and now maybe longer. And you have to go through all these tests. So they are going to be careful for a very long time. Now they are big enough, so their economy is growing. They are exporting. China is focusing much more on internal consumption than on an external export. That is a huge change for China. It was coming. This has accelerated that trend. And I think that is another major trend. You are going to see increasing internal focus on getting your own house in order. The first are businesses. And I wrote about this very early on. In March, I wrote about supply chain alteration, that it was very clear that the first impact is going to say diversify your supply chain right now. And that is a big business challenge. I think other major changes will be seen in commercial real estate. I have closed my offices in Hyderabad, in Delhi, in Singapore, in New York where we used to have real estate, where we had offices. I have not closed my offices in Beijing and Shanghai. They are open. Everywhere else, we still work. We work virtually. And so, what happens to those real estate tenants? You know, I tried to be gentle with them. We negotiated, but they did not have a very strong negotiating position, even though we had signed contracts. Everybody knows you could not sue us. So, we negotiated fair agreements. But now what is happening to these people with commercial real estate? That is another big area under threat. And if you go through the different areas, some are going to be very strong and some are going to be very weak. The other thing is deep preparation for shocks. SARS changed the Chinese government system for health and preparation. I can tell 2051
you exactly because I was partly involved in that. The moment SARS hit, some of my former students who were already well known in China for their work in vaccines were asked, what do we do? And especially one of my students, she ran a big vaccine institute said, “look, you have to learn from America how to control these diseases.” So, what did they do? We created at Harvard School of Public Health a special program that for more than ten years trained the top health experts of China. There is something called the Central Party school which educates everybody going up to the politburo and higher. There are all these other parties’ schools but the Central Party School is the one. And people from that school learn from Harvard School of Public Health. In fact, I am currently the head of the US-China Health Summit, which grew out of that program, where they spent years learning the best systems to prevent another major economic disruption. Because what they learned is that SARS could destroy their economy and they did not want that to happen. So, they prepared and other countries prepared. South Korea ran a SARS exercise in December before COVID arrived. China had all these plans on the books on exactly what to do if it happened again. For example, do you remember when they built all those hospitals in China? VS: Yes. WH: That was already planned. Why? To treat people with the plague and let the rest of the people go to the normal hospitals. Do we have that plan anywhere in the world? No. Why not? We might now. Should we learn from China? Yes. Not just how to contact trace, but how to organize. The other thing that they learned is you have to have a national policy. So much of what is happening is regional. In the United States, we have so many different jurisdictions, you cannot even count them. VS: Even in Italy, we have this kind of problem. WH: And you know something, our Supreme Court just made a horrible decision. Because there are religious evangelists that are now on the court, they just made a decision that the government cannot tell people not to go to church. Well, if the government cannot control in an epidemic congregation of people, what is going on? That is the defiance of law that goes all the way back to the Greeks and the Romans. They had laws that said, if there is a plague, government has plenipotentiary power. It can do anything it wants. 2052
It may not be able to educate you, but it can put you in a jail cell. It can stop you from getting together. It can lock down whole cities. So what is this loophole for churches? Think of that for a minute. Christmas time in Vatican City. Your government cannot touch whatever the Pope wants to do. What would that be for Italy? Every Sunday you want to pack the churches. “It is a religious wedding. Let us get all together.” Thousands of people that come to these weddings. That is exactly the wrong action. So, you cannot trust, at this point, the way Western civilization is organized to respond properly. And that is another lesson. The Supreme Court decision in the United States is a lesson that should not be taken parochial. It should be taken as a warning that social power, no matter where it resides, whether its unions or farmers or whoever's got the power in your country, can exert extraordinary measures that can thwart rational public health policy and do. It's going to be somebody in some country that has that kind of power, extraordinary power, from a minority that can mess up the whole system. And that is going to happen again and again and again, all over the world unequally. And again, that is going to mean that whatever happens medically is going to be ragged. It is going to be spotty. It is not going to be systematic except where it is already systematic. VS: Yes. It is a very interesting point of view. You almost view it like an ecosystem. We cannot take into consideration only one field of the situation. WH: Exactly. VS: You have to look at the whole plan. WH: By the way, that is what the virus is doing. The virus is exploiting our biological weakness, our and our sociopolitical weakness. That is what it is doing. VS: This should be the title of the book. WH: I have thought about writing that book, called the Code Cracker. VS: That is very interesting. I do not know how much we can hope for changes in the government. WH: Remember, you can always hope. VS: Yes.. WH: You know, I was just reading Jeffrey Sachs, whom you might know. He just today wrote a piece in Project Syndicate about things in America, Biden has to correct. The list is formidable, 2053
formidable. I am sending it around to my friends, but it is a very tough list. And, you know, we deal with a political situation now. People put past prejudices and power relationships first, even onto death. Look at Naziism. Just look at a country like Germany when it was collapsing. People were still supporting it when it was absolutely crystal clear that it could not go on. The first wave was ten million dead and the second was another ten million Germans dead, still supporting the system to the very, very end. So, you cannot count on rationality. VS: Yes. So thank you very much. It was very interesting. I want to tell you this last thing, just to close our conversation. What happened now in Italy when Maradona, the football player, died explains very clearly what you told me. Especially in Naples. Naples is in the Campania region and during the pandemic, the president of the region had these Facebook live speeches in which he told people, “I am going to kill you if you go outside. Do not try to go out of your house.” And then on social media, he became a funny person and now he is not managing this situation all. So, we have some situations right here in the North of Italy where we cannot go out. I took a train this morning in Milan, in the station, and they for the documents, the certification and everything. In Naples if you see some photos, there are people gathering in the stadium. And that is crazy because I mean, what is the government doing ? WH: It is more than just the government. First of all, in almost all societies, it is a very, very deep social issue about how society should function and what the right of the individual versus the state is. And that goes back a very, very long way. And if you look at Chinese history or you look at the history of different parts of the world, the evolution of the rights of the individual versus the state have changed enormously, and what we call the Enlightenment and the whole movement toward the individual against the right of the state has predominated. But the reason, if you go even further back in history, and the reason that the state had so much power, whether it was a king or whoever it was, was for protection. The world was a much, much more dangerous place than we perceive it to be. And the actual world is much more dangerous than most people perceive it to be. There are so many true uncertainties like asteroids or volcanoes, or earthquakes. We know those. But the real disasters are human disasters and we do not protect ourselves very much against 2054
those. But what we have is we have militaries, but we don't have ways to protect ourselves from other kinds of disasters very well. And in China, they do have a sense of social cohesion and an understanding of why you should, under certain circumstances, obey the state. Now that has downsides, clear downsides. Those downsides aren't yet apparent in China. I believe they will be. I believe you are going to see in the next twenty to thirty years serious problems with the way the Chinese have organized their economic and political life. But right now it does not look that way. There are advantages to individualism and resiliency that come from individual action, but it is always going to be a very complicated balance and things have obviously gotten out of whack. You know, Fareed Zakaria just wrote a very brilliant piece. I am reading his book, Ten Lessons From the Pandemic, it is really interesting. And one of the things he wrote is that if you look at the three great disasters, 9/11, you look at the 2008, and you look at this, they have a number of things in common. One, they were global. They reflected global trends. They reflected a small event triggering global collapse. Think of 9/11, small group of guys. We are still dealing with it. 2008, a few guys. There is a book that Gillian Tett wrote on the Anthropology of the Collateral Debt, the swaps. She's an anthropologist, journalist, but she wrote a brilliant book on who the people were and what they thought they were doing when they put together these credit default swaps and all these other things they did, especially with the bundling of the, and parceling out of the mortgage securities. Small intellectual group, $75 trillion business. And now we are facing a virus that is so small, a hundred thousand will fit on the head of a pin. So it is a very, very interesting book, and she is giving you very interesting lessons on what you have to do. It is not about the size of government, it is about the quality of government. How many people are going to heed those lessons? Some will, some won't. Hopefully what the Americans were doing when they were voting in Biden is voting for some change. VS: Yes. I think it was a very, very interesting discussion. I really thank you for your time. And for me, personally and professionally, it was a great pleasure. So thank you very much. And we will come back to you with some summaries of the insights of what we are collecting. WH: Give my best to Valerio. I hope you all stay healthy. 2055
VS: Thank you very much. WH: Thank you. Bye.
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Interview with Gloria Pallares Global health and development reporter & writer, El Pais November 27, 2020 | Interview
Gloria Pallares (PS): Doctor, thank you so much for taking the time to be here today. As I said, El Pais, which is the most widely ranged paper in Spanish globally, is working on a story. And we are very happy to have you be part of that. So, you were there at the outset of the AIDS pandemic. Now you are witnessing COVID pandemic. What are the similarities and what are the differences? William Haseltine (WH): Well, that is an interesting question. I wrote an article recently in Scientific American, and I have also just finished an autobiography called My Lifelong Fight Against Disease from Polio to HIV/AIDS to COVID-19. So, I have thought about this question a great deal. First of all, this is the third serious pandemic to affect my life. First one is polio, and very similar to what we are undergoing today, when I was a child. We had the same restrictions. You could not go out in groups. You could not go to movie theaters. You could not go to the swimming pool. The only difference was polio hit during the summer and this hits during the winter. But both of them are year-round in some respects. The polio pandemic was ended with a vaccine, but even today, polio is not eradicated from around the world. It is still persistent and there are still people who suffer from polio. So, there is a chance that we could eradicate it, but it is not yet eradicated and that is seventy years later. The second epidemic was HIV/AIDS and that has so far killed thirty seven million people. Fortunately, the medicine came to the rescue in two ways to diagnose those who were infected and to come up with combinations of treatments that can extend life of those who are infected, if they are properly administered and taken. With them, people can have near normal lifespans and can reduce the possibility of transmission. And we are on the brink of long-acting drugs that will prevent people from getting infected, when exposed. We have not gotten there yet, but after thirty five years of research, we are
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very close. I think within a year or two, a single shot will be able to protect you for a year. PS: Within a year or two? WH: One year, I think. Not more than two. PS: We are talking about a ten-year timeline. WH: No, that is too long for a drug. For the drugs, I think, we are talking about three or four months from a single shot. But I think that in a couple of years from now, it will be maybe a whole year from a single shot and that is really remarkable in teaching us what drugs can actually do, which will eventually be interesting for COVID. Now we are in the third pandemic of my lifetime. So, the first lesson is that we have not yet eliminated the virus. Let me go even further back. I was one of the very first civilians who was saved by penicillin in the early winter of 1945. I was an infant suffering from pneumonia and my mother persuaded the military doctors – my dad was in the service fighting the war – to give me penicillin because it was not approved for civilian use. And so, my life depends upon a remarkable revolution in medicine which is the antibiotic revolution. Vaccines and antibiotics have given the world more or less, especially the developed world, the idea that we have conquered infectious disease when in fact, of course, we have not. We are on the brink of another infectious disease disaster, where our massive use of antibiotics has created resistant organisms which are coming to get us. We have now experienced, in my lifetime, three really serious pandemics, the polio one which has plagued mankind for time in memoriam, HIV which was entirely new to the global population, and now COVID which is, again, entirely new to the global population. I just wrote an autobiography called My Lifelong Fight Against Disease. And in there I cite what I said in 1985 to the US Senate in a testimony. I said, this is not the first time, it is not the last time. And if we do not prepare ourselves, we are going to be hit again and again and again. And then in AIDS, I helped create BioShield and later BARDA that turned into official government documents about how you should, how you can, do research on this. So, we live in a world where infectious diseases are present, and are dangerous on a pandemic scale and capable of killing hundreds of millions of people. That is the first lesson, and we should never forget it. Therefore, we need to prepare. There are only very few 2058
countries in this world that were actually prepared for COVID. China was one of those countries and a few others that had SARS were some of those countries. Why? Because they knew from SARS that a new pandemic could cripple their economy. I am not so sure it was the number of lives that were lost that was important, but it was the economy, which is everybody's life, healthy, alive, or dead. If you have an economy that tanks and you are still alive, you are in trouble, everybody is in trouble. And so they understood that in a way we are now learning. It is sad that we could not learn that before, but the Western world, and AIDS never taught us that lesson. Why? Because AIDS was much more easily controllable by personal behavior and it was not nearly as contagious. This is probably the most contagious disease that we have experienced in modern times, except for measles. It is much more contagious than the flu. So, it is much easier to get this. I will tell you why I say that. In South America last winter, the very poor measures, inconsistent, irregular and not uniform that were applied to control COVID controlled flu, ninety eight percent decrease in flu cases. And already in the US, flu cases are way down, not COVID cases, but flu cases. So this is much more transmissible than the flu. It hangs in the air in small spaces for hours, as you breathe that air and get it into your eyes. If you are on an airplane and somebody on the plane has it, you are going to get it, some people are going to get it, even though the airplane say that it is not true, it is true. And so, again, the major lesson is these are coming to get us. The second lesson is you have got to be prepared. And we in the Western world were unprepared. Our governments in the Western world were unprepared. Now there is a third lesson and that is, in these pandemics, governments may respond poorly. Public health systems may respond poorly. Science shines. In the AIDS pandemic, or the AIDS epidemic, the one part of the global response that was instantaneous, massive, well organized was science. Science understood what it was very quickly, understood what we needed to do to control it, came up with diagnostics. And once we had a diagnostic test, in theory, we had solved the problem because we could tell who was infected, and we knew if you used condoms, it would stop the infection. But that was not enough because people, even if they know they are infected and know their partner is infected, rarely used condoms. So that tells you a lesson about public behavior, which we are learning 2059
again and again. Just today and yesterday, Maradona's celebrations. I do not know what it was like in Spain, but I suspect a lot of people got together. Not like Italy, not like Argentina, but there were gatherings to respect Maradona. So, people are not rational. And so, what has worked is science. Science, within weeks, understood what COVID was. Within weeks started preparing drugs and vaccines. And now within a very short time, and diagnostic tests, you are seeing that we can diagnose it. We still cannot treat it very well, but there are likely going to be some vaccines pretty soon that are going to work better than we could reasonably hope for. And science has been stellar, but, the other lesson is, science is not enough. It takes an entire society, it takes governance, it takes a sense of social solidarity, and it takes leadership to control this. And it also has a very deep resonance with how governments are organized and what sense of social solidarity we have in the West. And I think that the lesson, the biggest lesson to me from all of this is China versus the rest of the world. That is a lesson that people still have not absorbed that, last week when 1,200,000 Americans were diagnosed with infection. and probably as many as three million were actually infected because we do not pick up all the infections, China had eighty-nine people infected. 1,200,000 versus 89. That is a number that people should incorporate and understand. How can that be in a country that is four times the size of the United States? The same applies to Europe. What has happened? Is it that we are ignorant? No. Is it that we do not know what to do? No. It is that we do not do what we know to do. That is even worse. It is like a crime against humanity. And even the best organized governments in the world. You would say Scandinavian governments are well organized. German governments are well-organized. Italian governments are sort of organized and France and all these governments. They all failed. Why? PSv: What do you think is the answer to that question? WH: I think the answer to the question is the degree to which there is something called civil society. Europeans have thought before this that they were at the top of the pile in terms of civil society. And it turns out they are not. A civil society does what China did and everybody cooperates to save everybody else. Now you can say the government is so powerful that it makes them, but no government can do that. We have learned through the different 2060
colored revolutions that it is the power of the governed that gives power to the governors. And the governed are the ones who give power to the governors. And we have not given sufficient power to our governors to control this pandemic whereas the Chinese have. People do not write about that. They write about top-down power. No, there does not exist top-down power. Individuals give power to the state for security. That is what we do. That is the nature of the deal. I will give you my tax money, hard earned money. I will give you restrictions on my freedom not to drive drunk or without a seatbelt, but you protect me from some other guy who is drunk, from another guy who has not got a seatbelt, from some other guy who has got a deadly disease that could give it to me, and I will give you the power. That is how it works. And it works in China. They have a civil society that works, and we do not anymore. We have gone so far toward individual liberties, which are from the time of the Enlightenment, which seems to be progress, and great progress. And indeed, in some ways, it is great progress to liberate the mind, to liberate the spirit, but there are limits and we have exceeded that rational limit. When we have people saying, “it is my right to go to a pub and get drunk every night, however I want to do it, it is my right to go out in public without a mask. You cannot tell me what to do.” We have exceeded the limits of civil society and individual liberties. When our Supreme court can say the government has no right in times of deadly pandemic to tell people not to congregate in church and infect each other, we have gone too far. We have lost a sense of reality. Earth is not made for human beings. We are part of nature and nature is out there trying to figure out how to kill us. That is what viruses do. They figure out how to spread. They are out there every day, trillions and trillions, and even quadrillions of combinations, an intelligent machine trying to kill us. And we are not prepared for that. Some of us are, and some of us are not. So I think it's time for the Western world to realize that they have experienced a moment of collective hubris, that their pride in individuality has exceeded its normal limits. And actually, rather than being civic, is anti-civic. And we are paying a dreadful price in terms of people who are actually dead, in terms of economies that have crashed, and opportunities for hundreds of millions of people who are blighted. You think of the kids between the ages of 18 and 25 right now and what their future life prospects look like to them. You 2061
know, I have stepdaughters right now who are brilliant, hardworking, lovely people. Their prospects have just taken a tremendous dip in what their lifelong expectations could be. And that is happening around the world. Those who are wealthy at the top can survive, but everybody else has gone back twenty or thirty years or more in what their lifelong expectations could be because of this false notion that the individual right trumps every other right. It certainly should not trump the right to spare another person’s life by your individual behavior. PS: So, this means that the individual liberties have become selfishness in a way, and that being selfish gets us all collectively into trouble because that is an infectious disease. WH: In times of stress like this, the answer to that is yes. There is always going to be a balance between the rights of the individual and the rights of the state. And in times of panic and stress, those rights have to be adjusted and then they can be adjusted back again. We are used to that for wars, but in this case, our governments are so fractured, so weak, just look at what's happening in Italy, in Naples yesterday where people congregated in stadiums and you know what, they are going to get infected. A lot of those people are going to die and their older relatives are going to be killed by their irresponsible behavior. And what did they say? Nobody could tell me not to worship Maradona. PS: Then there is the issue, and I know WHO is also looking into it, the sexual dynamic to COVID-19 and how this is affecting sexual behavior. WH: Well, AIDS is, a sexually transmitted disease because that is how it is transmitted, either by blood transfusion or drugs or sex. And this virus adapted. The virus has to figure out human behavior through their random mutations. And this virus took advantage of the fact that people have sex and that is necessary for life. It is a fundamental part of life. It is built into life. Without sex, there is no more life. So people have to have sex. And young people have to have sex the most , because they are people who are at a reproductive age. And so what is this constraint? The constraint locks them up and says you cannot get together. Well, the one thing you need to do to have sex is to be close to somebody else, right? That is the fact, and people do not recognize the power of that dynamic for young people. Now, that is where years ago I developed for HIV, a test 2062
that took that into account. It was a five-minute test that I wanted everybody to be able to have so you could determine before you had sex whether your partner was infected. If you could do a fiveminute test with a finger prick, now with saliva, or external nares swab, you could tell whether anybody is infected. So that is another similarity. Identify people who are contagious, and those people should be isolated. They should isolate themselves, or somehow arrange isolation. So, with HIV, there were these tests. It took twenty-five years or more for the FDA to approve that test for HIV. So now they have them. People won't report themselves. People will not take their medications, they'll hide it, et cetera. Well, I think a part of the solution for this is to have a five-minute test, universally available in free to everybody, to know whether or not you're contagious. And if you are going to be with somebody, you should know if that person is infected and give each other a test, five-minute tests and you will know. That can make a big difference. Young people have to get together. There is no way you are going to stop young people getting together. It is just not going to happen. It is not in human nature to be isolated, but you can make it safe. So, Bill's version of the Western way to control this pandemic, learning from the Chinese, but adapting it for our individuality is to say the following: Flood the country with cheap, free, fast selfadministered tests. A drop of saliva, a nasal swab can give you an answer in a very short time. Now, even if it's only ninety eight percent or ninety percent accurate, it is going to be accurate enough to slow the pandemic and even stop it. And then pay people to stay home for two weeks with their families. And in America, pay them a lot, pay them $500 a day, more than they would get. Many people earn $500 a week, pay them $500 a day. Even with social benefits in Europe, pay them, give them incentive, have them stay home. Have everybody at work, everybody at school have these abundant tests. You can test everybody two or three times a week. And that can stop this epidemic within three or four months, no vaccine, no drugs. You do not need a vaccine. Then, a vaccine has a real chance of working, because when few people are infected, it is going to be much more effective. So, I think that that is a strategy that I wish we would adopt right away. The technology is now there. Britain has just ordered two billion fast tests, two billion. I think America needs 150 million a day. That is certainly within our capacity to produce 2063
and they should be fifty cents each. And then we should identify people who are infected. That is a lesson, again, you asked me about AIDS. That is something we learned from HIV/AIDS. If you have tests, you know you are infected, you can begin to control things. Before there was medicine, people did not want to take the test. Once there was medicine, everybody wanted to take tests because then they could go get cured. PS: Yes. Sos you said there is a need for like 150 million fast tests a day in the US. And how many tests have they procured now? WH: 150 million, maybe one day's worth. Now it gives you an idea of how effective our government has been. We have had a massive failure of governance in the US, leadership and social solidarity. The three things you need for any pandemic is leadership, governance and social solidarity. Leadership, we know we failed. In some European countries, you have satisfactory leadership. Governance has been a real issue because there has been too much power given to local governments, not national governments. That is a lesson from China. Local government in Wuhan failed. The national government stepped in and solved the problem. And it was a national effort. Only national efforts can do it because nobody else has the resources. And finally, you need social solidarity, where people agree to look after each other and sacrifice for the greater good of the country. And Europe fails on social solidarity, even though they pride themselves on social solidarity. This has been a massive failure of social solidarity. You know, I had people who were traveling around this summer. Two students in Bocconi who were doing work for me. They said, “Bill, you have no idea what is happening here in the summer. Nobody is pretending, it is as if there is no COVID.” That is how people behaved. And then what happened? France has experienced, maybe the worst spike in cases in the world for a while. They now got it a little bit under control, but their infection rate was three to four times that of the United States per capita. Unbelievable. So social solidarity is not as strong in Europe as the Europeans would like to believe. It failed in this case. You have China which succeeded. And as I say, people call it totalitarianism. I call it something else. I call it a sense of civic unity and civic unity has failed in the West. PS: There are issues in terms of behaviors, human behavior. Then there is the issue of communication. But the knowledge 2064
around COVID is changing all the time. How was that with AIDS and how can communication on COVID improve? WH: Let me give you a case in point about AIDS. We had a government that did not want to acknowledge AIDS under Reagan. It was a conservative government and they found it inconvenient. Well, viruses do not care about what governments think, whether it is convenient or not, but they found it inconvenient. They did not even want to talk about sex. And so, the CDC was run by people I used to call the seedy C because they were opposed to even thinking about AIDS as a sexually transmitted disease and heterosexual disease. They thought it was all gays and drugs. I would go on a talk show. Jane Pauley would put me on the couch with a woman who took her kids out of school because of AIDS. I said, “look, those are elementary school kids. They have no way they are going to get HIV. Do you have teenagers? They are the ones that are going to get it.” And finally, the CDC got fed up and they commissioned a book called The Myth of Heterosexual AIDS. And you still get the book by Fraumeni. The point was to attack Robert Redfield, a name you will know, and me personally, by saying these are false experts. They may know about viruses, but they don't know anything about public health. Do not listen to these guys. The book was titled The Myth of Heterosexual AIDS. That is denial. And so, governments deny. Now, does that sound familiar? The same kind of thing happened. Eventually we finally got through Ronald Reagan’s friends to say the word AIDS once before he left office, once. You mentioned AIDS where communication is vital. And that is part of leadership. In leadership, you have to be clear, consistent and credible. In most situations, leadership in this country and Europe has not been consistent, it has not been clear, and it has not been credible. In some places it has been outright lies. Take Sweden again. They thought there was going to be herd immunity. Britain too. And others thought they were going to get it under control. The virus left with summer. Very bad communication. But I think the real problem in the Western world is different. It is what we talked about before. It is a sense of individuality and how important the individual values are versus the state, which has got no better apotheosis, except for the Supreme court decision about churches recently. There is a Roman law that the public health is the greatest good. It precedes everything else. This is a violation 2065
of that fundamental law of human organization. Our Supreme Court has just broken one of the fundamental laws of government in the entire history of the world. And that is historic. That is almost incomprehensible and historic. This is a fracture in one of the major ways that government is intended to protect us. And it is a serious breach, because how many things are going to fall into religion now? You are going to see a huge social movement to label things religious so people can get and congregate in America. It is a major fracture in the way humans organize themselves. It is not a minor infraction. It is a major infraction. And it is driven again by small ideological factions that exert an extraordinary political power. Every country is going to have its own version of this. PS: Now, in the beginning you mentioned epidemic preparedness, the need to be ready for the next one because there will be other ones. But now there is the issue that political cycles are very short, four or five years in most countries. So, what would be the incentive to invest huge amounts of money in something that may not happen? WH: Let me respond to that with a question, which is, what aspect of government does exactly that in every country around the world? The answer is defense. Huge investment for something that may never happen that transcends every change in government. It happens, right? How much money do we keep spending on our militaries? You know, maybe in some countries more than others, but every country spends a lot, except a few. But it is that we do not properly perceive our risks. What is a guaranteed risk? Guaranteed risk is disease. No doubt about it. Guaranteed risks are pandemics. You may not know their timing, but you know they are coming. And look how many people it killed in America. We have killed two thirds of the number of Americans that died in World War II in a four-and-a-half-year war. We have already killed them. They are already dead. And how many more are going to die? Probably another half a million could easily die. So, we need to be prepared. What does it mean to be prepared? It means to take the lessons of what works in public health and what does not. What works is preparedness, which means you have the plans on the books. For example, the Chinese had the plans for quarantine on their books. The local government failed for a couple of weeks, but the moment the central government got the idea, they put their plan into effect. 2066
They quarantined Hubei, the whole province. Tens of millions of people were quarantined and were locked down in their houses. That was a plan. They created massive testing programs where they can test ten million people a day if they need to. They stopped travel within China. So that stopped it. They were willing to take a huge risk. They also had a plan to build hospitals, to treat those people who had the plague and let the other hospitals continue to function, which nobody in the West is doing. We build extra capacity, but we do not build special hospitals. And we do not have a plan to build special hospitals in two weeks just to treat the ill; those are part of the plans. So, all of those things they did right. We need to have those plans in place. They had these contact tracing apps, and these apps that tell you, are you green, are you yellow, or are you red? We still do not have that in the United States. In Europe, they have done better, but it has not really worked that well. And then in addition we have science. We could have had drugs that had been tested and approved. The anti-SARS drugs turned out to work for COVID, but they are taking a long time to go through the testing process. They could have been on the shelf. I developed a drug for anthrax. There is no market for anthrax. Why did I develop the drug? Because I knew and had worked out in advance that the government would buy it if I made it. They stockpile it even today. So, you can do things like that. And we have the legislation authority to do it for bio-terrorism. And we even put in the legislation for new and emerging diseases of manmade or natural origin. So, we have allowed ourselves to do that. And so, that is where the money flowed for these vaccines in the US, flowed through exactly that legislation. So, we were prepared in some ways, but certainly not from a public health point of view. But the other thing I would like to say is, I have been a businessman, been a scientist at Harvard before that. And then for the last fifteen years, I have been working on finding a way for everybody around the world to benefit from the same medical care, because the way societies are organized prevent that care from being distributed equally. It is either not available because the health system is faulty or it is not affordable, like in my own country. So yes, we have great medicine for those who could afford it, for those who know where to go, and those who happen to live in the right place. But on the whole, the American medical system is bad. It is no better 2067
than the Dominican Republic. It is about two standard deviations below the mean of a European country in terms of outcome, infant mortality, maternal mortality, death before the age of five, serious disease or death before the age of 25, longevity. All of the key measures we fall short, yet we spend twice as much. But in other countries they spend almost nothing and have terrible results. So, the question is, with all this technology, how do we make it available? And that is what my foundation has been working on, ACCESS Health International, for the last fifteen years. Well here is case in point. Some systems work well, and some systems do not. The big surprise to me is how poorly the well-organized national health systems of Spain did, in particular since it has very good outcomes and is a very robust system. Why did this fail in Spain of all places? You know, I think Japan, Spain and France are the best places to look for really good healthcare because they do not only take care of people who are rich. They take care of people who are young and take care of people who are old. Why has this failed in that system? And again, it is a really deep question because it is not a failure of governance or availability of healthcare services. It is a failure of, I think, public participation and of leadership and of lack of preparedness and of understanding about what has gone on. But it is a shocking failure, I have to say. In a system which otherwise functions well to have such a failure has got to cause people to have very deep reflection about what their life is actually like. And go back to fundamentals of governance. What is the government therefore, and who are we as people? What do we think our role in organized life is? What is our responsibility for our neighbor versus our responsibility to ourselves? These are very deep questions. And I think Spain has failed pretty miserably in answering those questions in the face of this pandemic, to be specific to your paper. It has been a failure. And you have to ask why when they have been so successful in other ways. And Spain is not alone in its failure. Almost all of Western Europe is united in the same kind of failure. PS: Now you mentioned the issue of access. As there are more and more promising vaccine candidates, there is more and more anxiety about who is going to get the vaccine first. How do you see the access issue in COVID? WH: Well, that is going to be the same. There are organizations that are working feverishly to try to make sure that access is fair, but 2068
the world is not fair and access to vaccines is not going to be fair either. And the vaccines that the Americans have developed are totally unsuitable for use in poor countries. You just cannot do it. You know, it is so hard in the United States. We have asked our military to deliver the vaccines to the States. Well, try that in Mali. I think you are going to have some pretty serious issues. So not that Mali is particularly bad, by the way, it is just to give you an example. And in December in the United States, there are probably going to be four thousand people vaccinated, because you need two doses. And then which vaccine are you going to get? And then there will be more in January and February and March. Who is going to get those? There is going to be a dog fight. That is what it is going to be in the United States. Do you think in the United States we are going to have an effective program to give it to the people who really need it most, like Latino and black minorities who have to go to work every day to survive because we have no social safety net? You really think that is who is going to get it first? I would be totally shocked. We do not have any systems to do that. We have no governance that can do that. We have no social organization or political organization to make sure that could happen. You think these minorities are going to rush to get vaccinated? The ones who need it most? And every country is going to have its own issues, which vaccine to use, how to use it, how to prioritize it, how to roll it out. And even when it is universally available and free, a lot of people are going to refuse to get the vaccine because we rushed it through. Vaccines are not the panacea immediately. If we are lucky, they are going to be like polio. They are going to make sure most people do not get it, most people will not die of COVID. That is the hope, but it is going to take longer than polio to get accepted. And so, there are going to be issues of acceptance and issues, especially at first, where there are very limited supplies. And then there are many other issues like the vaccine that is most likely to get approved in Europe first is the Oxford vaccine. Well, a lot of people are going to be resistant to that virus because of the way it is delivered and because it has some side effects. It is going to be apparent when you give it to more people. And you cannot give it a second time. I published a long time ago at the beginning of the pandemic publication by press release. Now it is even worse. These companies 2069
are not even bothering with a press release, they are going straight to publication by proclamation. The CEO says they have got a great vaccine, but the data is not available yet. But they have a vaccine. The market moves by trillions of dollars. That should be illegal to do that. If I were a CEO, when I was at my company, if I did something like that, I might even face a jail term. So, what is going on now, publication by proclamation, is crazy. PS: So how do we protect ourselves from bad science and this kind of proclamation? WH: That is a matter for governments. An individual cannot do that. We cannot do it individually. That is a matter for government and is yet another failure of governance. And I hope that they are honest and direct, but you have to look at what happened to both CEOs of those companies. The moment they had positive news, they sold a tremendous amount of stocks. And they did it in what was called program trading. Guess what? Some of those traded programs were put in weeks before the announcement. It sounds like program training. The SEC is now trying to make a new rule that if you are going to do program trading of your own stock, you have to have it at least six months in advance of the first sale, not six weeks or six days.. We have to believe CEOs who have got tremendous self-interest. The one thing we know about human behavior is self-interest colors behavior. We know that. It is not a secret. I am not saying they have. I am saying that it is cause for suspicion and regulation and it should not be allowed to happen, and it is a government failure if it does happen. PS: How instrumental has the research on AIDS been for COVID and could research on COVID be accelerated? WH: I think has been absolutely vital. You know, the same people I worked with in combating AIDS are the people who have been the leaders in combating COVID, Tony Fauci, for example, and many of the scientists. And my students and my grand students are at the forefront of the fight against AIDS all over the world. And that is true for all of us who were pioneers in AIDS research. Let me just give you a specific example. We have been struggling without success to create an AIDS vaccine for thirty-five years. And the infrastructure, the global infrastructure for testing HIV vaccines is that which was used to test the COVID vaccines. The programs that we set up in the wake of both 9/11 and the AIDS pandemic to 2070
accelerate drug approval are the programs that have been used. The very techniques for working out vaccines and trying these different variations of different types of vaccines and adjuvants and everything else have been in large part enabled by HIV/AIDS research. But if you take a step back, AIDS research was enabled by cancer research. We could not have begun to make an understanding of what AIDS was, what its approaches were, the various drugs that were developed, without decades of investment in cancer research. I can tell you for a fact, the very first drug that was effective against AIDS was a rejected drug for cancer. And the whole idea of understanding retroviruses, we could not have done that without decades of research and investment in cancer. And the hope that we have of control now comes from years of investments, not from social systems. We may have failed in our government response, in our public health response, but we did not fail in either case in our science and medical responses. And I am very pleased to say that today we have a partner we never had before in science and in medicine, and that is the Chinese. The Chinese are the equivalent of America in terms of their scientific and medical capabilities. And the world owed a deep debt of gratitude to the Chinese who published their work very early on. Within, I think, ten or fifteen days of isolating the virus, the Chinese published the sequence. Ten to fifteen days, they published the sequence and anybody in the world could work on it. Their doctors sacrificed sometimes their lives to treat their patients and publish their research instantly as fast as possible, so we in the West had a very good idea of what was happening. The Chinese announced, and did not keep secret, their lockdowns, their social isolations, all of the measures they took. That we did not learn from that is shame on us, not shame on them. It is true that the local Wuhan government messed up and messed up badly. But after that, we owe the Chinese an enormous debt of gratitude for their openness in science and medicine, which has saved many lives around the world and could save many more. PS: Do you feel that the current crisis will change the relationship between scientists and the public, and how so? WH: You know, there has always been at least some understanding that science is really important for your health and through ups and downs of our governments, there has been a general 2071
consensus, that science is critically important. And even in the US, the one thing we did right for COVID was put a huge effort into vaccines. We should have put the same effort into testing and the same effort into drugs, but we put it in vaccines, and you see it paid off. So, they did a good job on, in that respect; an amazing job as a matter of fact. But we were not alone. The Chinese did the same. The Russians did the same. The Indians are doing the same. So, science has a respected place, but under the government, you heard many people saying, “thank God we do not have to listen to scientists anymore. I am going to go with my gut. I am not going to wear a mask.” They think a public health person is the same as a doctor or a scientist. They are not. A public health person has to work with all the apparatus of society. They have to work with local health authorities. They have to work with community organizers. They have to work with selectmen and governors and politicians. Public health is not a matter of medicine. It is the interface between medicine and civil society. That is what public health is. And they conflated the two. So, I would say science, yes, public health, no. In fact, public health has taken in the US a serious beating as I think it should take in most European countries because it has failed. Public health has failed you in Spain. Medicine has not, science has not, public health has. I have been writing about seriously rethinking how we manage public health. We have to change governance of public health. You know, in Spain, you had provincial power which was exorbitant compared to what it should be in times of pandemic. We had the same problem, that there was too much local power. I understand that when it comes to health, but not public health. Those are two different things. Whether you have regional control over your hospital system is very different from whether you have regional control over a pandemic that is affecting the whole country and you made a deep and fundamental error that needs to be corrected. You need to have a unitary federal policy that is enforceable for public health. Public health has to be delivered locally but organized centrally. And that is a big lesson for Spain because, there have been all this fights between the power of the local provinces and cities versus the power of the state. And you suffered from that. And it is time to change that.
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PS: You mentioned the need for, ideally the need to do massive testing which would make the vaccine even more effective because fewer people will be infected. You also talk about the behavioral change that should ideally come about where people protect each other, et cetera. How do you see human behavior evolving in the next one to five years? WH: I think it is going to take inspired leadership to convert the failures and lessons from those failures into practical policy and implementation. And that is going to be uneven across countries. Some countries will be blessed with good leaders and a public that is willing to listen and others will not learn a thing. It is going to be really uneven, and that unevenness is going to be reflected in whatever happens with this pandemic and this disease. Because this is a recurrent type of virus. It is going to come back every year and how we handle that is going to depend on how serious COVID-19 is in the coming years, country by country. Over time, maybe we will learn, but it might not be serious enough for us to be forced to learn. And I think it is going to be a very uneven picture. Some countries will do it well. Most countries will make some moderate adjustments, and only very few will do it really properly. PS: So COVID is here to stay? WH: Absolutely. It is not going away. This is now endemic. It is endemic not only because of giant human reservoirs, but because there are animal reservoirs, our dogs, our cats, ferret, weasels, and minks, or bats. They are all getting infected. You know, we are a great vector. We go everywhere. And we have a lot of livestock and animals. They get infected and it is going to be around for a long, long time. It is going to be like the flu. PS: Dr., is there something I have not asked, and that you would like to add? WH: I just hope that people begin to understand the fundamental nature of civic society, that we give up freedoms for protection. And in some cases, giving up that freedom can be extreme and feel like being in jail, but it is not forever, and it is for the greater good. And until we make those fundamental adjustments in our own perception of the state's right to constrain our behavior for a greater good, we are going to have continued serious problems. This pandemic has exposed a deep and fundamental flaw in changes in society which have occurred since the Enlightenment. We need 2073
to protect individual liberty, but it is not sacrosanct. It must be subservient under extreme cases to a greater good. PS: Dr., it has really been an interesting conversation. You have also recently published an autobiography, My Lifelong Fight Against Disease, which I am looking forward to reading. Just out of curiosity, I read a paper talking about this cancer, which was a kind of face cancer. It passed from one to the other and was not a viral cancer. WH: That is true. There are several sexually transmitted and other transmitted cancers. There is a dog cancer that is transmitted sexually. And there is a Tasmanian devil cancer which is transmitted by contact. And what happens is the cells from one animal lose the ability to be rejected by all. We have built in protections, that protect foreign cells from getting into our body. One of the more delicate efforts is the balance. When a woman becomes pregnant, she has a foreign group of cells in her body. And what is the adjustment that takes place? Well, one of the consequences is women have ten times the higher rate of auto-immune disease that men do. So that is a slight failure, but it is an adjustment. We have really robust systems to reject cells, but the cells can mutate so that they no longer are recognized as foreign. And that is how these cancers are transmitted. They are actual cells. Now, about a good chunk of cancer is transmitted by viruses, hepatitis C, hepatitis B, papilloma virus. A number of other kinds of cancers are transmitted by viruses, but those have a different mechanism, may change the cell. But in this case, it is an actual cell that goes from one animal to another, and it is a cell of that species, but it has mutated any of its surface properties that tell the recipient animal there is a foreigner here and to go after it. PS: I hope that is not what the next pandemic looks like. WH: Me too. Take care. PS: Thank you, doctor. Bye.
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December 2020
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Interview with NHK World - Japan December 9, 2020 | Interview
US regulators are considering whether to recommend a COVID-19 vaccine. William Haseltine is an infectious disease expert and the founder of Harvard University's cancer and HIV/AIDS research departments. NHK World's Catherine Kobayashi spoke with him about how a vaccine might change the fight against the coronavirus. Click Here for to listen to the interview
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Q&A Session: COVID-19 Vaccines And Newest Updates with Dr. William Haseltine December 11 2020 | Interview
Learn from Dr. William Haseltine, frequent CNN contributor, president of ACCESS Health, and former Harvard public health professor. Please join us for a rare live question and answer session with Dr. William Haseltine, a leading COVID-19 expert. He will address COVID-19 vaccines, give you information to share with your team, and provide insights into the newest scientific developments that affect your organization. Scientific knowledge of COVID-19 is rapidly evolving. Researchers are learning more about how the virus spreads, why it attacks some people more aggressively, which prevention strategies are most effective, and when we can expect effective treatments and vaccines. Each fact can inform your employee communications, workplace precautions, and plans for the future. Click Here for to listen to the interview
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Interview with IE University’s Insights: Viruses Not Only Kill People. They Kill Economies. December 16, 2020 | Article
According to Dr. William A. Haseltine, viruses are intelligent machines trying to crack our biological code, our social code and our geopolitical code.viruses-not-only-kill-people-they-killeconomies/ William A. Haseltine has devoted his whole life to the fight against viruses. Researcher, professor, entrepreneur, businessman, philanthropist, Chair and President of ACCESS Health International, and a former member of the IE International Advisory Board, he talks with Cristina Manzano about the lessons we can learn from the pandemic. Cristina Manzano: Are we in the middle of a global rush to start applying the vaccine? William Haseltine: The global rush for vaccines is understandable and my hesitancy in the past had to do with the clarity of information that was being provided. I’m very pleased now to see the efficacy of the vaccines. Vaccines are the best treatments we have in medicine, because they prevent you from getting the disease, no matter what you do. For some of the great vaccines, you don’t even need a good health system. You can have an international program that sweeps through the country and vaccinates people. That’s how we eliminated smallpox and almost eliminated polio. With HIV AIDS, they haven’t worked. We don’t have vaccines for other diseases like malaria or most herpes virus. CM: And as everybody gets the vaccine, what else can be done? WH: If you’re going to treat with antiviral drugs, you’ve got to first know the people that are infected. That’s why I have proposed massive free universal self-administered home tests. The technology existed, and it’s a mystery to me why it hasn’t caught on. If there is one only thing we could do to stop this infection, it’s to make these tests virtually free. You can just dip a 2078
little piece of paper in the solution and watch it change. Vaccines are great; drugs are okay. But this test to tell you if you’re contagious… It is an enormous gap in what the world has done to respond to this pandemic. Another use for drugs is to prevent you from getting infected. It’s taken us about 25 years to get that right for AIDS. Now you can get exposed to HIV through a sexual encounter and if you’ve taken the pills beforehand, the chance you get infected is very low. It could be the same thing with COVID, but it’s going to take us a long time to get there. There is something we can do right now for healthcare workers: antibodies. They could be protected for two or three months. It is a good thing to do before the vaccines fully kick it. But those drugs are not widely distributed, they’re very expensive and they have to be given by transfusion. We should develop a whole array of preemptive drugs so that if a new coronavirus comes, we are prepared to stop it in its tracks. We could have done that for SARS, because the pills that were developed for SARS actually work against SARS II, the virus that is causing COVID 19. We could have stockpiled those drugs; also for diseases like the flu which could come back tomorrow in a nastier form. But with the vaccines, the impetus to develop those pills is going to be less. CM: What other lessons can we learn from this pandemic? WH: That viruses not only kill people. They kill economies. It’s not surprising that the governments that had SARS and understood that SARS killed economies took rapid action. We in the West didn’t. Hopefully this crisis will get translated into health care reform, preparedness reform, behavior modifications. Let me give you another lesson. Everybody is being encouraged to wear masks, to wash hands, to stay indoors – and around the world, people do it in a way that’s not uniform. In South America in the last flu season, flu decreased by 98%. The same thing is happening now in the United States. In Asia, they wear masks every winter. Maybe a lesson is let’s wear masks in winter, so we don’t get the flu and can save ourselves a lot of problems. In the United States, there are up to 60,000 unnecessary deaths from flu every year. CM: Which countries are doing it well from the health policy point of view, if any? 2079
WH: China is. These days, if I say China in the United States, everybody immediately says it is a totalitarian country and you can’t believe a word they say. That’s ridiculous. If you look at how humanity can confront this disease, China has done it almost perfectly. At the very beginning, local politicians tried to cover it up, but within less than a month they began to behave properly. In January, they locked down Wuhan. Once the central government caught wind of it, they just closed the whole place up and they knew what to do. When the SARS hit they were unprepared and their economy began to crash. So they went to Harvard School of Public Health and, for the next 15 years, had an exchange program where all their top health leadership spent five to six weeks. They learned the lessons that our Western world was teaching about how to control pandemics. They prepared because they wanted to save their economy and save their people. This time, within two months, they drove the infection rate to zero. After that, it’s only been exogenous cases. They tested millions of people in those cities where someone got infected and they added new control measures. While we have more than 200,000 people a day getting infected, 2,500 people dying, they have had nobody dying for months. I say this, in the United States, and get hate mail. For saying things like that in the US, people get threatened. In Europe, well you’re halfway between the US and China. I was terrified watching France in the early fall. When they finally realized they had to shut down, their infection rate dropped by twentyfold; Spain by three or fourfold. But Europe is forgetting the lessons. France is loosening up for Christmas and just guess what’s going to happen right after. The number of infections are going to go up again. CM: And what about health systems? WH: We are sliding into a vaccine disaster akin to our testing disaster. Different countries are going to give the vaccine to different people. Maybe I’m a pessimist, but I see a lot of turbulence over distribution and use of the vaccine, because we don’t have a central policy and we don’t have any troops on the ground. Don’t rely on underfunded, under-resourced, undereducated local Health Policy. Make sure it’s an entire integrated system. 2080
CM: What do you expect from the next US administration? WH: Our President-elect, Joe Biden, is a very refreshing voice. He tells you the truth. He gives you hope that things will get better eventually and he tells you what to do in the meantime, which is everything you can to protect yourself and your family. Does he go far enough in my mind? No. But could he go further and not get a violent reaction in the country? That’s a political decision. I’m no politician. I’m a scientist. A good politician has talents to speak to people in a way that they can understand and absorb the information and then act upon it. There are limits to what you can do in a diverse population such as the United States. What I would like to see them do, as we’re recommending in the common commission, is reorganize our public health service and integrate our disease intelligence. And I would like to see major research programs to provide stockpiles of drugs for all classes of viruses. On the international scene, there needs to be routine population surveillance for chronic and infectious diseases. Let me give you the example of an initiative in Egypt called 100 Million Healthy Lives, in which the Egyptian government, backed by the World Bank, focuses on the elimination of hepatitis C. They created 10,000 local testing sessions and everybody in the whole country 12 and over was tested over a period of eight months. It was very cheap, 50 cents for a blood test. They identified everyone who was actively infected with hepatitis C and everyone who had been cured. Why can’t we do that for all countries, for all diseases? Had we had a testing infrastructure already in place, we could have done a lot more to contain this epidemic right away. That is needed in every single country and doesn’t exist. We also need reform of the World Health Organization. The WHO didn’t perform as badly as some say, but it was slow. It was not decisive. CM: This pandemic has arrived in a very delicate geopolitical moment. WH: Viruses are intelligent machines trying to crack our biological code, our social code, and our geopolitical code. 2081
We’ve created our own fantastic populated world with seven and a half billion people, that travel like crazy. We’re going to have many more of these viruses. We better get together and understand to use our collective intelligence, our ability to reason, to adapt to this new phenomenon. If we’re not clouded by our nationalistic and our emotional responses, we should be able to respond to what has come and is going to come our way with increasing frequency only because we created a great new ecological niche. CM: You have also written about the clear link between climate change and new diseases, but there are still many people that deny it. WH: There are people that deny COVID too, even now. If you can deny COVID, you can deny anything. But it’s not surprising because climate change is slower. Our human species has gone through at least two major ice ages, and hominids have gone through maybe 50 ice ages. If the population shrinks 90%, humanity still goes on, but not as we would like it to do it. So climate change is real. There’s a big interchange between demography, climate, and disease. As populations moving disturb the environment, the environment changes, so that major diseases appear, like the bubonic plague, endemic probably in the eastern northeastern China region it spread all over the world. Those are the kinds of things that we can look forward to. Climate change is going to be a big determiner. It is another one of those things where you need global governance. All countries have to cooperate because everybody shares the same atmosphere. Not to mention the oceans, which are now filled with microplastics. The good news is that we have the technologies to make biodegradable plastics. It’s a field I’ve been very active in, which is synthetic biology. I call it constructive biology because you use the power of biology to make things that are environmentally friendly. It may be a little more expensive but this is nothing compared to the disaster that climate change is causing. CM: Together with COVID-19, we are suffering a misinformation pandemic. How can we tackle it? WH: That has to do with the nature of political man. People say Trump is not a good politician. He is and there have been many others like him, who understand something about human nature instinctively. They have a different sense of their environment’s 2082
psychological map and know how to manipulate it. Consider how a good artist does not just represent through their art but understands the wiring of our brains and has a sense of how to communicate with us based on the innate structuring of how we perceive things. Politicians have the same sense. This is not such a difficult task for them because we are mostly emotional – our emotions swamp our limited rationality and this determines that which we believe. We decide, emotionally, what is true and then construct a logical argument to support it. There are people who want power and they’ll use their understanding of this to manipulate us. And the only thing you can do is what we’ve tried in the US: build checks and balances. The people that put the Constitution together, they understood human nature. Only in retrospect will we see just how close we came to a dictatorship, or totalitarian government in the United States. There was effort there, which involved the use and misuse of a lot of information and, unfortunately, that ongoing effort got conflated with the pandemic. Any tool at hand is good when you’re in a battle. You can pick up a crowbar or a sword, whatever is there. It happened that the pandemic was there so it got picked up. CM: But it may be even more dangerous, since it is not just beliefs, but people’s lives that are at stake. WH: Twenty million Germans died in World War II, 30 million Russians died. Human life is not the primary concern of powerhungry people. It should be, but it isn’t. This article originally appeared in IE University’s Insights and is available online here: Viruses Not Only Kill People. They Kill Economies.
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Interview on Town Square with Ernie Manouse - The Year in COVID December 23, 2020 | Interview
This week Town Square reflects on the events that defined 2020 in a three-part special series. These memorable roundtable discussions feature some of our favorite guests in the past year to discuss the leading events that have shaped our lives. Town Square with Ernie Manouse airs at 3 p.m. CT. Tune in on 88.7FM, listen online or subscribe to the podcast. Join the discussion at 888-486-9677, questions@townsquaretalk.org or @townsquaretalk. The Year in COVID focuses on how a novel virus that began as a marketplace sickness became a global health crisis – and the worst in American history. What lessons have we learned as we enter the vaccination phase of the pandemic? This episode includes • Dr. William Haseltine, a renowned global health expert and president of ACCESS Health International • Dr. Catherine Troisi, infectious disease epidemiologist at UTHealth • Dr. Kirstin Matthews, Fellow in Science and Technology Policy at Rice University's Baker Institute. The photo gallery above contains the original captions to present a time capsule of our understanding, and progression, of COVID19. Town Square with Ernie Manouse is a gathering space for the community to come together and discuss the day's most important and pressing issues. This interview originally appeared in Houston Public Media and is available online here: Interview on Town Square with Ernie Manouse - The Year in COVID
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Interview on CBC’s Current: Even if new variant of COVID-19 isn't in North America, we might have made our own: expert December 23, 2020 | Interview
WILLIAM HASELTIN: Good morning. Laura Lynch: I'm wondering what your reaction is to to what we've been hearing about this new variant of COVID-19 in the United Kingdom. WH: Well, there are new variants popping up in parts of the world. Certainly this variant in U.K. is concerning for some of the reasons you just heard. There's a similar variant but independent variant in South Africa with many of the same characteristics. And what it's taught us is that this virus is far more capable of change than we had anticipated and that some of those changes are quite concerning from a public health point of view. It may be more transmissible. It appears to affect children more seriously, and it has some capabilities to evade at least some of our immune defences. Those are all very concerning and it would be very surprising if many more of these variants aren't already present, particularly in the United States, which is so heavily infested. LL: Yeah, I want to talk to you about that more in a second, but I just wonder if you could tell us about how what's known about how this mutation came to be. WH: Well, when you have a large number of people infected with viruses, the viruses try to adapt to that situation. And the way they do that is they create random changes. Each person may have several hundred trillions of viruses in their body during an infection, and each one of those viruses is slightly different from the other. It's what we've learned to, it's what we call machine intelligence, throwing a lot of random combinations to try to solve a problem. The problem this virus is trying to solve is how to get around in the human population and it seems to be doing it very successfully. Now, in particular, when you have some patients, for example, who 2085
are immunosuppressed and you give them convalescent antiserum, that is serum from people who have recovered, you are creating a condition almost ideal for viruses to become resistant to those antibodies because it turns out the convalescent antiserum doesn't completely play with the infection, it comes back more resistant. You can give more convalescent antiserum from a different patient and you're actually teaching the virus how to evade our natural immune responses. There's studies that show that it's occurring in real time if you do sequential sequencing of the virus in single patients. Well, that's probably happening not only to single patients, it's happening in an entire population and I think the more you look, the more you will find. LL: Is that why the virus seems to be, this new mutation seems to be spreading so fast because it's learned how to get around the defences so well? WH: It's learned to do two things, it's learned how to survive in an environment where the body is trying to suppress it. One way it can do better is to attach to cell surfaces more tightly. That has both the effect of allowing the virus to get around in the body, that's trying to stop it and get from one person to another more quickly and incidentally, into children who have less of a receptor. If it can combine more tightly to receptors, you don't need as much virus, you don't need as much receptors, and children have fewer receptors. And I think that is a consistent hypothesis of what this virus is doing, in addition to creating mutations that avoid the most prevalent antibodies that we make to protect ourselves. It's doing these two things that's a time. LL: I'm sure that a lot of people listening here are concerned about what you're having to say and I'm sure they're also thinking about the vaccine. We're anticipating some relief as the vaccines are rolling out. Will they work on this new variant of COVID? WH: You know, they will probably work partially, but we don't know that yet. They may work fully. They may work partially or in some cases for some variants, they may not work. You know, we're used to this kind of situation with the flu. We know that two things happen with flu vaccines. One, the virus can adapt and get around them, and two, that immunity to the flu vaccine doesn't last very long anyway because the antibodies fade. So it isn't that we haven't faced this situation before, it's that we just weren't anticipating 2086
having to face it with COVID. But I'm afraid it's looking more and more like we're going to have to be prepared to have a long battle with this virus, as we've had with the flu. LL: And will that mean that we will need new vaccines? WH: It'll mean we need variants of vaccines. Yes, it probably will. I think people are already thinking about it. A good thing is some of the types of vaccines — the messenger RNA vaccines — are ideally suited to be tailored to the current strains of virus. They can, the next batch of such vaccines that are made can be specifically tailored to what's being found. I think it means a lot of things. It means one, we have to do a lot more surveillance to really know what viruses are out there. Two, we have to be prepared to be flexible with our vaccine response. And three, we have to ramp up very significantly our efforts to find antiviral drugs. For example, for the flu, there is now a drug that if you're exposed to the flu, you can take and it reduces your chance of getting it from a family member by 80 percent. We need those drugs for this SARS-COV-2 as well. LL: We have under a minute left. So I just want to ask you why you are so certain that this mutation has arrived in the United States and presumably Canada as well. WH: You can't be certain until you find it. It would be extraordinarily unlikely that as many as 300,000 visitors from the UK per month over the last four months have not brought some of that here. But even if none of them brought it here, it's very likely that we have created our own home-grown variants, as they have done in South Africa. We have the world's largest population of infected people. We have many people under various kinds of treatments. It would be astounding if we didn't have similar variants here. We just haven't looked. That's something else we have to do. We have to ramp up our sequencing to see what's there. We're blind to what's happening in our own country. LL: All right. Thank you for your time, sir. WH: You're welcome. LL: William Haseltine is a former Harvard Medical School professor and president of the global health think tank ACCESS Health International and we reached him in Roxbury, Connecticut. Well the CBC News is coming up next. Then, we head to a tiny village in Italy where one family has been forging bells for a thousand
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years and is determined to keep the tradition alive. I'm Laura Lynch and you're listening to The Current. This interview originally appeared in Canada Broadcasting Corporation and is available online here: Interview on CBC’s Current: Even if new variant of COVID-19 isn't in North America, we might have made our own: expert
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Interview on CNN with Bianna Golodryga: To Discuss U.S. Hitting Record COVID Hospitalizations December 28, 2020 | Interview
Bianna Golodryga (BG): Breaking news, the US hitting record coronavirus hospitalizations tonight. It is now the twenty seventh consecutive day that hospitalizations have been above one hundred thousand. It comes as millions of Americans are traveling during the holidays, causing growing concern that we could be heading for a surge on top of the one we are currently in. Out front tonight, William Haseltine, groundbreaking HIV and AIDS researcher and former professor at the Harvard Medical School and the School of Public Health, and Dr. Jonathan Reiner, an adviser to the White House medical team under President George W. Bush. Welcome both of you. Professor Haseltine, let’s begin with you. The TSA says nearly 1.3 million people flew on Sunday alone. That’s a record during the pandemic. Of course, this comes amid a new hospitalization record tonight in a month that has been the deadliest on record. With so many people not staying home right now, do you think it could get even worse in the coming weeks? William Haseltine (WH): The short answer to your question is yes, it is going to get worse. It is not a question. It definitely is going to get worse. But there is a little bit of a half glass full here, and that is about half as many people are traveling this Christmas as last Christmas. About half the people have gotten the message. Unfortunately, the other half has not. Not only will they become infected. Not all of them but some of them. They will infect their friends and that infection will spread even more widely in the community. This is not a good time to travel. BG: Yeah, fewer people are traveling this year than last year. But still a record number just traveled over this weekend. And, of course, we expect more travel over the next week for New Year’s. Dr. Reiner, HHS says the number of patients in ICU with COVID 2089
was sixteen percent in late September. Now it is nearing around forty percent. We know it is particularly bad in California where 75 army and air force medical personnel have been sent to help with COVID response. The CEO of one hospital in Los Angeles saying that they may have to begin rationing care, if you can believe that. If the situation does not improve in this country, will we start seeing many more hospitals having these same types of conversations? Jonathan Reiner (JR): Absolutely, Bianna. I have had conversations with families, hundreds or even thousands of times, when a loved one gets acutely ill and we try and decide what the family would want. Would they want aggressive treatment? But what is going to happen in California when you run out of capacity of physicians and bioethicists in these hospitals will need to decide which patients are salvageable, potentially salvageable, and which patients are not. So, the final decision in many instances may not be up to the family. I have never practiced in a situation where that occurs, but we face that when we run out of resources. If you do not have respirators, you do not have nurses to care for patients, you do not have ICU beds, you will have to have these terrible discussions with families, which is why people need to stay home and when they go out they need to wear a mask. BG: And a reminder to just think of the doctors and nurses that are experiencing this surge and these types of conversations. Not the first time, not the second time. This is the third time now for so many of them. Professor Haseltine, the CDC order requiring travelers from the UK to provide a negative COVID test within 72 hours of boarding their flight went into effect today. Of course, it is in response to the U.K.’s more transmissible virus strain. But CDC researchers say that showing a negative test three days before travel only reduces spread by five to nine percent. So, will this policy make any meaningful difference? WH: The difference it is going to make is minimal. Most countries have banned travel from the U.K. altogether. That will be, of course, much more effective. The issue is how much of that virus is already here. We now know that some countries have had the virus since November. It would be very surprising if the U.S. does not have it already. But we need to increase our vigilance and it is just another argument for why you stay home. I have just been reading some of the British thoughts on what this means for them, 2090
and it means going beyond where they have ever gone before in terms of control using public health measures while doing maximum acceleration on vaccines. That is what I would recommend for our country at this time. Unfortunately, we have an administration that is ignoring this problem. If Rome had invented golf, Nero would be on the links while Rome burned. BG: Really interesting to hear you say that. Dr. Reiner, speaking of the incoming administration, Vice President-Elect Harris and her husband will be getting their vaccines tomorrow, we know. It follows both Vice President Pence and President-Elect Biden receiving theirs. The current President Trump still has not been vaccinated. Are you concerned that that is adding to the vaccine hesitancy that we are seeing in this country, particularly among Republicans? And let’s say he is going to wait to get vaccinated because he did have the coronavirus just recently. Would it be responsible for him to at least come out and say something publicly about that? JR: Absolutely, Bianna. He is basically past the point where there should be any interaction between the medicines he received and the new vaccine. The president should come out and get vaccinated in public. The Kaiser Family Foundation has shown that there is a huge split amongst Democrats and Republicans with eighty six percent of people who identify as Democrats saying that they will likely get the vaccine but only fifty six percent of Republicans. It would mean a tremendous amount for the president to come out, get vaccinated in public, and tell the folks that really adore him, his supporters, tell them that this vaccine is a major advance, he feels that it is safe and he urges all his supporters to get it. It is necessary. It will save lives. He should do it tomorrow. BG: Yeah. And it is a way for him to get credit and give himself credit for Operation Warp Speed as well. It is quite surprising why he is not doing that. Professor Haseltine, Dr. Reiner, thank you so much for joining us tonight. We appreciate it.
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Interview on ‘MSNBC Live’ with Lindsey Reiser To Discuss Coronavirus Vaccine December 29, 2020 | Interview
Lindsey Reiser (LR): Any moment now Vice President-elect Kamala Harris is set to get her first round of the COVID-19 vaccine live on television. Mike Memoli is covering the Biden transition in Delaware. Also with me, Dr. William Haseltine is back. He is an infectious disease expert, and Dr. Mario Ramirez, an emergency physician and managing director of Opportunity Labs. Mike, like I said, this is happening any minute. We are expecting to see her go through the doors. If I interrupt you, you will have to forgive me. But first off, talk to me about the decision to do this on live TV. Mike Memoli (MM): Well, of course Lindsey, we saw the president-elect get his vaccine here in Wilmington last week. An important moment to be sure. An important signal to be sent to the country about their confidence in the efficacy of this vaccine and encouraging the public to get it as well. But in the case of the vice president elect, an even more important moment, perhaps, when you consider what we have talked about since, of course, the historic election of Kamala Harris as vice president of the United States. The first woman, the first person of color in that role. When you talk about the concerns about this vaccine and whether or not people of color who our polling indicates less likely to be interested in getting this vaccine, of course, given the historic concerns about communities of color and how they have been treated in the medical community, perhaps an even more important signal to see the president-elect getting this vaccine today. And an important note as well about exactly where this is happening. It is at United Medical Center in Washington D.C. This is not the vice president elect’s hometown hospital. This is in the southeast neighborhoods of Washington D.C. This is a significant minority population there. The biggest concentration of African Americans in the District of Colombia, and when you talk about the Biden team has been talking about throughout the campaign which is really the inequities of the 2092
COVID impact on communities of color here that we are seeing disproportionately higher rates of infection. Higher death rates as well. So, it is an important signal for the vice president-elect herself to get the vaccine. It is going to be administered by a Guyanese immigrant to this country as well. A note about the vaccine as well. We know there are several different types of vaccines available to the public. She is getting the Moderna vaccine. Now, Biden last week when he got his vaccination, received the Pfizer vaccine. We also would note, Dr. Fauci, when he got his vaccine last week, he got the Moderna vaccine. This is the background that we have been given by the vice president-elect’s team as we expect to see her come through the doors at any minute. Again, important to send this message to the public about her confidence, and we expect her to make some brief remarks after she gets that shot in the arm. LR: United Medical Center is the only public hospital in D.C. Dr. Ramirez, I want to bring you in on that, really talking about the significance, not only of vice president elect doing this as the first black and Asian American female vice president but also the location at this particular hospital in D.C. Mario Ramirez (MR): Well, I think you are right, Lindsey. I think, and I will say as a Mexican American, I cannot presume to speak for all minority groups but I think as a whole what we see is the barriers to vaccination are twofold. One is certainly a trust deficit. And that is an issue that has been well documented and there is no question having figure heads like the vice president elect be vaccinated in a very public space is helpful. But I think we cannot discount the reason that people say that politics is local. It is because trust is very hard to build over time and folks in local communities build that through their church leaders, through their community leaders and civic organizations. When folks from minorities look out and say, well, who do I know that is being vaccinated. I am not necessarily certain they only look to folks like the vice president elect. They look to their local church leaders and folks who they know personally that have bought into this. Getting this, sort of, buy in and outreach from leaders like that is critically important. But the other issue that I think this brings up is a question of access and that is one of the reasons I think the location for the vice president elect’s administration is really interesting. I live here in D.C. So, the choice of United Hospital as a critical access point is great because it is very 2093
hard for folks from minority groups like this who sometimes work two and three jobs to get the time off to go and get vaccinated once or sometimes even twice for some of these different formulations. And so, the issue of access is just as important as the trust deficit. LR: Doctor Haseltine, earlier in the show we were talking about the rollout being a little bit slower, not meeting certain goals. We have seen vice president elect Biden get the Pfizer vaccine. We have seen Dr. Fauci get the Moderna vaccine, Vice President Mike Pence get the Pfizer vaccine. Now we are going to see Vice President elect Kamala Harris getting it. What are your thoughts on seeing these leaders coming out and saying, look, we believe this is so safe that we are going to do this on live television? William Haseltine (WH): I think it is really important. It is a big issue. People need to know leaders are willing to take these vaccines. I think it is also, as emphasized by Dr. Ramirez, it is important for local leaders to take the same role. One of the questions you asked earlier on is, what can this new administration do that can speed up the end of the pandemic? I think there are two things, aside from most of the obvious things people have talked about. One is the focus on universal testing that people can do at home, that is and free, that is frequent. I think that is something they should do all the ground to hit the ground running so we in this country can know who is contagious and they can be encouraged to stay home. The second thing is, controlling the pandemic in the United States is not enough. We have to participate on the world stage. There is nobody better prepared to do that than our president elect. He knows the world extremely well for many years and I think that being open, not only to the American vaccines, the vaccines made anywhere in the world that work that are stable, that can be used, that are cheap, that are accessible are going to be really important in protecting us by protecting the rest of the world. The United States really should play a leadership role and I think with this new president, we are going to be in a good position to do that. So, this is an important step for our country, but we have to think of the world because we are not alone in this world. What happens elsewhere happens here. LR: Mike Memoli, I want to bring you in again and ask why Kamala Harris was not inoculated at the same time last week president elect Biden was? Why stagger them?
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MM: Yeah, very interesting question and it is one we posed to the transition team when they announced both would getting the vaccine. They sited the guidance of their own medical officials. Of course, Biden has his own COVID-19 advisory board. He is going to be meeting with them virtually today here in Wilmington and said that is the guidance they were getting. The speculation, of course, was perhaps for continuity of government reasons, you want to make sure we have heard some cases very small about reactions to the vaccine that they wanted to see. The president elect separate from a week by the vice president elect getting her vaccine just to make sure that there were no adverse effects, of course, to it. The Biden team only simply saying this is the best advice they got from their medical experts about doing it. The other impact that this has, it is a second week of stories, a second week of coverage about getting the vaccines and one of the things we expect to hear from the president elect when he does speak later this afternoon is frankly some criticism of the Trump Administration, concern about the slow pace of distribution of the vaccine so far. According to the CDC.’s own data, we have more than 11 million vaccines already shipped and distributed and available throughout this country, but so far only 2.1 million Americans by the CDC’s own data have received the vaccine. And we are seeing, obviously, local officials express concern why they have not actually seen the vaccines available to them yet. So, part of I think what the president elect’s message today is going to be is trying to really amplify the public’s interest in getting a vaccine. A lot of people probably spent time over the last few days around holiday virtual or in person conversations about will you get the vaccine, are you confident. And I think that is part of another reason you stagger these two vaccinations is to help reinforce the idea, just like you have a double dose of the vaccine to make sure it is effective, spread out by three to four weeks, you have a double dose of top officials getting the vaccination to help reinforce the message of the previous week, which is they believe it’s safe, effective and should be something all Americans, once they have the ability to get the vaccine, do get it. LR: Dr. Ramirez, let’s have you respond to that. President elect Biden is going to attack the Trump administration for the slow pace of the vaccinations later today. Is that a valid criticism?
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MR: You know, it is hard to say, Lindsey. I think it is clear that we all wish this was going faster. There are certainly difficulties with getting a new vaccine program up and running and so I think that is certainly part of this. But the other thing I think a lot of us wish was going better was public messaging around the vaccine. You know, there is a lot of vaccine hesitancy several months ago during the end of the presidential campaign season, but what would be really helpful at this point is if we were seeing commercials and public messaging to the public about getting the vaccine and we just have not seen that yet and part of that is the highly fragmented nature of this where the federal government is essentially rolling this out to the states and giving them responsibility for rolling this out. But the other part of that, too, is just the very limited supply we had. So, you have to calibrate what is availability of the vaccine, you know, against developing an adequate public interest and we have not gotten that quite right yet, but my hope is that we can speed this up over the next few weeks. LR: Dr. Haseltine, what are your opinions whether we should see President Trump get the vaccine. Dr. Fauci recommended it, but we also know that President Trump contracted and recovered from COVID-19 over the summer. Still unclear how long the antibodies work. Do you think he should also publicly get the vaccine? WH: My opinion is he should but I do not think it will weigh too much in his mind. The general recommendation of the CDC and health experts that looked into the issue is if you have been infected with COVID-19 and you have recovered, you should get the vaccine. We know that some people are reinfected, and there is also the question will the vaccine stop the transmission of the virus. LR: Dr. Haseltine, we have to interrupt you because it looks like Vice President Kamala Harris and her husband Doug Emhoff walking in. Let’s watch.
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Interview on CNN’s ‘The Lead With Jake Tapper’ To Discuss COVID December 29, 2020 | Interview
Jake Tapper (JT): Joining me now William Haseltine. He is the chair and president at ACCESS Health International as well as a former professor of Harvard Medical School. Thank you for joining us. This month has been the deadliest for the pandemic so far. COVID hospitalizations are currently at a record high. This month has already been the deadliest of the pandemic so far. Do you suspect that hospitals will be dealing with another major surge in roughly two to three weeks following the December highs? How bad do you expect it to get next month? William Haseltine (WH): We cannot tell how bad, but we can tell it’s going to be bad, and it will be worse. What we have experienced is maybe a hump and we are looking at a mountain. A lot of people are traveling. I tell you the good news is about half as many people are traveling. The rest are staying home. That is good but it is not enough. Those that are traveling are exposing themselves to infection. I calculate there is about ten thousand people who were capable of spreading the virus on those planes, maybe twenty thousand as you travel. That is a lot of people spreading the virus. And when you go to meet with your relatives, you may carry that virus with you. So, it is a very serious situation. And hospitals are now at the brink of turning away patients. JT: Health experts warn, as you note there, that this record number of COVID hospitalizations could lead to more widespread rationing. As you know, people are being turned away. There are only so many nurses and respirators and general medical care. What would this actually look like if this starts happening even more, and what would that mean for anyone needing care, not just COVID patients? WH: Well, first of all, for COVID patients, we would move to something called crisis standards of care. That is basically a judgment of a panel to determine how many years of life you would have if 2097
we saved you. And if it is not many, like you’re old, my age, perhaps, if you have some comorbidity, like you have serious diabetes, they are not going to consider you as a good prospect, even if you need lifesaving treatment, they will send you home without treatment. That is what crisis standards of care is. We are, in California and some other places, very close to that. It is not because you cannot build facilities, it is because there is not people to staff them. You cannot bring them from other parts of the country because the whole country has a problem. You cannot bring them in from abroad because many other countries have problems. We are facing a really critical time, a time I don’t think, in my memory we have ever had, and perhaps you would have to go back maybe even to the great pandemic of 1918 or before. It is like a battlefield situation where too many soldiers are wounded to save all that could be saved. JT: It is the death panels we were warned about with Obamacare, but in reality, not just fantasy. So far 2.1 million Americans have been vaccinated in the U.S. And we just learned nineteen million doses have been allocated. The Trump Administration said that the goal was for twenty million Americans to be vaccinated by the end of the year, which is just in a few days. Was that ever a realistic number, and why do you think we are falling so short of that goal? What can be done to speed up the process? WH: Well, first of all, it is really the gang that could not shoot straight that is running the show in Washington, at least out of the administration. We have very good agencies, but they have been hampered and hamstrung. And why would we expect them to do better than they did with testing, better than they did with rolling out various medications than they have with vaccination? What they have done is basically punted and said, hey, it’s not us. We’re going to get it to the states and then it is up to the states to do everything. Without the money, without the training, without the preparation, how can that be? I was warning and other people were warning that this situation would arise. It is even a little worse than that, Jake, because once the vaccines get there, it can really be up to the local community who gets the vaccine. Yes, the government can say this is the group that should get it, but it is on the ground and there is some great inequities already being discovered in who is getting it, how they are getting it and where they are getting it. 2098
JT: Speaking of inequities, members of Congress are getting it right now. Thank you for joining me, we appreciate it.
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Interview with CNN’s Don Lemon To Discuss COVID Vaccination December 30, 2020 | Interview
Don Lemon (DL): The year is almost over and it is clear the Trump administration is not going to reach their goal of twenty million vaccinations by January. Of the 12.4 million doses the CDC says have been delivered, only 2.7 million have been administered. That is not good enough. Today we set a record for hospitalizations and according to a new forecast from the CDC, up to 424,000 people could die from the coronavirus by January 23rd. There have been over 341,000 total deaths over the pandemic so far. According to this projection, we could be looking at over 82,000 additional lives lost in the next three weeks or so. So, I want you to think about that. More than 82,000, 82,000. We cannot afford slow starts. We need to get shots into arms and we need to do it right now. Joining me now is William Haseltine, former professor at Harvard Medical School and chairman and president of ACCESS Health International, and CNN national security analyst, Juliette Kayyem. Good to see both of you. Thank you so much for joining. Professor, I have to start by getting your reaction to the CDC’s new projection, 424,000 dead by January 23rd. That is about 80,000 additional deaths in three weeks. The numbers are shocking, hard to comprehend. I think it is hard to comprehend the loss of life because when you say it with so many, right, I do not think people can really register because it is so many deaths. William Haseltine (WH): It is true. It is a real tragedy. It is an American tragedy. It did not need to happen. It happened because of inattention, denial. And now we are in a real mess. We are in the winter. People want to celebrate the new year. They are traveling. It is all the things they should not do. In addition to that, there is a new variant, at least one and probably more, that are increasing the rate of transmission. This thing is accelerating, not decelerating. We need to take a whole series of actions. Vaccines are the long-term answer, but they are not the short term answer. They are not going 2100
to save us in the next two to three months. What will save us in the next two to three months is government doing its job to help people stay safe. DL: I got to tell you, when you talked about that variant, and we will get back to it at warp speed, but this is the first time I have had the COVID test where I have actually been really, really worried because of that variant. I got the results back. I just got it tonight. It was negative. But I was like, oh, man. What if? Because it is just people are, I think people are even more afraid or more nervous than at the beginning of the pandemic. Is there something wrong with me, professor? WH: No. It is very much more likely that people can get infected. Fewer viruses, shorter time and children. And this virus, and a similar one from South Africa, is not only more infectious, it is infecting children and it is making more children ill because it can get into children who have lower numbers of receptors than adults do. This virus sticks more tightly to those receptors, so you need fewer. The other thing if you look at these viruses carefully, they are much more tricky than we had thought. We had thought they were relatively stable. It is like saying, yeah, I know that enemy. It turns out this enemy can change. So, we do not know the enemy as much as we thought we did. We need to know it more and we have to really surveil it and we have to be prepared to react to changes. DL: Yeah. So, Juliette, Operation Warp Speed, great, this is incredible. It was a great job getting it out after the president was saying, oh, it is not a big deal and I cannot wear a mask. Operation Warp Speed did get the vaccine out fast. But this mass vaccination has been dumped on the states to deal with. We know that is hard to do. But you say that it can be fixed. What does a Biden team need to do because it is abundantly clear that the Trump folks are not going to do it? Juliette Kayyem (JK): I want to begin with one factor, is that even before Biden is president things will look better. I have confidence in that because I have seen a lot of the state plans but also because this is the nature of a big logistics campaign. It starts off clunky. Data management is really complicated. You know, person X is not talking to person Y. It is hard to get to rural areas. It is the holidays. I know we want it fast, but that does matter. That will start to smooth out. When president Biden comes in, two things that the 2101
Trump White House did not do throughout COVID is consistent with testing and surveillance to now. You set a floor for the states. In other words, what is the minimum they need to do? Because states are different, so you want to give them some leeway and then you provide the resources to make sure they have the funding and that you invoke the Defense Production Act or whatever to make sure they have the supplies coming. That can be done on day one. It is still going to be a little bit clunky because it will take a while. But I am still — you know, I know it feels like the sky is falling, but I have been through this before. It takes a while for things to, not something like this, but H1N1. It takes a while for systems to get into place. We will have a course correction for January 20th. I am still holding, and so is Dr. Fauci, to an idea we will start to get to the general population in April/May. Anyone who promised otherwise was not telling the truth, and that is true of this White House. And that we will feel general population herd immunity in the sense that we will feel like the world is different by early to mid-summer. I am still consistent with those numbers. Look, a million vaccinations a day seems like a lot today. If CVS and Walgreens were doing them, there is 20,000 stores in the United States, they only have to do fifty shots a day. So that is doable, right? But think about all the other places doing shots. Hope springs eternal at the end of 2020. So, these things will get fixed. More money, more resources, more support for the states. And I think we are going to have a president who does not view this as an ego thing. I think that will make a meaningful difference. DL: I hope you are right because it feels like the nation is in my old VW Beetle when I was in high school. You have this momentum and then you get to the top of the hill and you are like whoah. Feels like we are running out of power and we are close to the top, right? We just need to go a little further. I hope you are right. JK: You have grown up, Don. You own a fancy car now. Takes a while for it to start. DL: Yeah, a subway in New York City. Thank you. And we lost professor and his shot. Thank you. Happy New Year to you.
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Interview on CNN’s ‘New Day’ To Discuss COVID December 30. 2020 | Interview
Alisyn Camerota (AC): Joining us now is William Haseltine. He is the chair and president of ACCESS Health International and a former professor at Harvard Medical School. Professor, what disturbing news we wake up to this morning. Let me just start with the variant because that is the news that everyone is waking up to. So, a man in Colorado, he is in his 20s. No travel history that we know of. He has been identified as having the first case of that U.K. COVID variant that is more transmissible. What do we need to know? William Haseltine (WH): Well, what we now know is that the virus is here, like it is in so many other countries. We know the virus is much more transmissible, and we know we have got to take more serious measures to control what is inevitably going to be an increased rate of infection in our population. Male Reporter: You are saying that these measures should include a lockdown. The U.K. shut down virtually completion in response to this variant. We are seeing other countries take steps, ban international travel, et cetera. What specific steps do you believe are now necessary in this country? WH: Well, I would take a good look at France. France has this variant. France had a rate of infection higher than the United States and in three weeks brought it down by twenty times, saving thousands and thousands of lives. We could save those same lives here if we took the same very strict measures, including travel bans, for example, not allowing over a million Americans to travel by air and many more by train and bus. We could put this thing back in the bottle very, very quickly, if we did that. It would be, I think, highly controversial, but it is what we need to do. We now know this variant is here. And I suspect we have our own homegrown variants that are doing the same thing. This virus is much trickier than anyone said it was. It was able to evade our immune system in 2103
convalescent anti-serum. It is a very tricky virus and we have got to understand what we need to do to save lives. AC: A few more things that we know about this. This young man worked at a nursing home in a very rural area in Colorado. There is a second suspected case, another, I believe a young man, who also works at that nursing home, but that has not yet been confirmed. We will report it as soon as it is confirmed. And so, the idea that neither of them have a travel history, as far as we know, does that tell us that there is already community spread happening in that county in Colorado? WH: It does. But we do not need even that to know that we are in deep trouble. You are citing very serious numbers, over 3,700 people dying yesterday. That number could easily go up to 5,000 to 7,000 people a day if we are not careful. This is a very dire situation as all of our public health officials are warning us. It is time to take much more serious measures. Now, the good news is that there is help on the way. We can see vaccines around the world being improved. The British vaccine, the Chinese vaccines, two different versions. These are stable vaccines. They work pretty well. And I think it is time to consider importation of many of these vaccines to bolster our own efforts. The sooner we vaccinate most people in this country, the better off we will be. Relying on our high tech vaccines rather than the traditional, more traditional measures of vaccines may have been a mistake. We should have many more doses available that are easy to deliver like the rest of the world is getting. And it is time to open our borders to vaccines from other countries. Male Reporter: Well, amazing turn, right, and the question is would the U.S. share these vaccines with the world, now may need help. Tell us about this vaccine rollout effort because it is proceeding far more slowly than promised. We were supposed to have twenty million people vaccinated by the end of this month. That is tomorrow. It is not going to happen. It’s 2.1 million, the latest figures right now. Has that exposed a fundamental issue with the rollout plan and with this country’s ability to get this vaccine out to the maximum number of people quickly? WH: This country has the ability to do almost anything. The fact that we are not doing it is a fault of this administration. They blame it on the states, but they have not given the states the money and the resources they need to do it. States do not have unlimited 2104
borrowing capacity like the federal government does. So, this is not an American problem. This is an administration problem that has resulted in a very serious situation. The other thing we did is put all of our eggs in a high-tech basket for vaccines, not long-term, proven technology which other countries have used, particularly the ones in Asia. And so, I am hopeful that when we think about how we can accelerate protection of our own people, it is not America giving vaccines to other people, we should be sourcing them wherever we can get them where they are shown to be approved and to work and to be relatively safe. AC: Professor, can I ask you a couple of questions about that? You are referring to the messenger RNA. The lingo we have all learned over the past several months. And so, the U.S invested in that because it showed great success rates, right, I mean, ninety-plus percent. But what are you saying that we overlooked? WH: We overlooked the fact that you can make a vaccine by just growing the virus and killing it, just what we did for the polio virus in the 1950s. Many countries have invested in that technology and those vaccines are now showing to be effective, at least eighty to ninety percent effective vaccines. Now, all of those numbers are a little bit soft. They may be less effective than that, even the American vaccines. But what is clear is these are much more robust technologies. You can make a lot more of the vaccine quickly. It is much more stable. And it’s going to at least 1/10, maybe 1/20th of the virus. AC: That sounds so simple. Why didn’t we do that? WH: It is amazing to me that we did not. It was a major oversight. Just like we did not put out very cheap tests. We should have fifty cent or twenty five cents tests available for everybody to do at home. We have made major mistakes in the way that we have approached this. We have looked at a high tech solution that is amazing. But let us not pat ourselves on the back when the rest of the world will be getting an effective vaccine at 1/10th to 1/20th the price and a lot more of it. Male Reporter: Can I let me ask you before you go just quickly. You are talking about major course corrections here to solve this problem. Distribution, a new plan, but also possibly distributing different vaccines than the ones this country is focused on. Twenty one days, new president, how quickly can a new — by the way, the 2105
current president seems to have checked out of this pandemic. How quickly can the new administration make those necessary course corrections? WH: I think they can make them pretty quickly. It is not too hard to make an order for a vaccine. And it is not too hard to get these stable vaccines imported. It will take courage to do that, because we have got so much invested, tens of millions of dollars invested in our own, but if our own cannot meet the need, which it does not seem it is going to be able to. Look at a country like England, they say they are going to vaccinate everyone in their country by March, maybe before. Why them, not us. AC: William Haseltine, thank you very much, for all of your sobering take on this morning and all of your expertise. We really appreciate talking to you. WH: You are welcome, thank you.
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Interview on ‘MSNBC Live’ to Discuss COVID Vaccinations Host: Yasmin Vossoughian, John Torres and William Haseltine December 31. 2020 | Interview
Yasmin Vossoughian (YV): Joining us now, NBC news medical correspondent Dr. John Torres and infectious disease expert Dr. William Haseltine. He is also the author of My Lifelong Fight Against Disease. Welcome to you both, guys. Happy New Year’s Eve. Thank you for joining me today. Dr. Torres, I am going to start with you on this one. Those are some are grim numbers I talked about. You have over three thousand folks dying, yet again, from the coronavirus and all predictions are pointing to the fact this thing is going to get worse. Now we have confirmation of this new variant that came yesterday in Colorado. Now in California as well. What are we to make of this and how worried should Americans be seeing that at this point, the reports are it is seventy percent more contagious than the current coronavirus we are dealing with. John Torres (JT): And Yasmin, you are right. Those numbers are going even higher because of what has happened over the Christmas and New Year’s holidays where people are getting together. What we are seeing now are the after effects of the Thanksgiving break where we knew those numbers would come up and we are coinciding with these holidays. We think those numbers are going to go even higher and people have called January the darkest period of this pandemic looking forward here. Now we have this variant here. Just so people understand, a variant means the strain has mutated, the strain has changed, this coronavirus strain, which happens with viruses in general. This one has changed and looks like it is making it more infectious. People are going to be able to catch it easier and spread it more easily than they were the old strains of coronavirus. But luckily, if there is any luck in this, it does not seem to be any more deadly, does not seem to cause any more complications. However, the fact that it can spread more means we 2107
will have higher numbers of cases, higher numbers of deaths because of the sheer numbers of cases out there. However, as far as people being worried about it, I think they just need to be worried overall about coronavirus in general because this variant strain like the other strains, you can be protected against it by using those measures we always talk about. Wearing a mask, social distancing, washing your hands. It is the same old story, Yasmin. YV: Dr. Haseltine, I want to talk about this new piece you have out and it is titled There Will Be No Quick COVID Fix. You have a lot of amazing stuff in there. I have to say, I was shaking my head through most of it thinking, wow, I cannot believe this is what we are dealing with. One part of it I want to read for folks, despite its virulence, many simply assume that the pandemic will end some time in the year 2021. But such hopes are misplaced. Talk to us about this. William Haseltine (WH): Well, we just heard how bad the infection is. This is not just in the United States. It is all over the world. And we are going to have a better 2021 than we did 2020. We are going to have vaccines, better drugs. We will have fast tests. We will have a better president. All that is good news. It does not mean it is going away. One thing that we have now learned, and we should have known, is that these viruses adapt. If there is no resistance, a virus does not have to change and that has what has basically happened for the first part of the pandemic. Now the virus is running into people who have already been infected. It is running into people being treated with convalescent serum and it is adapting, and adapting pretty fast. Some of the ways it is adapting, particularly south African strain, are really dramatic. Big chunks have changed all of a sudden. So, we know this story before. We know it from the flu. I think we are going to have to start thinking of COVID like we think of the flu. It does not mean it is hopeless. It does not mean it is end of our world as we know it. It just means we have to keep up a steady fight. The other thing I would like people to think about is, science will save us, but it is sad it had to come to that. It is good that we have our science, but our government has not done what other governments have done. Even today our government is not doing what it needs to do. We ourselves are not doing what we need to do. Science will come to our rescue and put this thing in a
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manageable place. It may not eliminate it, but it will put it in a manageable place, but we can help and we should help. YV: It is interesting you say we are going to have to start to think of this thing as the flu. That is pretty difficult considering some of the numbers we have seen, the death rates of this in comparison to the flu. I understand your meaning here, but if not 2021, when we can see this thing, I guess, nipped in the bud, right, to get rid of coronavirus once and for all, when can we expect an end to this pandemic or do you think this will never end and we are going to have to live with this? WH: I think we are very likely going to have to live with this like we live with the flu. The flu we know how to handle. When the flu first arrived, it was worse than this. We now handle it. We can do this. And science is way more advanced than it was. But remember, this is all over the world. We may control it here. Parts of the world have already controlled it. That does not mean that it is going to go away all together. These viruses, I think, are going to stay. There are other coronaviruses that come back every year and give us our colds. One-third of all our colds are these things coming back year after year after year. That is what we have to look for. Not these conditions. I do not want anybody to think that we are going to be anywhere as bad off as we are. But this is going to be another life-long fight. YV: You write in your piece and I recommend everybody, I tweeted it out. I recommend everybody go to my Twitter and read this piece. But you write at one point, we are at war with the virus. Few doubt the importance of personal liberty, but this is a time we need to forgo certain conveniences for the sake of those around us. Dr. Jon Torres, Dr. William Haseltine, thank you both and Happy New Year’s. Dr. Anthony Fauci will join Andrea Mitchell to talk about the latest on the vaccine rollout later today.
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January 2021
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Interview with Bloomberg Radio January 5, 2021 | Interview
Dr. William Haseltine, Chairman and President of Access Health International, provides a coronavirus and vaccine update. Bloomberg News Legal Reporter David Yaffe-Bellany talks about the story “After Trump's Pardons Bonanza, Reform Will be Harder Than It Looks.” Bloomberg Government Congressional Reporter Emily Wilkins and Bloomberg News National Political Correspondent Gregory Korte walk through the Georgia runoff elections for the U.S. Senate. And we Drive to the Close with David Dietze, Managing Principal and Senior Portfolio Strategist at Peapack Private Wealth Management. Hosts: Carol Massar and Tim Stenovec. Producer: Doni Holloway. This interview originally appeared in Bloomberg Radio and is available online here: Interview with Bloomberg Radio
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Interview on CNN’s ‘New Day’ Alliyson Camerota : Discuss Record Number of U.S. COVID Deaths January 6, 2021 | Interview
Alisyn Camerota (AC): Developing this morning, the United States again shattering records for deaths and hospitalizations from COVID. Three thousand seven hundred seventy five American deaths reported yesterday. This morning more than 131,000 Americans are hospitalized. How about those vaccines? The Trump Administration promised more than twenty million Americans would be vaccinated by now. We are very far away from the projection. Joining us now is William Haseltine. He is the chair of ACCESS Health International and a former professor at Harvard School of Public Health. Professor, great to see you this morning. Can we just start there, that something has gone wrong with the vaccinations? The projections from all of our top health officials was that at least twenty million Americans would be vaccinated. That was supposed to be at the end of December. We are now in the first week of January and we are at 4.8 million Americans. We talked to Monsef Slaoui, the chief advisor to Operation Warp Speed, this week and he basically admitted there’s no one spearheading this. Every state, every CVS, every local public health department has to figure this out on their own and they are not. William Haseltine (WH): Thanks for bringing that up. That is a systemic problem we have had since the beginning of the pandemic. You cited some pretty horrifying numbers at the beginning of your comment. Those are a direct result of the lack of coordination from our highest administration officials, the president on down. It has been a terrible situation where essentially they made a political decision to punt the hard stuff to the states and keep what they thought would be the good stuff for themselves. What turns out to be the good stuff for them is not good and what is the bad stuff is really bad for us. That means the hard work and organization 2112
that was needed from the very beginning has not been done even to this very day. It was totally predictable. When I saw and read those plans in August and October and November of what they were planning for the vaccine rollout, it looked a lot like what they did for the testing. Let the states do it. Let the communities do it. Let the local townships do it. That is a recipe for disaster. They do not have the resources to do it. They have all the will to do it, but they do not have the organization and the resources to do it. That has been the problem from the beginning and it is going to continue to be a problem until we get new leadership that puts the power of the federal government at the service of the people. John Berman (JB): Professor, as you noted, we read you those hospitalization figures and the US now at record hospitalizations again, more than 130,000 people hospitalized. A big jump overnight. Three thousand more people in the hospital after a big jump the day before that. Why? What is the proximate cause? Why are we seeing more and more people getting so sick they need to go to the hospital now? WH: Well, one of the reasons is more people are infected. A lot more people are infected. That is the proximate cause. The second question is why are they infected? They are infected because they are not observing the control measures that everyone has recommended, and there is a second possibility in some areas where there are control measures being at least partially implemented is there are new virus strains that are more transmissible. What does that mean? It means lower numbers of virus, shorter exposures can infect you and it also has a very serious implication for children and for our schools because the virus can latch on the small amount of receptors that are in children. We are seeing an increased ratio of children to adults being infected. I am afraid that may translate to increased numbers of disease in children as well. That is what seems to be happening in some parts of the world and possibly in California now. AC: Obviously there is a lot of fatigue with the virus. Then there are the people who never thought any of the protective measures were worth doing to begin with. Just yesterday there was this big Washington, D.C., event, pro Trump supporters and one of the speakers encouraged the crowds to engage in life threatening events.
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I mean, you do not often see leaders asking people to do something publicly really risky, but this one did and so let’s watch this moment. Speaker: Turn to the person next to you and give them a hug. Someone you don’t know. Go hug somebody. Go ahead, spread it out. Mass spreader. It is a mass spreader event. It is a mass spreader event. It is a mass spreader event. There you go, hug it out. AC: So chilling to hear a leader asking people to take their lives in their hand. WH: Well, it is not just their lives in their hands. It is their neighbors lives, it is their children’s lives, it is their community lives, it is the nation’s lives, it is the world lives they are taking it into their hands. The more people who get it, the more dangerous this virus becomes. This virus is changing much faster than people anticipated. It is adapting to what we are doing. It is learning to get around better and it may be getting to learn how to get around our immune defenses, natural immune defenses. This is really, really dangerous. It is exactly equivalent to shouting fire in a crowded room. That is what we learned in our civics class you cannot do. Well, you just heard someone do it. JB: Unbelievable scene right now in light of where we are with record hospitalizations, record deaths. Professor, thanks so much for being with us. Appreciate it. WH: You are welcome, thank you.
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Interview on NDTV "There Will Be No Quick Fix For Coronavirus": US Scientist January 11, 2021 | Interview
Political leaders are promising that mass vaccinations will help life return to normal as a more contagious variant of the coronavirus spreads across dozens of countries, adding urgency to the race to end the pandemic. But vaccination efforts are rolling out slower than promised, raising doubts about an imminent way out of the crisis. William A Haseltine- American scientist, businessman, author, and philanthropist - wrote an article about how there will be no quick fix for coronavirus and how most countries have failed to tackle the pandemic. This interview originally appeared in NDTV and is available online here: Interview on NDTV "There Will Be No Quick Fix For Coronavirus": US Scientist
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Interview with The Heat: US Battles COVID-19 Crisis Host: Anand Naidoo Dr. William Haseltine Gavin Macgregor-Skinner, Director of Global Biorisk Advisory Council Dr. Kate Tulenko, CEO and Founder of Corvus Health Katie Barlow, An attorney and Media Editor for SCOTUSblog January 15, 2021 | Interview
Anand Naidoo (AN): COVID 19 rages across the United States as the number of people who have died from the virus and the country closes in on 400,000. Hello, I am Anand Naidoo and this is The Heat. While the last week here in Washington has been dominated by the attack on the US Capitol and the impeachment of President Trump for the second time, the country continues to battle a COVID-19 crisis. The number of those dying from the virus across America is staggering with the death toll now almost 400,000 and over the last week, the daily average of new cases being reported is around 250,000. More than twenty three million people in the US have been infected so far. To discuss the crisis situation, joining me now via Skype from Roxbury, Connecticut is Dr. William Haseltine. He is a former professor at Harvard Medical School and he is the chairman and president of ACCESS Health International. With us too via Skype from Washington, DC is Gavin Macgregor-Skinner. He is an infectious diseases expert and director at the Global Biorisk Advisory Council. Also with us is Kate Tulenko. She is the CEO of the global firm Corvus Health. And here in Washington, DC too is Katie Barlow. The former journalist and lawyer is host of the Words Matter podcast. Welcome to all of you. William Haseltine let me start with you. And as I said, these figures are staggering. They are alarming. The US is averaging 250,000 cases a day. Thirty eight 2116
thousand Americans have died just in the first two weeks of 2021. And the CDC is warning that there could be up to 92,000 more deaths in the next three weeks. What is behind these numbers? William Haseltine (WH): The first thing behind these numbers is failure to control the pandemic through public health measures. We have dropped the ball at the federal level, at the state level, and we have dropped the ball at the level of individual responsibility. That is what is behind this. Other countries have controlled the virus well. We seem to be in a position uniquely with Israel right at the moment that are in the most dire straits on a population basis. There are other countries not doing particularly well, but we are doing worse and it is because of our failure to institute proper public health measures. AN: Is there a time in the near future, do you think, when we will turn that corner? I mean, have we reached the peak right now or could this even get even worse? WH: It is almost certain to get worse. The holiday travel infected tens of thousands, hundreds of thousands of people. They were warned it would happen. They ignored the warnings for the most part. And we and they are repeating the consequences. And will there be a rapid turnaround? No, there will not be a rapid turnaround. It is going to take a while for this to tamp down. Yes, we will get over the holiday surge and settle in at a different number, but there is another dynamic which is happening in this country and around the world and that appears to be new variants of the virus. Not only are they more transmissible, there is emerging evidence that they be immune to people who are, the people who have already been infected may not be immune, and vaccines, whether they are developed in China or the United States may not be fully effective. AN: Kate Tulenko, there are more than three million cases that have been reported since the beginning of this year. Hospitals must be under immense pressure and strain right now. How has the country&#39;s healthcare system coping with this? Kate Tulenko (KT): Unfortunately, in certain cities, it is not doing very well. For example, in Los Angeles, it can take several hours for ambulances to respond to a 911 call. In addition, the ambulances have been told to preserve oxygen and that if they think a patient probably won&#39;t make it to not transfer them to the 2117
hospital at all. We are also seeing COVID wards being set up in garages and parking lots and other facilities. And there is no way we can give the same quality of care in these types of facilities. We also do not have the number of therapeutics that we need. There was yet another study showing that some of these interleukin six inhibitors can reduce mortality by as much as twenty four percent and we have not used the Defense Production Act to make these available to everyone who has COVID and needs it. AN: And what kind of pressure are the hospitals coming under, Kate, with people going to hospital with other ailments, other things that they are suffering from? KT: If you need to go to the hospital for stroke, a heart attack, an injury, something else, you are not going to receive the same quality of care that you would a year ago. There is no doubt about it. Hospitals are overwhelmed, they are busy, they do not have the supplies they need. They still do not have the protective equipment they need. So, it is going to affect what we call all calls mortality. So, not just mortality from COVID, but mortality from other things as well, such as heart attacks, strokes, cancer, and trauma. AN: Gavin Macgregor-Skinner, let&#39;s talk about vaccines. So far, eleven million people in the United States have received the first dose of the vaccine. There are about thirty million doses that have been distributed. Some states talking about setting up mega vaccination sites, but what needs to be done right now to get more people vaccinated? Gavin Macgregor-Skinner (GM): That is a great question. And we are setting up mega sites. We are using convention centers, stadiums and arenas. So, just a few days ago, I was working at a vaccination clinic that is using a stadium as a drive-through. We can do 260 cars an hour, about 1,500 a day. And that is it. We are maxing out. We need more people. And again, to understand how many people it takes to get the vaccine out of the ultra cold freezer into where the vaccination site is delivered, the person that has to be registered at the state level to actually do the injection, the ability to do the paperwork, and then the ability to then to watch that person for fifteen minutes in case there is any adverse reactions. So right now, we need more people. In some of the counties that I work in, we are seeing so many of the community volunteer that that is helping us accelerate the vaccination numbers each day. 2118
AN: Gavin Macgregor-Skinner, what are your thoughts on what William Haseltine just told us about some variants of this virus which make it more transmissible on the one hand. On the other hand, they also may be resistant to some of the vaccines being produced. GM: This is a concern that all of us have. What we know here that we in the US, we were not doing enough genomic sequencing. That is that testing for looking for variants or mutations. So, when we saw the B117 variant strain emerge in England, got into London, became the predominant strain. And then we started looking for it here, and we did not just find it in one or two states. We found it on the East coast, the West coast, in the South, it was all over the country. We are now also looking for the South African strain, but one thing that I am very concerned about is the news that is coming out of Columbus, Ohio than in the past three weeks there is a new mutation, a new strain up there that has at least three significant mutations in it that has now become the dominant strain in Columbus, Ohio. We do not have the answers just yet of how this will affect the vaccine, but it is important to take those antibodies out of people that have been vaccinated, and then challenge them against the mutation strain, the variant strain to see how efficacious the vaccine still is or if we have to change. This is information, research that is ongoing. We just do not have the answers right now. AN: Okay. One other development, very quickly, Gavin. Johnson and Johnson, the big pharmaceutical company, is talking about a one dose vaccine. What do we know about that? GM: That one dose vaccine we are seeing go through the phase three trials and the initial results that many of us have seen we are very encouraged by. So, we are seeing good phase three results at the moment. It would be a game changer for us at the moment. We are using the Pfizer vaccine and the Moderna vaccine. Pfizer needs to be given twenty one days apart, two doses. Moderna is two doses, twenty one to twenty eight days apart. The logistics is so challenging for us. Going to a one dose vaccine is going to be a big game changer. AN: William Haseltine, what are your thoughts on what Gavin just told us about this mutating virus in Ohio? WH: Well, I have just written a blog on that for media. It is a very serious issue. We are going to find many more variants of this in the United States, after all, we are the largest center of infection, 2119
and this virus changes. Let me point out there is something else, though. We already know that there are virus strains out there the convalescent sera does not touch, or does not touch effectively. It reduces the neutralization by as much as sixty fold or more. We know those mutations exist. One is in a Brazilian strain. One is in a South African strain. And there are other variants that have even, let me say, more sobering effects when you treat them with convalescent serum. So, we already know this virus is mutating to resistant to convalescent serum. Will it be resistant to vaccine sera, sera in people who have been vaccinated? Possibly. We do not know the answer yet. And as the other gentleman said, we are looking at that very carefully, but this is going to be a long-term problem, not just for the United States, for the world. It looks like this is going to be more of a long haul, like the flu, coming back year after year with various variants. We had hoped this virus would be stable. It has not turned out. That hope has been dashed. It is not stable. AN: Okay, let me bring Katie Barlow into this conversation. Katie, of course there is a big political dimension to this. We are in a time of change right now. Next week at this time the United States will have a new president, Joe Biden. He has already outlined a plan, $1.9 trillion plan. And part of that, $400 billion will be used to combat the virus. He is talking about an economic rescue package as well. What can we expect from Biden starting next week? How different will it be from what Donald Trump has been doing? Katie Barlow (KB): Well to Gavin&#39;s point, they need more people to help prioritize distributing the vaccines and part of the $1.9 trillion plan, one of the top five priorities that Biden has listed is money that will go to vaccine distribution. We will also see individual checks increased to citizens across the country, back to the $2000 that was originally discussed in the Senate, $2,000 to individuals, $1400 on top of the $600 that has already gone out. We will also see increased unemployment benefits and increased child tax credits and state and local government funding. State and local government funding is something Democrats have been fighting for in the Senate. Senate Republicans have balked at it at every step. And now that there is a 50/50 split in the Senate with vice-president elect Kamala Harris casting the deciding vote, president elect Biden can basically write his menu that he would like to see move forward in a Senate now that he has basically the majority. And those two 2120
Senate seats that they just won in Georgia were hugely critical to that and him being able to implement his priorities in both combating COVID and distributing the vaccine. AN: Although Katie, president elect Biden may have some problems because as you point out, it is 50/50 in the Senate right now. There are some wavering voices among Democrats. So, he would have to seek the help of Republicans, wouldn&#39;t he? KB: That is absolutely right. And look, Joe Biden had thirty six years in the United States Senate. That will be the most experience in the Senate that any president in US history has ever had. And just as President Trump touts himself as a deal-making president, Joe Biden will tout himself as somebody who has experience on The Hill and somebody who knows how to reach across the aisle. That will be the type of president that he shapes himself as going forward. And so, he will look to folks like Joe Manchin, Chris Coons, who he has strong relationships with, but also Republicans like Senator Lisa Murkowski of Alaska, who is up for reelection in 2022, but she will look to be able to help contribute to vaccine rollout and combating COVID. And he also has a strong relationship with Mitch McConnell, the outgoing Senate majority leader. When Joe Biden was finishing his time as the head of the Senate when he was vice president under Obama, McConnell said on the Senate floor, he trusted Joe Biden implicitly. So, those words will certainly be tested in the coming days, but Joe Biden is not coming into this blind. He worked in the Senate for thirty six years, and he has the experience to at least attempt to reach across the aisle. The question will be who will be receptive to that? AN: William Haseltine, that huge stimulus bill that we were talking about, $1.9 trillion that Joe Biden would like to pass, $400 billion of that would go towards combating the virus. What would you like to see Biden do? WH: Well, I think many of the things that I have seen now in that paper that he has put out that he will be talking about are very positive. For example, I am very happy he is going to be supporting rapid testing. I would like to see that ramped up even further so there are free home tests, self administered home tests that people could know if they are infected. So, they know to stay home. They know if their family is infected. Schools know if any students are infected and workplaces know if their workers are infected. I think 2121
that is a critical piece. But as I said at the beginning, the failure that we have had in the United States is a public health failure. It is a failure to do the simple blocking and tackling. If other countries have done better, China in particular, they followed the rule book that we wrote. I was a professor at Harvard School of Public Health. After SARS, many of the Chinese leaders came to the United States to learn how to control a pandemic and they brought those lessons back. We even sent people to the Center Party School to make sure they had those lessons. They sought those lessons. They implemented them. Well, that is what we have to do. And we need the cooperation of our entire country. This does not happen because somebody in Washington says it should happen. It happens because everybody from the community level on up believes that public health is the answer. I think that medicine, we put too big an emphasis on medicine. Yeah, medicines are great. We need them, but we need to put this genie back in its bottle through public health control and I would like to see a much greater emphasis than I have seen in that in particular, AN: Kate Tulenko, it has been almost a year since this pandemic hit the world and the United States. We are hearing about this term COVID fatigue. People are really, they have had enough of this. In many places, they are not observing social distancing, restaurants remain open. We are also seeing students wanting to head back to college. Are Americans taking this as seriously as they should? KT: Well, I think the elephant in the room is that the US is in the midst of a public health, mental health crisis. The combination of the chronic crisis that we have been in over a year. When you think about it, when there is a hurricane, an earthquake, it is over within hours or at least days, and this has been going on for about a year. Plus we had the real shock last week of what happened on the Capitol and a lot of people are reeling from that. And there has not been adequate outreach to help people identify sort of their shock and their mental health problems, seek care or take care of themselves. I do think that needs to be addressed. And yes, people are getting tired of not seeing their relatives, are tired of not living their lives the way they need to. We need to be able to teach people how to do those things in a safer way. Just to give an example, most Americans are still using a single layer cloth mask. We need to make 2122
better masks available. Many Asian countries have provided all their citizens with higher quality masks for free. We need to do that. We also need to push the vaccine down to the community level. I think stadiums and hospital vaccination has its place, but we need to be vaccinating people in the empty schools, in drug stores, even in firehouses where the EMTs and the fire people can give vaccinations. So, I think there is a lot more that we can do to help people be safer as they go out along their lives. AN: Kate, one other thing, and that is Joe Biden is talking about reopening schools within a hundred days of the passage of that stimulus bill, that $1.9 trillion stimulus bill. Well, is that practical? Can that be done? KT: I think it is possible. It will be difficult, but if he can get every teacher who wants to be vaccinated vaccinated, it might just happen. AN: Gavin, the last time you were on the show, the last time we talked, we talked about herd immunity and were told at the current rates of vaccination that it could be up to three years before we see herd immunity kick in. How does this work? GM: No, you are absolutely correct. We have to get a certain percentage. You know, it may be say sixty percent of the population, depending on how dense that population is, whether it is a city or a country town, but we have to get a certain percentage of the population immunized, let&#39;s say it is sixty percent, to ensure that we start to break that cycle of transmission. Now, I have recently been involved in some of these calculations. Based on what we have done, and where were given the first dose and the second dose, based on the number of people, based on the number of doses that we can give each day, we are seeing some of the neighborhood county levels. Maybe will be able to do what they need to do in six months, but some are two years. But the worst case scenario I have seen in some of the vaccination clinics, it is going to take three years. We can&#39;t do what New York City is doing where they have gone to a twenty four hours, seven day clinic where I work because we just do not have the people to do that. We are working twelve hour shifts at the moment. And at the end of that twelve hour shift, we are done. And if we make mistakes, we are going to screw things up more. So, we have got to be really careful that people do need time
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off as well as to keep working towards the mission of getting as many people vaccinated every day that we work. AN: Katie Barlow, looking at the politics of this again, if we look at the last few years, in fact, the last couple of decades, politics has been very divided in the United States. The two sides are polarized. They are further away from each other than they have ever been. Do you think with a new Biden administration that the two sides can come together when they look at the gravity of the situation that the country is facing right now? KB: Well, they are going to try. And the first test is going to be right out of the gate in the Senate. And look, the Biden administration is going to need the Senate to walk and chew gum. They are going to, right out of the gate, have three different priorities. Because of the events of last week, they are now going to be grappling with handling a Senate impeachment trial of President Trump. At the same time, they are going to immediately need to focus on confirming president elect Biden&#39;s nominees, particularly focusing on national security first as a priority. And then at the same time, they are going to have to deal with now president elect Biden&#39;s $1.9 trillion proposal for COVID relief. All three of those things are going to happen at the same time in this highly polarized environment, to your point Anand, and they are all going to have to work together to get it done. The Senate could not be more divided. It is literally 50/50. There is going to have to be reaching across the aisle from the Biden administration and from both sides of the aisle in the Senate. And they are all going to have to come together to get it done, to get this country through this crisis. AN: In fact, the Democrats, Katie, had been talking about doing this piecemeal. On a certain number of days, you deal with the impeachment. And then on other days, you deal with confirming the nominees that Biden has put forward. KB: Right. The Democrats would prefer to focus on confirming Biden&#39;s nominees and getting the COVID relief package through. Now that President Trump is out of office, he is not an immediate threat any longer and so they can kind of kick the can down the road on a potential impeachment trial. I suspect that the Republicans may also want to throw the impeachment trial into the mix. That may be politically beneficial to them to help stave off the 2124
focus on some of the COVID battles that they are going to have to go through when it comes to numbers and what they will actually agree to. So, I think it is going to be tough and I think impeachment is at least going to be on the menu in the first week. They are going to have to come to an agreement in terms of priority and scheduling and what comes first. And the Democrats do have the power there, even though the Senate is split 50/50. Because Kamala Harris will have the deciding vote, the Democrats will have the majority and they will be able to guide where the Senate goes, but they are going to need some Republicans on their side to get things done. AN: William Haseltine, getting back to the virus, there was a study done in the United Kingdom, a new study, which found that although those who have had COVID are likely to have immunity for up to five months, there is evidence that those with antibodies may still be able to carry the virus and spread the disease. What can you tell us about that? WH: Well, one of the big questions for the vaccination programs is we have seen this effective in reducing mild and serious disease and even death at this point. But we do not know whether it will actually stop infection and will stop transmission. There are hopes that it will, but there is no certainty. What we do know is people can be reinfected by viruses that are quite similar to the original virus. And now that there are variants, it is very likely they can be reinfected and may even get sick again, whether or not they are vaccinated. That changes our entire perspective, and it should change the world&#39;s perspective about how long we are going to be in the soup with respect to COVID-19. AN: And given those changes that you are talking about, will we get to a situation like the flu shot that we would have to get a new shot every year? WH: If we are lucky, that is where we are going to be, I think, and it may be every other year. We do not really know how long immunity lasts. I can say the cousins of this virus come back every year like the flu. And if you look at the cousins of the coronaviruses that causes the cold, it looks like natural immunity may last about a year and then it wanes and the virus can come back, and the patterns are
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almost identical to what you see with flu. So, it looks like, contrary to what we were hoping, this virus is a change artist. AN: Kate Tulenko, looking at the current rate of vaccinations and the rollout, what is your best guess what will happen in the months ahead in 2021? KT: Well, there are several states that have vaccinated less than two percent of their populations, but with the Biden administration really rolling out the vaccinations, giving money for the vaccinations, and the vaccinations being done at the community level, we know that Moderna and Pfizer are going to deliver 400 million doses over the next six months. So, it might be possible to vaccinate every American who wants to be vaccinated over the next six months. AN: And how concerned should the country be over the fact that there are large numbers of people, there is one figure I saw that said up to fifty percent of people, would not accept the vaccine. They would not agree to be vaccinated. KT: It is concerning in that it means that we have to practice mask wearing and social distancing for longer. And I think as Dr. Haseltine was alluding to, we are going to end up with sort of a COVID tax that every year we&#39;re going to have to spend billions of dollars on new vaccine development, vaccine distribution, people are still going to get sick. So, you know, billions of dollars in lost productivity, billions of dollars in hospital bills. So, unfortunately this tax, this COVID tax is a new reality because people are refusing to wear masks and social distance and refusing to get the vaccine. AN: Right. Gavin Macgregor-Skinner, this is a global pandemic. We have seen it. It has just gone around the world in such a short space of time. But as you look across the globe, what concerns you the most? GM: Right now, it is equity. Just because we cannot measure equity does not mean we do not do it. And even now, what we are seeing now is we have gone through the first dose and second dose in the vaccination clinics that I am working with, we are looking at who are we vaccinating, who has access to the clinics, and it is not equitable. And we are not doing a good job at identifying the more vulnerable people that may not have the socioeconomic means, the money, the transport means to get to the clinic, the ability to get on
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the internet to make an appointment. And again, they may have chronic diseases. They may have maybe a cancer patient or a diabetic, and we are not reaching out to those vulnerable populations to decrease the burden off the hospitals in a way that is going to work. And we do not have systems in place then to ensure that those populations are being equitably given access to these vaccines. At the moment, it is a first come first serve basis. AN: But isn&#39;t there a system in place right now, Gavin? I mean, how do authorities reach out to people who need the vaccine? I mean, I have seen some states for instance, in the state of Virginia where I live there is three separate categories of people who are going to be vaccinated, 1A, 1B, 1C. How are people informed about that? GM: You need access to the internet, and you need to be able to go on to an internet site and you need to register and get an appointment. The clinics I am working in, no one can just turn up. They must come with an appointment. The challenge I had, and I was working with a family of doctors and nurses the other day, they made their appointments, but because of where they lived here and where I live in Washington, DC, they were told to go to different clinics all over the city. It just did not make any sense based on the zip code where they lived. So, at the moment you need to have access to the internet, you need to have access to transport. And again, all of us are working twelve hour days right now. If I am told to go and get vaccinated in the afternoon, I cannot leave the hospital. I cannot leave work. It has to be in a way, so we have to start bringing the vaccines into the place of work, whether it be school teachers, airports, or hospitals, so that we can actually facilitate and expedite this system. AN: Yeah. And we have also seen some reports about the fact that vaccines are actually being held up in warehouses. I mean, a lot of this has to do with logistics, getting it out there, getting it to people. But what do you know about that, about these vaccines that are basically stuck in warehouses? GM: A lot of information. We have been looking at this now since September of 2020, when we started to do drills and exercises, based on that logistics was going to be our weakest area. It is going to be the biggest gap. It is going to be our biggest challenge, 2127
especially we knew the Pfizer vaccine had to be kept at minus 94 Fahrenheit. The Moderna vaccine at minus four. But to get them out of those freezers into areas where we can, they come in those pizza boxes, into those clinics where we could hold them and then actually administer safely. We need transport, we need refrigerators. And that&#39;s what we need. We just did not have them. AN: Okay. Dr. Haseltine, very quickly, I have got less than a minute left. You know, one of the questions I hear very often from people is this talk about returning to normality. When will the country get back to normality? Realistically, when is that going to happen? WH: We are not going to get back to normal life as we knew it before the COVID for many years. We are going to have to contend with COVID from whatever source. You know, this is a global disease and wherever there is a center of disease, there is a threat of disease for all of us. We have to treat this globally and that&#39;s going to take a long time. I would say my best guess to get even close to normalcy, it would be 2025. AN: And on that note, we have to leave it there. It has been a great discussion. Thanks to all of you for joining us. That is it for this edition of The Heat. See you next time. This interview originally appeared in CGTN’s The Heat and is available online here: Interview with The Heat: US Battles COVID19 Crisis Host: Anand Naidoo Dr. William Haseltine Gavin Macgregor-Skinner, Director of Global Biorisk Advisory Council Dr. Kate Tulenko, CEO and Founder of Corvus Health Katie Barlow, An attorney and Media Editor for SCOTUSblog
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Interview with CBC Radio - The Current January 20, 2021 | Interview
Matt Galloway (MG): William Haseltine is a former Harvard Medical School professor and former professor at the Harvard School of Public Health. He is the president of the global health think tank ACCESS Health International. William Haseltine, good morning. William Haseltine (WH): Good morning. It is a pleasure to be here on this auspicious day. MG: Well, it is an auspicious day and I want to talk about that in a moment. Take a look at the days that lead up to this day. You understand that. We are almost a year into this. How did the United States end up with millions of cases and hundreds of thousands of deaths from COVID-19? WH: It is a series of political, governance, and social solidarity errors as well as some serious medical and scientific misjudgments on the seriousness of the disease. MG: So, when you take a look at this auspicious day, how much will change do you think with a new president? WH: We will have good leadership. We have an effort to reform our governance but it is going to be a major job. We have social fracture and we have not achieved the level of social solidarity that we need. The scientific and medical community, I believe, is still underestimating the nature and the magnitude of the threat that this is poses not only to the United States but to the world. MG: You have used that phrase a couple of times, social solidarity. There is this phrase we are all in it together and a lot of people have torpedoed that phrase given the fact that this affects different communities in disproportionate ways. But how much of that social solidarity comes from the person at the top? WH: There is some very interesting work that has been done recently. I am interviewing people, for example, in China who are subject to what we would call very, very harsh restrictions. They had 2129
COVID or their relatives had COVID and those interviews pointed out something very interesting. To a person, they said yes, it was hard for us, but we need to protect others so we ourselves can be protected. I think that is a very fundamental and very deep concept that has not fully permeated, certainly in the culture in the United States. MG: So, when Joe Biden says, one of the first things that he has talked about when it comes to tackling this pandemic is that he wants people to wear masks, particularly federal employees. There is a mandate that he has to wear masks. He admits that wearing a mask has become a partisan issue. Is that likely to change do you think? WH: I think it will change. Overtime, I think the heat will be taken out of the issue with the active opposition of a political leader. I do not think we can underestimate the power of leadership in times of crisis. Good leadership can lead to good results. Bad leadership can lead to terrible results. And we have had a great example of terrible leadership. MG: One of the things President Biden wants to do is get a hundred million people vaccinated in his first one hundred days in office. Practically, is that possible? WH: It certainly is possible. Whether it will be achieved depends upon many factors. That includes the ability of the manufacturers to produce the vaccines. I think they will be able to do that. It depends on an infrastructure to get the vaccines to where they are needed. We can do that. But it then depends upon the local communities to make sure they have the wherewithal, both the training and the facilities, to deliver the vaccine. That has been a problem. We have a governance issue where we assign much of the responsibility to health to our states, to our counties, and to our townships and they are very typically underfunded. And if that were not enough, there has been a very heavy impact of COVID on healthcare professionals. In addition to that, there is vaccine resistance in nursing home staff, in people in various communities, and all that makes a very complicated situation. There are plans. Both this administration and our senator, Senator Gillibrand from New York, introduced various plans that measures, that strengthen the local communities that are needed to deliver these vaccines. But that takes time and whether that will occur in the first hundred days I think is a question. We do not know that yet. It is possible. Can we do what is necessary over 2130
the next five or six months? Yes. But whether we can do it over the first hundred days I think is open to question. I hope we can. MG: What else would you want him to be focusing on in those first few days and weeks in office when it comes to tackling this pandemic? WH: Getting people vaccinated is a first really good step. But overall, we really have to think about, not only in the United States, in the world, how we manage our public health. Our public health has been neglected in many ways. Yes, you need good hospitals. Yes, you need good clinics. But you need beyond that really deep integration of public health concepts into all health management and disease management as well. And very few countries have done that well. MG: In the face of this and in the face of a new approach, there is still massive polarization across the United States. There are millions of people who not want to hear a message like this, who do not feel as though the pandemic is as severe as doctors and nurses and scientists are saying. How do you go about getting that message across when many people do not want to hear the message in the first place? WH: All public health is a matter of patience. You cannot change public perceptions immediately, but you can through persistent, patient messaging with good leadership from the top on down. It has worked. I do not think we are going to heal the divisions. The divisions over COVID have been political, more than they have been medical or public health. I think with the new administration, we have a chance to at least heal some of those political differences. We are seeing some movement I think, even in the opposition, now the opposition party in taking a more serious attitude toward many of the issues which have divided us. MG: If you and I were to speak a year from now, what would you hope to tell us about the state of COVID in the United States, twelve months on? WH: I mentioned on the outset that we have seriously underestimated this disease, both medically and scientifically. We are still just coming to grasps what that is. I think we have gone through a series of differences in perception. First is, it is a disease over there, it is not going to get us. Then, oh it is here, likely to get us but it 2131
will not be that bad. Then, oh, it is going to be pretty bad. We have got to do some lockdowns. Then, oh, we have done our lockdowns, it is ok. Then, oh, our lockdowns really did not work, now we have to do something else. But we are divided. We do not know exactly what to do. Oh, now we have a vaccine. Things are going to be better. I think right now we are entering, just about to enter what I call a period of vaccine euphoria. We have got the vaccine, everything is going to be ok. That is coming just at the time we are realizing that this is not going to be like measles or mumps. It is much more like the flu. All our assurance that this virus would stay put and not change has just gone out the window. Look at coronaviruses. Between twenty and thirty percent of all our colds every year are coronaviruses. They come back and get us every year. There are four that have been circulating for as long as we looked at them, sixty years in some cases. We thought they were the same. But they were not the same. We just realized that they changed and the extent at which they changed, these cold causing viruses, is phenomenal. We have to think of this much more like the flu. We are in this for the rest of my life and your life. We cannot just say one vaccine and done. And as we try to control it, it will change to avoid our efforts to control it. This is a long term battle. We need to mobilize our scientific, our medical resources, and our political will to fight this disease for the long haul, not the short haul. MG: It is an important day in that battle and I really appreciate you joining us this morning and we will speak again, I hope. In the meantime, William, thank you. WH: Thank you Matt. This interview originally appeared in CBC Radio - The Current and is available online here: Interview with CBC Radio - The Current
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Future Of Biotech & Global Vaccine Landscape | Nathealth Thought Leadership Series | NewsX Nathealth | January 21, 2021 | Interview
Siddhartha Bhattacharya (SB): Good evening, everyone. Welcome to the Nathealth Thought Leadership Series. The topic of our discussion today is future of biotech and the evolving global COVID vaccine landscape. We have a very interesting set of speakers today to take us through this discussion. First and foremost, I would like to introduce Dr. William Haseltine, PhD. Dr. Haseltine is a scientist, businessman, philanthropist, and an author. He is an internationally recognized expert on COVID-19 and is often sought after for advice on how to confront the pandemic. He was a professor at Harvard Medical School and Harvard School of Public Health and is well known for his pioneering work on cancer, HIV/AIDS, and genomics. He has founded more than a dozen biotechnology companies, including Human Genome Sciences and seven pharmaceutical products from companies he founded and currently approved by US FDA. He is the author of more than two hundred peer reviewed manuscripts and ten books, including two books on COVID, The Family Guide to COVID, a COVID Back to School Guide and his autobiography, My Lifelong Fight Against Disease From Polio and AIDS. He is currently the chair and president of the global health think tank ACCESS Health International. Welcome to the webinar Dr. Haseltine. Secondly, I would like to welcome Dr. H. Sudarshan Ballal who is the chairman of Manipal Hospital and is the immediate past president of Nathealth. Dr. Ballal was the best outgoing student, a Blue Ribbon awardee of Kasturba Medical College Manipal and is the recipient of many gold medals in MBBS and MD. And later on, he furthered his training in the USA and had the distinction of being one of the few to be triple board certified in internal medicine, nephrology and critical care. He has the rare distinction of being appointed as professor of medicine at St. Louis University School of 2133
Medicine, USA, and is also an adjunct professor of medicine at Manipal University. Dr. Ballal was conferred the fellowship of the Royal College of Physician London for his contribution in medicine. A warm welcome to you, Dr. Ballal to this webinar. Ms. Preetha Reddy is currently the president of Nathealth and she is the executive vice person at Apollo Hospitals. Ms. Reddy leads one of India&#39;s foremost, integrated healthcare providers, the Apollo Hospitals group. She is widely recognized for her contribution in making high quality healthcare accessible to millions across the country. She is known for her support to various entities and industry bodies working for the betterment of India. Apollo Hospitals is acclaimed as the pioneer of private healthcare in India and was India&#39;s first corporate hospital. In addition, Ms. Reddy works with industry bodies and the government of India to advance policy decisions on healthcare. She was the founding member of the Quality Council of India, and under her guidance, teams from Apollo worked with the government of India in introducing the NABH accreditation. In 2013, along with Dr. Prathap C. Reddy she had championed the establishment of Nathealth, the healthcare federation of India, representing the unified and credible voice of the India&#39;s healthcare community. She is now the president of Nathealth for the year 2021. She is also on the board of governors of the Management Develop Institute, MDI Gurgaon. A warm welcome to you Ms. Preetha. Now I would like to request Ms. Preetha Reddy to kindly give the opening remarks. Over to you, Preetha. Thank you so much. Preetha Reddy (PR): Welcome and thank you so much Dr. Haseltine for accepting to be on this program. I understand that we have almost a thousand viewers, so my welcome to all of them too. And I think it is a privilege for us as Indians, as global citizens, to have this opportunity to even hear you. The past twelve months, the past ten months significantly has been tumultuous for us as Indians, for humanity at large, and every minute there is an overload of information. And for us who are literally frontline workers in different ways, Dr. Ballal being a very senior, most respected clinician in the country, and me just working with the hospitals and Siddartha, of course, bringing together every aspect of healthcare under one umbrella. For us to be able to hear from you what your
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thoughts are would be really, you know, we are really looking forward to it. I know that genomics is such of late, has been literally the keyword and it has made a huge difference with vaccines, for example. I do not think even six months ago or a year ago, we could even have imagined that vaccines would really come into being in and we could fast track something as significant as that, which would make such a great difference. And if it was not for really being able to adopt and adapt this quickly, we may not have been able to do this. Genomics has played a vast role. We all understand that, you know, you can actually extrapolate the knowledge quicker, faster, and we do not have to wait that long for solutions. In fact, a very big magnanimous person like the owner of Microsoft said that what we have done in two months is what could have possibly taken us two decades to achieve. So that is what Bill Gates said. And Satya Nadella said it in a different way. So, I think we are working, all of us, at warp speed and the mind is also trying to absorb things at warp speed. And sometimes for, I think ordinary citizens like us, it is a bit hard. And that is why we are really looking forward to you telling us what would be the right thing to do. And in this space, whether it is in the space of innovation, whether it is in the space of research, whether it is in the space of genomics, whether it is in the space of biotech, we know that we can look forward to many solutions for healthcare. And we really know that we need to have faith. We understand that India is a land of astrologists. I am sure you know that astrology plays a large part in our beliefs, in our thought process and so on and so forth. But if you put science sometimes, you know, it might seem like a far reaching prediction, but it actually comes true. So, the debate sometimes in my mind is that maybe astrology is true too because what the astrologist says happens and what the scientist says happens. But the scientist comes with facts, with proof, with long odd results of like really hard work behind computers, behind labs, behind benches, with an army of people working with them. So, I think we should really give credit to the hours of research and thought which has gone in to producing the kind of drugs, the vaccines, the predictions of the future, because I would put my faith and trust in that. So, thank you so much Dr. William Haseltine for your time. I know that the viewership is huge and they are really 2135
waiting to hear from you. And you cannot have a better moderator than Dr. Ballal because every word he speaks is measured and it is words of wisdom. So, I am going to turn it over to both of you and really enjoy listening to this healthy and fantastic debate. Thank you. Welcome to India and to the rest of the audience. Namaste. Dr. H. Sudarshan Ballal (HB): Thank you very much, Preetha, for the generous introduction. Before I get started, I have a word about astrology since Preetha mentioned that. There is a famous astrologer who is a patient of mine. And he came to me sometime in June or July when we were at the peak of COVID, that all of us looked very harassed. He said, do not worry, doctor, it will go away in October. I do not know what the scientific basis for that was. But lo and behold, the last week of October, there was a dramatic drop, almost eighty percent drop in COVID cases in India. So be as it may, we have a scientist with us. So good evening to all of us in India and a very good morning to our esteemed guest from the United States. At the outset, I would like to congratulate Preetha, Siddhartha and the team at Nathealth on organizing this Nathealth Thought Leadership Series and a big thank you to the media partner, NewsX, for their support. 2020 has been the most devastating year for me in my fifty years of being in the medical field. The world has been turned topsyturvy. All of us have been bruised and battered by COVID. And finally, there appears that there is some hope at the end of the tunnel with the advent of the vaccine. And it is my privilege and honor to welcome our distinguished speaker, Professor William Haseltine, and moderate this session on the evolving global COVID vaccine landscape as part of a Nathealth Thought Leadership Series. Professor William Haseltine wears multiple hats. He is a scientist, business, philanthropist, and author. Siddhartha has given a brief introduction. I say it is brief because his true introduction would probably run the entire course of this debate. So, we are fortunate to have him with us, a true brilliant mind in the field of COVID and many other illnesses and viruses that he has dealt with. So, what we would like to do in the next forty five to fifty minutes is sort of scratch Professor Haseltine’s brains about some of the thoughts that need clarity in the time of COVID. The first point that I would like to ask him or ask for his comments is a brief overview of the devastation caused by 2136
corona, which of the countries did well in their fight against corona, and which are the ones that failed. And what do you think, sir, are the reasons for the success and failure of these countries. Over to you Professor Haseltine. William Haseltine (WH): Well, thank you for, and thanks everybody for their generous introductions. And thanks for the opportunity to speak on this important topic. An overview of COVID would be hard to give in a few minutes, but I would just say that we know this was a new virus that probably started circulating maybe as early as October of 2019. It became manifest as an outbreak in a Chinese city, Wuhan, in a demonstrable way in December, although there is evidence where a few cases scattered about. It caused a serious issue in that city that was not recognized for about three or four weeks. Once it was recognized, the Chinese central authorities took very strong measures to control its spread in that city. What happened in Wuhan was truly devastating for the weeks of January, February and March. I was in Wuhan in November. Probably was circulating at that time, just beginning. But I was in daily contact with my team in China. I have offices of ACCESS Health in China, as well as in India and other countries. And so I had a firsthand view. One of my key people there lost three grandparents in three weeks, give you an idea of how serious it was. His uncles would stand in line for hours at a time to get medical aid. His family members were infected and if they were not infected, they were cowering at home terrified of what was going on. In a relatively short time, three to four months, that situation was controlled. It was controlled by a very simple process which is instituting standard public health measures which is attributed to the Chinese government. They had sent for ten years people to the Harvard School of Public Health to understand how to control a pandemic. They understood that SARS not only destroyed lives, had the potential to destroy economies. And so, they had studied in great detail what to do, and they implemented almost a textbook case on what to do. You identify a case, you do contact tracing to understand who was exposed and you quarantine everybody exposed, potentially exposed. Whether that was a person, a whole plane load of people that has happened to some friends, an apartment building, a city block, an entire city or an entire province. That is what you 2137
do, especially in the early days of pandemic when you have no other tools. Who is sick, who was exposed, control. That worked, it worked in a spectacular way. China is virtually the only country other than a few island nations that instituted that kind of control. And it had to contend with something the island nations did not have to control, which is a major epidemic in one of their biggest cities. And the city I would say is probably equivalent to Hyderabad, maybe even more, kind of a Hyderabad Bangalore. It is a nexus for all their transportation. It would be equivalent to the US Chicago. It was a big city and they quarantined eleven million people. That taught the world a lesson which they should have learned but did not, to our great distress, that you can control this virus through public health measures alone, without the benefit of all our fancy science. You do not need to do that. The Chinese did not do that. Now, you could say that telecommunications helped, which it did. And they had their apps, which said you were green, yellow, or red, depending on your status, but they did not even need that, actually. That was a bonus. When you look at what happened in the rest of the world, it just did not happen. We minimize, and I think a continual theme for the world outside of China and a few island nations in Asia, is that we minimized the danger of this virus. And to my mind, we are still minimizing the danger. Now, let me just take the India situation for a minute. There is some hope that having reached a peak, and you see the case numbers decline, that you reached a point where you have population immunity. I have argued from the beginning that is a poor concept for coronaviruses. You know, as a virologist, I have learned over the years to look at nature, not to look at what we think should happen, but what does happen. That is actually, surprisingly an unusual situation for most scientists. Most scientists get deep buried into their specialty and do not look up. Really important to look up. When you look up from the coronaviruses, what do you see? Well, the first thing you see is SARS and MERS. That turned out to be a false lesson in one way, and a good lesson in another. The false lesson is it just went away. I remember our president saying, oh, do not worry. It is just going to go away. Fifteen people are infected and it is just going to go away. Well, 400,000 deaths later, and two and a 2138
half million people infected in the United States. It has not gone away. The lesson from SARS and MERS were coronaviruses are out there and can adapt to humans and we better be careful. We dropped the ball globally. We did not do our research on those viruses. We were not prepared for the next one that came along. Why not? I can tell you, rooms of scientists started to work on coronaviruses, got drugs almost ready for the market, got vaccines ready to go and stopped. Money was not there. One thing I can tell you as a scientist, and we know as human beings, without money, you cannot do much. And if governments aren&#39;t going to give you money and private foundations are not going to give you money, what can you do? There were a few brave souls who soldiered on. You can count them on one hand. That was it for all coronaviruses after they had scared the wits out of a lot of people. That was the first thing we did not see, but there was another lesson we should have paid more attention to. Coronaviruses are not new to us. Every one of you I am speaking to has a coronavirus infection every year. You call that a common cold. And we get on average about three common colds every year and one of those on average is a coronavirus. So, if you didn&#39;t get it last year, you got it the year before. And what we know is they keep coming back and back and back. It is like a bad headache. They just keep coming back like a bad penny we call it. And it is like the flu. Now, that is the lesson of the coronaviruses and I kept warning from the very beginning, do not count on population immunity. I hate the term herd immunity because I do not want to be part of a herd, but population immunity does not exist for these viruses, for coronaviruses. People are like, oh, well it will for this one. Well, that is a big underestimate. So, the idea that it would go away just was not in the cards and it has not gone away and it has gotten much worse. Now, you asked me a very specific question. What distinguishes countries that did well or don&#39;t. I have a couple of answers. One is a little bit facile, and that is, if you are afraid for your economy, you took some action. Chinese government and East Asian countries knew that SARS was about to destroy their country, their economy. Now, an economy is different from people dying, but it is in some ways, even more important because if you don&#39;t have economy, everybody suffers, every single human 2139
in the whole country suffers. Whereas you have a bad pandemic, some people die and some do not. When the economy crashes, you get a depression, everybody suffers. So, the Chinese knew that these viruses could crash the economy and they took very rapid action that they had studied on what to do. And as I say, at Harvard School of Public Health, we helped them learn those lessons. Other countries in Western countries, India, did not have this problem. So, they did not take the same kind of action. That is one answer. Another answer is a deeper answer. Countries, this is something for the future. If we are going to deal with pandemics, we need good political leadership. Some countries had it and some countries did not. We in the United States did not. Brazil did not. Eastern Europe on the whole did not. Russia did not. And I leave it to you to think whether or not you in India had it. The second is governance. You need a public health system that really works. And a public health system cannot work without a health system. And it cannot work without a health system that is well-organized and deals with community health because where the rubber hits the road for pandemics is in communities, local villages, townships, small towns, and big towns. And if you do not have a health system that can reach right into those communities, you cannot control the pandemic, cannot be done. That is a fundamental lesson. We in the United States have a very odd system of public health and health systems. We devolve most of our responsibilities to the states and within the states to the towns, et cetera, et cetera. So, we had no uniform way of dealing with this. Now, in theory, the federal government could have stepped in and said, we are going to take over. They chose not to. Now some European countries did have good leadership leadership and do have, and even in those countries, there were other mistakes which I will talk about in a second. That is the other thing, you need that. And finally you need social solidarity. I am my neighbor&#39;s keeper. If I do not take care of myself, the neighbors are unlikely to take care of himself and we will both give each other disease. That is really fundamental, solidarity. The notion that you are responsible for your health, your family&#39;s health and your neighbor&#39;s health, and they are responsible for your health. That is a message that the whole world needs to learn again and again and again. We are our brother&#39;s keepers. If they get sick, 2140
we&#39;ll get sick. And it is true of the whole world. China could control this disease within their borders, but they are constantly bombarded by packages that contain COVID on the outside, by people who come in with lingering COVID, and they have to shut down city after city. It says if one week, Hyderabad. It actually reminds me of traveling around India during the monsoons. Uh oh, Hyderabad is closed for these two days, or Mumbai is closed, or you cannot go here or there. That is what has happened only this is much more serious. It is weeks of isolation and shutting down the whole economy. And no nobody is isolated on this planet. HB: Thank you very much, Professor Haseltine. I think you emphasized the role of public health leadership and social responsibility in your yard stick of which countries did well and which did not. We move on to our next question. That is your views on our path to the early development of vaccine and the role of innovation and technology and the development of the vaccine. WH: You know, I have some different views from most people. I know that everybody is celebrating how great science is and how we have solved this problem so fast. I would say, yeah, science is great and we have not solved the problem yet. But that being said, I would argue that we have missed the ball in a couple of ways. We did not need high science, and I say that as a genomicist and I am very grateful for the wonderful comments about genomes. In a way, the simplest thing to do was to grow up the virus and kill it like we did with the polio viruses in the 1950s. In fact, some companies are doing that now. The very first vaccine was not a high-tech vaccine. It is the Sinovax and Sinopharm vaccines. They just grew up the virus, killed it, and we probably could have had vaccines for many more people, much more quickly if we had taken a simple route, not a complex route, and it may be in the end that those are the vaccines that are not what I call the Lamborghinis. They are the Toyota&#39;s. They are the ones that go around the world. You need a heat stable, simple to make, possible to make in huge quantities. And we know that these kinds of vaccines work. That is why it worked for polio and still works today for polio. So, in a way, our emphasis on high science rather than the fundamental blocking and tackling that you need to do in healthcare has led to some problems. The reliance on science, not on public health has been a disaster for America. We have 400,000 people dead 2141
today because we relied on high science, not public health and more effective science. Same thing goes for diagnostics. We decided we needed PCR diagnostics, very fancy genomic based, where lateral flow antigen diagnostics to detect people who were infectious would have done far better. And today we still do not have access to tests anywhere like what we need, nor does the world. That was a fundamental mistake made early on that has perpetuated. So yes, it is great that we have these technologies. Now, these vaccines are wonderful that we have them now. We have a variety of them, and I am happy to discuss them in more detail as we go on. SB2: Thank you very much again, Professor Haseltine. So your message is very clear, more Toyotas than Lamborghinis. And I think I will buy it for mater Toyota tomorrow. I was thinking of buying a more expensive car, but I&#39;ll stick with the Toyota. I think you also covered my next question but would like to elaborate a little more. You had mentioned that you felt that the testing could have been very different for corona than the RPPs alone. Would you like to elaborate on that? WH: Well, you may remember the early days of detection, the CDC prepared tests that did not work. They were PCR based tests. What could have been done once we understood what this virus was, is develop simple antigen tests measuring the concentration of protein in saliva and nasal fluids. And we would have been able to define those who are contagious. What do you want to do on a pandemic with a diagnosis? You do not want to know somebody who has had it. You do not even need to know that they have got a little bit of it. You want to know if they are infectious, if they are contagious and if they are contagious, you want to do something with that information. So, we relied on a test was broke down and has never, even to this very day been widely available and is very expensive compared to other things. You can make a simple antigen tests that cost ten cents, that little strip of paper. Somebody can do it in fifteen minutes. You do not need a prescription. You used to do it like a pregnancy test or some other kinds of tests. They are very simple to do. Yet, almost nowhere in the world do you have free universal, simple tests that can be self administered by a parent to their family, by a business to their
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workers, to a school for their children to know who is likely to be contagious. Now, finding out who is contagious is not the whole story. It then has to be followed by making sure you can isolate that person. Now, Britain is doing an experiment right now to try to do that. The problem is voluntary isolation does not work without economic support. People are avoiding these rapid simple tests because that means I will have to stay home from work for two weeks and who is going to support them. If you have got a good social safety net, yes, but even in London, they do not have a good enough social safety nest. So, I have actually proposed that if you are going to do those tests, you pay people to stay home. You got to have a policy which is a realistic policy, simple tests, simple solutions, pay people to stay home. Or if you have a good social system like happens in some European countries, you make sure that that social network functions for everybody. HB: Now, that is a very, very important point. I think we need testing on a mass scale and that has to be less expensive than what it is. And very honestly, this rings a bell. A lot of people did not want to get tested because they thought the minute they are tested their house is locked up and they have a family to feed. There is nothing, no income coming. And a lot of people are actually scared to get tested. So we have to literally force them to get tested. So, if we had an answer of a social security net to protect these people, maybe more people are tested and would have known the infectiousness of the illness much earlier. So, that is a great take home point. I think even the best of the countries or the most developed countries are not able to provide the social security net. And it will probably be very difficult for the developing countries to do that at the current stage. But that is a very important point that you make. Now, come to the vaccines per se. We want the types of vaccines and their safety and efficacy. And which one would you take if you had a choice of picking one of them? WH: Well, there are a number of different choices for vaccines. I would take the simplest one, which is the killed vaccine for a couple of reasons. One, it has a huge safety record for vaccines of that sort. We know how to make them, we know how to use them. Secondly, it is a whole virus. It is not a piece of the virus. This is the whole virus. So, when you get that, you have antibodies, not just to 2143
the envelope protein, but to the N protein, the M protein and a lot of other proteins. And so those are the, that is the reason I would take it because we know when the virus tries to escape, it does not just change the envelope. It changes a lot of other pieces too. You can actually see what it is doing. And when you look at what it is doing to escape, you know what the body is doing to repress it. And it is not just the envelope protein and it is not just a piece of the envelope protein that some of these high tech companies are developing. Second reason is, let&#39;s take the mRNA vaccines where you take a messenger RNA. That is a really unproven technology on a broad scale. We do not know manufacturing reliability. We have had some problems now with a California batch of the vaccine, which causes a lot of adverse reactions. We are not getting the full story yet of what the adverse reactions are to those vaccines. Whether you believe the stories from Norway of people dying or many people getting allergic reactions. We do not know about that. Let me say, I do not want anything I am saying to dissuade people from taking the vaccines. If you have a chance to take the vaccine, take it, okay, whether or not. The chances you will get very sick are very small. When you give it to tens of millions of people, the chance that somebody will get sick is pretty high. But if you have a chance to take the vaccine, get vaccinated, no matter what else you hear me say. That is the message I want everybody to hear. So, everything I am saying is like a variation on that fundamental thing, get vaccinated. Now, you asked me which one I prefer. That is the one I prefer. After that, I would prefer subunit vaccines, where you are taking a piece of the protein, make a virus using genetic mechanisms, produce a piece of that virus and use that as the antigen. That is also very, well-studied. The Indian companies make that by the hundreds of millions. That is the hepatitis B vaccine. It works extremely well. And we know what the relative side effects of those vaccines are. So, there are many other things you could say. Now, there is one vaccine that I think is the one that I think our esteemed colleague here has taken that I would actually not prefer to take and that is the adenovirus one. And the reason for that, and that is widely available in India, is that it is only usable once. Once you had that vaccine and you make antibodies, not just to the SARS virus or the COVID 2144
virus, you make it to the carrier, the adenovirus. And so, you cannot use it again. So, that is one of the reasons I prefer not to have that one. And I hope I haven&#39;t made our interlocutor uncomfortable by saying that. There are other vaccines you can take in addition, so it is not going to be a tragedy. SB2: Thank you. Very strong comments from our scientist. And I think the biggest message was that take the vaccine, whichever one is available for you. And I think right now none of us have a choice, really. The government promotes the vaccine, and you either take it or you do not. It is very interesting that you talked about the inactivated or the killed virus as probably being one of the better vaccines. There is a lot of controversy there and a lot of people in India for various reasons, actually think that vaccine is more hazardous than the other vaccine available. So, I think it is important to know that that vaccine is safe and obviously some data on phase three trials are yet to come. But coming from you that this vaccine is safe and probably has the entire virus and it is inactivated and will have the best response is good to know. Thank you very much. And once the private sector or the private citizens of this country have a choice, I am sure will listen to your advice, but until then we have to take whatever the government gives us. WH: And take it when you can. SB2: And the logistics of the production, storage and distribution across the globe, and your comment on maintaining the extreme cold chain that the mRNA vaccines need. WH: Well, we have known in the global vaccine business for a long time that a cold chain is a problem. Actually, two things that are a problem, cold chain and multiple doses. Those are the two things that limit. And how do we know that? We have vaccinated virtually everybody in the world to eliminate smallpox and it is gone. We have vaccinated almost everybody in the world to eliminate polio, and it is not quite gone, but it is almost gone. And in those processes, we have learned the two big barriers to global vaccination. One of them is cold chain because not everywhere in the world can you maintain a cold chain, especially some of the extraordinary cold chains that are required for these new vaccines. And secondly, how 2145
many doses you need, whether it is now two or some people even talking about three doses. That is difficult because it is a lot of recordkeeping. It is asking people with very few resources to come back. And there is a third, I say third or fourth component of vaccines that are important. One is can you get it to every community? Really important to get into that last mile in the tiniest village, very important, and to work with community leaders who are trusted, because if you don&#39;t have the community trusted leaders to promote the vaccine, there are going to be people who are afraid to take it. So, you need that whole process. And anywhere along that process you have interruption, like a cold chain, extreme cold chain, multiple doses, lack of interdigitation between the central government supplying the vaccine and the local community that is giving it, you are going to have a problem. That last problem is the one we are having right now in the United States. We will get over it, but we have it right now. SB2: I think one of the reasons that the mRNA vaccines may never reach or become popular in India is the extreme cold chain to be impossible to maintain. And also, it is pretty expensive. While we were talking, I saw a quick question on, would you recommend vaccination for the children? Maybe a quick answer for that. WH: The answer is we do not know yet. Right now, it is being tested. I certainly hope it will protect the children because some of the new strains that are popping up infect children more than the previous strains. SB2: The reason this question asked, I am sure is in India right now, they do not vaccinate children, pregnancy and lactating women, rightfully so. So, I think we will have to wait for more data before we start this category of people to be vaccinated. I know you are very big on mutational viruses. You spent almost half your life on mutations in viruses. The other day, you gave me a number, but I still have not been able to calculate how many zeros to add to the ten. So, the number of mutations that the virus can have. Can you tell us a little more about that? WH: Well, one thing that we had learned recently is going back to the cold coronaviruses. They come back every year, just like flu. It turns out, much to our surprise and nobody had really looked, they change just like flu. We should have known that. There are two reasons you can get reinfected every year. One is the immunity 2146
drops, and the second is the virus changes. In flu, we have recently learned that immunity drops. We always knew the virus changed. In COVID, we knew immunity dropped, but we did not know the virus changes, and now we know both things are going on. So natural immunity, you have it for a while. It does not last very long for these viruses, especially the immunity that may stop transmission, which is called mucosal immunity, that type of immunity that stops things from getting into you and from you giving it to somebody else. That does not last very long, but the virus changes. And as we start to look, we are seeing that the virus changes. Now, in some ways the Chinese were lucky. They got the weakest version of this virus. That was what was happening in December and January. By February, it had mutated to become more transmissible and that&#39;s spread all over the world. First in Europe, then across the world that if you have the virus today, that is what you have got. Over the summer and early fall, it has changed again all over the world in different ways. You become even more transmissible, so it can get around even better. And I think one of the things we are seeing in these huge surges in the United States and other places is measures that could sort of keep the virus in check last summer are not keeping it in check anymore because we have new virus variances. It is not just one. And we know that these are escaping our immunity and becoming more infectious. That is kind of worrisome when we think about vaccines. Now, it is not that we have not solved that problem. We have with flu and we sort of solved it. We at least contend with the problem by making new vaccines every year. So another lesson from this virus is think of it as flu. It is a little bit more deadly. So, you are going to have to make vaccines, not last year&#39;s vaccine, this year&#39;s vaccine and the community is just beginning to understand that. And vaccine companies are rushing like mad to try to understand how to deal with it. But it is kind of like pruning a tree. You have a stub which is the original virus. Then you have branches, you have branches and you have branches of those. And the vaccine companies are not sure where to look. Well, there is an answer to that problem. Cut down the tree with public health. Do not try to deal with the branches, cut it off at the root. And that takes public health. Not necessarily the vaccines. That is a lesson that you are going to hear over and over again in the coming months, but has not been well 2147
absorbed at this point by the biomedical community and certainly by our policymakers. It is a lesson that we need to push and push pretty hard if we don&#39;t want to get hit again and again with this very tricky virus. HB: I have a very philosophical question for you. That is what about the equitable distribution of the vaccine between the haves and have nots of the world? WH: That is a very deep question. And it is one that is very important to discuss. John Donne, an English poet, said it a long time ago. “No man is an island entire of itself. Each man is part of a whole. If a clod be washed away, England is the lesser.” That is true for our world. We are connected as never before. And that is the lesson for all of these viruses, whether it is a flu virus or the COVID viruses. Starts somewhere in Southern China, gets to Wuhan, spreads around the world and it is here to stay. Well, if we do not eliminate it everywhere, we are not going to eliminate it anywhere. That is the lesson. China is learning that every day. It is eliminated internally. But even if it has restricted travel like crazy, it is still coming in. We cannot isolate ourselves from these diseases. We have to be able to help everybody. That is what we learned with smallpox, and we did it. That is what we learned with polio and we are doing it. That is what we need to do for this. And India is the country that has the history of supplying those vaccines to the entire world. Why? Heat stable, safe, and cheap. Now, how cheap can a vaccine be? I years ago created a company to create animal vaccines. Now you would say, oh yeah, there is a lot of animals, eighty billion chickens a year. What is wrong with that? Well, a vaccine for a chicken cost about 0.01 cents like a Rupee, right? That is how much it costs. That is not a very good business, but it does tell you that vaccines can be made really, really cheaply, something that most people do not talk about. You know, the cheapest price right now I know for the COVID vaccine is a dollar. Why not 0.01 cents like a chicken? Could be just that the profit is not there, but you could still do it if you subsidize it. HB: I think this is a truly, truly very important message to the entire world because we have become very country-specific in the vaccination protocols. And we are not thinking of the world being one. I think, unless that&#39;s done, we will have viruses pop up 2148
in some country and it will move around the rest of the world within a matter of hours with the current sort of traveling norms that we have people travel. And the world is one and it&#39;s become a really, really small world. I think this is something that you should emphasize, Professor Haseltine. Maybe the UN, the WHO, and whoever else is willing to listen. WH: You mean I have not emphasized it enough? I try my best. Many, many voices for this, as you know, to change people&#39;s ideas. It is not one voice. It is like a chorus. We need many of us. I hope some of the people on this call will join our chorus and say, let&#39;s help the world to help ourselves. It is like that man in China. I am willing to restrict my freedom because that means I am going to protect others and I hope other people are willing to restrict their freedom in order to protect me. HB: Now, another question that I am waiting with a bated breath is when can we breathe easy, literally and figuratively? WH: Well, it is going to be very spotty in different places. And let&#39;s just take again, I go back to China because that is the exception. I have teams of people in China who are traveling, enjoying life, pretty much normal with one big exception. They cannot get outside the country, or if they do get out it is trouble and they have a heck of a long time to get back in. They have to go through a long testing procedure. But life in China is very pretty normal. They got back to normal in about five months. Other countries can do that but do not because they are not willing to put in the effort to control the pandemic through public health measures. And unless countries are going to do that, I do not see them getting back to normal anytime in the foreseeable future. The vaccine is not going to do it because there will be variants that come back and start the whole thing over again. This is not a problem that medical medicine alone can solve. Medicine can help shrink that tree, but to cut off the root, you need to combine it with public health. We need to shrink the tree so it does not exist anymore. And when I say it doesn&#39;t exist, it doesn&#39;t exist on the planet anymore, not just in your country. You know, we are entering a period now what I call vaccine euphoria. We are going to say, okay, it is all over. This time next year, everybody is going to be like, hey, wait, it is coming back. Why the heck is it coming back? Well, flu keeps coming back. Okay, well we are going to get it this time. So, we are 2149
going to go through a period of ups and downs in what we consider normal life. It is not until we really squeeze that, cut it off at the root that we are going to be able to have back to really normal life. And then I hope we have learned a lesson to be vigilant. There is one other lesson we need to learn from this, which is science has got to pay attention. You cannot shove something off into the corner like we did coronaviruses. Nature was nice to us. They warned us not once. They warned us twice. Nature was good. Hey guys, figure this out. We did not figure it out. So let&#39;s not make the mistake again. HB: So, I assume from what you have told me that this will be our partners for life, if not life, thenat least for many more years to come. WH: Yeah, we call it moving from pandemic to endemic. Endemic means it is with us. It is our companion. Something that we have got to live with, contend with. And by the way, we do that with many diseases. Think of heart disease, kidney disease. You know better than anybody how many diseases we live with, right? We live with a lot of things. It does not mean we stop. It just means we have to be more careful. And it means we have to do our best to take the institutions, our leadership, our governance, our social solidary, and our science and tune them to their maximum efficiencies so we can have as close to normal life, what we want to have as normal life. You know, if we look back at my life in the last fifty years, it is longer than that. But if you look back at my life, I have been extremely privileged, except for HIV/AIDS and polio in the early days, to be pretty much free of pandemics and disease. That was not life before. Before World War II, that was not life. But remember even before World War II, people built cities, they built Rome, they built London, they built Paris. They built Beijing. They conducted huge wars across continents with huge disease hanging over their head. Humanity will prevail, but let&#39;s hope we prevail and we are happy while we are doing it. HB: Thank you. And finally your message to the citizens of our planet. WH: Care for one another. You know, the Bible says treat your brother as yourself. Take care, you are your brother&#39;s keeper. If you take the precautions to protect yourself, you are protecting yourself, your family, and you are protecting everybody around you. 2150
And if they do the same, they will protect you. That is the message, not only on the individual level, but on the country level. Make sure your country is as safe as it can be and disease free as it can be, and other countries do the same and then help countries that cannot help themselves. Not all countries have the same advantage as in India or China or Europe or the United States have. Help those countries too. India is now in a position to help many other countries and it does it. And so we need to join as a community to help our neighbors because in so doing, we help ourselves. HB: Well, thank you very much, Professor Haseltine. Some very, very important messages. The messages being that public health and governance and good leadership is probably the key in sort of cutting down the tree and making sure that sprouts do not come up. And then the important message is that public health measures should continue in spite of the vaccine. Care not just for yourself, but care for the society. The world is one and we have to treat it as such. And it is not always science and innovation alone. Simple things first and simple things can conquer this disease, but do not think that disease will just go away. If not a pandemic, epidemic, it will remain as an endemic and do not shun away from all the masking, distancing, hand-washing and treating the world as one. Thank you very much. I think we may have a few questions from the audience. Siddhartha, if they can type in, we may have another five minutes before we sort of conclude, and I would like you to conclude after another five minutes. SB: Please go ahead, Dr. Ballal. HB: Yeah. Yeah. Any questions from the audience? I see one or two questions that come which I asked Professor Haseltine, but is there any other questions? They can type in the questions, I guess? PR: There are some questions in Q and A section Dr. Ballal. HB: Found it. We will take as many questions as we can. Will we need a new adjusted vaccine by the end of 2021? WH: I think we could use one right now. HB: Okay. Okay. The next question is what is your perspective on building confidence about the vaccines that are addressing public reluctance to taking them? WH: Well, I think the message is that it can save your life and it can save your family&#39;s life. So, you should take the vaccine. You have to be clear there are some side effects to these vaccines, 2151
but to the best we can tell these have been measured very carefully versus their benefit and the side effects are quite rare. And as we get more data, we are getting more information about where those are. HB: While vaccines are being administered, what do we all do to avoid COVID infections? Do we continue our focus on testing? WH: We, first of all, make sure that we are wearing masks, washing our hands and avoiding, as much as we can, being with people that we do not know. I would advocate one other measure in which most people are not doing, which is wearing a face shield when you are in public with people you do not know, because in addition to a mask, a face shield works. The other thing people should know is some of these new variants require more complicated masks. You have to have multi-layered masks because the particles are now so infectious, that many fewer of the kind that can get outside of a mask can be infectious. And so, you want multilayer mostly to protect yourself and to protect others and face shields are very cheap. You can keep using them again and again and prevent it from getting into your eyes and curiously prevent it from getting into your nose as well. So, it is a good thing to do in addition. The other thing I recommend if you are going out in public, wear gloves, disposable gloves, and make sure that you change those gloves as frequently as you would wash your hands. HB: Okay, great. Would you recommend screening of neutralizing antibodies instead of binding antibodies to access population immunity of the vaccine in clinical trials? WH: That is a complicated question. Certainly measuring neutralizing antibodies would be better, but it may not. We do not have tests that measure all the neutralizing antibodies. You know, almost all the neutralizing antibody tests are measured against the receptor binding domain. And it turns out that there are many areas of that virus where neutralizing antibodies work, N protein, M protein, the ORF 1A, 1B, the N terminal domain. And so most of the tests are incomplete for neutralization and those that aren&#39;t incomplete are very, very expensive to do. So, at this point, I think that measuring antigens and if need be to confirm that with a PCR test is the way to go to measure infectivity, is somebody contagious.
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HB: There is a question from a close friend and an eminent transplant nephrologist, Dr. Sundar. Can transplant patients who are immunosuppressed take the COVID vaccine? WH: That is going to depend upon their doctor&#39;s evaluation of their immune status. The things to worry about with those patients is that they get chronic COVID. So, they get the virus and it doesn&#39;t leave them. And in that, that is a very, very different kind of treatment regimen you have to propose for those people. And you have to be very careful because the treatment regiments in those people can lead very rapidly to resistance variants in that person that can then spring out and be transmitted to others. That has happened in probably have most of the resistant variants. So you&#39;ve got to be, I would say anybody who has got a chronic COVID infection because they are immunosuppressed needs to be taken very seriously as a source of a new global pandemic. And that means isolated under very careful condition so it does not spread out of that patient. I think people are thinking about it. That is a very important thing for hospital administrators to understand that that one patient could trigger a global pandemic, because there are good studies of where patients like that have been treated repeatedly with drugs and convalescent sera and the virus adapted in that patient. And those adaptations are almost identical, are identical to those that are spreading all over the world today. So treat those patients as time bombs. HB: The next question, I assume, is someone from the pharma industry. What is the role of pharmacists in the development of vaccine? WH: Pharmacist? Somebody who distributes the drugs? I think maybe in distributing, yes. The problem when giving vaccines, especially these newer vaccines, is you have to have somebody on hand who can treat an adverse reaction, like an allergic reaction. And I am not sure that that can be done in all pharmacies, in some pharmacies, yes. But EpiPens have to be on hand and somebody who is licensed to use the EpiPen might need to be there. So, in the US, we are requiring any vaccine distribution center to have the ability to treat anaphylaxis and I think that is a good thing. So, I would think that would be a good, figure out the licensing that is necessary for that. 2153
HB: The other question is about something in Australia, comments on the national sewage water survey for COVID-19 study in Australia. Is it worth exploring? WH: It is worth exploring. What they are talking about is one way to know if there is COVID around or any virus around is to survey the sewage, whether it is a big common sewer, or one that comes out of a school building, for example. It is pretty sensitive. The Israelis have perfected it and a few other people have. It is a good public health measure, but it does not really tell you, I would say a short answer is in some situations, it is worth it. As a general method, I do not think it is worth it. Maybe continual survey of a metropolitan area in several places is worth it to know if there are new viruses coming up. Probably worth it for that, but it has got limited utility. HB: The next question is from the African continent. Which vaccine will be the best to African countries considering the weather of the region and storage facilities? WH: Yeah. I think you need a heat stable vaccine. And I think that the subunit vaccines and the killed vaccines are going to be preferable in that circumstance. HB: Okay. Thank you. There is one more question whether anti-microbial resistance played a part in this pandemic. WH: Well, if you consider the virus to be a microbe, which it is, the answer is definitely yes, both in terms of developing resistance to drugs. I will give you an example. If you give the Lilly antibody to a patient and that patient survives, that person will have a virus population in them that is resistant to that antibody. And some of the variants are resistant to the Regeneron monoclonal antibodies, two. And they use two at once and mutates in a couple of places. So, these viruses have to be thought of as wily and changeable. The only way we dealt with that with HIV is you use combinations of drugs. And I think we have to use them different targets, not everybody targeting RBD or this or that. There are plenty of targets in this virus. I think there is a huge amount to be learned about these viruses. They are big, they are complex, they are doing many things we just do not know about. And they are vastly understudied from the problems that they have caused.
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HB: We will probably take two more questions for time constraints. And I think this is from a concerned mother. When will the vaccination of children below 18 commence? WH: I think it is going to come in stages. The way they usually do it is they do it from 16 to 11 and then 11 to five and then five to one, and they are doing their best to make sure those trials are done as fast as possible. You do not have to do all the elaborate bells and whistles for first approval, but you do have to do the trials. And those are currently underway for some of the vaccines. And as vaccines will come along, they will be done for others, but you have to do it for each and every vaccine. HB: And the last question we will be able to take before I hand over to Siddartha. Are there any guidelines issued by the WHO to handle and dispose biomedical waste generated during the vaccination? WH: I do not know if it is the WHO that does that, but certainly each country has biosafety disposal requirements. That is going to be an issue when you do tests, et cetera. Most of the tests, for example, that have been done, if you are going to swab your nose, come with an inactivation aspect and you will need that. HB: Thank you very much, Professor Haseltine. It has indeed been a great pleasure, very informative listening to your experience and your thoughts on COVID and the COVID vaccine. I will hand it over to Siddhartha. SB: Thank you for a fantastic webinar. I think the key messages, what we take out of this webinar is for the genie to be put back into the bottle. Pure science alone won&#39;t do it, and that is a scientist speaking. It will require the combined efforts of humanity, leadership, a spirit of collaboration, and most importantly, an underlying strong public health infrastructure, which all governments in the world have to develop. I think there&#39;s a lot of lessons out of this. I was just reading some of the comments and I deeply appreciate Dr. William Haseltine, Bill, for being in this webinars, sharing your thoughts. We hope to get you back again probably in a few months and maybe next year, again, to see to what extent some of these projections hold good. Thank you, Dr. Ballal for moderating this wonderfully well, and as well as to Ms. Preetha for giving the opening remarks. We really appreciate from Nathealth’s perspective. For those of you who may want to 2155
listen to this webinar again, our media partner NewsX will be broadcasting it again tomorrow at 7:00 PM Indian standard time and on behalf of Nathealth and the Thought Leadership Series, we hope to bring back to you many of these interesting sessions around COVID and the vaccination efforts in short order. With those words, I&#39;d like to thank each and every one of you, the audience who have joined from all over the world. Thank you to the speakers and have a wonderful evening. Have a wonderful day ahead. Thank you so much. This interview originally appeared in NatHealth - Youtube and is available online here: Future Of Biotech & Global Vaccine Landscape | Nathealth Thought Leadership Series | NewsX
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Interview with Margaret Hamburg : Roosevelt House Public Policy Institute at Hunter College January 21, 2021 | Interview
Roosevelt House is pleased to present a live Zoom discussion of the timely and inspirational memoir, My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19 by renowned scientist, entrepreneur, healthcare expert, and author Dr. William A. Haseltine. In this deeply relevant story, Dr. Haseltine tells for the first time the riveting tale of his extraordinary life and career. He will be in conversation with former Commissioner of the Food and Drug Administration Dr. Margaret Hamburg. Newsworthy, hopeful, and exhilarating, My Lifelong Fight Against Disease delivers a fast-paced insider’s account of some of the most brilliant medical breakthroughs in modern history—including Dr. Haseltine’s work to confront devastating public health crises such as the COVID-19 pandemic. At once candid, evocative, and revelatory, Dr. Haseltine’s much anticipated autobiography explores what it really means to make science your life. While encouraging greater appreciation for science among general readers, this is a book that promises to inspire the next generation to improve the health and well-being of humankind. As CNN’s chief medical correspondent, Dr. Sanjay Gupta, put it: “Place this book at the top of your list. You will be inspired to make an impact on the world, with a remarkable guide to help show you the path.” William A. Haseltine, Ph.D., has an active career in science, business, and philanthropy in addition to his prolific work as an author of books including World Class: A Story of Adversity, Transformation, and Success at NYU Langone Health. He was a professor at Harvard Medical School and Harvard School of Public Health, where he was Founder and the Chair of the Division of Biochemical Pharmacology and the Division of Human Retrovirology. He is known for his pioneering work on cancer, HIV/AIDS, and genomics. He founded twelve biotechnology companies and eight 2157
pharmaceutical products from those companies are currently approved by US and international regulatory agencies. Haseltine is the Chair and President of ACCESS Health International, a foundation active in the United States, India, China, Singapore, and the Philippines. Margaret Hamburg, M.D., is a physician, scientist, and public health executive. She served as Commissioner of the U. S. Food and Drug Administration under President Barack Obama, and Assistant Secretary for Planning and Evaluation at the Department of Health and Human Services in the Clinton administration. She has also served as Commissioner of the NYC Department of Health and Mental Hygiene, founding Vice President for Biological Programs and Senior Scientist at the Nuclear Threat Initiative, and Board Chair and President of the American Association for the Advancement of Science. This interview originally appeared on Roosevelt House website and is available online here: Interview with Margaret Hamburg : Roosevelt House Public Policy Institute at Hunter College
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Interview on CNN’s ‘New Day’ To Discuss COVID January 27, 2021 | Interview
John Berman (JB): Joining us now, CNN national correspondent Kristen Holmes and William Haseltine, president of ACCESS Health International and a former professor at Harvard Medical School. Kristen, I want to start with you because you have been on the phone with states around the country, officials dealing with the vaccine rollout and the actual administration. I just want to ask you what they are saying about what difference they think that these announcements will make. Kristen Holmes (KH): Well, John, the response is really twofold. One, they are breathing a huge sigh of relief. Keep in mind, the state officials did not believe that they were going to see any sort of increase in the vaccine until late April or early April, late March. This is a welcome discovery here. This is very welcome. But there is a lot of skepticism here. I want to read you one thing that one state official said to me. He said, so Sunday they said they don’t know what the vaccine supply is and now two days later, they not only know, have a handle on it, but they say they can increase the supply. There is some skepticism here. One thing we have to keep in mind is these states have really been through it all. They are on the front lines fighting this coronavirus and they have been promised things before that really haven’t come to fruition. Even the most optimistic state officials I talked to yesterday essentially said that they really, really hope that this is going to happen, but they also are waiting to see it to believe it. Alisyn Camerota (AC): Professor, we have heard some of that sentiment from Governor Cuomo yesterday from New York. Listen to him. Governor Chris Cuomo (CC): It’s true, it’s not enough. Is sixteen percent going to make the difference for those states that can administer the vaccines at a higher rate? No. Look, at this rate, we are talking about months and months, obviously. 2159
AC: That is obviously the news that governors got, that they would be getting sixteen percent more vaccine supply soon. William Haseltine (WH): It is good news that they will be getting more vaccine. But it is also good news that they are getting the vaccine, because that was a question. How much was there? So I think the fundamental message is a very positive one, and also, it helps them plan. Now that they know three weeks in advance, they can plan. Let me say there is another part of the plan that is really important. The states desperately need more money they can help implement the vaccine program. It is not just enough to get the vaccines to the states, we have to make sure that once the vaccine is there, people can receive it and that is a very local matter. And the states are desperate for money. Some are totally out of money. Some are just at their wit’s end as to what to do. Putting in The National Guard, paying for The National Guard, all of those are really important steps. Also, when you try to get the vaccine to minority groups, it is going to be expensive because rather than going to all of the major centers, you have got to distribute it to many local centers where people are, where those people can get to the vaccine early. That is expensive and it is going to require state money and the state money has got to come from the federal government because the states just do not have it. JB: Professor, can I ask you? We are going to hear from the government’s top scientists today for the first time in a long time. We will hear from Fauci, the CDC director Walensky, and they will be talking about all kinds of things. We have not been able to ask them questions like this in one place. What would you ask them? What is the one thing that you would want to know right now from the government’s top scientists? WH: I would want to know where are the rapid tests? Where are the tests that will allow people to know whether they or their families are infected and how soon will we get them? That is a very big question. Second question I would like to ask is, are you planning incentivized isolations. What has happened with that program? It is not enough to know somebody is infected. You have got to do something with those people and help them isolate. Where are those programs? Those are the two big unanswered questions I have because mitigation is absolutely essential while we wait for the majority of the population to be vaccinated. 2160
AC: Okay. Let us talk about the other big news on this front and that is schools. And there is new research from the CDC that shows that on balance, it appears, that kids have really suffered, as we know, being out of school mentally, their education, their emotional level, and that going back into school, schools have not been seen as super spreader places. They are not the same as nursing homes or meat packing plants. Here is one study that was from Wisconsin schools. I believe maybe in rural areas. Thirty seven percent lower incidence found of coronavirus in schools versus the surrounding community. In other words, it’s safer to be in school than to be out of school, Kristen. And then 191 cases found amongst students and staff, but only seven student cases linked to in-school spread. And so now there is this push to get kids back into the classroom, but of course, there’s all sorts of complications, because teacher’s unions and teachers want certain parameters hit in terms of safety measures and not all schools have those. KC: That is right, Alisyn. Remember, this all comes down to money. I, myself, am a former public school teacher, and when I wanted any resources when I was teaching, I bought them myself. So, when you are talking about these studies and talking about what these federal officials are saying, they are saying with proper social distancing and proper precautions in place, that that’s when it’s safe to go back to school. Well, what are those precautions and how costly are they and can these schools actually afford it? There has been a lot of talk about how private schools have gone back but public schools have not. A lot of this comes down to money. These teachers want reassurances that they will be able to actually afford and pay for the precautions necessary to keep them safe when they go home to their families. Obviously, this is incredibly welcome news. As you said, we know that kids are struggling at home. They aren’t meant to learn on computers and they are meant to interact with ore children. It is just how exactly this can be implemented. JB: Kristen Holmes, Professor Haseltine, thank you very much. As I noted, we are going to hear from the nation’s top scientists later today, their first coronavirus briefing. And then again tonight, Dr. Anthony Fauci, Rochelle Walensky, head of the CDC and others.
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Interview on NHK: Biden's Coronavirus Strategy January 28, 2021 | Interview
US President Joe Biden has been in office for a week. But he's already laid out plans to fight the coronavirus and get Americans the vaccines they need. William Haseltine is an infectious disease expert and the founder of Harvard University's cancer and HIV/AIDS research departments. NHK World's Catherine Kobayashi spoke with him about Biden's strategy and what to expect. This interview originally appeared in NHK World and is available online here: Interview on NHK: Biden's Coronavirus Strategy
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Interview on CNN Tonight With Don Lemon to Discuss Covid-19 Vaccinations January 29, 2021 | Interview
Don Lemon (DL): A big jump in coronavirus vaccinations today, almost 1.7 million new doses administered, well over President Biden’s hope for a target of 1.5 million doses a day. We are also getting closer and closer to a new vaccine becoming available in the war against the virus. Global trial data is in for drug maker Johnson &amp; Johnson’s vaccine. Their single dose shot is eighty five percent effective against severe coronavirus disease but only sixty six percent effective in preventing moderate and severe disease. So, joining me now is Dr. William Haseltine, a former professor at Harvard Medical School and the chair and president of ACCESS Health International. Professor, thank you so much. Good to see you. Eighty five percent effective at preventing severe diseases with no deaths or hospitalizations during the trial. Dr. Fauci says Johnson &amp; Johnson results are encouraging. Listen, I was going to say do you agree. I do not care if it is eighty five or seventy five or sixty five, I would still want it. But go on. William Haseltine (WH): Well, I would say the news over the past week has been good and it has also been concerning in another respect. But the good part of the news is that there are two vaccines that seem to work reasonably well. One is Novavax. It is a vaccine using a protein and an adjuvant. I actually used a vaccine very much like that thirty five years ago to create a vaccine against cat leukemia. These are good vaccines and they work. The second is Johnson &amp; Johnson, which you have just pointed out also works reasonably well, with a caveat for both of them, in some populations for some viruses. As we now know there are many variants and unfortunately these vaccines are not nearly as active against one of the variants in particular, the South African. And we are looking at them at their very, very best, just after they are fresh into people. These vaccines as they age will become weaker against the natural 2163
viruses and will become even weaker still against the variants. So that is a problem. Those who are vaccinated, if the variants are circulating widely, are going to still have to take precautions against being infected with the variant and we now have evidence that if you have been infected you can be reinfected by some of these variants. So, you are going to have to take precautions there. DL: But still take it. WH: Take the vaccine for sure because there are a lot of variants, a lot of natural variants that have not varied out there. They will help you. The vaccines may be partially effective against the new variants. Take the vaccine when you have the chance. DL: So, let us talk more about these variants, since you mentioned them, all right. IHME is updating their model to predict 85,000 additional deaths by May because of them. They say the death toll could get as high as 654,000. Are we in a race against time to get the situation under control before these variants start to take over? WH: We definitely are and the variants are already on the move. I think another way to look at it is what is going to happen next fall? Will we through vaccination and strict public health measures be able to cut this off at the pass? Will we be able to drive this down to close to zero where it needs to be? Or will we do what we have done before without vaccines, which is drive it down, but not eliminate it. If we do not eliminate it with a combination of vaccines and very strong public health measures, both are needed, one is not alone, if we don’t drive it down to zero, we may be looking at a big problem next fall. These viruses come back like the flu. We have a vaccine for flu. We have some public health measures for flu. It comes back. These viruses are the same kind of behavior. DL: You have to update the flu one every season, right? WH: Right. DL: And the same for this? WH: Same for this. Not only that, you do not even know exactly what to shoot for because these viruses change very quickly. It is like a growing tree. Which branch of the tree are you going to go after? The right side? The left side? The middle? The top? Maybe all of them together. It is difficult.
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DL: Hey, professor, listen, I have to run. But, so, if you can get the Johnson &amp; Johnson one and then later on get another one, should you do that? Will that help? WH: I think it surely can because people will be making boosters, like they do for the flu, that are hopefully going to catch the new variants as they pop up. Thanks a lot for the question. DL: Professor Haseltine, good to see you. Have a great weekend. Be safe.
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February 2021
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Interview on CNN’s ‘New Day’ To Discuss COVID February 1, 2021 | Interview
Speaker: …from England is going to happen in the next six to fourteen weeks. And if we see thathappen, which my 45 years in the trenches tells us we will, we are going to see something like we havenot seen yet in this country. Alisyn Camerota (AC): A dire warning about the new COVID variants. So, where are we this morning with tracking the coronavirus? Right now, new infections in the United States are down fifty percent from their peak in January and hospitalizations have fallen below 100,000 for the first time in two months. But January was also the deadliest month of the pandemic, with more than 95,000 Americans killed. Joining us now is William Haseltine. He is the president of ACCESS Health International and former professor at Harvard Medical School. Professor Haseltine, I think Americans are confused about whether things are getting better or getting worse. What is your take this morning? William Haseltine (WH): It is a good time to be confused. They are getting better. But you have to remember, we are actually about twice the peak of infections that we had the last time around. So, things are getting better, but they are not great. They are getting better because the rate of infection is falling. But that comes against a background of understanding that this virus is changing fast with a potential that the vaccines may not be as effective and that prior infection may not protect you. And it is not just the U.K. variant or the south African variant. Today, at least half of the new infections in the L.A. area, the California area, is from our own homegrown variant. And I believe there will be many. And the homegrown variant is really different from the South African or the Brazilian variant. So, we are going to be dealing with a host of variants that we are going to have to be trying to control. And so, I think that is what is behind the previous speaker’s
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comment, that there are lots of variants that may evade immunity from vaccines or natural infection. John Berman (JB): I think one of the problems that we have had is that leaders for months and months have been suggesting that there is light at the end of the tunnel. The end is just around the corner and I think it has been raising irrational hope that there are days or weeks away from this being over and we are just not. We are just not and people need to understand this is a long process and we are just at the beginning of turning whatever corner we are. To that end, professor, Michael Osterholm and others, it is not just him, others have now suggested that in order to battle what could be a new wave as these variants take hold, that maybe we should get as many people as possible the first dose of a coronavirus vaccine, Moderna or Pfizer, not worry about getting the second dose to them yet. Get as many people as possible one dose. What do you think of that? WH: You know, I understand what he is trying to do and it is admirable, trying to give at least some protection to as many people as possible. We have two problems with that. The first, they may not get fully protected, and that might accelerate the rate of variants taking over and causing us much more trouble in the future. And secondly, we really do not know if delaying the second dose for a long time is going to give you the same degree of protection as putting two doses at the same time. So, there are two issues. So, I would come down with the CDC and the health department at this point of recommending the doses be spaced equally. Let me just say, in terms of the first point you made, how long is this going to go on? We know that flu comes back every year. If you look at coronaviruses in their natural habitat, that is us, they come back every year. And there is no reason at this point, with the information that we have about variants, to think that immunity won’t wane and that the viruses won’t come back in a different form, just like flu. We live with flu. We contend with flu, with changing the vaccines and soon, I think, we’ll have better drugs for both flu and for coronaviruses. This is going to be a long, long battle. Not a year-long battle, a decades-long battle. AC: Professor, one more follow-up question to what you were just saying about the homegrown variants that are being discovered
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now. Do we know their characteristics? Are they more contagious? Are they more deadly? What? WH: Well, they are very likely more contagious because they are taking over the previous virus that was there. That is how you know it’s more contagious. If you have two types of viruses that are infecting the same population and one dominates the one that was there previously, you have prima facia evidence that that is more infectious. That is how we understood the UK virus, the South African virus, the Brazilian virus. The southern California virus looks very much like that. In Ohio, there is a similar situation, where a completely different variant looks like it is been taking over infections in Ohio. Whether it is more lethal or not, there is some slight evidence from the U.K. that one of the strains is. Another worrying feature of some of these variants is some of them prefer, actually have a higher preference for children than the original strain. So, we have to be more careful with what we do with our children and we have to consider that as we think about opening our schools. AC: That would be a game changer on every level if kids were becoming more sick. WH: Well, they definitely are. They definitely are, in the south African strain and there is some good evidence that has happened in the U.K. strain, as well. AC: Professor Haseltine, thank you very much. We always appreciate getting information from you. WH: Thank you, Alisyn.
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Interview on CNN’s ‘Erin Burnett OutFront’ To Discuss COVID February 1, 2021 | Interview
Erin Burnett (EB): Breaking news. President Joe Biden just wrapping up a meeting with republican senators on coronavirus relief. It comes as the CDC director tonight warns the United States is not doing enough to identify those highly contagious strains of coronavirus. Up front now, Professor William Haseltine, groundbreaking HIV and AIDS researcher. Also author of the new eBook Variants: The Shape Shifting Challenge of COVID-19. That is what this comes down to right now, Professor Haseltine, these variants. They are coming up in multiple places, mutating in different ways, that they are more transmissible, and that some of them are certainly also more deadly. How far could these variants set us back? William Haseltine (WH): These variants could set us back a good deal. If we look at the immediate future, we are going to have relatively good news. Rates of infection are declining. We have to look forward to what is going to happen in the fall. At that time, the variants, there are three from abroad, at least two serious variants here home grown in the United States, those can evade, at least partially, our vaccines and those people who have already been infected will not be protected from some of the variants. We can look forward to a recurrence. Whether it is a category five hurricane that is predicted by Dr. Osterholm or whether it is a category two or three, it looks like it will be serious come fall. EB: That is a lot of death in either case. Let me ask you about something we saw in The Wall Street Journal. They were going through a sobering timeline from the education minister of Singapore and that minister says, “It may take four to five years before we finally see the end of the pandemic and the start of a postCOVID normal. You said this will be a decades long battle, much worse than what we see every year with the flu. Explain.
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WH: Well, if you look at the coronaviruses, it looks like it is behaving just like those. They come back every year and they come back pretty much in the same form. Only difference is they give you a cold and this kills about one out of every 200 people it infects. The flu virus comes back every year. It is about one-tenth as lethal as this. Even so 20,000 to 60,000 Americans die every year. Multiply by ten, we have a serious problem. I think the vaccines that are being developed now will have a blunting effect on that. They will not make it go away anymore than the flu vaccines make flu go away given their short duration and virus variation. So, we have to prepare ourselves for a long battle. That means obeying public health advice, it means staying home when requested to, and it means doing everything you can to avoid you and your family getting infected. And it means the government doing everything it can with its great resources to prepare us with new drugs, new tests, and new vaccines. EB: And your view on this is, yeah people are hopeful. Even Dr. Fauci said maybe there will be spectators, he did not say how many, but spectators in the stands this summer. You think that is when we will see things shift again? What you are saying is that this is a very long time before any of us would be in a world that anybody would define as normal. WH: We live with flu, but it is not killing as many of us. I think what many of us are afraid of is we have seen two periods of hope followed by this terrible disaster of the winter disaster. We have seen what happens if you do not eradicate this virus. Four countries in the world eradicated this virus and are in a much better position than we are. We cannot do it. We have to muster the popular will to do it. It cannot be done only by leadership. It has to be done by each and every citizen. We have to muster the will to do what’s needed that four other countries have already done to eradicate this so it does not come back and damage our economies and damage our life. EB: Professor, thank you very much. I appreciate your time. WH: You are welcome. Thank you.
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Interview with Conversation on Health Care: COVID-19 Is Shape-Shifting: Dr. William Haseltine Warns Variants & Lack of Containment May Weaken Vaccine Efficacy February 1, 2021 | Interview
This week hosts Mark Masselli and Margaret Flinter speak with scientist and entrepreneur Dr. William Haseltine, founder and CEO of ACCESS Health International, who warns the growing number of COVID-19 variants will help the virus evade the vaccines currently being deployed. He cautions that lack of strict public health measures, particularly in the US, will lead to more widespread infection and endemic outbreaks. Dr. Haseltine urges the pharmaceutical industry to provide more nuanced data on the long term efficacy of vaccines, along with more widespread genomic testing of COVID strains to better understand their impact on COVID-related illness. This interview originally appeared in CHCRADIO.com and is available online here: Interview with Conversation on Health Care: COVID-19 Is Shape-Shifting: Dr. William Haseltine Warns Variants & Lack of Containment May Weaken Vaccine Efficacy
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Interview with Erin Burnett on CNN February 1, 2021 | Interview
Erin Burnett (EB): Breaking news. President Biden wrapping up a meeting with senators on Coronavirus relief, as the CDC warns the United States is not doing enough to identify those highly contagious strains of Coronavirus. Up front, professor welcome Hazeltine, author of variants, the shape shifting challenge of Covid19. It comes down to these variants, they’re coming up in multiple places, mutating in different ways, that they’re more transmissible, and that some of them are certainly also more deadly. How far could the variants set us back? William A. Haseltine (WAH): These variants could set us back a good deal. If we look at the immediate future, we’re going to have relatively good news, rates of infection declining. We have to look forward to what’s happening in the fall. At that time, the variants, there are three from abroad, at least two serious variants here home grown in the United States, those can evade partially our vaccines and those people who are already infected, will not be protected from some of the variants. You can look forward to recurrens. Whether it is a category five predicted or whether it is a category two or three, it looks like be serious come fall. EB: That’s a lot of death in either case. Let me ask you about something we saw in “The Wall Street Journal.” They were going through sobering timeline from the education minister of Singapore and that minister says, quote, it may take four to five years before we finally see the end of the pandemic, and start of a post Covid normal. You said this will be a decades long battle, much worse than we see every year with the flu. Explain. WAH: Well, if you look at the Coronavirus, it is behaving just like those. They come back every year and pretty much in the same form. Only difference is they give you a cold, this kills one out of every 200 it infects. Flu virus comes back, one-tenth as lethal as this. Even sio, 20 to 60,000 Americans die every year. Multiply by ten, we have a serious problem. I think the vaccines that are being 2173
developed now will have blunting effect on that, they won’t make it go away and more than the flu vaccines don’t make flu go away. So we have to prepare ourselves for a long battle. That means obeying public health advice, it means staying home when requested to, and doing everything you can to avoid getting infected. And it means the government doing everything it can with its great resources to prepare us with new drugs, new tests, new vaccines. EB: And your view is that people are hopeful, even Dr. Fauci said maybe there will be spectators in the stands this summer, you think that’s then when we’ll see things shift again? I don’t think any of us would say we’re in a world that’s defined as normal. WAH: We live with flu, not killing as many of us. What many of us are afraid of, we have seen two periods of hope followed by a terrible disaster, winter disaster. We have seen what happens if you don’t eradicate the virus. Four countries eradicated it and are in better position than we are. We can’t do it. We have to muster popular will to do it. It can’t be done only by leadership, has to be done by each citizenH. We have to muster the will to do what’s needed that four other countries have done, eradicate this so it doesn’t come back, damage our economies and life. EB: Professor, thank you very much. I appreciate your time. WAH: You’re welcome. Thank you.
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Interview on ‘CNN Newsroom with Michael Holmes’ To Discuss COVID February 8, 2021 | Interview
Michael Holmes (MH): Professor William Haseltine is the president of ACCESS Health International, a think tank and advisory group. He is also a former professor at Harvard Medical School and the author of the new book coming out February 15 online, Variants: The Shapeshifting Challenge of COVID-19. Professor, great to see you. I wanted to ask you about this because you are the expert in it. How alarmed are you about the various variants and the vaccine efficacy, the UK and South African variants in particular? And, of course, remembering the UK lags the world in sequencing, so we do not really know the true spread, do we? William Haseltine (WH): Well, thank you for asking me the questions and I have just been deeply immersed in the issue of variants. Let me just begin by saying we are so fortunate to have these vaccines. We are rolling them out around the world as fast as we can, some places faster than others. But the vaccines are going to give us an additional wall of protection. But unfortunately, we are now learning that protection may not be complete. This is a virus, like all viruses, that has to adapt to a circumstance. It has to go from one person to another through the air or the surface or in the water. It has got to get into your body. It has got to replicate and it has got to get out again. And it has got to fight off your defenses while it is doing that. Now, your body has a lot of defenses. You have your immune system. You have surface barriers. There is a lot of defenses your body has, but the virus has its own ways of attacking us. I call it machine intelligence, artificial intelligence It just throws trillions of combinations at a problem that the one that works is the one it takes. MH: You think that we are going to just have this around forever and maybe we will just get a shot every year the same as we do with the flu. With variants and so on, do you think it will be more deadly? 2175
WH: What is the virus actually doing that we see? It has become more transmissible. It has become able to evade our immune defenses, whether you have been previously infected and making the vaccines only partially effective. And it is more lethal. The British just published a study that says it is thirty percent to thirty five more lethal in younger people and in older people then the previous variants. So, it is already pretty lethal. It is about one out of two hundred as compared to one out of two thousand or less with flu. So, we are facing a really serious issue if this thing gets out of control. Now, I will tell you the really good news and bad news. The good news is human beings can use their intellect to fight this virus. That is what five countries have done. They have tamped down this infection to zero or as close to zero as you can get in a world that is infested with virus. How have they done that? Public health, identification of the infected, rigorous contact tracing, isolating all those possibly exposed for two to three weeks then you get back to normal. Very few countries have been able to do that. That is what we need to do. Vaccines will help us make the problem simpler. But unless we eradicate the virus, you know, if you look at the history of Europe, first wave, people relaxed, second wave, people relaxed, third wave, people may relax. Unless you drive it to zero through a combination of vaccines and really strict public health. And with really strict public health, you do not have to do it that long if you do it right. If you look at all the countries that succeeded in stamping out their major infections, they have done it in a matter of three or four weeks. That is all it takes. Three or four weeks of real discipline. So, together with the vaccines, if we can get the will and the leadership together, we can beat this. But if we do not beat it, we are facing something like the flu, but much more deadly coming back every year. It is time to get serious. MH: Indeed and good advice. Professor William Haseltine, thank you so much. I really appreciate your expertise. WH: It is a pleasure. Thank you for your time.
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Interview on Euronews To Discuss Covid-19 February 8, 2021 | Interview
Jack Parrock (JP): The EU has changed its guidelines on the Pfizer/Biontech jab increasing the number of doses that can be given out. Now doctors can draw up to six doses from each vial of the vaccine instead of just five, boosting the number of available doses by twenty percent. For more on this, we are joined by Dr. William Haseltine, the president of the think tank ACCESS Health and author of My Lifelong Fight Against Disease. Thanks so much for joining us tonight on Euronews Tonight. This is already approved and practiced in the United States and in the United Kingdom. Is it something you would recommend? William Haseltine (WH): Well, taking more, six rather than five doses from the same vial is actually giving as far as I understand the same dose because they overfill, deliberately overfill the vials. That is certainly okay, but I think what isn’t ok is suggestions that you dilute the vaccine by fifty percent. That is probably dangerous. We have no idea what that will do. What it could do is give us some optimal immunization which is a good condition to develop viral resistance, resistance to the vaccine. If people are not fully protected, the virus can learn how to get around whatever immunity that vaccine gives. So, one extra dose is not a problem because the vials are overfilled usually, deliberately overfilled. But the suggestion to dilute it by half is not a good idea. JP: Now, this is all about the Pfizer/Biontech vaccine. Could this happen with the other vaccines? Is that an option to draw more doses out of vials from the other options? WH: I suspect but do not know for sure that all vaccine manufacturers overfill a little bit. But giving a suboptimal dose, a sub approved dose, a sub tested dose of a vaccine is not a good idea. As I said before, what that can do is teach the virus how to evade the immune system. We know now from real observations of patients who have been exposed and infected to the virus for a long time and given convalescent serum that the virus learns how to get around the 2177
human immune response. It knows how to do that, and it will do that if we are not careful. It is doing it right now in some ways to getting around our normal response. We do not want to do anything to accelerate that process. JP: Now, the British government is suggesting that they are going to delay giving out the second dose of the vaccine so everyone can get that first dose first. Is that something you would advise or would you advise against it? WH: I would advise against that also because you are extending the period in which you have a very large number of people with partial immunity. Partial immunity is a very good way for the virus to learn how to evade whatever immunity we are trying to do. When a virus encounters a person that is vaccinated, you want the virus to be suppressed right away. You do not want it to be able to get in and learn how to get around the immune system. It is exactly like giving somebody a suboptimal dose of an antibiotic. That is how we create antibiotic resistance. That is why doctors will tell you take your full dose of your antibiotic so the bacteria that are in you do not learn how to get around it. Well, the same thing for with a virus. Well, we do not want a large population of people around with a sub-optimal dose of the vaccine. So, we know what is shown to work. We should stick with it until we do a trial to know that a suboptimal dose or a lower dose works as well, otherwise, we are running a grave risk. And by the way, the people are discussing this in Britain know that. They have said that. We are taking a risk. I do not think they calculate how bad that risk will be to have a whole other strain that is resistant to all the vaccines. I do not think they are really thinking that clearly about what they are talking about. JP: A stark warning that the virus could adapt. Dr. William Haseltine, thank you so much for your time on Euronews Tonight.
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Interview on WGN Infectious Disease Expert William Haseltine Discusses COVID-19 Variant Concerns February 9, 2021 | Interview
William Haseltine, Ph.D., joined WGN-TV Morning News to discuss the concerns about the variants of COVID-19 that are spreading around the world. He's written a new e-book called "Variants! The Shape Shifting Challenge of COVID-19" out on February 15. Dr. Haseltine is also the author of "My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19". His books are available at williamhaseltine.com. This interview originally appeared in WGN and is available online here: Interview on WGN Infectious Disease Expert William Haseltine Discusses COVID-19 Variant Concerns
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Interview on CNN’s ‘Erin Burnett’ To Discuss COVID Vaccine February 17, 2021 | Interview
Erin Burnett (EB): So, I want to go to now to Professor William Haseltine, groundbreaking HIV/AIDS researcher and our own Abby Phillip, our senior political correspondent and anchor of Inside Politics Sunday. Thanks to both. Professor, let me start with you. The Johnson and Johnson vaccine rollout going to be slower than initially thought, presuming it gets that approval. Ten million doses short of what they expected, and this comes as Dr. Fauci has pushed back Biden’s timeline for all Americans now to the end of July. Fauci said he wanted that to be April anyone who wants a vaccine can get it. Now it is July. Do you think the administration is being aggressive enough here? William Haseltine (WH): I think they are doing what they can. One of the things that is clear from the beginning is when you are manufacturing new drugs, new vaccines, which is quite complicated, you cannot be sure what you are going to get at the beginning. Over time, you get confidence in what you are doing. But these are complicated vaccines. Johnson & Johnson is a virus that in itself is complicated. You cannot predict how much doses you will get from each batch. To me it is amazing that Moderna, that Pfizer/Biontech has done as well as they have but we surely would like them to do better. EB: So, Abby, today, Vice President Kamala Harris refused to say whether to be mandatory for teachers to be vaccinated before going back to school. Obviously, the CDC has been clear on this. They do not think that vaccination should be a predicate for teachers going back to school, but the vice president did not go that far. And shortly after she did not do so, the White House press secretary, Jen Psaki said this: Jen Psaki (JP) : Neither the president nor the vice president believe that it is a requirement. It is not a requirement to reopen schools, but they believe that teachers should be prioritized. 2180
EB: Alright, so Abby, she knows what the CDC said so she is trying to stick with that. But look, they are having trouble. They are struggling on this issue, and perhaps because the CDC was pretty clear that you do not need teachers vaccinated to open schools. Why can’t they get this straight? AP: Yeah, it seems pretty easy actually to say what Jen Psaki said and what another White House advisor earlier today Jeff Stein said exactly the same thing which is the CDC’s recommendation is one thing to, that it is not a requirement for teachers to be vaccinated in order for schools to reopen, but yes, we would also like for teachers to be prioritized. It is not clear why they will not take that extra step. I think one hint is the obvious one which is that this involves an issue of teacher’s unions who are a major democratic constituency. They want vaccinations to be a pillar of the reopening plan. They also want a lot of other things. They want class sizes to be smaller. They want the metrics to be tied to community spread. But the Biden administration is clearly trying to walk this line and it seems almost as if there is a distinction between what they are willing to say through surrogates, through the White House press secretary, for example, and what Biden and Harris themselves are willing to say. At the end of the day, Biden and Harris were the ones who campaigned on the science. Their unwillingness to reiterate what the science is seems to undermine that pledge. EB: Right, right. I mean, that is the thing. When that was your entire message and the science is now saying you do not need this predicate, it is a pretty hard position to be in, as Abby points out. Professor, we know of a lot of variants now around the world, right? Some of them here in the United States. The ones we seem to know the most about are both more transmissible and likely more deadly. Now, we found a new study that the Pfizer and Moderna vaccines are still effective against the variant first identified in South Africa less so then the others. Antibody activity dropped. But, how far ahead of things are we when you look around the world and you see so many variants coming up and this thing mutating as quickly as it does. WH: Well, it is a rapidly evolving situation. The first thing I would say is the news that it is partially effective against these variants is very good news. We have seen some indications that is going to be true. The higher the immunity you get from these vaccines, the 2181
broader their activity. But it is also a matter of time. Over time the strength of the immunity drops somewhat and the difference between the first strain you are vaccinating against and the other strains gets wider, gets wider. That means it does not necessarily protect for going four months. So, I think there are some real questions on that score. There are also questions about how many variants are out there. Right now, I count five major variants spreading in the United States. There are likely to be more and we have to know the answer for all of those variants. So, it is a rapidly evolving situation. We are not going to know much more. We actually learn, almost every day goes by we are learning more about these variants, how they are spreading. I would just say one thing. People should be, first of all, get vaccinated and be even more careful. These variants can get through the standard masks and infect other people. They can begin to infect children more than they did before. EB: Well, I think it is important for people to understand this too. A lot of people seem to think a vaccine is going to be ok, now I can go back to seeing friends and family and people are starting to hear that that’s not yet the case. It’s hard to hear but significant. I know it has been consistent from you and others. Abby, I want to ask you one thing before we go. This is about the pushback that Biden is getting from the left flank of his party. They wanted this massive student loan cancellation, right, $50,000. He was asked about it. Stood firm, not going to do it. Today, AOC, Elizabeth Warren were actually joined by Chuck Schumer, a moderate, vowing to keep fighting on this issue. Can Biden hold back the progressive wing on this? AP: You know, Biden ran on not signing on to a lot of these things, but particularly on the student loan issue and that was reflected on how quickly and clearly he answered that question. I think for both sides it is important for them to make their positions clear on this issue. It does not hurt Biden to say I am not for $50,000 in student loan forgiveness because he is trying to be somewhere to the center and progressives also themselves really need to basically say we are pushing for our priorities. So, I think on both sides, it is really important for them to do that, but we also have heard even before the election from some progressives who suggested that a narrow majority in the senate and the house will almost force their 2182
hand. They know they do not want to lose out on some big wins in the interest of just pushing back on Biden. I think at the end of the day, they will sign on to COVID relief bills and other things if it means getting something instead of absolutely nothing. EB: Thank you so much.
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Interview on ‘CNN Tonight with Don Lemon’ To Discuss Winter Storms Delay Vaccine Shipments February18, 2021 | Interview
Don Lemon (DL): So, right now we need two doses of the coronavirus vaccines to be effective, but there is promising new research about the Pfizer vaccine. Let’s discuss with William Haseltine, former professor at Harvard Medical School. Thank you so much. Good to see you, sir. Also, by the way, he is the author of Variants: The Shapeshifting Challenge of COVID-19. Again, so good to see you. So, there is a new study out. It is out of Israel. It is published in the Lancet Medical Journal and they found that the Pfizer vaccine eighty five percent effective after the first dose. They looked at seven thousand healthcare workers who got the vaccine. So, tell us what this means. Good news? William Haseltine (WH): Not necessarily. We have seen hope versus reality many times. Our government experts do not recommend one dose only. The company does not recommend one dose only. I personally would say it is taking a risk. We know these variants are ready to pounce and it does protect, one dose, for a while, but it does not give you full protection and it may not last very long. The moment it weakens, a variant can come in and get you. I do not think we should keep putting hope against reality when we know we have kept on doing that and we have 500,000 dead Americans to show for it. So, I am not a big fan of one dose. DL: So, the White House says that weather is causing delays in vaccine shipments and deliveries, and the country is seeing a small dip in the average number of doses getting into arms. Do you think that we will be able to make up lost ground that happened over the last week or so? WH: You know, this administration seems committed to getting as much vaccine into people’s arms as the industry can make, and they are helping do that by supporting the local government with 2184
federal resources. The more we can do that, the better things will go. And I think by the time the first 100 days is over, we will exceed the goal that has been set. I would like to see and we would all like to see a lot more, but I think that they can make up for lost time. DL: So, Professor Haseltine, if someone is having trouble getting their second dose because of these delays, is it okay if a few extra days go by, or do they have to start all over? WH: No. A few extra days is fine. You know, you can wait a long time. It is that period between the two doses, the longer you go before you get your second dose, the immunity you have starts to decline. It may never be what it should be, and it declines somewhat. And that is where the variants can come in and take advantage. We know that we are in the midst of a wave of variants. There are five variants at least and probably more in this country spreading, and we know how fast they can spread. In Great Britain, they were a small fraction of the viruses at the beginning of the year, and they are almost all the viruses today. It can spread very fast and they are more dangerous. They are more lethal. They spread more rapidly. We have just learned something else. That one of the reasons for that, at least for the British variant, is it lasts twice as long in your body. It gives you twice the chance of getting sick and twice the chance of spreading it. So, these variants are nothing to fool with. This virus is a dangerous, wild beast, and you give it a chance, it will get you. And so that is why I think we have got to be really careful with a one-dose strategy. DL: Professor Haseltine, thank you so much. Appreciate it. WH: You’re welcome.
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Interview with Global News Radio: Covid-19 vaccine’s global approval process and efficacy February 22, 2021 | Interview
Charles Adler (CA): Our very first vaccine town hall as promised. Jimmy de Argensola [spelling, ??] and company have been working on this for a long time now. Questions and comments will be welcomed by you. And of course, we have got some of the best guests available all this week, second hour of each show every night this week here on Charles Adler Tonight, a vaccine town hall. Our very, very first special guest is Professor William Haseltine and it makes so much sense because he is a pioneer in so much that we talk about, groundbreaking research on cancer and HIV/AIDS. Professor William Haseltine, former Harvard Medical professor, and thank you so much for joining us tonight, professor. Appreciate it very much. William Haseltine (WH): Thank you. It is my pleasure. CA: Now, recently you have been commenting a lot about the variants. I want you to just tell us about what it is about the variants that you are focused on and how you feel they may be a game changer in 2021. WH: Well, the variants are a natural phenomenon. The virus is adapting to a new host, us humans, and the virus is adapting to what we do. I call it Protean in its approach. It is like the ancient myth where Menelaus grabs a hold of Proteus to try to get him to tell him the future, and as he grabs him, the very act of grabbing changes his shape. Well, that is pretty much what is happening with this virus. What are the characteristics of these variants that are of concern? First is, they are more transmissible. What does that mean? It means it takes fewer viruses to infect you. Fewer viruses that can get through a mask. Longer times in the room. It can hang in the room longer times. A fewer number of viruses can latch onto you. And the second thing is once they get into you, they grow better. They make more of themselves. They compensate for what your body is trying to do to shut it down by making more. They are also capable 2186
of evading many of your immune responses, some more than others, but some do it pretty well. That means they can get into people who have already been infected, especially if that infection has taken place a few months ago. And it also means unfortunately that many of the vaccines are not working. Now if that were not bad enough, it also we find that the virus replicates to higher concentrations. That means it is making you sicker and it can last longer in your body, not one week to clear, but at least two weeks in a very healthy person. So, all those spell danger to the very ways we seek to prevent this disease from spreading,our social distancing measures, our masks, and our vaccines. CA: We had a professor on a few moments ago, professor Haseltine, Amir Attaran his name, professor of law and medicine with a career in immunology. He spent time at places like Oxford and some others that you are very, very familiar with. Professor Attaran was saying that because of the variants that you are looking at, variants that you are describing, herd immunity is off the table for now. What is your response to that? WH: Well, starting last March, I said herd immunity never was on the table. It had two big problems to begin with. The first it was murderous to just let this virus roll as it would. It kills about one percent or half a percent of people it infects and if you let a whole country be infected, that is a lot of people. It is many millions in the United States. I call that a murderous policy. Second of all, it is a feudal policy because it cannot work. From the very beginning, I pointed out that the coronaviruses come back every year like the flu. The same virus comes back to get you again and again. And looking at that, it seemed to me like there is no reason to suspect that SARSCoV2, a coronavirus would not do exactly the same thing. And there were two reasons for that. The reason that was clear back then in March is that our immunity to natural infections does not last all that long. But what is clear now is not only does immunity not last, but the virus changes just like flu and the two shaping factors for flu, the annual recurrence, is short-term immunity and virus change. And we know something more about the virus change than we did before. In every person that has been studied so far that has what is called persistent infection, they have an immune defect. So, their immune system is not quite up to snuff. The virus can persist for many weeks. In every person that has been looked at, that virus 2187
accumulates many mutations, the same mutations in many cases that we see in the viruses that I was just talking about. So, these variations can take place in one single person. So, the concept of herd immunity was always a deadly concept for this disease, inappropriate for public health officials and government officials that have espoused and futile because it just did not apply. CA: So, the term herd immunity used to be applied, as you mentioned, the idea of just let the thing run its course, and a number of people will get killed, but eventually because people develop immunity you will get a herd immunity. The herd immunity that I was referencing is what is used a lot these days, not by people who want to let the virus run its course, but it is used by people who talk about the effectiveness of the vaccine. And once you get something like seventy percent of the population vaccinated, you will get herd immunity. The professor that we had on a few moments ago was pushing against that because of what he saw as the constant mutating of the virus and the so-called variants. Your take. WH: Well, I have coined a term I call seasonal population immunity. That is how I would describe influenza, seasonal population immunity. That is how I would describe the seasonal cold viruses, seasonal population immunity. I believe that is what we are going through right now in many parts of the world. What you see is you see a spike and then it falls off quickly, but that is not the end of the story. It smolders and then the next winter it comes right back. I think your previous professor has it exactly right. Now what can vaccines do? Well vaccines, of course, can modulate that if they prevent infection, but if the virus can escape the vaccines as influenza does, you have the same pattern over and over again. Now every year using the US perspective, we have 20 to 60,000 deaths. That virus kills about one out of a thousand to one out of two thousand people it infects. That is ten times less deadly than this virus. And this virus as it mutates, contrary to what people had hoped, is not getting less infectious, less mild, it is getting worse. It is very clear now that the British variant, B117, is more virulent, more deadly to older people and to younger people than previous strains. So, we are not going to have, I think at least, unless we are very, very lucky a situation where the vaccines give us our immunity. We are going to be playing catch up for, I think, decades to come unless we do what
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we should have done from the beginning is put in very, very strict public health control measures. You know, we are not hopeless in face of this virus. We have six countries, three of which had major epidemics, which have eliminated the virus from their shores. They have eliminated it. The only infections they have come in from outside. Why haven't other countries done this? Now we have the benefit of the vaccine. We must take maximum use of the vaccine combined with very strict public health control measures to put this thing to rest once and all in our countries, and then help all countries do the same. We can end this. There can be no COVID, but not with the kind of programs we are currently espousing. CA: Doctor, I want to give you the first question from listeners audience members in this vaccine town hall and I encourage everyone to text us right now or call at 1-877-399-9898. That is toll free, 1-877-399-9898. Professor Haseltine, text from Saunas in Salt Lake, Alberta. Here it is. Within the world of influenza, do we know if there are scientists already working on vaccines that can fit as many combinations, as many variants as possible to stop a future pandemic? WH: People have been working on that for a long time. It is a good question. Some of my former students are the leaders of that research. Unfortunately, it has not yet been successful. There are a number of good reasons. If that could be done easily, our bodies would have figured it out. The virus, you have to think of it is a biological war. Our bodies do one thing and the virus responds to doing something else. I look at it as two types of artificial intelligence, throwing random combinations at a problem. The only problem when it comes to humans versus virus, virus replication time is in minutes, ours is in decades and the way they can recombine, there is trillions of them. There is billions of us. They do it a lot better than we do it. And for all of the time that there has been interaction between these viruses and human beings, the viruses have learned to hide their key parts. And I worked for years on HIV, many people around the world who worked on HIV, despite huge amounts of effort, we have never cracked that problem. By the way, we have not cracked it for malaria, for tuberculosis and for respiratory syncytial virus, and many of the common colds. Nature through evolution over millennia is very clever at hiding most sensitive parts. That does not mean we cannot eventually be 2189
successful, but vaccines are going to be hard to do to knock out everything at once. Drugs, possibly, combinations of drugs I think very likely, but vaccines are going to be a much harder stretch. CA: Must be sure frustrating as a researcher, as a scientist, you, your colleagues. You throw the best brains in science around the world at these various diseases and they continue to outsmart us. WH: It is true. It is a machine intelligence versus our logical intelligence, but our logical intelligence tells us something else. It tells us that an organized society, Australia, New Zealand, Singapore, Taiwan, China can conquer this virus. We can beat it using our logic, not necessarily our vaccines, but our social effort. That is when people talk about public health efforts, I see going forward walking on two feet. One, we suppress it with the vaccines and with our drugs and the other, we come at it as strongly as we can with our public health measures. Together, we can conquer it. Medicine and science alone never has been a solution to most big medical problems. It is public health combined with the best medical and science. And I am far from being discouraged. I am energized by the excellence of the science around the world, and by the knowledge that we can be successful in eradicating it. It takes willpower. It takes organization, but certainly about one third of the world has mobilized itself to protect itself. We, unfortunately, have not. CA: It is a special vaccine town hall here on Charles Adler Tonight, taking your calls and texts at 1-877-399-9898. The germ guy, Jason Tetro coming up in just a few moments. We have got pioneer researcher in HIV and cancer, Dr. William Haseltine, former Harvard Medical professor with us right now. Doctor, here is a question from Brian about the goalposts that keep getting changed by the government and by others. This has to do with the fact that we were first told that the Pfizer vaccine, for instance, the world standard right now, that we would have to have a booster shot twenty one days after the first shot, then governments and others are moving these goalposts saying, well, maybe we can wait for thirty days, maybe forty five days. Some are now talking about even longer. What is your take on this business of delaying that second shot? WH: Well, the first thing I would like to say is that I recommend everybody who can get the vaccine to get the vaccine as soon as it is available to them. Second thing is, I am not a big fan of a long 2190
period between the two shots. The reason for that is the first shot does not give you full immunity and that immunity that does get give you it wanes and because the variants are there, the difference between the levels that might have protected you from the original virus are unlikely to protect you from the variants. So, it is much better for people to get both shots. There are people, and I think it is reasonable to believe that partial immunity in a large number of people can even accelerate the formation of a new variant. So, I am not a fan of that nor are the companies that make the vaccines nor are US government officials. CA: You have just brought up, what for me at least doctor, is the nightmare scenario. Could you explain to me why if we make people wait for that second vaccine, having millions of people with just one shot can enhance the variant process? Please explain that to me, if you could, in a minute or less, if that is possible. WH: What happens with variants is they get into people who have partial immunity and that allows the virus to replicate, but it is got to fight against part of the immune system. And the way it fights is it throws up all sorts of variants and the ones that succeed are the ones that get out of that person. And so having a large population that is only partially immune protected is a very good recipe for developing a lot more variants with nasty characteristics that can increase not decrease the problem. That is why I, and many people like me are not for delaying the second shot. CA: So, the takeaway from this, just to be clear, Dr. William Haseltine saying that waiting for a long time beyond the twenty one days for the second shot enables the production of variants. WH: We think it may enable is a better way to put it, but it is likely to enable, that is correct. CA: Well, I want to be as accurate as possible cause I take what you are saying very, very seriously. There is nothing more serious than this discussion right now, especially when it comes to the variants That is the last thing in the world that anybody wants to do. That is why I call it the nightmare scenario. Professor William Haseltine, thank you so much for your time as always, sir. Appreciate it very much. WH: My pleasure. Thank you.
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This interview originally appeared in Global News Radio and is available online here: Interview with Global News Radio: Covid-19 vaccine’s global approval process and efficacy
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Interview on ‘MSNBC Live’ To Discuss Covid February 26, 2021 | Interview
Stephanie Ruhle (SR): I want to bring in Dr. William Haseltine in. He is an infectious disease expert and president of ACCESS Health International. He is also the author of the new book Variants: The Shape Shifting Challenge of COVID-19. Doctor, let’s start talking about this Johnson & Johnson vaccine. The numbers seem to indicate that its level of effectiveness is not as high as it is with Moderna and Pfizer. Is that a big deal? William Haseltine (WH): It is not a very big deal because it is comparing apples to oranges. It is very difficult when you are running vaccine trials on different populations at different times with a different mix of viruses out there. When the earlier vaccines were being tested, we did not have the variant issue and the populations are different. So, I would say it looks pretty much equivalent. They all seem to be working pretty well and that is good news. SR: You are laser focused on these new variants, particularly the New York variant we heard about earlier this week. Yesterday New York City health officials said do not jump to conclusions and assume this is super dangerous. What do you think? WH: Well, when you look at the virus it looks a lot like a combination of the South African and the Brazilian variants which are the most dangerous out there. They are the most resistant to vaccines. When they infect you, they can infect you for a longer period of time. They can infect children at a higher rate than they did before and they are more lethal. I do not know why they say they are complacent about these. I would not be so complacent. These are potentially quite dangerous variants. That does not mean we are hopeless. We can use the same methods to protect ourselves, face masks. I actually recommend a face shield as well. So those methods work. The vaccines work partially but they do not work completely in protecting against these variants. As time goes on, the efficacy of the vaccine not only wins against the parent virus but it will wane even more rapidly against the variants. These are issues 2193
that we have to consider. It is not hopeless but we have got to know what we are doing when we confront these. SR: Deaths and new cases are starting to tick up a bit. Any idea why? WH: Well, I think there are two reasons. I look around the world and if you look in most industrialized countries, and in India, they have ticked up this week fifteen percent. In Italy, they have ticked up forty percent. There are probably two things going on. One is people are relaxing, It is getting to be spring, at least where it is warmer and people are getting out and mixing around more. In India they are going to mass weddings again where they had stopped and now they are. And then the variants issue. It is a mixture of both. It is hard to tell. But it is worrisome. We were hoping this would fall at a very steep rate. It is not doing that. At least now it has ticked up. It is a little ski jump in the U.S. and we do not want to see that ski jump get too high. We do not want a fourth wave. We have got to be careful. SR: We certainly don’t. Dr. Haseltine, thank you so much. >> If you are struggling to get vaccine where you live go to plan your vaccine.com or swan the qr code on your screen right now. There’s an interactive state by state guide and you can sign up for alerts to tell you when you’re eligible.
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March 2021
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Interview on CNN’s ‘New Day’ To Discuss Covid and Measures March 5, 2021 | Interview
John Berman (JB): Joining us now, William Haseltine. He is the president of ACCESS Health International and former professor at Harvard Medical School. Professor Haseltine, you say we are at an inflection point right now in the pandemic and we could go either way. What will determine the path? William Haseltine (WH): Well, what determines the path is the rate of the vaccine, how many people get the vaccine and how widely it is spread. And the second is people’s personal behavior. We know how this virus spreads. It is not a secret anymore. We know there are people not wearing masks, people going to restaurants, going into bars in big groups. You know, everybody can sympathize with the idea we have to recover. It is like a patient in a hospital. If you have had major surgery, many people are very eager to get out. And of course they want to resume their normal life. But we also know what happens if you get out too soon. You go right into the hospital. That is what we are worried about for society at large. We have seen big waves and we are just in the middle of the third or coming out of the third wave. Are we going to do what we did before and have a fourth wave? It is no longer decreasing rapidly in the United States. It is more or less a plateau at a very high level. It is plateauing at the highest level that we had back in July. Sixty thousand people infected yesterday. A thousand people died yesterday. If you project that forward and we just stayed at that plateau, that would be six hundred thousand people dying. This is not a time to be impatient. There is a light at the end of the tunnel, finally, and to get there, we have got to hold on until most people are vaccinated. Alisyn Camerota( AC): Professor, we are going to work on your audio. There is a little bit of an echo. MB: You got the Peter Frampton setting on for Professor Haseltine. 2196
AC: Which is not good. But I am going to ask you about, it was jarring for our medical experts to hear that Texas was going to, next week, end the mask mandate, given everything that you have just spelled out. But there are also a dozen other states, a little more, that have already done that or are in the process of doing that. And then there is West Virginia and the governor there, Republican Governor Jim Justice, who says that this is wrongheaded. Listen to him. Jim Justice (JJ): We are going to do the smart thing in West Virginia. We are not going to do the thing that is just politically correct. I do not know really what the big rush to get rid of the mask is because these masks have saved a lot, a lot of lives. AC: I mean, what do you think, professor? WH: Well, you know, West Virginia has done a great job. They have done it by following the data. They follow the data probably better than any state in the U.S. and they have had very good results. They have had very good results with the vaccination programs. They have had very good results with control. You know, we do not want to have another wave. And if we have one, it is because people are relaxing too soon. And they are relaxing in the face of what clearly are more dangerous variants. They are more transmissible. That is why people are [00:03:19,??] get rid of a mask and add a new mask. The immune response effects people again who have already been infected and possibly people who have been vaccinated. And finally, they can get through our [00:03:33,??], which in a previous virus, they couldn’t do very well. This is not a time to relax, it is a time to look forward to a time we can relax. AC: The Peter Frampton voice box works really well with “Show me the way,” but not as well with medical advice and expertise. Professor, thank you very much. Sorry for the audio issues.
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Interview with Susan Ryan of The Green House Project: A Sobering Look at COVID-19, Variants & Immunity March 10, 2021 | Interview
Susan Ryan sits down with William Haseltine, PhD, scientist, researcher, author, philanthropist, and currently president of ACCESS Health International. Perhaps best known for his work on cancer, HIV/AIDS, genomics and currently, COVID-19, he is an internationally recognized expert on the COVID-19 pandemic. Dr. Haseltine is dedicated to ensuring that quantum advancements in medical technology translate to improved health outcomes around the world. He is the author of more than 200 peerreviewed manuscripts and 11 books, including two on COVID. His new book, Variants! The Shape-Shifting Challenge of COVID-19, addresses the questions and issues around the virus, variants, and immunity. Dr. Haseltine offers his perspective on the pandemic, including what the U.S. got right, and what should have been done differently. In addition, he offers his thoughts on herd immunity, vaccines and variants, as well as strategies he identifies as essential to controlling the virus, and the brutal consequences of not controlling it. His thoughts (and warnings) are sobering and likely controversial, but definitely worthy of a listen. Finally, Dr. Haseltine casts a vision for eldercare that incorporates his perspectives gained from his career and global observations that places value on elders and their integration into the community. Susan Ryan (SR): Hello, everyone, welcome to the Green House Project’s podcast Elevate Eldercare. I am your host, Susan Ryan. And as we embark on a new year and think about what is on the horizon, speculation abounds on the opportunities and emerging trends that lie ahead. Never before have we been at such a significant time in our history. And in a new season of Elevate Eldercare, we continue the crucial conversations incredibly respected thought 2198
leaders, tapping into their wisdom and insights gained amid a tumultuous 2020 and how that informs where we go. We can and we must go beyond better and build and embrace a system that prioritizes people. In today's episode, I talk with Dr. William Haseltine, scientist, researcher, businessman, prolific writer, philanthropist, and currently president of ACCESS Health International. For nearly two decades, Dr. Haseltine was a professor at Harvard Medical School and Harvard School of Public Health where he founded two academic research departments, the Division of Biochemical Pharmacology, and the Division of Human Retrovirology. He is best known for his work on cancer, HIV/AIDS, genomics, and currently COVID-19. An internationally recognized expert on the COVID-19 pandemic, Dr. Haseltine is dedicated to ensuring that quantum advances in medical technology translate to improve health outcomes around the world. He is the author of more than two hundred peer reviewed manuscripts and eleven books, including two on COVID. A new book, Variants, The Shape Shifting Challenge of COVID-19, addresses the questions and issues around the virus, variants and immunity. Today, Dr. Haseltine begins our conversation by sharing his personal story of growing up amid the myriad physical and mental health concerns his mother experienced, and how that experience and sense of injustice drove him to pursue a very prestigious career as a scientist. He talks about the work of ACCESS Health to improve health systems globally and shares an example of how this unique approach works. Dr. Haseltine provides his perspective on the pandemic, including what we got right and what we should have done differently. He further dives into a discussion that covers his thoughts on herd immunity, vaccines and variants, and strategies he identifies as essential to controlling the virus and the brutal consequences of not controlling it. His thoughts and warnings are sobering and likely controversial, but definitely worthy of a listen. Finally, Dr. Haseltine cast the vision for eldercare that incorporates his perspectives gained from his career and global observations that places value on elders and their integration into the community. Let the conversation begin. Good morning, Dr. Haseltine. I truly find it an honor to be sitting across from you. We were saying how to bet it is by Zoom. And I know we had planned about a year ago to actually visit in 2199
person and that never happened due to COVID. But thank you for taking time to spend with me this morning on Elevate Eldercare. William Haseltine (WH): You are welcome Thank you very much. SR: So, I always enjoy hearing a person's why and really diving into what makes a person who that person is, what drives them. And for me, because I heard about your autobiography and downloaded it on my Kindle, I think you and I share a fascination with reading on Kindles. Nevertheless, I did begin reading your book and was fascinated with your why. But more than that, just kind of what got you to go into the field in which you have pursued and made a lifelong career. So, talk to me about that. WH: Well, first of all, when you talk about Kindle, I get messages from time to time saying congratulations, you are a great reader. You have been on Kindle for 792 days. SR: Oh, that is so cool. So, I must admit when I was traveling eighty percent of the time it was the way I took my library with me. WH: So, that is the best thing because you do not have a ton of books in your bag. SR: Exactly, exactly. So, I guess I am an aficionado of Kindle. WH: But anyway, so enough about Kindle. Thanks for the question. I wrote the autobiography to help young people think about careers in science in medicine. And I am actually writing a new version for even younger people, ten to fifteen. This is for young adults and older people to understand science and life. But the new one is called Science as a Super Power. SR: I love it. WH: And the reason is is that one person can make an enormous difference to the whole world. Certainly, Jonas Salk and John Enders made a great deal of difference to my life as a young person. They ended the polio epidemic. John Enders discovered the polio virus and Jonas Salk turned that into a vaccine. That is just one example that is relevant to COVID-19 today. But there are many examples along the way of people who I have encountered who have made a difference. James D. Watson, one of my mentors, worked together with Francis Crick, solved a really important problem, how we inherit, and not only solve the problem, but turned that into the most powerful tool for science and medicine that has opened up untold opportunities to understand, treat, and cure disease. So, it is 2200
trying to give people an idea, young people in particular, an idea of what a scientific career can be. Now, the other part of that is sort of a recurring theme is what is your purpose in life. I think that is something that young people really struggle to find. For me, it was pretty simple because I was very close to my mom, and she was very sick with many, many things, starting age four, or five. I still get angry when I think about the injustices that disease visited on that woman. Many, many diseases, psoriasis, septicemia, detached retinas, bipolar disorder, you name it. There were terrible things that she encountered one after another, and eventually it took her life, these diseases. And as a young person, I just did not think that was fair and I determined to do something about it. But it was not until really my first year at the university that I decided that the thing I could do is not be a doctor but be a scientist. And I still was ambivalent until I got to graduate school. And then a very eminent scientist, said, you know, I actually watched him doing some Nobel Prize winning experiments. I actually was in his lab watching him doing experiments and he said, you know, you can do more for medicine through science than you can as a doctor. And at that time, it was not so easy to be a doctor, physician, scientist. It is now. And I really decided that I wanted to do that. And that is how I have dedicated my life. But it has been broader than just using science. It is what I can do, through science, through business, through advising governments, whatever I can do. So, the common theme that goes through my various aspects of the career is what can I do to help other people leave suffering from disease. So, whether it is science, whether it is applying that science through creating new drugs, whether it is advising governments about health systems, and health systems reform, how to improve the care of the elderly, it has been a consistent theme. Right now, all of my expertise is sort of combined for COVID-19 because I look at it from a scientific point of view, I look at it from a public health point of view, I look at it from a government systems point of view, and I look at it from the point of view of its special impact on the elderly and what we can do. So, it is every chapter of my biography. Actually, I end the biography with the next chapter, which is turning out to be my work on COVID-19.
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SR: Just fascinating, I think when I started reading your book, I think first of all, I was struck. I do not know, I think for me, I had kind of a preconceived idea of what your background might have been like with an incredibly intelligent, stable family life. And when I hear you talk about your affection for your mother and the concern that you had for the diseases that she was faced with, and that ultimately took her life. And you go into great detail in in your book, which I found really just riveting. I kept reading and reading, but I think that is what drove you to make a difference and it sounds like that really has been the impetus of your very long and impressive career. You use the word dedicate. WH: One thing in the book that I think is important for kids to know is my family was difficult aside from that. I had an Asperger father, a bipolar mother, and there were a lot of troubles. And as a result of that, as a young kid, I was repressed to the point that I barely made it through school. SR: That is what I found fascinating. WH: I was considered to be one of the slower students. And it was not until fifth grade where I discovered I did not have to be where I was through reading that my world opened up. And I think that is something that young people need to know. A tough beginning does not mean a tough end. SR: I love that. And, actually, I have shared this with my grandchildren and said, so I am glad to know that there will be another version, the Science as a Super Power. That sounds pretty exciting to me. WH: That is already drafted and we are doing the artwork. We are looking for a publisher now. I am thinking about doing one step more. I have become a big fan of graphic biographies. There is a fellow I have met who has done six or seven graphic biographies of well known scientists. Most recent one was E.O. Wilson. Just before that, he did one of the three women who were involved in really interesting primate studies, Jane Goodall, Farsi, and others. So, it turns out that a six year old or a sixty year old can pick it up. I have just read six biographies that I might not have seen if they were not in this graphic format. So, I am going to be working to see if I can reduce it to a graphic format as well. SR: Well, you have to keep us posted on when you deliver on that. That sounds pretty cool. The word that you said, though, that 2202
I thought was a great word, it is you have dedicated your life, and that you went into it with a passion to really make a difference and to study it as a scientist, to use skill as a businessman, to look at government systems. So, there was so much that you said there. But I wanted to take us a little bit to what you did in establishing Access Health Foundation. Tell us a little bit about what it is, why it exists, kind of why you thought it was important, and kind of its broad reach. WH: Well, thank you. It is sort of a natural progression that I went through in trying to understand how you can use whatever power you have to make a difference. I had a couple of really excellent guys. First of all, I had mentors who had made major scientific discoveries and really changed the way we can solve our problems. And I have been really privileged to that. I have had four direct mentors who had Nobel prizes, and a couple of other really wonderful mentors. The second thing was, my progression was, what can I do to understand science better. As a young person, I wanted to get every single tool I could get so if there was a problem I was presented with, I was not limited by tool. The first kinds of tools I got were chemistry, biology. But I got all the way up to field theory in physics and mathematics because I did not want not to be able to solve a problem that I encountered. And I actually used my mathematical training, my physics training to understand some biological problems. But then I realized being an, and I put myself into a hospital setting where there was great research and great medicine. I realized that it was the pharmaceutical industry that turned ideas into practical medical solutions. I had no idea about that. I grew up on a military base where there was no business. I did not understand business. But I actually bought some books to learn about business, learned about venture capital, and started creating companies as a professor to do that. It was sort of early in the biotech revolution. And I created over the last, I do not know a number of years, about twenty five companies, directly involved in about twelve and brought about eight drugs to market. SR: Wow. WH: But then I created a very big company called Human Genome Sciences, which was not only to create a new series of drugs, but to create a whole new way to do research using genomics 2203
as a start. And just to make a long story short, it used to be that you see a phenomenon, you would go into the organ, the tissue, the cell, the protein, and the gene level. And that was about thirty years of work. With genomics, you could say, here is a gene, and a month later, you could start to do research to try to solve that problem. And it is not the genetics part of it, it is the genes are the instructions to make little micro bits of your anatomy and you can compare what is going on in a disease or healthy tissue, and very quickly home in on a couple of targets. So, we quickly opened up the entire field from a hundred targets to two to three thousand targets for antimicrobials, for antivirals, and I first used that for HIV, to find targets for HIV. Then I realized I could use it for all human genes. And that worked and we showed by example it worked. And then when something works, everybody copies it. That is what you want. You want to be inspirational so everybody sees this tool and it becomes such a natural part of your work that you do not even realize, it is like breathing. You do not realize this air that you are breathing. So, you just use that tool. I think that is one of my biggest successes, that was to change the way people think about how you do the beginning of drug discovery. But as I traveled the world and look out even further, I realized that we had all these wonderful new tools, we are going to find great new drugs. But unless we can get the drugs to people, it did not make a difference to health. And I started thinking about health systems. And that is how I got the Human Genome Sciences. What can I do that could allow these wonderful new drugs and vaccines and medical devices to get to more people? And there, again, I had some very good mentorships. I was very close to the Lasker Foundation. That was a tiny foundation. They used whatever resources they had to leverage government to do something more. And then later in life, I became part of the Brookings Foundation, Brookings Institution. I have been there now for twenty years, and they do the same thing. What can we do to make American governments work better? So, combining these two ideas, I thought, I am going to create a foundation that helps governments do their job better, to do health system strengthening. And the way I am going to do that, I am going to look around the world for the best examples, I am going to study them in detail, and then create organizations that are local, not 2204
somebody flying in from the US, a group in India, a group in China, a group in the Philippines, and a group in Southeast Asia, wherever they are, to establish roots, understand what is needed, and then work very closely with the highest government officials we can reach through real knowledge of what is in that country and what other countries do well. Let me give you a sort of one example. It turns out that India, fifty years ago, had no real ambulance system. And a very brilliant information technologist combined with Stanford groups to create a modern ambulance system where there is one call center for fifty million people, for fire, police, and ambulance and worked out all the information systems and all the medical, to train medical technicians, to create these ambulances, showed that it worked, got the government of Andhra Pradesh to do it. And today, it serves 850 million people. SR: Unbelievable. WH: It provides fifteen minutes in the city, twenty minutes in the countryside. Even if you are on a mountainside, they will go up with a stretcher for free, okay, for free. And the cost to them is about $15 a pickup. It is extraordinarily efficient. So, I wrote a book about it called Every Second Counts, and the idea is, here is an example. You would not think of it that it would happen in that kind of chaotic situation. But it is by far the best ambulance system in the world. If we did what they did in the United States, we would have a better system and save two hundred times our money for emergency services, according to a McKinsey study, and I found many examples like that. And so, we tried to take those examples and have countries that are willing to work on it adopt those systems. We created something called the Joint Learning Network for universal health care coverage sponsored by the Rockefeller Foundation, and work together with a group called Results for Development. And together we have issued like, something like, it is now continuing, but there are like fifty white papers on best systems like this ambulance system, or like an accounting system. I have taken that one step further and then studied the best transformation that I could find in the United States of an academic medical center that went from very poor results to the best in the country and maybe the best in the world in terms of patient care, research in their areas of research, and teaching. It went from losing a ton of money to making a lot of money, or they call it surplus. It went from being one of the bottom third in quality 2205
and safety to number one in the country for three years in a row. It went from forty ranking in medical schools to number three in the country. So, in all respects, patient care, teaching and research, it went from very low rank in number of NIH dollars for researchers to number one in the country for dollars per researcher. So, that is kind of, how do you do those transformations. This book goes into nuts and bolts. It is called Affordable Excellence. So, that is the kind of thing we try to do. We try to find the best examples wherever they are. And we have written two books on eldercare and dementia care, both in Europe and the United, actually three books looking at Sweden, Europe, and America, who has got the best kind of ideas for eldercare, and it is not clear, by the way who does. That is a very, very difficult area. And so that is how I got there and that is kind of the work we are doing now. SR: Well, that is fascinating. So, which countries are you working with predominantly? WH: We have a big program in China working on a number of issues there. The relationships with government are a little bit different from India. With India, we have a major program there. I would say it is our biggest success. We are a very active part of providing the infrastructure, information and other infrastructure and knowledge and training for a new program which is designed to give 500 million Indians at the bottom of the pyramid a guaranteed $7,000 a year in the medical care, which is about $35,000 in the US. That is a program that was designed. And we helped structure that program. We have helped, actually now helping in some areas to implement it. Very fortunate that we are trying to work now on information sharing to make sure that information is transparent across the entire 1.4 billion, almost now 1.4 billion Indians. So, it is really exciting work. SR: I am sure it is. Something that you were talking about, emergency medical systems in India, kind of the ambulance, every second counts kind of a thing. Why don't we adopt practices such as that? What gets in the way? You are talking about some things that, healthcare costs, I mean, when you are discussing WH: It is the cost and the outcome. I am so disappointed in our country. We invent the best medical technologies. SR: Sure, absolutely.
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WH: We have the best in the world hospitals. But if you look at our country, we are just a little bit better than the Dominican Republic in outcome. We are number thirty fourth and thirty fifth. We used to be in the top five in medical outcomes in the fifties and sixties. It keeps going downhill. We do not have a system that is equitable. I have done many, many workshops and I think the East Asians say if best, if you want to control cost, control price. We have such a powerful lobby to change our government regulations and we just do not do that. I will give you an example. I also began by looking at India cataract surgeries. They can do a total cataract surgery for a cost of about $27. Every cost included, including surgeon’s time, and they do this one group about a half a million a year, and one doctor will do fifty a day. Why don't we do that? We invented every single thing that goes into that. It has to do with what we are willing to do, how hard we are willing to work, how we are willing to control our costs. And by the way, their outcomes are better than ours. I was once at a Johns Hopkins surgeon who is observing them, he said poor the Indian who gets to me. These guys who do fifty a day are much better than me. Same with open heart surgeries, same kind of methodologies even better than ours. They do not even use heart lung machines, which are bad for your brain. Why don't we do that? We have no incentive to do it. We do not have a cost incentive and we do not have a quality incentive. That is part of what I looked at in this book, Affordable Excellence. Those are really deep questions about cultures. But I gave up on saying, here is a great example, take it. I now come to the conclusion that you have to find people who have decided they need what you are selling. That is a fundamental principle. Any kind of business deal I have ever done, the other guy knows before I show up what they need, and if I have got what they need, they will open their mind. But if they do not think they need it, no dice. They just will not talk to you. It is like a blank wall. So, talking to American ophthalmologists about efficiencies in India, no way. There is another problem. I remember having a conversation with Giulio Tremonti, when he was the Finance Minister and the Deputy Prime Minister of Italy. I say, we can show you systems that make your healthcare system much more efficient. Please do not do that. It is the only jobs we have that are growing in Italy I will be out of a job and our party will be out of power if I try to make things more 2207
efficient and reduce jobs in the healthcare sector. That is really deep. I call the healthcare lobby deeper than the grass. It is the dirt lobby because it is everywhere. Everybody has got a clinic, everybody got something. So that is the lobby, and it is a huge amount of our money. It is about, conservatively, twenty percent of our GDP. And it is the only sector which continues to grow. I call it also the ballast of our ship, of our economy. Other things may rise and fall, but healthcare, jobs and costs, and percent of GDP just keeps on rising. Those are deep and fundamental problems. And until those problems impact the health of the entire economy, it is just going to keep going. Very distressing. But we work where we can. We are optimistic. We see some very big changes over the year. And I do think when you see something like NYU Langone and how they have basically said, we do not care what the government is going to do, we are going to get better ourselves. You look at Rush in Chicago, same thing. We are going to work with a complex system that exists, and we will get to be the best. And they do. And that is the spirit that I think we have to be in. Yeah, there are big problems all over the place. But let's focus on what we can do locally to be the best we can be. And then whatever happens, like COVID happens, these two hospitals, by the way, that I just mentioned, Rush and NYU, are amongst the best in this time in COVID. NYU is one of the best when the hurricane hit. They got up and running. Tulane took four years. They took four months. So, these kinds of management changes are deep and important. It can change the equation for many people. And you know, but I tell you disappointments, too. I talked to Mayor Bloomberg about the ambulance system. He said, “Bill, what do you think people want to learn?” That was pretty cynical. And I talked to over the head of another major New York hospital about the book that I just written on NYU and how they transformed. He said, “I don’t want to read that book.” So, you know, there are serious issues. I don't want to minimize them. But there are still lots of opportunities and I remain optimistic. SR: And that is exactly the word that I was going to come back to. I still appreciate your optimism, and certainly the tenure of your career and your persistence and continuing to just believe that change can happen and let us start as they did at Rush or NYU, and let's be the best in that area. You also brought up COVID and so I 2208
would like us to transition to COVID. And, actually, that is what precluded my being able to visit you in person in New York City in March because that is when COVID was hitting New York with a vengeance. And your role has been somewhat significant. I have heard you kind of opine on different news outlets as well as I have seen some of your work in Forbes. So, talk to me from your perspective about the COVID crisis, a little bit about what we got right and what we did not get right, and we should have done differently. WH: Well, start from the beginning. I got deeply involved in AIDS at the very beginning and I realized that AIDS was a problem like cancer, it was not going to go away. And we did need an episodic response, we needed a systemic response, we needed to build in an institution like cancer research, cancer care, cancer management, patient management, for HIV/AIDS. And so, I did everything I can from research to government lobbying to private foundations, working with the top people, to try to create the framework for an institutional response. As part of that, I had come to realize that actually [29:42] this is not the last virus. There are going to be more. Here are the institutional things we need to do. We have not done very much of that. And again, through the years, other people and I have continued to warn. The famous warning came I think five years ago from Bill Gates. But it wasn't the only one. Everybody in this field knew things like this were coming. There were war games that were done, Dark Winter. There were movies, Contagion, that show exactly what is likely to happen. These are deeply scientifically, culturally, organizationally, government based views of what this can be. And there are many people, Laurie Garrett has been on this, as well and written a lot about this. So, we knew something like this could come, yet we were not prepared, even though we said the US was amongst the most prepared. Now, you asked what we got right and what we got wrong. We got a lot wrong, from government to science. Now, most people think we did science great. We got a lot wrong, and I will tell you about that in a minute. First of all, you need good leadership in a crisis, and we had terrible leadership, probably the worst we have ever had. And that has led us to a huge amount of death. We had poor governance, that is structural, that preceded leadership. We do not have a system where we can centrally control or manage health 2209
problems. It is all up to states and it is sort of a very weird government, and the powers that the federal government had were not used, and some of the powers they do not have. And even just now we are trying to deal with those problems. And then we have got a real problem of social solidarity in this country that was exacerbated by political leadership that politicized this issue. So, we know about those things. And are we going to get through that? Well, it has created four percent of Americans are responsible for twenty five percent of the deaths from this. It has been a total disaster. Now, nurses and doctors have done whatever they can. But with a virus spreading like this, it has just been terrible. But we have made some scientific and public health mistakes. We should have known from the very beginning that this was an aerosol transmitted disease, and we did not want to believe that. We did not want to believe it because it was inconvenient because there were some precedents that are dicey precedents. But if we looked closely at SARS, we would have known that. People got it on airplanes. It went through air conditioning vents in big buildings. And in fact, if we did not think that was true, President Xi told our president it was back in February. They knew it was so and then we blame somebody else for it, the Chinese are all to blame for it. They were not to blame for it. It happened to them to. They just controlled it better. So, aerosol transmission masking was a problem, then testing. Testing has been a horrible thing. Even today, even as late as today, when I read what this administration is trying to do with home testing. It is awkward and horrible. It is just not right. We should have cheap, free tests, paper strip tests for everybody so there's 100 million people a day who can use them at a nickel a piece. That is all it should cost. Test yourself, you can test your family, you can test school people. Just do the antigen test or whatever test. You can make it very cheap. We are still not on that track. And why we are not there? Another big mistake. We focused everything on vaccines, not on drugs. We are way behind where we should be on drugs. These are scientific misjudgments. Then to put everything onto the vaccine and not on to public health, even though public health people were screaming about that, has been a global misjudgment. Now, we realize that vaccine resistant variants are all over the place. That is an exaggeration, are popping up. We realized that is 2210
not the right strategy. And that now we are realizing this is going to be much more like the flu coming back and back again, we have got to, again, create an institutional response that looks at the whole society, how we manage this. One other problem that we have talked about is the issues with eldercare. Almost forty percent of people who have died have been in long term care homes, not just older people, people in long term care facilities. If there are anything that tells us that we have to rethink eldercare, it is that. If you think this is the only disease that is badly managed in eldercare facilities or long term care facilities, you would be wrong. This is just telling you how bad it is when flu comes around, when anything comes around. They are not just doing their job. And in a way you can understand that. These are vulnerable people, and they are much more likely to get some serious infectious disease and suffer from it than other people because older people immune systems are not well, they have multiple comorbidities. So, the idea that we are putting all those people together, and usually with inadequate staff, by the way, as hard as those people may work, they are just overburdened. And in some places, there are a bunch of crooks running these places, to put it not too mildly. That is the fact. And ever so often there is huge scandals, and it just shows you a weakness. I have been really worried about eldercare for a long time. I have written three books about it, as matter of fact, looking at best examples in other countries. And my conclusion is, we have to really deeply rethink how we are doing eldercare. We have to think about it as much care at home as we can. And by the way, that is what we have to do for all medical care. The biggest advance that NYU Langone made is to realize that eighty percent of all care can be done outside the hospital, including hip replacements, etc., on an outpatient basis. The next step is home care. So, we have to restructure our healthcare systems so that most of the care is done in communities. The VA has been trying to do that for a long time because they have a lot of people who have many serious diseases, they are not generally very well off, they have lots of comorbidities, they cannot afford to get to a hospital for kidney dialysis, for example. So, the peripheral rising care. And I think the more we can do that, talk about good examples. I have seen great examples in China. Fr example, there would be a housing complex, big buildings, you see them, in the middle of the city. But 2211
right in the center, there will be an eldercare, entertainment, healthcare facility, and people with beds and nurses. And they can go from their apartment if they need a few days in bed and go back to their apartment It is a continuum of care. And that is not all over China, but it is some places that are pretty successful. So, there are really interesting new ways of thinking about it. And I think COVID is really stressed that. We have put many of our older people at very serious risks not only for this. I am sure that if you looked at other disease indications, you would find they are dying at much higher rate from other diseases that are communicable that they should not be dying from if they were properly cared for. And the idea that, yeah, we are busy people running our lives that we cannot take care of old folks. Well, maybe that is true, but we should not shove them into long care facilities where they are liable to die. So, I think we have got to do a lot of work on restructuring how we think about eldercare. It is a whole of government, whole of society approach. It can't just be, let us leave it up to the healthcare system. It has got to be taken seriously by governments, state governments, and federal governments. It has got to be taken seriously by social workers. Another huge problem. We do not integrate medicine in social work and mental care. Those three things really should be integrated. Montefiore is trying to do that now. integrate social care, health care and mental care. That is a good thing to do, but it is a heavy lift, and we need a lot of our best minds thinking about really how to do that. I have gotten a little hobbyhorse here. SR: No, you have actually said so many great things. I am trying to think which one shall we tackle first. And, obviously, as you very astutely observed, a lot of mistakes were made. We have a new administration in and I heard you say that there are still concerns. You use testing as an example of where we are still not able to do what we could or should do with regards to that. You also talked about the vaccines, and we have put a lot of hope in this vaccine. There is much we are going to unpack here, but I would like to start with the vaccine and the variants that are out there, the efficacy of the vaccine, the belief I hear, espoused by many that to get shots in arms. Let's get the vaccine out there so that we can go back to normal, so that we can go back to living life, that normalcy we all crave. So, I would love for you to kind of set the record straight 2212
from your perspective as a scientist, researcher, as someone who has been in this. I love the way you said, let's go back to talking about HIV and AIDS and that virus and kind of we could have predicted this and in fact, we did. So, talk to me from your perspective about the great hope in the vaccine and what is wrong with that? WH: Well, I just was reading something Mike Ryan said. He is the person in charge of WHO Emergency Responses. He said, I hope we do not go back to normal. What he meant by that is not what we think is normal life, what public health thinks is normal, that we ignore, we don't have surveillance, we don't pay attention to things till it's too late. That is what he meant. So, it depends what you mean by getting back to normal. With respect to the vaccines, let me say, first of all, there is a myth in the US that this is the fastest vaccines that have ever been produced. No. In 1956, Maurice Hilleman produced a flu vaccine in four months. The Chinese beat us by a long way just by growing up the virus and killing it. And by the way, that might be a better vaccine than the ones we are making. We relied on super high tech. Well, the problem of those super high-tech ones, I have looked at them pretty carefully. They do not last very long, maybe three, six months, nine months. There half Life is about three months, especially in people over sixty. Wait and see. Some of these more traditional vaccines may be more robust. Just grow up the virus and kill it. So, we actually put our eggs into a super fast, super high tech basket, which may have been the right one. We have to see it, certainly I can see all of these vaccines losing potency after, certainly after a year and needing to be refreshed, and maybe even changed. That is a very specific thing now. But deeper than that is the notion that you can control this with a vaccine. You can control this without a vaccine or a drug. The biggest lesson unlearned is what happened very early on in Wuhan and in China. And that is, and when I say that, boy, everybody calls me a commie, a Chinese lover, who knows what they call me. Terrible names and emails pour in. It is a fact that six countries in control this disease, eliminated from their borders. Three of them had big epidemics, China, Australia, and Singapore. And they got it down to zero, except for a few cases that come in from the outside, to zero. And they did it within about two months, two months. And we know exactly how they did it because we taught them how to do it. After SARS, they spent a lot of time sending their top people 2213
over to the Harvard School of Public Health. And our professors went to even speak to the Central Party School for the top leaders on how to control a pandemic. They just instituted all the lessons that we in the West and we at Harvard, in particular, had perfected. We just have not used those methods. Now, if you ask what is a limitation to Biden's program? It is not testing. It is the failure to promote isolation of those who are infected and exposed. Mandatory isolation, whether incentivized or enforced, is the only way, in my view, to stop this infection. Vaccines can help. They are not going to stop it because the virus is going to vary and is varying and is going to come back. China eliminated within two months and got back to normal. Economies growing, people going to movie theaters. I have offices in Shanghai and Beijing. Maybe they say that prejudices me. It does not. Same is true in Australia, New Zealand, Taiwan, and Singapore. You can control it. And there is, I understand it. There are huge issues of social solidarity. Do not tell me what to do. Do not isolate me. Well, if the government doesn't have the power to save at least half a million of our lives, right, more than died in World War Two, and another half a million may die. What do they have the power to do? In my view, government's job is there to protect us. I give them my tax money so they will protect us. Okay, if they do not protect us, what are they doing? So, Biden's goes partway, but does not get to the core of the issue because they are afraid of political pushback, which I believe is real, and strong, and vicious. All of those things. I can understand why they do not do it. But if you don't do it, you can expect this thing to end. You cannot expect it to end. There is a known way to make it end and it is not the vaccine. We have had vaccines for flu forever. And is it over? No. Well, they say well, so it is like flu. Well, 20 to 60,000 Americans die every year from flu. This is at least ten times more lethal than flu. You want 200,000 to 600,000 people die every year and maybe more? Well, if you do not control this, that may happen. And it is not only medical control. So somehow, we have to confront that reality and that is something that the Biden administration is yet willing to do. They know it. I am not the only one who knows this. This is obvious to anybody who has my kind of background, or people in school of public health. We know what China has done. We know what Australia has done. We know what Taiwan has done and Singapore 2214
has done. We wrote the books. Right? So of course, we know what they did. We just not reading the books we wrote. I talked about that before. You need people to follow. You know, a political leader can just do things. Even in China, you can't just say it will happen. People have to agree, and we do not have a culture in this country which allows that kind of social solidarity. And it turns out, in Western Europe, it is kind of dicey too. So, what has happened? Everybody behaves for a little while, virus goes down, they loosen up, boom, and come back, close down again, comes back. We are in our third wave now. Why? because we did not squish it the first time or the second time. When I mean, squish it. I mean, no more transmission. I do not mean 100 or 200. I mean, none. One person can start the whole thing all over again. So, you have really got to get on it, and isolated. And so that is how I look at the vaccine. Yeah, vaccine is a great way to shrink the problem. These vaccines may be partially effective in saving lives for people who get infected with a variant. We do not know that yet. These variants are different from ones in flu. Some of these variants are much more transmissible, some of them are more lethal. There is going to be a lot of different variants, each one with its own flavor. And the more we do, actually, my analogy is Proteus. You grabbed him and he shape changed, right. And that is what we are doing. You wear a mask, the virus will adapt to get through your mask. You give him a vaccine, the virus will adapt to that vaccine. Drugs, the virus will adapt to that. That is the nature of these viruses. They are artificial intelligence machines that work really fast. So, we have got to use our real intelligence, our social intelligence, not just our medical intelligence, every aspect of our intelligence, we have to use to control this. SR: That was fascinating. And I want to ask one question about your thoughts on herd immunity, and a lot of people are, that is the other thing. WH: I call it population immunity and I have written to the very beginning is a fantasy, a dangerous fantasy, dangerous because many people die. If you allow 200 million people to be infected with a disease that kills one out of two hundred, well, you just do the math, that is a lot of dead people. Okay, that is the first fallacy. Secondly, it does not exist. And from the very beginning, I looked at coronaviruses and I realized that the four coronaviruses come back 2215
every year like flu. Well, it if they are coming back every year, what does that mean? And I looked it a little bit deeper and I found they are infecting the very same people. Same kind of virus, same one of the four infecting the same person. In one study, a number of people got infected two, three and one, even four times, in a six year period. So, what is that about? Natural immunity is bot protecting you. There is no herd immunity for these coronaviruses. There is no population immunity. I have a new term for it. I call it seasonal population immunity, flu, seasonal population. And the more you look and the deeper you look into what flu does and what this virus does, and I am looking really deeply down at the atom to atom level, it is very similar. The idea that this thing does not change as fast as flu, no. It changes just as fast. Maybe it does it differently, but it changes just as fast, and it comes back again. So, that is the kind of situation that we are looking at. We are looking at one where the only thing we can do to really put it to rest is systemic public health, isolation of those people who are contagious and exposed. And if we do not do that, we are in for years of trouble, which I think we are. SR: Well, which gets to your point about testing and really making it widely available so we know who is infected. WH: Testing is just the first part. What do you do with a positive test? SR: Right? Well, but my point is, you have to know who is infected to know how to isolate. WH: The Chinese did not do it that way. A lot of others did not. They said who is exposed? So, if you were on an airplane and one person on the plane was infected not by a test, because he got sick, everybody was quarantined for two weeks. SR: So, through contact tracing, then they were very WH: Yeah, contact tracing, everybody on the plane, or if somebody in the building is infected, whole building quarantine for two weeks. Somebody in a city, whole city quarantined. Even today, huge chunks of city are sporadically quarantined all over China as a new virus will come in from the outside. That is what is happening in Australia, New Zealand, Taiwan, same thing. That is how you do it. SR: Well, you have given me a lot to think about for sure. And I know that our listeners are going to be really challenged to some of the assumptions and beliefs that they have been holding on to. 2216
WH: I hope I do not get more hate mail. SR: You know, being a leader and taking a stand, never necessarily, it can be polarizing. And you know, if you are saying, offering an idea WH: I have a saying in my autobiography from my years of experience. You could not take a position that is controversial that later turns out to be right. What do people remember? That you were controversial? SR: Exactly. WH: Remember, you were right. SR: Well, one of my words for 2021 is courageous and I think you have just exhibited a lot of courage by just putting out there some things that certainly are in contradiction to the narrative. WH: Now, let me say one thing. I am a big fan of the Biden administration and what they are doing. They are doing what they can, and they are doing what they think is politically possible. So, they got to keep pushing that envelope. They know what to do. Let's push it further and further so what is needed becomes possible. SR: I appreciate your saying that. So, let's now talk about elevating eldercare, and you have alluded to it, you have written a few books about it. I had read Aging Well, and which, that was certainly how we got acquainted when I saw that there was reference to the Green House model as some hope. I would love to hear kind of your thoughts, and given all the constraints, those things that get in the way of meaningful change. What do you offer as your vision for elevating it? And I did hear you say homecare would be a part. There is so much more we can do in home care. As a nurse who does home care for years, I could not agree more with that assessment. WH: I think it is to make it economically and socially possible. I did a study of the Swedish eldercare system and it turns out, they do many aspects of healthcare well That they did not do well. In fact, there was so many scandals that the government fell over that particular issue. And they tried to privatize eldercare. But when you look at it deeper, and I talked to many of the people who are the frontline workers who are doing these innovative systems trying to improve it, their common issue they all had was integration of social care with medical care. Extremely difficult because one is ministered at the municipal and the other is a county level. But there are other 2217
issues that are involved in that. And there are a number of examples where you can see that integration takes place. And as I said, I think it is important to integrate mental health with all that. So, you can conceive of an eldercare operation that has all three thoroughly integrated in a way that none of them take precedence. Usually when you have an organization like that, the doctors are going to be the boss. No. For these kinds of situations, it may be the physical therapist who is the boss, or may be the social psychologist who is the boss, or the best ones, they rotate and they have no hierarchical structures. That is sort of an organizational mentality of how you organize it. Beyond that, we need to have these kinds of centers because you cannot do everything in people's houses and homes. Sometimes you need to have these, like I was mentioning in China, you have their facilities where they go back and forth. That is even more the case for people who have mental disorders. If you leave them in their house, they are going to wander around. In Japan, I worked there for a while and what we found is that their biggest problem, they said, find me a way to get these people to wander around at night home. We do not have enough people to find all the people wandering around at night and every night some do not ever come on. So, what can we do? There are so many good ideas in this field, really good ideas and good people. The problem I also found is that none of the ideas are scalable, and that is because they are not scalable. I do not think you are going to ever solve that problem. Therefore, you have to have a different kind of approach We are not going to have one big institution where everybody is. We have got to have a series of dispersed institutions which are coordinated. We are not just going to take a good model and grow it and grow it. It cannot grow because the kind of care that is needed is a very intimate kind of care, understanding who that person is, what their proclivities are. If they have a mental issue, what is the nature of their mental issue. That is not scalable. You can scale it in the way a tree scales its leaves, but each leaf is very firmly attached. And it is very particular, even though there is a whole lot of leaves, I think that is more of a dendritic structure we have to build when you are thinking about how to do structures. And in each one of those, you have to have the philosophy that we are going to give integrated, patient centered care. And we are going to relate that to bigger centralized systems 2218
that can give us the knowledge and the technologies that we need to address the individual problem that we see. SR: I still appreciate. One of the things that I always say it is whole person approaches and it is individualized. WH: Right. To do that and then make it systemic, to make a system that does that, that is what modern information theory practice management should be able to do. We now have these very powerful tools we never had before to understand the individuals, to understand their history, to manage huge amounts of information that comes right down to the individual level, like, do you like purple socks and blue socks? Right? Somebody knows that. So, that is the kind of technologies we have. You just have to start using them. SR: So, I know we are getting, we are at the top of our hour, but I would love for you to think about a call to action. You are obviously, as you said when we started, just dedicated to making a difference. And you are actively involved in our current pandemic. But I would love for you to think about what would you issue as a call to action to those that are listening to this podcast? WH: Well, the first thing I would say is what can you do in your own life to make sure everybody around you is healthy and safe and you are safe in this particular environment. What I asked people to do is if they go out, wear an n95 mask and a face shield and gloves. That is a pretty big ask it turns out, but that is what I ask them to do. And that is a recognition of how serious this issue is. I think beyond that, to be involved with your healthcare system, to actually interact with it in as a positive a way that you can, interact with your local, and your state, and your federal representatives. Get to know who they are. These are people. Their job is to listen to you, and get to know who they are, and then organize with like minded people in your community. So, this is not a single voice that is speaking to them, it is a united voice. We need to treat our eldercare our, elders better. We need to control our costs. We need to get better outcomes for the experience we have. We need for you to work with government to allow them to control price, not to let the big guys push you around to give you more money, but we are going to hold you accountable. I think those are the kind of community things each person can do. Everybody has a pretty good idea of what their needs are. They have a pretty good idea of where they are met 2219
and where they are not met, and where they are not met, they should be working with others to try to make sure that everybody's responsible for meeting those needs meet those needs. And do it in communities. Do not do it, necessarily, as an isolated person. Do what you can do personally, but do it with others. SR: I love what you are saying. And you have really cast a beautiful vision of what can be and to really recognize, to me, it is a societal call to action, but it happens at a personal level. You have given us global perspective. And really, I know for me, challenged me to think differently and to see things through the lens of somebody who has literally looked through the lens of a microscope and beyond to really understand more broadly and deeply what we are currently facing, and it is multifaceted, for sure and you have helped to unpack a lot of that. Dr. Haseltine, it has truly been an honor. I am glad to have spent this time with you and I look forward to continuing the conversation. I think I would love to have you back again. Let's get a few months down the road and see where we are. And hopefully, perhaps, we have learned some of the lessons that could be powerful teachers if we let them. WH: Thank you very much for the opportunity. SR: Thank you so much. Take care. This interview originally appeared in The Green House Project and is available online here: Interview with Susan Ryan of The Green House Project: A Sobering Look at COVID-19, Variants & Immunity
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Interview on Bloomberg Daybreak: Australia: Dr. Haseltine Says It's Too Soon to Relax Covid Measures Bloomberg | March 11, 2021 | Interview
Dr. Haseltine Says It's Too Soon to Relax Covid Measures William Haseltine, a former Harvard Medical School researcher and a pioneering AIDS researcher who now chairs Access Health International Inc., a New York-based think tank, discusses the Covid-19 vaccinations in the U.S. Haseltine, who is author of "A Family Guide to Covid" and "A Covid Back to School Guide," speaks with Shery Ahn and Haidi Stroud-Watts on "Bloomberg Daybreak: Australia." (Source: Bloomberg) This interview originally appeared in Bloomberg and is available online here: Dr. Haseltine Says It's Too Soon to Relax Covid Measures
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Interview with CGTN The Heat Covid-19 battle. Third wave hits Europe CGTN | March 18, 2021 | Interview
It’s déjà vu all over again as COVID-19 is on the rise across Europe. It is wrestling with a third wave of the coronavirus pandemic as a number of countries raise concerns over the AstraZeneca vaccine. The EU, plagued by vaccine delays, is also dealing with concerns that the AstraZeneca vaccine could lead to an increased risk of blood clots – something the company denies. Nevertheless, Germany, France, Italy and Spain joined with 11 of their neighbors this week to suspend use of the vaccine until the matter could be studied. Meanwhile, here in the United States, vaccinations are on the rise amid warnings not to become complacent in the race to eradicate the virus. To discuss: • Rishi Desai is the chief medical officer for health at Osmosis.org. • Dr. Xi Chen is an associate professor of public health at Yale University. • Chris Smith is a Consultant Virologist at the University of Cambridge and the co-presenter of the “Naked Scientists” podcast. • William Haseltine is the Chair and President of ACCESS Health International and the author of “Variants — The Shape-Shifting Challenge of COVID-19.” This interview originally appeared in CGTN and is available online here: Interview with CGTN The Heat Covid-19 battle. Third wave hits Europe
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April 2021
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Interview with CGTN: The Heat: Vaccine inequality and Brazil battles COVID-19 April 8, 2021 | Interview
As rich nations snap up vaccine injections, poorer countries are struggling to meet demand. Vaccinations are ramping up in the U.S., but President Joe Biden warns the country is still in a war against COVID-19. Meanwhile, in Brazil, hospitals and morgues are being stretched to the limit, and the prognosis for other low-income countries is similarly grim, as vaccine distribution continues to be a major challenge. To discuss: • William Haseltine is the Chair and President of ACCESS Health International and the author of “Variants — The Shape-Shifting Challenge of COVID-19.” • Dr. Gary Richwald is a Communicable and Infectious Disease Expert and the medical director of Curative California Vaccination Project. • Gustavo Ribeiro is a journalist and founder of The Brazilian Report. • Yaneer Bar-Yam is the Co-founder of the COVID Action Group and President of the New England Complex Systems Institute. Male Speaker: This pandemic won't end at home until it ends worldwide. Anand Naidoo (AN): The United States and vaccine inequality. Rich nations are snapping up injections while poorer countries struggle to meet demand. Hello, I am Anand Naidoo and this is The Heat. Vaccinations are ramping up in the United States, but President Joe Biden warns the country is still on a war footing. Meanwhile, in Brazil hospitals and morgues are being stretched to the limit. And the prognosis for other low income countries is 2224
similarly grim as vaccine distribution continues to be a major challenge. There is much to discuss. Let's bring in our panel. Joining us from New York, Dr. William Haseltine is chair and president of ACCESS Health International. From Los Angeles, Dr. Gary Richwald is a communicable and infectious disease expert and the medical director of Curative California Vaccination project. Gustavo Ribeiro is founder of The Brazilian Report and joins us from Sao Paulo in Brazil. And with us from Boston, Dr. Yaneer Bar-Yam is president of the New England Complex Systems Institute and cofounder of the COVID Action Group. Welcome to all of you to the show. And Dr. Haseltine, let me start with you. Let's start with the availability and distribution of vaccines around the world. Inequality to access vaccines remains a big issue. This is the Secretary General of the World Health Organization talking about it. Let's listen. Tedros Adhanom Ghebreyesus (TG): The scaling up production and equitable distribution remains the major barrier to ending the acute stage of this pandemic. It is a travesty that in some countries, health workers and those at-risk groups remain completely unvaccinated. AN: So, Dr. Haseltine, according to The Washington Post, the world's richest countries control eighty percent of available vaccines and low income countries have, in some instances, only been able to access about one tenth of one percent of the available vaccines. So how do you see that being resolved? William Haseltine (WH): I think it will be resolved as the richer countries vaccinate their population. I think if you look at from the political leaders’ point of view, it is extremely difficult to ship large amounts of vaccine abroad when your own people are not vaccinated if you are the ones making the vaccine. There is, of course, an exception. China has great potential to produce vaccines, and it has virtually no COVID. So, it would be my best candidate to ship the largest amounts of vaccine. India, of course, is a very large company with tremendous vaccine capability. They produce about half the vaccines in the world, but they have an enormous problem right now. So, I think there is going to be, for some time, inequities in distribution. AN: Dr. Yaneer, Bar-Yam, no country, of course, has been spared by this virus. But some have managed it. We have seen that. Some have managed it better than others. It is also having a major 2225
negative impact, of course, on economies around the world. The United States Treasury Secretary Janet Yellen, she talked about this making the point, and we have heard that before, we just heard it a moment ago, that no one is safe until everyone is safe. This is what she had to say. Janet Yellen (JY): Many middle and low income countries are in a different place, lacking the finance to support their economies and people during COVID-19. What is less obvious, but equally true, is that this divergence would also be a problem for America. AN: So, Dr. Bar-Yam, the fact that these vaccines are not being distributed more credibly, is that extending the duration of the pandemic and is it making it worse? Yaneer Bar-Yam (YB): Well, one of the key issues is the Brazilian variant that arose there because of the large number of cases there, which also affects everyone. It may, at least partially, undermine the vaccine. We do not know yet. But it is already present in the United States, in Canada and in Europe. And so, the risk that a variant will arise that will then undermine the major efforts of vaccination is very present. Now, of course, that is only one of the implications of having a virus that is global and transmitting globally. But that is an important one when we are relying so heavily on the vaccines as a method for reducing the impact of the virus. AN: What are the alternatives, or at least not the alternatives, but what should be done in addition to the vaccines? YB: Well, you know, we know how to control the virus and in fact, the statement that China does not have the virus that was just made before is because they controlled it. So did Australia, and New Zealand, and Vietnam, and Taiwan and so on. The point is that we have the ability to control the virus. It has always been a choice, but it is a choice that we have not chosen to execute. We have gotten the virus down and then opened up because we believe that there was a tradeoff between economics and health. That has been shown simply not to be the case because once we can get rid of the virus, then economies open normally. The economies of those countries that have eliminated the virus in Asia and in Oceania have done much, much better than other economies that have tried to live with the virus, believing that that would save economic activity where it has, in fact, not. It has caused the tremendous amount of harm that we have experienced over the last year. 2226
AN: Right. I want to get back to that point of what other countries have done. But I just want to bring Dr. Gary Richwald into the conversation right now. Gary, there is almost 117 million Americans, according to the CDC website, who have had at least one shot of the COVID vaccine. President Biden says he hopes that there would be two hundred million people who had been vaccinated, at least one shot, on his hundredth day in office. That is not far away. That is about twenty two days. He looks like he is on target to meet that deadline. But we also heard some disturbing news. There was a poll done by National Public Radio which show that one in three Americans say they will not accept the vaccine. And there is a range of reasons for it, some political, some health, some people do not trust the government, etc. But can the country overcome the pandemic if one third of its population say they will not take the vaccine? Gary Richwald (GR): Of course, the answer is, it depends which third, and that is where the United States is in very tricky territory. For the most part, we would say maybe half to two thirds of our frontline workers, of our healthcare providers have been vaccinated. But that leaves a large number of people in the non 170 million that you mentioned earlier. And many of those people have a lot of contact with other people. They are often young adults. And you know, the bottom line is, the longer we drag out the vaccination effort, the greater the opportunity for misinformation and straight out lies and politicization of vaccination just becomes larger and larger. You know, first we politicized mask wearing. Then we politicized vaccination. And now we are politicizing vaccine passports. And so, I think the United States is not setting a good example for the rest of the world. We need to get people vaccinated now. And it seems like health equity has been thrown out the window, frankly, when we start having states just saying anybody can be vaccinated. AN: But has the President got the right approach right now, Gary, because as you point out, the longer the rollout goes on, the more the chance of misinformation getting around, but now we are seeing up to three million people being vaccinated on a daily basis. President Biden says he hopes that will be two hundred million by his one hundredth day. So, is the country on the right path right now? 2227
GR: You know, you have to interview the virus. And that is one of the most troubling issue here. It is not so much how good the vaccines are. It is what the virus is going to do. And of course, the answer to that question is we do not know. And because we do not know, we better have in place a testing system, a contact tracing system, all of the things that have largely receded into the shadows of our public health efforts. So yes, Biden's done the right thing in terms of vaccine. But there is a much bigger picture in terms of being able to prevent what may occur over the next three to six months. AN: Gustavo Ribeiro, Dr. Yaneer Bar-Yam a moment ago talking about the situation in Brazil. If we look at the situation in Brazil, it has now become the epicenter, really, of the worldwide pandemic. Four thousand deaths recorded in just one day in the country. And we know that the healthcare system in Brazil is stretched to the limit. Yet we have President Bolsonaro who is downplaying the seriousness of the crisis in the country. This is what he said recently. Let's listen. Jair Bolsonaro (JB): Now the discussion is whether I am going to vaccinate or not. I will decide. I have already had the virus. I will get vaccinated when the last Brazilian gets vaccinated, then I will decide whether to get vaccinated or not. That is the example a boss should set. AN: So, Gustavo, give us an idea of what the situation is like in the country. Gustavo Ribeiro (GR): Brazil is in a what we consider a pandemic perfect storm. We have economic anxieties which are pushing people out of their homes because we have an extremely informal economy. So, for a lot of people staying home is not an option. They have to go out and they have to make ends meat and find a way to earn their living. We have an uncontrolled spread. Also because of pandemic fatigue, a lot of people who could stay home simply will not. Vaccination rollouts in Brazil were extremely slow. We have vaccinated around ten percent of the population with at least one dose, but less than three percent with both doses. Several state capitals here have suspended rollouts because of lack of inputs and a lack of doses. And we have a government that has, from the beginning of the pandemic until now, send mixed messages to citizens. There has been a vector of disinformation. The President has talked against mask use, has talked against a vaccination rollout. 2228
And you said four thousand deaths confirmed yesterday. Health Ministry officials have told us that they expect within a span of two maybe three weeks that daily tally to get to five thousand at least. And now we are not only facing a health collapse but another collapse of the funerals, the funerary system, because a lot of cemeteries simply are not being able to cope with the sheer demand that they have right now. AN: And Gustavo, what about the situation deep in the Amazon in cities like Manaus, for instance? What is going on there? GR: Well, Manaus, for instance, the biggest city in the Amazon suffered two collapses, one in March/April last year and one at the beginning of this year. The number of deaths has slowed down a little bit because the government was forced by political pressure to ramp up vaccination rollouts there. And it is one of the states which have the highest rates of vaccination. But last year we saw in some regions like the Amazon, like poorer regions, the coronavirus spreading faster and now we are seeing a generalized spread of the virus and a generalized state of near collapse for health systems. I spoke this week with the president of the Brazilian Virology Society and he was telling that at this point, Brazil is becoming a sort of petri dish for new variants. There was a recent study that was published last week with eleven mutations found in a handful of people. So, while these are not prevalent, if we do not control them fast enough, they could become widespread like the Amazon variant or like the British variant. AN: Dr. Yaneer Bar-Yam, you were talking about this earlier on, and as Gustavo tells us that this virus is mutating all the time. So, there may be more than just one variant to two variants. There could be up to a dozen, couldn’t there? YB: Yeah, what we are doing right now is we are labeling or naming variants, the UK variant, the Brazilian variant, they have technical names too, the South African variant. But the way to think about it is that the variants we are concerned about now are the ones that happen to be growing rapidly, so we see a lot of them. But no matter where you look, there are more and more variants, more and more mutations, and there is this cloud of these variants. And so rather than thinking about it as one or two or three variants, we have to understand that there are many variants out there, and depending upon what we are concerned about, we will identify different 2229
variants. And so, if we are worried about the rapidity of spread or how deadly they are, or whether they spread in children more aggressively or cause more effects on children, that is the kind of thing that we have been seeing in these variants. But the variant that is going to be the most important variant pretty soon is the variant that can evade the vaccine because if vaccinated people get together, then that is when those variants will transmit. And if it undermines the vaccine, then the strategy that we are using in the United States and in much of the world is not going to be effective. And in fact, unfortunately, that is what people are projecting. They are projecting that the disease will become endemic, which means that instead of having the vaccine stop the virus from transmitting and getting to the kind of situation we have in China and Australia and New Zealand, they are expecting it to bypass the vaccine and then we will need next generation vaccines or new vaccines. And all of that is kind of programmed into how people are thinking about the process. There is, of course, the different way, which I can just mention briefly, which is that if we use vaccination to get rid of the transmission, then we can achieve elimination as has been done in other places. AN: Dr. Haseltine, that brings us back to the point I was talking about earlier on one with one in three people here in the United States, according to this polling, telling us that they will not take the vaccine. I mean, what can be done about that? How does one convince people that this is for the common good? I mean, could one put some kind of strategy in place? WH: Well, the obvious strategy is making it compulsory for various activities, schools, jobs, hospital workers. Certainly, that is the case for many vaccines today. You cannot work in a hospital today if you do not have a hepatitis B vaccine, or hepatitis C vaccine, and then a whole list of others. You cannot go to public schools without vaccines. There is nothing new about that. And in fact, as far as travel goes, I remember very well the yellow cards where you could not go to many countries unless you show your passport for yellow fever, or smallpox or polio, or you name it. You had to have that yellow card. So, that is all possible. But I would like to reiterate something that has been said a few times now and that is we can control this pandemic, even without vaccines or drugs. We will have vaccines, we have them. We will 2230
have very effective drugs. But you have to couple that with public health. And I am very disappointed at this point in this administration that is not putting the same effort into laying the groundwork and making sure we have the infrastructure so we can rapidly test. Britain is going to have tests so every person in the country can test themselves twice a week, twice a week. That is what we should be able to do in homes, workplaces, etc. And then follow that up with contact tracing, and isolation. I call it assisted isolation. I have written about how we should make sure people have the economic means to stay home with their families. If one member is infected for a reasonable period of time, whether that is ten days or two weeks, we should subsidize that, make it possible, make sure they get the care they need. But if we do not do that, as you have heard, the variants can take over or other issues can get in the way. And it has been extremely disappointing for, I think, all of us who are talking right now to see the response, not only in this country, but in many other countries with respect to the basic ABCs of public health. You need vaccines, you need drugs, and you need to have public health measures to control and that is very simple, identification, contact tracing and assisted isolation. AN: Gary Richwald, what are your thoughts on that? We have heard President Biden say or warn, rather, that it is premature to lift restrictions right now. He has appealed to people to wait just a little bit longer. He has also moved up that deadline for states to make all adults eligible for the vaccine by almost two weeks. Go ahead, Gary, can you hear me? GR: Sure. Now I can. Well, Angela Merkel and President Biden have one thing in common. They have a state system in their countries, and we have fifty states and what Dr. Haseltine is disappointed about is what is going on in probably two thirds of the states. Basically, vaccine policy that is telling people that you do not need to wear a mask, and you do not need to social distance, and you do not need to use proper hand hygiene because you are vaccinated has the potential to undo all the benefits of vaccination. Nobody has the political courage to say that. It is so connected that we are not going to get people vaccinated unless we give them some free pass at the end, that now they are vaccinated, and the free pass has the potential to put us all back in the slammer in terms of infection with this virus. So, what Dr. Haseltine just said is, I doubled 2231
down on it and say that I am going to be, I may be back here in a month saying if we had only not, you know said you can do anything, you can travel anywhere. You know, grocery stores, they are not going to be able to say shoppers have to show their vaccine card. Some states already making vaccine cards illegal as a basis for entering a particular business. I think Texas did this in the last few days. So, these messages are undoing the benefits of vaccination. D AN: Dr. Haseltine, is that the problem here, that there is not a single policy, there is arguably fifty policies? WH: Well, it is certainly one of the problems, and I think that if we look ahead and plan for future pandemics, we have to really examine very carefully how we have structured it. I have always said the problems in a pandemic are leadership. And we have good leadership now. But the second problem is governance. We do not have the right kind of governance. And there is a third very deep issue, which is social solidarity. It is almost a no, no word in the United States to even say social solidarity. But without that, it is very hard to introduce and implement sound public health policies. You need all three working in tandem along with what we do have is excellent science. So, we have two of the four ingredients that you need to control the pandemic today, but we lack two essential ones. You can probably get away with bad leadership. We have seen that, and some countries have done okay. But you cannot do away with good governance and social solidarity. Those are two things you really need to have if you are going to control these pandemics. And I think that that is something we have to work on for the long haul in the United States to try to reform our public health system and try to create a sense of shared value that I am my brother's keeper. AN: Gustavo, you have something of a similar situation in Brazil, don't you, because you have the federal government which issues the guidelines, imposes the restrictions, etc. But state governors have quite a lot of autonomy, don't they, on how they implement those measures? GR: Yes, but I think we had in Brazil, a sort of reverse situation from what happened in the US, which is in here, the federal government bent over backwards to stop governors from enacting social restrictions. And we have the matters taken to the Supreme Court. The Supreme Court had to step in and recognize the jurisdiction that governors could enact social restrictions. Jair 2232
Bolsonaro has changed health ministers three times, and all officials have one order, there will be no talk about a lockdown in Brazil, even if health experts say that, at least for two weeks, and at least in state capitals where the bulk of the population live, we should close down the economy for a couple of weeks in order to try and tame what has been a brutal wave of infections. For instance, it took us ten months to go from one thousand deaths per day to two thousand deaths per day and one month to go from two thousand to four thousand. AN: And, Gustavo, what about public compliance of these measures in Brazil? I mean, are people basically going by the guidelines or are they just defying them? GR: There is no public compliance and in a country like Brazil, as vast as Brazil, with police forces as reduced as we have, you need a lot of public buy-in. And there was a lot in the beginning. But like I said, we have a very informal economy. Tens of millions of people simply cannot afford to stay home. For instance, the city of San Paolo enacted a ten day holiday, finishing on Easter, to try and increase isolation rates and they failed. Not a single day isolation rates on GPS monitoring showed more than fifty percent of compliance, and their goal was seventy five at least. AN: Dr. Yaneer Bar-Yam, I want to move a little bit away from this region, from this hemisphere, to Europe. Many European nations still struggling with a pandemic. France and Italy have imposed new lockdowns. Travel to Spain is restricted. Germany is talking about another lockdown as well. What has gone wrong in Europe? YB: I mean, the situation there is because of the relaxation of restrictions and the new variants. And the fact that cases have gone up in some countries is leading to them to take new restrictions. There are some positive situations, like in Portugal and Spain has also taken stronger actions that have led to cases going down dramatically. And they are actually in a position, particularly Portugal, if they were to do some additional restrictions now, they could actually open up as have New Zealand and Australia. Again, it is a matter of choice and want to go back to this idea in in a very key way. We control the outbreak. The collective of social action, guided by clear information, is able to control this outbreak and the fact that we have control then raises the question, do we choose to 2233
exercise it? And what we have seen as we have talked about now in Brazil, in the US and now in Europe, it varies quite a bit what choices are being made? And what we see is, of course, happening is that the outcomes and the process over time going up and going down in these yo-yo lockdowns is what results from making decisions at the collective level. I have one more thing I would like to add on this conversation about social cohesion, which is extremely important. But I think part of the point is that when there is clear communication about the choices and about the science, then public can trust what they are being told. And I think a major failure is not just the implicit or the deep structure of the society, but how we appeal to people. That has not been done very effectively throughout the outbreak. AN: Gary Richwald, I have only got a minute left. The only region in the world that has enjoyed relative success in controlling this pandemic is Asia. What have the Asian countries been doing that should be emulated here? GR: Well, I mean, above and beyond social cohesion and trusting the government, at least in the public health and medical area, I think they wear masks. Mask wearing with influenza was a long standing, personal choice and often chosen, social distancing. They did enormous amounts of testing. They made it very convenient, and the contact tracing was in place. So, our testing may or may not be able to come back up to the level it is going to be needed if we have an outbreak if the vaccines begin to fail, and our contact tracing is just abysmal. I mean, we are running, in most places, at a quarter to a half of the staffing that is recommended. So, Asia did it all right, text book. They had experiences with previous pandemics and epidemics. That is what they did. And they did it, I think, with A plus success and the success that followed. AN: Okay, and that is what we have to leave with. Thanks to all of you for being with us on the show. That is it for this edition of The Heat. I am Anand Naidoo in Washington, DC. Thanks for watching. This interview originally appeared in CGTN and is available online here:Interview with CGTN: The Heat: Vaccine inequality and Brazil battles COVID-19
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Interview with HPM-Houston Public Health Radio A Lifelong Fight Against Disease: Dr. William Haseltine Talks About Global Health, From AIDS To COVID-19 April 9, 2021 | Interview
Ernie Manouse (EM): Today’s social media is filled with celebrities of the moment, folks that are known simply to be known. Andy Warhol’s army of famous for fifteen minute people. Before then we admired rock stars, actors, athletes and TV personalities. But there was a time in our past when we honored and admired scientists, astronauts, great thinkers and intellectuals, when we actually listened to individuals who actually had something to say. Today we welcome just one of those thinkers. In addition to wanting to make today’s youth see scientists as the superheroes of the future, he has worked tirelessly at educating and advancing our understanding of COVID-19 and global health initiatives. He has been called the father of regenerative medicine and the biotech bad boy. Dr. William Haseltine is our guest for the full hour. Hello. I am Ernie Manouse and this is Town Square. Time Magazine named him one of the twenty five most influential global business executives. He is the chair and president of the global think tank ACCESS Health International, the founder of more than a dozen biotechnology companies, and his name is Dr. William Haseltine. His career has always been at the forefront of modern medical research. He has educated a generation of doctors at Harvard Medical School, designed the strategy to develop the first treatment for HIV/AIDS, and he is known for his groundbreaking work on cancer and the human genome. An internationally recognized expert on COVID-19’s pandemic, he is also the author of eleven books, including his new autobiography My Lifelong Fight Against Disease From Polio and AIDS to COVID-19 and his newest Variants - The Shape Shifting Challenge of COVID-19. Welcome to the program our good friend Dr. William Haseltine. Hello there, Dr. Haseltine. 2235
William Haseltine (WH): Hi Ernie and thank you for that generous introduction. EM: Well, it is not a generous introduction. It actually skimps on a lot that you have accomplished in your life and career. I guess I just should start with you sat down to finally write a really inclusive biography of yourself, your autobiography. Are you kind of surprised of all you have done? WH: You know, maybe, but to me it has just been a wonderful journey to be able to realize some of your purpose in life. I set that purpose early on. I had very traumatic experiences as a kid with disease, my parents’ disease and some of my own. I just did not think it was fair that people that I loved suffered so much. So, from very early on, I think five or six years old, I decided that I would do whatever I could. I have been privileged that throughout my life doors have opened. I did not even have to bang on the doors. They just opened. And it has been just a wonderful journey and I feel extremely fortunate that has been possible. And by the way, COVID has opened up other doors and I am pleased to be able to make, at least, some contributions there as well. EM: Take me back, though, when you talk about when you were young and having illness close to you and surrounding you and realizing the impact it makes on not just the individual who is sick but in a sense the community around them, the family. WH: Certainly the family. My earliest memory of really serious disease was my mom. She had a lot of different diseases. She had eczema which would lead to psoriasis which then would lead to infection of her veins and she could die. I remember as a young boy two or three occasions, separate ones, where she would be lying in bed soaking her hand in Epsom salts and there would be a red streak up her arm. If you turn the arm over, you could see the infection climbing up her arm and I had been told that if it ever got past her shoulder toward her heart she would die. I kept standing by the bedside watching that streak and watching it go up and then slowly watching it come down. That is something that is indelible. You just never forget that. I was very close to my mom and she was a wonderful, wonderful woman. She had ups and downs. She had a lot of issues, but she was a tremendous mom, especially to me I might say. So, I just did not think that was fair. Then later she had detached retinas. I can describe it but really in those days it was a terrible 2236
ordeal. She had two. Then she had psychiatric problems once I came to realize as I was older. All of that was just pushing me forward for a career in healing in one way or another. EM: It pushed you forward, but your siblings have also all become quite well accomplished. What was it do you think in your family that said education, science, technology is an important aspect to invest in? WH: Well, I would say that was, it was actually a couple of things. Both parents were extremely highly educated. My mom went to Reed and I graduated from Berkeley. My dad had a graduate and undergraduate degree from MIT in advanced physics. He was an instructor at University of California where he met my mom. That was part of it. They were very deep intellectual, both of them. Everything in science my dad really knew almost everything about everything. He had one of these memories which was not photographic, but almost perfect. He had access to it from like the time he was two. His entire life he had access to it, and everything he had ever read. And he read really widely, from fashion magazines to a twenty one volume of the eye that I bought him. After he finished it, he said, well now I know more about the eye than I need to. That is twenty one volumes that he went through. My mom was deeply interested and passionately interested in art and literature. She was an artist herself. She was a fantastic cook. Invented recipes. I was her sous-chef. So, there was a deep, deep love and appreciation of knowledge. In addition to that, it was a hot house where I grew up. Not literally. It was in the middle of the desert, but it was also a hot house of intellectuals. It was a group of people the Navy had assembled for their advanced weapons research. And most of the people we interacted with all had PhDs from the best East Coast or Midwest universities. It was after WWII when we were just gearing up to make sure we had all the weapons we needed. Each of these people not only were scientists, they had other interests. One was a passionate orchard collector. Another built his own glider planes. It was a fascinating community in a real hot house. I think that influenced all of us. My sister went on to get a PhD at MIT and then an MD and had a spectacular career. She is now with you in Texas at Texas University where, at age 76, she was offered a tenured job which she is still doing and testing people for COVID like crazy. 2237
My brother has had an amazing career. He was a neurophysiologist. He became a top scientist at Hughes Aircraft designing man machine interfaces. He then became a top executive at the Disney Corporation, sort of the head of all of their technology and acquisitions, technological acquisitions. He then went on to become the head of all our intelligence technologies at NSA and then at the Director of National Intelligence. My other sister took a different course. I have another sister who is extremely smart. She decided to have a quiet life. But all of us were imbued with that really intense focus on the mind. EM: So, this was a path that pretty much was, pretty much laid out, that you had little choice at running from. But was it your passion? WH: It certainly was my passion. Healing was my passion. The healing is sort of, I took that as, even early on, I was not so fascinated. As a kid, you like weapons, you like to see things explode. Of course, I liked that. But when I got to be a little older, like in high school, I decided I did not want to do that. I wanted to do the other side of science, science for health, not science for war. And so, it might seem like it was a natural, but to me it was rebellion. I was rebelling against the community that I came from. I later became a prominent anti-war activist, the same war that the people I grew up with produced all the weapons and my specialty was understanding what the weapons were, how they were used and the damage that they inflicted. So, in a way, it gave me a grounding, but also gave me a desire not to do what I had grown up seeing done. EM: I am curious, you make reference to science quite a bit and I am curious in your own mind do you separate science and medicine or are they the same thing? WH: They are definitely not the same thing. I know lots of scientists and you cannot go to Harvard and MIT and live in a life of science. A lot of people, and it is a wonderful thing to do. It is curiosity driven science. What is the cosmos about? That is not medicine. It maybe about us and our heart and our soul and our mind, but it is not about medicine. I always knew that I wanted to acquire the tools of science for the purpose of healing. I later broadened that to understand the tools of politics and policy for healing, but as a young person I wanted to get all the tools under my belt, whether it was chemistry, mathematics, advanced physics. I 2238
actually took an extra year between my undergraduate and graduate work to do theoretical physics and chemistry at Harvard to get right up to the very edge of what graduate work would be in advanced physics, field theory, all the stuff that Fineman was doing. It was fascinating and I did not want to have, I did not want to be able to attack a problem because I did not have the tools. I wanted to have every tool in my kit. By the way, over time I have used many of the tools and added more, not more from science so much as more from sociology, from history, policy and politics. Those are all tools you got to use if your goal is to heal as many people as possible. EM: I was going to ask, can you approach a problem like COVID-19 without all of these disciplines working together? WH: I can say, this last year, I started out working eighteen hours a day and now I am down to about fourteen hours a day. But every single one of those tools I acquired I applied to try and understand COVID. Let’s just take government policy. At the very beginning, I identified three really important things to get right about COVID, political leadership, governance and social solidarity. There is a fourth of course which is science and technology. All those things have to work together to address this problem. I have been writing about all four of those at this point. Now we have good leadership in the country for fighting this, but we do not have the governance. We do not have the tools. You can see that our president is frustrated and it turns out good leadership is not the answer to solving all our problems. Right now we are in the middle of a forth wave and it is not because we do not hear our public officials screaming at us, please do something. I am entreating you to stop it. That is not what we heard last year at this time. But they do not have the tools, they do not have the public health service. They cannot issue a command from Washington and have it implemented uniformly across the US. It is fifty different ways. Actually, it is about five thousand ways because once the decisions get to the state, many of the states refer that to the local communities. So, that is just the beginning of it. EM: More of this in a moment. We got to take a quick break. We are talking with, I can call him the biotech bad boy. He has also been called the genome king. We call him author and global health expert Dr. William Haseltine. He will continue with us. I am Ernie 2239
Manouse This is Town Square. We will be right back. I am Ernie Manouse and this is Town Square. We continue our conversation with global health expert and author, Dr. William Haseltine. Dr. Haseltine, one of the big things you are known for is your relationship to the human genome and I am curious when that first started, you started to become aware of it and started to think there is something here worth me getting involved with? WH: It goes back to my graduate days with Wally Gilbert who is one of the two discoverers on how to sequence DNA. He was just beginning to putter. I just saw his puttering. He brought a bunch of Russian scientists in who understood DNA chemistry. It turns out, and it is kind of interesting, because of Lysenko, Russians could not study genetics, so they became the world’s expert on DNA chemistry. So, some of those people came over to the lab and I knew them and they were looking at chemistry and Wally was figuring out how to sequence DNA. I went on to work with Dave Baltimore and then got my own lab. But I was actually, and Maxim who is his technician, Maxim Gilbert sequencing method, we sequenced the first novel piece of DNA and it was a piece of a retrovirus. I am pretty sure that is true. People who only sequenced DNA sequenced what they already figured out. We sequenced a little piece, about a hundred fifty nucleotides. It had an important role in replication and one of the things I did is figure out how replication starts in retroviruses. Then I used those methods to sequence part of a leukemia virus. I was working on how cancer is caused by mouse viruses. Then when the first human cancer virus, leukemia virus came along, human T cell leukemia virus 1, I sequenced it. So, I found a whole gene which turned out, after a lot of work, six or even years of work, to be the gene that causes cancer. So, I was familiar with it. Knowing that virus, when AIDS came along, a few of us hypothesized it would be a retrovirus because it behaved just like HTLV1 in transmission and other things. It would sort of go in, hid for a long time and disease popped up. It was transmitted by sex, by blood, from mother to child. So, we really thought it might be. So, when that came along I sequenced that. That was my big revelation because HIV we knew we needed drugs. I was sure really early on we probably would not get a vaccine and it is now thirty five years later and we just failed again to get a vaccine. But I thought we could get drugs. We had combinations of 2240
drugs. I was head of cancer pharmacology and what is cancer pharmacology but drug combinations and had been working on drug combinations with the head of an institute, Emil Frei. So, I knew that if we could get drugs in combination we could probably treat and prevent people from dying. So, all of a sudden we have all of these targets and we shortened what is normally twenty or thirty years of work into two or three weeks. Then I thought, a light bulb went off, boy, this is a way to find new drug targets. If we can do this for one little virus, we can do it for the human genome. EM: Let me jump back for a second when you are talking about HIV. You said that you realized you would not be able to get a vaccine, it did not look like you would be able to get a vaccine but you would be able to get drugs to treat it. What was it that told you a vaccine would not work? What were you noticing that said, this is not going to be easy? WH: I have always tried to tell my students observe nature if you want to understand the big picture. You can go as deep as you want into any scientific question. But you should also have the whole picture of what is happening in nature. So, I was looking at what was happening with the immunology of HIV. Why did it go into people, last a long time, five or six years, and then kill them? It is odd. That is very peculiar behavior. A few viruses do that. Herpes viruses do that. Malaria could do that. But I thought, let’s measure the immune response. Right at the beginning a sky high, we have never seen to this day. There is nothing that issues an immune response like HIV. It is in you and keeps growing and growing and your immune system keeps pounding. You even get enlarged lymph nodes, lymphadenopathy. Also, T cell and B cell responses were off the chart. So, the way I would explain it is that a vaccine is not a shield. A vaccine is an early response like a fire alarm. You do get infected. It does not stop you from getting infected. The virus gets in, but your immune system reacts to shut it down. So I thought, if this virus can get in and live in you for a long time and you can never shut it down, we cannot do better than nature. How are we ever going to do better? We do not know enough. So, I did not say we would never get a vaccine. What I said was we do not know enough to know if we will ever get a vaccine. And I can say that thirty five years later. We do not know enough. It does not mean we will not. It just means we do not know enough to see. Now 2241
when I said that at the second annual AIDS conference two years after the virus had been discovered, everybody was hot on the trail maybe a year after, everybody was hot on the trail of getting a vaccine, they had to pull me off the stage the audience was so angry. I have never seen such an angry audience. Boo, hiss. If they had tomatoes they would have thrown them. They actually pulled me off the stage, you know like the hook. They dragged me off the stage. EM: That kind of fascinates me, though. When you say that, I think about people’s reactions to science when it is not the answer they want to hear. Have you seen human nature change in that regard over the years? WH: Human nature will never change. People do not want to hear bad news. The easiest thing to sell is hope. Hope sells. Whether you are in a biotech company or whether you are the head of one of the biggest corporations, people are hoping your sales are going to go up so they buy. Hope, you can look at hope in two ways. Either it is the cure for ills or it is the last evil that came out of Pandora’s box. It is supposed to be the cure for all the evils. But hope itself, if badly placed, can cause a lot of trouble. I think that, for example, let’s just take COVID. We hope that it would not be as bad as it is. But it is worse than we thought it would be. That is a good example of hope hurting rather helping. Now, if somebody is infected, you hope they are going to get better, with all your heart you hope they are going to get better. That can help. That can give the support the people need. Hope is a double-edged sword in answer to your very specific question about hope. EM: I want to ask a little bit more. I want to go back to the HIV period. Here now when we are speaking about COVID, about how this virus got here, and there is talk about it being in a lab and being manufactured and breaking out. That is not a new story to you. If you go back to HIV/AIDS, there was Russian propaganda, if I understand correctly, that you were the one who let loose AIDS on the world. Not true. WH: It is not true, but it is certainly true that, even maybe, the tools that Putin uses today have been honed for decades, misinformation. We actually traced that story back. Also, US misinformation I will talk about in a second. But that came they would place stories in the Indian newspapers because there was a big 2242
strong communist party there. The communist party would put these papers out and I was working with visna virus and HTLV1 and they said I combined them because, in fact, it looks a little bit like a combination. They actually said it was cooked up in an American lab to kill black people. Very specific, and I was the one that did it. Of course, I did nothing like that. But that was misinformation. But the same kind of blame your enemy today when you try to find out where does COVID come from. When WHO sent that mission to find out where the virus came from, I would have rather the WHO looked at why is it China has been so successful in containing COVID. Much more useful than trying to find an answer you are probably not ever going to find because most people in America do not know that since this time last year, on a bad day, twenty people get infected in China, twenty people, not twenty thousand, not a hundred thousand, twenty people. I think in the last six to eight months two people have died, not a hundred thousand, not five hundred thousand, two. That is good containment. Why don’t we learn, or learn from Australia or New Zealand. So, these stories by focusing on did it get out is really beside the point. It came from nature, that we know. And it is going to come again from nature. It came last time from nature. Now, exactly the details of how it came, maybe we will unravel it. I was just talking to talking to an expert in Singapore that has a lab very much like the lab in Wuhan and they are convinced that it came from a cave in southern China. There are bats that have viruses very similar, maybe not identical, but really close. The people there have evidence of having been infected by those and it probably had a chance to adapt. I have looked at that question very, very carefully and it has no evidence that it was manipulated by people. Did it escape? No evidence it was there and escaped. In fact, there is quite the contrary. There is some evidence it was in other parts of China first. So, that is a whole argument, but the main point I want to get back to is we have to get the tools. I was on a conversation yesterday with a bunch of experts. Yes, we have vaccines, but we need more than vaccines. We need to do solid public health. We know what to do. The Chinese did not invent what they did. We taught them at Harvard School of Public Health exactly what to do for ten years after SARS. We had a program and it was identify the people infected, contact trace, and isolate. We still have not done that. In 2243
fact, if you want to look for one huge weakness in our current response is testing. I have been an adviser to senior people in Britain on what they should do and I am very gratified. I cannot say it is just me but at least part of the advice I gave them is put tests out so everybody can test themselves twice a week. They just did that. They are going to have the ability to test everybody in England twice a week and the government is paying for it. If they are positive, they are going to contact trace and they are going to ask people to stay home. Now my American version of that is to pay people to stay home with their families. Pay them so it is really worthwhile like $500 a day and I think you will overcome a lot of resistance. People will want to be tested so they can stay home for two or three weeks with their family for $500 a day. So, I think that is the kind of program that we need but we do not have. It is a mystery to me why we are putting all our eggs in a basket of vaccines when we have to have a joint process because we can see that in the state that has the most vaccines, one of them Michigan, that is not stopping this virus. There is a huge uptick. If you look around the world, I look every day at the statistics and this virus is on a super roll around the world. India is off the charts. Brazil is off the charts. Japan is off the charts. Philippines is off the charts. When I mean off the charts, more infections than they ever had by far. Today, yesterday, the day before and will happen tomorrow. So, it is not just about vaccines, and it is not just convincing people that they have to do various things, it is helping them do it, making it easy for them to do it. Give them a test so they test themselves and they know if them or their family are infected so they can do something about it to protect the people they love the most, to protect your schoolmates, to protect your coworkers. EM: We have talked a lot in the past, and I do not hear it talked about as much anymore, the inexpensive paper tests where people can test at home. WH: That is what the British are doing, and where did it go? People put all their energy. I actually think when I look back and you think about who is driving the American response, it is not the CDC it is the NIH. That is kind of an oddity that the face out front is the NIH face whether it is Francis Collins or Tony Fauci. It is only recently you have a serious face from the CDC. But even now it is about vaccines and drugs. Tests are, ok, we can do tests too. I can 2244
tell you from a research point of view, I was an advisor to Tony Fauci and his whole team back for the AIDS days. They are fantastic for research. But is it public health? It is kind of the wrong foot on the wrong shoe. It is not public health. It is researchers who are driving the train, not public health. There is now much more of a unity then there was before. But I think that is reflected in just the question you asked. Why aren’t we testing as much and why aren’t we hearing as much about these fast tests? EM: Before we run out of time in this segment, I want to go back to just for a minute to something you said earlier when you were talking about AIDS/HIV and the search for a vaccine for it. I know there were some trials going on for something called mosaic. Are we finding that these are not working still? WH: They are not working. It was a recent publish, a week before last, big paper came out. Not only did it not work, it might have made things a little bit worse. So, it is really a bomb and a double bomb. But that is a special case. HIV is a special case. These vaccines are working. They are safe. The Moderna and the Pizer, they are miracles. They are really wonderful vaccines. How long they will last? Will it protect against all the variants? Those are questions, but we are darn lucky to have these vaccines. EM: I want to dig deeper into all of that in just a little bit about how we developed these drugs and these different companies and what is going on and the vaccines. We will get to that in a minute. I do want to stick with HIV for one more minute. The success that we have had with PREP or Truvada and Descovy and all of these things, what have we learned from that kind of approach? WH: One of the biggest gifts from HIV for COVID is all the technologies. First of all, the scientific technologies for how to find these drugs and how to find these vaccines. That is really a direct gift. Almost all the scientists that I know who are working on COVID were former HIV scientists. They are some of my grand students, my students, my grand students and great grand students. So, that has been amazing and that investment has paid off. Just like the breast cancer program paid off for HIV, HIV has paid off for this. A huge investment in research. But it is more than that. We built an infrastructure for testing vaccines all over the world. That is the infrastructure that was used, exactly that infrastructure. So, they did not have to rebuild an infrastructure to test a vaccine in Brazil, South 2245
Africa or another country. We had it and that was the HIV vaccine network, directly, same people, same structure. Also, after the anthrax attack, we set up a whole bio preparedness. We had special government regulations that allowed us to pour money very quickly into programs. Actually, I worked with Tony Fauci to help set those up with the FDA. Those are exactly the same programs where the billions that went into creating these vaccines went. We had those structures. I wish we had had the same structures for public health. Government structure works when it is there and prepared. When you do not have it, just look at the difference between our vaccine work and our public health work. So, when I say that governance makes the difference, it makes a big difference. We had governance. Every piece of the governance we needed, from a vaccine network to how to pour money into an emergency preparedness program. It was there, those instructions were there. On the other side, we did not have a public health governance structure. So, one failed and the other has been a spectacular success. EM: I am going to stop you right there so we can take another quick break. Then we will continue our conversation. We are talking with the author of My Lifelong Fight Against Disease From Polio and AIDS to COVID-19, Dr. William Haseltine. Up next we are going to look at public health, global health and the whole concept of herd immunity. Plus, what is going on in all these labs and the information we are getting out about our vaccines. We will get to the bottom of all of that. I am Ernia Manouse and this is Town Square. Now, back to our conversation with global health expert and author Dr. William Haseltine. Dr. Haseltine, one thing a lot of people get confused with talking about, I am not sure if it’s confused it is just they do not think about it as broadly. We could get the virus under control in the US. We could vaccinate everyone. We could be out there and running around if the rest of the world is not there with us, we still face trouble in this country. Talk about this from a global perspective. WH: Well, you summarized it very well. The world is not isolated. One person started this whole thing. One person got the virus and now 150,000,000 people have it, and more on the way every day. So, we are a global world. One thing I think about is why is this happening to us. Same with HIV. What has happened, some people say is we are encroaching into the ecosystem. We have done 2246
that for three thousand, five thousand, ten thousand years. That is what we do. Cut down forests, raise herds. What is different now? What is different is there is so many more of us. There are about five billion more people than when I was born, five billion of us. That is a lot of people. We travel like crazy. 4.5 billion people took airplane trips in 2019. And we live jam packed together. When I was born, eighty percent of the world was rural. Now eighty percent of the world is urban. We are a great new ecological niche, and that niche is going to get exploited by viruses that are trying to crack our biological code, our sociological code, our medical code, and our political code. That is what they do. They are dumb machines but pretty smart. Dumb computers can solve some pretty complicated questions and these viruses are doing that every day and there is a lot of different viruses. So, we have created a big fat ecosystem for them. I think that is what it is happening. It is what happened with HIV. It is not this is the first time HIV got into human beings back on the eighties. It is the first time it got all over the world. This is not the first time these nasty viruses got into people in Southern China and Southeast Asia or other places. It is just now they go all over the world. The virus that causes MERS started with a camel from a bat in Egypt and is causing trouble in the Middle East. That is what is happening now. We are a united world. You can now look to those countries that have been pretty much protected. Right now, for example, Thailand has been pretty much clean of this. Right now, they are suffering a terrible infection. Now they think it may be months before they can control it. It came in from somewhere else. It is one of the variants that got in. It is the British variant that is now in Thailand. It is causing a heck of a lot of trouble. They never had such a problem before. What does China do or what does Australia do or New Zealand do? They do not let anybody in that has not been thoroughly tested. China is so careful. You have to take an IgM test. This is something people do not pay attention to. About five percent of us shed virus for many weeks through the gut. So, China does something else. They take an IgM test which says that you have not been infected for about six or seven weeks before you get on a plane. Then you are two weeks there and now they are doing fecal and anal swabs because they know that that is where some of the virus comes out. How do they know that? They do not have any so any time it pops up they track it right down 2247
to its origin. It is on frozen food. It does come in on ships at sea. It does come in from the outside of cold containers. That is what they found. And it persists in people a lot longer, a few people, for a lot longer than we think, then we are used to. There is an oral fecal route and a fecal aerosol route that we just do not talk about. Back to your question, as long as people are infected in the world, we are going to have a problem. Even if we clear it out from here, we are going to have to be continuously vigilant as China is, as New Zealand is, as Australia is. EM: But if we think that, well if we are vaccinated than we are safe, so if this persists other places, so be it. We are not going to get sick. That mentality is wrong. Why? WH: It is wrong because the variants can evade vaccines. The thing that bothered me most from what I have seen recently is the Astra Zeneca vaccine in a real test in Africa was ten percent effective against the African variant, ten percent. Ninety percent not effective. That is like not effective. Now, why is that so perturbing? Because the antigen they used is exactly the antigen that everybody else uses. It is the whole protein, the exterior protein, the spike, from the Wuhan strain. So, what is the difference? The difference is how many antibodies you make. So, with the Pfizer and the Moderna, you make a high level of antibodies and it protects somewhat, maybe tenfold less against that strain. But what happens over time? Over time these vaccines fade. Now, we do not know what the exact time is. Natural infection is quite variable by people, but it could be a matter of weeks or almost a year. For this it looks like, so far, maybe it is going to be a year for the best vaccines. But those that are not working so well, a lot shorter. And it is even less for the variants, and there are going to be new variants. I am seeing the variants of the variants of the variants now. As you mentioned, I wrote a book about it. Every day I track the variants. Just before I got on the phone, I was going with mutation by mutation by mutation which part of what virus it changes and exactly how. There is now a variant from India that is really different from anything we have seen showing up in California. There is a variant of the British virus that picked up a really nasty mutation from the South African and Brazilian. So, we are getting variants that are going to be resistant to our vaccines. A hundred percent resistant or ten percent resistant, it depends on where you are on that scale. Are you at a high level of 2248
protection or a low level? Can we do anything about it? Yes, we can. EM: Let me ask a quick question here before we get into what we can do about it. When you talk about variants, and I often hear this talked about, and I do not know that people fully understand. We say we want to get as many people vaccinated now with the vaccine we have because that helps stall the spread of variants, but if the variants are not dependent on that, why? Explain WH: Now, that is a theory. There is a counter theory. The theory is that these vaccines, it is a random chance that these are going to occur randomly and the more the virus grows, the more it is going to have a chance to make these. That means it is a population based resistance. So, the idea is that the variants pop out of populations, big populations that are infected. I made a calculation that says there is probably ten to the twentieth variants. That was about six months ago already made. So, it is going to be double, triple that now. But the other day, and this is coming from observations, is that many of these variants come from single people and if you are immune suppressed and you are infected, you can get a persistent infection that lasts for many weeks, ten, twenty weeks, and during that time your viruses are mutating to overcome what is happening in a person, and if that virus gets out, you got a big problem. We know that under those circumstances, you see the same kind of changes we are seeing in the population. That is a counter theory. You do not need a whole lot of people infected. EM: What it is saying, though, is if most people are vaccinated and the initial virus cannot get in, it does not have the host to mutate in to then come out and be worse. Is that safe to assume? Am I missing it or am I getting it? WH: People who are immune suppressed do not make good antibodies so they are never protected. So, if that is the population that is driving it, which is a theory, but it seems to be a pretty good theory now. We did not have that theory, we had a little bit for flu. But now we have a very good idea that is happening. So, it is true in the one sense. Let me just say this. We want to contain this. Anything we can do to shut it down we should do. Vaccines are really going to help protect most people, but we are not in the clear. We were doing what I do personally. I am vaccinated with the Pfizer vaccine and I still isolate. Why? Because I know these variants can 2249
come and get you. I do not know how high my level is. I am of a certain age. I am not going to make the same level of antibodies that young kids do. It may last longer, it may be shorter, there may be a variant. So, I still am very, very careful. Now I have the luxury of being careful. Not everybody does. But we should be as careful as we can be and we should, as a society, help people protect themselves. I like OSHA laws for example. We need OSHA laws so that people can help others protect themselves. That is what we need is the society to protect each other. EM: You made reference a minute ago to the flu which is a great segway into another area I want to talk about which is this concept of herd immunity, and you kind of use the flu to kind of illustrate the idea behind or the lack of logic behind herd immunity. WH: Right, from the very beginning I did not think we would have permanent herd immunity. Seasonal herd immunity, yes. Herd immunity so you are once and done, no, why? First of all, I looked at the coronavirus as it causes colds. There are four of them. They have been around a long time. They come back every year. Same virus, same person, same cold. That is nailed at this point. We did not know exactly why. At the time we thought it was fading immunity. It turns out it is both, fading immunity and virus variation. Natural immunity fades and the virus changes. It is almost identical to flu. The problem is, this virus is more lethal than flu and can get a lot more lethal than it is, and it is more transmissible than flu. The methods we use to control this pandemic wiped out flu. No flu in South America last winter. No flu in America this winter. Very few colds. Ask yourself, are you getting the same number of colds you got before? No. These methods, even as ineffective as they are, let’s hope they stay in place. Some of them saves us from the flu because of the natural history of these things, they have evolved for hundreds of thousands, actually tens of millions, maybe even longer, to do what they do. This is their ecological niche to get in, cause trouble, get out and cause trouble again. There are some viruses that prey only on children, like mostly polio viruses and measles and chicken pox. They get in once to a vulnerable population, then you are protected for the rest of your life, for the most part. That is this ecological niche. Coronaviruses have perfected something else. Now, one of the things I am studying in detail right now is one of their major tricks. They mess with our immune system. I can 2250
show you a chart that will show you about twenty ways that these things mess with our immune system. That is their trick. So, you do not remember that you have had it for very long, so it can come back. And then they change. That is what they do. It is how they have evolved. So, we are dealing with an organism that is actually built to come back again and again and again. To think that we are going to get permanent herd immunity from a vaccine or from natural infection has never be in the cards. That is one thing that I think has been a really unfortunate part of public dialogue. EM: Within the labs that are creating these vaccines, do they look at it as a target they are trying to tackle, or do they look at it as a range of where this virus can go and they are making vaccines that can be effective across a range? How is that developed? WH: That is a very good question. I would say, to begin with, for the first, let’s say until September, we are going to get a vaccine that is going to knock it out, this virus is not going to change very much. September on, they have changed. Now they are saying we are going to have to have a vaccine every year, either the same or an approved vaccine. I actually think their techniques, there are two different approaches. There are new vaccines that are in the works called mosaic vaccines. They present a very wide range of coronavirus antigens, including mat and other species that seem to give higher and better protection, even against homologous and maybe giving broader protection against many, if not most of the variants. That is a hope. I am actually helping some people develop such vaccines and there are some that are already look like they are moving along and it looks good. So that is some hope. Second is drugs, just as we developed the drugs for HIV. This is a target rich virus. It is bigger and has many more parts. We can mess with those parts. We have fantastic tools to do that. We have underinvested in that. We are now beginning to invest and the investment is paying off. We already know that if you give drugs early to people who live in congregate settings like the antibodies that Lilly and Regeneron have made, you can stop people from getting infected. You would much rather have a pill than an infusion that you have to sit down and get injected into your veins. So, we will, I think, within minimum of two years, maybe optimistic, maybe before that, we will have pills you can take. Right now, most people do not realize there is a pill you can take that if somebody in 2251
your family gets the flu, you take it and your chance is about eighty percent less. It is called Xlofluza. I have written about it. Actually, before COVID came along, the public health community was about to make a big push. I talked to my friends at John’s Hopkins. They were going to make a big push, ok, we cannot do that now. But you will see Xofluza is a drug you can take prophylactically. Now if you combine that with vaccines that are broader and you have the chance that if you are in a school or a family or in a workplace that somebody gets COVID, you pop a pill, you are protected, and you pop what is a combination pill like we have for HIV now. Not one but two or three drugs that work on different parts of the virus that are having a hard time getting resistant. I think we have really good strategies. Again, let’s not put all our eggs in the science basket. Let’s put them in both. Let’s walk forward with two feet, science and public health. Both important. EM: We only got about a minute left. I am curious where you see us a year from now? How do you see this playing out? WH: We are not going to be out of the woods a year from now. We are still going to be fighting in the United States, and the rest of the world is going to be struggling as well. We are going to be better off then we were. Most people will be vaccinated we hope. I hope more and more people decide it is a good thing to get vaccinated. But we are still going to have to be vigilant. It is still going to be popping up in various places and there will be some nasty variants. The rest of the world in some places are still going to be in dire straits a year from now. That maybe very different three or four years from now. But when you are thinking about hopping on a plane, first of all, as an American you are not welcome very many places today, and be careful where you are going because you could go to a place that is even a hotter spot than America. There is going to be continued disruptions. We hope that we can get to where New Zealand and Australia is. I think that is a far reach for us. But that is my hope that we could do. EM: I hope that you will continue to follow this and come back and join us with the information you gleam and the new ideas that you have behind it. Dr. Haseltine, thank you so much for joining us. WH: It is my pleasure. Thank you Ernie.
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This interview originally appeared in HPM-Houston Public Health Radio and is available online here:Interview with HPM-Houston Public Health Radio A Lifelong Fight Against Disease: Dr. William Haseltine Talks About Global Health, From AIDS To COVID-19
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May 2021
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The Heat: China leads multilateralism talks at UN CGTN | May 5, 2021 | Interview
The United Nations Security Council met in New York on Friday to discuss joint efforts to combat global challenges. The virtual gathering, chaired by Chinese State Councilor and Foreign Minister Wang Yi, sought to reaffirm support for multilateralism – nation’s working together – and to promote a greater role for the UN in international affairs. To discuss: • Victor Gao is a current affairs commentator and Chair Professor at Soochow University. • Anton Fedyashin is a Russian affairs expert and a professor of history at American University. • Joel Rubin is former U.S. Deputy Assistant Secretary of State. • Klaus Larres is a Distinguished Professor of History and International Affairs at the University of North Carolina, Chapel Hill Also on Friday, the WHO approved China’s Sinopharm Covid19 vaccine for emergency use, easing the way for developing countries to get access to another much-needed tool to help end the pandemic. To discuss: • William Haseltine is the Chair and President of ACCESS Health International and the author of “Variants — The Shape-Shifting Challenge of COVID-19.” This interview originally appeared in CGTN’s The HEAT and is available online here:The Heat: China leads multilateralism talks at UN
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Interview with Bloomberg: TSMC Stuck in Middle of Global Panic Over Chips (Podcast) Bloomberg | May 11, 2021 | Interview
Dr. William Haseltine, Chair and President of Access Health International, explains why vaccine booster shots may be needed to fight new Covid-19 variants. Bloomberg Businessweek Editor Joel Weber and Businessweek Technology Editor Joshua Brustein talk about how Taiwan-based manufacturer TSMC has mastered the chip market but needs to navigate a tricky geopolitical landscape. Businessweek Contributor Robb Mandelbaum discusses some small businesses imposing surcharges for consumers who use credit cards. Bloomberg News Tech Reporter Lizette Chapman breaks down why Uber and Lyft are losing the race to the electric future. And we Drive to the Close with Barry James, CEO and Portfolio Manager with James Investment Research. Hosts: Carol Massar and Tim Stenovec. Producer: Paul Brennan. This interview originally appeared in Bloomberg BusinessWeek Radio and is available online here: Interview with Bloomberg: TSMC Stuck in Middle of Global Panic Over Chips (Podcast)
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Interview with Minor Memorial Library: COVID 101: How will the Virus Evolve? with Dr. William Haseltine | May 19, 2021 | Interview
SARS-CoV-2 variants are now at the root of many of our questions about the future of Covid-19 – will the vaccines work? Will we need new shots each year? Will the pandemic end or can we expect a renewed surge of Covid-19 cases every year, like we see with the flu? Understanding virus variation is critical to understanding how the pandemic will unfold and how Covid-19 may continue to affect our global economy, our societies and all of us individually. In this lecture, infectious disease expert William A. Haseltine, Ph.D., will explore these questions and provide insight into how the pandemic may continue to evolve over the course of the year and into the next. William A. Haseltine, Ph.D. was a professor at Harvard Medical School and Harvard School of Public Health from 1976-1993 He is a pioneer in biotechnology and is the founder of Human Genome Sciences, Inc. and several other biotech companies. This interview originally appeared in Bloomberg BusinessWeek Radio and is available online here: COVID 101: How will the Virus Evolve? with Dr. William Haseltine
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The Heat: Coronavirus pandemic — more than 1.7 billion vaccine doses given globally CGTN | May 27, 2021 | Interview
The number of people vaccinated from Covid-19 continues to rise in some countries. The European Union says it’s on track to inoculate over 70 percent of its adult population by September. However, people in rich countries are getting vaccinated more than 30 times faster than those in poorer countries. Latin America and India continue to struggle against rising death tolls. Joining the panel to discuss: • Arthur Dong is a professor at Georgetown University’s McDonough School of Business. • Dr. Bharat Pankhania focuses on infectious disease management as a senior clinical lecturer at the University of Exeter. • Gustavo Ribeiro is a journalist and founder of The Brazilian Report. • William Haseltine is the chair and president of Access Health International. This interview originally appeared in CGTN’s The HEAT and is available online here: The Heat: Coronavirus pandemic — more than 1.7 billion vaccine doses given globally
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June 2021
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Houston Public Radio: Reflecting On 40 Years Of The HIV/AIDS Epidemic | June 17, 2021 | Interview
Town Square with Ernie Manouse airs at 3 p.m. CT. Tune in on 88.7FM, listen online or subscribe to the podcast. Join the discussion at 888-486-9677, questions@townsquaretalk.org or @townsquaretalk. This month marks the 40th Anniversary of the first reported cases of what later became known as Acquired Immune Deficiency Syndrome, or AIDS. It's also HIV Stage III. Since the start of that global epidemic, more than 32 million people have died from HIV worldwide. Currently, 38 million people are living with HIV. Decades later, where are we now in the fight against the disease? Today, experts join us to talk about how far we've come in terms of treatment, combatting stigma and living with HIV, and how far we still need to go to end it. Do you – or a loved one – live with HIV? What have been the challenges? And what progress have you seen or experienced in maintaining quality of life? Guests are: Dr. William Haseltine • Chair and President of the global think tank ACCESS Health International and founder of more than a dozen biotechnology companies. • Known for his groundbreaking work on COVID-19, cancer, human genome and HIV/AIDS, including designing the strategy to develop the first treatment for HIV/AIDS Maggie White • Nurse Practitioner and Sub Investigator for Infectious Disease Research at The Crofoot Research Center Derrick Brown • Chief development officer, AIDS Foundation Houston Dr. James Carroll 2260
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Internal Medicine and HIV Specialist, Legacy Community Health Transcript:
Ernie Manouse 00:03 This month marks the 40th anniversary of the first reported cases of what later became known as Acquired Immune Deficiency Syndrome, or AIDS. Since the start of the global pandemic, more than 32 million people have died from HIV worldwide, and currently 38 million people are living with HIV. Today, experts join us to talk about how far we've come in terms of treatment, combating stigma, and living with HIV, and how far we still need to go to end it. What impact is HIV or AIDS had in your life? What challenges have you noticed over the years and what changes for progress? Have you seen or experienced in maintaining quality of life? Or are you or one of your loved ones living with HIV? Our phone lines are open to hear from you today. Unknown 00:49 Town square with Ernie manouse is made possible with support from listeners like you subscribe to our daily podcast and find episodes at townsquaretalk.org. Ernie Manouse 01:04 Joining me right now though, to begin the conversation, is a global health expert and pioneer in AIDS research, and looking for the solutions to a problem that has plagued us for 40 years now. Dr. William haseltine is the chair and president of the global Think Tank ACCESS Health International, and the founder of more than a dozen biotechnology companies. His career has been consistently at the forefront of modern medical research, including groundbreaking work on COVID-19, cancer, the human genome, and HIV/AIDS. He designed the strategy to develop the first treatments for HIV and AIDS. Welcome back to the program, Dr. haseltine. Hello there, sir. William Haseltine 02:01 It's great to be back, Ernie. Thank you. Ernie Manouse 02:03 It amazes me that this month marks the 40th year of HIV and AIDS in this country. I guess the first place to start with this is what 2261
are your earliest recollections of this, this virus coming into our domain? William Haseltine 02:24 Well, it was December of 81, I believe, perhaps 82. I was in a corridor and a friend, a doctor, stopped me. He said have you heard about the new kind of cancer, Kaposi sarcoma? I said no. He said, well it usually hits older men and older people, but now it's hitting younger people: do you think it's a new virus? Because he knew I was working on viruses. That piqued my interest, of course, and then over the next few months, I started to pay a lot of attention to it and began to work on the topic. That was my earliest recollection, it is very clear. It was in a hallway connecting two buildings; I still remember it as clear as it happened yesterday. Ernie Manouse 03:14 Wow. Could you have imagined at that very beginning moments what it would grow into? And is that something that your mind all of a sudden goes to, this is what we're just finding out, hold on this could be big? William Haseltine 03:31 Well, the answer is I was very worried from the very beginning and the more I learned the more worried I got. I'd been working on another human retrovirus, called human T cell leukemia virus, a rare form of leukemia, at least in the US, and more prevalent in the South Pacific in Japan. That is a transmissible form, a virally transmissible form, of human leukemia. I'd been very interested in viral cancers for for many years, even hosting an International Symposium on the topic that led to a book. But it took me a few months to recognize, specifically it took until we had tests for HIV, to recognize the threat that it was. I have to say, Discover magazine interviewed people asking whether it was going to be a major threat. I was the only one of 20 scientists who actually stepped forward and said I think it's going to be a really big epidemic that we've got to make a major effort. They went with the other 19, but 25 years later, 30 years later, they did a retrospective and said that was the one story they got wrong, and there was one scientist that got it right. That was me. I wrote back and said that's a good thing for young scientists to read- if you have good reason to believe your point of view, stick to your guns. Scientific truth is not a matter of democratic opinions. Ernie Manouse 05:06 2262
You mentioned already that early identifiers believed this to be a cancer. How did you know, what led you to believe and understand that it was a virus? And how is that different than the way cancer exists in our systems? How is HIV/AIDS different? William Haseltine 05:28 Well, it turns out that HIV is damaging to the immune system. And people who, especially those who caught HIV disease early, AIDS early, had weakened immune systems and were also exposed to many other viruses. One of those viruses caused the Kaposi sarcoma. So, it was a manifestation of immune suppression that later, very quickly we realized, there's a whole syndrome with pneumocystis carinii for the lungs, and many, many other infections that most people who have a normal immune system don't get. The key discovery was a group of scientists out in Los Angeles realizing that there was a very specific defect in CD4 cells, the T cells that are protective, and they were just absent in many of the patients that showed up with a common immunodeficiency, and then it became clear it was an immunodeficiency disease. So with respect to cancer, many people don't think of viruses and cancer, but many of the most prevalent cancers in the world today, liver cancer from Hepatitis B or hepatitis C, cervical, and throat cancer in men, from human papilloma virus, and even some tumors in Africa caused by the mononucleosis virus. So there are many viruses that actually cause tumors in animals and in people. And of course, human T cell leukemia virus, and many retroviruses like that, that's the virus of which HIV is a member, of causing cancers in animals. Ernie Manouse 07:07 We may have a misguided idea of science, especially today, after seeing how quickly the COVID vaccines were developed, and we were able to get that under control. What made it possible to get a lasso around COVID so quickly, and yet 40 years on, we still don't have a vaccine against HIV? William Haseltine 07:33 Well, you're fighting nature in the case of HIV, and you're going with the flow of nature with COVID. And what I mean by that is, HIV has evolved, like malaria and tuberculosis, to infect us and never leave. There are a few other parasites that do the same thing. They are usually sexually transmitted or transmitted by very intimate contact, for example, mothers masticating the food for babies, or a 2263
blood transfusion, or through sex, they get into adults, and they never get out and your immune system can't fight it off. One of the things I said very early on, and actually the first and maybe the only time I was booed off stage, at a second International AIDS symposium, was that I don't know if we're ever going to have a vaccine for AIDS. And the reason for that is that a vaccine is not a shield, it doesn't prevent you from being infected. What it does is an early reaction, it sets up a very quick reaction, if you've seen it before, or something like it before, you will mount a very rapid immune reaction, and you may prevent the virus from growing and taking hold and causing disease. But what I realized is every aspect of the immune system was fully active in patients who were infected, and getting ill and dying, from the AIDS virus. And, if your body can't do it naturally, can't fend it off naturally, there was nothing that we could think of at the time, and even now, nothing much we can do to stop it. The same is true for tuberculosis and malaria. And there are different reasons for each one, but it's an ecological niche that these parasites have: they get into adults, they may cause a disease many years after they've read it, the person has been infected, and your body just simply can't fight it out. Now, COVID is different. Most people who get the COVID virus fend it off very well. They don't even know they've had it, or they have very mild symptoms. But there's a problem, and I think it's a problem we have to be cognizant of, with the effectiveness and the vaccines we now have. It may be the people who get Coronaviruses, including cold viruses and COVID, don't know they have it or have a very mild reaction and the body fights it off. But that isn't the end of the story, because COVID is very much like flu. It infects adults, with competent immune systems, who have seen the virus before. So the virus has adapted, mostly in bats, which like humans are long lived animals that live in densely packed caves and breathe the same air, sort of think of an inverted Super Bowl, when you're looking at all those heads packed together. That's what a Batcave looks like. Lots of little heads all packed together. And they live a long time, so the virus to survive in that environment has to learn to come back to immunocompetent adults, even to adults that have been infected with the same virus before. So we and bats share a lot in common. We're now a massive ecosystem packed into cities. And guess what, like bats we fly-- there were 4 billion flights of human beings from 2264
one place to another in 2019, four and a half billion! So we have made a great ecological niche for this virus, and we have to be very worried that it has amazing tools to overcome those tricks and get back in. Look at Brazil. Look at India. In Brazil, you had large populations that were almost entirely affected with one strain, then a new strain came along and infected the same populations with lethal consequences. In India, look what's just happened. There were days in India where there were 5-600,000 people a day getting infected. And many, many thousands dying every day. And many of those people had already been infected. And so, the good news is vaccines may prevent most people from getting sick, but they may not prevent us from getting infected. And so that's sort of a long answer to a short question. Ernie Manouse 12:16 Well, Dr. Haseltine, we're gonna take a quick break here, I, I guess the odds would be out if you put you and I in a room together, we're gonna end up talking about COVID at some point, and there we are. We're going to talk more about AIDS research and treatment. We're going to talk about Dr. Heseltine's three prong effect of how to combat this, that he started back in the 80s, which has proven to be the best way to approach this, even today. This is Town Square, we'd love to hear from you and your thoughts and questions at 888-486-9677. If you've ever had any questions about HIV or AIDS, this is the man to ask about the origins and what we can do today. So please, keep listening. We'll be right back. I'm Ernie manouse, and this is Town Square. We continue our conversation now with AIDS pioneer Dr. William Haseltine. And joining into the conversation is Maggie White, nurse practitioner and sub investigator for Infectious Disease Research at the Crowfoot Research Center. Hello there, Maggie. Maggie White 13:36 Hi, Ernie. How are you? Ernie Manouse 13:37 Welcome back to the program. We are talking with Dr. Haseltine, and I know a lot of the work that he pioneered and continues on with today influences the work that you folks do over at the Crowfoot Research Center. Keep Stumbling on the word research today. I apologize. Meg, I asked Dr. Haseltine a little earlier,
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so I'll ask you now, first time you became aware of HIV/AIDS, what's your earliest recollection? Maggie White 14:03 Oh my god. Well, it's funny because HIV/AIDS, for lack of better terms, turned 40 this year, which is what we're talking about, and I also turned 40 this year, so I was the exact same age. I turned 40, a few months earlier. Now everybody knows my real age. My mother was a nurse and she was a nursing professor and did a lot of work in the community. She was my earliest memory because she did hospice outreach with her church when we were growing with our church when we were growing up taking care of the patients that were dying of AIDS. And it's funny because as I'm telling you the story I'm looking at, in my office, I have it from Saturday, February 7th 1987, it's the front page of the religion section of the Houston Chronicle, and it's a picture of my mother and it says focus on AIDS. It's an article where she was pretty much saying, hey, God loves everybody, you know, gay people. God loves them just as much they're not sinners, and they deserve, you know, to be taken care of. And so she gave me an impression at an early age. So that's really my first memory of HIV/AIDS, was my mother doing outreaches when I was a slightly younger child than I am now. Ernie Manouse 15:17 Dr. Haseltine, Maggie brings up a really important point, and I'm curious back in the 80s, because I have recollection of this, it was how to separate this as a disease, as opposed to a moral issue. And a lot of people had issue with that, especially because the predominance of this virus in in the gay population, correct? William Haseltine 15:39 That's absolutely true. Remember, the first name for this disease was Gay-Related Immunodeficiency: GRID. It wasn't until later when it was realized. And, to give you a sense of what the spirit at the time was, there's a book written about me and Robert Redfield, the former head of the CDC, called "The Myth of Heterosexual AIDS". And it's ironic that that was sort of sponsored, sub rosa, by the Centers for Disease Control. At that time, it was part of the Reagan administration, they didn't want to talk about AIDS, it was inconvenient. They stigmatized Haitians and gays, as having AIDS, and being the carriers of AIDS, were very loath to consider the fact that it might be a heterosexually transmitted disease. And hence, the 2266
title of the book. I recently bought a copy of that book, which you can still obtain. That gives you, I think, a flavor of the time. Ernie Manouse 16:45 Yeah, we had one of our regular listeners write in and they were curious about your opinion: was it fair to have labeled that Canadian male flight attendant as patient zero? Couldn't help but wonder about the emotional and psychological pain he got from being labeled as someone to have started this disease that ended up killing millions of people? Dr. Haseltine, your thoughts? William Haseltine 17:08 Well, a lot more epidemiology has been done with the newer techniques of sequencing viruses. And we know that wasn't fair in any way. There were many, many origins in the United States of the HIV virus. It came in from many different people. It is true that he, and his particular virus, was associated with a number of people, but he was not the only one-- there were many variants. One of the things I've worked out early in my scientific career is how to fingerprint a virus. And then sequencing came along and you can do it even better, but it's clear that he wasn't the only one. and it wasn't fair. It wasn't fair. But this shows you how strong that association is, even now, almost 40 years later, I can remember the man's name. Ernie Manouse 18:00 Maggie, let me ask you this, in today's day and age with the work you're still doing, is the stigma still there? Is there still this reaction to people being HIV positive or having AIDS that we suffered through back in the 80s? Maggie White 18:15 I think so, I think it's attenuated very much. I don't think there's necessarily the large scale collective paranoia that people had maybe initially when there were so many more unknowns to the virus. And I think it depends on education, exposure, and there's a lot of different things. But you know, I tell patients, especially my newly diagnosed patients, and I, whenever I talk to somebody who's newly diagnosed with HIV, I tell them, hey, you may not remember a lot from this visit today, because you've probably got a lot going on, you know, you've got a lot of questions. But the one thing I want you to keep in the back of your mind is that you're going to be fine. You know, we'll take care of you. HIV is not what it was five years ago, 10 years ago, 20 years ago, 40 years ago, right. But I also 2267
understand that when you walk out the store, it's a different story. And if somebody, for example, finds out they're newly diagnosed with cancer, they might be posting on social media, "hey, you know, I just found out I have cancer, and I'm going to start chemotherapy and radiation" and everybody's like, "oh, we're so proud of you. We're, we're, you know, we're praying for you, you're so brave, you're so strong", and you don't see that with HIV. Typically, you don't see people posting like, "Oh, I just found out I was diagnosed with HIV and I'm going to start treatment". I mean, there's still, whether or not we want to address it, and maybe a little bit more subconscious now than conscious, but there's definitely still stigma attached to it and, and certain segments of society may be more stigmatized than others. I think PREP has done a very good job, from what I've seen, of normalizing the conversation a little bit more where I see so many more relationships or couples where they're in what we call sterile discordant relationships where one partner is positive and one's negative and there's not the stigma or the sterile selection, meaning like I'm only going to date people that are my status. I think we've made a lot of progress, but you know, there's still a lot of education and outreach and, and messaging that we need to be diligent with doing in the community. Ernie Manouse 20:13 Doctor Haseltine, please excuse me if I'm oversimplifying what I'm about to say here, but it seems as though you approached HIV/AIDS research and work as kind of a three three prong approach. One being you needed to understand the virus. Two being you needed to conduct research on the epidemic. And three being you had to raise public awareness of what this really was. Is that characterizing it correctly? William Haseltine 20:40 It's actually four: you need to find drugs to stop it. But yes, that is correct. And I think one of the most important things that happened, I'll give you a single event that sticks in my mind, and that is the moment that Princess Diana held an AIDS baby, the moment she hugged an AIDS man. Before she did that, the world was terrified that HIV was highly contagious, and people would take their kids out of school for fear that somebody in that school might bite their children or do do something to infect them. The moment she did that, that turned around. And I like to mention one other 2268
thing about what Meg was talking about, and that is, I looked globally at HIV and there are parts of the world just two years ago, where I was in Durban, and I have to say, as much as I knew about AIDS, I was totally shocked to learn that young women, say between 17 and 25, 70%, seven-zero % are HIV positive. I want you to think about that a minute. That is, like astounding, that is like the worst nightmare that we ever could have imagined. And it isn't that it's so much more contagious, it has to do with social practices, and who has sex with who and who has sex with how many people, and how many people those people have intimate relationships with. So this has, under certain circumstances, been extraordinarily dangerous. There are other parts of central Africa, for example, where we don't understand all the reasons for it, but it's been about 2,3,4% for the last 30-40 years. And so you really have to understand not just the virus, you've got to understand the social structure of a community if you're going to work to prevent it. And those were not caused by drug users, they were caused by people who had intimate relations with a broad network of people as a way of life. And I think that's something you have to get your head around. It's like, every virus has its own ecological niche, and it finds the weakest parts of human actions in society. I think if we're thinking about any infectious disease, you have to take it not just not just from a scientific point of view, you have to take it from a social and an anthropological perspective as well. Ernie Manouse 23:31 I am curious, I'm reading up on this. And I'm thinking about the times and what we learned, had it not been for the moral component, would we have been in a better place to slow the spread much more quickly, Dr. haseltine? William Haseltine 23:45 The answer is yes, because I'll give you one very specific instance: in 1985, and 85/86, of the next year's budget, Health and Human Services, we already knew it was a big epidemic, allocated a mere 1 million additional dollars for research. That's all they asked for. Congress would have given it to them. Rock Hudson had died and people realized maybe this is more serious or you got sick. And I was able to go to Congress and get 360 million. What does it take, I realized that Rock Hudson was such a hero, and was not identified as being gay, that it shocked people that somebody like Rock 2269
Hudson could get it that means, maybe I could get it and all of a sudden, the government purse strings opened up and we needed that money earlier. That money allowed generations of scientists to begin to work on viruses. And if we are ahead of the game today for COVID, almost every single one of the COVID leaders in research is a former HIV researcher, all my students, and even students of my students. And now even students of my students, of my students are COVID researchers. But they all cut their teeth, whether they're drug developers, whether epidemiologists, whether they're sociobiologists, all cut their teeth, on HIV/AIDS. And so if you asked me, where did our fast rapid progress come from, even, for example, the infrastructure to test our vaccines and the administrative greasing of the wheels that was done by ACT UP and other people to allow rapid drug development, all of that came from HIV. So it's had some really positive benefits. But I can tell you an answer to your question. We could have done a lot more if it hadn't been so dreadfully stigmatized. Ernie Manouse 25:46 We're talking with AIDS pioneer, Dr. William haseltine, and Maggie White nurse practitioner at the Crowfoot Research Center, talking a little bit about funding and money. And so of course, it's a perfect time to introduce Derrick Brown, Chief Development Officer of AIDS Foundation, Houston. Hello there, Derek. Derrick Brown 26:05 Hey, Ernie, how are you doing? Ernie Manouse 26:07 I'm doing well, I wanted to bring you into the conversation for a moment to remind people as much as we talk about the history of HIV and AIDS, it is still an issue we deal with today in Houston, Texas, fourth largest city in the world, and it's dealt with across the globe. And I'm kind of curious about some of the work that you folks are up to that are helping those who still find themselves in the situation of being diagnosed with HIV. Derrick Brown 26:31 Absolutely. And thanks, again, for having me and great to be with you, again. Really, the work that we're doing is trying to end the epidemic here in Houston, and hopefully, around the world. And by doing that, there are four pillars, as I'm sure the doctors all know, to ending the HIV epidemic. And really, our work revolves 2270
around those key elements that make it easier and more accessible for people to who are living with HIV, to get the things they need, in order to to take the medication, be adherence, and get back on their feet. Most of the folks that we deal with are homeless, or coming out of a relationship or something like that, where they need housing for which we provide, or it's nutrition, we provide food through our food pantry, supportive services, linkage to care, hospitals, things of that nature. So really trying to give them the wraparound services they need in order to get back on their feet, be medically adherent to their medications, and hopefully live a healthy and full life. But the other part of the thing that we're doing a lot more of now is prevention work. And so with the PREP drug being out there, and us educating people about PREP, so that we are lessening the transmission of HIV in our communities. That's the other way in which we're going to end HIV epidemic here in Houston as well. Ernie Manouse 27:51 I do want to correct if I said this wrong. A moment ago, I may have referred to Houston as the fourth largest city in the world. It's actually the fifth largest city in the country. But I'm so proud of Houston, I had to elevate us there for a minute. I know that as we seem to perceive AIDS as being under control, yes, life is much better for people who are HIV positive than it was 20 years ago. What does that do to your funding? Derrick Brown 28:21 So it's, again focuses more on the prevention side. So I think that a lot of the funding we get for the people that live with HIV comes from the federal, state, and city level. A lot of our other funders, corporations, private grant foundations, really are interested in the medical work we're doing in the prevention side with PREP, and impacts and things that we're doing on that side. But I will say that the word AIDS is still stigmatizing, the word HIV is still stigmatizing. And therefore, the more we're able to do, like I think one of the doctors mentioned earlier, with the younger community which wasn't here 40 years ago, which didn't live through the 80s and 90s of HIV, don't have that educational component to you know, their history of their life. And so for them, it's take a pill every day, and you know, I'll be fine. And/or "it won't happen to me, this is over." So I think that we're really trying to reach out and re-educate. HIV 2271
can impact anyone at any time. No one is immune. And we're very thankful that pharmacology has come a long way, but we still have a long way to go. Ernie Manouse 29:28 Derek for people listening right now that would like to reach out to AIDS Foundation, Houston for help and services, how can they find out all that you folks do? Derrick Brown 29:36 They can go to our website at AShouston.org. And on the website, you can donate you can find out all about our services, you can get HIV and STI testing for free, you can get PREP for free. All the services that we offer to our clients and to our patients is all free of charge. Ernie Manouse 29:53 Derek, thank you very much. We'll also put that information on our website at TownSquaretalk.org. Thank you for joining Derrick, and thank you for the work that AIDS Foundation Houston continues to do in our community. Derrick Brown 30:04 Thank you, Ernie. And thank you for your continued support. Ernie Manouse 30:06 Thank you. Maggie, he brings up a really good point how important it is to take your medication. And that is one of the things you have trouble with, especially with the homeless population or the underemployed population, correct? Maggie White 30:18 It can be yes. And, in general, I mean, it's, it's really funny because there's this dichotomy with HIV, it's really easy to be very positive and put this really great spin on it. It's very controllable. It's very manageable, it's very, you know, it's a chronic disease, like you have high blood pressure medication, you take medication for that you have HIV, you can take medication for that. But that's only half the picture, just like everybody else was addressing, there's so many social determinants of health, that affect it, you have to have access to care, you have to be able to afford the medication, you have to know your status, you have to have a place where you're receiving care and treatment receiving those medications or maybe you don't feel judged or stigmatized. Or maybe you don't want to out yourself as somebody with HIV by going to a clinic that you think is, you 2272
know, predominantly for people with HIV. So there's so many other factors involved, that really by the time that that patient gets in the door, and I'm seeing them and I'm writing them a prescription and managing their care, or we're getting them on a study to, you know, to manage their care, they're in the minority, or they can be and there's still so many new diagnoses when we use the phrase in the epidemic. I mean, we have the tools to end the epidemic today, if everybody in the world is screened, knows their status gets people that are positive get on treatment, the people that are negative that are you know, perceived or at some sort of risk get on prevention like PREP, that can stop the epidemic, but it's the secondary and the tertiary factors that need to be addressed. Ernie Manouse 31:49 I want to remind everyone, this is Town Square. I'm Ernie manouse. We're talking with Maggie white from the Crowfoot Research Center, and Dr. William Haseltine. Our phone lines are open at 888-486-9677. We're going to take a quick break. We'll be right back. We are talking right now with Maggie White from the Crowfoot Research Center and Dr. William Haseltine, a true pioneer in AIDS research and study. Dr. Haseltine, before we move on with this, there is another interesting point in all of this, which is that when you looked closer at the HIV, I guess virus, you noticed that there were unknown proteins involved there. That sounds very scary. As of today, are they still unique? Or have we learned more? William Haseltine 33:20 Well, all organisms adapt in very interesting ways. And one of the things we were doing, I was studying the genome, it was very early genome studies of HIV, and we were the first along with the French group to sequence the entire virus. And we noticed, by analogy with other viruses we had just sequenced, that there were big gaps between where nothing seems to be there, you would see chunks of the genome. So we carried out a systematic program to introduce mutations all the way through the virus to see what it did. And then we found, doing that, six, and some argue seven. proteins that nobody had ever seen before. And one of the things when we studied it in great detail we learned is they did things we had never seen in biology before. And some of the things they do, are still being worked out. But some of the things they did, I think they're still unique in the way they do it. And other ones have opened up 2273
entirely new vistas for biological research, how the virus tries to inactivate the immune system, something that Coronaviruses do, how the virus cuts itself from being tethered to a cell so it floats free, a few other viruses do that. But there's some things that it does, by regulating its nuclear export from its RNA from the nucleus, that we'd never even knew could happen. And so it was is new to a lot of biology. Now is that scary? Not to me, because some of the best drugs that we're talking about, PREP, that have just become available. So the ones where one shot may last you eight months, come from understanding those proteins, and understanding that if you stopped them, it's so different from what our bodies do, the drug virtually has no effect on you. The big problem with most drugs against viruses, like a protease inhibitor or a polymerase inhibitor, is you have many proteases, and you have many polymerases in your own body and you're always dealing with what's called a sort of the difference between you and the virus. And if they're too similar, which many are, you'll get a therapeutic window, which is narrow, which means a little bit more of the drugs than you should take could have a very nasty effect on you. That isn't true with some of these really exotic things the virus does. So you can really load up a person with these antiviral drugs that last a long time, some of them even three or four months half life, and protect people for a long time. So PrEP is getting better and better. I predict for the next few years, there'll be a single shot that protects you for a year as well as flu protects you from flu, and maybe even better. So a single shot every year may be all you need to protect yourself. Ernie Manouse 36:25 I'm gonna listen, I'm gonna listen closely to you, because your predictions on this all along for the last 40 years have been pretty accurate. So if I were a betting man, I'd be betting on you being correct there. Before we continue on with our conversation on the phone. Now we have Dr. James Carroll, who's an internal medicine and HIV specialist over at Legacy community health. And if I'm not mistaken, I think I know this Dr. James Carroll. Dr. Carroll, is that you? James Carrol 36:57 It is me. How are you doing Ernie? Ernie Manouse 37:00
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Well, it is good to hear from you again. Sometime we should talk off air and catch up. But, you are back here and you are over at Legacy Community Health. Help me understand a little bit about how Legacy's history is tied to this virus and what people can come to you for today. James Carrol 37:16 Well, legacy started I believe back in the 1980s as one of the first clinics, it was started out as an STD clinic, that became one of the first clinics in Houston caring for patients with HIV. And over the years, they've expanded their services, and become an FQHC. Offering health care to all and having in having ways that people can access health care, that might typically have barriers to getting health care. Ernie Manouse 37:48 We tend to have the misnomer, we've talked about this already a little bit on the show today, that with these protease, or with the the PREP drugs, and all of that out there, that pretty much HIV and AIDS is something we don't have to worry about as much. And we see less funding for it and things like that, from where you sit, the work you do day in and day out, what's your take on this? James Carrol 38:08 What's my take on it, you know, with the numbers of patients that come in as newly diagnosed daily, weekly, monthly, it's still a very serious problem and fortunately we have medications that are really effective, potent, and with few side effects. But we also have ways to help prevent HIV with all the PREP medications and potential injections and stuff that they were discussing earlier. So it's good to take that approach, just like everybody has said, prevention as well as treating and preventing the spread through treatment. Ernie Manouse 38:43 Dr. Carroll as someone who works with patients, what's the biggest challenge you face when dealing with this? James Carrol 38:50 The biggest challenge? Well, you know, that there's all sorts of little challenges that kind of add up along the way, but, you know, places where patients can access specialized HIV care, tend to know the workarounds I guess to get over these these these hurdles. You know, my recent work, the biggest hurdle is actually transportation, lack of telephones, things like that. In certain populations there can 2275
be big barriers, obviously, to them being successful with their their treatment. Ernie Manouse 39:30 If folks want to find out more about the services offered by legacy, community health, how can they find that out? James Carrol 39:37 Well, we've got a wonderful website, legacycommunityhealth.org, and it explains all of our services. We offer everything from HIV care, preventative care, adult medicine, Behavioral Medicine, even Geriatric Care, ob gyn, and pediatrics. So, the services that legacy offers to the community has greatly expanded they've got clinics all over the city. And, you know, it's an excellent source of accessing care for the city of Houston. Ernie Manouse 40:09 Dr. Carol, thank you very much for joining us. In full disclosure, Dr. Carroll used to be my GP for many years, and so it's good to hear you're back in the area, and thank you for all the work you do. James Carrol 40:19 Thank you. Ernie Manouse 40:20 Dr. James Carroll is an internal medicine and HIV specialist at Legacy Community Health. Back to our conversation now with Dr. William Haseltine and Maggie White. Maggie, let me ask you this. We've talked about all of what we know leading up to today. Well, we haven't said everything we know, but we've talked about the topic of things we know: what are you folks doing today, and what is on the horizon that we can look forward to as far as research and combating this? Maggie White 40:47 Well, I think Doctor Haseltine already hit the nail on the head with looking at long acting things to prevent HIV. He said 12 months, I mean, currently here in Houston, we've got a lot of different trials going on at our site. We're starting a PREP study looking at a medication called lncaprevere, which is an every six month injection for prep. So we're not quite at 12 months, but six months is a good start. In the queue for the FDA to approve is another medication called Caboteggrevere, which we think will work for every two months. We're also doing an HIV vaccine trial here. So that's looking at a vaccine, that's different than PrEP, which 2276
is medication you take to prevent HIV, if you're exposed to it, you know, vaccine is a vaccine, training your immune system, but we have that as well. So, you know, what I think we all have to look forward to is maybe just putting us all out of jobs as far as HIV treatment, you know, if we can get to the day where we can vaccinate everybody in in the epidemic, or get people on prep, and, you know, take care of the people that are the people that have been living for a long time with HIV. You know, let us stop working. And we can focus on that people that their blood pressure, which is less easy to fix these days, it feels like compared to HIV sometimes. Ernie Manouse 42:03 I know the Crowfoot Research Center was involved with the recent, much hoped on vaccine against HIV. Dr. Haseltine, though, early on you mentioned to us preliminary results, we're not looking that great. What do we know now? William Haseltine 42:19 Yeah, the results still don't look that good. It's been one major disappointment after another. What I actually said that got me thrown off the stage many years ago was I didn't say we won't ever have a vaccine, I said we can't tell you, from what we know today about the virus and the immune system, whether we can solve the problem. We have to do much more intensive research on the immune system, and on the virus and the interaction of the two. That statement I made 35 years ago is as true today as it was then. We need to know more about immune system, we need to get better tools. And I have to say, as a scientist looking at the rate of progress, over the last 50 years, it has been phenomenal, much more than anybody could have hoped for. And we saw that pay off with the vaccines for COVID, and many other diseases. We've seen immunology being used to fight cancer, which was a hope, only a dream when I started at the Dana Farber Cancer Institute, so that I'm hopeful that we will learn enough that we will have a vaccine. But in the meantime, these new PrEP drugs are really important. Let me just tell you an experience I had last night, I have a stepdaughter that had to go to the hospital for an accident. And I was there for many hours, so I got to look at all the advertisements. I was very pleased to see that they had big posters up around that hospital in the Bronx, actually in Brooklyn, advertising PrEP! That was great, great news, because that is something that, as you've just heard, can really 2277
prevent people from getting infected. And is quasi vaccine. What is the flu vaccine? You take it every every year. And actually, it turns out, you should probably take it every eight months. And you are not necessarily immune to it, but you certainly don't get as sick from fluids as you might otherwise. And so we're accustomed to that kind of annual exposure and treatment. And I think that is where we can see the reality of that happening for HIV. And there is always the hope that there'll be that key breakthrough in vaccines and maybe even one that Maggie's clinic is working on will be that one. There's always the hope. Ernie Manouse 44:52 Our phone number here is 888-486-9677. I'm actually going to finally go to the phones and Brandon is on the line. Brandon, you are actually our first caller of the day and probably our last at this time. But anyway, what's on your mind? Brandon (Caller #1) 45:06 Hey, so yes, I've been on PrEP for about five years now, and I always had this question about missing like a day of not taking the pill I usually that's the first thing I do. I wake up in the morning, take my pill, drink some water and get on with my day. And there's some days that, you know, I forget, or even recently, there was a I had a little weekend trip, and I forgot my prep at home. So it was like two or three days, I didn't take it. But that Monday, got right back on it. I want to know, what does that do or anything like that? Ernie Manouse 45:38 That's a great question. And we're gonna toss this over to Maggie, and Maggie, I also want to put in I had a friend who came to visit me from Canada, and his doctor had instructed him it's two days on one day off, and a doctor here said, take it every day so you don't forget that which days are your day off. But to address even the bigger question of Brandon's, what happens if you miss a day? And for people who aren't caught up on it, PrEP is the pill that you take, and you should take according to most doctors daily, that helps you prevent you from getting infected with HIV. So you can go about your life without worrying that you may get infected. Okay, over to you, Maggie. Maggie White 46:13 Right, so the short answer is, you're probably okay but you want to take PREP consistently. It's really it's just a matter of looking at 2278
the drug levels in the bloodstream. We know that PREP, you know, from clinical trials was over 99% effective in preventing HIV and people who are at risk for HIV, if it's taken correctly and consistently. There's two medications right now that are currently approved by the FDA in the United States for PREP. One is Descovy, and the other one, which was the first one, is Truvada, which also is in a generic form. They're both equally effective, they both work incredibly well, if taken correctly. You know, we know that if people miss doses, that percentage, that 99% drops. When you look at some of the studies that efficacy trials looking at PREP, they did testing on people that were infected with HIV that were on PREP on the study, and they can do a special kind of testing where they look at the drug levels in their blood essentially. And that's a good correlate of adherence. So we know even if people miss a dose or two, you know, generally, if they were taking at least five or more doses a week, their adherence is good, and they weren't necessarily at an increased risk. That being said, that's not something I'm going to advocate, you know, for having a skipping a day, once a week. But generally, if you miss a day, it's not the end of the world. Generally, I tell my patients like an 18 hour rule of thumb, if you realize you missed a dose, if it's been less than 18 hours, since you were supposed to take it go ahead and take it, if not wait until the next day. Sometimes when you go out of town for sure you can forget it or forget to take it or get busy. You know, it's always best to have a backup method of HIV prevention like a condom just because you know, the data is looking at daily dosing. You can always call pharmacies, sometimes they'll give you emergency pills or like a weekend because I certainly wouldn't want anybody to have to stop PREP, just because they left their bottle at home. Now there is an alternate way of taking PREP, which has been approved in France for a while, Canada may be doing it, the CDC did update the guidelines this past year to talk about it, which is called the 211, which is where it's more incident, or you know, exposure based. Meaning it's not something that you have to take every day, but if say, you know, you may potentially be exposed. So if you're going out or you're going to you know, something's going to happen. You can take two doses, within 24 hours of exposure, you know, sexual activity, for example. And then you take one pill two days later, or for the next two days consecutively. So say if I'm going out on Friday 2279
night, I could take two pills on Friday, take one pill on Saturday, one pill on Sunday. You know, the caveat that that's just based off of that single exposure on Friday, if I was potentially exposed or sexually active on Saturday, then those two days afterwards would be Sunday and Monday, two days after the last potential exposure. Ernie Manouse 49:04 As always, we recommend you talk with your primary care physician or primary care practitioner to find out the best way to keep yourself safe. Unfortunately, that music means we have reached the end of the show. I want to thank Maggie and Dr. Haseltine. Maggie is a nurse practitioner and sub investigator for Infectious Disease Research at the Crowfoot Research Center. Dr. William Haseltine, a friend of our show, he is the chair and president of the global Think Tank ACCESS Health International and the founder of more than a dozen biotech companies. Dr. Haseltine, that I do want to just take a moment and say if it hadn't been for your work and foresight, God knows how many more people would have died from HIV over the years and we really can't thank you enough for the work you've done. William Haseltine 49:46 You're welcome, Ernie. Ernie Manouse 49:47 Dr. haseltine. Thank you, Maggie white. Thank you And that wraps up the show for today. If you missed any of the show, remember town square with Ernie manouse is available as a daily podcast. You can subscribe at our website, townsquaretalk.org, or wherever podcasts are available, remember to join Craig Cowen tomorrow morning at 9am for Houston matters and then we'll be back at three. Have a good day. Unknown 50:10 Town square with Ernie manouse is a production of Houston public media. The opinions expressed by guests and callers do not necessarily reflect the views of the staff management or underwriters of this station. Medical opinions should not replace consultation with a medical professional. This interview originally appeared on Houston Public Radio’s “Town Square” show, and is available online here: Houston Public Radio: Reflecting On 40 Years Of The HIV/AIDS Epidemic Interview with Middle East Broadcasting Network 2280
| July 10, 2021 | Interview An interview with MBN featuring: • Dr. Talal Nsouli o An allergy and asthma immunologist with clinics in Washington DC and Northern Virginia. He is affiliated with Georgetown University Hospital and is the Director of the Watergate and Burke Allergy and Asthma Centers. • Dr. William Haseltine • Chair and President of ACCESS Health International, Virologist, Philanthropist and Author No transcript available.
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Interview for GLOBAL TEEN MEDICAL SUMMIT (The Health Museum) | July 12, 2021 | Interview
The annual Global Teen Medical Summit is The Health Museum’s flagship program for teens. The Summit was created to bring high school students and experts in science and medicine together to engage in dialogue about current global health issues. 2021 Program Theme On March 11, 2020, the World Health Organization declared COVID-19 a global health pandemic. For over a year, we have experienced the quintessential global health challenge in real-time, and the Global Teen Medical Summit has been the perfect vehicle for exploring it with the next generation of global health problem solvers. Last year’s Summit focused on understanding the pandemic. This year, we will focus on the technology that we are depending on to bring an end to it: vaccines. Because we are not yet able to resume our traditional in-person program, we are moving forward with a virtual format, bringing together researchers, clinicians, entrepreneurs and policy makers to talk about what’s happening behind the scenes and on the front lines of the COVID-19 vaccination effort. One special guest for this year’s summit is Dr. William Haseltine, the Chair and President of ACCESS Health International and an internationally recognized expert on the COVID-19 pandemic. Featured Experts: • Dr. Lu Tang • Dr. William Haseltine • Dr. Peter Hotez TRANSCRIPT: Host 00:04 Hello everyone. My name is Gabe Raitzel, I'm a Smithsonian affiliate intern at the Health Museum, and I have the distinct pleasure of introducing Dr. Haseltine on the first day of the 2021 Global Teen Medical Summit. 2283
Dr. Haseltine has been at the forefront of medical research and application, he's educated new generations of doctors at Harvard Medical School, designed the strategy to develop the first treatment for HIV/AIDS, is well known for his groundbreaking work on cancer, and led the team that pioneered the development of new drugs based on information of the human genome. He has founded more than a dozen biotechnology companies, where he remains active president of the Haseltine Foundation for Science and the Arts, and serves as co-founder, chairman, and president of ACCESS Health International and not-for-profit organization dedicated to improving access to high quality healthcare worldwide. He's authored a new book, Science as a Superpower, as well as several other notable titles published earlier this year, such as Variants: The Shape Shifting Challenge of COVID and My Lifelong Fight Against Disease, where he discusses the devastating public health crises over the course of his career from Polio and HIV/AIDS to the COVID19 pandemic as well as highlighting exhilarating moments of medical discovery. He's listed by Time magazine as one of the world's 25 most influential global business executives, is named one of the 100 most influential leaders in biotechnology by Scientific American. A scientist, a businessman, an author, a philanthropist, Dr. Haseltine, welcome and thank you for being here. Dr. William Haseltine 01:37 Well, thank you for that very generous introduction. It's a pleasure to speak with you. Host 01:53 So let's dive into it. So I read in your early career in academia, you published papers on the composition of Martian atmosphere in science, and the use of isotope shifted lasers for communication to outer space, and Applied Physics letters. With such a wide ranging career in depth of interests, can you speak to your experiences and influence on how do you decided on your career path? Dr. William Haseltine 02:15 Well, that was pretty easy. Because as a young kid, I saw my mother really desperately on three or four different occasions. When I was very young, she had recurring bouts of septicemia, she had psoriasis and it would start in her hands and go up her arm, and all I know is that if the red streak went too far she would die. And I remember standing by her bedside, as a young boy, probably five, 2284
six years old, and seven or eight, and just thinking it was a horrible thing and it just wasn't fair. Later, she had to test retinas, which were really traumatic for her because she had to lie in bed sandbagged for a few weeks, and then they had pinhole glasses. And that wasn't fair. And then there were some other events as well. So I just determined that what I would do everything I could, as a person, as a young person and as an adult, to cure disease and make sure that other people didn't have to suffer as much. So I had a life career set very early on. Host 03:15 Indeed, and it transformed over the course of multiple decades. I mean, you in your, your book, you've, you know, catalogued and seen changes across polio, HIV/AIDS and COVID-19. I was wondering what sorts of similarities and differences have you seen in the efforts of combating these maladies? Dr. William Haseltine 03:37 Well, the first and foremost thing is science has been a superpower. Science is a superpower that changed my life as a seven or eight year old when we had, just like the kids today, all these restrictions. I couldn't be with more than two friends, I couldn't go to the swimming pool, because it was a summer disease, I couldn't go to the movie theaters. We had almost the same restrictions. And there was a fear, which may be even greater than the fear we have today, because we didn't know what it was. We didn't know it was a virus. We just knew there was something that might be water associated, that was deadly dangerous. And as a kid, if you don't know what it is, it's like this big, terrible monster out there, waiting to get you. Thank god science came to the rescue. When aids first appeared, it appeared in multiple forms, cancer and immunodeficiencies, and finally, I had to come up with a theory that it was a retrovirus and I worked with a very small group that thought that retroviruses were going to be a serious cause of human disease. Everybody poo pooed us, they didn't believe it. It turned out it was a big cause of human disease. Right now I think 35 million people have died, and a million people a year still die from it. But at least we figured out that science at that time when everybody was denying it was even a serious problem. Science really chipped in, and my friends and I did a lot of really important work to understand what kind of a virus it was, what we could do about it, and today, if 2285
you're in the right place and you have good doctors you can live, just a month ago was published, almost the same lifespan as somebody who's not infected within a year or two. That is, you know, from a 99% death sentence, when we started. It's Science that was a superpower there. And I wasn't alone, there was a huge group of people, and one of the things I was able to do is help get the money to fund the research, work with really terrific people in the pharmaceutical industry, and I understood the bio power biotechnology and we used biotechnology to find many of these drugs. And now with COVID it's been the same. You know, the response of the governments around the world has been vastly different. But the one consistency: scientists in every country are working together, like we almost never could dream possible. Data comes right off the laboratories, and I tell you, we're learning so much about it. The fact that we have these vaccines, it's amazing. And let me say the other thing that most people may not realize, the reason we're able to move so fast with COVID is because all the work was done with HIV. Almost everybody who's a COVID researcher, cut their teeth as AIDS researchers. My students, my grandstudents, and my great-grandstudents are all COVID researchers today. And they're doing fantastic work, but work is being done all over the world. To make that a little bit more of a point. Vaccines were done amazingly fast. How in the world do you enroll 50,000 people in a couple of months? The answer is that the AIDS Vaccine Consortium was already created. The NIH created this fantastic worldwide web of vaccinologists, and people who knew how to do it, and control it, and get the answers. We've been working on an AIDS vaccine, we don't have one, but we've done all the infrastructure. And so that was just ready made, boom, away it went. So the common theme is that science is a superpower. Host 07:17 Science is a superpower and sort of regardless of nation, it goes around the world. And sort of with the interagency collaboration, and that's, that's super interesting. Dr. William Haseltine 07:29 It really is. It's a lingua franca. Everybody speaks the same language in science, and it's really the one language we all speak.
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Maybe music; we speak music, and we speak science. That's right, that's what we speak. Host 07:45 Some sort of universal language is definitely there. And so I was wondering, with, of course, your vaccination efforts and these medical advancements, like health technologies, how does our understanding change as these sorts of discoveries are coming in? Both in terms of the public perception of these diseases, as well as, you know, our medical understanding and how we can resolve these diseases? Dr. William Haseltine 08:19 Well, you know, for all diseases, they're, they're complex, because they hit societies in really deep and fundamental ways. They hit our children, they hit our parents, they hit our loved ones, they change the way we live. I mean, COVID is a really good example of that. People do not like change. Who wants to not go to work and give up your job? How many people have been thrown out of work? When you look at those curves of what's happened to unemployment at the beginning of the COVID epidemic. It's massive, it changes the fundamental nature, and changes something even more fundamental, it changes the way we think about our role in the universe. Are we primary, or are we incidental? You know, if you live near a volcano and it exploded, you'd think you were incidental. If you get hit by a tsunami, you know, you're incidental. The universe goes on. It has its own rules, its own laws, and we're darn lucky to be here the way we are. And we live, I think, on a very thin margin. You don't normally think about that, but when you get hit by something like COVID, it's not manmade it comes from nature, and we expected it, many of us expected this two or three decades ago, we're darn lucky we didn't have it until now when we have even more powerful tools. Just like with HIV, if it came 20 years earlier, we would have been sunk. We didn't have the tools. If it came 15 years earlier, 10 years earlier, COVID, we wouldn't have had the tools we have to get the vaccine in a matter of months. We just couldn't have done it. So in a way we're fortunate, it's bad this has happened, but we're fortunate we have the tools to make it. It changes your fundamental understanding of what your life is, and what your life in relation to nature is. 2287
And I hope that is a lesson that we really take to heart, because we do live in an unstable world. We live on a small planet, which we're poisoning the atmosphere and we're poisoning our water, and they're going to be serious consequences. If you're in Canada right now, you're at 110 degrees temperature, and you don't know what's happened to you. So these are really serious things, but it's hard to adjust. People don't like to change, and I understand that. Host 10:44 Especially with lockdowns and different regulations imposed and such, you get a very different sort of whiplash of what is normal. I was wondering, speaking to what's incidental and how we can use agency, what sorts of measures can we as citizens adopt in order to be able to maintain health practices and make sure that we're keeping others safe as well? Dr. William Haseltine 11:19 Well, the first thing is, of course, get vaccinated. The vaccines are really safe, your chance of getting seriously ill and dying from COVID is enormously greater than any harm you might get from the vaccine. That's not to say, there's not one in 1,000,00, 1 in 100,000 people that will have adverse events, but your chances of getting COVID if you're unvaccinated and getting seriously ill, especially some of these new strains that are much more transmissible than they were at the beginning, much more disease causing, much more impact on young people than the earlier strains, you get vaccinated if you can, is the first thing you could do. Second is, if you are vaccinated, are you completely safe? The answer was yes, it's now maybe not. And that's a big change too, it's kind of uncomfortable for all those people saying, "hey, I'm vaccinated, I'm in the clear," you know, it's more like flu. If you're vaccinated, are you really in the clear for flu? Well, maybe for a few months, and if you get it, you might not get as ill. But you'll need a booster, and it's looking, I can't say for sure yet, but it's looking more and more like the flu, where you're going to need boosters, and we're going to need to adjust what's in those boosters. Fortunately, we can do that. And we can do it fast now. Host 12:39 I wonder how this perspective applies to the soemwhat similar stories of like polio or HIV, and granted, you know, they're not
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necessarily respiratory viruses or Corona viruses, but I'm always wondering, are there any sort of lessons that carry over? Dr. William Haseltine 13:03 Yeah, there really are. That is, it's our behavior that really drives these infections. For example, with HIV it was really easy; sexual behavior is what did it, and if you used condoms, or you were practicing safe sex, or you got to know your partner, you were less likely to get it. And people changed their practices, and it worked. People are now slipping somewhat, and the infections are ticking up even in the US they're taking up a bit. So with Polio, we didn't know what it was, but now we know it's a virus that's waterborne, mostly. The other interesting thing is it's not a direct chain for polio, or with COVID. It's a little harder because polio, and this disease, only really, let's say, COVID, it makes about one out of five people sick. Polio made one out of 100 people sick. So it's really hard to know what was out there. And so it is behavior that makes a difference. The other way you see behavior make a difference is when people get together in the winter, the viruses burst out. Now until COVID came along, everybody said, "Well, that's because the virus does better in the winter." Uh-uh, it's our behavior that does it because now we know with COVID, a virus like flu, it does really well in the heat as long as people get together. It's a little more transmissible than influenza it looks like, but when people get together in the summer, they get together in the winter, it gets them. You know, India had this huge surge of cases in the middle of a heatwave. Okay, so it's the behavior, the congregation of people, you know, and that's what does it. We have agency. The best proof of how behavior can change are countries like Australia, or New Zealand, or Taiwan or China, where they put in strict rules, and in those countries, especially in China, a huge country, you can count on one hand how many people died in the last year, where we've had 400-500,000 people, not counting the first 100,000 who died, they've had maybe five or 10. That's behavior. So our behavior can make a really big difference. And that's a lesson I don't think most people really believe or have learned, but it's agency that is important. The virus knows that, the virus knows if you're dispersed it's had it, if you're isolated, it's had it. You know, COVID grew up in a bat cave where they come 2289
together every night, millions of them, okay. So that's what it likes. But if the bats were all flying away and went to the individual caves, it wouldn't have a chance. So behavior does change, and can make a big difference. Well, you know, I tell you, most people think it's our encroachment into the environment. I don't think that. I think we have made a great ecological niche. You know, when I was born, there were 2 billion people. Now there are 8 billion people. When I was born, 80% or 90%, of people were agrarian, now 80% are urban. And talk about flying. Well, bats fly, we fly! There were four and a half a billion flights, individual flights, in 2019. We move around like crazy. So that's a perfect ecological niche for this, and unfortunately, other viruses and things like TB. Host 16:45 Right, yeah. I mean, there's, I mean, even over it, like an entire career, sort of, from from polio, HIV AIDS and COVID. I mean, there's, there's influenza, there's, you know, Mr. TB, in a bunch of other districts. Dr. William Haseltine 17:03 Yeah, there is. One thing I would like to say to people, though, because of the book Science is a Superpower, being a scientist is a great life. You're with wonderful people who are trying to do something good. They're using their minds to their maximum capacity, they're sharing their knowledge around the world. And you don't have to be confined to lab, or even be in the lab. You can use it to help in public health, you can use it to help create businesses, and there are many businesses dying for highly trained scientists, and you can start your own businesses. The one thing that everybody should know about a scientist, if you want to know a good restaurant, anywhere in the world, ask a scientist. That tells you it's a good life! You've traveled to these conferences, you know the best restaurants anywhere in the world, and you can afford them. You know, when I talk to young kids, they say, "Well, how can you make money being a scientist?" You make good money being a scientist. It's above average income, more than, you know, middle income, and you get all these free perks to go to these conferences. It's a very good life with great people. Host 18:12
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And so sort of, in recognizing, like, more pursuing towards the Health Sciences, versus like a sort of doctor, or Doctor of Medicine approach? What sort of Have you found to be sort of like hallmarks of your experiences both, both in terms of your work on biotech, your terms of advocating for policy and change? Sort of what what lessons have you gleaned across making a career out of health science? Dr. William Haseltine 18:40 Well, you know, I did think about being a doctor, but I realized that I really love science. And I was advised by very important scientists that you can probably make a bigger difference to medicine through science than being a doctor. Or you can combine the two, and I have friends who've done really well combining the two. That's the first thing, if you really want to make a really big breakthrough, that helps lots of people, science is a wonderful tool to the world. Whether you're a doctor or a scientist, you use that, to really think about how you can help the most people. Second thing, I can tell you, in at least three different areas, I've been able to advise governments at the presidential level. First of all with cancer. In the early days, we had wars on and all sorts of things, but they were looking for real advice and I was in a position doing work to help solve cancer problems, with science, that people would listen to me. I had new ideas that they hadn't heard, that seemed to work and in fact, did work to save many, many lives. It's really satisfying when you can see the survival rate from a cancer that you've worked on with a whole team of people go from 20% to 80% in five years. We saw that happen, that was really satisfying. Then with HIV/AIDS it was just at the beginning and a very small handful, and even fewer handful, that could talk to the public. I always thought the speaking of the public was really important. Some of my scientific friends said, "Don't bother Bill, just do your work." I said, "no." And not all scientists like it when they see you on TV, I can, I can tell you that, you know, people get jealous for one reason or another, but I always thought it was my responsibility. And in fact, I learned that from my mentors, that if you have knowledge, you've got to share that knowledge with everybody, not just with your scientific community. You know, there's room for lots of people, but there's certainly room for people who speak to policymakers and who speak to the public. And I was one of the few 2291
people in the early days, who would say, "Hey, this is not your kid who's in grade school, worry about your teenagers, they're the ones going on having sex." Whoops. I can tell you that set people back, and there was even a book written about me and Bob Redfield in the early days, he was the former CDC director, that's called "The Myth of Heterosexual Aids." A whole book on that topic, okay, attacking us. So it gives you an idea. And now with COVID, I've had the opportunity to write a lot of books on it. I wrote a book called "A Family Guide to COVID", I've written another book, a back to school guide for COVID, and I'm writing these more technical things, like the shape changing nature of COVID-19. I wrote that way back in January, and now it's the topic. Everybody's interested in: What are these variants? Where are they coming from? How are we going to deal with them? Which is the issue right now, and is a serious issue. I'm writing another book, just about to come out now, a very different kind of book, called COVID-Related Post-Traumatic Stress Disorder. How it really affects us, and if you really look at it, and the book's almost done now. COVID really affects us in many ways, personally, it affects us, and societally it affects us. There's a huge number of people who have gone through a very traumatic time. And there's a way of analyzing it, and there's a way of treating it now. And I think we have to recognize this is something we have to take as a societal trauma, and is in some cases, individual trauma, and use every piece of knowledge we have in medicine from what we've learned from people who returned from war, what we've learned from people who've gone through terrible personal crisis. And we've learned a lot, you know, if you just look at the history of post traumatic stress disorder, people called it shell shock, they called it cowardice before, shirkers. You know, they called it all sorts of things, and it took a long time to understand what this was. We now understand it, but I don't think we understand we've all had it. We've all gone through it. And what that means for us, and how we have to take care of ourselves, and how if we really have serious issues, we need help. I think that's going to be an important contribution, as important as some of the scientific ideas that we come up with. Host 23:13 I mean, that is absolutely brilliant. I mean, like public public education in and of itself, like you sort of stemming from that is just 2292
absolutely critical. I wonder if I could go backtrack a little bit you sort of mentioned your book about sort of the myth of heterosexual AIDS. In sort of like OSI and in educating the public government officials, policymakers, even fellow scientists, when when sort of like groups are identified like that, like, oh, HIV AIDS only affects the for ages, or be of post-polio own only affects children or COVID only affects the elderly. Yeah, right. This disproportionate population, how do you sort of as a scientist, as a researcher, but also with with your other sorts of backgrounds, sort of navigate that line and say, No, I mean, while there may be a disproportionate number here, there, really, this is sort of a calamity that affects all of us. Dr. William Haseltine 24:21 I think that's, you know, the idea that we're really all in the same boat, even if we're not equally likely to suffer the consequences. You know, if you look at COVID, many of the people that are suffering the worst consequences never got COVID. They just got thrown out of their job. They got thrown out of their house. You know, maybe their mother died. I have lots of friends, I have people who've worked for me who recently died in India, and a lot of their relatives have died. So there's tragedy everywhere. You know, during the HIV epidemic. I knew that this was heterosexual, early on, because we could see what was happening in other countries. In Africa it's never been anything but a heterosexual disease. And you know, it's true that there's other ways to get it. But that's 90%. I'll give you a number that is still terribly shocking to me. About three or four years ago, I was in Durban, and there was a new HIV center and a malaria center, wonderful research centers in Durban. The number of young women infected, the percentage between the ages of 15 and 25, was 70%. That's correct. 7!,0! %. That's what could have happened if we weren't more careful. 70% You know, it's a number that seems so totally shocking. And I checked it three or four times I say, You're kidding me? Can't be that. Oh, yeah. Look at the numbers, and they show me the numbers. So that's something that affects everybody. And these diseases can affect them, you know, just look at what's happened to India. I mean, and maybe on the verge of happening again to India, with yet another variant spreading. Like there's an uptick right now, I just checked this morning. Look at England, if you want to see something frightening go onto your Google and 2293
search COVID cases, whatever country, look at UK, it's got an uptick, they look just like the last wave. And there are a lot vaccinated, it's not comfortable to look at this. Now, how do you explain that to policymakers? I have some stories in my books, not necessarily for kids, about how we explained it to some policymakers. One thing I have to say, no matter what the field is, in HIV, I found some really compassionate people. I worked very closely with Elizabeth Taylor, to create amfar, and to work to help Congress and she did everything she could because she had friends with HIV, Rock Hudson was one of her really close friends. And he was one of the first really big public figures to acknowledge that he was ill with AIDS, and died. I worked with Princess Diana, who did more than maybe anybody who hugged an AIDS baby and hugged a gay man who was dying of AIDS, to tell people don't stigmatize this, you're not going to get it. A friend of mine, a great artist, wrote a book, which is "AIDS, You Can't Get It Holding Hands." Okay? Those are really important messages. And so you have to work with people who are recognized, people who are trusted. Politicians, listen to those people as well as other people. I taught a course at Harvard for maybe 20 years. I created it with some friends as a graduate student, called "biology and social issues," and what we are trying to do is educate a future generation of leaders to understand how science and social policy interact. And that they're going to be people on one side using one set of facts, and another people on the other side using quasi-facts, and how you deal with that? So that's one of the things we did in that course is analyze things like nuclear power, diethylstilbestrol. You know, you name it number of different major issues, we would discuss about what that what the social dynamic back and forth, push and pull is because that's the way we are as a culture, you have to understand that. And then you have to be able to see through what signs of it, you don't have to be a scientist, you have to be like a lawyer to be able to analyze the two sides of an argument and come to your own conclusion, based on what you can use your own mind and reason your way through to an answer. I think that's really important. It's helped me when AIDS came along, and it's helped me now that COVID is here. Host 29:10
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If you want to talk about science as a sort of lingua franca, talk about like the ultimate sort of mediating language, like it's absolutely remarkable. In in sort of, and sort of navigating how we reduce, like, stigma surrounding the diseases, what, what sort of like ways do you go about winning over public trust? Dr. William Haseltine 29:39 That's a very tough question. It's an especially tough question in our country today, that seems so divided on so many issues. And unfortunately, issues that should have no political content seem to get political content. You know, when it comes to your health you should be listening to your doctors, your healthcare workers. But you shouldn't necessarily be listening to politicians. I'm not going to take sides on this, one side or the other, you should consult your doctor is what's going on. Not the kind of political dialogue that's there. And so, you know, one thing I found in life is that belief trumps logic: belief trumps logic. And so what you have to do with people is you can't say you're stupid, or your set of beliefs are nuts. You have to work with them within their framework. What do they really care about? All of us care about our children. I don't care what your politics are. You love your children, you love your dogs too, okay? I don't care what your politics are, you want to have a better life for yourself. You want your children to have a better life than you did, right? All of these things are there, you know, you want to have friends, all of these things, you cherish those who are close to you. And what you try to get across as much as you can, is that the diseases affect all of the things you care about. That's what they affect. They care what you really care about, no matter what your politics are. They affect those people closest to you. And in fact, some of them even your animals, in fact. So that's how you try to get understanding with people. You don't try to say you're this or you're that or anything else, you just try to talk about the most common basic human values, which I think everybody shares, regardless of where in the world you are, or what your politics are. Host 31:48 Absolutely, tapping into some of that universality is sort of the bridge over any sort of great divide. And sort of no contour like having concert, your experiences with polio, polio, HIV AIDS, and COVID-19. In the event that there's a future public health calamity, 2295
perhaps of some known form, perhaps of some unknown form, where do you sort of see the field going over over the next few decades? Dr. William Haseltine 32:22 Well, that's a really tough question too. One thing you learn, if you live long enough, is that memory is short. Our memory of calamities is not as long as you'd like it to be. I remember, and I've even resurrected some of my quotes, saying this AIDS isn't going to be the last thing to come and get you, be prepared. And many people have warned over the decades since the early mid 80s, in the 90s, in the early 2000s, in 2010/15, is things that I gotta get SP prepared, yet when it actually came, we weren't prepared. We just weren't. We were prepared. In some ways our scientists leaped into action. That's fantastic. But in terms of our public health systems, in terms of our preparedness to have all the medical needs satisfied? I remember being in New York when ambulances were screaming down the street, and they didn't know where to put the sick people, they didn't even know where to put the bodies. I live on the upper east side of New York, and we had a morgue, three blocks over from me, at one time with 40 bodies in it on the street. That's how bad it was. And we weren't prepared for anything like that. We didn't have the equipment. So it isn't that it was unanticipated. I have seen the wargames that people did, one of them called dark winter, where you have everything spelled out in detail. If you want to see what that looks like, look at the movie Contagion. Everything plus that we experienced is in that movie. Why? Because we knew what would happen. We knew. Okay, and we know it's gonna happen again. So my only hope is, and there's some positive hope here, that we will have learned something because diseases people think, as you have said, maybe somebody else's problem. But the economy is everybody's problem. And this tanked the economy. If there's one reason that the countries in East Asia may have done better is because they knew about SARS, they saw their economies almost disappear overnight, and they were determined not to let it happen again, and they took actions that nobody else took because they had it. Japan that didn't have SARS so much, I was just speaking to a very senior Japanese Ambassador recently, he said "well, we didn't have SARS so we weren't so worried." Well, 2296
maybe they should worry now look at what's happening with their Olympics! Okay, so the lessons are: be prepared, continue to invest in science, and if you want to be a scientist it's a great thing to do. Continue to work at the cutting edge so those tools are available when we need them. Like that mRNA. mRNA was an idea that everybody threw in the trash can, over and over again. Finally, it kind of made its way into a company. Finally, it began to do something, and this was its big moment, that's for sure. Alright, a technology that had been really pretty much discounted except by a few brave souls. And so that's the kind of thing that you can do, you can prepare yourself, but help your society understand that if you take a look at this structure of our public health systems, it's not prepared for the job, even today, that it's got to do. And so we have a lot of work to do, to understand, to get prepared, and the whole world has to do that, too. Host 35:57 I'm, in addition to sort of the the curiosity and knowing to understand the public health systems, what would you say to aspiring students in the next generation on how to make significant contributions to human life and to appreciate science as a humanistic enterprise? Dr. William Haseltine 36:18 I'm glad you said that, the humanistic enterprise, because many people think there's a, CS Lewis, you know, the divide between humanists and scientists. In fact, science is a tool. It's actually a tool for answering questions. That's what most people don't understand. It's a tool that tells you: you have an idea, is it true or isn't it true? And it gives you a recipe for how to do that. But science does not tell you what question to ask, what question to answer, it can't do that. It's a tool. If I have a screwdriver, I can use it to stir my soup, I can use it to pry the lid off a can, I can even stab somebody with it, okay? It's a tool, I can use it for my own purpose, right? And science is a tool you use for a purpose. So the issue is, what do you apply that for? And that's where humanism comes in. One of the things I've always done, and I was very fortunate to have parents that were interested in every idea that came along, no matter what it was, whether it was in art or music or fashion, you name it they were interested in. And that gives you a perspective, 2297
you know, when in business, and one of the things I think has helped me in business, is what is a business? It provides something somebody thinks they need. That's a business. Okay? Now that part of that, you know, thinks they need, you try to create a need, but it's really, that's what you have to do you have to provide something. But to do that, you have to understand humanity. What do we need? And those are the questions that I've always chosen to work on. What is it that we need? My answer is we need better health. And we need to know more about cancer, we need to know about more infectious diseases, we need to know about immunology, we need to know you name what you need to know about. And those are how you find your questions. There's another process, which is really interesting. And that is you go to the edge of what's known, and you'd be surprised how much isn't known when you get in there. And that's what I always would try to do, I'd get into a new field and I tried to learn, not what people knew, but what they didn't know. I would talk to the doctors in the cancer hospitals. What do you need to know? What's your problem? I would sit through hours and hours of patient consultation where they would talk about each and every patient, I would say what do you need to know? And they would tell me, we don't know this, we don't know that. That's where the questions are, okay? That's where the real interest is, what is that boundary? And a lot of things you think you know, you don't, okay? It turns out, you just assume people know this. And all of a sudden you find out they don't they say hey, great, I maybe have a tool I can figure that out is one more piece that's really important. You can ask a question like, what was before the big bang? How did the universe start? Well, that's an interesting question, but you're never gonna answer it, at least with any tool I know now. Okay, maybe someday we will have the tool. You have to find the question that the tools exist to solve. And that's fun, because the tools are continually evolving. Let me just give you an example. When we wanted to work on human genome. At the very beginning, the tools weren't there. They didn't have the automated machines to sequence DNA. They didn't have powerful enough computers to put it all together. They didn't have laboratory robots that make it all happen simultaneously. But at about the same time, in about 1988/89, all those pieces started to come together. All of a sudden we had the robots. We had the 2298
machines that would sequence and we had the computers that could interpret it. And bingo, we could do the genome, you couldn't answer the question, you might want to know it. But you couldn't have done it. And I once did a look back, I said, Could I have started Human Genome Sciences six months earlier? Probably not. Probably not. Because the tools just weren't there. So that's the match: what's the question, what are the tools, and how do they match? There's one other aspect I try to inculcate in all my students. Answering any question is hard. Science is hard. It is not an easy process. Because you don't really know how unknown an unknown is until you work on it. But if you're going to ask and spend your life doing that, or a good part of your life, make sure the question you ask is important. Because it takes just as much time and effort to answer a little question as a big question. Because if you're working as hard as you can work, that's all you can do. So make sure it's an unimportant question. So those are the three things: what is the question, are the tools there, and is it an important question? Host 41:13 Brilliantly stated, brilliant. Before we open up the floor for questions, I have one last quick question I wanted to ask, What is one thing that you did not expect from your career and experience as a whole. Dr. William Haseltine 41:26 I never expected to be in business. Never. I grew up on a military base, my dad was a scientist developing rockets, there was no business. It's the purest socialist existence you can ever find. It's kind of interesting the military guys don't like socialism, because they are living a socialist existence. Everything is determined. When my dad got a promotion, they gave us a bigger house, for example, they told us what color our house would be painted. Okay, excetera. You know, and everything was, you know, everything was organized. And I had no idea about business. The most I knew about businesses, there was like a frosty freeze outside of the base, and they could sell you shoes outside of the base. That was business to me. I had no idea. To find myself the CEO of a company was pretty astounding. And to understand how you could turn a piece of paper into 10s of millions of dollars was even more astounding. And it's still kind of alchemy to think about. But all those things happened.
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I would say the other thing that was surprising to me is, when you are using your mind, there's a community of minds in the world that's in harmony. It's a wonderful thing. You're in harmony, like today, I'm in touch with people in all corners of the world. We're all thinking about the same thing. I read these papers. Some of them are so beautiful, I mean, I get the chills down my back just reading how good their work is. And then I have the privilege of calling them up and talking to them, and having a real dialogue. "Hey, this is interesting, but what about that? What do you think about this? And now ask me ``Well, you know, what do you think about that?" It's a wonderful sense of harmony, which I didn't expect, as well. So I'd say those are the two biggest surprises for me. Host 43:26 We'll go now to the question and answer portion of the session. Let's see, is Rebecca Renee in the chat? She wants to unmute and ask a question. Rebecca Renee 43:54 Hi, so I just wanted to ask as many schools are removing their mask mandate, how can students protect themselves against the spread of the virus other than getting the vaccine? Dr. William Haseltine 44:03 Put on your mask, okay? Keep your mask on. Use the N 95 mask, they are available now. That's what I would do. And I would me personally, I'm vaccinated, but I'm over a certain age and know that my vaccine isn't giving me the full protection it should, I'm still taking pretty careful precautions. When I meet people that I know don't know, I'm going out. I put on my mask. And I try to stay away from crowded places. I'm still not, you know, I used to spend half my life on an airplane literally three or four months, I would travel around the world. I haven't done that since this thing started, and I don't intend to for a while. So you can protect yourself up to a certain point by your own activities. And so that's what I do and that's what I recommend you do too. You know, there's a new variant out. It's nasty. If you're not vaccinated, it's much worse, easier to catch, and maybe worse for you. And even if you are vaccinated, if you're my age, or you have some other underlying problem, it may not be enough. So to protect myself, to protect others I'm still careful. I'm fortunate the family I'm living with is also careful too. The idea this is over, it's not over. 2300
That's not good news, but you know, if you're vaccinated at least you might not die you might get a little sick. You know, I have people who have worked for me that just last week got infected. So, not so good. And they were pretty sick, two young healthy people. They've recovered now, but they were pretty sick. Host 45:47 I sort of I sort of blends the intersection between behavior and medicine from from pharma as well, just sort of showcasing how, let me tell you where it's going, Dr. William Haseltine 45:57 Let me give you a little happiness. I'm writing a piece I called multimodal COVID control. Don't put your eggs in one basket. Vaccines are sine qua non, and everybody should get the vaccines. There will be new generations, I now see vaccines that are 10/20 times as potent. Ideas in laboratories, 10 to 20 times better than our current vaccines, they work against many different variants, not just one. We'll have those, but even those aren't going to be foolproof, then we're going to have a whole series of drugs right now, who can get infused with antibodies that will protect you if you're exposed. And if you've been exposed early on, it will stop you from getting disease. What we've done with HIV is have a cocktail of pills, you take one pill a day, you don't get HIV. Pretty soon, there'll be one shot, you take every six months, you don't get HIV, even when exposed. That will change things because then if you want to travel, you get a shot. No problem. You don't have to stay in a hotel room for three weeks to go to China. I have offices in China, I'm not going to go there until I don't have to stay in a hotel room for three weeks. My very good friend just came to visit me here. He went back to China, he's still in a hotel room! And it's only like his 10 days on he has another 10 days to go. So that changes. So that's good news. Then, you know, public health does make a difference. As I was saying earlier, this fire hates it when we're scattered and can't jump from one to another if there's nobody to jump to. Right, it's got to be, as I say, grew up in a Batcave, and if you ever been there, it looks like the Super Bowl upside down. All these little heads packed together. Well, they're indoor Super Bowl, those bats. And that's how this thing grew up and kept hopping from one to another. So we have good public health measures like the mass that I was telling 2301
about the kind of help slow it down. And then there's another big lesson. We're not safe unless the world's safe. Take Australia, Australia shut its borders, traced everybody who had it, eradicated the virus: the virus eliminated in Australia for many months. This new strain came along. One guy walked through a mall infected 20 people, half the country shut down. One guy. He was shuttling people back and forth to the airport. He walks through a mall, and these guys bring that it breathe it in 20 of them. In fact, the day in fact more and right now it's out of control. That even if you do your very best, so that's why I say multi modal global effort. That's what we need. And I hope we'll get there. I think we will. Certainly science is doing its part we're going to have the vaccines, we're going to have the preventive drugs that I'm sure of. And they're going to get better and better over time and hopefully superfast. In my book, Science as a Superpower, one of my favorite ones is a picture of President Biden bumping elbows with Kimsey Corbett. Who is she? Over a weekend she made the moderna vaccine. A young, black scientist from NIH made that vaccine over a weekend because the Chinese gave her the information that she needed, and she had the tools and the know how to do it. I've seen her on television, boy is she telegenic! Wonderful young woman! But there she was bumping elbows with the President. It was really a wonderful scene to see. Ashley Alexander 49:36 Hi, my name is Ashley Alexander, I'm an education program specialist at the health museum and the program coordinator. So we have a couple more student questions that I just want to get to before our time is up. Thank you Gage for being a wonderful moderator. Dr. William Haseltine 49:51 He read the books. That's amazing. Thank you, Gage. I can tell you read at least the first part of the books! Ashley Alexander 50:01 So I have a question from Hashmi here and says, with behavior being a key factor in spreading diseases, are there any ways that organizations can better convince people to change their ways for the cause of human health? Dr. William Haseltine 50:15 There are and one of the things we've learned over the years is that people trust local leaders, people they know more than people 2302
who are at some distance. Like your senators or, you know. People trust people they know. And there are wonderful organizations: fraternal organizations, organization, women's groups, churches, synagogues, mosques, those leaders really make a difference. It's important to work with those local leaders. Your selectman is more important than your congressman. Okay? Because, you know, he's, he's a neighbor, she's a neighbor. These are, you know, your city councilors, you know, you grew up with him, sometimes, you know, they were your, you know, they were the schoolyard bully, maybe. Now, you know, you know, you know who they are. Alright, so, or maybe they were the conciliator. So those are the people that really make a difference. I was recently asked a question by an influential group, they said, "Bill, what do you think we can do that we're not doing for vaccines to get people to take them?" I said, local, go local! As much as you can get the message, you know, give the information to people on a local basis. Let's take your county, your community, your zip code, how many people got infected in your zip code? Yesterday? How many people got this variant? Yesterday? How many people are in the hospital yesterday? Okay, really local, showing them and it could be zero, and then you're fine. But it could be more than zero. And maybe then it's cause for concern. Take it extremely local. And get it as I think that was an I did a lot of anti war work in the anti Vietnam War. And that's the lesson I learned from that. I would go around the country talking about people talking to people, but trying to get it really local, what they were doing, and how that affected the war. And I think that's the kind of thing that makes a difference is, you know, local connections. So that's what I think you can do. Ashley Alexander 52:35 So I have a question here from Dr. Pinkney. She asked, When will your book be out, and how can she get a copy? Dr. William Haseltine 52:42 Which one? The one on COVID related traumatic stress disorder? I'm pushing to get that done. We have almost the draft than I was just over the weekend saying, Hey, we got to get this out. The way I do books is different for most people, I actually can get them out really fast. I do it all myself now. And this is something that people should learn. Now with the Internet, and Amazon and places like that. So what I do is I write the book, and I have teams 2303
of people who are helping me, put the book together, put it into a internet-friendly format. There's a service that you post it on that gets it on Amazon. But it's at a different form. I call it a living ebook. And what a living ebook is is like wiki, Wikipedia, you can change it all the time, you'll update it all the time. So somehow my books updated three now, planning the fourth edition of Variants because the Variants, guess what? keep varying. So it really, it's a format. Same thing with this book. We're going to, it'll be on Amazon, probably in two weeks, I would say maybe three the most. And that's where you get it. And we try to charge very little, for example, for science as a superpower it's free to schools. We make it free to teachers in schools. I think it cost $1, maybe 99 cents. And if you want a hardcopy, then you order a print on demand. It's a whole new world out there where you diss the intermediate. You know, when I published books before, I'd hand them a manuscript, and maybe a year and a half later, a book come out. This is like a day and a half later, maybe a week. It's a whole different world. And thank goodness for it. So that's that's the answer to that. And I encourage everybody to try to look at that. If you go online, I've got a website. I think it's William haseltine. calm. ww William haseltine.com. You see the books that I've written, but almost all the books I write now are written that way. I'm even thinking about doing a really serious textbook on COVID that way, because the truth I can tell you from when I started looking at this to now let me give you one big realization I've just written a big essay on this. We think of COVID It is inciting a hyper, hyper immune disease, right? The end of the disease. That's not as strict. Its trick is the opposite. Its trick is to get in you, shut down your immune system. So it has time to get in and get out. And then it doesn't care if your house catches on fire, it's like a burglar. He goes in, breaks the alarm puts everybody to sleep, steals, ready, wants gets out of the house burns down or not, he doesn't care. He's onto the next house. That's what this is. So this has so many tricks, not to make you sick, to shut it down and get in and out. That's a surprise. Who would have thought? Well, I'll tell you who would have thought: other virologists. Because when you start looking at that, all viruses have to do that. They all got it, we have a lot of defenses. You know, we're not here by chance. We've gone through a trial by fire millions of times in our evolution, we got a huge 2304
number of defenses, these viruses got a huge number of countermeasures. And once you figure them out, you'll figure out how to defeat their countermeasures. Maybe a fire alarm that can't be broken. Or make a hair trigger fire alarm. Those are kinds of things we're doing right now. But you don't know to do that until you figure out the other. So those are the kinds of things that keep on changing. You know, you have to be in science, they have to realize there's no final answer. There's always a truth below a truth below a truth. And you can believe one thing is you just have to keep observing. And that's what makes it exciting. There is no final answer. Ashley Alexander 53:25 But we do have a final question! So from Maya-Kamala Anjali, her question is, do you know of any other ideas or tech that people shun, but that you think will serve a big purpose in the future? Dr. William Haseltine 57:09 Oh, yeah, there are many! You know, this is a golden age. If I were a young guy again, I would, there's so many fields. One of the things I'm really excited about is synthetic biology. I helped fund a company and now I'm actually involved in companies, you can now the whole manufacturing is going to be done. Tremendous amount of manufacturing is going to be done not by big factories, by micro factories, we're going to have by micro-organisms. If you think of your body, think of a virus, it's so tiny you never ever see it, you can make something that small, or you can make a redwood forest, all from the same tiny pieces. You make a whale you make a bacterium, all from the same pieces. Well, we now have that power to engineer things. You know, in engineering, they talk about tolerance: if you make it so there's a gap of an inch, five inches, or one millimeter, that's the tolerance. The tolerance we now work with, is an atomic radius. You are architected, your tolerance is the fraction of an atomic radius. If you move those atoms one atom away, it's not going to work anymore. So we can start a whole manufacturing a whole material world with biological engineering specifications, right down to the individual atom and where it is in three dimensions. That's what we're doing with our computers. That's what we're going to do with tables. That's what we could do with our food. That's what you can do with anything.
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And there was I think, as a science fiction writer called the diamond age, which should have projected forward what that's going to be, you can say, okay, I'd like a gourmet dinner from China. Boom, there it is. I'd like a new Ferrari. Boom, there it is. That is where we're headed. That is really exciting. That's only one of the very exciting things that are happening, but I think that's enough to get you going. Okay, biology, used for manufacturing. And it's real. I can tell you it's real. I have a company now that's just making tons of stuff. We're actually we had a company we started that made gasoline and planes fly on our gasoline starting from sugar, sugar into gasoline. You can do I even make plastics, you make the biodegradable plastics. There's lots of anything you can make. So it's fantastic. Ashley Alexander 59:39 Absolutely amazing. Well, Doctor Haseltine on behalf of the team, and I'm sure Gage as well, I would like to thank you for your time today. You have been an amazing, amazing keynote speaker, and we are certainly glad that you chose to join us today. Dr. William Haseltine 59:58 I mean, I would say something else. I'm happy to see you in a health museum. I was chairman of the National Health museum for a number of years we never got it off the ground was one of those Washington things you know, this one wants it that one doesn't there's one things that are the other things the other, it became pretty discouraging. So I'm really happy to see you at a health museum, warms my heart. Congratulations. Ashley Alexander 1:00:30 Thank you so much, and I certainly appreciate those warm words as well. Dr. William Haseltine 1:00:35 Okay, be well take care.
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Interview with BBC World News BBC | July 19, 2021 | Interview
BBC Host Okay, let's take a look at the front pages of today's newspapers. Now the Daily Telegraph is reporting that Boris Johnson's under pressure to end the mad system of self isolation, as he and Rishi Sunak went into quarantine ahead of so called 'Freedom Day' in England. The Express says the prime minister and chancellor were forced into a U turn after a public backlash against their attempts to avoid isolation. And as I was saying, a warning that Britain could have 200,000 new Coronavirus cases a day by mid August, with an opinion poll suggesting most voters do not support the relaxation of restrictions. As 'Freedom Day' arrives today in England, a group of international scientists have called the government's decision to lift all restrictions murderous. Dr. William Haseltine is part of a group of scientists who signed the letter condemning Boris Johnson's plan. Now this original letter was signed by 122 scientists, a further 1400 globally have now added their names. Good morning to you. Thanks very much for joining us this morning. What are your fears then, about the consequences of lifting restrictions in England? Dr. William Haseltine There are two general fears. One is for the people of the United Kingdom, who are now going to be essentially guinea pigs in a very unfortunate experiment, which is at the height of a pandemic on the exponential rise of a pandemic, to lift measures that could protect the people. From an international perspective it is quite concerning, because what happens in the UK happens in the rest of the world. We've seen the UK variant, the so-called Alpha variant, spread around the world-- first detected in Kent. If I were to design a massive experiment to create a more dangerous virus, one that is capable of blasting through our vaccines, I would do what the UK is proposing to do. Half the population vaccinated in the midst of a rampant pandemic which would allow the virus to learn how to avoid our vaccines. That's what I would do, and the rest of the world 2307
is justifiably concerned. So I join my colleagues, over 1000 colleagues around the world, doctors, epidemiologists, scientists alike in expressing our concern over this policy. BBC Host Okay, I mean, the government, pinning their hopes that the vaccination rates that we have here are going to be the way forward with this. 87.9% of adults have had their first dose, 68.3% have now had both doses of their vaccine. The government here is put in the position of, "If not now, when do we relax restrictions?" Summer holidays for children are about to start so they won't be at school, when the weather turns colder in autumn and winter we'll then be into flu season: so, when is the right time to begin relaxing restrictions, if it's not at this point? Dr. William Haseltine We can certainly tell you when is not the right time. And that is during the exponential rise of a new variant, which is far more infectious and possibly more lethal than others. The vaccination programs that have taken place in the UK have not abated the rate of increase of this dreadful disease. You can see that in the numbers that are rising sharply every day. If my numbers are correct, yesterday there were 53,000 people infected, and the numbers are rising every day very sharply. It is the wrong time to take such an action. BBC Host The Prime Minister has urged caution from the public, although the restrictions have been lifted and says the data will be continually assessed, contingency measures will be brought back in if needed. Do you foresee then that we're going to have to go back into restriction, back down into a lockdown as a consequence of this? Dr. William Haseltine His advisor should be telling him the time is now to reimpose the restrictions. In fact, if anything, tighten up those restrictions to lessen the impact of what is already occurring. BBC Host Okay well listen, Dr. William Haseltine, thanks very much for joining us this morning. We appreciate your thoughts. Dr. William Haseltine You're welcome and I wish you all the best of luck. Thank you.
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Interview with MBN’s ‘Alhurra Tonight’ Alhurra Tonight | July 22, 2021 | Interview
An interview on MBN’s ‘Alhurra Tonight’ featuring: • Dr. William Haseltine • Chair and President of ACCESS Health International, Virologist, Philanthropist and Author • Dr. Ahmad Al-Mushatat • Consultant Urological Surgeon at Royal London Hospital, Barts NHS Trust. He has been a Consultant Urological Surgeon for 11 years, with broad urological experience and particular expertise in minimally invasive surgery of the upper renal tract. No transcript available. Interview with ABC4 Utah, ‘Kids Under Construction: Pediatric mental health’ ABC4 | July 16, 2021 | Interview SALT LAKE CITY (ABC4) – This week, parenting expert and journalist Donna Tetreault and former Harvard Medical School professor Dr. William Haseltine discuss pediatric mental health. Dr. Haseltine says COVID-19 has had a profound impact on everyone’s mental health, particularly young children. *** TRANSCRIPT: Host Welcome back, everyone. It is Friday and time for 'Kids Under Construction,' Donna Tetreault joins us twice a week to navigate the journey that is parenting. Today she's joining us via zoom from LA and also with us today you see on screen, Dr. William Haseltine. He was a professor at Harvard Medical School and Harvard School of Public Health. He is an author and philanthropist, and in a recent article in Forbes, he writes about the pediatric mental health crisis in our country. So Dr., let's talk about how the pandemic has really unleashed a syndemic. Dr. William Haseltine 2309
Right, a syndemic is a bunch of things that happen at the same time. COVID is a typical syndemic: it's a medical crisis, it's an economic crisis, it's a personal crisis, and it's a traumatic crisis for parents and their children. And doctors are seeing that, increasingly, both at pediatric health clinics and in hospitals. Donna Tetreault And doctor, talk a little bit more in depth about this pediatric mental health crisis and what it looks like and what is happening, and what we really can see moving forward with our kids. Dr. William Haseltine Well the first thing is, for young kids, it's confusion. They really can't understand what's happening. So 5,6,7,8 year olds are beginning to understand, but it's really difficult for them, all they know is their life isn't the same. And for most children, they take things very personally, "this is this is something against me." And then, if they don't feel like they can do anything about it, they get a feeling of hopelessness. There are a lot of mental health issues that come with that: behavior problems, depressions, sleeplessness, anxiety. Those are what you see in younger children, older children have somewhat of the same thing, it takes a while to realize that the world isn't against you. And this just magnifies all the problems that adolescents and teens have growing up. You see it again, in behavioral issues, and depression and anxiety, drug use, and even I hate to say suicidal behavior, and some suicide. So it's a very serious problem for parents to cope with, while they're coping with their own problems, Donna Tetreault It's a serious problem, and it's so scary. So what can parents do to try to help our children navigate this? Dr. William Haseltine But one thing is to try to help them understand what's happening, to let them know it isn't going to go on forever, to have them talk and feel about their emotions, which many parents are reluctant to do. One of the most important things is for kids to feel that they're being heard, that there is somebody listening to what their problems are. Many kids will just retreat you know, they won't express themselves. And it's important to try to get kids to express themselves. So a lot of ways to do that. One is, you know, help them play games, draw pictures, discuss it. But the health professions have 2310
a big role here to play, and they're being completely overwhelmed by young children and adolescents and teenagers that are coming in, with their parents, and suffering from serious problems. Donna Tetreault And Doctor, what can schools do? I mean, teachers are going to have these kids coming back into their classrooms, hopefully, I mean, that's what it's looking like at this point. But what can administrators and teachers and schools do to help kids navigate this as well? Dr. William Haseltine Well, you know, teachers are going to be really overwhelmed. And I think it's important for schools to beef up their psychiatric and social work services, they're going to need more people who are well trained in understanding how to deal with these issues in kids. Teachers are going to be having all sorts of problems: they're going to have to do catch up for the homeschooling, and that hasn't turned out as well as people hoped it might, and there's tremendous variation, the kids are not going to be used to being in school. So the teachers are going to have so much on their hands, that they're going to have to have professional counseling of what to deal with, and know when it's important to send a kid for special help. The schools are going to need to beef up and increase the number of people they have helping the kids get back to school and overcome some of their problems. Host It's such an important conversation, and we do appreciate both of you joining us today. Of course, Donna Tetreault, who joins us every Monday and Friday, and Dr. William Haseltine, who we had the pleasure of speaking to today. You could get more information on Donna's podcast online at ABC4.com. You can also send us a question for Donna to kidsunderconstruction@ABC4.com. Dr. and Donna, thanks so much for joining us. Have a great day. This interview originally appeared on ABC4 and is available online here: ‘Kids Under Construction: Pediatric mental health’
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August 2021
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The Benefits of Being Vaccinated If You Still Get COVID NPR Houston | August 12, 2021 | Interview
Just like earlier in the pandemic, thanks to the Delta variant, COVID cases and hospitalizations are way up. Although science tells us that masks & Vaccines do prevent community spread, the debate about both is still going strong- thanks to politics, misinformation, and bans on mask mandates. Today, local and national health experts are here to field your calls and to explain where we are with the surge, vaccines, boosters, children, and more. And Sebastian Bach, the original voice of the heavy metal band Skid Row recently shared that he has a breakout COVID case. He shares his experience with combating the virus and why the vaccine has saved him from the worst-case scenario. Guests: Dr. William Haseltine • Chair and President of the global think tank ACCESS Health International and founder of more than a dozen biotechnology companies. • Author of Covid Related Post Traumatic Stress Disorder (CVPTSD): What It Is and What To Do About It Dr. Saad Zaheer • Medical Director and Chief medical epidemiologist at Harris County Public Health Sebastian Bach • Singer, actor, and the original voice of the heavy metal band Skid Row. • He recently dealt with a breakthrough case of COVID TRANSCRIPT: Ernie Manouse I'm Ernie Manouse, and this is Town Square. Do you have a question about boosters? FDA approval of vaccines? Want to share 2313
your COVID experience? We're a resource and a safe space for the community to come together to learn and support each other during this time of the Delta surge. I also want to say if you are still unsure about vaccines, and you have a question about the science behind them, or why they are beneficial, especially in light of the Delta surge, call in right now. We're not going to the right people who didn't get vaccinated. We encourage everyone to get vaccinated, but if you have concerns, and you want to go someplace to get solid, factual information, call us right now. Our phone line: 888-4869677. That's 8884 Town Square. Joining me right now to discuss all of this and so much more is a regular contributor to this show. It's Dr. William Haseltine. He's the chair and president of the global Think Tank ACCESS Health International. He's the founder of more than a dozen biotechnology companies, and is the author of yet another book COVID related Post Traumatic Stress Disorder, CV PTSD, what it is and what to do about it. Please welcome back to the program. Dr. William Haseltine. Hello there. Dr. William Haseltine Hi Ernie, it's good to speak with you. Ernie Manouse It's always good to have you on since we already started talking with your office about having you back, we heard that there's going to be movement on these booster shots. What do we know? And who are they for? William Haseltine Right now, I was listening in on the White House conference a couple of hours ago, they've announced it's for people who are not immunocompetent. The definition of that isn't exactly clear now, but it probably, to me, means people who have medical conditions, for which they have been treated or as a result of treatment that has compromised their immune systems. I'm pretty sure, it doesn't mean older people whose immune systems aren't fully competent. Ernie Manouse So there's a difference between immunocompromised and comorbidities. Correct? William Haseltine That's very well put Ernie, exactly. For example, if you're an organ-transplant recipient, if you're on immunosuppressive drugs for arthritis or for some other conditions. They were pretty clear, this is 2314
going to be a limited approval. At the same time, they also mentioned that they're aware that over a million Americans have already received a third dose. So a lot of people are taking matters into their own hands, and where they can, are getting themselves extra protection. I suspect many of those people are over the age of 60. Ernie Manouse And I know when we talked last time, we talked about your thoughts that a booster shot is the right direction to go and that we would be heading there. And here we are. I'm curious if you can explain your reaction to this happening this quickly, and what that tells you about what the science is telling them? William Haseltine Well, it's the epidemiology which is showing you that the Delta variant can infect many people who have already been vaccinated, and it's also a consequence of some new studies, particularly in organ-transplant recipients, which show that a third shot makes a big difference. So I think the difference between having a good immune reaction, or moderate immune reaction and fading over time, and having very little immune reaction, like many of the organ transplant recipients had, even after two shots, that a third shot boosted about half of those to what might be protective levels, or at least protective, not of infection, but protection from disease. And that's what was the motivation. They actually cited a new study that came out yesterday which showed that if you're on immunosuppressive drugs, combinations of them, in particular, because you're an organ transplant recipient, two doses did basically nothing, but a third dose of the mRNA, for half of those people seemed to do the trick. And I think that's what really triggered their movement. But they were very clear, they're watching this on a day-by-day, week-by-week basis. It's a very fluid situation, and I would not be surprised if, by the end of the month, they end up recommending a booster shot for everybody over 60, or in some cases over 50, as has been done in Israel. Ernie Manouse I know we can get, you and I, a little into the weeds, and I'm fascinated by it when we do so, I'm going to ask you one of those kind of questions right now. The science behind why booster shots work? If we've taken the first shot, and we take the second shot, 2315
what does the booster shot do physiologically within our system that tends to boost protection so much stronger? And we've even heard talk of potentially after a booster shot, that could mean maybe you don't need another shot ever? What happens? Why is the booster so effective at that point? William Haseltine Well, first of all, I think you have to think about it like the flu. I don't think there's ever going to be a booster, or at least not in the foreseeable future, that protects you for a very, very long time, like the polio vaccine. But the reason it works is to do with thresholds. Let's put you on a scale, let's say you need a level of 10 to protect you. Any concentration of neutralizing or binding antibodies that are below 10, you are effectively not protected from infection. You may be protected in some respects from disease, but not infection and transmission of this particular variant. Then, if you get your second shot, you may go up to 50. That's pretty good. If you get your third shot, you might go up to 100. Now, that has a couple of advantages: one, the higher the initial titer the more protection you have and, secondly, the longer it may last. Most people are familiar with the term halflife, it's when something decreases in value by 50%. So the halflife of protection seems to be somewhere around six months, at this point. So if you start at 10, six months later you're at five, that's not so good. If you start at 50, then six months later it might still be protective for many people, but after a year, it's not protective. If you start at a 100, you get more time between shots. I hope that helps. Ernie Manouse Yeah, it does. But it also makes me wonder, why can't we get a larger dose initially? William Haseltine That's a very good question! As you know, the vaccines can also have an immediate adverse event. Some people faint, some people feel like they've got the flu for a couple of days. So you try with most vaccines to get to a level where the initial dose doesn't wipe you out. If you go up too high, you're going to get some really serious adverse events; people are going to really feel like they had the flu, some people may get very sick, and some people may even have more serious consequences. So you are already pushing the dose close to the maximum tolerated dose. You've got to give your 2316
immune system time to recognize it, to get primed, to calm down a little bit. And your body naturally seems to react better when it sees things multiple times. You've got what's called a "memory response," and that gets triggered mostly by things you've seen before. So it's quite helpful to space it out. And if you space it out, maybe by six months, you can give them another dose and you get a very good reaction. Now, we don't have all the data for that. What we're really waiting for, I think, is hard data where we see people have actually waited six months and then been given a third dose to see how high it goes. We have anecdotal evidence, that means small numbers of people, that it works very well, but we really need a more systematic study. Ernie Manouse What I was gonna say, and I think you kind of jumped on it too and had the answer formed before I even asked the question, I had read or heard somewhere that Pfizer was looking at the difference in effectiveness if you take the booster shot one month after you had your first two shots and completed that cycle, or if you waited six to eight months, and to see the difference in how the body reacted, and what kind of response it gave you. William Haseltine You know, this is where we're lucky we have vaccines that work as well as they do. And that they're as safe as they are. We are extremely lucky with the mRNA vaccines. But, we ought to remember that our experience with them is less than a year old. So we still have a lot to learn. That said, I think it's very clear at this point, and what's driving these decisions, is the increasing numbers of people, still not huge, but significant, that are getting reinfected. And that is almost certainly the consequences of the concentration of protective antibodies decreasing. That's not new for vaccines. That's happened with respiratory syncytial trial vaccine. It happens with the flu vaccine. Now, I think what people have to get into their mind is this is pretty much like the flu but a lot more deadly. And we know about flu, we go get vaccinated on an annual basis! At least, many of us do. And that's how we should think about it. We should think about it as something we're going to have to keep our antibody levels up for, and not imagine it's going to be so different. Nobody thinks that if you get a flu vaccine one year it's going to protect you
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very well the next year. Why would you think that about COVID, which seems to be operating in exactly the same way? Covid is a lot worse, it kills a lot more people, and is different in the sense that so far it isn't seasonal. You know, almost nobody gets the flu in the summer. What's happening right now, at least where I am, it's like 90 degrees, and people are worried because a lot of people are getting sick. So, it's different from the flu in some ways, but the fact that the vaccines are protective for a only a certain duration of time holds true. I mean, that's the word that people are not thinking about: time. Time matters. The longer you go after you've had your last booster, the less likely it is that you're going to remain protected. Variants change that and shorten the time. Age changes that and shortens the time. Immunodeficiency shortens the time. So we have to start thinking about time, and I think the shoe that is yet to drop, which I'm worried about, is that time will also erode protection from disease and death. You're already beginning to see some people get seriously ill who've been vaccinated, and you're beginning to see people die. Just like flu, it isn't a shock, and it shouldn't be a shock. You know, there's a huge effort to get people vaccinated, and we should put everything we have behind that. Ernie Manouse And you know, I've got somebody here with me right now, who is putting everything he's got behind that. I want to remind everyone this is Town Square, I'm Ernie Manouse. We're talking with global health expert and author, Dr. William Haseltine, of ACCESS Health International. But joining us right now is somebody who is the perfect illustration of what the doctor was just talking about. It is Sebastian Bach. He's a singer, actor and the original voice of the heavy metal band Skid Row. He recently dealt with a breakthrough case of COVID. And I'll let him tell you the story himself. Hello there, Sebastian. Sebastian Bach Hey, Ernie, how's it going? Ernie Manouse It's going great. I don't know if you were able to hear the doctor beforehand, but he was just talking about people who get vaccinated, there are cases of these breakthrough infections happening and you happen to have called at the perfect time. Sebastian Bach 2318
Yes. Well, I am one of those breakthrough cases. I got the j&j vaccine back in March. I was one of the first people that I knew to get vaccinated. But I'm a singer, and all I read about COVID is that it attacks the lungs and you can't breathe, and I'm like singing this stuff is hard enough as it is. So I'm not getting this disease. And I was completely determined. You know, I didn't leave the house for all of 2020. The first time I really went out was April 3 2021, which is my birthday. Back then things started to seem to be going in a positive direction. So we started booking lots of concerts. And what happened was I went and did two shows, one was in Tulsa, Oklahoma, one was in Beaver Dam, Kentucky, a couple of hours outside of Nashville, and we rehearsed in Nashville and I also went to my wife's 30th highschool reunion in in Arkansas. And when I got home, I was fine. I felt great, the show went great. It was outside in Kentucky, and so I figured it was outside that's a positive thing. But the day after I got home, at about 5pm, I had a fever, and I go, what is going on? The next morning, I got tested, and it came back positive. Looking back, I really think that I might have got it in the airport, to be honest with you. Because in in all the other instances --my concerts or wherever-- I was able to practice some sort of social distancing. But there's none of that when you're in an aeroplane next to the guy next to you, like it doesn't exist. I mean, I'm not a doctor, obviously, but to me the airports and the TSA checkpoints, and layovers. I was a layover in Dallas, and there was a COVID testing site in the airport, as you walk through the gate, which was right in, in the gate, in the terminal with like, just like a rope around it no wall or screen, and in the COVID testing site in the Dallas airport there's like three people like lying down, and I walked right by them and I go, what am I doing? What? How can this be in the airport? Like, with everybody walking by? I mean, again, I'm not a doctor, but I remember going this can't be safe, right? Ernie Manouse You know, a lot of people are listening to your story and saying, "well, he got vaccinated, and he got sick, so why should we get vaccinated?", you have a much better message than that. Sebastian Bach
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Well, because if I didn't get vaccinated, I probably would be having real problems trying to be a singer, which is my job, which involves the lungs. And everything that I've read about the vaccine is that it concentrates the illness in the upper respiratory area of the body, not the lower lungs, which is where I sing and I get my aerobic capacity from, where I can get in shape, and go running and all that kind of thing. And I'm telling you, if I didn't have this vaccine, then I probably would be in the hospital! Luckily, instead I'm coming out of quarantine. I had a fever for a couple days and that was about it, then the fever subsided, and that was at least a week ago, and I've just been hanging in my house not wanting to spread anything and the doctor says, after 10 days, then my levels should be low enough to resume life. But you know, I don't want to get it again. Ernie Manouse Yeah, definitely. And Sebastian, I appreciate that you are going out there and talking to your audience and letting them know how important it is to get vaccinated. Because a lot of people out there still are resistant to this. Sebastian Bach Well, I don't understand that. And I don't I don't understand why someone would get a vaccine for polio when they're in the third grade, but then when they're, you know, an adult, they won't get a vaccine for this? Like what is what is the difference between illnesses? I mean, everybody gets sick. And you know, the whole political thing is null and void when Joe Biden points out that the the vaccine was introduced by the Republican Party, and then it was administered by the Democrats. So what's the problem here? Like, we're all in this together. That's the thing. Like, yeah, you know, Ernie Manouse Sebastian, I appreciate your taking the time to call us today and share your story. I hope you'll come back another time when we can talk about your career and all that you've done and the great work and the music you've given us over the years. And all the great acting too. I hope you'll come back. Sebastian Bach Sure, okay. Thank you. Ernie Manouse Thank you very much, Sebastian. Sebastian Bach 2320
All right, everybody stay safe out there! Ernie Manouse That is Sebastian Bach singer, actor and the original voice of the heavy metal band Skid Row, and he'll be in Houston playing warehouse live on October 7th, if all things go good out there, so we hope you'll come to town and be with us. We are going to take a quick break. When we come back. We're going to continue our conversation with global health expert and author Dr. William Haseltine from ACCESS Health International. This is Town Square, I'm Ernie Manouse and we'll be right back. Ernie Manouse I'm Ernie Manouse, and this is Town Square. We'll get back to our conversation about COVID in just a moment. But first, coming up on tomorrow's show, it's been a pretty intense week of COVID News, and rightly so: from the Delta surge to the legal challenges to the governor's mask mandate. So let's give ourselves a break. And we kick off the weekend with the universal language of pizza. Yep, we're gonna do a whole pizza show. It's our own pizza party. So who has the best pizza in Houston? We want to figure that out, and we want your help to do it. You can even start emailing us your thoughts right now from favorite local pizza, to pizza trends. You can send those to questions@townsquaretalk.org, or tweet us at Town Square Talk. But now, back to our conversation with global health expert and author Dr. William Haseltine of ACCESS Health International. Sorry, Doctor, we're not having a pizza party for you today. William Haseltine Well I'll go out and get a piece myself. Ernie Manouse Okay, that'll be tomorrow's show! I want to shift the conversation a little bit. First of all, for what Sebastian Bach said about the importance he feels by having gotten the vaccine first, it helped him weather this breakthrough case, and science supports that correct? William Haseltine That's correct. It reduces your probability of catching it, and if you do catch it, so far it has been very protective of keeping you out of the hospital and keeping you alive. Ernie Manouse 2321
And you were talking about concern that over time, that may weaken as the length of your last vaccination or the potency of, William Haseltine You know, we don't know that yet for sure. It's something we have to watch, and there are a lot of scientific arguments on both sides of that issue. I think we just have to wait and see. One thing that concerns me is there are some serious cases of people who've been vaccinated, fell seriously ill, and unfortunately, some have died. So whether that's going to be a matter of time and increase or whether it's going to stay stable, we need to watch. But right now, the message is clearly: get vaccinated to protect yourself from getting sick and to protect your family too. Ernie Manouse I want to change conversation a little bit toward our children. And I know you've written books for children, I know that you have grandchildren, I know you are concerned about this area, too. And I'm sure you've been following the news, and Texas along with Florida have had governors who have tried, or are trying, to block mask mandates. I'm curious if you can talk to us a little bit about how this virus seems to be spreading in children, why it's important we pay attention to this, and what we should be doing about it? William Haseltine You know, I've watched this topic very closely for the reasons that you mentioned. My conclusion is that this variant, Delta, is much more dangerous to children. I believe over time the data will show, and is beginning to show, that children are more susceptible to infection, young people are more susceptible to infection, and once infected, have the probability of falling ill and dying at a higher rate than before. We're really in the early stages of observing that, but the news from the United States and around the world does not look particularly good. We do have some more hard data, and that is we know that children, even very young children, once infected with Delta, produce as much virus as adults. We also know that children are a major vector of bringing the infection into the adults and other children in their house. So if a child is infected, just like with the cold, the chance of the other children and the adults getting infected is very high. And so I really worry. That means that children infect children. 2322
You know, one thing I want everybody listening to realize is that this is not the same disease that we had last year. This is worse. It's like flu season, sometimes there's a mild flu season, sometimes there's a bad one. This is a bad one. This year is a lot worse than last year. It takes a lot shorter of an exposure, and much smaller of a distance, to get infected. And once infected, it is worse for you. That's pretty clear. And the same is true for adults and children. So we really don't have all the data yet but I am very, very worried about what's going to happen in schools. And I just don't understand why people would put their political careers above the lives of children. I just don't get it. Ernie Manouse You talk about distance and the impact in distance, too, for spreading this. And I've always been skeptical of the six foot rule; people have been saying that with the strength of the Delta variant, and how transmissible it is, that six feet really is negligible, it doesn't really matter at that, that you would have to be further away for the protection because so much more viruses in the air when it exhaled from someone that the distance it needs would be greater to dilute it. Am I missing the science point here, or is that accurate? William Haseltine You said it very, very well, Ernie. But I would point out that one of the mistakes that was made early on was to think that the virus was transmitted by droplets, not by aerosols. What's the difference? Whether a little bit of spit falls off and falls to the ground after a short distance, or whether, like cigarette smoke, it lingers in the air? From the very beginning, this was more like cigarette smoke. And by the way, a number of epidemiologists, particularly the Chinese epidemiologists early on, said that! The world didn't believe them. Even the original virus has that property of being in the air. So the six foot rule, it kind of worked but not really. And now, it's very unlikely to work. You know, there's one example where there's been an infection that occurred, where one person opened the door in a corridor in an isolation hotel, 30 minutes later another guy opened it and got the same virus. That happened in a very well documented case, in Australia. So that's what we have to worry about. In fact, there's another case in Australia where a number of people were infected in the mall by a guy who just walked through the mall. And that started a whole lockdown of the city of Sydney. 2323
So this thing is not just droplets, and six feet isn't what's making all the difference. Ernie Manouse So hearing all of that, I would assume that your message, your warning to parents, is to make sure our children are masking up, make sure, if they're of age, that they get vaccinated, but before they can get vaccinated, make sure they are wearing their masks, is that correct? William Haseltine Ernie, I couldn't have said it better, you summarized it exactly right. You know, some kids may take off their masks, but I think, even if the school doesn't require it, the parents should ask the kids to wear masks to keep them on. Ernie Manouse It makes me think of an email that we got from Patricia, and she said: "I live near a shopping area, and last spring when I was in my yard, I frequently would see children going past with their parents and the child was wearing a mask and the parent wasn't. The children had learned at school to wear the masks, and they were fine with it. Children want to conform to whatever their friends are doing. And so the idea that we can teach them to wear masks, that they are okay with it, we can make it fun, we can make it comfortable. And even if there aren't mask mandates, parents need to take that step up and say wear the mask to stay safe." William Haseltine You know Ernie, I've noticed the same thing. Young children seem to be very comfortable with wearing masks. I haven't seen a problem with young kids. Yes, kids below three. It's hard to get them to do anything. But, four and above? I think that kids I see seem to be very comfortable wearing masks. It doesn't seem to bother them at all. Ernie Manouse We had a couple questions come in dealing with pregnancy. I'm trying to find the question right here. The one we had was from Blanca, she said her daughter is pregnant at 32 weeks received the first Pfizer found out she has gestational diabetes, should she take the second shot? And I know you're not a medical doctor, but I'm curious from the research. What do we know about the vaccines in pregnant women? 2324
William Haseltine Well, there's new data, and in fact that was mentioned in the White House Conference today, that there's a very strong recommendation that whether you're thinking about getting pregnant or are pregnant, you should take the vaccine, it's safe for you and for your child to be. Ernie Manouse Do we know about gestational diabetes, when that's at play? Is there an issue between the vaccine and that? William Haseltine That's a little bit too specific and I don't know the answer to that. Ernie Manouse All right, that's fine. Another question we got from Erica was do COVID vaccines affect women's menstrual cycles? Should she be concerned for her teenage daughters? William Haseltine That's another piece of misinformation that's been circulating. There's no evidence that it does. It's now been studied pretty thoroughly. I know that that's out there on the web, along with the fact that they're injecting a microchip vaccine. Ernie Manouse I went off the other day about the microchip. And I just want to clarify with you, I said in my rant against this concept is that we don't even have the technology to put a microchip in someone through the vaccine when you take into consideration, the needle, the vaccine, all of that. Am I wrong? Is the technology out there? And we're just not doing it? Or is there no technology to do this? William Haseltine Ernie, that's a question I don't want to answer. Ernie Manouse Uh-oh, okay. I don't want to know why you don't want to answer but I'm gonna move on from that one. William Haseltine But I can tell you there's not a microchip in the vaccine, that's for sure. Ernie Manouse Okay. Martha wrote in and said she donated blood two weeks ago and it showed she didn't have antibodies. She used to. Did she lose her protection from the vaccine? 2325
William Haseltine Now, it really depends which tests you get. If you want to know if you're protected by the vaccine, you have to get an S protein, an S antigen, that's the spike protein. And many of the tests don't test for that, they test for the N protein. And vaccines will test negative for the N protein. So you have to know what test you got. If you were vaccinated, and test negative for the S protein, it means the vaccine didn't take. And that does happen. I know people where that's happened. On the other hand, if you've been infected, you make antibodies to end but they're not going to last forever, either. So if you've already had COVID, and your test shows you were positive, over a long period of time, you might test negative because just like the vaccine antibodies wane, the antibodies to the N protein will wane too. Ernie Manouse Okay, another question came in from Thomas. He wanted to know, can my dogs get the Delta COVID virus and reinfect me despite me being properly vaccinated? There's a lot in that one little sentence to unpack. William Haseltine First of all, dogs can be infected-- that's absolutely clear. In fact, most dogs that are in a household where there's COVID have antibodies to COVID. Well, let me say many dogs. However, there is no documented case of a dog transmitting it to a human. That may mean that the virus doesn't replicate very well. But there are examples of animals like minx, transmitting it to people. And very recently, it's been found that most wild deer carry antibodies to the virus. They've been infected. We don't know how! Was it a human who infected it? I doubt it. When I come near the deer that are near me and my property, they run like the Dickens. I don't get close enough to infect them. So where are they getting infected? Now, Delta and Alpha have a nastier trick. They infect wild mice --field mice and the mice that come in and out of your house-- so my suspicion is that the virus gets into the mice and then gets into the deer. Now that is disturbing, because it means that this virus is now not confined to humans, or bats, but rather is moving into our ecosphere. It will mutate in our ecosphere, and has the possibility of coming back. That happens with viruses like the flu. The flu that we 2326
get can get into pigs, into birds, and there's an exchange between pigs, birds and humans. Sometimes that ends up with a really nasty version. So, it's disturbing to me. That question has a lot of ramifications. But yes, we are infecting our ecosystem with the virus, and it's not just Delta. Ernie Manouse So when you say what you just said, how should we interpret that for the future? How has this played out with other viruses? William Haseltine You know, Ernie, I talk a lot about that, and again, the model is the flu. But recently there's been a breakthrough with flu, one that everybody should know that but I don't think many do. And that is, there's a brand new drug called Xofluza. And that drug, if somebody in your household comes in with the flu, like your child and your husband, you pop one pill and you're protected 80% against infection by the infected person in your household. So the transmission rate for flu is about, let's say 20% of the people in the household will get the flu. Xofluza drops it down to two or 3%. It's actually experimentally shown now, and it's a brand new drug. I stock up on that drug. I'm asking our government to have a warp speed effort to make that same kind of drug for COVID. So if anybody has been exposed, they can pop a pill. Now already, there are some treatments but they are expensive, and they're hard to administer. Those are the monoclonal antibodies, and a few of them work against Delta. So a combination of these monoclonal antibodies, which you have to infuse, can protect and have been shown in experiments to protect you from catching the virus. And, if you've got it early enough, stop it from growing before it can make you sick. That is a whole new dimension, which I call multimodal COVID control: vaccines, and prophylactic drugs. We've fought for years with HIV to get in under control with no vaccine, and just now we're getting to a point where one shot is going to be able to protect you, I'm pretty sure, for six months. That's preventive chemotherapy. You don't even have to be sick to take it. The trick with that, if you're gonna give it to a lot of people who are exposed, it better be very safe, and we need a lot of research. I'd like to see a lot more money being poured in by our government and pharmaceutical companies to develop that drug because together 2327
vaccines plus a prophylactic drug can really be a medical solution to COVID. Now, medical solution doesn't mean itself, you got to get the country on board, you've got to get the tracing on board. And you've got to know who's exposed, you got to make sure that people are going to take the drug. But at least the medical community will have done this job and said, we can stop this if you accept these drugs, these vaccines and these drugs. So we're we're missing one critical component to putting this thing to bed, and that is prophylactic drugs. And I hope my message, and messages from other people, are getting through saying we need warp speed to find those drugs. Ernie Manouse In the 10 seconds that I have left with you, your message to parents right now about to send their kids back to school: one more time, what should they be doing? William Haseltine Make sure that if they're old enough, they are vaccinated. And if they're not old enough, make sure that the environment is safe, their teachers are vaccinated, and that your children are wearing N95 masks. Ernie Manouse Dr. Haseltine. Always a pleasure to have you here. There's so much more on the list I wanted to talk to you about but we have run out of time. Thank you for joining me again. William Haseltine You're welcome, Ernie. Thanks for your time. Ernie Manouse Thank you Dr. Haseltine. Dr. William Haseltine is the chair and president of the global Think Tank ACCESS Health International founder of more than a dozen biotechnology companies and the author but even get a chance to talk about this of the new book COVID related Post Traumatic Stress Disorder, CV PTSD, what it is and what to do about it. If you missed any of today's show, remember town square with Ernie Manouse is available as a podcast. You can get it wherever podcasts are available, or on our website townsquaretalk.org. For Houston public media, I'm Ernie Manouse. Thanks for listening, we'll talk again tomorrow. Unknown
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Town Square with Ernie Manouse is a production of Houston Public Media. The opinions expressed by guests and callers do not necessarily reflect the views of the staff, management, or underwriters of this station. Medical opinions should not replace consultation with a medical professional. This interview originally appeared on Houston Public Media, and is available online here: The Benefits of Being Vaccinated If You Still Get COVID
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Interview with Don Lemon CNN | August 12, 2021 | Interview
TRANSCRIPT: Don Lemon More than 90% of counties in the US are at substantial or high levels of community transmission. Louisiana, my home state, has the second highest rate of COVID-19 hospitalizations per capita. We saw that firsthand today. And joining me now is William Haseltine, the former professor at Harvard Medical School and the author of My Lifelong Fight Against Disease, and Variants!. Dr. Haseltine, thank you so much for joining us. Most of the people I saw today, their hospitalizations could have been avoided. I want you to listen to some of those patients. Radio Montage Why didn't you get vaccinated? So you're not anti-vaxx? Why didn't you get vaccinated? Just apprehensive, you know. The reason I didn't get vaccinated? My choice was I wanted to wait. Let this first batch go through, you know, see how it works. Don Lemon So these particular people I spoke to weren't anti vaccine; they were a little apprehensive, they were scared or didn't feel the urgency, for whatever reason, some worried that the vaccine was rushed. Now, I'm sure they're not alone, and plenty of other people out there feel the same way. What do you say to those folks? Dr. William Haseltine Well Don, I've watched your program and it was one of the most moving programs I've ever seen on this topic, because what you saw was just ordinary people suffering, understanding that they made a mistake, and trying to communicate with you to do their best to help others. I think we have to look at this, as we're in this for the long term. I look at this virus every day as closely as I can, and it seems to me that we may not be out of this in my lifetime. I think we will do much better than we are today. We have good vaccines, we'll get better vaccines. We have some drugs in work, we'll get 2330
better drugs at work. We need time, we need to support the people, our doctors, but we need something else that you touched on in this program, which was a culture of caring, caring for ourselves, caring for each other. And what you see with these people is they're calling out, "help yourself, help your family, help others." We don't need to get so sick to do that. We should begin to change now. And I think your program, more than any politician or scientist or talking head saying what you need to do, is the kind of thing that can help change this situation, move us toward a culture of care. Don Lemon I am looking at my notes and the computer here because it's just coming in, Dr. Haseltine. It's breaking news, the FDA has approved a booster dose of Pfizer or Moderna for some immunocompromised people. And is this our reporting, producers? Yes. Okay. This is CNN's reporting, I wanted to make sure that I didn't have to attribute it to anyone. So is this booster eventually going to expand to a broader population? Dr. William Haseltine It has to. You know, you have to think of this like the flu, it comes back every year. This one is coming back every winter, and now every summer for two in a row. So we're beginning to understand its pattern. So yes, we're going to need boosters, and we're going to need better vaccines. And we're going to have to keep our vaccines current, for the kind of viruses out there. This virus changes just like the flu. I think we know how to confront this, because we do it with the flu. If you think of this as a more serious kind of flu, that is really going to require continual vigilance. You don't go once and get your flu shot, you go every year. That's what we're gonna have, and we're gonna have better drugs, we're gonna get better vaccines, even though these are great. We'll get better ones and we'll get better drugs. So if you're exposed, you can take a pill and not get sick. We will have those. It's going to take time, it's going to take a lot of hard work. Don Lemon Yeah, and we rejigger the flu vaccine every year for certain strains and certain variants. And so, yeah, they update it. Thank you, Dr. Haseltine. I really appreciate it.
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The Black Stallion; Dear Me: Letters to Myself, For All of My Emotions – an interview with Dr. William A. Haseltine Dream Gardens | August 16, 2021 | Interview
Podcast #106 For my one hundred sixth Dream Gardens children’s books podcast, I interviewed Dr. William A. Haseltine about two children’s books: The Black Stallion by Walter Farley, the classic story of a boy and his horse; and Dear Me: Letters to Myself, For All of My Emotions by Donna Tetreault, illustrated by Elisena Bonadio, a picture book guide for young children on understanding and coping with all of their feelings. Dr. Haseltine is a scientist and author, and he is the Chair and President of ACCESS Health International. His books include COVID: A Family Guide to Covid, A Covid Back to School Guide, and My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19. His latest book for younger readers is Science as a Superpower: My Lifelong Fight Against Disease and the Heroes Who Made it Possible. You can find his website at williamhaseltine.com. In addition, after the interview I will be reading the next two chapters of my own debut Middle Grade novel Hush-a-bye, chapters five and six. You can find chapters one and two at the end of my podcast interview with Ben Zhu. You can find chapters three and four at the end of my podcast interview with Amy Makechnie. For more information about my debut novel, please visit my author page at jodyleemott.com. Podcasts are available on iTunes, Stitcher, Spotify, or wherever you get your podcasts. Please link, share, comment, write a review or subscribe. Let me know what you think! If you are interested in participating in the Dream Gardens podcast, send me a request through my contact page.
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This interview originally appeared on the Dream Gardens Podcast, and can be listened to online here: The Black Stallion; Dear Me: Letters to Myself, For All of My Emotions – an interview with Dr. William A. Haseltine
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U.S. To Offer Covid-19 Boosters in September Bloomberg | August 18, 2021 | Podcast
Dr. William Haseltine, Chair and President of Access Health International, discusses the Biden administration offering Covid boosters starting in late September. Bloomberg Businessweek Editor Joel Weber and Bloomberg News Finance Reporter Sri Natarajan talk about Wall Street bringing out the money cannon to lure junior bankers. Bloomberg News Cross Asset Reporter Katie Greifeld and Isabella Weber, Assistant Professor of Economics at the University of Massachusetts Amherst, discuss China's crackdown on tech companies. And we Drive to the Close with Doug Ciocca, CEO at Kavar Capital. Hosts: Carol Massar and Tim Stenovec. Producer: Paul Brennan. TRANSCRIPT: Carol Massar This is Bloomberg Businessweek. I'm Carol Massar. Tim Stenovec And I'm Bloomberg quick-take, Tim Stenovec. We're here every day bringing you the latest news from the worlds of Business and Finance. Carol Massar Technology, politics, economics, all harnessing the power of Businessweek reporters and editors. Tim Stenovec Not to mention our 2700 journalists and analysts in more than 120 countries. Carol Massar You can download Bloomberg Businessweek at iTunes, SoundCloud, or Bloomberg.com. Tim Stenovec You can also listen to our radio show at 2pm Eastern Time on Bloomberg radio. Carol Massar Or watch us on YouTube, search Bloomberg global news. 2334
Tim Stenovec Well, the big news when it comes to the spread of the Delta Varian and the latest with COVID is of course the United States today announcing that it's expanding boosters to all American adults to head off the Delta variant. We have with us now Dr. William Haseltine, chairman and president of ACCESS Health International also the author of CV-PTSD: What It Is and What To Do About It. He joins us now on the phone from Connecticut, Dr. Haseltine was with us back in May. And he actually brought up the topic of booster shots, take a listen to what he had to tell us just a few months ago. William Haseltine This morning, we got the first shoe that dropped; that is, one of the best of all the vaccines, the Moderna vaccine, doesn't protect against two of the common variants, after about six months very well. At least as judged by the ability of the antibodies in people who were vaccinated to neutralize the virus. That is different from a real vaccine test, which is showing that it's failing to protect people in real life. But it's a pretty good indication that it's not going to protect people for very much longer. So the net result is also quite positive. In the very same report it said if you get a booster at six months, you're golden again, you're maybe better off than you were before. So what I've done is I put in my calendar, six months from when I got my last shot, I'm gonna get another. Tim Stenovec You put in your calendar, Dr. Haseltine, six months from when you've got your last shot, you're going to have another. Do you stand by what you said a few months ago about the durability of the Moderna vaccine? William Haseltine Oh, you know, it's not just Moderna vaccines, it's all vaccines. The two best vaccines, of course, are Pfizer and Moderna. And we just today have some pretty sad news from Israel that not only are the rates of infection rising very, very sharply, but 60% of the people who ended up in the hospital are fully vaccinated. So not only is it not protecting you from infection and transmission, it's not protecting you from serious disease in many cases. Tim Stenovec That's really concerning data from Israel, because the data that we're seeing here in the United States is 85 to 90% of those who are 2335
in the hospital haven't been vaccinated, why do you see the discrepancy? And also, we should say that not all studies are created equal. You know, we have to take all of this data with a grain of salt. William Haseltine No, we don't. Tim Stenovec Why not? William Haseltine This is really good, hard data. There's a new study out that says your degree of protection is a function of how much time has elapsed since your last vaccination. So, there's about a tenfold difference in hospitalization based on the time that has elapsed since your last vaccination. I think it's very clear now, and that's why the government has moved the way it has. It's very clear now that to protect against serious illness, most people are going to need a booster. They've pegged that at about eight months, that's probably about right for most people. For people who are older, it's probably a little shorter than that— six months will do. So I would stand by my statement that six months from my last vaccine, I'm certainly planning to get another booster, and I think the government's official recommendation now is every adult get a booster beginning eight months from the last vaccination. This isn't magic. This is kind of like the flu. We knew. We think every year we have to get a new flu vaccine. I don't know what’s so special about this, why people are so surprised. Tim Stenovec Yeah, and every few years we do have to get boosters for other vaccines as well. I mean, we certainly do that. I think perhaps the question that people would have about this is, is it specifically related to the Delta variant? Or does the durability of the vaccine decline regardless of whether or not we're being hit with new variants? William Haseltine You know, that's a good question. The answer is yes to both: Delta is better at evading the vaccines, but as time goes on, the vaccines will wane in effectiveness against all variants, even the original ones. So, that's to be expected. You know, if you go back and look at what I was writing a year ago, I was predicting that any vaccine that would be developed would be of relatively short duration. That's because we have a lot of experience with viruses 2336
like this, particularly the flu. I think the more people start thinking about this as a very dangerous virus, like the flu, much more like the flu than anything else, the better off we'll be. Something that has to be observed, and will come back every year, maybe twice a year. The odd thing about this one is it's coming back in the United States in the summer, and the winter. And so it's a little different in that respect, it's more lethal. So we've got to be more careful. But we've probably got to keep up with our vaccines every six months to every year. That’s not the best news, but it's not the worst either. Tim Stenovec Is it fair for the United States to encourage booster shots, when the vast majority of the world has not yet even had access to these vaccines? William Haseltine You know, it's our country's responsibility to take care of people in our country first. That is what the government's job is, to take care of us. Having said that, we should do everything possible to make sure that others in the world also have the advantages that we have. It's unfortunate that many areas of the world have neglected their own vaccine programs, and they're now paying the Piper. Yes we should help, but not at the expense of our own citizens. Tim Stenovec Well, let's get right back to Dr. William Haseltine. Chairman and president of ACCESS Health International, also the author of many books, his latest CV-PTSD, COVID, related Post Traumatic Stress Disorder, what it is and what to do about it. Dr. Haseltine, before we get to the book, I want to talk a little bit about vaccine availability. Here in the United States, vaccines are still only approved under emergency use authorization for people over the age of 12. How do we get past this pandemic, especially as kids go back to school when millions of children cannot be vaccinated? William Haseltine We start vaccinating our children as soon as possible. I think that once the results are in, I'm pretty confident that this vaccine will be safe for children, but until you have done the studies, you don't know. I know our government is working as fast as possible to get those studies done. I hope it's done, let's say by Thanksgiving, I would certainly hope so. Tim Stenovec 2337
You think that it's realistic to think that we could get emergency use authorization by then? William Haseltine Yes, and I think by that time we'll have actual approval for the Moderna and the Pfizer vaccines. We'll have a real approval, not just emergency use authorization. Tim Stenovec Do you think that we'll have approval for emergency use authorization for ages zero to 12? William Haseltine Probably not zero, but maybe two or three to 12, yes. I think that's what we're heading for. I know that people are working as hard as they can to get that data so they can, if it proves to be safe, go ahead and do it. And my guess is it looks like it will be safe. Tim Stenovec Well look, it's been a tough year for many, many people, not just specifically because of COVID —if they got it or even if they didn't get it— perhaps they've suffered from what you describe as CV-PTSD. You write that it encompasses the full effects of all that we've endured over the past year and a half, manifested daily in rising rates of depression, anxiety, drug addiction and the ongoing loss of academic opportunities for the young. I wonder how we get past this. If you say that COVID is going to be endemic like the flu, how do we get past CV-PTSD? William Haseltine Well, first thing, we have to recognize that it exists both for individuals and actually for the whole society. In addition to the normal stresses that we undergo, this has been a tremendous economic stress, it's been a stress of fear of getting the disease. There have been a lot of conflicting messages; both official conflicting messages and unofficial conflicting messages. It's the perfect storm for creating stress and anxiety. If you look at the numbers of people who report Anxiety, it's close to 50%. People who report depression much, much higher. A lot of young people are feeling especially stressed. Now what can you do about it? As I say, the first thing is to recognize it, you know, we didn't recognize combat Post Traumatic Stress Disorder until 1980. We called it shell shock or malingering, we had all sorts of names for it. Once we had a name for it, and we 2338
recognized what it was, we began to develop treatments. There's a very well developed treatment program, and paradigm, for post traumatic stress disorder, the Veterans Administration uses it all the time. And it involves counseling, recognition of what's happened, and then sometimes, some drugs that may help. But I would say for what's happening now, let's take schools, for example. All the kids are going back to school, and teachers are stressed, because they're going to be dealing with a lot of stressed children. I think we have to support our teachers and our children with additional social work, and psychiatric social work in our schools. Because that's where we're going to see it first. As children go back to school, there's going to be learning problems, there'll be behavioral problems. That can manifest itself as people who were totally withdrawn or totally unruly, you get both extremes as a result of this, and we're going to have to recognize it. As more and more people get back to work, I think many big businesses are going to have to help their employees with special counseling. And it's going to be really important to do that, to get over this both as an individual and as a society. Tim Stenovec We've seen that start to happen in some instances, but in most of those cases, it's the companies that white collar employees work for who already have great benefits. Dr. Haseltine, Chairman and president of ACCESS Health International also the author of CVPTSD: What It Is and What To Do About It. It is always great when you join us. Thank you so much for taking the time. This podcast originally appeared on Bloomberg, and can be listened to online here: U.S. To Offer Covid-19 Boosters in September
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'That's Insanity': Former Harvard Medical Professor Responds to No Plan for Covid-19 Measures in School ‘Saskatoon Morning’, CBC | August 19, 2021 | Interview
A former Harvard medical professor breaks down the vulnerable position of children as we head into a new school year. Host Leisha Grebinski speaks with William Haseltine, infectious disease researcher. TRANSCRIPT: Leisha Grebinski The number of supporters for public health measures to be in place for schools is growing. The latest comes from the Saskatchewan Medical Association and the Saskatchewan College of Family Physicians. Dr. Eben Strydom is the president of the SMA. Dr. Eben Strydom We are calling for mandatory masking of children in school, in all of those spaces: the classrooms, the common areas, etc. And to only revisit those when the numbers come down so that, you know, you have a fair amount of certainty that the risk is lower. You know, we want to make sure that vaccinations are done expeditiously for all of those who are eligible, 12 and older, and so we applaud the SMA for their stance on vaccinations for all their staff and students. Leisha Grebinski Well, the two organizations are also calling for mobile vaccination clinics in schools and other measures such as physical distancing, and regular cleaning and testing of H vac systems. So to break down the risk of returning to school, we are joined now by William Haseltine. He's a former Harvard Medical professor and infectious disease researcher. Good morning to you. William Haseltine Good morning. Leisha Grebinski You know, I want to start by asking about the latest understanding of how COVID and its variants affect children? 2340
William Haseltine We now know that, particularly the Delta virus, is very efficient at infecting children. And in fact, children transmit the virus to one another and to adults better than teenagers or adults do to each other. So that's the first thing we know, it's highly transmissible amongst children, between children, and between children and adults. Second thing we know is that, as compared to earlier versions of the virus, it's more infectious for young people— that's young adults and young children. There is also emerging evidence that it is a much more serious disease. The concentration of virus in the upper respiratory tract is about 1000 times more —1000 times more!— than the earlier variants, and that is showing up as a lot more ill young people. There's a big debate as to whether, because it's more infectious, there's a higher proportion of sick children, or is the virus more intrinsically dangerous. But I think it's probably a mixture of both at this point. So, it's really important to take care of our children. Leisha Grebinski And just how sick are some children getting? Are we seeing an increase in hospitalization? Are we seeing more deaths? William Haseltine It depends where you are in the world. In some parts of the world, you're seeing a lot more deaths. That is particularly among disadvantaged children, or children who live in some pretty rough conditions. In the United States, we're not seeing a huge increase in death, but we're seeing a very significant increase in the number of children that are being admitted to the hospital. A very, very big increase across the country. Leisha Grebinski So what is the risk for children under 12, who have not received a vaccine, going back to school? At this point, in Saskatchewan, in Saskatoon here, there are no safety measures in place. William Haseltine That's insanity. It's just insanity, and why that would happen in any civilized society is beyond my understanding. This is a very deadly virus. It's a dangerous virus for our children. Simple procedures like mass and social distancing are critical, vaccination for teachers, and all workers in the school, is essential, and beyond that there should be wastewater management so that you know if any 2341
child is infected. Wastewater detection of the virus is so specific now, if you tested the wastewater from one school, you could easily know if there was one person in that school system that was infected. That then gives you the impetus to test everybody. You don't need to test everybody if there's no virus there, but the moment there's one person, that changes. I'll give you something I read this morning, in Australia there was one person that they've now traced to have infected 10,000 Australians and, as a result, shut down Sydney. One person was infected while at the airport, and infected 10,000 people in Sydney, Australia. They had to shut down the whole city for a long time, and they're still going through a series of shutdowns. This is not something to play around with, and officials, government officials, public health officials, are just not doing their job and the people should let them do their job. Leisha Grebinski Do we need to drop the thinking that COVID doesn't affect kids all that much? You know, the number of times I've heard "Oh, for the most part, they get a runny nose, you know, a bit of a cough, but it doesn't really affect children." Do we need to drop that thinking? William Haseltine We do, we really do. You know, there are many, many myths that are killing people. The myth that it's only transmitted by droplets, the myth that it's gonna go away in the summer, this is the summer by the way, and it certainly hasn't gone away. And now unfortunately, although it's not exactly a myth, but the story that the vaccine will give you a shield of protection. It will for a while, but then you need boosters. The thing that we're now seeing in Israel is that even though most people are vaccinated, you need to vaccinate them again. You should think about it like the Flu; it's not a mystery. Everybody lives with the flu, we know about the flu, it comes back every year, we get protected every year with new vaccines. I don't know why people are putting this disease in a different category. Think of it like a much more deadly flu, and you'll have the right attitude toward it. Just business as usual. Go get your shot every year, and you'll be reasonably safe. And we know that the flu affects children, and this thing does too. It's just just not right. Leisha Grebinski
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So I have one more question before we let you go, and we don't have a lot of time, but for parents listening, I'm a parent, I have two children, two and four, one's heading into kindergarten. What are parents supposed to do right now? William Haseltine You know, I really sympathize. I'm a grandparent, and I agonize over my grandchildren. But first of all, your children have to wear masks whether other people are wearing masks or not. And that's hard for kids, but that's what they have to do. Second, you should lobby as hard as you can for your public health officials and your schools to make sure vaccinations are mandatory for everybody in the school. And then you should work with the public health authorities to do wastewater screening of each school facility, so you know if anybody's infected. And then you do individual testing of everybody in the school, and isolate those who've been infected and those who've been in contact with those with infections. In the US, what I'm finding is a lot of kids are being sent home; all my friends' children are being sent home from school because one person in the school has been infected. So why do they send their kids to these schools that are unprotected in the first place? So I really sympathize with you as a parent, and it's a very difficult decision. Leisha Grebinski William Haseltine I really appreciate your time today. Thank you so much for being with us. William Haseltine Yes, my pleasure. Thank you and good luck. This interview originally aired on CBC’s ‘Saskatoon Morning’, and can be listened to online here: 'That's Insanity': Former Harvard Medical Professor Responds to No Plan for Covid-19 Measures in School
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Infectious Disease Researcher Calls for Strict Public Health Measures for Back-to-school to Protect Kids from Delta Variant ‘The Morning Edition’, CBC | August 20, 2021 | Interview
This week, the Saskatchewan Medical Association joined the call for public health measures to be in place for schools. An infectious disease researcher will update us on the risk the Delta variant poses to children. TRANSCRIPT: Stefani Langenegger That's Dr. Eben Strydom, head of the Saskatchewan Medical Association in our province. We've also heard from a doctor with the Saskatchewan health authority that masks and distancing should be required in schools this fall. But so far, the provincial government has said that those rules aren't necessary. For more on that we've reached William Haseltine, a former Harvard Medical professor, and infectious disease researcher. Good morning. William Haseltine Good morning. Stefani Langenegger What do you make of the government's stance that students can go back to school without any provincial guidelines this fall? William Haseltine It's deadly. Stefani Langenegger What makes you say so? William Haseltine The virus is spreading rapidly in children, children are becoming ill, our pediatric ICU units in the United States are filling up and there is no reason to suspect that it will be any different in Canada. It is entirely irresponsible to send unprotected children back to schools. I recommend several different measures. First is mandatory vaccination for every adult who enters the school. That's a teacher, maintenance personnel, cleaning staff, etc. That's the first thing. 2344
Second is mandatory masks for children of all ages. Third, is a maximum push to have children over 12 vaccinated. Certainly in the United States, that's possible. School aged kids should be required to have a vaccine to attend school. These sound today, like very strict measures. But tomorrow, once we see what we're seeing now, in the United States, many children being sent home and others being sent to the hospital, it will sound reasonable. In addition to that, schools should all make major investments in ventilation. Even if you are masked and the teachers are vaccinated, this virus can penetrate even the best vaccines at this point. And it's important to have ventilation where the amount of air per classroom is exchanged every hour, at least six or seven times. Stefani Langenegger What do we know about the risk to children of COVID? We've just heard they don't do that poorly in general. William Haseltine That's not true anymore. That was true for the old virus, but it's not true for Delta. Delta is infecting large numbers of children, and, as I said before, we're now witnessing the effect of that which is hospitals, pediatric hospitals, filling up with children in their ICU units. These children are very, very ill. This is a different virus. One of the things we know about the virus is that in children, as in adults, it produces about 1000 times more virus than the previous strains did. That means the children not only can spread it to each other, but it makes them sicker. It's going to take a while for all that data to come in, but I can tell you from conversations with doctors and from looking at statistics now in the US and other places, there's no doubt. It hits particularly hard, the underprivileged children who may not have the best nutrition and who may have some other health problems. And in some countries, there are quite a number of fatalities associated with children of less than optimum health-- from babies on up. So this is not anything to mess around with, and the authorities in your province should, in my opinion, begin to take this very seriously. Otherwise, they'll be responsible, not only for the death of adults, but the deaths of a number of children. Stefani Langenegger
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What's your sense of leaving it up to school divisions to see how their school fits into the community rather than blanket rule? William Haseltine You know, you can't tell where it's going to hit. And the problem with this is that almost all the carriers are asymptomatic: they feel perfectly fine, but they're spreading the virus. This virus has a very nasty trick of going into people and suppressing any sign of disease until it gets out. By the time you're feeling a little sick, the virus is already on its way out and has gone wherever it will go. And it's highly contagious, much more than the previous strain. This is not what happened last year, and it should be considered to be a completely different type of infection. Stefani Langenegger I think we have higher vaccination rates than many US states, which are seeing high numbers of cases right now. Although my province is still the lowest in Canada, I think we're doing better than some US states. How much will that protect us? William Haseltine It protects some, but it's a function of several things. First of all, what vaccine you got. It works best if you got the Pfizer or the Moderna vaccines, the others don't work quite as well. It's a function of the Delta variant being able to penetrate even the best vaccines after some time. What we noticed, and the best data comes from Israel, is that the first wave of the Pfizer vaccine was very effective at driving down the infections. Israel then opened up, and now they're in the middle of a very sharp spike in vaccinated people. 60% of those who are in the hospital and are severely ill are fully vaccinated with a Pfizer vaccine. So immunity depends on how long since the last effective vaccination. It can be, for an older person, as short as four or five weeks, and for a younger person it may be five or six months. But, these vaccines don't last forever. Stefani Langenegger Thank you very much for your time this morning. William Haseltine Right. I'm concerned for you and I hope your health authorities take this very seriously, as they should. Stefani Langenegger Thank you very much. William Haseltine is a former Harvard Medical professor and an infectious disease researcher. What are 2346
your thoughts about our plans here in Saskatchewan? morningedition@cbc.ca This interview originally aired on CBC Saskatchewan ‘The Morning Edition’, and can be listened to online here: Infectious Disease Researcher Calls for Strict Public Health Measures for Back-to-school to Protect Kids from Delta Variant
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September 2021
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Doctor warns of the toll this pandemic is taking on our mental health and the hangover is longterm ‘Action News’, ABC Tampa Bay | September 6, 2021 | Interview
The psychological scars of COVID-19 will likely outlast the pandemic itself and a doctor says we must be mindful of the toll it's taken on our mental health. "If you have seen really horrific things, and some of us have through this pandemic, it's normal to be anxious. It's normal to be depressed," says Dr. William Haseltine, a Doctor of Philosophy and author of 12 books, including three books on COVID. He says we've all been traumatized in many different ways from this pandemic and the psychological scars don't just disappear. "It's like a war. When you come home from a war, the war is over. But it's not over for you. We've learned that through Post Traumatic Stress Disorder," he explained. *** TRANSCRIPT: Wendy Ryan Turning now to the after-effects of the coronavirus, a doctor says the psychological scars of COVID-19 will likely outlast the pandemic itself. And you may have already felt some of the anxiety or PTSD from the protocols still in place. So as we take steps towards a rebound, that doctor says we must be mindful of the toll it's taken on our mental health. Dr. William Haseltine If you have seen really horrific things, and some of us have, through this pandemic, it's normal to be anxious, it's normal to be depressed. Wendy Ryan Dr. William Haseltine, is a Doctor of Philosophy and author of 12 books, including three books on COVID-19. He says we've all been traumatized in many different ways from this pandemic. And the psychological scars don't just disappear. 2349
Dr. William Haseltine But it's like a war. When you come home from a war, the war is over, but it's not over for you. We've learned that through Post Traumatic Stress Disorder. Wendy Ryan And recent statistics prove he's right. According to the Kaiser Family Foundation, over the last year four in 10 adults in the United States have reported symptoms of anxiety or depressive disorder, which is a dramatic increase from the one in 10 reported in 2019. Dr. William Haseltine People are much more anxious and are likely to be anxious. They're much more likely to have long-term depression. Wendy Ryan And children are also feeling the effects of this pandemic. Dr. William Haseltine Pediatric social workers and pediatric psychiatrists are reporting a huge uptick in very serious mental issues of children anywhere from the ages of four to 15/16, including suicidal ideation in kids as young as 10. Wendy Ryan So Haseltine believes more social workers are needed in schools to help our kids recover. And there needs to be a reimbursable diagnostic name called COVID-related Post Traumatic Stress Disorder. Dr. William Haseltine I think that would make the biggest difference in society because then you engage the social work community and the medical community in trying to give the help that people need. Wendy Ryan And if you'd like to read Dr. Haseltine's most recent books, they include: COVID-related Traumatic Stress Disorder: What it is, and What to Do About it; a Family Guide to COVID: Questions and Answers for Parents, Grandparents and Children; and, Variants! The Shape Shifting Challenge of COVID-19. To order his books and read his COVID commentaries, go to his website at williamhaseltine.com. We've also included that information on our website at ABCactionnews.com/rebound.
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This interview originally aired on ABC Tampa Bay’s ‘Action News’, and can be found online here: Doctor warns of the toll this pandemic is taking on our mental health and the hangover is longterm
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The Heat: 40 million COVID-19 cases in the U.S. ‘The Heat’, CGTN TV | September 7, 2021 | Interview
The number of coronavirus infections in the U.S. has reached another grim milestone. 40 million cases – more than 10% of the population contracting the virus since the pandemic began. Three months ago, the number of daily new cases had dropped to around 15,000. But with the highly contagious Delta variant, we are now seeing over 160,000 new cases confirmed – every day. To discuss: • William Haseltine is Chair & President of ACCESS Health International. • James O’Dea is Vice President of Operations at Hartford Healthcare’s Behavioral Health Network. • Rafael Bernal is a reporter for The Hill. • Peter Chin-Hong is Professor of medicine and an infectious disease specialist at the University of California, San Francisco. TRANSCRIPT: Anand Naidoo COVID-19 cases in the United States climbs to a staggering 40 million amid a fourth wave that continues to spread. Hello, I'm Anand Naidoo and this is the heat. The number of coronavirus infections in the US has reached another grim milestone: 40 million cases. More than 10% of the population contracting the virus since the pandemic began. Three months ago, the number of daily new cases had dropped to around 15,000, but with the highly contagious Delta variant, we're now seeing over 160,000 new cases confirmed every day. To discuss these numbers and what can be done, let's bring in our panel from Connecticut. William Haseltine, is chair and president of ACCESS Health International, also from Connecticut, James O'dea is Vice President of Operations at Hartford healthcare's Behavioral Health Network. Peter Chin-Hong is a professor of 2352
medicine and an infectious disease specialist at the University of California, San Francisco. And here in Washington, DC. Raphael Bernal is a reporter for The Hill. Welcome to all of you. Dr. Haseltine, let me start with you and let's look at some of the numbers. New infections are up 156% in the US from Labor Day last year, and hospitalizations up 158%. And of course, these numbers are being blamed on the Delta variant, and of course, people who are still refusing to get vaccinated. What is your assessment of what is going on right now? And, does this mean that efforts to overcome this pandemic are going to take a lot longer than we initially expected? Dr. William Haseltine Well, to start with your last question, the answer is yes. It's obvious this is not over by last summer, which people hoped. It's going to be quite a while, I think many years, before we finally put this back into a manageable pandemic. That's the first point. Second is, it's both the virus and people's behavior. It's not the virus alone, it is the relaxation of many of the strictures that we operated under: social distancing, mask wearing, etc. And despite the fact that we have very good vaccines, there are a couple of things that have been going on. One is, a fair proportion of our population in many regions are not vaccinated even though they could be. But beyond that, there is behavior which is relaxing, and that means the virus has an opportunity. The virus is more dangerous than it was before. It's more transmissible. Delta is not the virus we first encountered. You need shorter exposures, doctors are saying you get it quicker, you get it more seriously, and more younger people are getting it. So it's a different virus. And we can look forward to other viruses, unfortunately, that have some of the same characteristics, different mixes of characteristics. So it's a witches' brew, but it's not a good one. And we're really suffering. Anand Naidoo And Dr. Haseltine, when you say we need to get to the point where the outbreak is manageable. What kind of criteria are you looking at? Dr. William Haseltine Well, I think it needs something that I've called Multimodal COVID Control. That means vaccines, first and foremost, for the eligible population, hopefully soon including our children down to 2353
the age of five and then down to the age of two, so most people. Secondly, that doesn't mean we can stop our mitigation measures. Even with vaccines, this virus is kind of like the flu, it will get around most of our vaccines one way or another-- for the last six months, I've been studying its various methods. It's not just the outside of the virus. It has many opportunities to change, as do other viruses, to become more transmissible and more deadly, and it's moving along that trajectory. Then, of course, we need very strict mitigation measures, we need to do identification, contact tracing, and isolation. We need to keep up our warp speed research for new vaccines and new drugs to prevent transmission. We know that we can take care of vaccine resistant viruses or viruses for which we have no vaccines by prophylactic chemotherapy, but we need to ramp up our research to do that. And then of course, we need international cooperation. We can do better in every one of those issues. Every country can do better on every one of those four or five things I've just mentioned. And I think over time, we will. And above all, we need something which I call a "culture of caring." We need to realize that restrictions on our own freedom are for others' safety, and restrictions on their freedom are for our safety. That is a deep cultural change. I'm afraid it's gonna take a while to come. Anand Naidoo James O'dea, great to have you on the show. Another issue that we're hearing a lot about these days, is booster shots. We know that the effectiveness of some of these vaccines starts to drop over time, and then that leads to the likelihood of people needing booster shots, especially those who have weak immune systems. But now experts are saying that the White House needs to back off booster shots until more data is available. Here is the White House Chief of Staff, Ron Klain, speaking over the weekend, let's listen: Ron Klain I want to be absolutely clear. No one's going to get boosters until the FDA says they're approved until the CDC Advisory Committee makes a recommendation. What we want to do, though, is be ready as soon as that comes. Anand Naidoo
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So James, what can you tell us about the need for booster shots? And ultimately, will everyone need that? James O'dea Well, first of all, thank you for the opportunity to be on the show, and I agree with so much of what Bill had to say. Well I think it's still early, frankly, for us to be talking about the efficacy of booster shots. At this point, I think we're still waiting on additional information, especially as it relates to both the Pfizer and the Moderna, and the j&j vaccine. I actually think there's a different approach that we need to be taking rather than focusing on the booster shot for those who have already chosen to be vaccinated. While that will offer protection to those individuals who have already moved in that direction, I think we have a much more compelling issue in front of us, which is the fact that we've plateaued across this country, and in many countries, around people getting an initial vaccination. And as Bill points out, that is probably one of the most important issues: getting people vaccinated, along with the social behaviors and the masking and the other things that Bill mentioned. And I guess I would go so far as to say that the plateau is concerning. And I think the science that we have at this point about the efficacy of vaccines is so abundantly clear, and yet we still have so many people that are choosing not to be vaccinated. I think we need a new strategy, just as Bill was saying, we need a new strategy to think about this as a chronic condition and not one that's going to go away in the near term. I also think we need to approach people who so far are choosing to not be vaccinated and to engage more deeply with them about what their hesitancy is about. And, how do we support them in the choices that they're making? Because those choices affect all of us. Anand Naidoo Yes but James, I'm guessing that, you know, one could come up with very reasonable, cogent, scientifically based arguments for the need to be vaccinated. But this has been politicized to such an extent that in many instances there's an ideological battle going on here. So it makes that job much more difficult, doesn't it? James O'dea It's an excellent observation, and that is actually what I have focused on over the course of the last two to three months. Engaging with people to better understand that reality. And it's true that there 2355
are identity issues, there are political issues. There are also very significant issues around race, and different communities that are responding around the vaccination question in very different ways. As a psychologist, one of the things that I know is that it's very important for us to listen to those realities. And I think we're past the point where we're simply going to debate with people and talk past each other, the value in a person like me or other scientists saying, please go get vaccinated, please go get vaccinated. That's gone. That's exactly where we are. And so those individuals who were receptive to that approach have already been vaccinated. I think we need a new strategy that engages people with a much more generous attitude and a willingness to really listen to what is their resistance about and how do we help them maybe get to a place, if through listening to their reality, they might begin to contemplate a different approach. Anand Naidoo Peter Chin-Hong, great to see you again. Peter, you are out west in California, one of the most populous states in the country, what is the situation out there? Peter Chin-Hong Well, we have a higher proportion of folks who have received one shot, at least 80% right now in the state, and of course, in certain areas like where I'm at, San Francisco County, about 80% have received two shots. I think what we're focusing on now is really having some of the invisible population also approach, because again, the people we count up as the denominator isn't only the people who should be receiving vaccines. For example, today an initiative was outlined where there's a grassroots organization looking at day laborers, you know, we don't count them, even as part of the denominator. So I think that is the approach. And I agree with the others, we have to have a new approach of, you know, listening to people. Humble inquiry, I think,. Finding out where people come from. I was struck by a recent survey showing that only 17% of the unvaccinated were approached to talk about vaccinations. Speaking from my own experience, we, you know, sometimes treat them as other and not engage, and I think maybe an engagement might be worthwhile. Anand Naidoo
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And Peter, what can you tell us about the situation in schools because there's quite a vigorous debate going on, not just in California, of course, around the country, about young pupils returning to school, in person teaching, the debate over mask mandates, etc. There was a survey done by a New York based tracking agency, which shows that 1000 schools in 35 states remain closed, and we know that there's been an increase in the number of emergency room visits as well as hospitalizations for teenagers aged 17. Peter Chin-Hong Well, I think a lot of the school debate has been political, a lot of it has been centered around masking. And of course, we know in the UK, for example, the students going to school are not masked. So people are looking at that, of course, it's just one of many strategies that we are we are listening or using in schools. I think what has really shaped the school debate too, is the mayhem it's caused. A lot of folks have been pulled out of school for contact tracing, quarantining, etc. and that's led to some disruption. But if you look at the hard outcomes of hospitalizations in highly vaccinated areas, like San Francisco, in my own hospital, for example, we probably have four kids that are hospitalized. And I think the idea that, or the fact that 1%, 1 to 2%, of kids who are under 12 get hospitalized is really something that I think people are not really communicating as well. Anand Naidoo But available now, the situation in schools has led to a bit of a battle between states rights and federal rights right now. In fact, the Biden administration is investigating up to five states that have banned mask mandates on the grounds that it violates children's rights. How is the White House handling this, you know something that's become overtly political right now. Rafael Bernal Well I think, broadly speaking, the medical realities, as very well explained by all of your other guests today, they paint a grim picture for Biden politically. COVID-19 was the reason that Biden's poll numbers during the first six months of his presidency, sustained a pretty high level, that has gone away and attention has gone on to other maybe crises, the White House pushes back on the idea that
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maybe Afghanistan isn't really a crisis, but a situation that they're dealing with. But COVID and the economy seem to be where voters are, so it's given an opening for Republicans to push back on the issue where Biden was strong. And that's what's happening with the issue with schools, and it's happening with the issue of not being able to, for example, convince people in Mississippi to get the vaccine. So you have very different realities, where, like they were talking about, the San Francisco Bay Area, 80% are vaccinated and Mississippi, I believe the number is about half that. And you can't govern a country like that, you can't create overarching policy. Add on top of that, that Republicans in many states and many very populated states like Florida and Texas, are sort of trying to do whatever politically is least convenient for the for the Biden administration, and politicizing a medical issue even further. And you know, that I don't think the Biden administration has had a good answer for that either because the result is people are put in danger. And neither side of the political debate seems to have the answers to get either more people vaccinated or somehow reduce contagion or implement mask mandates. There are simply no answers that are working right now. Anand Naidoo Rafael, as we heard from our other panelists, there needs to be a different approach right now, especially when talking to people who are not vaccinated. We've heard President Biden on many occasions --in his addresses to the nation, in his white house appearances-calling for unvaccinated people to get the vaccine right now, but is it time perhaps, for this administration to try a new approach? Rafael Bernal It has to be! I think it's actually sort of uplifting to listen to the medical experts on this panel, talking about new approaches, talking about having a conversation with people who have not been politically engaged, to do something to save their own lives. The Biden administration has not been able to sell the science to that group. And then there's a group of people who support the Biden administration, and have been sold on the science in this case. And then there's that group in the middle. And I think the risk is, of course, the people who haven't listened, they maintain themselves at risk. And as the virus mutates, apparently that risk is getting higher. 2358
And that group in the middle, they start losing them. If booster shots become necessary and people don't want to take them, for instance, people who did get the vaccine the first time around, that's the worst case scenario. And frankly, it's a very possible scenario. So that's the real danger, and the Biden administration has to figure something out. Some way to reach across the aisle that actually works. And frankly, if they do, everyone in the political world will be very surprised. James O'dea I'm sorry, if I may. You know, I thank you for that comment, and I very much appreciated my colleague in San Francisco using the term humble inquiry. We've talked so much about the science, the infectious disease science, and the epidemiological science, which is very clear, but there's another form of science that would inform our strategy to engage with people who have been disengaged: cognitive science offers us a way forward, which is again, entering into an inquiry with a genuine sense of curiosity, with a genuine sense, actually, of generosity. Really wanting to understand what is leading someone to adopt the position that they're in. The science is very clear. When we engage with people in a generous sense of really wanting to understand where they are, they actually become more ready to contemplate a different approach. And so I think cognitive science is something that we need to enlist a bit more of, as we think about how we move people from being in a contemplated place to possibly taking a step toward getting vaccinated. Anand Naidoo Dr. Haseltine, I want to get back to the Variants for a moment. Dr. Ashish Jha of Brown University, he is the dean at the School of Public Health there, he tweeted this, he said, "Worried about the Mu Variant? Maybe Lambda? How about C.1.2? That sounds scary. Don't be. While we are still learning, I doubt they'll displace Delta. And our vaccines should hold up fine. I don't lose sleep over new Variants, I worry about people's fatigue with the current one." What do you make of that? Dr. William Haseltine Overly optimistic, to put it mildly. If you made that same statement when the Alpha variant was around, you would have regretted it. He will regret that statement. These viruses have the 2359
potential to change, and the potential change can make them very much more dangerous. Now, we don't know the future for sure, and I could be wrong, but I haven't been wrong so far in the predictions I've made about the dangers of this virus. We've underestimated it from the very beginning, and I go through 15 different ways we've underestimated it-- it's a really big mistake. But I think I'd like to say something about what the other panelists have been talking about. And from my point of view, the issue is a deep cultural issue. Do we actually care for one another in this country? Yes, we do if there's an emergency like 9/11, or a hurricane, everybody chips in. Both Republicans and Democrats and everybody are helping the Afghan refugees that are coming into United States, for example. That's our strongest suit. But when it comes to something like this, and the only way we're going to get to a better place, is if we suffer enough to know that we have to change. And nobody knows when that will come. Yes, we can listen to people, but there are people who aren't headed and don't even want to be engaged. So engagement isn't the only way. It is an important way, and I agree with my colleagues on this panel, but a culture of caring, it might take 1000 years to develop, or longer. I don't think we have time to do that. But we have to somehow understand that I am my brother's keeper, and my brother is my keeper. That's what we have to get to. And we are so far from that today! The science is clear: vaccines help, mitigation measures help, wearing masks helps. All those things are important, and the science is really clear. Regarding the vaccines, a third shot helps, it definitely helps. Especially people my age, where the immunity is waning and people can get reinfected and get re-hospitalized. So the facts are there, but it turns out that humans are not fact-based decision makers, we're emotion-based decision makers. And we make decisions in groups, not only by ourselves. We have to engage people at that level, and how we get from where we are, to where we need to be, is really distressing. When I see a country like China, that's had fewer than maybe 24 people die in the last year and a half, and we're heading towards 800,000 people dead by the end of the year, it is heartbreaking. All those people didn't have to die, but they did because our culture is callous and uncaring and selfish. Anand Naidoo 2360
James, I'd like to get your thoughts on that, you know, you were talking a moment ago about cognitive science. But you know, as Bill points out, there are deep cultural differences, deeply entrenched cultural differences in the country, that have polarized us and, you know, this debate right now over whether one should get vaccinated or not has become part of that culture war, hasn't it? James O'dea It's certainly true. But I think at this stage, you know, we're at a time where leaders have an opportunity to engage. I've been deeply heartened, actually, by many of the very individual conversations that I've had with people where I've entered with a genuine sense of, I just really want to understand what's leading to this, your hesitancy to become vaccinated. And I've ha d many people look at me and say, you know, "do you really want to know what I have to say about this?" And we've engaged in very, very heartfelt conversations. I've had many persons, black Americans and nursing professionals that I work with closely, who have echoed things that happened in the Tuskegee experiments, back in the 1930s and 40s, which, parenthetically, those experiments, which were the most awful, heinous things, went on until 1972. So this is not ancient history when this was happening. And my experience is that when you genuinely get into a conversation, and really explore what is leading a person to, at this point, choose to be hesitant to become vaccinated. I've been very impressed by how many people when really, genuinely understood, have actually said, "Can you tell me a little bit more about your perspective on this?" I think that's a way forward that we need to do much more on. Anand Naidoo Peter, getting back to the Variants that we were talking about, is there a risk that unvaccinated people could become incubators for even more virulent Variants, if they you know, if they continue to refuse to get vaccinated? Peter Chin-Hong Well Anand, the maxim goes, every two weeks there's a new variant being created, but only some of them rise to the ranks of the Rogue Gallery of Variants. So the more transmission events you have, the virus is not precise enough to make an exact copy of itself every time. So yes, transmission occurs with wild abandon in the
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unvaccinated group, proportionally speaking. So that group is going to be the incubator for new Variants. Anand Naidoo Rafael, it would appear that one of the big problems that this administration is facing right now is the huge amount of disinformation that is floating around, especially on social media. Is the White House making any kinds of efforts to approach the big social media companies, companies like Twitter and Facebook, to try and control and regulate this disinformation that's getting around? Rafael Bernal There is regular communication, just like with other large industries, but I think it's pretty clear that there's not enough. There exist bad actors locally, nationally, and internationally, who are trying to disseminate more misinformation. Plus there is mis- and disinformation that is created sort of organically, if you will, not with the purpose of damaging, but it is damaging. So you have an ecosystem of bad information, two ecosystems of bad information, and certainly the government is not doing enough to stop it. Again, it's a matter of creativity. There's no game plan on how to stop misinformation in the internet age, because the internet age is still relatively young. But you know, that is part of the role of government, to invent those techniques. Rafael Bernal The big question that this entire panel leaves me is, I don't know who is the appropriate vector to give out correct information to different groups. From, you know, African Americans who are reluctant for historical reasons to people who are reluctant for political reasons. You know, I really don't know if that answer exists at this point. Anand Naidoo All right, let me put that question very quickly to Dr. Haseltine. Bill, I've only got about 60 seconds left, but should there be one central authority that determines what's right and what's wrong? Dr. William Haseltine You know, that's a very profound question. It's not so much a matter of determining what's right and what's wrong, but rather: does a government have central authority to stem a crisis, such as this? It seems to me that a lesson that we can all draw from this is that our public health services are in dire need of restructuring. Now, 2362
the problem with that is if we had a central government with power over states, and Trump was the president, we would be in even worse shape than we are today. So there is a very strong argument that says, decentralization under a bad leader is much better than centralization, even if sometimes you get a good leader. And it's a debate that we have to engage in, and we have to understand. And it depends on people, not just central politics, to make sure that we put this epidemic behind us. People have to care for each other as they want others to care for them. Anand Naidoo Okay, and that's where we have to leave it. Thanks to all of you for being with us. That is it for this edition of 'The Heat.' I'm Anand Naidoo, live from Washington, DC. Thanks for watching. This panel originally appeared on CGTN TV’s ‘The Heat’, and can be watched online here: The Heat: 40 million COVID-19 cases in the U.S.
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“The Power of Science” // Interview with Neal Howard Health Professional Radio | September 14, 2021 | Interview
Returning guest, Dr. William Haseltine, President, Access Health International, discusses his latest book “Science as a Superpower: My Lifelong Fight Against Disease and the Heroes who Made it Possible” (June 2021). Dr. William A. Haseltine has dedicated his life to healing as many people as possible through science. He was a professor at Harvard Medical School where he developed and helped find cures for diseases such as cancer and HIV/AIDS. He led the team that pioneered the development of new drugs based on information from the human genome and created more than a dozen biotechnology companies and influenced public policy at the highest levels. He’s built two foundations, one to foster collaboration between the arts and science, and another—ACCESS Health International— to advise governments worldwide on how to bring high-quality, affordable healthcare to all. In 2001, TIME Magazine named him one of the “25 Most Influential Global Business Executives” and in 2015, Scientific American named him one of the 100 most influential leaders in biotechnology. TRANSCRIPT: Neal Howard Hello, and welcome to Health Professional Radio. I'm your host, Neal Howard. Thank you so much for joining us for another segment. In this segment, we're going to be speaking with returning guest, Dr. William Haseltine. He's joining us here as president of ACCESS Health International to talk about his latest book, Science As a Superpower: My Lifelong Fight Against Disease and the Heroes Who Made It Possible. Published June of this year, as a matter of fact. Welcome back, Bill. How are you? William Haseltine I'm very well Neal, thank you. Neal Howard 2364
Well, for those who may not recognize you, as a contributor, give us a bit of your professional background. Tell us a little bit about who you are and what it is that you do. William Haseltine I'm a scientist; I was trained as a chemist, a biophysicist, and a molecular biologist. I've had a career in academia at Harvard, where I helped create two departments --cancer pharmacology and human retrovirology-- to work on HIV/AIDS. I was a professor for 20 years, taught a lot of brilliant students and trained many scientists myself. I then had a career in biotechnology. At this point, I've started 12 biotech companies, the most well known of those is called Human Genome Sciences. All the companies together have brought about eight drugs to the market. For the last 15 years, I've been working on improving health systems around the world, trying to make sure that everybody has access to high quality, affordable medical care. Neal Howard You've dedicated your life to healing as many folks as possible through science. Now, your brand new book, Science as a Superpower, what prompted you to write this book? It reads as a children's book. William Haseltine It's intended for young people, seven to 15 years old. It's a compliment to a book I wrote for older people, a somewhat official autobiography, called my lifelong fight against disease. But the reason is to give back some of what was given to me. I've been fortunate to have wonderful mentors from the time I was quite young all the way through my professional career, and the ones that were most important to me are the ones that encouraged me to take up a life in science and in medicine. I'm very happy I did, I've had a great life. Science and medicine and medical science, it's a wonderful career for young people. And I thought I'd give back a little by trying to encourage the younger generation to take up what can be a really wonderful, exciting career and life. Neal Howard Talking about the younger generation, very impressionable minds-- seven years old to 15. If that age group has been watching the news and social media in any capacity, then science could quite possibly not be viewed as a superhero at all. There's lots of misinformation, lots of unscientific information out there. 2365
William Haseltine Well, I would hope the kids would have a different take. When I call it a superpower, I mean that one person can save the world. One scientist who's made the right discovery could save hundreds of millions of lives. And that's a superpower. How many other careers can you think of where one person, through their own mind and their own discoveries, can save the world? It's what superpowers are meant to do, save us all. And let's just take a look at who created one of the most effective vaccines of all time. A young woman, Kizzmekia Corbett, who was working in the National Institutes of Health, got the information from the Chinese about the genome of the SARS-CoV-2 virus, and over a weekend, created what is the Moderna vaccine. That, and a very similar vaccine, will save hundreds of millions of lives. Young woman, working over a weekend, having trained her whole life to do this kind of work. She's the kind of superhero I have in mind. Neal Howard Absolutely. You know, you mentioned that going into medicine, science research is a great career for young people to pursue. What does it take to pursue that type of career? You've been in for quite a while, what do you have to be made of? William Haseltine Well, you know, I don't think you have to be anything really special. Everybody thinks you have to be a genius to be a scientist. I'm not a genius and I've done really well. I'm smart, but then, you know, there are a lot of smart people. And what it really takes is drive and desire. You really have to have a desire and the drive to do something unusual. I always wanted to heal people, you know. When I was a kid, I thought it was really unfair that people get sick. I was subjected to the same thing kids today are, for example, with restrictions over polio. I couldn't go out with my friends, I couldn't go to movie theaters, all these things I couldn't do. Fortunately, the discovery of the polio vaccine, by a man I later came to know, Jonas Salk, changed all of that. So here's another example of one person, changing the world, changing my own personal life. And even earlier, my mom tells me I was about to die of pneumonia when I was four months old, and I was one of the very first American civilians to get penicillin. That saved my life. And that was Alexander 2366
Fleming, who made an observation that penicillin, bread mold, made something that kills bacteria. That subsequently has helped save hundreds of millions of lives, including my own. So it takes the desire to do good. It takes curiosity. But you know, how many kids have a desire to do good, and curiosity? What's important is to open the doors for them, to create pathways. Every step along my education and my young career, people just opened the doors. Sputnik had flown up, people wanted scientists. Today, with COVID, people want scientists. There's money flowing into science, like never before. When I was a graduate student, people paved my way. When I was a young scientist, there were new grants available. So, all the doors were opened. It's older people's job to open the doors for younger people. But the younger people have to walk through it, and they want curiosity, drive and desire to do good. Neal Howard Talking to the younger generation about these vaccines, about science, as far as convincing young people to do or not do something your book doesn't politicize or anything like that in any shape, form or fashion. It simply lays out the argument that science changes the world. William Haseltine Well it's also a career that's open to anybody who wants to be part of it. You know, when I was a young scientist, almost all the people in science were young men. Today, the majority are young women. More young women are in science than young men. When I was a young guy, it was almost all white guys, today it's people from all over the world: Hispanic, Asian, Black, women and men. It's just, the whole world has transformed. I think it's a very positive thing. It's a career that judges you on what you do, not who you are. Neal Howard Do you think that your book will combat some of the misinformation that's out there that some of our young people are seeing on television and on social media? William Haseltine You know, combating misinformation is a huge task. I don't know if this book will do it. But what I hope this book can offer to many young people is a lifeline. If they're feeling like they're lost, they need to do something, and not doing so well. Buckle down and 2367
open your eyes. Look at what science can do. You know, I almost failed fourth grade. I had a lot of problems in my family, I was really depressed, almost failing. And when I started fifth grade, I started to read and I realized that there was a whole other world for me. And it just kept opening up and getting better and better. So science is a lifeline for kids in trouble as well, it can pull them right out and open a wonderful path for the future. My own life has gone through academia, business, philanthropy. I've met people all over the world, from all walks of life. You know, my scientific grandchildren are making big discoveries about COVID and I'm in touch with them. It's a life that just keeps on giving. My real grandchildren are too young to do that; I'm hopeful, I keep nudging them that direction. But my scientific grandchildren are doing spectacularly well. It's just so wonderful to see. And the great thing about it is, I'm in touch with them. And we share ideas. They give me ideas and I give them ideas, it's a wonderful exchange. Neal Howard Science As a Superpower: My Lifelong Fight Against Disease and the Heroes Who Made It Possible. Give us a website where we can learn more about you and get some information about the book as well. William Haseltine williamhaseltine.com Neal Howard Bill, always a pleasure, and I'm hoping that you'll come back and speak with us again in the future. William Haseltine Neal, I'll be happy to do so anytime! Neal Howard You've been listening to health professional radio. I'm your host Neal Howard in conversation with returning guest Dr. William Haseltine. Audio copies of this program are available at hpr.fm and healthprofessionalradio.com.au. You can also subscribe to the podcast on iTunes. Listen and download at SoundCloud. And be sure to subscribe to our youtube channel at youtube.com/healthprofessionalradio. This interview originally appeared on Health Professional Radio, and can be listened to online here: “The Power of Science”
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COVID-19: Finding A Way Forward
Center for the National Interest | September 24, 2021 | Interview
The Covid-19 crisis remains the most acute issue confronting the Biden administration. After an initial flush of enthusiasm that the virus had been defeated, President Biden has grappled uneasily with the delta variant and is now issuing what amounts to a vaccine mandate. How should America proceed? Will a mandate work? Should booster shots be recommended not simply for those 65-years and older but also for the general population? To assess these and other questions, the Center for the National Interest convened a distinguished panel of experts for a probing discussion on September 24, 2021. • William Haseltine has educated a generation of doctors at Harvard Medical School, designed the strategy to develop the first treatment for HIV/AIDS, is well known for his groundbreaking work on cancer, and led the team that pioneered the development of new drugs based on information from the human genome. Dr. Haseltine’s relentless focus on delivering world-changing results led TIME magazine to name him one of the “25 Most Influential Global Business Executives.” He is the author of more than two hundred peer-reviewed manuscripts and eleven books, including two books on COVID: A Family Guide to Covid and A Covid Back to School Guide. His most recent book, My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19, was published in October 2020. He is currently chair and president of the global health think tank ACCESS Health International. • Kavita Patel is a Nonresident Fellow at the Brookings Institution and a practicing primary care physician. Previously, she was the managing director of clinical transformation at the Center for Health Policy at Brookings. She is the author of a recent op-ed in the Washington Post criticizing the Biden administration for the confusion 2369
surrounding booster shots. Dr. Patel is an advisor to the Bipartisan Policy Center and a member of Health and Human Services Physician Focused Payment Model Technical Advisory Committee. She also served in the Obama administration as director of policy for the Office of Intergovernmental Affairs and Public Engagement in the White House. As a senior aide to Valerie Jarrett, President Obama’s senior adviser, she played a critical role in policy development and evaluation of policy initiatives connected to health reform, financial regulatory reform, and economic recovery issues. She currently advises healthcare technology and services organizations through New Enterprise Associates. Jacob Heilbrunn, editor of the National Interest magazine, moderated the discussion. Watch the full discussion here:
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COVID-19: Finding a Way Forward: Houston Doctor “Optimistic” COVID-19 Vaccines For Young Children Could Be Approved Before Halloween NPR Houston | September 28, 2021 | Interview
We're another step closer to COVID-19 vaccines for young children. Pfizer and BioNTech have submitted data to the FDA that shows "robust" antibody response and "favorable" safety outcomes in their clinical trials for kids ages 5 to 11. They plan to submit a formal request for emergency-use authorization in coming weeks. If that all plays out and approval is granted, this would be huge news to parents and schools, eager to protect children from the spread of COVID. The timing could come well before the holiday season, with more families hoping to gather and reunite. Today, medical experts are here to discuss what we know so far about vaccines, as well as boosters, in the continued fight against COVID — which has now killed more than 690,000 people in the US. Guests: Dr. William Haseltine • Chair and President of the global think tank ACCESS Health International • Founder of more than a dozen bio-technology companies • His latest book is Covid Related Post Traumatic Stress Disorder (CV-PTSD): What It Is and What To Do About It. Dr. Anthony R. Flores • Chief of Pediatric Infectious Diseases at UTHealth Houston Dr. Katelyn Jetelina • Assistant Professor at UTHealth School of Public Health 2371
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Author of “Your Local Epidemiologist,” a newsletter and Facebook blog that has gone viral since the pandemic TRANSCRIPT: Ernie Manouse We're another step closer to COVID-19 vaccines for young children. Pfizer has submitted data to the FDA that shows robust antibody response and favorable safety outcomes in their clinical trials to kids ages five to 11. But they have not yet formally requested emergency use authorization. But when they do, and approval is granted, this would be huge news to parents in schools eager to protect children from the spread of COVID-19. The timing could come before the holidays and, with many families hoping to gather and reunite, that would be welcome news. Today, medical experts are here to discuss what we know so far about the vaccines as well as understanding all the current discussions about boosters at the FDA and the CDC. All this as COVID has now killed more than 690,000 people in the US alone. Our phone lines are open, call us. Ernie Manouse Hello, I'm Ernie Manouse and this is Town Square. Today we catch up on the latest on COVID. From boosters to vaccines and other headlines. Our phone lines are open for your questions, concerns, comments, it's 888-486-9677. That's 8884 Town Square. But joining me right now is Dr. William Haseltine. He's the chair and president of global Think Tank. ACCESS Health International is the founder of more than a dozen biotechnology companies. His latest book is COVID-related Post Traumatic Stress Disorder, CVPTSD: What It Is and What to Do About It. Welcome back to the program, Dr. Haseltine. William Haseltine It's a pleasure to be with you again Ernie. Ernie Manouse Hello! You know, when we were talking about all of this last week your name popped to the front of our list as somebody who could help us understand all of what's going on, because I'm sure you have faced this before in your career. When it comes to booster shots, the decision whether or not we should get them had to be vetted by the FDA and the CDC. It started with the FDA, who met in a very public hearing, listened to questions, statements about it and came up with a recommendation. Then the CDC did the same 2372
thing and came up with a slightly different decision on it, and then the head of the CDC said something that seemed counter to exactly what their panel had said. Can you help me understand the process of what happens during this period, and what we are trying to get to? And how do we have faith and where we've landed on this? William Haseltine Well, let me pick it from a slightly different angle. Okay, what makes sense for most people to do? To me, it's absolutely crystal clear that if it has been five months or longer since your last vaccine, you should do everything possible to get a booster. No matter what your age, no matter who you are. So, boosters are necessary. In fact, the more I look at it, the more it looks like this is actually a three dose vaccine. Like many vaccines, the one for human papilloma virus, and I could list a lot of others, people seem to react better if you first prime then boost and then boost a third time, sometimes even a fourth time. But the data is absolutely crystal clear. Let's just put it on a scale of one to 100. First boost gets you to, say, one, the second boost gets you to 10, the third boost gets you to 100. That's a lot of protection! That's in terms of the concentration of antibodies that you make against the virus. Now what's important is the higher those concentrations, not only the more protected you are, but also the longer you're protected, and the broader the protection. You want that third booster. For those of you who have gotten the j&j vaccine, get an mRNA booster. So really, that is simple no matter who you are. By the way, there's a number of people at the NIH who agree with me. Not everybody agrees. But that is clearly my reading of the situation. Ernie Manouse Let me hold you right here though, and say, what you said is crystal clear and makes perfect sense. Why then does the FDA meet, and they come up with one set of recommendations and how did they get to where they got? Well, just stop right there first. William Haseltine There are two things that I would say. First, not all of the data is in-- and my reading of it is based on the data that I've seen. But also, I would say err on the side of precaution. Because we don't have all of the data yet, we've got to be cautious and do what seems to be best. The data that I've seen suggests we need a third shot. 2373
However, not all of the data the FDA normally would want to make that decision is in yet, particularly safety data for younger people. There is an issue of myocarditis in young men, they don't know how serious that is and they would like to have more data. So, they're in the job of being more cautious, and limiting possible downsides. My view is it is very important that you've got to protect yourself from this virus. And the risk of myocarditis is far less than the risk of what will happen to you if you get infected no matter what your age. Ernie Manouse But they don't come to this conclusion. I guess what I'm trying to get at is, is it politically motivated? Is it concern regarding limit of vaccine supply, and they're so concerned that everyone gets their initial doses? But we know they're throwing away vast quantities of the vaccine because it's going unused. So why can't the FDA come to a position that endorses it for everyone? Instead they come back with "comorbidities and over a certain age", and then they kind of stop there. And then the CDC looks at it, and they're slightly broader, but then the head of the CDC comes out with an even broader attempt? What is going on there, and why are these three different positions coming up? William Haseltine Well, in my view none of them are coming out with a broad enough definition. In my view, everybody over the age of 12 should be eligible for a booster. I think that's what I would recommend if I were them. I've written about it, I've written that this is the decision that they're likely to regret. But you really don't know that until we have more time. Ernie Manouse And by those you're talking about the CDC and the FDA, right? William Haseltine It's very understandable to me why an agency, which has both efficacy and safety in mind, might err on the side of safety. I think it was a mistake. It's not one I would have made. it's not what everyone recommended, but it is the decision they made. I think you're going to see over time, and hopefully relatively soon, the recommendation moving more toward the position I've stated. But this is my recommendation to all of my friends who have asked me: get the booster if you're over 12. 2374
Ernie Manouse Okay, then help me understand. Today Pfizer-BioNtech forwarded their documentation upward, but did not ask for emergency use authorization (EUA). Why doesn't that come forward with the data? What are they waiting for? William Haseltine Well, that's a strategic decision on their part. And I don't want to second guess them. I would only suggest that there's been a lot of pushback on the EUA process by people who are vaccine skeptics, saying "I don't want the vaccine because it's only been approved for emergency use." Maybe Pfizer-BioNtech think, at this point, they have a good chance of getting it fully approved, and that will make it more acceptable to some of the people who are vaccine skeptics. That's a guess, it's just a wild guess. Not based on what I know, Ernie Manouse From where you sit right now, and from what you know and what you're seeing, globally, who is doing the best job with this? And what are they putting in place that's making them have success against COVID? William Haseltine Well, you know, the first thing to say is vaccines are the sine qua non: without that, nothing. You need the vaccines and you need to keep a very high level of immunity, which is what the booster does for you. Over time, immunity wanes and you can get reinfected, you can get sick. We don't know yet how sick you can get. Maybe you get just a little sick, or you get very sick and some people die. So in fact, some people have died even though they've been doubly vaccinated-- a tiny fraction of people. But that fraction may grow. You know, the protection that the vaccines offer, any vaccine, is contingent. It's contingent upon when you had your last vaccine, it's contingent upon the variants that exist, and it's contingent on who you are. If you have an immune deficiency, if you're over 75 or 65. It's all contingent. But the biggest contingency most people have to worry about is time. Over time protection wanes. How much is protection is going to fall away? Clearly protection against infection wanes, protection against transmission waves. Will it wane against serious disease and death? We don't know that yet. So, I would again err on the side of caution. Since we don't know, keep everybody's immunity high. That's what 2375
we do for flu with our shots every year, we err on the side of caution. Maybe there's going to be a really nasty flu, let's protect people from dying, let's keep their antibodies high and not only rely on immunologic memory. I didn't answer your question, "who's doing best?", and the reason I start that way to that question, is that the best isn't only vaccines. Let's take Israel, Iceland, and Singapore, three countries that have vaccinated, you know, 85% or more of their population-Israel is a little lower than that. Once they released all of their mitigation efforts, infection rates shot sky high in all three countries. Now, does infection mean hospitalizations? So far there's a difference in different countries. In Israel hospitalization has gone way up, whereas in Iceland and Singapore it didn't go up so much. But, you've got to do more than just vaccines. When a virus like Delta is around, it will penetrate those vaccines at some point, and you've got to be willing to keep reasonable mitigation measures in place. And eventually, and very soon I think, we're going to be able to add a third arrow to our quiver, which will be prophylactic treatments. Right now, people have got a shot --an immunoglobulin shot, a monoclonal antibody shot-- that may protect you for up to a few months, if you've been exposed. I think in the next six months or sooner, we'll have a pill to pop if we've been exposed. And I think vaccines, popping a pill against variants that the vaccines don't protect against very well, and reasonable mitigation measures, like wearing masks in crowded places, may be a recipe for success. Ernie Manouse I read somewhere that by fall, maybe winter of next year, life could be back to normal, if we follow what's being recommended to us, are you that hopeful? William Haseltine You know, I wouldn't say normal. But I'm very hopeful that with a combination, and I've written about this called "multimodal COVID control," with a combination of strategies, which include vaccines, prophylactic drugs, testing, contact tracing, and isolation or prophylactic drugs, and mitigation measures during peak periods of concern, including worrying about what you might get in a crowd wearing masks, like they do in Asia for every flu season, we can get back to normal economic life. We won't be throwing people out of their jobs. We can get back to a close-to-normal social life. 2376
You know, people have called this the forever virus, and I think they're right. It's like the flu, it's a forever virus. It's around, we live with it. If we're diligent, we take our shot every year. What we should be doing is a little more than that, we should be wearing masks during flu season, but we haven't, but in Asia they do. So I think there's a number of things we can learn over time, maybe slowly, maybe more slowly than we should, that can get us back on track to something very closely resembling what we remember, but never quite the same. Ernie Manouse Dr. Haseltine, thank you very much for joining us. I always sit enraptured by what you're saying and take in as much as I can. Thank you for joining us. William Haseltine You're welcome. It's a pleasure, Ernie. Anytime. Ernie Manouse Thank you. Dr. William Haseltine is the chair and president of the global Think Tank ACCESS Health International. He's the founder of more than a dozen biotechnology companies, and his latest book isCOVID-related Post Traumatic Stress Disorder, CVPTSD: What it is and What to do about it. Up next, we've got our doctors on the line waiting to answer your calls about all the vaccines, the booster shots and so much more. Give us a call at 888486-9677. That's 8884 townsquare. I'm Ernie manouse. We'll be right back.
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Covid PTSD - It’s vital we can all receive support for both the individual adversity and communal stress of Covid-19 with Dr William Haseltine “Mental” podcast | September 29, 2021 | Interview
We’re joined by pioneering scientist Dr William Haseltine to discuss the mental health impact of the pandemic and how to make sure those of us who need additional support do receive it. Here we go! Mental is the brain-child of Bobby Temps, who lives and thrives while managing his own mental health. Each Thursday we delve into a factor or condition that affects the mind and how to better manage it. Find Dr Haseltine’s book HERE TRANSCRIPT: Bobby Temps To give you some more background on our guest: Dr. Haseltine, is well known for his pioneering work on cancer, HIV and AIDS, and genomics, and has been making regular appearances throughout this whole period on channels like MSNBC, CNN, Bloomberg, here in the UK on the BBC, and so many other news outlets, giving his perspective as someone that has been very involved in the science around tracking the pandemic. So with that all said, we hope you find this episode as fascinating as we did. We'll be back in a moment with Dr. William Haseltine. Dr. William Haseltine Hello, I'm Bill Haseltine, speaking to you from Connecticut this morning. The first thing I've been asked to talk about is, what has been my first contact with issues of mental health? I have to say it started, unfortunately, very early on. My family has the unfortunate affliction of bipolar disorder. Now I've been lucky, I've been spared. But many members of my immediate family and more distant family have not been so lucky. And I've lived with the consequences of people very close to me suffering from bipolar disorder, both treated 2378
and untreated. And that has sensitized me to the whole idea of mental health. As I say, from a very young age. It's one of the reasons I decided to take up a career in health. At first I thought I'd be a psychiatrist. I'm now not a psychiatrist. I've been a scientist, businessman, philanthropist, a lot of other things. But I've always been interested in mental health from a very, very young age. Let me say something about mental health that I think most people who haven't had the kind of experience I've had don't quite realize, and that is, when we encounter somebody with a serious mental health issue, our first tendency is to try to squeeze them back into what's normal. And unless you experience it, and you really live with it, and you understand it, it's very hard to know what it is you're witnessing, what it is you're seeing, how to relate to it, and how to get help. One of the reasons I wrote COVID-Related Post Traumatic Stress Disorder is because our whole societies under stress, are all undergoing mental stress, some of us will have pre existing conditions, which are exacerbated by the stress of COVID. Some people will experience it really for the first time. We're undergoing a global stress of an extraordinary nature, and it is manifest. That's why I wrote the book, "what it is, what we can do about it." Bobby Temps And I just want to draw back a little bit to those early experiences you shared around mental illness in family members. Was that something that was openly discussed at the time? What level of understanding did you have at that point? Dr. William Haseltine Well it sort of gradually as I grew up, you know, going from a three, four, five year old, six year old, seven year old, I was so stressed as a young kid, people thought I was stupid. In fact, I behaved functionally stupid. I can tell you what stupid feels like, it feels like you don't understand what's happening around you. People will tell you to do something and you won't understand what they've said. And so I barely passed through third and fourth grade, I almost most flunked, I almost didn't get to fifth grade. But in fifth grade, I discovered I can read and I sort of escaped. So I was under such pressure. But you asked me very specifically, when did I realize the kind of pressure I was under. I think I was probably in my junior high, that's about 11 to 13/14 years old, when 2379
it became inescapably clear when people close to me would be institutionalized. That's what it was about. Then as I was in high school, and during high school, it was very openly discussed: what the role of psychiatrists were, what the role of mental institutions were. So it was inescapable, and it was part of a very open discussion. Later I came to understand it was, you know, an issue not only in my family, but of families that were related to us. And up to 1/3 to one half of all those members of the family had the same kind of issues. Now bipolar is interesting because sometimes they're either catatonic, they're so depressed that they can't speak, and sometimes they are hyper. And there's all sorts of continuums in between. The thing that people don't really understand is how fast that can change-- from depressed to hyper. It doesn't affect everybody exactly the same way either. Even in the same family, there are many differences in the way it manifests. And so that became very clear to me and, you know, when you deal with it firsthand, it's sort of a day to day battle. Not my own personal battle, but a battle for people that are very close to me. And it's something that just never lets up, it's there every minute of every day. Bobby Temps Right, and it can lead to, I would imagine, a lot of turbulence in your young life? Dr. William Haseltine Well, the worst thing that happens is suicides. And when that happens close to you, it's a life changing event. Untreated, it's a it's a very serious affliction, a very serious disease. The problem is that people don't recognize it as a disease because it's not physical. I actually explored that very carefully when I tried to understand that. I worked in a state mental hospital, I volunteered as a graduate student at Harvard in a state mental hospital. And I took a while to try to understand that, that mental illness is a disease as serious as cancer or any other disease that can be lethal if it's not recognized and treated. Bobby Temps Right, well absolutely. And that's why we make sure to talk about that week to week and have our particular focus on stigma, because so much of that comes from people not understanding those differences, because so often, we react badly to what's different. So I took you back there a little bit to those earlier experiences, and now 2380
we'll move back to where you were talking about COVID-PTSD, and what you've seen as someone who's followed the COVID pandemic very closely, and being someone that's been an authority called on by all kinds of media outlets, including here in the UK. And so what have you seen throughout the pandemic, in terms of potential symptoms that would necessitate a new diagnosis of PTSD? Dr. William Haseltine First of all, let's talk about Post Traumatic Stress Disorder. Until about 1980, people didn't even want to recognize it. It just wasn't recognized as a treatable disorder. So people called it "shell shock", "battle fatigue", "malingering", and they would sometimes execute people because they thought they were shirking their duty in a time of war. So it was very late that we recognized that one of the costs, and it was really the Vietnam War in America that did it for our country, becuase there were so many people who had experienced traumatic experiences --witnesses to war crimes committed, the killing of innocent people, they saw all sorts of horrible things-- and they came back, and they were really disturbed. It manifested as anxiety. That's one of the first things, they are really anxious. You know, I have a brother who was in the Iraqi war, he was a senior intelligence officer, he was living with me for six years between marriages. We lived together and I actually watched what happened to him. He was about as put together a guy you could get. He was very brilliant, doing work at a very high level. You know, whatever grades they have, he was like a very senior, multi-star general and equivalent. But when we were driving around Washington, I was living in Washington at the time, there would be a noise and he would duck! He was so traumatized. He had a really serious kind of breakdown as a result of that. So I had watched that happen firsthand with that war. But then when I was thinking about COVID, and watching COVID, you know, I had a ringside seat to COVID from very early on. I was in Wuhan in November of 2019. I was there, because I'm the head of the US China health Summit, we held our meeting there. I came back with a dreadful cold but I don't think it was COVID, because I tested negative. But I can tell you, I have lots of friends in Wuhan, a lot of people work for my office in China, and so I was witnessing things firsthand.
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In January of 2020 one of our employees lost three grandparents to COVID in three weeks. So I could see the impact, right there. I remember talking to him about his uncles, who were standing in line for hours, 18 hours to get tested, and they got COVID standing in line, okay. When the whole place shut down, it was dramatic. And I saw the power of this pandemic, from the very first moment, that means the last week of December, the early weeks of January. At first I told my friend, like many people, we try to dismiss things. I said it's just like the flu. He said, "Bill, this is not the flu, get that out of your mind. This is not the flu, this is deadly serious. What's going on is not the flu." And that, you know, had me look at it much more closely. And I followed ever since. But let me talk about trauma in a couple of ways. Trauma is something happening to you, and there are terrible things that happen to people: you lose people close to you, you yourself may get sick and barely survive, or your husband or your wife or your child may be intubated, and you can't even see them as they go through their extremities and die. That's traumatic. So there is direct experience that happens to you. When you see trauma all around you, that's traumatic too. But there's a special kind of trauma I've written about. It's called "moral injury". People in this epidemic have been morally injured. Now normally that's confined to soldiers who are ordered to do something horrible. But it also happens when you see people in authority doing things they shouldn't do. And we, throughout the pandemic in many, many countries, also suffer moral injury. And doctors and nurses suffer moral injury. They know they're not given the equipment that they need to protect themselves and to treat their patients. We know, especially in America, that our government denied what was going on, minimized the pandemic. So there's a moral injury, which is part of this definition of COVID related posttraumatic stress disorder, which is part of what's gone on in all wars. You know, I've done research now on moral injury and it goes right back to the Greeks, and certainly earlier. People recognize that in times of war people are called on to do things which are morally repugnant in any other circumstance. But even in that situation, there are things you should not do. Bobby Temps
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I just want to pause on that actually, around moral injury. In particular, I think what has been so difficult for many people to wrap their head around is the newness of this danger. Whilst there can be many similarities with other viruses in the past, the majority of us have never lived through something like this. And so there was a necessary amount of encouraging fear so that people would take this seriously and abide by the health guidance and the restrictions put in place. But does then add to that in a way that people have this moral quandary of being encouraged to look out for others, because of the risk that they could harm them by passing on this virus? And then that becomes like an additional mental load of, "Could I have harmed anybody and not know about it?" Dr. William Haseltine Let me make it very specific for the UK and the US. You will recall, there was a time when your government talked about herd immunity, and that's what we should get to so we should just let this virus roll. That is seriously morally unjustified! It's really saying we're going to let x millions of people die and not do anything about it; that's murder. That's knowledgeable, they know they should do something, they choose not to do it. That is a good definition of, if not first degree murder, then some kind of homicide, or manslaughter. It is killing your fellow humans through inaction, and that is horrible to witness. We don't talk about that trauma. We don't talk about the trauma that people are having right now, with people putting their fist in each other's face over masks, and somebody's screaming at you. Or the kid I saw on television the other day who was talking about losing his grandparents to COVID and he was being ridiculed and jeered at by parents in the school. That's a moral trauma for that kid. And it should be a moral drama for anybody who sees. So in this particular COVID, there is real trauma that we experience, and there is moral trauma, and there is societal trauma. And what are the symptoms? Anxiety, and you measure it off the charts in most countries. There is depression, off the charts in most countries. There is inner family violence, which is higher than it has been. There's suicidal ideation and suicide. Now it's interesting, suicides have not gone up so much. In this particular case there is a lot of suicidal ideation, but it's not really gotten to that. But all of the other disturbances, drug abuse has skyrocketed, whether it's 2383
alcohol or opiates, or other kinds of drug abuse. And it's affected a group of people which are normally buffered, which are children. When you look at the numbers for children who are expressing various symptoms of post traumatic stress disorder --anxiety, depression, and then acting out-- it's affected a very large group of people. And now that they are going back to school, they've got to cope with it. So the first part is, I think, and I'm glad we're speaking about this, is to get the message out that this is a societal mental health problem, that this isn't normal. We're going through a stress that is not normal, and there are going to be serious reactions. And the first thing to do is to diagnose that something's going on. And that hopefully leads to some action to do something about it Bobby Temps For sure, and very much a similarity, I think, in how healthcare works both in this country and in the states is, because we lead with a diagnostics model, you in most cases need a diagnosis in order to access treatment. And so what elements do you see that are distinctive to what could be COVID PTSD, beyond what PTSD currently encompasses? Dr. William Haseltine Well, as you have properly said, in order to be treated, and in this country to get paid for treatment, because that's a bigger issue in the United States-- if there's no diagnostic code, there's no payment. So what will qualify? Well, if somebody comes in and they're anxious and so and so forth, if that person hasn't been in a terrible car accident, if that person hasn't been in a war, you might not be able to write down that code. And even then, somebody may question it for payment, because insurance companies in the US are always questioning, "is that really justifiable code?" And you can see why, because they have to pay. Whether there are people close to you dying, whether you're just hypersensitive to the trauma that's around you, whether you are just completely horrified by the inaction of your government, those should all qualify for a diagnostic inclusion in post-traumatic stress disorder. Now, there's another problem with calling this post traumatic stress disorder, because we're not out of the stress, we're in the middle of the stress. So "post" should be in quotation marks. We are under stress right now. You know, in the United States we have more people overflowing our hospitals in the south than we ever 2384
had before. We're going into something called "crisis standards of care". That's happening right now, "crisis standards of care". And I written about it before, during the last epidemic where we were turning away patients. Right now, I was just reading in Utah, no elective surgeries. None, canceled! That is not good. Or maybe I got it wrong, maybe it's Colorado, but one of those states has now canceled all elective surgeries. Pretty soon, they're going to have to cancel other surgeries, too, because there's just no more room at the hospital. That is a real crisis that those healthcare workers are going through. There's a wonderful book that was written by a British nurse about moral trauma, about what she's gone through, about being asked to go to the frontlines again and again and again without the proper support. So part of this book is a call for what to do about it, how to treat it. In hospitals, make sure our health care workers who are out there getting traumatized every day at least have the support and the extra personnel, and they have some time off to cool down. You can't go through trauma every single day, like these healthcare workers are doing, and not have tremendous consequences. Same now with our kids. We're sending our kids back to school, and there's going to be a lot of behavioral issues. Some that are already showing up. The staff is either not prepared or schools don't have extra staff to take care of it. We need extra support for our teachers and our school administrators, they can't handle it all. There's going to be a lot of issues with kids. Some are going to be totally withdrawn, and some are going to be at the extreme opposite and totally aggressive. And already there are reports that there are more kids like that than there were before. Not every kid in the world is happy to go back to school, some are really traumatized, and some are absolutely terrified to go back to school. And you can understand if they've been kept aside why that is. So there's so many issues, that if we recognize what's going on, we should begin to do something about it. Bobby Temps Absolutely. And am I right in understanding then that your pitch for this will be to broaden the diagnostic capabilities of PTSD currently? Or would it be to have a separate diagnosis specifically for COVID PTSD? Dr. William Haseltine 2385
It's much easier to broaden the current definition than to get something new. So I would like included in the entry criteria for consideration, the current experience that many people are going through: Did you have COVID yourself? Did you have people close to your family who had COVID? What is your attitude towards protective measures? Let's also take the other side of this. There are COVID deniers, and there are people who don't think they should take the vaccine. And they can be equally traumatized by people who are forcing them to do things they don't think they should be doing. Now, I think what we have to do is take a much broader and more sympathetic attitude, not from a societal point of view, but from a medical point of view. Because they may be just as concerned about action as some people are about inaction. And when it comes to mental health, you can't discriminate on the basis of what their political beliefs might be, you have to treat them for the disease that they've got. I think there are many people in that part of society, which truly believe this is a conspiracy. They truly believe there's evil planned and going to be done to them. That's going to create trauma on that side. We have to be sympathetic, not to their point of view, but to them as a human being in trouble. Bobby Temps Right. I think that's very important and you've talked about certain groupings in society and how their experiences differ. So would you see, potentially, if it was a young child or a young person, a health care worker, someone in the general population and adult, would you see different elements of diagnose ability to match those different groups? Dr. William Haseltine That's a complicated question and my expertise doesn't go deep enough to answer that question. But you know, you asked about personal experience, I lived through polio. I didn't get it myself but I was a kid that had many of the same restrictions that our children are now experiencing. You can't have more than two friends over at a time, you can't go to the swimming pool in the hot summer, you can't go to a movie theater, you can't be in crowds. There's something out there coming to get you. And as a kid, I can remember, and remember I was kind of a stupid kid, I was really upset. Very, very upset. What's going on? I don't know what's going
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on? Why can't I do these things? Nobody came to me and said, "You're upset, we want you to calm down." These are real traumas, for kids. And because you don't fully understand what's happening. There's a sort of veil put over things, you don't necessarily understand what a virus is. You just understand the immediate barrier and that your life has changed. And I remember how that felt. You know, "why can't I do these things? What is it? Is it me? What's going on in the outside world that it's changed my life so much?" I don't know if you could say I was traumatized but I was really upset during those polio summers, I can remember. And I was so relieved when in junior high we got the polio vaccine. Bobby Temps I can imagine, and that's something that I'm very passionate about us not underestimating how much kids pick up because, whether you understand what's happening or not, you can feel the fear. Dr. William Haseltine Kids are very sensitive to their parents, and when their parents are fearful, which they are, they can feel that and they know there's something really wrong. And they just don't know exactly what it is. I can still recall that feeling, and it's a very bad feeling. You know, even thinking about it gives me the shivers. It's a bad feeling. Bobby Temps And so as someone that has been following the pandemic so closely and researching it, what do you see will be coming next for us in terms of how successful the vaccine rollout is in our two countries, but also more broadly? How is that going to help globally? And how would you see that impact the mental health crisis as well? Dr. William Haseltine Let me sort of take it from a broader perspective. I have started writing about multimodal COVID control. You need multiple layers of protection. Suppose you're in a castle, and you're the last person in the castle keep and you want to be safe, alright? Well, you first want to know what's going on out there in the world. You need spies, and you need to know intelligence. That's surveillance, which we failed at pretty miserably. Then it's in some of these countries, you have to know really what's going on there, what they're doing, and do your best so it 2387
doesn't come to you. We failed at that pretty badly. We knew what was happening in China and we didn't really do anything to stop it. We eventually put in some sloppy border control but, whammo, it's way too late. Next thing you do is say, let's try to do what we can to protect ourselves through behavior change. There we really failed, and still today. And that's where society has to go. It's how we moderate our own personal behavior, and societal behavior, when faced with a mortal threat. Now, the Chinese did everything right, from what I see, from month two or three onwards. The first month was a mess, but after that, they did exactly what our textbooks say: test, contact trace, and isolate and control your borders. That's in every public health textbook. We at Harvard School of Public Health, I was part of, helped train them. The specific group I'm head of, the US China Healthcares Forum, was designed to help train, at Harvard School of Public Health, the leadership of public health in China, and we did it and they just followed the textbooks exactly. We have not and don't do it today. New Zealand they do it. They've tried in Australia, and they do it pretty well. But if you don't have that kind of protection, then you rely on vaccines. Think of it as a moat, around your castle. They're already there at your wall. And finally, of course, the castle keep. There's all these new therapies that, fortunately, are working better than they were before. But if you don't take a global view of this, look what happens in China. China's doing what they can do with public health and now with vaccines, but every so often, they'll have to shut down 200 million people. Shenzhen all the way to Macau, that's 200 million people. By the way, that's like the biggest port in the world. So you can't get your goodies for Christmas. Same thing with Ningbo, it got shut down. The second biggest port in the world, part of it shut down because of COVID. And so it goes around the country. I talked to my team in China. Okay, how is it today? Oh, oh, well, there's a few cases in China, they've in Shanghai today. They've closed it down, we can't travel to Beijing. Oh, everything's fine now, we can go to Beijing back and forth, we go everywhere we want except we can't go to X, Y, or Z. So they have got it pretty much under control, but only through massive, massive effort. And it's going to have an effect can't go to China. Unless you're going to 2388
spend two weeks in a hotel. You can't do it. And it's kept them safe. That's unbelievable. Look at us, 650 million people dead. Well, humans can do it. We need to do it as our really major line of defense. I don't know, is it a moral trauma to see that it can be done and know your country is doing it? For me it is. I don't know about others. Bobby Temps Yeah, I could definitely see that. And you mentioned earlier, how it's tricky even to talk about this in terms of PTSD because the the "post" element of that term, we have not yet reached. So in lieu of there being any solution that is going to create perfect eradication. That's not what we're aiming for. Where would you see us needing to get to in order to lessen the impact on mental health? Is there a position you could describe that we could get to globally in combating this and have enough measures and suppression in place that the mental health impact is significantly decreased. Dr. William Haseltine Yeah, I would say the people of New Zealand and the people of China, they have COVID amidst their midsts occasionally, but it's for a tweak. It's a short period. You know, one of the things that makes COVID so dreadful for us, is it just goes on and on and on. And if you think of this summer, for a very short moment, "I can finally breathe easy." I didn't breathe easy, but most everybody else. Okay, I saw what was coming next, but most people were breathing easy and saying, "Okay, now it's going to be over." Then it shut down again, and then it's come back. It's like that poem, "I regained my freedom with a sigh." If we get used to be in this, and all of a sudden it's relieved and whammo, they shut it down again, that's traumatic. So I'm confident that, over time, human beings will live with and we’ll adjust our behavior whether it means wearing masks in the winter, whether it means getting ourselves tested more frequently, whether it means getting jabbed every six months, we will do it. I have to say, when I think of my own life, I think we have to undergo a different relationship to nature. And we have to be sensitive to the rumblings of nature, whether it's our atmosphere, our seas, or our diseases. It's a different kind of mentality. And we've had in the past. If you look back at pre-antibiotic, pre-vaccine times, you see that people had a different attitude. And even in those countries, 2389
where hygiene is not universal. You see, everybody is much more careful in their personal behavior than they are in countries that are so called hygenic. They're very careful to wash their hands, are very careful to wash their vegetables. They're much more dirt averse for one thing, but they're also much more disease averse. Those are deep cultural patterns. We need to absorb this new reality and absorb those cultural patterns as part of our life. Bobby Temps For sure, and we will start wrapping up there then. So you've written about this so much more extensively in your book, could you share a little bit about that and where people could find it? Dr. William Haseltine Right. It's a book called Covid Related Post Traumatic Stress Disorder (CV-PTSD): What It Is and What To Do About It. It's available on Amazon, it's available as an ebook, and it's available as print on demand. And also, I've created this genre I call a living ebook. And that means if you buy one copy, you get all subsequent editions for free. And in many of the books I've written, for example, Variants! The Shapeshifting Challenge of COVID-19, what I've done with that is I've updated I think three or four times now. And if you bought one copy, you get all the updates for it. Once you get it gets updated all the time. I would recommend it if you are thinking about the stress that you or your family is under. If you're in a position where you might be able to help the healthcare system recognize the stress that people are under, and the consequences. I wrote it for both policymakers and for everybody who's going through this experience. Bobby Temps Brilliant, thank you so much. And I definitely recommend our listeners check out your book, because you've written so many and they're for, like you said, a range of different backgrounds. In particular, I took a look at the Family Guide for COVID you designed and I thought that was really impressive; an accessible way of having up to date information to protect your family. Dr. William Haseltine You got to see some of my grandchildren! The pictures of those kids, many of them are my grandchildren. Bobby Temps
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Brilliant. Well, thank you so much for talking to us today. And best of luck with your work. Dr. William Haseltine Well thank you and I want to thank you all for your great program. This is a really important topic and just keep up the great work. Thanks again. Bobby Temps Thank you. Thank you for listening. This interview originally appeared on the Mental podcast, and can be listened to online here: Covid PTSD - It’s vital we can all receive support for both the individual adversity and communal stress of Covid-19 with Dr William Haseltine
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October 2021
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Heat: U.S. battles Covid-19
CGTN America | October 9, 2021 | Interview
Church bells rang out in Washington, D.C this week as the U.S. COVID-19 death toll surpassed 700-thousand. But, will this stark reality make the 70 million unvaccinated Americans get the shot? Meanwhile, on Friday U.S. President Joe Biden spoke with Chicago area companies to address the importance of vaccine mandates. To discuss: • William Haseltine is the chair and president of Access Health International. • Mike Wagner is Assoc. Professor, Univ. of Wisconsin • Dr. Ziyad Al-Aly is Dir. of the Clinical Epidemiology Center, Veterans Affairs St. Louis Health Care System • Georges Benjamin is Executive Director, American Public Health Association Watch online here: Heat: U.S. battles Covid-19
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A proposal for long-term COVID-19 control Brookings Institution | October 15, 2021 | Interview
In a new paper, renowned scientist and AIDS researcher William Haseltine argues that the COVID challenge is serious enough to require steps we have not yet taken as a nation or a world. He proposes a multimodal strategy for long-term COVID control, one that sets up multiple barriers of protection so that we are able to not only contain SARS-CoV-2 and eliminate COVID-19 as a major life-threatening disease, but also return to a new social and economic life. The strategy uses the best of what we have on hand today—a rapidly growing arsenal of vaccines and antiviral drugs and public health measures— with an eye toward future improvements and developments. On October 15, Brookings hosted Haseltine in a conversation on his proposal for long-term COVID control with Senior Fellow Michael O’Hanlon. Viewers submitted questions via email to events@brookings.edu or on Twitter using #COVIDProposal. Watch the full talk online here: A proposal for long-term COVID19 control TRANSCRIPT: Michael O’Hanlon Greetings, everyone. I'm Michael O'Hanlon with the Brookings Institution and I have the particular privilege and pleasure today of having a conversation, that we'll bring you into as well, with Dr. William Haseltine, who is, to my mind, one of the great living scientists on earth, and one of the most accomplished philanthropists and lifesavers of our day. He is, as many of you will know, one of the key scientists on breakthroughs for HIV/AIDS understanding and treatment several decades ago, and therefore, as I calculate it, has had a direct hand in the savings of millions of lives around the earth. He is also the president and chairman of ACCESS Health International, which is an organization that promotes health in various developing countries all over the planet. He has been associated for a couple of decades with Harvard public health school 2394
and medical school there, done countless other kinds of research, and you can see some of his books behind him, including my lifelong fight against disease, and then a recent book on how to handle COVID. And it's really a practical guide, as much as it is a scientist's explanation of what's going on. We're here to talk today about COVID and Dr. Haseltine's paper. It's on the Brookings website, you can easily find at brookings.edu, a very readable and digestible paper that has to my mind just the right amount of science to help understand and bring along the reader, but that is easily accessible and digestible in a single sitting. And I think basically proceeds from the position that we still are not taking this virus quite seriously enough and not doing nearly enough to deal with it, either in terms of our immediate well being, or the longer term. In a second here, I'm going to stop talking and let the the expert explain to you, first of all, his assessment of the situation and then the four step plan, actually four part plan, with each of those parts, having a number of components within that he advocates for how we should be thinking more rigorously and dealing more rigorously with the COVID challenge today. So first, Dr. Haseltine, welcome. Thank you, and we're honored that you also are a trustee at Brookings, a real privilege for all of us who have had the chance to spend time with you over the years, and really grateful to you for joining us today. Dr. William Haseltine Thank you, Mike. It's been a real pleasure. Also watching your career grow. I remember I've been associated with Brookings now almost 25 years. And I remember you as a young guy just starting out and one of our brightest stars. And it's just tremendously gratifying to see your great promises come true and help the institution, and help the United States in a very difficult transitional time. And also, it's just been a wonderful association with Brookings; the people, the scholars, the fellow board members, the ideas that we've seen, the places we've gone, and the impact we've had on public policy. I did have the great privilege of working with your president, John Allen, on a proposal for a commission, one that the British have just finished right now parliamentary commission, which come up with some pretty sobering results. And I would say I wouldn't like to be on the other end of that lash that they wielded. It was a tough 2395
report, as ours should be. I might say it would be a tough report, not only for the Trump administration, but in some respects for the current administration, too, which is a little bit concerning because these guys have their heart in the right place. So let me just begin by asking a fundamental question. And that is, is this an accident or what's happened to us? How did it happen? And I think the answer is we humans now weigh heavily on the earth. What do I mean by that? So, when I was born there were 2 billion people alive. There are 8 billion people now. When I was born, 80% plus people lived in the countryside, 80% plus live in cities now. We're a new ecosystem, we're a new ecosystem for microbes to exploit; we're a big, fat, juicy target. There are a lot of us, we live close-packed, and we travel like crazy. I saw that first with HIV/AIDS. It had obviously been in Africa for a long time. Why did it get out it? It's killed 37 million people by now. It got out because we started traveling internationally. It isn't that we encroached on the natural environment, we've done that forever. Go back to our hunter gatherers, we were out there, right there in the wild. It's that we are now a new ecosystem. This is not the first, it's not the last, and there are going to be many more with increasing frequencies as microbes discover this great new food source, that's us. And we'd better get used to it, and begin to think very seriously, not only about this pandemic, but about pandemics to come, and how we're going to lead our lives. We are living on a volcano, and we better listen to it rumble. Because the natural world is out to get us. That's what it does. Read Darwin. Darwin will tell you, that's the nature of life. And we're a great new ecosystem. Now, what has actually happened? When you look at what's happening right now, what we might have been able to do, Michael alluded to the fact that, in my view, we've underestimated what this pandemic is about, from the very beginning til this very day. Where are we today? Well, if you were to read the papers, as I did this morning, you would think COVID is on its way out. When you look at the numbers, I just jotted down some numbers. There are about half a million people infected every day, there are about 1000 of us who die every day; the infection is not going away in many parts of the world. If you look at countries that are controlled it, like New Zealand, or Australia, or Singapore, they don't control it anymore. It's out of control in those countries, and it's a very, very 2396
big burden. You even look at the UK, which has more vaccinated people per capita than we do, and yet infection rates are going up. We are not out of the woods. When I look at our own country, looking abroad has been a foreshadow of what happens in our country. Britain did go down a little bit, then just kept going up and up and up. And it doesn't look good in the UK today, it looks bad. If you want to see for some place that looks really terrible, look at Russia. And that's only what we see. So we're year two, almost year two, of a really serious event. And if you actually stand back and say, is this really that bad? Well, and I've talked to my virologist friends, they'll say something like, "we do pretty well at handling this infection. Maybe one and a half percent of us die. So our bodies are really fighting off pretty well. And most of those people are old. They've already had their children, they're already supported their grandchildren. So this virus can be a lot worse." In fact, they're not wrong. Except for the fact that there's something called long COVID; we're counting the dead, we're not counting the wounded. It's like a modern battlefield today. It used to be a ratio of like one to one or two to one or three to one. In a modern battlefield it's 10 to one, at least for our troops, but the same kind of thing isn't true for long COVID. If you actually looking at the future disease burden, and present disease burden, whether it's 20, or 40% of people even have mild COVID. It's a serious problem. So the magnitude of the problem that we're looking at is at people who are dead, which is still horrendous in the US-- 700,000. It could be 10 times that number of people who have long COVID, or some serious symptoms. Our health care systems are looking at this and saying "Oh, my goodness, this is bad. Look at what's coming at us in addition to the age wave, we're going to have a long COVID wave." So this is a serious event. And Michael, I'll stop with my brief introductory remarks there, and then you can take me through a more structured presentation if you'd like. Michael O’Hanlon Fantastic, although it's obviously foreboding and frightening as well. Before we get into your detailed proposal, I wondered if you could, with whatever crystal ball you might have handy, sort of prognosticate for us where you think we might be in a year under current policy, the current approach at home and abroad. And in terms of whether you want to say how many fatalities per day we 2397
might be having in the fall of 2022 or some other metric, whatever occurs to you and you find most compelling. Then, with your plan, if it works as well as you would hope, I realized there are a lot of dimensions and a lot of uncertainties, but if much of it worked as you hope, just in an order of magnitude terms, how much mitigated might things be in a year relative to the baseline that we're on, as it is? Dr. William Haseltine Well, let me give you an answer to your last question. 1/5 of humanity has been free of COVID deaths for 18 months. No COVID deaths, and that's China. Now, you might say they're not reporting a few. Well, let's give them 50, give them 100, give them 10,000, but it surely isn't 700,000 dead, okay? It's close to zero. I have offices in China, it's close to zero. Human beings can control this. So the answer is, if my plan were implemented, the death rate a year from now would be zero, or close to zero. What is the chance that that's going to happen? Close to zero! Because we don't do well. The fundamental aspect of COVID control is in every public health book. You know, one thing that people may not realize, is when SARS hit China, they looked around the world for help, and where did they come ? Harvard School of Public Health. For 10 years they sent their top people over every summer for workshops, and we went to their Central Party School, and wrote the book on how to control a pandemic. And guess what, they followed it to the letter. Yes, there was a glitch at the beginning, which has cost them and all of us a lot of problems, but once the central government realized what was going on, whammo, they just executed what the plan was. I can't tell you how it breaks my heart to realize the plan we wrote works, but we don't use it. And what's that plan? It isn't rocket science. It's find out who's infected, contact trace everybody who was infected, and treat them, whether they're infected or not, as if they are infected. Because they might be, which means isolate them from everybody else. If it means isolating a whole city for two weeks, if it means testing 10 million people in five days, they will do it. Do have the capacity to do it? Yes. It's not technical. It's not complicated. Yeah, we have apps, we have this, but we didn't do it, and we won't do it. That's the problem. We see this example. And everybody says, "oh, they're authoritarian." Well, that's a group think, that is not what I see happening. I see a government that 2398
follow the rulebook, and I see people who are willing to temporarily sacrifice their convenience, because other people will do that for them. The outcome is that China is virtually COVID free now. Yes, COVID keeps coming in. So first they're shutting down Ningbo and then Shenzhen and then Harbin and then Nanjing. Yeah, they're whacking them all, but they're keeping it low, and people are not dying. Can any country do that? Yes. But what's going to happen to us is that we're going to continue to suffer from repeated bouts of COVID. Just take a look, I urge the people who are listening, go on and put into your computer "COVID cases UK." Look what you see. You'll see they've gone through terrible times, they're going through bad times now, and it's on the way up despite all of the vaccines. That's because they're not following the public health rulebook. And that's true. Look at Singapore, they controlled it, they relaxed, whammo, higher than it's ever been. New Zealand relaxed, higher than it's ever been. Australia relaxed, higher than it's ever been. Not that these countries didn't know what to do, they just decided not to keep doing it. We aren't in good shape going forward. This virus is complicated. And there's a question you asked before we talked, how badly did we underestimate this pandemic? First of all, just to list a few: we thought it would stay in China, of course it didn't; we thought it wasn't very lethal, and it turned out to be a lot more lethal than flu; we thought that our very sloppy border controls would work, and they didn't work; we thought it wasn't airborne even though the highest level of Chinese government taught our highest levels of government that it was airborne. We continue, and even today continue, to assume it's not really airborne. When Delta is even more obviously airborne than other strains. You know, somebody in one end of a hall opens the door, half an hour later another guy in the isolation hotel opens the door, and the other guy gets infected. Same sequence of the virus, he gets released, infects a whole bunch of other people, and about a third of Australia shuts down. That's how it happened. You can actually trace the viruses. One guy walks through a shopping mall, and 20 people get infected and infect all of their peers, that's airborne. So we know it's airborne. "It's not going to change, don't worry about it." Do remember that? Now, "you're vaccinated, you're protected." No. "You're vaccinated, you're not going to die." Maybe, but we don't really 2399
know and we're basing policy on that assumption, which I think is a bad idea. So we've underestimated what this pandemic is and translated that into policy. And when you read what the British government parliamentary Commission's have said, they say, this is a great example of bad groupthink. They all drank the same kool aid, and came to the same bad result, which has resulted in hundreds of 1000s of our fellow citizens dying. That's the British report. Michael O’Hanlon Well, let's go through your four point plan and see how much we can convince some listeners to adopt at least some of it, I assume some of it would be better than none of it. Dr. William Haseltine Absolutely! Michael O’Hanlon Just to sort of telegraph in advance. Vaccines, and also the microbiological research to understand the virus better, so as to make better vaccines and other things, category one. Antivirals and prophylactics, category two. Public health, including things like contact tracing and isolation with compensation, number three. Then a global element, number four. So again, in shorthand: 1) vaccine, 2) antiviral, 3) public health, 4) global strategy. I'd like to walk through each of those and ask you to just say a couple of words about each and, again, I encourage folks to read the paper, but maybe you can highlight some of the key recommendations, you know, just going one at a time starting with the vaccine and research issue. Dr. William Haseltine Well, you know, vaccines are a wonderful story. In public health in general, it's the cheapest, best, most effective public health tool we have. That is, other than what I just discussed, what the Chinese have done, without the vaccine. They have one now, but they did all that without the vaccine. Also, new technologies have allowed us to make these vaccines super fast. But one thing I knew, sort of from the inside baseball, is that these vaccines weren't gonna last very long. They made these vaccines, same ones, mRNA vaccines against Ebola, cytomegalovirus, and others. And we knew three months, six months, that was it. And by the way, that's true for flu vaccines, which we've recently discovered, they don't last very long. The current advice is, if you want to be protected in February, take them in November, not in September. That isn't official government 2400
policy. But that is, I think, the upshot; the vaccines fade in their effectiveness. So, that's a fundamental thing you have to know about vaccines. Yes, if you have high levels of antibodies, and you have a very good fit with what's infecting you, that high level of antibody won't stop the virus from getting into your body, but it will stop it from doing anything more. But if that level fades, and the same thing comes in, you get infected again, or if this changes, and you have a high level, it can still get it. And once it gets in, it can cause a lot of trouble. Whether it's going to kill you is a whole other story, and we don't know the answer yet. But one thing we do know is you will get infected, you will transmit the virus, and you will get at least mildly ill and some people will go to the hospital. How many go to the hospital and how many get sick? Time will tell. The simple answer to the question, what to do, then, is keep those antibody levels high. And that's what third, fourth, fifth shots are all going to be about. And if we get more clever, it'll be about broadening that protection. So if the virus changes a little bit, if that's what it's doing to get back in, like flu virus does, then you make a slightly different vaccine. And all these questions about which vaccine should I use? "I got Pfizer, should I get Pfizer again?" I ask you a question, those of you listening, who made your flu vaccine? And who made the one before that or the one before that or the one before that? You don't know, I don't know, who knows, okay? So, of course you mix and match vaccines since we've been doing that forever. Same thing with all the vaccines you've had, they're all mix and match. So I wouldn't worry too much about that aspects of vaccines. The policy, in my view, should be keep the antibody levels high for everybody you can do it for. That means repeated doses of the vaccine. You know, this really should have been a three dose vaccine, the Pfizer and the Moderna. Because if the first dose gives you a protective level of, say, one, then the second is a level of ten, and the the third is 100. We didn't have time to do the three dose, nine months regiment. Had we had the time, that's what it would have looked like. Now we're saying, well, maybe some people should be getting the booster, some shouldn't. I call that a decision to regret. Kind of like the captain of the Titanic steaming full speed
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ahead. It's not a smart thing to do. You're betting against the unknown, and so far we've lost every one of those bets. Okay, so the first thing is vaccines. And are we going to have better vaccines? Yes. We're gonna have vaccines that give you higher levels of protection and that give you a broader immunity. Is that going to solve the problem? No, because these vaccines will fade and the virus will change. So we're gonna have to keep going, whether it's biannual, whether it's annual, or semiannual, is the only open question at this point in terms of vaccines. But yes, vaccines are a very powerful tool that we should make maximum use of. So, that's the first point. Let me ask two related points on that issue before we move on to antivirals. So, one question would be, are we ramping up production capacity for vaccines enough to essentially comport with your view? Do we need to, whether it's through incentives to the private sector or, you know, suspending patents or something else, to just get the production levels up to a much higher level? I guess, let me just ask you that question. Well, the answer is, the world does not have enough vaccine production capacity. And we should be ramping that up dramatically here in the US. I know the Chinese are now doing their mRNA vaccines, Indians are doing mRNA vaccines. I wish other continents would be doing that; South America and Africa and Central Asia. We need a lot more vaccine capability. One of the things that's the biggest regret of mine is, for people like me, we knew that this is going to happen. I predicted it after HIV. But there have been many, many predictions all the way along the line. And Mike, you'll remember after the anthrax attack, all the bioshield, BARDA, all the effort that went into that, but nobody took it really seriously. If you look at vaccine capacity around the world, the continent of Africa may have five vaccine production facilities, and they're not very modern, they're not very good. South America, also, may have around five. Those are big continents with a lot of people, and they're not protected. And that has just been a systematic problem, not for America, but for them. Yeah, they can point their finger at us and say, "give us the vaccines." But, they have to do it themselves. Now maybe, you mentioned patents, the way the problem got solved for HIV drugs wasn't by abrogating patents, it was by saying 2402
there's exceptions where you don't have to follow that rule. If you're in an emerging economy, and that's actually built into the trade agreements, the world trade agreement, that you can have exceptions, if it's an emergency for your country, you can make the drug without paying attention to the patents. For example, Egypt has recently taken a drug that in the US costs $80,000 to treat hepatitis C and cure it, not just treated but fully cure it, they have the highest per capita rate of the world by far. What costs us $80,000 costs them $45, okay? They managed to get a ruling that they didn't have to follow the patents. It wasn't that they were given the patents, they simply declared, "we're not going to follow the patents, according to these rules." The result? It cost them $45 per treatment. And they identified, by testing with the latest advances with PCR, who is infected and treated them all for free with a $250 million loan from the World Bank, and they have no more hepatitis C. So you don't need to hand over the patents. You just have to make exceptions where people don't necessarily have to pay the patent rules if there's an emergency situation. It already exists. So what we should do, and these countries do need, is increased vaccine manufacturing capacity. Now, you also mentioned, last question on the vaccine, you mentioned research and development to better understand the microbiology of the virus that causes covid 19. And I wonder, how do we implement that recommendation? Do we need to provide more government funding to university research facilities? Just how does that get followed. You know, there's a direct line from fundamental research to applied progress. Let's take HIV, and then go from HIV to COVID in a second. I was able to do the work I did on HIV, because we had 20 years of something called a Special Virus Cancer Program, which gave us recombinant DNA and gave us a deep understanding of retroviruses. Even though there was no evidence that retroviruses caused human diseases, I actually thought maybe they did so I kept a lab going on that and was one of the only labs. The knowledge all of us used was knowledge that came from the Special Virus Cancer Program. 20 years of heavy investment, by Republican and Democratic governments, that led to our ability to know what that virus was, understand it in detail, and then two and a half to $3 billion from 1987 until today of consistent research. Where's that led 2403
us? There's not going to be a vaccine in the foreseeable future, for HIV, but there are combinations of drugs, which should be available within a year or less, where, if you're infected, all you need is one shot every six months. On top of that, if you have a lifestyle that's likely to predispose you to catching HIV, one shot will prevent that, too. The same shot. But that took 30 years of fundamental research, to get drugs that have what they call a therapeutic index, i.e. kills the bug and not you. So you can load somebody up with a million times the dose needed to kill the bug and then protection might last six months. There are two drugs like that now, fantastic progress. We can do that, but it takes huge investment; all the research we invested, those $3 billion a year, plus whatever the pharmaceutical companies did, pays off for COVID. We know what to do. And not Incidentally, almost all the molecular biologists in math the immunologist who work on COVID, were previously HIV researchers. It's directly translatable research. Do we have the programs right now? I haven't seen the kind of program I'd like to see, but I think it's just because I'm not sitting, as I used to, at the right elbow of Tony Fauci as we're planning out which kind of grants to give out. He knows what to do, I have great confidence in him. He's done it before and he's done it successfully. Our government is really good at this kind of thing, but we really need to do it. I haven't seen the papers that I'd like to see coming out, but I think that just might be a matter of time. We do need to keep sustained fundamental research on coronaviruses, and a few other viruses also. So thank you. And now let's move to your second key elements, and that is antiviral and prophylactic treatment. A lot of people, obviously mistakenly, have thought that "Well, that was just something we did temporarily until we got vaccinated or until vaccines became available." But you're saying, no, even in a world of plentiful vaccine, you want to have antiviral treatments, which are different and work differently that achieve other benefits. So could you please explain a little bit about that? Well, antiviral drugs do two things: one, if someone's sick, you give them the drug and they get better, that's what we hope, or they never get sick, or, two, you give it to them so that they never get sick in the first place. For example, all of us have gone to an area where you need to take the malaria drug and we really thought 2404
about, "am I going to take the anti malaria drug?" We might not have done it, but we certainly thought about it, right? And I know you've been in the Congo, so you certainly thought about it, maybe you did it. Okay, we're not going to ask you the truth or consequences here. Michael O’Hanlon I took all my antimalarial drugs. Dr. William Haseltine Okay, so you had bad dreams for two years, but, be that as it may, the idea of prophylactic drugs is a powerful idea. Because we don't have, we don't have the prospect of a vaccine for HIV --we may someday get it, but it's been 40 years gone by already-- we rely on drugs. And so, thank goodness we have them. And thank goodness, we now have prophylactic drugs as well. So that is a whole body of knowledge. And we know exactly which combinations you have to use. So you sort of find unusual targets that give a good therapeutic index. So we're on the break of getting some good ones. Now, we already know it works because monoclonal antibodies, kind of a mimic of what a vaccine will do, we've made those and given those to people in congregate living settings, old age homes, or, you know, elderly care homes, and shown that if somebody gets infected, other people aren't getting infected if you protect them. That's ideal. The problem right now is that there's two problems with monoclonal antibodies. First of all, right now you have to infuse them, so it's not just a shot. They're going to solve that, it's going to be a shot or subcutaneous. They'll work it out and it'll work for five, six months. That said, there's a deeper problem: if the virus is mutating in response to your immune system, it's going to mutate in that response, and the monoclonal antibodies aren't going to work anymore. And that's what's happening. The virus does mutate to get around our immune response, and it's exactly because you take the antibodies from infected people. There are now ways of getting other kinds of antibodies, but that isn't the ideal, the ideal is [recording unclear]. Now, we're going to have those, and over the next X years, and that X can shrink, depending on government investment, and we've seen how fast it can shrink when there are billions of dollars being handed out to make it shrink. It's a very good lesson, by the way. One of the most positive lessons we ever had is, you put enough 2405
government money out there and a seven/eight year program shrinks to eight months. It's fantastic. And we do that in war research anyway; radar that may have never come, zippo, came really fast. So, when you put a lot of government money somewhere, you can get really good results. Fantastic. So that's a lesson, but we're not doing that. I've advocated for a warp speed, not a great name, but a warp speed effort on anti viral drugs, and I haven't seen it. There's some money there, but it's not a warp speed effort, where you have a very directed effort like we did with vaccines. So why do we need them anyway? We know the vaccines aren't perfect. We know even if you think you're gonna be protected, you're not. First of all, if you're older, like I am, you'd never make a good response. In every textbook it says, "Oh, you make great responses to vaccines unless you're old, or you have any of 10 different/20 different underlying inherited predispositions." Okay, we know that pretty well. So vaccines were never going to protect me completely. A little bit, yes. But perfectly? No. I would like to have drugs that if I'm exposed, I can take or if I'm in a situation, like I was in New York, where everybody around me was getting infected I loved prophylactic drugs, because I can't count on vaccines. So that's the first thing. Second of all, what's the problem with testing, identification, contact tracing, and control of those who are exposed? It's the fact that nobody wants to change their lifestyle. I mean, I can take you back to HIV days, before there was a treatment for HIV nobody wanted to be tested. There was a huge fight. "Don't test me!" Why? First of all, it's a death sentence. Second of all, it's the end of their sex life. So that was not a good thing, and people really resisted. The moment there were drugs to treat it, people wanted to be tested; "oh, I can save my life." It flipped around completely. I was involved in developing a test, so I knew what was happening there. So if we have drugs, people are going to maybe want to get tested. In fact, the consequence will be identification through a test, then contact trace, and finally, instead of isolation for two weeks, just pop a pill. That's a much better outcome. And by the way, if you pop a pill you're not going to get it even if you were exposed. I think we need that, we don't have it. It's got to be really safe because you're treating a lot of people who aren't infected-you're treating healthy people. 99% of the people you're going to 2406
give that pill to are not infected, so it better be a safe drug. And by the way, the new drug, Molnupiravir, is not that drug. It has the potential of mutating, it can't be used for pregnant women for sure, and it may supercharge the virus variants. It's a mutagen for the virus, it mutates the virus to death. What happens if you have too low a dose? It's going to mutate the virus and might end up killing more people. So, that's not a drug I like but there are other drugs coming along that I think won't have those problems. So that's a long answer to your question, but I hope it helps. Michael O’Hanlon No, it's great. Is the most important next step therefore in the research realm, just given where we are in this whole process and the quality of the existing drugs versus what we need? Dr. William Haseltine It's a lot more research and a very focused government effort to move those drugs along as fast as we can. And I can tell you by looking at this, I've been studying it now for a year and a half, this virus is absolutely rich in targets. You know, as is your body is doing pretty good job. Remember in HIV, 99% of people infected die. 99% of people die! That was a nasty son of a gun. Is still a nasty son of gun. In contrast, 1% of people die with COVID-19. Your body's really doing a good job, the virus is just cranking along, trying to struggle its way through. There are a lot of vulnerabilities, all we have to do is a little bit more and the worst thing this will do is give you a cold. So the tremendous number of targets will turn it from something that's lethal for 1/2% of people, to something that's not lethal to anybody. I think we have tremendous opportunities, and I can list 30 different targets that we should go after. Michael O’Hanlon And once we have these better antivirals, should the government buy them for us? Or.. Dr. William Haseltine Well, you know, one of the great things about the COVID vaccines is that the government buys it and gives it for free. How many other drugs is that true for? I can't count too many, and nor can you. So, it turns out it's a very good thing, you know, that government buying and giving out drugs. You know, all my friends are asking, "Oh Bill, I'm not quite qualified right now to get a third shot. Should I get one anyway?" I said, look, the pharmacist gets 50 2407
bucks for every vaccine they give you. They're not going to ask you too many questions. The government pays them $50 for every shot. Of course they're going to want to give you a shot. They'll ask you a few questions, you say, "oh, I've got asthma or something like that." They'll give you a shot. Go ahead, go to Walgreens. If Walgreens says "no", go to CVS. So, of course, I hope the government does give it out for free. The answer is, will they? Who knows. That's a matter for the Brookings Institution to look at more carefully through their policies? Michael O’Hanlon Well, you know, it is interesting, because just to jump ahead to your last category of global strategy, which involves buying, you know, we have we've given about half as much money to COVAX so far as it needs, right? And it's not just vaccine supply, it's also monitoring around the world, and so forth. But we'll come to that. But the interesting thing is, if I put together some of your ideas, you could imagine writing a piece of legislation that would appropriate money to do a number of these, and there might be a staggered effect, like with the antivirals, maybe the r&d happens first, the production happens later, but you can imagine sort of a five year funding stream that you create and enact in policy. Dr. William Haseltine That's what Brookings is good at! I'm glad to hear you're imagining that, and I'm happy to give any advice I can. I love that imagination. Michael O’Hanlon Well, thank you. Maybe we'll come back to that. But before we go to the global part, we'll go to the public health part. And you've already alluded to a lot of it with contact tracing, but there are a couple of pieces, I know from your paper, that you could probably elaborate on further, like trying to make people more willing to self isolate if and when they learn that they have it. So could you perhaps expand on the public health dimension? Dr. William Haseltine Well, the politicization and what's happened in America and other countries with COVID is, from a public health point of view, just disastrous. Because the things you would like to do, the things you should do, the things you know that will work, you can't do. It's made me think about the nature of government, and leadership, 2408
and it's also behind one of my remarks I made earlier about China. You can't lead a nation to do things they don't want to do; If people don't really want to do something, you can be the right leader, but at the wrong time. Think of FDR, who knew we should prepare for World War Two, he knew it, and I've read several books on the topic, and I'm sure you maybe even wrote one, Mike. But people have gone and studied what he tried to do. He tried to lead America at a time when we didn't want to go where he wanted to lead us and knew we had to go. Right? It's a really good study, and that is what's happening right now with COVID. Dr. William Haseltine We have a government that knows where they want to go, but they can't because of individual decisions and what people are willing, and unwilling, to do. It's really a sad thing. It's a heartbreak. The way we dismiss that is we say, "well, the Chinese are authoritarian so they can do it but we can't." Is that true for the New Zealanders who did it and have now given it up? I don't think so. Is it true for the Australians? The Australians I know may be more individualistic than Americans, but maybe there's something in their background, their island characteristics, something that's different, that allowed them to do something. But if you're a leader in Britain or the Americas, good luck. Just read what the MP report says, it lays it out absolutely clearly. These leaders made a judgement about the people they were leading, and it led them to a slaughterhouse. Now, whether that's murder or manslaughter is a tricky question. These leaders knew it would lead to death, and death on a huge scale, but they pursued those policies anyway. As did Trump with his Scott Atlas. I call that manslaughter in its most mild form, okay? It's knowledge of what you're doing and adjusting your actions despite the knowledge that people will die as a result of your actions. That is what happened in this country. And it's what's happening today. Now this government really wants to do the right thing, but it knows, I think it knows, that a lot of people, it just can't do it because a lot of people are going to object so intensely that things will fall apart in ways they don't want them to fall apart. That is a tragedy. This is a question I keep coming back to: what is it that allows people to be altruistic enough to say, "I'm going to isolate myself in a single hotel room for two weeks, and even if I have to pay for it 2409
like $10 a day, I'm going to do that, as long as the other guys are doing it, too."? The alternative, "I'm never going to do that. I would die before anyone tells me to do that." And maybe you will die. So those are the two extremes. Can we make it easier? Well, one way I've thought about it is giving people $500 a week to isolate. Will that do it? Well it will do it for some. Mandates, we've seen, work for many. I would say at this point, when I look at hospital systems, I know that of 30,000 people there are maybe 5000 resistors. With mandates there were only 500 resistors. That's kind of the numbers that my friends are telling me that they're seeing, and I think it's probably around the country. Mandates are moving us in that direction. Because people don't want to give up a job, when they actually thinking about giving up a job, they say, "well maybe I should get that vaccine." So there are ways to do it. I've written about the hole in our COVID control program, and what that hole is, is identification of who's infected, contact tracing, and isolation. Without that we are sunk, and our future doesn't depend on us, it depends on what the virus decides to do. If we want to put the future in our hands, that's what you have to do. Hopefully, we get a pill making it easier. So maybe pay people and provide a pill. Importantly, we have to get over where we are now, where the fundamental tool to control this is not medical, it's public health. So on my list of things, it's number three, it should be number one. Because that's what actually, if you look around the world, what really works. Zero deaths and almost no infections, we count them in the low 1000s in the last 18 months, it's what China's done. Every other country that was doing it has given up now. Michael O’Hanlon It does strike me though, given that we spend several trillion dollars on COVID relief, largely focused on the economy, but somewhat focused on, you know, the medicine and the public health requirements. I'm not persuaded that Biden wouldn't be able to get that kind of a bill through Congress. Admittedly, if he waits much longer here that much. I mean, if you wait too much longer, I Dr. William Haseltine think what we can do, Michael O’Hanlon 2410
I think we should be I think now's in a way the sort of the last he's you know, he's still in his first year, if he waits too much longer people are going to say, "Well, why didn't you do it when you had a chance early", and then it's going to be almost like a concession or an acknowledgement of earlier failure. Dr. William Haseltine And, you know, I say one thing, I know the people that are in this administration, and they're good people, they know what they should do. And Biden, you know I've worked with Biden for, I don't know, 35/40 years, he understands health better than any president we've ever had. He's been at scientific conferences I've been at going way, way back. He's really interested and he's picked wonderful people. And for the first time, we have a cabinet officer, who's an excellent, outstanding scientist, who also has sharp elbows, which is good for a cabinet officer to have. He's got sharp elbows and a sharp mind, and he's sitting there in the National Security Council, he's sitting there in the president's office, he knows what we should do. And let's hope that we're able to at least take the risk to do it. How disappointing is it for most people to think that the vaccine is going to save them and to be told it's not? Well same thing with the drugs, you're going to be told drugs are now a bad good backup, it's gonna save you, but it's not the whole story, it's a piece of the story. The real story, the heart of pandemic control, is public health. Michael O’Hanlon So, the last piece is public health done globally; a global strategy. And you've already talked a little bit about this, but maybe if you could add one or two more points. I've been very selfish, I've been taking most of the hour with my questions, there are about a half dozen questions I'd like to try to get to from the audience after I hear your last point. Dr. William Haseltine I created ACCESS Health with the realization that we had tremendous opportunities to save lives all over the world. But because of the organization of health, what I learned from my years with Brookings and others, is that it's really a matter of public policy. The health of a nation is based on public policy decisions made by a series of leaders. And therefore my foundation works tries to help, like a mini Brookings, leaders who want to improve policy get access 2411
to the best examples, and we're willing to work with them to help them do that. That's what we do. But the hardest part of that whole equation is not finding things that work, it's finding people who want to make them work. I wrote a book on the Singapore healthcare system. I wrote it because it has the best outcomes in the world, certainly as good as any others, at 5% of GDP. Proof of principle. I wrote the book, handed it Mike Bloomberg, and he said, "Oh, Bill, that's great. What a great idea! But, what makes you think anybody wants to learn?" Okay? And that was a deeper comment than just a smartass comment, it was true. You know, I wrote a book on NYU transition, how you take an academic medical center, and go from really mediocre to the best in the world. And I've had CEOs of hospital systems that don't want to read that book: "yeah, I know, I know you did, I don't want to read that." Okay, how arrogant and stupid is that. Now maybe they think I'm a promoter, but I'm an outsider, I just saw what worked well. So what you find when you look around the world, and this is true for public health as it is for, you know, having an appendectomy or cancer treatment, it's so low on most countries development agenda that you're not even there. Before the year 2000, it just wasn't even there at all. Think of your own work with the Peace Corps, some health was there but it wasn't the national agenda. It wasn't like infrastructure, or education, or industrial policy. But it turns out, it may be precedent, all of that. And it's important to get that on the agenda. And the UN has done a pretty good job with its Millennium Development Goals and then the Sustainable Development Goals, they've actually put it there. How much does that really translate? Well, when you travel around the world, it has penetrated, it's a very good step forward. Are we going to meet those sustainable development goals? No, did we meet the millennial goals? Some. That's where we need to go, we need to make sure that countries aren't looking to the US for a handout. A country's leader's job is to protect its own people, and if they can then protect other people that's great. Now the pandemic is a little different, because those people over there are going to kill us over here. So of course, you have to protect yourself, protect other people. But it's a broader issue than just self centered.
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The other thing that you see is there's so many divisions. I would talk about, just a minute, about one other topic. To me, the tragedy of our tension with China, moving into the scientific realm, is cutting off our hands in the future, because they are our closest knowledge partner. They are our knowledge partner, we created them. My students and my fellow students are them, they are us. And they're taking their science to new heights as we are. But to cut that off, which we are doing, I can tell you all my friends who say I'm not going to send my students to the U.S., I don't know what's gonna happen to them. These are the brightest people in the world that are trained, like unbelievably well-trained. Or, "I'm a venture capitalist and I'm not going to put my money into America anymore, because they don't want me to. I'm terrified to put my money there because they're going to come after me." These are really big mistakes. And they're especially big mistakes when it comes to pandemic control. And now, let's get some questions in. Michael O’Hanlon Well, that's very good framing: China as a knowledge partner. That's not something you hear a lot in Washington, but I think it's very useful. Dr. William Haseltine You do not. And you know something, there is no such thing as a secret in technology. If anybody thinks there's a secret, they should look at their own computer. You know, Stalin back in the day knew more about the atomic bomb than Truman did. And that was the middle of nowhere in Los Alamos for Pete's sake. Michael O’Hanlon So there are four questions. I'm gonna I'm gonna Read all four because you've already touched on most of them and and then go back and reread whichever one you want to answer. But just so you know, where folks have their curiosities, and some of them came in before our conversation. Question one is, what do you propose to do about political opposition to health strategy? Some of the problems we've been talking about. And then, second question, what are the right metrics to watch for in evaluating success against COVID? I guess that's beyond the obvious ones of infection rates and death rates. Third question, how would you see long term COVID control in high density areas like refugee camps? And then, finally, is there a way to expand the whole research agenda by 2413
looking at cancers which may be precipitated by viruses? I guess, question would be, does that approach help us understand COVID better? But I can go one by one, if you like. Dr. William Haseltine I can answer some, I can't answer the other ones. I'm not a politician as you could tell by how I speak. I don't have that natural guard that says, if this phrase gets out your sunk. I'd be at the bottom of the ocean 100 times already. Okay, so I can't answer the political question of how we do that. I can only say that the deepest answer I could come up with is control of pandemic is cultural. And there's a book that goes through that, instrumental to my way of thinking, called "Plagues and People", written about 40/50 years ago, by a historian, who came to the conclusion that the way people survived plagues is through cultural adaptation. That's one of the things I've been talking about. You know, implementing the golden rule with your life, and in public life, is a very good thing to do. And that's my hope for what this teaches us. How soon it will teach us, how many bad lessons we have, how many of us have to die before that lesson sinks in, I don't know. But I do hope that that's the lesson we learn. With respect to cancer, I've talked about that in a way, because the tools that we have today that we had with HIV, and even more so the tools we have today are driven by a tremendous amount of research, fundamental research. So if you really want to understand the immunology of COVID, you go to the best immunologist, and almost all of them are cancer immunologists. One of the greatest advances in the last 10 years in cancer, is the application of immunology: applied immunology to cure tumors which had never been cured before. I have friends who are alive and well today who would have been dead, if they had what they had 10 years ago. So the answer is yes, these tools are really, really important. Developing the fundamental tools, whether it be for cancer, or the other great disease, Alzheimer's. Now curiously, and sort of a quirk of fate, it may be that COVID is teaching us about Alzheimer's. It's a strange kind of thing. Some of the same genes that make you susceptible to Alzheimer's, late onset Alzheimer's, make you susceptible to COVID. And if that weren't enough, those people with long COVID, serious mental issues with long COVID, if you look at their blood, it looks like they have Alzheimer's. It is quite remarkable 2414
that we're now making connections that nobody ever thought possible. So when you make real research progress in one area, there are great positive repercussions in many other areas. Michael O’Hanlon There was one question about any metrics beyond the obvious ones, and maybe that some of this gets into your public health monitoring and syndrome, surveillance and that sort of thing. And then the last one would be any special methods. I think this is sort of a softball for your prophylactic/antiviral concept, but any specific strategies that would work in high density areas, like refugee camps? Dr. William Haseltine Well, I think the prophylactic one is the answer. Make sure they're vaccinated and have prophylaxis available if the vaccines are waning. I think the most practical suggestion for everybody listening is, go out and get your third shot. Five months, no matter whether you're 18 or 80, you need that third shot. And it should be a Moderna or Pfizer, it shouldn't be one of the others. Not all vaccines are equal. And you really need that protection. So that's the thing I would say. In terms of how to understand things that are getting better or worse, I don't think there's anything beyond the obvious. I'll think about that. I can't answer that question easily off the top of my head. Michael O’Hanlon Well, this has been, you know, a fantastic hour. And I could run out the clock with one more question, if you like, where we can, we can declare victory, at least on the explanation and the education. Maybe not yet on the policy front. But I will throw in one final question, because we talked about global health a bit, but not in quite as much detail. You mentioned in your paper that you haven't yet fully funded COVAX, and in fact, I think we're at about the halfway point, and it's only a few billion dollars. So, am I reading your paper correctly to understand that we could make substantial headway, at least in ensuring long term availability of enough vaccines, by adding maybe somewhere in the range of five or six more billion dollars to our COVAX requirement. Dr. William Haseltine COVAX from its outset was poorly conceived. Because, if you actually read it, it says, before anybody gets above 20% everybody gets 20% vaccinated, every country in the world. That was like, what 2415
planet are you on my friend? Okay. Okay, so that was like "huh?" Secondly, the answer may not be giving more money to COVAX, it may be giving the vaccines, just giving them vaccines. Now, there is something that I think is a little bit odd. You and I have traveled around the world, to the most remote parts of the world, but wherever I have gone, and this I recognized when in 1966 I took my first trip around the world, there was Coca Cola everywhere! I could go to a Cambodian, you know, way the hell out and back, and there was Coca Cola stand. Not Pepsi, there was coke. It was the most ubiquitous thing, like a Snickers bar it's everywhere. Okay, now there are some places that's an exaggeration. You go to someplace deep in Brazil and maybe they don't have a coke machine. But it's pretty ubiquitous. There's an equivalent now, which is a vaccine center for children. It's as ubiquitous as coke. And it's a high quality vaccine center, there's people working there who have all the records for everybody who's born. They have high quality freezers, and great vaccines that protect all the kids from childhood diseases. And it's in many places. That's an infrastructure that's been built with countries and internationally. That is the example that I'd like to see for adult vaccines and adult drugs. If you ever go to Africa, and you look at PEPFAR, that's what you see, too. PEPFAR is in an isolated hut that takes you 12 hours to get to the last hour by motorcycle. PEPFAR reaches there in Africa. It can be done, but it has to be done together. What allows PEPFAR to do it for HIV, and not for malaria or for some other disease? It's our money. So yeah, their infrastructure, but our money. So there are ways of doing that. And I'd like to see that as a global program. The same thing we do with childhood vaccines do for adult vaccines, and some selected adult drugs, build that very, very expensive network. And that takes cooperation between the local government and international resources. And those resources we've got. So that's what I mean. And you being in the Peace Corps out there and watching what can be done, you know that that can get done. So when people tell me, "Oh, well, Bill, yeah, you can give them the vaccines but they don't know what to do with it." Wait a minute. They have it for childhood vaccines, and they know exactly what to do with it. What are you talking about? "Oh, well, you can't
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translate that for adults we translate for children" is a different way of thinking, well, how different, I ask. Michael O’Hanlon Really good. Listen, thank you so very much. Your assessment of the situation, your four category strategy, and your explanations for the elements are just so helpful. And I hope that a lot of folks are listening, I hope the Biden ministration which is doing an okay job can take its game up a notch or two, to an even higher level, as you've advocated. And I want to thank everybody for tuning in today. This will be on the website forever, living there forever. And I hope it gets a lot of attention because Dr. Haseltine you're a real hero, and a great educator as well as a great scientist. So thank you. Signing off for Brookings. Have a great weekend, everyone.
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Dr. William Haseltine // Interview with Bloomberg Businessweek Bloomberg Businessweek | October 25, 2021 | Interview
Dr. William Haseltine, Chairman and President of Access Health International, on virus news and the development of the drug Molnupiravir. Listen online here: Facebook in the Spotlight
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‘We are not done with the virus. And the virus is not done with us,’ says global health expert about omicron NPR Houston | November 30, 2021 | Interview
Experts discuss the latest information on the omicron variant, as well as boosters and other COVID headlines. “This variant is a cause for concern — not a cause for panic.” That's how President Biden put it, in his speech yesterday after a meeting of the COVID-19 response team at the White House. So what exactly are we learning about the new omicron variant? The World Health Organization warns that it poses a “very high” global risk because of the possibility that it spreads more easily and might resist vaccines and immunity. But we still don't know for sure how dangerous omicron is. Today, national and local health experts help us understand this latest pandemic situation, and they answer listeners’ questions from omicron to boosters and other ways to protect yourself. Guests: Dr. William Haseltine • Chair and President of the global think tank ACCESS Health International • Founder of more than a dozen bio-technology companies Dr. Jill Weatherhead • Assistant Professor in Tropical Medicine and in Infectious Disease at Baylor College of Medicine Town Square with Ernie Manouse is a gathering space for the community to come together and discuss the day’s most important and pressing issues. Audio from today's show will be available after 5 p.m. CT. We also offer a free podcast here, on iTunes, and other apps. This interview originally appeared on NPR Houston’s “Townsquare with Ernie Manouse,” and can be read online here: ‘We are not done with
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the virus. And the virus is not done with us,’ says global health expert aboutomicron
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Media Mentions
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January 2020
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Could The Coronavirus Scare Have Been Avoided? One Leading Health Authority Thinks So Milwaukee Journal Sentinel | January 29, 2020 | Article
"We neglected to develop rapid diagnosis tests and neglected to develop and stockpile anti-coronavirus drugs, which we could have and should have done," Haseltine said. Haseltine said the genetic sequence for the new coronavirus appears to be a combination of two different kinds of SARS. A drug developed to fight one of the coronaviruses, he said, "will work against the whole family." The CDC in Atlanta was sent copies of Haseltine's comments but did not return calls and emails seeking comment. The article is available online here: Could the coronavirus scare have been avoided? One leading health authority thinks so
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Is America Ready?
USA Today | January 30, 2020 | Article
William Haseltine, an infectious disease and drug development expert and president of the global health think tank ACCESS Health International, said a coast-to-coast outbreak is not unfathomable. “We’re definitely not ready. This virus can spread, and it can be deadly,” said Haseltine, who headed research on an anthrax antidote. “We’ve prepared for bioterrorism in general. We haven’t prepared for coronavirus as a potential threat specifically.” The full article is available online here: Is America Ready?
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February 2020
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World Should Have Been More Prepared For Coronavirus, Says US Scientist William Haseltine The National UAE | February 3, 2020 | Article
Dr Haseltine, who was a professor at Harvard for two decades, and founded the university's HIV/AIDs and cancer research departments, said "China and perhaps India", and in fact any country with major population centres should do the same. "You can prevent a person who is exposed to HIV from contracting HIV with antiviral drugs," he said. "Those drugs work against most viruses. Especially if there’s a combination of those drugs." "I've actually worked on the flu, and we're due a much worse epidemic. "We're about 20 years overdue for a really nasty flu that will make the coronavirus look mild," he said, saying he is almost certain there will one day be a virus that spreads easily and is highly lethal. "Our brains are keyed to understand differences, if you actually look at numbers in terms of what kills people, in the US in the past 10 years we’ve had between 12 to 15,000 people die of the flu each year. So that’s a much bigger number, but we’re used to it. You believe you’re going to survive the flu, but this is new and unknown which is why there’s a greater fear factor." He said the major economic impact the coronavirus has had worldwide keeps the disease in the mind’s eye. "It’s shutting down China and airports, and that has a huge impact on our life. It’s changing our lives in a way the flu doesn’t. Now, should we quarantine flu because it kills on average 25,000 Americans a year? We don't because we know its limits. Or we think we know its limits." The full article is available online here: World should have been more prepared for coronavirus, says US scientist William Haseltine
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Coronavirus Death Toll Hits 564; Infant Infections Add Troubling New Element To Outbreak USA Today | February 6, 2020 | Article
William Haseltine, a former Harvard Medical School professor who recently returned from the central Chinese city of Wuhan after chairing a U.S.-China Health Summit, told USA TODAY he had never heard of a coronavirus infection from the womb. "However the infant is infected, it is certainly worrisome," Haseltine said. "The lungs in infants that young are not fully formed, putting them at greater risk than an adult." The article is available online here: Coronavirus death toll hits 564; infant infections add troubling new element to outbreak
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The Gross And Uncomfortable Way Doctors Test For The Coronavirus New York Post | February 13, 2020 | Article
Dr. William Haseltine, a US-China Health Summit chair and former Harvard Medical School professor, added that the more invasive respiratory testing is only conducted in cases when doctors determine “somebody can’t provide sample results with the more standard tests.” The article is available online here: The Gross and Uncomfortable Way Doctors Test for the Coronavirus
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First Coronavirus Case Of Unknown Origin Confirmed In US. What Does That Mean? USA Today | February 27, 2020 | Article
William Haseltine, a former Harvard Medical School professor who returned last fall from the Chinese city of Wuhan – the epicenter of the global outbreak – says the unknown exposure indicates many people may be unaware they have the virus because they barely notice the symptoms. "On one hand that is good news as it means the virus causes very mild symptoms in many people," Haseltine said. "On the other hand, it means that people can unknowingly infect others." The article is available online here: First coronavirus case of unknown origin confirmed in US. What does that mean?
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Coronavirus May Explode In U.S. Overnight Just Like In Italy The Daily Beast | February 27, 2020 | Article
Dr. William Haseltine, the president of the global health think tank ACCESS Health International who recently chaired the U.S.China Health Summit in Wuhan, China, where the outbreak originated, said it more plainly: “The wrong way to handle it is a quarantine.” “We should never consider stopping air travel or locking down cities,” said Haseltine. “Do we do that for the flu? No. Why would we do it for this? We know what its nature is. If we were treating this like we’d treat the flu, there’d be no lockdowns. There’d be no flight restrictions.” Haseltine argued that, ultimately, a long-term overhaul to the entire public health system was necessary, on everything from training and education to the supply of respirators. Still, the worst case scenario likely won’t be as bad as some fear, he said, calling the possibility of a boom in U.S. cases that pushed the American medical system to the brink “very unlikely.” “It’s much more likely that even more deadly strains of influenza arise and to strain our capacity,” he said. “We should be prepared for something worse,” Haseltine continued. “We could have already been prepared for this if we’d taken warnings seriously.” The article is available online here: Coronavirus May Explode in U.S. Overnight Just Like in Italy
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Is This Coronavirus ‘The Big One’? New York Times | February 29, 2020 | Article
William A. Haseltine, president of a think tank called Access Health International, told me that a vaccine might take at least six to eight months to develop and test — some other estimates are longer — and this should involve an immediate federal investment through Project BioShield. We also need better diagnostics and treatment as well as more ventilators to keep people alive. The article is available online here: Is This Coronavirus ‘the Big One’?
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March 2020
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China Constructed New Hospitals In Days, And Other Lessons From Their Response To The Coronavirus Mother Jones | March 5 | Article
William Haseltine, chair of the global health think tank ACCESS Health International and an infectious disease expert, echoed those concerns. Like Garzon, he found the WHO report sobering—the United States would have a hard time matching China’s response, he said. “It’s a sad day when China is outperforming the US in terms of public health.” Haseltine notes that all of this would be a lot easier if the United States had invested in outbreak preparedness measures before a crisis. As I wrote a few weeks ago, the Trump administration has hardly made this a priority: It did away with pandemic leadership, shelved a biodefense plan, and slashed emergency preparedness budgets. One helpful step, Haseltine said, would be training social workers to help with disease surveillance and intervention. “Social workers understand what the vulnerable populations are and how to communicate with them,” he said. “They need to be trained and integrated into our medical system.” He also underscored the importance of the federal government creating incentives for pharmaceutical companies to develop drugs. The article is available online here: China Constructed New Hospitals in Days, and Other Lessons From Their Response to the Coronavirus
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Pull The Pieces Together And Find The Soul Provider Magazine | March 2020 | Feature
Biologist, author, and educator William Haseltine pointed to Swan’s Market Cohousing, an urban community building in California that houses residents of all ages, including older adults. The building features common meals, monthly parties, and a neighbor-helping-neighbors philosophy. “There is so much that younger and older people can do for each other, and these relationships are mutually beneficial,” says Haseltine. Expect to see more of such efforts. In his book, Aging Well, he wrote, “In the United States and internationally, there is a continuing focus on community support and inclusive societies that allow older adults to remain active and engaged. This focus includes age-friendly cities, inclusive housing, and employment opportunities.” The article is available online here: Pull the Pieces Together and Find the Soul
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Could Widespread Coronavirus Testing Make Things Worse? Prevention Seen As Key IBTimes | March 5, 2020 | Article
Dr. William Haseltine, chairman of the U.S.-China Health summit and a former professor at Harvard Medical School, told IBTimes it’s likely we already have drugs that can combat the virus developed in research for fighting cancer, AIDS and other diseases. “This type of virus has occurred and spread three times in the last 20 years,” he said, adding, “We very likely have all the tools needed to develop combinations of drugs that will cure those infected and protect those who are not. But as we’ve learned from our experience, ignorance, complacency and denial are as much an enemy as the virus itself.” The article is available online here: Could Widespread Coronavirus Testing Make Things Worse? Prevention Seen As Key
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What To avoid In NYC This Weekend If You’re Worried About Coronavirus New York Post | March 5, 2020 | Article
“It’s overkill right now to tell people to stay home,” said Dr. William Haseltine, a US-China Health Summit chair and former Harvard Medical School professor. “But that could soon change. It’s unpredictable.” The article is available online here: What to avoid in NYC this weekend if you’re worried about coronavirus
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Coronavirus Vaccine at Least a Year Away, But Treatment Could be Here in Months Newsweek | March 10, 2020 | Article
Antivirals are much less strain-specific than vaccines because they target parts of the virus that don't change as easily, Dr. William Haseltine, chair and president of ACCESS Health International, told Newsweek. So researchers can develop a potential antiviral for a coronavirus strain before an outbreak even occurs. After three coronavirus outbreaks in 20 years—severe acute respiratory syndrome, Middle East respiratory syndrome and now SARS-CoV-2—it's an investment that needs to be made, Haseltine said, "These diseases are as much a natural disaster as earthquakes and hurricanes," he noted. "We can't prevent natural disasters, but we can certainly prepare for them, and we should treat these the same way we treat other natural disasters." The article is available online here: Coronavirus Vaccine at Least a Year Away, But Treatment Could be Here in Months
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Is The U.S. wasting The window Of opportunity To Contain COVID-19? China Global Television Network | March 11, 2020 | Article
When comparing what has been done to contain the COVID19 virus in the U.S. and in China, William Haseltine, chair of the global health think tank ACCESS Health International, said "It's a sad day when China is outperforming the U.S. in terms of public health." Former Assistant Secretary of Defense for East Asian and Pacific Affairs Kurt Campbell noted that the United States was "given some time by the unbelievably draconian steps that the Chinese have taken. I'm not sure we used that time effectively.” The article is available online here: Is the U.S. wasting the window of opportunity to contain COVID-19?
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Norwegian Cruise Line Managers Reportedly Pressured Employees To Lie To About Coronavirus Danger People | March 11, 2020 | Article
Another suggested talking point from the leaked emails stated: “Scientists and medical professionals have confirmed that the warm weather of the spring will be the end of the Coronavirus.” This is also misleading, according to Dr. Haseltine. In temperate climates, most people contract the cold or flu in the winter and cases slow down in the summer, but that’s not necessarily true of the tropics, he explains. “If you look at the distribution in tropical climates, it’s not that people don’t get colds and flus — they are more persistent and not as seasonal. They persist throughout the year at a lower, but nonetheless, cumulative level. It is less common for any given month, but collectively over the year, it’s pretty common.” Cruise companies received more bad news on Sunday, when the State Department issued a warning that U.S. citizens “should not travel by cruise ship” during the coronavirus outbreak, noting that the “cruise ship environment” can foster an “increased risk of infection.” The CDC issued a similar statement. Despite the official warnings, many major cruise lines, including Carnival and Royal Caribbean, are continuing to operate their planned itineraries. “Cruise ships are very unfavorable environments for disease transmission,” says Dr. Haseltine. “To continue running cruise ships is irresponsible. And we can see what the consequence is.” The article is available online here: Norwegian Cruise Line Managers Reportedly Pressured Employees To Lie To About Coronavirus Danger
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What Aggressive Coronavirus Lockdown Might Look Like In The U.S. Daily Beast | March 12, 2020 | Article
Dr. William Haseltine, president of the global health think tank ACCESS Health International who recently chaired the U.S.-China Health Summit in Wuhan, China, where the outbreak originated, said he believed the United States was “close to” authorities implementing such lockdowns. “Once you do something like in New Rochelle and stop people attending gatherings, I think it’s a real possibility,” he told The Daily Beast. “If the infection really gets out of control, and, if they’re accompanied by rigorous testing, I think China proved that it works. Everyone who moves at all in China has to report where they’ve been and where they’re going and then gets tested when they arrive.” The article is available online here: What Aggressive Coronavirus Lockdown Might Look Like In The U.S.
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Exclusive: A Spike In Coronavirus Cases Could Overwhelm U.S. Hospitals By The End of March, Defense Department Monitoring Shows Daily Beast | March 13, 2020 | Article
"There's very little substitute for ventilators and without ventilators, you can die," Dr. William Haseltine, chair and president of ACCESS Health International, told Newsweek. Telemedicine, where people can call their doctor rather than coming in for an examination, could be another crucial option, Haseltine said. He noted that the remote system isn't sufficiently integrated into America's system. Under the national emergency declaration, Health and Human Services Secretary Alex Azar, however, now has the ability to waive laws that could expedite building telemedicine systems. The article is available online here: Exclusive: A Spike In Coronavirus Cases Could Overwhelm U.S. Hospitals By The End of March, Defense Department Monitoring Show
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Four Ways Experts Say Coronavirus Nightmare Could End Daily Beast | March 16, 2020 | Article
As major cultural events are forgotten, workplaces, bars, and restaurants close, and prominent politicians around the world go into quarantine, two simple questions about the novel coronavirus pandemic seem to rise above the rest: How long will this last? And how will it end? William Haseltine, president of the global health think tank ACCESS Health International, who recently chaired the U.S.China Health Summit in Wuhan, where the virus likely originated, has a theory. “There are four ways,” the doctor told The Daily Beast. “One, it peters out with the weather. Two, everybody gets infected, so it’s got no new places to go... so it ends—but that’s a pretty horrible ending. Three is a vaccine, which is about a year away. Fourth way is the most likely: We’re going to have a few drugs, within a few weeks to a few months, that prevent people from getting infected— like PrEP for HIV—and for treatment.” The article is available online here: Four Ways Experts Say Coronavirus Nightmare Could End
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Asymptomatic Carriers May Still Transmit Coronavirus, Says New Research Health.com | March 17, 2020 | Article
Despite the most recent information and research, US agencies, including the CDC, maintain that the coronavirus is mainly spread by symptomatic people—but according to William Haseltine, PhD, president of the global health think tank ACCESS Health International, it's this way of thinking that may render the current mode of testing for the coronavirus in the US as "dramatically ineffective." Instead, Haseltine recommends a testing system known as "contact tracing," which, he says, has already been implemented in Singapore and South Korea. The method involves testing everyone with symptoms first; then, after identifying those with the virus, attempting to find and test every person the infected individual has come into contact with over a period of two weeks. Essentially, says Haseltine, it's not necessarily about how many tests an area has, but how they're used. "You want to catch people early, before they get sick," he says.
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Does Taking Ibuprofen Make Coronavirus Worse? Here's What Experts Have To Say People | March 18, 2020 | Article
Haseltine echoed his sentiments, noting that he hasn’t seen any data on the topic and it would require multiple controlled studies in order to determine the drug’s effect on patients. “The only way you can know that is through a controlled study,” he says. “You can suspect it, but unless you actually do a controlled study on people given an inflammatory and those who aren’t, you can’t tell.” Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, naproxen and ibuprofen, have been known to potentially suppress one’s immune system, according to a 2015 study called “Possible Immunosuppressive Effects of Drug Exposure and Environmental and Nutritional Effects on Infection and Vaccination.“
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Social Distancing, Self-Quarantining, Under Lockdown: Here's What Each Term Means People | March 18, 2020 | Article
Social Distancing The most flexible of these terms, social distancing is aimed at healthy people who do not have any signs of illness. The idea is to stay indoors as much as possible, avoid large groups (current guidance from the federal government recommends that Americans do not congregate in groups larger than 10) and stay six feet apart from other people. This is aimed at slowing the spread of COVID-19. The virus is highly contagious and can spread in several ways — through air molecules from sneezing or coughing, or on surfaces, where it can live for around 24 to 72 hours, depending on the material. People can also be asymptomatic or carriers for the virus without realizing they have it. All of these factors mean that healthy people can unknowingly spread the virus to people who are at a higher risk of developing a severe, life-threatening reaction. By social distancing, those people are reducing the chance that the virus spreads. “It’s important right now, because we don’t know how many people are infected,” Dr. William Haseltine, an infectious disease expert and Chair and President of ACCESS Health International, tells PEOPLE.
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Here’s How to Tell If That Sneeze Is Coronavirus, The Flu Or Just A Cold People | March 18, 2020 | Article
COVID-19 vs a cold At first, COVID-19 will seem very similar to a cold, with coughing and sneezing. “You start to see a cold, and the reason it’s called a cold is because you don’t have a fever,” Dr. William Haseltine, infectious disease expert and Chair and President of ACCESS Health International, tells PEOPLE. The initial symptoms are all upper respiratory, much like a cold. But if coughs begin to move down the chest, into the lower respiratory region, that’s when people should be concerned. This is a sign that it could be coronavirus. “If it feels like it’s in your chest, and then deeper in your chest, that’s when it’s quite serious,” Haseltine says. “That’s when your body starts reacting to it. Your body overreacts to it and creates the damage in your lungs, and that’s when it’s the most serious. The moment it moves from a light cold to a chest cold, you’ve got to go see a doctor, immediately.” But, Haseltine cautions, people should call their doctor or hospital first before going over to get tested and treated. That reduces the chance that an infected person will spread COVID-19 to other people in transit or at a doctor’s office. “In a serious case, though, call an ambulance,” he adds. “But about 15 percent of people will get a serious chest infection, and some of those are quite critically ill, and some people die from that,” Haseltine says.
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Public Health Experts Say Trump Is Bungling The Coronavirus Response Salon | March 28, 2020 | Article
A public health expert told Salon that President Donald Trump's handling of the coronavirus pandemic has been abysmal. "It definitely made it worse," Dr. William Haseltine told Salon when asked about Trump's reluctance to acknowledge the severity of the pandemic in January and February, when news of it first broke from China. "And his reaction was — it’s not the worst in the world — among the worst in the world. It was dangerous. It was spineless. It was heedless. It was self-serving." Haseltine is a biologist renowned for his work in confronting the HIV/AIDS epidemic, for fighting anthrax and for advancing our knowledge of the human genome. He is also the founder and former CEO of Human Genome Sciences, and is currently the chair and president of the global health think tank Access Health International. By his estimate, Trump's performance was very poor — and "did, and will" cost lives. "He should have been warning us it was coming," Haseltine told Salon. "He should have been preparing by stockpiling all the necessary equipment. But even today we're not doing what we should do. Let me put it that way. What we should be doing is contact tracing [identifying people who may have come in contact with infected patients] and having mandatory quarantines for everybody who's been exposed. And quarantining not at home, but in hotel rooms, single occupancy hotel rooms." He added, "That's how the Chinese control the epidemic. Anybody who was exposed, was confined to a hotel room for at least 14 days from the time of exposure. And they were served meals by hazmat-clad attendants. They weren't allowed to open their door. And even today, if you come into China from outside, you're required to do this quarantine at home without opening your door for 14 days. If you've come from another city within China — to
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Beijing for example — you've got to self-quarantine for 14 days. Even if it's a low-incidence area, you have to self-quarantine." Haseltine still believes these measures are warranted. "We've got to do very serious contact tracing, followed by mandatory quarantine for anyone who is exposed," Haseltine explained. "At this point, for example, that would include most of the Senate who encountered Rand Paul [the Republican senator from Kentucky who was diagnosed with COVID-19]. If we were in China, every single senator who had contact with Rand Paul would be in a 14-day single isolation hotel room. That's how they control the virus. And we don't."
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Docs Buck Bosses To Beg Cuomo For Coronavirus Protective Gear The Daily Beast | March 31, 2020 | Article
Dr. William Haseltine, president of the global health think tank ACCESS Health International, who recently chaired the U.S.China Health Summit in Wuhan, said that other countries— including India and Peru—do reuse medical equipment, including N95 masks. “I believe it can be done, but it should be done in ways that are controlled and are approved,” Haseltine said. “It shouldn’t be done fly-by-night or in the unapproved protocol. The whole purpose of regulation is to show that there’s assurance they will be safe.”
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April 2020
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Should You Be Wiping Down Your Groceries When You Get Home from the Store? Experts Are Divided People | April 1, 2020 | Article
Dr. William Haseltine, infectious disease expert and Chair and President of ACCESS Health International, recently also told PEOPLE that he believed sanitizing the packaging of products was “a little too much,” as they pose a low risk for transmission. “If you’re really worried about that, wear gloves when you open the packages,” he suggested. “Other than that, I wouldn’t worry about it.” When it comes to produce, Haseltine added that washing with soap “can help” minimize risk, but questioned the practicality of it. “I wouldn’t wash your lettuce with soapy water,” he said, “but something like a potato or an apple or a plum you can wash, the outside of a mango you can wash.”
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Tucker Carlson: Not Job Of Public Health Officials To Make "Big Decisions" About COVID-19 Response Salon | April 3, 2020 | Article
A public health expert explained to Salon last week that Trump's response to the crisis made things worse. "It definitely made it worse," Dr. William Haseltine — a biologist renowned for his work in confronting the HIV/AIDS epidemic, for fighting anthrax and for advancing our knowledge of the human genome — told Salon when asked about Trump's reluctance to acknowledge the severity after news of the pandemic first broke in January and February. "And his reaction was — if not the worst in the world — among the worst in the world. It was dangerous. It was spineless. It was heedless. It was self-serving." He added, "He should have been warning us it was coming. He should have been preparing by stockpiling all the necessary equipment. But even today we're not doing what we should do. Let me put it that way. What we should be doing is contact tracing [identifying people who may have come in contact with infected patients] and having mandatory quarantines for everybody who's been exposed. And quarantining not at home, but in hotel rooms, single occupancy hotel rooms."
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Medical Expert Gives Fox News A Stern FactCheck About Unproven Coronavirus Drug Huffington Post | April 6, 2020 | Article
A noted medical expert threw cold water on the idea that the anti-malarial medication hydroxychloroquine is a game-changing coronavirus treatment on Monday, delivering a stark fact-check on Fox News, which has repeatedly pushed the theory along with President Donald Trump. Fox News host Dana Perino asked biologist Dr. William Haseltine, who is president of ACCESS Health International and a former Harvard Medical School professor, to weigh in on the drug’s potential use as a treatment for COVID-19, the respiratory disease caused by the new coronavirus. “It’s sad, to me, that people are promoting that drug. We know already, from studies, at best it will have a very mild effect — at very best,” said Haseltine, who is well known for his groundbreaking research into cancer, genomics and HIV/AIDS. The scientist noted that a number of studies conducted on the drug’s effects against coronavirus have yielded conflicting results and that its use against other viruses in the past has been ineffective. He also highlighted the life-threatening impact it could have on people taking other medications. “It is not something to take unless a doctor prescribes it,” he said. A day earlier, the president had reasoned that there was nothing to lose by trying the unapproved drug as a treatment, prompting multiple medical professionals to speak up about the many dangers of taking hydroxychloroquine when it’s not yet proven to work in this setting. Perino then brought up exaggerated claims about the drug’s efficacy that have been pushed by her Fox News colleagues. “I know you don’t go by anecdotal evidence, but there are stories of people saying that they’ve had this Lazarus effect by using this drug,” she said. Haseltine labeled the stories “complete and utter nonsense.” 2453
“In any situation, there are always going to be people who promote one kind of quack cure or another. And there are Lazarus effects. In every epidemic I’ve ever looked at, it’s always the case. Let me just repeat, we know that at very best, this drug will have a very mild effect on changing the course of the disease, if it has any effect at all,” he said. “That is what the data has shown so far, and I am convinced that that’s what further studies will show. And it’s not without adverse consequence. It is irresponsible to promote this drug at this time.” The full article is available online: Medical Expert Gives Fox News A Stern Fact-Check About Unproven Coronavirus Drug
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How The Very Rich Are Different In The COVID-19 Fight CNN | April 6, 2020 | Article
\But the irony of an elitist approach during these times is that it may well backfire, according to Dr. William Haseltine, a biologist and former Harvard medical professor who recently chaired the ninth US-China health summit in the pandemic epicenter of Wuhan. According to Haseltine, the people who have left the city have put themselves at greater risk than if they had stayed put and practiced careful isolation and hygiene, because they have put themselves further away from the best hospitals. His opinion was echoed by New York Gov. Andrew Cuomo in his April 3 press conference, where he talked about the spike in Nassau and Suffolk counties. "Long Island does not have as elaborate a health care system as New York City ... and that has us very concerned," he said. Haseltine says it's "a fundamental mistake" to think you are safer in a wide-open space. "It's comfortable to be in a country house ... People feel they have more control," he says. "You have more space, you think that you're not one of many, you're more special. But it's all psychological." The risk of COVID-19, he says, is equated to how many people you meet who might be infected. It's not like the bubonic plague of London that was spread by fleas and rats. With COVID-19 there is no reason to think that people in the countryside are any less infected than the people in New York City. The full article is available online: How the very rich are different in the COVID-19 fight
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Fox guest describes malaria drug as 'quack cure' for coronavirus The Hill | April 6, 2020 | Article
A guest on Fox News is criticizing calls to use the anti-malaria drug hydroxychloroquine, calling it a "quack cure" typical of epidemics. "That is nonsense, complete and utter nonsense," Access Health International Chairman William Haseltine said in response to a direct question from Fox News's Dana Perino about the drug, which repeatedly has been touted by President Trump as a treatment for coronavirus victims. Haseltine said that it was "sad" to see people in positions of authority promoting usage of the drug without sufficient tests for its effectiveness. "In any situation, there are always going to be people who promote one kind of quack cure or another, and there are Lazarus effects. In every epidemic I’ve ever looked at, that is the case," he said. "It is not something to take unless a doctor prescribes it," Haseltine added. On Sunday, Trump hailed the drug as a potential treatment, acknowledging that he was not a doctor but asking what people had to lose in trying the drug. Experts have said there are risks, as the drug has side effects that could be dangerous to some people. The administration's promotion of the drug is reported to have caused a dispute during a meeting of the White House coronavirus task force on Saturday, during which White House trade adviser Peter Navarro supposedly aimed a line of sharp criticism at Anthony Fauci, the nation's top infectious disease expert, over his discomfort regarding such remarks. In her interview, Perino described the treatment as a drug that health experts say has not been proved to treat the coronavirus.
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The full article is available online: Fox guest describes malaria drug as 'quack cure' for coronavirus
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Top Biologist To Fox News Host Dana Perino: Unproven Drug Treatment Hyped By Trump Is A "Quack Cure" Salon | April 8, 2020 | Article
Dr. William Haseltine, a biologist renowned for his work in confronting the HIV/AIDS epidemic, fighting anthrax and advancing our knowledge of the human genome, told Fox News on Monday that an unproven drug treatment for the new coronavirus hyped by President Donald Trump was a "quack cure." "It's sad to me that people are promoting that drug. We know already from studies at best it will have a very mild effect — at very best," Haseltine told Fox News host Dana Perino about hydroxychloroquine, an anti-malarial drug that Trump has repeatedly promoted against the advice given by Dr. Anthony Fauci. After reviewing how previous studies show the drug to either have no effect or only a "very mild" one, Haseltine said "the thing that makes me sad about that story is some people may take it who are on other medications or have other underlying conditions and may have very serious — even life threatening — consequences. It is not something to take unless a doctor prescribes it." Perino then asked Haseltine about "stories of people saying that they've had this Lazarus effect by using this drug," an apparent reference to a claim made by her Fox News colleague Laura Ingraham. Haseltine replied, "That is nonsense — complete and utter nonsense. And, in any situation, there are always going to be people who promote one kind of quack cure or another, and there are Lazarus effects. In every epidemic I've ever looked at, it's always the case." The full article is available online: Top biologist To Fox News Host Dana Perino: Unproven Drug Treatment Hyped By Trump Is A "Quack Cure"
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Trump Lashes Out At Fox News Reporter: You should Say "Great Job Instead Of Being So Horrid" Salon | April 8, 2020 | Article
Dr. William Haseltine, a biologist renowned for his work in confronting the HIV/AIDS epidemic, for fighting anthrax and for advancing our knowledge of the human genome, told to Salon last month that Trump had failed to effectively confront the pandemic. "He should have been warning us it was coming," Haseltine told Salon. "He should have been preparing by stockpiling all the necessary equipment. But even today we're not doing what we should do. Let me put it that way. What we should be doing is contact tracing [identifying people who may have come in contact with infected patients] and having mandatory quarantines for everybody who's been exposed. And quarantining not at home, but in hotel rooms, single occupancy hotel rooms." The full article is available online: Trump Lashes Out At Fox News Reporter: You should Say "Great Job Instead Of Being So Horrid"
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For Fox News hosts, The Hydroxychloroquine Controversy Is Fuel For The Culture War Washington Post | April 10, 2020 | Article
On Monday afternoon, for example, daytime host Dana Perino interviewed a former Harvard Medical School doctor, William Haseltine, who called the drug a “quack cure” with potentially dangerous side effects. But the skeptical interviews have occurred outside prime-time hours, when the audience is far smaller than those attracted by Carlson, Ingraham and Hannity. The full article is available online: For Fox News hosts, The Hydroxychloroquine Controversy Is Fuel For The Culture War
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Experts Fear Coronavirus Vaccine May Only Provide "Short-Term" Immunity From Virus Salon | April 10, 2020 | Article
William Haseltine — a biologist renowned for his work in confronting the HIV/AIDS epidemic, fighting anthrax, and advancing our knowledge of the human genome — told Salon on Wednesday that he has questions about how coronavirus immunity is conferred. "The situation is more complicated than either of those arguments," Haseltine explained. "The fundamental question is, what type of immunity does the coronavirus infection engender? Is it lasting immunity or is it short-lived immunity? And for those types of immunity, how broad of a spectrum it is. So there is definite evidence that infection with coronaviruses — SARS and MERS included, and studies with this component of this virus — suggest that infection does induce protective immunity. That's the first thing." He added, "But the question is, for other coronaviruses, that protection is neither broad nor long-lasting. And there's some evidence from earlier studies with other coronaviruses that reinfection can occur after one year. Now there's a little bit of that, whether it's reinfection with precisely the same strain or a slight variant of the same strain, which means that protection isn't broad and may not be long-lasting." Salon also asked Haseltine about a recent report from a Los Angeles doctor, Dr. Anthony Cardillo, that he was able to combine hydroxychloroquine with zinc to effectively treat COVID-19 patients. Haseltine had previously told Fox News' Dana Perino that the drug, which is being touted by President Donald Trump (who has a financial stake in a company that manufactures it), is a "quack cure." "I do not believe him," Haseltine told Salon. "I say he's exaggerating. Either that or he is using a very selective group of patients. But let me say, I tell you what normally happens when you 2461
read these papers: What people find is, it is very difficult — especially in the early stages — to tell whether or not hydroxychloroquine is having an effect. The major reason for that is that most people, 80% of people, resolve normally. So 80% of the time, if you don't test them, if you give them water, they're going to recover. How do you know whether your drug is having an effect? Unless you have a very large controlled clinical trial, you're not." He added, "Anecdotal evidence does not cut it. 10 patients, 20 patients, 30 patients, it doesn't cut it. You need a large controlled study and you need to introduce the drug at different stages of the disease. When people are fully healthy, do they progress when they're beginning to get ill? Does it shorten the progression? Does it change the course for a large numbers of patients?" The full article is available online:Experts Fear Coronavirus Vaccine May Only Provide "Short-Term" Immunity From Virus
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Here’s How We Extricate Ourselves From This Lockdown The Daily Beast | April 13, 2020 | Article
According to William Haseltine, a former Harvard Medical School professor and the president of the global health think tank ACCESS Health International who recently chaired the U.S.-China Health Summit in Wuhan: “It should be a hand-held device for $5 a pop.” “That could be done by the end of the summer,” he told The Daily Beast. “We could do it if our economy depends on it.” Of course, elsewhere around the globe, tests have been performed by the hundreds of thousands—in other words, far more per capita than the United States. And many experts still say it’s necessary for the U.S. to reach that capacity, including those at the right-of-center American Enterprise Institute who put forward a plan this month that would require about 750,000 tests per week in the U.S. The full article is available online: Here’s How We Extricate Ourselves From This Lockdown
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Limbaugh Falsely Claims Criticisms Of Trump's Coronavirus Preparedness Are "A Political Hit Job" Salon | April 15, 2020 | Article
"[Trump] should have been warning us it was coming," Dr. William Haseltine, a biologist renowned for his work in confronting the HIV/AIDS epidemic, for fighting anthrax and for advancing our knowledge of the human genome, told Salon last month. "He should have been preparing by stockpiling all the necessary equipment. But even today we're not doing what we should do. Let me put it that way. What we should be doing is contact tracing [identifying people who may have come in contact with infected patients] and having mandatory quarantines for everybody who's been exposed. And quarantining not at home, but in hotel rooms, single occupancy hotel rooms." The full article is available online: Limbaugh Falsely Claims Criticisms Of Trump's Coronavirus Preparedness Are "A Political Hit Job"
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Rickter Scale: In Search Of The Lost Cure Victoria News | April 15, 2020 | Article
We will thankfully, mercifully, eventually emerge on the other side of the killing fields of COVID-19. For the time being, however, this crisis of pandemic proportions caused by an invisible virus currently has the Grim Reaper working overtime in every part of the planet. The question we must grapple with moving forward is whether to heed the advice and take to heart the lessons learned from those who saw it coming. Doctor William Haseltine is one of the voices that raged before this particular tidal wave long before it crashed onto our shores. The chair of ACCESS Health International had seen this before. When you have forged a career teaching at Harvard Medical School and founded two departments dedicated to research on cancer and HIV/AIDS, it’s a given that your opinion should carry considerable weight. In a recent interview, Haseltine said when scientists worked on a SARS vaccine in 2003, all kinds of drugs were developed in China, Singapore and the United States that showed promising results in dealing with that particular viral scourge. Unfortunately, these breakthroughs in research were only uncovered after SARS had run its course, so there was no “economic model” for Big Pharma to continue down that path. Although I’m not an expert in deciphering scientific jargon, I believe “no economic model” roughly translates into there was no evidence testing and production of those drugs would increase the companies’ profit line. Haseltine said the same pharmaceutical companies are now “racing to recover those chemicals.” He strongly suggests that if governments had stepped in and demanded the ingredients and recipes be kept in the drug companies’ cupboard, we might be in a much better place than we are today.
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The full article is available online: Rickter Scale: In Search Of The Lost Cure
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Was That Cold I Had In November Or December Coronavirus? Daily Beast | April 19, 2020 | Article
On Friday, preliminary results from the Stanford study pointed to as many as 4.6 percent of the Santa Clara County population possibly having antibodies for the coronavirus—85 times the number of confirmed COVID-19 cases there. But experts told The Daily Beast that even those numbers are still a long way off from creating so-called herd immunity, and there was still little-to-no evidence of U.S. infections back in 2019. “It’s possible but I wouldn’t say it’s very likely,” said Dr. William Haseltine, president of the global health think tank ACCESS Health International and former Harvard Medical School professor, who recently chaired the U.S.-China Health Summit in Wuhan, in an interview with The Daily Beast. Those who lived in current COVID-19 hot spots back in the fall and had recently travelled from Wuhan or hard-hit areas in Europe, had an unusually bad cold with a prolonged fever, were tested for the flu and had the results come back negative—“maybe they had this,” was as far as Haseltine would go. But he remained skeptical that there were very many, if any, such cases that had not yet been detected. The full article is available online: Was That Cold I Had In November Or December Coronavirus?
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Arizona Has Done 51,000 COVID-19 Tests. The State Needs Double That Each Month To Safely Reopen, Expert Says Arizona Republic | April 19, 2020 | Article
The state is missing demographic data about positive cases and deaths, its location data mixes hospitals with private residences, and the state won't provide data about cases and deaths on Indian reservations or in nursing homes. "It just isn't going to work unless you have crystal clear data," said William Haseltine, an infectious disease expert and president of the global health think tank ACCESS Health International. "If Arizona doesn't have that they are miles away from being prepared to reopen." ... Serology tests are "vital to know who is at risk and who isn't," giving those who are not at risk more freedom of movement, including returning to work, Haseltine said. "If you have a high concentration of antibodies against the virus, you're likely to be protected," he said. "Not 100%, but more likely than not." Haseltine, who is a former professor at Harvard Medical School, said both the PCR testing and serology tests are critical to safely opening the economy. "The two kinds of testing have to be available and they need to be available to test most people repeatedly," Haseltine said. Without tests, 'you have a blindness' ... Haseltine, the former Harvard Medical School professor, said rigorous contact tracing, where health authorities track down everyone who has potentially been exposed, is needed before reopening the economy. Arizona has not done a good job of contact tracing, which involves requiring people who've been exposed to isolate themselves and to be monitored by health officials. 2468
Haseltine said people who have been laid off during the pandemic could be hired by health departments to help do this work. "It requires training, manpower, organization and access to tests, and it requires compliance by the population," he said. "And if the compliance isn't voluntary it should be made mandatory with sentencing, fines and imprisonment if necessary. That's tough medicine but it's the only way to get back to work." The full article is available online: Arizona Has Done 51,000 COVID-19 Tests. The State Needs Double That Each Month To Safely Reopen, Expert Says
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How To Avoid A Pandemic Patriot Act Washington Post | April 21, 2020 | Article
The last time the United States faced a big, hard-to-track threat, we ended up with the Patriot Act and a mass-surveillance program that still rankles. This time, how do we use technology to combat the novel coronavirus without creating elements of a police state? Technology ought to be our best weapon in maintaining public health as the United States transitions back to work. High-tech testing can identify who had covid-19 (and is more likely to be “safe” now), and who’s most vulnerable to infection as the country opens up. Contact tracing can help minimize second and third bounces of the virus — while we all wait for the vaccine that, hopefully sometime next year, will bring some real relief. This transition is doable. The tools are in our hands, literally, in the cellphones most Americans carry. The two giants of cellular telephony, Google and Apple, have already created a joint contact tracing technology that would live on our Android and iPhone devices. ... Let’s start with the first step back, which is the public health puzzle: How do we fight what President Trump calls the “invisible enemy” without creating a “Patriot Pathogen Act” that grossly compromises civil liberties? How, in short, do we avoid the mistakes of the post-9/11 surveillance state? What’s needed is a trusted national intermediary that can coordinate public and private efforts better than this administration seems able or willing to do. One good candidate would be the National Academy of Sciences, as proposed by Glenn Gerstell, another former NSA general counsel. The academy could help coordinate public health authorities at the federal, state and local levels. It could connect doctors and hospitals through their national associations in a coherent national testing program. It could act as a fiduciary to collect testing and contract-tracing information.
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China shows how surveillance technology can help restart a country, at the cost of freedom. William A. Haseltine, a prominent health researcher, described in an email last month how China has managed the transition from lockdown using a color-coded system that’s part of a WeChat app on everyone’s phone. If your code registers green at the doorways of stores and restaurants, you’re free to enter. Otherwise, forget it. The United States doesn’t want to be China. But we need a framework that allows us to use technology to recover from economic paralysis. Tracing and tracking using cell phones will not be silver bullets for covid-19, but they will help. Augmenting our currently slow testing regime with immediate-result antibody tests is a vital step. There will be gaps, and statisticians will have to make inferences based on limited data, stresses Sean Roche, a former top technology officer at the CIA who’s advising nonprofit groups and companies on digital technology issues. Certainly, we’ll need rules for how data is collected, how it’s anonymized, when it is used and how long it’s kept. But we need to get started, now. The full article is available online: How To Avoid A Pandemic Patriot Act
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Fox News Hosts Go Mum On The COVID-19 Drug They Spent Weeks Promoting Washington Post | April 22, 2020 | Article
At the height of Fox News’s coverage of a would-be treatment for the novel coronavirus, the network’s medical correspondent, Marc Siegel, offered a remarkable testimonial during Tucker Carlson’s show. Siegel said his 96-year-old father, suffering from symptoms of the virus and fearing he would die, made a full recovery thanks to the drug, hydroxychloroquine, and a course of antibiotics. “He got up the next day and was fine,” Siegel told an astonished Carlson. Siegel’s miraculous-recovery story was part of a near-campaign for hydroxychloroquine by Fox News and its sister network, Fox Business. Echoing President Trump’s description of the drug as a “game changer,” Carlson, Laura Ingraham, Sean Hannity, Lou Dobbs and “Fox and Friends” hosts spoke of its potential benefits in dozens of segments from mid-March to mid-April. They also criticized those in the media and the medical establishment who raised concerns, turning a debate among researchers and scientists into another front in the culture wars. But in the past week or so, Trump has all but stopped talking about hydroxychloroquine. And so have Fox News’s hosts. ... Given the new data, Fox News has an obligation to give equal time to the doubts and potential dangers of hydroxychloroquine, said William Haseltine, the eminent biologist and biotech entrepreneur. “That’s just public responsibility,” said Haseltine, who is chairman and president of Access Health International, a nonprofit organization that seeks to expand access to health care. “They have a duty to inform their [viewers] that they made a mistake. It’s not a crime to make a mistake, but they do need to correct it.”
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In contrast to the network’s popular commentators, Fox’s News’s programs and website have been more cautious and have reported on the new research. The full article is available online: Fox News Hosts Go Mum On The COVID-19 Drug They Spent Weeks Promoting
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Coronavirus diary – Part 3
The Guardian | April 22, 2020 | Article
I have been impressed with the urgency of doing. Knowing is not enough; we must apply. Being willing is not enough; we must do—Leonardo da Vinci. In a prognostic reflection, Professor Devi Sridhar, chair of Global Public Health at the University of Edinburgh cast four scenarios in the battle against COVID-19 in the absence of a vaccine. One is a global consensus and collaboration that would be “dependent on a rapid and cheap point-of-care diagnostic”; simultaneous border closure by all countries with time frame; and “an aggressive campaign to identify carriers of the virus and prevent transmission.” Two, without a vaccine yet, effort would be to delay the spread of the virus over a period of a year plus with comprehensive preparation to treat those infected. Three, the adoption of the South Korean model which include “increase testing to identify all carriers of the virus, trace the people they have contacted, and quarantine them for up to three weeks” as well as “large-scale planning, the swift development of a contact-tracing app, and thousands of volunteers to help with swabbing, processing results and monitoring quarantine.” Four, treatment of the symptoms of COVID-19 by administering antiviral therapies that stabilise patients to reduce the need for intensive care, or prevent fatalities at critical point. Additional thereto, is the use of “prophylactic therapy to prevent the onset of COVID-19, in combination with rapid diagnostic testing to identify those who have been infected”. Why the World Health Organisation has developed a comprehensive and imaginative research blueprint to deal with the COVID-19 pandemic, nations have largely followed one or more of Sridhar’s typologies. The South Korean model may well be rechristened the Asian model that was seeded in China’s Wuhan and has fared well in Singapore. It entails widespread testing including preemptive test even before any manifest symptom, aggressive contact-tracing and compulsory quarantine. In “Why America is 2474
Losing to COVID-19” William A. Haseltine gave a vivid picture of some of the measures that the Chinese authorities took. In her account, “In China, quarantines are monitored through an app. Everyone receives a unique QR code showing their status – green if you’re clear of infection, yellow if you’ve been instructed to stay indoors, red if you are under quarantine. If you’re roaming the streets and your QR code flashes red, you will immediately be moved back to quarantine, or else you may face fines or jail time. Singapore has taken this technology even further, launching a new Trace Together app that people can download to help protect themselves and those around them. If a user passes within two meters of someone who is found to be infected, the app immediately notifies the user of the risk”. … The full article is available online: Coronavirus diary – Part 3
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Arizona Has Worst Day Of Confirmed Coronavirus Cases Yet The Hill | April 27, 2020 | Article
Arizona experienced its worst day of the coronavirus pandemic on Thursday, reporting 310 new infections which pushed the state's total confirmed case count to 5,769. Additionally, 66 Arizonans have died from the disease in the past three days, the most the state has seen in that time frame to date. Nearly 3,000 of the state's cases have come from Maricopa County, where the cities of Phoenix and Mesa are located, according to data compiled by The New York Times. Also on Thursday, the Arizona Department of Health Services (ADHS) announced that it was receiving an additional $12.4 million from the Centers for Disease Control and Prevention (CDC) to combat the outbreak. ... The percentage of positive tests has increased since the end of March, from 9 percent to 12 percent. Many lawmakers and experts have indicated that more widespread testing across the country is needed before states can start lifting the restrictions they have put into place during the pandemic. William Haseltine — an infectious disease expert and president of the global health think tank ACCESS Health International — told the Republic that Arizona would need to have the capacity to test 100,000 people a month before it can reopen its economy safely. The full article is available online: Arizona Has Worst Day Of Confirmed Coronavirus Cases Yet
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Early Funding Key To Finding Drugs That Will Fight COVID-19 Karma Impact | April 27, 2020 | Article
It all comes down to money and early funding to develop drugs against COVID-19. Ground-floor funding of drug research makes all the difference in whether a potential pharmaceutical solution hits the marketplace in a timely fashion, Dr. Deepak Srivastava of the biomedical research organization Gladstone Institutes, said on a conference call this week that discussed funding antiviral solutions to COVID-19. The pandemic has mobilized scientists worldwide to work in concert in “an unselfish way.” … According to Nature, as of April 8, the global COVID-19 vaccine research and development landscape includes 115 vaccine candidates, 78 of which are active. All but five of them are at the exploratory or preclinical stages, and some more advanced projects are now in clinical development, which can include drug discovery and product development, pre-clinical research (used on microorganisms and animals) and clinical trials (used on humans). “Science will save you,” William A. Haseltine, chair and president of ACCESS Health International, said Wednesday at the Boundless Impact webinar. “It may not save you tomorrow, but eventually it will save you from this pandemic. I am 100% confident we will develop drugs for those infected.” Haseltine, a former professor at the Harvard Medical School and the Harvard School of Public Health and a noted researcher on HIV/AIDS and cancer, said that compounds used in the treatment of earlier global diseases, such as SARS and MERS, have shown promise in fighting COVID-19. He added that no remedies on the market today have proven effective in countering the virus. … The full article is available online: Early Funding Key To Finding Drugs That Will Fight COVID-19 2477
May 2020
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Challenges, Opportunities, And Innovations In The Health And Well-being Of Tthe World’s Aging Citizens Caring for the Ages | May 1, 2020 | Article
William Haseltine, PhD, is cautiously optimistic about the future of aging in this country. However, he also acknowledges many challenges still need to be addressed. In his most recent book, Aging Well: Solutions to the Most Pressing Global Challenges of Aging (Palgrave Macmillan, 2019), he and coauthor Jean Galiana, MASM, RCFE, identify some of these challenges and offer innovative solutions. Through interviews with experts and leaders in the field, they have created a vision of how providers and government entities around the world can work to improve elder care and social support systems and enhance the well-being of older adults. From Workforce to Ways We Work: Change and Challenges Dr. Haseltine and Ms. Galiana addressed several issues of great concern to both practitioners and providers, including the workforce shortage in geriatrics. “This shortage threatens to grow as the population ages,” they wrote. “The World Health Organization cites that to meet the need of the growing older population, all health care providers must be educated in gerontology and geriatrics.” They also discussed the move to value-based care, noting that managed care and home-based care “are two trends that can lower costs and improve care ... this value-based care reimbursement arrangement is an incentive for health care systems to be efficiently integrated and provide higher-quality, lower-cost care.” They further noted, “Value care arrangements shift health systems from a medical model to a public health model.” A Vision of Integrated Care
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A move to integrated care is key, Dr. Haseltine stressed in an interview with Caring for the Ages. “The solution we’re not looking at but should be involves integrating social and medical care. We’re not really doing this now, but I believe that the ultimate goal should be total integration,” he said. For instance, he noted that social determinants of health aren’t captured in even the most sophisticated medical records. He said, “The integration of this information with medical data is extremely valuable and can have a positive benefit.” He suggested that it can help ensure management of comorbid diseases in a coordinated way that enables people to stay healthy, active, and engaged for as long as possible. “What better way to do this than to know the social determinants of health for each person?” he asked. “This is where we should be heading.” One thing is clear, Dr. Haseltine told Caring. “You can’t always treat patients in hospital. Many of our patients shouldn’t be hospitalized. Increasingly, most care takes place at home and the community. We need to be transferring functions to a different kind of health care worker who has some specific education and can provide quality care at lower costs.” He offered an example where such a model is working. In India, he said, workers are educated in six weeks to become ambulance medical technicians. “They do extremely well. They’ve saved millions of lives, and there is a huge difference in cost,” he said. “By changing who delivers care and using tools to manage, monitor, and measure performance, we can get to where we need to be.” This is not mission impossible, Dr. Haseltine said. “There are many people who would love to do these jobs. We have to find them, find ways to allow them to work here legally, and train them.” However, he added, “There are huge challenges caused by demographics and immigration, which are very tightly coupled.” Dr. Haseltine and Ms. Galiana also addressed housing models, such as villages and naturally occurring retirement communities, that can contribute to lower long-term services and supports. However, they noted, “Even with better emerging delivery and reimbursement models, health systems around the world are facing challenges in financing higher-quality, lower-cost long-term services and supports for older adults.” One of the challenges of efforts to move to a more cost-effective system of care, Dr. Haseltine told Caring, is that health care is an 2480
extremely profitable industry and this is “vital to the way our economy is structured.” He observed, “It isn’t that we don’t know what to do, but there are powerful disincentives to do what is right.” Drilling Down to Innovations in Dementia Care Aging Well, of course, included a thoughtful discussion of dementia care, with insights and best practices from communities implementing Eden Alternative principles and the Green House Project model. These two concepts are designed to maximize person-centered care, which puts residents at the center of the organizational structure and creates a home-like environment that often includes pets, gardens, and other amenities. These concepts also stress the value of a team-based culture, which “creates consistency and deeper connectedness to the residents … and lowers overhead costs.” These initiatives are showing great promise and enabling positive outcomes such as lowered use of antipsychotic medications. Dr. Haseltine told Caring that despite efforts to understand dementia, many studies continue to show that significant improvements are needed in the diagnosis and treatment of this disease, especially in terms of access to services, disease management, communication, and coordination. “In terms of what we can do to manage the care of a large, growing population with cognitive dysfunction, we’re doing little. However, in the U.S. and other countries, there are wonderful examples of innovative care and the use of new tools to improve quality of life and reduce risks,” he said. Voices in Dementia Care In their book Voices in Dementia Care: Reimagining the Culture of Care (Greenleaf, 2020), Dr. Haseltine and coauthor Anna Dirksen interviewed numerous dementia care experts across the United States and Europe. They painted a clear picture of the struggles and challenges of caring for people with dementia, especially in light of a rapidly growing older population worldwide. Based on their interviews, the authors identified critical best practices that they believe all post-acute and long-term care providers should consider when delivering care to people living with dementia: inclusion, person-centered care throughout the continuum and in 2481
all settings, reducing risks associated with dementia, creating environments to promote autonomy and freedom of choice, embracing the potential of new technologies (to support care, quality of life, functioning, independence, and autonomy), coordinating care at the highest level, and supporting informal caregivers. These practices, Dr. Haseltine said, “can be adapted and applied by family and other informal caregivers as well.” In his conversation with Caring, Dr. Haseltine stressed the importance of reaching out to family members and other informal caregivers. He said, “People with dementia often receive fragmented and uncoordinated care that doesn’t properly address their needs or the needs of the family and friends who care for them. Even diagnosis, the first step to treatment, is out of reach for most.” Lessons Learned From his many conversations with experts and his deep dive into aging issues on a global scale, Dr. Haseltine has learned several lessons, which he shared in Aging Well. Among these are: • The availability of affordable long-term care insurance is essential. • Person-centered care is a lynchpin of quality care and wellbeing for older adults, regardless of where they are receiving that care. • Support and palliative care in the home and community are key to making quality care assessable and ensuring that people’s wishes are respected as they move through the care continuum. • Coordinated primary care improves care for older adults and lowers costs. • Social inclusion and opportunities to live purposeful lives are necessary to older adults’ happiness and well-being. While Dr. Haseltine and his coauthors see many needs and opportunities for change and improvement in care systems, social supports, financing, education, and other areas impacting PALTC, they also see hope. The best practices and examples of innovation they share in their books show that positive, problem-solving, productive work is already being done by passionate, skilled, committed people. These stories are inspiring and empowering for 2482
readers and can be adapted for further innovations moving into this new decade. The full article is available online: Challenges, Opportunities, And Innovations In The Health And Well-being Of Tthe World’s Aging Citizens
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Science Without The Luxury Of Time Scientific American | May 8, 2020 | Article
It’s long been a sticking point between the public and science: a disaster befalls us unexpectedly, and we, of course, want answers immediately. But in the cruelest kind of irony, most science cannot be done in a rush. The beauty of the scientific method is its careful use of observation over time—tracking the migration patterns of birds for decades, for example. Or, when it comes to drug development, the gold-standard randomized controlled clinical trial, where an equal proportion of patients are given no treatment at all to serve as a baseline against which researchers can compare any effects of the drug being given to the other participants. These careful procedures give us the best science. They take time and a kind of cool detachment, allowing data to roll in before conclusions are drawn. But tell that to the family of a woman in severe respiratory distress from COVID-19. Waiting to know which of the handful of potential treatments for the novel coronavirus might be effective is a privilege of time that many patients don’t have. In this issue, health and medicine editor Tanya Lewis gives a detailed survey of the batch of drugs researchers are rushing to test scientifically, even as they are being put to the test on a case-by-case basis (see “Here’s What We Know about the Most Touted Drugs Tested for COVID-19”). Elsewhere, journalist Stacey McKenna takes a sobering look at what researchers actually know about immunity to the virus (see “What Immunity to COVID-19 Really Means”), and biologist William A. Haseltine evaluates the limitations of a vaccine solution (see “Can We Really Develop a Safe, Effective Coronavirus Vaccine?”). The common theme to all these riveting stories? Making safe and effective medicine needs time—the one luxury we now cannot afford. The link to this article can be found here: Science without the Luxury of Time.
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Kellyanne Conway Criticizes Anti-Trump Group Co-Founded By Husband Salon | May 8, 2020 | Article
Kellyanne Conway, who serves as a White House counselor to the president, denounced the members of a conservative anti-Trump group co-founded by her husband as failures during a Thursday appearance on Fox News. Conway told Fox News host Harris Faulkner that the group of strategists and consultants who run the Lincoln Project "never achieved what I achieved, which is success as a presidential campaign manager. They all failed." She disagreed with a disclaimer by Faulkner that her line of questioning was unrelated to the identity of her husband, saying that it "certainly" was about him or "you would've quoted other people in the group." George Conway commented on Trump's response to a recent Lincoln Project ad titled, "Mourning in America," which blamed the president for insufficiently responding to the coronavirus pandemic in a Washington Post editorial published Wednesday. After calling out Trump for referring to members of the Lincoln Project as "loser types" who were "a disgrace to Honest Abe," George Conway claimed that Trump "fears the truth. He fears being revealed for what he truly is. Extreme narcissists exaggerate their achievements and talents, and so Trump has spent his life building up a false image of himself — not just for others, but for himself, to protect his deeply fragile ego." An April ad from the Lincoln Project argued that Trump "just didn't care" about the coronavirus pandemic and instead spent his time at "campaign rallies and golfing." George Conway refuted the Republican claim that Trump was too distracted by impeachment to respond to the pandemic in March by noting, "Look at the calendar. The impeachment trial ended on Feb. 5. In reality, it was over before it even started, thanks in large part to McConnell. The only drama was about whether there'd be any witnesses — and that 2485
ended on Jan. 31, when the Senate voted not to hear testimony. That left plenty of time to deal with the virus." Two months earlier, the Lincoln Project took out an ad against Sen. Susan Collins, R-Maine., which claimed that her support for a Trump ally, Senate Majority Leader Mitch McConnell, R-Ky., showed that she is "there to support corruption and loyalty to a political party." George Conway has also contributed to the campaign of former Vice President Joe Biden, the presumptive Democratic nominee for president. Trump implemented a number of policies which critics claim to have weakened America's ability to respond to the coronavirus outbreak, including disbanding a National Security Council pandemic panel praised by experts, advocating for major budget cuts to the Centers for Disease Control and failing to provide Americans with accurate scientific information. "He should have been warning us it was coming," Dr. William Haseltine, a biologist renowned for his work in confronting the HIV/AIDS epidemic, for fighting anthrax and for advancing our knowledge of the human genome, told Salon in March. "He should have been preparing by stockpiling all the necessary equipment. But even today we're not doing what we should do. Let me put it that way. What we should be doing is contact tracing [identifying people who may have come in contact with infected patients] and having mandatory quarantines for everybody who's been exposed. And quarantining not at home, but in hotel rooms, single occupancy hotel rooms." The link to this article can be found here: Kellyanne Conway criticizes anti-Trump group co-founded by husband
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New York’s Antibody Testing Spree Could Be A Game Changer Daily Beast | May 10, 2020 | Article
New York City remains under seemingly interminable pandemic lockdown. But as researchers around the globe chase the promise of antibody tests—which have faced criticism for their mixed accuracy and dubious reputation as harbingers of COVID19-immunity—a new wave of such testing in America’s largest city offered a glimmer of hope. Mayor Bill de Blasio on Thursday detailed a plan to ramp up antibody testing locally, and specifically to survey about 140,000 people over two weeks in order to “understand COVID-19 spread and provide New Yorkers with more clarity,” as his office explained. Five testing sites will be set up in each of the five boroughs, according to the mayor, the idea being to provide free tests to 1,000 people per day by appointment through a hotline. Results from the tests will be available within 24 to 48 hours, he said. So-called serology, or antibody, tests can determine if a person recently had the infection and may—may—have developed enough of the right kind of immune response to offer some protection from illness. De Blasio’s announcement came a few days after Gov. Andrew Cuomo detailed the results of a New York State antibody initiative that tested 15,000 people and concluded roughly one in five NYC residents had been infected. But as Dr. William Haseltine, a former Harvard Medical School professor and the president of the global health think tank ACCESS Health International, explained, there are a few issues even with some of the antibody tests that have received that preliminary OK. Some are not specific enough about what coronaviruses they pick up on. This means that even if most people who were infected developed an effective immune response to the virus, some tests might not determine if they’ve had COVID-19 or an unrelated cold. What’s worse, tests that have not been given such authorization have dominated the market, bringing concerns about accuracy and 2487
credibility to all antibody tests, even those that can perform with excellent specificity and sensitivity. But perhaps the main issue, according to Haseltine, is that experts are still uncertain that people who recover from COVID-19 can even create enough of the right immune response to protect them from reinfection. There simply isn’t enough data to know for sure yet. On the first point, though, there’s growing optimism that these tests may play a part in pandemic surveillance—sooner than later. “It really depends on which test you’re using,” said Wajnberg, who has been directing a team testing serum antibodies to identify donors for Mt. Sinai hospital’s convalescent plasma program since the pandemic began to ravage the city. The serology test Mount Sinai is using in her department has an “extremely high specificity and does not cross-react with other coronaviruses,” she said. Still, Wajnberg and Haseltine cautioned there were still too many unknowns to say for sure that someone who tested positive for antibodies—especially given the varied quality of tests—has any actual immunity. Essentially, the test might be a game-changer for data collection and knowledge about the virus, but it won’t definitively be able to tell you that you can safely return to work. “It definitely does not mean that you are protected,” added Haseltine. “But it can give you an idea of how widely the infection has spread within the population.” To that end, he continued, “If they really want to have an idea of how widespread the infection is, they should make every possible effort to represent every group in the city, particularly underserved minority groups. Look at people who are homeless, in jails, in eldercare homes, people who are on food stamps, to get a crossrepresentation of the city and map it by geographical area, then make that detailed information public.” Ultimately, Wajnberg argued, a survey like New York City’s forthcoming one could be valuable because it might provide vital information to policymakers about how and when to open the city. For example, she said, “if this has affected 30 percent of our population, that’s very different than 1 percent. In terms of reopening, it will help modelers and epidemiologists plan better for what we can expect to see in three months or six months.”
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The link to this article can be found here: New York’s Antibody Testing Spree Could Be a Game Changer
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WHO Says Some COVID-19 Medicines Can Shorten Illness — But Hydroxychloroquine Is Ineffective Salon | May 12, 2020 | Article
The World Health Organization (WHO) announced Tuesday that there are treatments which seem to limit the severity or length of COVID-19, and that they hope study four or five of the most promising ones. "We do have some treatments that seem to be in very early studies limiting the severity or the length of the illness, but we do not have anything that can kill or stop the virus," WHO spokeswoman Margaret Harris explained during a briefing, according to Reuters. She added, "We do have potentially positive data coming out but we need to see more data to be 100% confident that we can say this treatment over that one." Salon spoke with Dr. William Haseltine, a biologist renowned for his work in confronting the HIV/AIDS epidemic, for fighting anthrax and for advancing our knowledge of the human genome. He is also the founder and former CEO of Human Genome Sciences, and is currently the chair and president of the global health think tank Access Health International. "I trust the World Health Organization," Haseltine told Salon when asked about whether their findings are credible, given that the WHO has been attacked by President Donald Trump as "Chinacentric" and of having "missed the call" by not warning about COVID-19 earlier. Haseltine added that they have "very high quality advisors and they're generally pretty careful" and said that those denouncing the WHO "are not trustworthy themselves." At the same time, Haseltine cautioned the public against exaggerating the meaning of the WHO's report, which is reliable but does not necessarily indicate that we are out of the woods in terms of the pandemic.
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"What they say as far as I can say, according to the quote, is we do have some treatments that seem to be in very early studies limiting the severity or the length of the illness, but we do not have anything that can stop the virus. That is exactly my understanding of the current situation," Haseltine told Salon. He also acknowledged that the report disparaged hydroxychloroquine's effectiveness as a COVID-19 medication. Trump has repeatedly touted the drug's supposed benefits. "The report shows that hydroxychloroquine is ineffective, has no measurable effect on the symptoms, has no measurable effect in modifying the course of COVID-19. There is evidence that it can be harmful to patients," Haseltine explained. Dr. Eric Feigl-Ding, epidemiologist and senior fellow at the Federation of American Scientists, cautioned people to not misinterpret the WHO's findings in an overly-optimistic light. The link to this article can be found here: WHO Says Some COVID19 Medicines Can Shorten Illness — But Hydroxychloroquine Is Ineffective
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Here's How That Rumor That Smokers Can't Get COVID-19 Got Started Salon | May 12, 2020 | Article
Old cigarette ads often made outrageous claims about cigarettes, including, infamously, that they could cure asthma. (They can't.) So the rumors that smokers might be at lower risk for contracting COVID-19 seem similarly specious. Oddly, such rumors seemed to be rooted in a grain of truth. (We'll get to that later.) Still, Salon spoke with three experts, all of whom said the same thing: it is almost certain that smoking puts you at greater risk of dying from a coronavirus infection. "They're not saying that smoking prevents [coronavirus]. They're saying that nicotine prevents it," Dr. William Haseltine, the founder and former CEO of Human Genome Sciences, and currently the chair and president of the global health think tank Access Health International, told Salon regarding an April study in "Comptes rendus biologies" led by French neuroscientist Jean-Pierre Changeux. "Smoking clearly exacerbates it. The nicotine, maybe an acetone," Haseltine continued. "I can tell they have to show the data, and I don't think they show the data here. All they do is speculate. But the danger is that many people may conflate nicotine with smoking. That's definitely bad for you." He added, "There are many studies around the world, many different populations have shown that if you are a current smoker, your chance of dying from an infection is much higher than if you were not. This paper opens the possibility that nicotine may be a useful treatment; it doesn't show it, but speculates based on some detective logic. That logic may be correct. I can't say because I have to do the experiments to know if it is correct." The study that Haseltine referenced was popularized by a Vice article last month with the headline "Why Are Smokers Being Hospitalized Less Often From Coronavirus?" It noted how the Changeux study found that "of 343 hospitalized patients, only 4.4 2492
percent were recorded as smokers; of 139 outpatients, only 5.3 percent were recorded as smokers." Changeux notes that "more than a quarter" of the French population smokes cigarettes. The article also featured a study led by Greek cardiologist and tobacco harm-reduction specialist Dr. Konstantinos Farsalinos, which concluded that their "preliminary analysis does not support the argument that current smoking is a risk factor for hospitalization for COVID-19 . . . . Instead, these consistent observations, which are further emphasized by the low prevalence of current smoking among COVID-19 patients in the US (1.3%), raises the hypothesis that nicotine may have beneficial effects on COVID-19." It acknowledged that "other confounding factors need to be considered and the accuracy of the recorded smoking status needs to be determined. However, the results were remarkably consistent across all studies and were recently verified in the first case series of COVID-19 cases in the US." ... The link to this article can be found here: Here's How That Rumor That Smokers Can't Get COVID-19 Got Started
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Trial Coronavirus Vaccine Only ‘Partially Effective In Monkeys – As It Fails To Stop Spread’ The Sun | May 18, 2020 | Article
A CORONAVIRUS vaccine being developed by Oxford University may not stop people becoming infected with the disease, experts warn. The latest animal trials of the "front runner" vaccine carried out using six monkeys revealed all went on to catch the killer infection. The revelations come as Drug giant AstraZeneca said it will make 30 million doses of the vaccine by September if it works and the UK will be the first to get them. Oxford finished its first phase of human trials this week - with everyone planned having received their vaccine doses on schedule. However, following the publication of detailed trial results it was revealed the vaccine was unable to prevent monkeys from catching COVID-19. On the upside, none of the vaccinated animals displayed pneumonia which suggests that, while not stopping the virus, it may be partially protective. The setback has led some to question the effectiveness of the jab and in particular whether it will be able to prevent the spread of the virus. Dr William Haseltine, a former Harvard Medical School professor, said: "All of the vaccinated monkeys treated with the Oxford vaccine became infected when challenged, as judged by recovery of virus genomic RNA from nasal secretions." He wrote in an article on Forbes: "There was no difference in the amount of viral RNA detected from this site in the vaccinated monkeys as compared to the unvaccinated animals. Which is to say, all vaccinated animals were infected." ...
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The link to this article can be found here: Trial Coronavirus Vaccine Only ‘Partially Effective In Monkeys – As It Fails To Stop Spread’
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Fighting Coronavirus Conspiracy Theories Bloomberg | May 18, 2020 | Podcast
Dr. William Haseltine, President of Access Health International, provides a coronavirus update and says hard data is key for tackling the pandemic. Bloomberg Businessweek Editor Joel Weber and Bloomberg News Technology Writer Joshua Brustein share their insight on a tiny U.S. agency that is fighting COVID-19 conspiracy theories. Bloomberg New Economy Editorial Director Andy Browne discusses U.S.-China relations hanging by two threads. And we Drive to the Close with George Young, Partner and Portfolio Manager at Villere Funds. Hosts: Carol Massar and Jason Kelly. Producer: Doni Holloway. The link to this podcast can be found here: Fighting Coronavirus Conspiracy Theories
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Doubts Over Oxford COVID-19 Vaccine After Animals Tested Catch Virus Newsweek | May 19, 2020 | Article
Doubts have been raised over a much-lauded Oxford University COVID-19 vaccine which experts say could fail to prevent individuals catching the virus, after trial results emerged. The government has promised to invest £20 million ($24m) to support teams at Oxford University engaged in the global race to find a vaccine. However, following the publication of detailed trial results last week, it was found that the vaccine was unable to prevent monkeys from catching the COVID-19 virus. This has led to experts questioning the effectiveness of the jab, should it be approved for wider use among the population, and in particular about whether it will be able to prevent the spread of the virus between affected individuals. Dr. William Haseltine, a former Harvard Medical School professor who had a pivotal role in the development of early HIV/Aids treatments, said: "All of the vaccinated monkeys treated with the Oxford vaccine became infected when challenged, as judged by recovery of virus genomic RNA from nasal secretions." He wrote in an article on Forbes: "There was no difference in the amount of viral RNA detected from this site in the vaccinated monkeys as compared to the unvaccinated animals. Which is to say, all vaccinated animals were infected." The vaccine, which had been dubbed as a "front runner", was trialed in rhesus macaque monkeys. The vaccine, catchily titled ChAdOx1, was given to six monkeys, exposing them to COVID-19. A control group of three non-vaccinated monkeys was also infected. Both the immunized and non-immunized monkeys were then monitored for seven days for signs of developing COVID-19.
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Dr. Haseltine said: "It is crystal clear that the vaccine did not provide sterilizing immunity to the virus challenge, the gold standard for any vaccine. It may provide partial protection." Although all of the monkeys were found to have been infected with the virus, none suffered from pneumonia, which suggests the vaccine could help fight the severity of COVID-19, which may give optimism to some. The link to this article can be found here: Doubts Over Oxford COVID-19 Vaccine After Animals Tested Catch Virus
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Stocks surge after Moderna announces promising early vaccine results Sydney Morning Herald | May 19, 2020 | Article
Washington: The first coronavirus vaccine tested on humans appears to be safe and able to stimulate an immune response against the virus, the American biotechnology company Moderna has announced. The results sent the US stock market soaring despite the small and early nature of the study. The findings were based on results from eight people who each received two doses of the experimental vaccine starting in March. The participants - all healthy volunteers aged 18 to 55 produced antibodies that were later shown to stop the virus from replicating in infected cells in a laboratory, the key requirement for an effective vaccine. ... "All of the vaccinated monkeys treated with the Oxford vaccine became infected when challenged as judged by recovery of virus genomic RNA from nasal secretions," William Haseltine, a former Harvard Medical School professor who helped develop early HIV/Aids treatments, wrote in Forbes. "There was no difference in the amount of viral RNA detected from this site in the vaccinated monkeys as compared to the unvaccinated animals. Which is to say, all vaccinated animals were infected." … The link to this article can be found here: Stocks surge after Moderna announces promising early vaccine results
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Let’s Remember That The Coronavirus Is Still A Mystery The New York Times | May 20, 2020 | Article
This article links to Bill’s Washington Post oped (link here): Let’s Remember That The Coronavirus Is Still A Mystery
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Global report: Don't Count On Vaccine, US Scientist Warns, As Cases Pass 5M The Guardian | May 21, 2020 | Article
A top US scientist has said that people should not count on a COVID-19 vaccine being developed any time soon, as global infections passed 5 million after surges in Latin America, including Brazil, which has recorded nearly 20,000 new cases. William Haseltine, the groundbreaking cancer, HIV/AIDS and human genome projects researcher, has said the best approach to the pandemic is to manage the disease through careful tracing of infections and strict isolation measures whenever it starts spreading. He said that while a vaccine could be developed, “I wouldn’t count on it”, and urged people to wear masks, wash hands, clean surfaces and keep a distance. “Do not listen to the politicians who say we’re going to have one by the time my re election comes around,” he said. “Maybe we will (but) I’m just saying it’s not a slam-dunk case by any means ... because every time people have tried to make a vaccine – for Sars or Mers – it hasn’t actually protected.” Vaccines developed previously for other types of coronavirus had failed to protect mucous membranes in the nose where the virus typically enters the body, he said. The United States and other countries has not done enough to “forcibly isolate” people exposed to the virus, Haseltine said, but praised China, South Korea and Taiwan’s efforts to curb infections. Haseltine said the US, Russia and Brazil – which rank first, second and third for infections – have done the worst. As global infections passed 5 million, Brazil reported a record 19,951 cases on Wednesday, according to the ministry of health, taking total infections to 291,579. If the trend continues, the country would shortly overtake Russia’s cases (308,705). Brazil’s health ministry, meanwhile issued new guidelines for the wider use of anti-malarial drugs in mild coronavirus cases, a
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treatment touted by President Jair Bolsonaro in defiance of public health experts warning of possible health risks. ... The link to this article can be found here: Global report: Don't Count On Vaccine, US Scientist Warns, As Cases Pass 5M
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U.S. Raises Ante in Vaccine Race With $1.2 Billion for Astra Bloomberg | May 21, 2020 | Article
The U.S. threw its weight behind one of the fastest-moving experimental solutions to the coronavirus pandemic, pledging as much as $1.2 billion to AstraZeneca Plc to help make the University of Oxford’s COVID vaccine. Funding Trial The U.S. funding will support a final-stage clinical trial with 30,000 participants, as well as tests in children, AstraZeneca said. Some doubts have been raised about the potential effectiveness of the Oxford vaccine after early results in monkeys were released. While the shot may have protected animals against severe infections, the results were weak compared with those of a test of a vaccine under development by Sinovac Biotech in Beijing, said William Haseltine, a former Harvard University HIV researcher, in a blog post. The comparison is inapt for studies carried out with different types of vaccines given in varying doses, in monkeys who were infected with different levels of virus, the Oxford researchers said in a statement. “In the end it is the impact on clinical disease that matters,” they said. The link to this article can be found here: U.S. Raises Ante in Vaccine Race With $1.2 Billion for Astra
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Coronavirus Is Vanishing So Quickly In Britain that Oxford University's vaccine trial only has a 50% chance of success, professor leading project warns Daily Mail | May 21, 2020 | Article
A much-anticipated coronavirus vaccine trial only has a 50 per cent chance of success, the professor leading the project has warned. High hopes have been pinned on the vaccine from Oxford University, with a deal for 30million doses by September already in place. But Professor Adrian Hill said the upcoming trial of 10,000 Britons may flop and produce 'no result' because the virus is vanishing in the UK. Normally in large-scale trials, participants will be given the vaccine and mingle among society to see if the jab is effective at preventing them picking up the virus - in this case SARS-CoV2.But the virus is circulating at low levels. Around 0.25 per cent of the population is currently infected and this will drop further if lockdown continues to work. Business Secretary Alok Sharma said earlier this month the Government is ambitiously hoping to be in a position to roll-out a mass vaccination programme in the Autumn of this year. Professor Hill urged caution of 'over-promising' a vaccine, adding: 'We don't know if we can do it. We think we can. You know, mistakes happen. That needs to be understood.'It comes ahead of plans next month for the university to release results of a first trial conducted on more than 1,000 volunteers during the disease's peak in April. But top scientists dealt a blow to the hopes of millions of Britons longing for an end to the pandemic when they warned a working vaccine is unlikely to be ready until 2021. Doubts have been cast about the jab – one of eight front-runners in the world's vaccine race – after studies on monkeys suggested it didn't stop them getting infected.After trials of the vaccine carried out on rhesus macaques, all six of the participating monkeys went 2504
on to catch the coronavirus.Dr William Haseltine, a former Harvard Medical School professor, revealed the monkeys who received the vaccine had the same amount of virus in their noses as the three nonvaccinated monkeys in the trial.But Professor Hill said today the article in Forbes magazine was 'misleading' and that Dr Haseltine was not a vaccine developer. Meanwhile, stock markets were sent into a frenzy this week after promising results that showed another experimental vaccine, made by US firm Moderna, could block the virus in humans. The link to this article can be found here: Coronavirus Is Vanishing So Quickly In Britain that Oxford University's vaccine trial only has a 50% chance of success, professor leading project warns
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June 2020
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Researchers Race For Corona Vaccine But Question Effectiveness The Media Line | June 5, 2020 | Interview
The latest COVID-19 information and statistics for the Middle East and North Africa The race is on for a coronavirus vaccine, with more than 130 in development globally, including 10 in clinical evaluation, according to the World Health Organization. Out of those 10, there are two leading candidates entering Phase 3 trials in the next month. One from US-based biotech company Moderna and the other a collaboration between the University of Oxford and UK-based biopharmaceutical company AstraZeneca. According to Friday’s update from the Johns Hopkins coronavirus tracker, globally there were 6,639,228 infections with 391,261 deaths and 2,872,815 recoveries in 188 countries and territories. But is rushing a vaccine to market about protecting public health? Not everyone agrees. “If a vaccine is to be approved, my guess is that it will be approved because there is a rush to get a vaccine. Not to necessarily satisfy the medical problem, but to satisfy political and economic concerns,” Dr. William Haseltine, chair and president of ACCESS Health International, told The Media Line “And that means a vaccine is likely to be partially effective and possibly dangerous because it won’t be thoroughly tested. It cannot be in that amount of time.” Until there is a completely effective vaccine for COVID-19, Haseltine said that countries in East Asia and other regions have already demonstrated that public health measures such as mass testing can protect the entire population. Haseltine emphasized that he is a supporter of vaccines as the most effective tools for health that we have, but that realistically by the end of the year there is more of a chance of prophylactic
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antibodies and drugs being used to prevent infections in high-risk populations. In the best-case scenario, according to Durbin, Phase 3 clinical trials would demonstrate by mid-to-late fall that a vaccine effectively prevented coronavirus by producing neutralizing antibodies. However, it would still take a couple of years, in Durbin’s estimation, to manufacture enough doses for the entire population. ... The link to this article can be found here: Researchers Race For Corona Vaccine But Question Effectiveness
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Biotech Pioneer Calls For Transparency In Coronavirus Vaccine Development University of Miami | June 11, 2020 | Article
As a scientist and businessman, William Haseltine has created 10 different companies that have produced a range of products approved by the Food and Drug Administration and other agencies, including medicines that help combat diseases such as cancer, lupus, diabetes, and AIDS, as well as agents that provide protection against bioterrorism with Anthrax, among others. Fifteen years ago, he founded ACCESS Health International, a nonprofit think tank and foundation that aims to expand access to health care for all. Through the foundation’s global offices, Haseltine has developed relationships with government officials in a range of nations—China, India, Japan, and others—that have advanced collaborative health care solutions. With the outbreak of the COVID-19 pandemic, Haseltine has riveted his attention on the virus, using his expertise and collaborative network to address the immense challenges involved in generating an effective vaccine. He talked about those efforts in a virtual conversation with University of Miami Patti and Allan Herbert Business School leaders on June 10 as part of the Southern Glazer’s Distinguished Leaders Lecture Series. “Six months ago, we had one person infected with the COVID19 virus. Today we have seven million people infected globally and nearly 20,000 new cases every day in the U.S.,” Haseltine pointed out. “What’s going to happen? It’s not predictable, and any prediction you make doesn’t look so good.” President Julio Frenk welcomed Haseltine as “a renowned innovator and gifted scientist who has become a prolific commentator who offers clear-headed commentary” regarding the COVID-19 pandemic. Karoline Mortensen, professor in health management policy, moderated the webinar together with Dean John A. Quelch. She 2509
asked Haseltine about his new book, a family guide for COVID-19, and for recommendations on consumer behavior in the absence of a vaccine. He responded by offering two radically different government responses to the virus: China, which imposed tight restrictions and has now controlled the spread, and Sweden, which set almost no controls and now has the highest rate of deaths-per-capita in the world. The United States, he pointed out, followed a partial model in regional fashion, shutting down some places tightly, like New York, while allowing other states to set the loosest of restrictions. “And now we have 20,000 new cases—that’s what happens when you don’t close up tight,” he said, adding that “some of those are going to die, and many of those who don’t die are going to be severely injured for the rest of their lives—fibrosis lungs, hearts that don’t function well, lost kidneys, brains that suffered strokes, and more. “We’re not counting those people, we only count the dead,” he said. “What is the price we’re going to be paying?” Haseltine shared his childhood experience growing up during the polio epidemic, prior to the development of a vaccine, as a reference for the present COVID-19 pandemic. “I remember the tangible fear,” he said. “We were afraid, and we didn’t know exactly what we were afraid of.” In his first laboratory job, he was assigned to work in the same lab where John Franklin Enders had isolated the poliomyelitis virus, a discovery that led to the vaccine. “I decided then that I was going to learn a lot about polio,” he added. He learned that the virus is much like a cold virus, and out of every 200 people it infects, one gets paralyzed, and out of every 2,000 people, one dies. “That sounds very familiar to COVID-19,” he said, noting that a marked difference between the two is that once you get infected with polio, you never get infected again. “There’s a difference with this disease. They’re doing experiments that show that if you infect a human being with a cold coronavirus, you can come back a year later and reinfect them—that means this virus has a different strategy,” he said.
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He said that there are “at least 20 tricks we know of now, and we’re still counting,” that this virus uses to mess with our immune system. “Each virus has its own strategy, and this one is a very tricky one, halfway between polio and HIV in terms of certainty for finding a vaccine that’s going to solve our problem,” he said. According to Haseltine, each person’s response to reengaging their lifestyle is tempered by their own individual experience. In his own case, he explained that the previous day he entered his New York apartment building just as a COVID-19 fatality was being wheeled out on a stretcher. “That was a reminder that it ain’t over in New York either, so I’m worried,” he said. Companies working on developing a vaccine for COVID-19, Haseltine said, should share information on all aspects of development. “It’s transparency I’m calling for,” he said. “We need to know the regulations of what the Food and Drug Administration will require for safety. We’re the ones at risk, and we should know how our money is being spent and know what the plans are in some detail. “The transparency isn’t just for Moderna,” Haseltine said, referring to a biotech firm he has criticized for not providing data on its work. “We need to tear away the cloak of opacity around this massive effort." The link to this article can be found here: Biotech Pioneer Calls For Transparency In Coronavirus Vaccine Development
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‘All of a Sudden It Blows Up’: Arkansas’ COVID Problem Is Just Getting Started Daily Beast | June 14, 2020 | Article
For months, New Yorkers saw their hospitals flood with COVID-19 patients and bodies pile up in refrigerated overflow morgue trucks. Meanwhile, other parts of the country never even implemented a statewide lockdown. For those hoping a slew of Southern and rural states might have avoided the worst of the pandemic entirely, Friday’s case counts provided a grim answer. Arizona, North Carolina, California, Florida, and Texas hit record daily highs of COVID-19 infections this week, as state public health leaders pleaded with their communities to take the ongoing crisis seriously. But there are few states whose experience of the coronavirus pandemic has shifted more radically in recent weeks than Arkansas. On Friday, the state reported that there were 731 new cases, a record increase. Those numbers brought the cumulative total there to 11,547, of which 3,764 were active. At last count, 176 people had died from the virus. Even if Arkansas saw its first COVID-19 case in March—and has had its share of “super-spreader” events—experts painted a picture of communities there facing the pandemic’s full fury for the first time. “It’s part of a broad pattern in the U.S. of resurgent infections that are sweeping across many states,” said William Haseltine, a public health expert, former Harvard Medical School professor known for his work on HIV, and the president of the global health think tank ACCESS Health International. “We’re about to see hospital systems in states like Arkansas…. begin to experience what we did in New York, with facilities being overwhelmed by this epidemic.” Washington Regional Medical System in Fayetteville, Arkansas, called attention to the “serious public health emergency” caused by 2512
a “significant” surge in community spread in the northwest region of the state in a letter on Wednesday. ... The link to this article can be found here: ‘All of a Sudden It Blows Up’: Arkansas’ COVID Problem Is Just Getting Started
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Worried About a Second Lockdown? Pray Things Work Out in NYC Daily Beast | June 26, 2020 | Article
In the most remarkable turnaround of the coronavirus pandemic, New York is the place to be. For now. For months, as the global epicenter of the novel coronavirus outbreak, New York City wasn’t just a place to avoid. It was a symbol of pandemic preparedness gone horribly wrong. Amid those rising infection counts in California, Arkansas, South Carolina, Oklahoma, and elsewhere, public experts told The Daily Beasts that New York’s progress is a sign of hope that a more socially distant—and mask-clad—society can function. “Texas could follow New York’s trajectory,” said Dr. William Haseltine, a public health expert and former Harvard Medical School professor known for his work on HIV, and the president of the global health think tank ACCESS Health International. “We were far worse off than Texas. Our peak was 11,000. They’re not there yet, and we did it.” He compared the city’s plight—and the example it has set for other hot spots—to the classic Frank Sinatra line from “New York, New York”: “If I can make it there, I'll make it anywhere.” New York’s reversal, said Haseltine, has proven that there are several key features a community must have to fight the virus effectively: “good leadership that’s clear, compassionate, credible, and consistent,” “centralized public health” marked by a good faith effort to rapidly increase contact tracing and testing, and civilians with “a sense of social solidarity and personal responsibility.” “Europe proved that it works, and we’ve proved that it works,” said Haseltine. “We’re not used to following rules like the French or the Japanese, but we’re doing OK.” And ultimately, he added: “New York has always come through in times of crisis.” Most importantly, he added, instead of pretending the virus no longer exists, “We’re learning to live with this disease.”
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As of June 22, the city is in Phase 2, which reopened outdoor dining at restaurants, hair salons and barber shops, offices, in-store retail, real estate firms, and a slew of other businesses and activities. ... The link to this article can be found here: Worried About a Second Lockdown? Pray Things Work Out in NYC
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July 2020
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How A Chinese Firm Jumped To The Front Of The Virus Vaccine Race Bloomberg News | July 1, 2020 | Article
When a group of Chinese scientists gathered over barbecue and beer in a Toronto backyard a decade ago, talk drifted to their homeland’s vaccines, which had long lagged the developed world on quality and safety. Four of them decided to act. They left top positions at global pharmaceutical companies in Canada to set up a biotechnology firm half a world away in Tianjin, China, hoping to produce vaccines on par with Western countries. Now, that company, CanSino Biologics Inc., is vaulting into the global spotlight as connections on both sides of the Pacific make it one of the front-runners in the race for a coronavirus vaccine. ‘In the Game’ For upcoming trials in Canada, CanSino has added a booster shot for some participants to attempt to address the lackluster response from those with pre-existing immunity to the adenovirus vector, according to a person with knowledge of its trial design who didn’t want to be named discussing information that’s not public. “CanSino is in the game and it’s about where the other so-called leaders are,” said William Haseltine, a former Harvard University HIV researcher. “Whether anybody will cross the finish line where we ever can see safety data that we would like to see is unknown.” Final-stage trials could yet stymie CanSino’s outsized ambitions. Its Ebola vaccine was approved on an emergency basis after two stages of human testing, but the company never completed the final phase as the epidemic petered out in Africa. CanSino doesn’t generate much revenue because most of its products, including two late-stage meningitis vaccines, are still in development. The company has received some funding from Beijing for the coronavirus vaccine, although the amount isn’t large, the person familiar with its trials said. — With assistance by Natalie Obiko Pearson, Dong Lyu, and Yunong Wu 2517
The link to this article can be found here: How A Chinese Firm Jumped To The Front Of The Virus Vaccine Race
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Interview with Poppy Harlow CNN | July 8, 2020 | Interview
POPPY HARLOW, CNN ANCHOR: Well, this just in, tomorrow will be the final day of opinions from the Supreme Court this term, and we are learning that they will issue opinions on the two cases related to the president's financial records and his taxes. The cases center on whether or not the House of Representatives can subpoena the president's accounting firms and banks for his financial documents, and also whether the Southern District of New York can access the president's tax returns that he has so closely guarded, for examination by a grand jury. The president's lawyers have argued that the president should enjoy immunity from both because he's president, but it is the High Court that will have the final word and we will all know at 10:00 a.m. tomorrow. The coronavirus crisis in Arizona is growing dire. Hospitalizations are spiking as cases in the state now top 100,000. Some E.R. doctors there, saying they're losing hope and Phoenix mayor Kate Gallego says she fears her city is nearing an unbearable level of crisis. She joins me now. ... GALLEGO: I watched a constituent of mine who was an older man, struggling to breathe. His car ran out of gasoline, and he had to deal with that while waiting for a test. Particularly the west and southern portions of our cities have a huge need for low-barrier testing. I believe a testing surge could help us with a backlog, and we also need help processing those tests. People are having to wait more than a week to get results. This is critical health information that they need to live their daily lives. Texas, Florida, Louisiana have received testing surges recently. I've been asking for months, Phoenix is literally the per capita hotspot. We need our federal government to partner with us. I am taking any city resources we can and putting them towards testing. We have librarians and Parks workers who are helping with 2519
testing, but their force and their efficacy could be magnified if we had specialized medical experts who know about testing. HARLOW: Sure. Mayor, I'd like your reaction to something we just heard from a former Harvard Medical School professor, Dr. William Haseltine. Listen to what he told me about what he says is happening in your state right now. (BEGIN VIDEO CLIP) WILLIAM A. HASELTINE, CHAIRMAN AND PRESIDENT, ACCESS HEALTH INTERNATIONAL: There's something called crisis standards of care that is about to be -- it's already implemented in Arizona, and it may be in a number of these other states. What does that actually mean? It means that if you're old, you get sent home without care and you die. That's what it means. (END VIDEO CLIP) HARLOW: Is that happening in Phoenix? GALLEGO: Unfortunately, our medical professionals don't have the resources they need, and so they are being asked to make difficult decisions. I want to stress, if you are having a heart attack, if you think you may be having a stroke, please go to the emergency room. There is the ability to care for individuals. But we are not meeting the standards of care in all cases that we want. We've been very stretched with intensive care beds. We also need the federal government to help us with both more resources for our medical personnel, more medical personnel and then additional funding, particularly for our safety net health care system. HARLOW: That is a sobering reality, that yes indeed you in Phoenix have people that you cannot treat, no matter their age, that is -- that's tragic. Mayor, good luck. GALLEGO: Thank you. The link to this article can be found here: Interview with Poppy Harlow
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Phoenix Mayor's Office Clarifies Hospital Capacity Comment On Cable TV Interview The Center Square AZ | July 9, 2020 | Article
(The Center Square) – Phoenix Mayor Kate Gallego’s office is out to set the record straight after a cable news host sent out a tweet saying the mayor confirmed hospitals there were turning away patients who could be gravely ill. Gallego appeared on CNN’s Newsroom Monday to give host Poppy Harlow an update on Arizona’s COVID-19 response. Harlow played a clip of former Harvard Medical School professor William Haseltine saying that crisis standards of care, which Arizona Gov. Doug Ducey allowed to be activated, means that “if you’re old, you get sent home without care and you die.” Asked about the sound bite, Gallego responded. “Unfortunately, our medical professionals don’t have the resources they need, and so they are being asked to make difficult decisions,” she said. “I want to stress, if you are having a heart attack, if you think you may be having a stroke, please go to the emergency room. There is the ability to care for individuals, but we are not meeting the standards of care in all cases that we wanted. We’ve been very stretched with intensive care beds. We also need the federal government to help us with both more resources for our medical personnel, more medical personnel, and additional funding, particularly for our safety net health care system.” Harlow tweeted Wednesday afternoon about the segment, saying “Phoenix @MayorGallego confirms they are having to choose who gets care and who is sent home possibly to die. ‘Our medical professionals don’t have the resources they need so they are being asked to make difficult decisions.’” The link to this article can be found here: Phoenix Mayor's Office Clarifies Hospital Capacity Comment On Cable TV Interview
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The GOP is a suicide cult Raw Story | July 11, 2020 | Article
Welcome to another edition of What Fresh Hell?, Raw Story’s roundup of news items that might have become controversies under another regime, but got buried – or were at least under-appreciated – due to the daily firehose of political pratfalls, unhinged tweet storms and other sundry embarrassments coming out of the current White House. … Again, this is all coming from the top. Politico reported this week that in Trump’s Virginia campaign headquarters, staffers are packed tightly together and told that they are only required to wear masks outside the office in case they’re spotted by reporters. “You get made fun of, if you wear a mask,” said one person. “There’s social pressure not to do it.” And, after Trump’s consistent resistance to using the Defense Production Act to compel companies to produce more PPE, we’re now facing a second shortage. And in the midst of all of this chaos, Trump, having claimed that his own regime’s guidelines for reopening schools are too onerous, is attempting to coerce state and local governments into packing kids into classrooms for in-person instruction this fall with no plan to do so safely. It’s a total clusterfuck. And the worst is likely yet to come. On Friday, Dr. William Haseltine, a former professor at Harvard Medical School, told CNN, “all people who study these viruses think that the summer is the quiet time. Think about that. This is the quiet time for coronavirus. If this is the quiet time, I hate to think what winter is going to be like this year.” ***** The link to this article can be found here: The GOP is a suicide cult
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Moderna Fires Up COVID Vaccine Race With Promising Early Results Bloomberg News | July 14, 2020 | Article
In the trial, participants received the two shots 28 days apart. After the first dose, all of them generated antibodies that bound to the coronavirus, but most did not yet produce antibodies capable of neutralizing the virus. But all 42 people who got both scheduled doses of the vaccine generated antibodies capable of neutralizing the coronavirus, according to the study results. The final-stage trial will compare the vaccine to placebo shots in 30,000 healthy people at high risk of contracting COVID-19. One significant limitation of the data is it includes information only from the first 45 patients in the study, all of whom were from age 18 to 55. Results from a second portion of the phase 1 trial that included older people -- a key demographic for any COVID-19 vaccine, given the high death rate in older patients -- are not available yet. William Haseltine, a former Harvard Medical School researcher who chairs Access Health International, said the levels of neutralizing antibodies produced were “respectable” and possibly protective. But he said “the jury is out” on the vaccine’s safety. The link to this article can be found here: Moderna Fires Up COVID Vaccine Race With Promising Early Results
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COVID-19 Vaccine Trial Produces Antibodies In Everyone Tested, Report Says New York Post | July 14, 2020 | Articles
William Haseltine, a former Harvard Medical School researcher who chairs ACCESS Health International, told Bloomberg that the levels of neutralizing antibodies produced by the vaccine were “respectable” and could possibly provide protection against the coronavirus. But “the jury is out” on the vaccine’s safety, Haseltine added. The link to this article can be found here: COVID-19 Vaccine Trial Produces Antibodies In Everyone Tested, Report Says
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Moderna’s Coronavirus Vaccine Produced Antibodies In All Patients Tested Fortune | July 14, 2020 | Article
The final stage trial will compare the vaccine to placebo shots in 30,000 healthy people at high risk of coming down with the coronavirus. One significant limitation of the data is it only includes data from the first 45 patients in the study, all of whom were from age 18 to 55. Results from a second portion of the phase 1 trial that included people older than this -- a key demographic for any COVID-19 vaccine, given the high death rate in older patients -- are not available yet. William Haseltine, a former Harvard Medical School researcher who chairs Access Health International, said the levels of neutralizing antibodies produced were “respectable” and possibly protective. But he said “the jury is out” on safety of the vaccine. The link to this article can be found here: Moderna’s Coronavirus Vaccine Produced Antibodies In All Patients Tested
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Should I Get Tested For Coronavirus? Here's What Parents Need To Know Romper | July 17, 2020 | Article
Then there are some cases in which you should definitely get tested for coronavirus ASAP. "If someone in the household has tested positive, the mother should definitely be tested repeatedly for at least 10 days at 2-day intervals," William Haseltine, Ph.D., Chair of the US-China Health Summit and founder of Harvard University’s cancer and HIV/AIDS research departments, tells Romper. And of course, get a test if you're experiencing any symptoms of coronavirus as defined by the CDC, such as fever, shortness of breath, or loss of taste or smell. The link to this article can be found here: Should I Get Tested For Coronavirus? Here's What Parents Need To Know
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10 Tips For Returning To Work In The Midst Of A Pandemic The Zoe Report | July 18, 2020 | Article
Safety Tip For Returning Back To The Office: Wear A Mask Dr. Astrakianakis says to wear a mask in the office when you're working closely with someone within six feet or when distancing from others is difficult to do, like in an elevator, and when you're transiting through common spaces. Pambianchi says Verizon employees are allowed to remove their mask while sitting at their desk, but must put it back on before getting up to go to the bathroom or to leave. The desks in Verizon's offices are all marked to be six feet apart from one another. Another alternative to a face mask is a shield, according to Dr. William Haseltine, chair and professor at ACCESS Health International and author of A Family Guide to COVID. "It protects your eyes as well as your nose and mouth," he notes. He says it's a little more protection for you, and that a typical mask isn't protecting you very much as the virus can go right through it. To be safe, he suggests wearing it while you sit at your desk. "Because you may cough something out, and aerosols get into the air," Dr. Haseltine states. "And this is something we are sure of now that we weren't sure of earlier, if you're in an enclosed space, people breathing out put little particles into the air fomites and aerosols, which can be in the air for four or five hours." The link to this article can be found here: 10 Tips For Returning To Work In The Midst Of A Pandemic
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An e-Book For Families Provides Answers To Important Questions About COVID-19 Washington Post | July 20, 2020 | Article
Will school start again this fall? How many tests do we really need to tackle covid-19? How long should people quarantine if they do contract the virus? Adults have all of these questions, but so do kids. William Haseltine, a medical researcher and public health veteran with a history of pioneering ambitious projects to tackle HIV/AIDS, cancer and genomics, is tackling those issues with “A Family Guide to COVID.” The free, downloadable e-book answers all sorts of questions about covid-19, the illness caused by the novel coronavirus, from “Why has my life changed?” to “What are the long-term effects?” Written in a Q&A format, the book contains a section specific to children’s questions and a much longer portion devoted to answering adults’ queries. It also has a long list of resources to help those who want to know more about antibody testing or the effectiveness of gloves. “My friends and colleagues know I am plainspoken, and I don’t pull my punches when I see truth,” Haseltine writes. And he doesn’t. In response to a child’s question about whether doctors can save people who are sick, he writes, “Doctors can save most people if they can get to a hospital in time, just like with other diseases. It is sad they can’t save everyone.” Haseltine acknowledges that he doesn’t have all the answers — we’re still learning basics about the disease and that answers, and even questions, will be changing as we learn more. To that end, he’ll be regularly updating the book. “A Family Guide to COVID” can be read or printed on demand at accessh.org/covidfamilyguide. It’s also available on Kindle at Amazon. (Jeff Bezos, chief executive of Amazon, is the owner of The Washington Post.)
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The link to this article can be found here: An e-Book For Families Provides Answers To Important Questions About COVID-19
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The Inside Story Of How A Sleep Tracker Became The Hottest Device Of The Pandemic Maker | July 20, 2020 | Article
Even so, William Haseltine, BA, PhD, an infectious disease expert at ACCESS Health International and author of A Family Guide to COVID suggests it’s a “good idea” for people to purchase wearables because they make people more aware of social distancing and their symptoms. “There is variable accuracy,” he admits, “but the ask is to call their doctor — that’s not an onerous intervention.” They give people back some autonomy, he says, “where they’ve been left to their own devices as the government isn’t protecting them.” And of course, he adds, their data’s valuable for epidemiologists. The link to this article can be found here: The Inside Story of How a Sleep Tracker Became the Hottest Device of the Pandemic
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12 Back-To-School Essentials Every Kid Will Need During A Pandemic RD.com | July 21, 2020 | Article
If you want to take the concept of a face mask up a few notches, consider sending your child off to school with a face shield, as current evidence suggests that they are superior to a standard surgical mask or cloth mask, especially for children and teachers. “Face shields allow more visibility, are more comfortable than face masks and provide protection for the eyes, which is important,” notes William Haseltine, PhD, infectious disease expert and former Harvard Medical School professor, author of the new book A Family Guide to COVID. “At the same time, they give equal or better protection from infection by droplets.” These V by Vye ten-pack of face shields are sized right for kids. The link to this article can be found here: 12 Back-To-School Essentials Every Kid Will Need During A Pandemic
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Quartet Of COVID-19 Vaccine Candidates Head Toward The Homestretch Geneng News | July 22, 2020 | Article
Viewed as a horse race, none of the four COVID-19 vaccine candidates whose developers released early clinical data this month fully broke away from the pack galloping toward regulatory approval. However, a trio of distinguished experts interviewed by GEN, and two investment firms that track biopharma stocks, agreed that three of the four candidates showed sufficient promise in Phase I or Phase I/II studies to warrant interest from researchers, industry observers, and others in upcoming trials for: • AZD1222 by AstraZeneca, the University of Oxford, and its spinout Vaccitech • BNT162b1, the most advanced of four vaccine constructs by Pfizer and BioNTech • mRNA-1273 by Moderna • Ad5-nCoV by CanSino Biologics All four are among the 18 “Front Runners” of the more than 270 COVID-19 therapeutics included in GEN’s updated “COVID19 Drug & Vaccine Candidate Tracker.” “You can’t bet on this race,” William A. Haseltine, PhD, the HIV research pioneer and chairman of ACCESS Health International, told GEN. “The vaccine that I’d bet on is the one that’s the safest, and I can’t tell you which that is at this time.” ... All the leading vaccine candidates showed better results after two doses compared with one—yet a single-dose vaccine would be optimal, Haseltine noted. “This should be a vaccine that could be used around the world, for everybody, in rich and poor countries, as a constant. And for that, you need a vaccine in which a single dose will do you,” Haseltine said. “The reason for that, as any vaccinologist will tell 2532
you, is that in difficult to reach areas, it’s hard to get people once, it’s even harder to get them twice. Some of the vaccines are two weeks apart, some of them are 28 days apart, so it’s difficult. That’s not optimal.” ... “The Moderna vaccine knocked a couple of young healthy people on their ass, and it was only 2.5 times the actual dose they plan to use. That’s not good. That is a warning sign,” Haseltine said. “If I were the CEO of that company, I wouldn’t have proceeded until I knew a lot more about the safety profile in target populations: Older people, and people with some comorbidities, say mildly obese and relatively healthy diabetic.” ... Haseltine said the scramble by biopharmas to develop a COVID19 vaccine brought to mind the words of the Biblical book of Ecclesiastes: “I returned, and saw under the sun that the race is not to the swift, not the battle to the strong, neither yet bread to the wise, nor yet riches to men of understanding, nor yet favor to men of skill; but time and chance happeneth to them all.” The link to this article can be found here: Quartet Of COVID-19 Vaccine Candidates Head Toward The Homestretch
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The US Reported More COVID-19 Cases In The Last Two Weeks Than It Did For All Of June CNN Health | July 23, 2020 | Article
Hoping to catch up to the spread, at least 27 states have hit a pause or rolled back their reopening plans. In Houston, Mayor Sylvester Turner spoke again in favor of a second stay-at-home order amid a rise in cases. In Los Angeles, the mayor said the city was on the "brink" of another lockdown. But in Georgia, the governor slammed Atlanta Mayor Keisha Lance Bottoms' decision to revert back to Phase 1 -- where residents are ordered home with the exception of essential trips. What comes next is unclear: With now at least 41 states requiring face coverings, some have said strict measures like limiting gatherings and enforcing social distancing and masks can be as impactful as another lockdown. But others aren't as hopeful. "Masks will help, but I think we need a lot more than masks to contain this epidemic that's running through our country like a freight train," said William Haseltine, the chair and president of the global health think tank, ACCESS Health International. "Until we see major changes of behavior and until we see the public health services here stepping forward with many more resources, we aren't sure of containing this." The link to this article can be found here: The US Reported More COVID-19 Cases In The Last Two Weeks Than It Did For All Of June
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How COVID-19 Coronavirus May Affect Your Heart, Here Are Two New Studies Forbes | July 29, 2020 | Article
A majority (76%) of the patients had detectable troponin in their blood. Seeing troponin in the blood is like seeing ping pong balls on the floor when they are supposed to be in a lottery ball machine. That means something must have happened to the lottery ball machine. Similarly, troponin is a protein typically found in your heart muscles. When your heart muscle gets damaged, troponin can then leak into your bloodstream. Moreover, on the day of the MRI, 17 patients were still suffering from chest pain, 20 from heart palpitations, and 36 from ongoing shortness of breath and general exhaustion. From this study alone, it’s not completely clear what was causing all of these findings. Remember this was over two months after the COVID-19 diagnoses. Were these patients still infected with the virus? Was the immune response to the virus still causing problems? Was this residual damage from the infection? Were blood clots the culprit? After all, as William A. Haseltine has covered previously for Forbes, studies have found that COVID-19 coronavirus infection could lead to blood clot formation. How permanent is the damage? How common is such damage? Keep in mind that the samples for these studies were relatively small and not random. So do the numbers really apply to everyone who gets COVID-19? As with the movie Donnie Darko, there are still so, so many questions. The link to this article can be found here: How COVID-19 Coronavirus May Affect Your Heart, Here Are Two New Studies
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Why You Should Stay Away From Bars During COVID-19, According To Experts Popsugar | July 30, 2020 | Article
If you're craving a cocktail, break out the shaker and a recipe book and make your own drinks at home, because going to a bar during COVID-19 just isn't worth the risk. Infectious-disease experts agree that, even if bars in your area are open, it's best to stay away in order to protect yourself and others from spreading the highly contagious coronavirus. William Haseltine, PhD, chair of the US-China Health Summit, founder of Harvard University's cancer and HIV/AIDS research departments, and author of A Family Guide to COVID: Questions and Answers for Parents, Grandparents, and Children, told POPSUGAR that bars are one of the most dangerous places for transmission of COVID-19. "They're often small, they're often crowded, and people are disinhibited by alcohol, and droplets and aerosols can hang in the air and infect you through your nose, eyes, or mouth," Dr. Haseltine said. He added that, in any area where there's COVID-19 infection, there's really no way to protect yourself at a bar, so it's best to simply not go. The link to this article can be found here: Why You Should Stay Away From Bars During COVID-19, According To Experts
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Even the Best-Case U.S. Coronavirus Scenario Is Horrific Daily Beast | July 31, 2020 | Article
But the next years of the pandemic will also be shaped by political leadership. Social distancing, mask mandates, business closures, economic assistance, messaging, hygiene, quarantines, isolation, and mass congregations are all in various ways subject to the whims of local, state, and federal elected officials. “We are at a crucial decision point,” said William Haseltine, president of the global health think tank ACCESS Health International, who recently chaired the U.S.-China Health Summit in Wuhan, where the virus likely originated. “Right now we have 150,000 people dead, and it’s up to us to decide if we are going to have 300,000 or 400,000 or 500,000 or 600,000 or more. And that depends on what we do now. If we behave as we have in the past, especially in many of our states, there is no telling what the end in sight is.” “We also have 100 days before the election,” said Haseltine. “A new administration is very likely to have the right leadership and messaging. Our current president is not just not slowing the infection, he’s actually accelerating the virus.” “No other country has our situation,” said Haseltine. “You need a calming, persuasive voice for a national leader.” ... But even in the worst scenario without new vaccines and therapies, other countries have shown that mass testing, contacttracing, draconian closures, quarantines, social distancing, and maskwearing can work to control the virus. Without a vaccine, said Haseltine, “The only real way to end it is the way the Chinese did. Every day the Chinese are teaching us how to do it, and here we’re deliberately choosing not to do that.” The link to this article can be found here: Even the Best-Case U.S. Coronavirus Scenario Is Horrific
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August 2020
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For Homemade Face Masks, 3 Layers Are Better Than 1 Healthline | August 8, 2020 | Article
The single-layer face mask was made from a folded piece of cotton T-shirt and hair ties following the CDC recommended nosew method and a two-layer mask was produced following the CDC guidelines for a sewn mask. “Single-layer cloth mask is not as effective as a standard paper surgical mask. If you’re going to use a cloth mask, you should use one that has at least two or preferably three layers,” William Haseltine, PhD, chair of the US-China Health Summit, founder of Harvard University’s cancer and HIV/AIDS research departments, and author of “A Family Guide to COVID,” told Healthline. ... Although this research focused on silk to extend the life of N95 masks, the findings indicate silk may be a good idea for improvised, multilayer masks as well. Haseltine emphasized that preventing droplet spread is key to reducing COVID-19 transmission, and people shouldn’t worry too much about the material used in a mask. “As long as your mask prevents droplets from exiting your nose and mouth, such as a paper surgical mask does, it will help prevent the transmission of COVID,” said Haseltine. The link to this article can be found here: For Homemade Face Masks, 3 Layers Are Better Than 1
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3 Steps To Take Before Going To A Newly Reopened Restaurant Healthline | August 23, 2020 | Article
You've been stuck at home — or in your backyard — eating takeout for months now, so the idea of sitting with friends sipping wine and devouring a plate of pasta sounds, well, fantastical. Across the country, restaurants have reopened, but in the era of COVID19, just because something is open for business, doesn't necessarily mean it's safe. 1. Check Local Infection Rates The first thing to think about before you venture out for dinner is how widespread COVID-19 is in your community. A good rule of thumb is to look at average cases in your immediate area. "In your zip code, it should be less than 5 a day, in your city less than 10 a day and in your county less than 20 a day," advises infectious disease expert William Haseltine, PhD, chair and president of ACCESS Health International and author of A Family Guide to COVID. But even if rates are low, you should only eat outdoors, he stresses. "It's generally not safe to eat indoors, because the virus may linger in the air as small aerosols for a long time, even if only a single person is infected," Haseltine says. The link to this article can be found here: 3 Steps To Take Before Going To A Newly Reopened Restaurant
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September 2020
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If You Have No Choice But To Wear A Disposable Mask Again, Take These Doctors' Advice Popsugar | September 15, 2020 | Article
With masks now being a part of everyday life, it's almost inevitable that you'll find yourself running short on them at some point. So, if you really need to go somewhere, and all you have is a disposable mask you've already worn, can you wear it again? "Wearing a disposable mask that you have already previously worn is better than wearing no mask at all, but you should do your best to change your disposable face mask every day," William A. Haseltine, PhD, author of A Family Guide to COVID and A COVID Back to School Guide and chair of the US-China Health Summit, told POPSUGAR. Dr. Haseltine noted that disposable masks can get very dirty from just one use and they can't be properly cleaned like a fabric face mask. The link to this article can be found here: If You Have No Choice But To Wear A Disposable Mask Again, Take These Doctors' Advice
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5 Experts Lay Out How They'll Determine Whether A Coronavirus Vaccine Is Really Safe And Effective — Here's What To Know To Evaluate The Data For Yourself Business Insider | September 22, 2020 | Article
Vaccines are given to otherwise healthy people. That means there's far less tolerance for serious side effects, such as a severe allergic reaction, than there would be in a treatment that's given to people who are sick. "We've already seen a couple of safety signals that are concerning, and we want to make sure the vaccines are entirely safe," said William Haseltine, a pioneer in HIV/AIDS research and a longtime biotech executive. Haseltine noted that a volunteer in AstraZeneca's trial experienced a serious neurological illness, leading the company to temporarily halt the trial to investigate. The link to this article can be found here: 5 Experts Lay Out How They'll Determine Whether A Coronavirus Vaccine Is Really Safe And Effective — Here's What To Know To Evaluate The Data For Yourself
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October 2020
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Doc Rips White House Embrace Of ‘Herd Immunity’ To CNN: ‘Another Word For Mass Murder’ Mediaite | October 14, 2020 | Interview
Dr. William Haseltine didn’t mince words about the embrace of “herd immunity” as a solution to the coronavirus pandemic — by advisers to President Donald Trump — calling it “another word for mass murder.” On Wednesday morning’s edition of CNN’s New Day, anchor John Berman brought Dr. Haseltine in to discuss the prospect of a “winter surge” of the coronavirus as the weather gets colder. “No states in decline, professor, 50,000 cases reported in the last 24 hours, hospitalizations at a level we have not seen since the end of August,” Berman said. “We’ve been worried about this possible winter surge. It’s not even a month into fall and we’re seeing this alarming increase. So what does that tell you?” “It tells us that we don’t have this pandemic, this epidemic under control,” Haseltine said, then volunteered “And I’m extremely concerned that the president is being advised by people who speak of herd immunity.” “Herd immunity is another word for mass murder,” he continued. “That is exactly what it is. If you allow this virus to surprise as they are advocating, we are looking at two to six million Americans dead. Not just this year, but every year. The reason for that is that there is no such thing as herd immunity.” “These viruses, coronaviruses, come back here after year and infect the very same people,” Haseltine explained. “We know that from very teals on detailed studies of the viruses, their cousins the coronaviruses that cause colds. Every year they come back and in fact the same people. The same virus. This is an unmitigated disaster for our country to have people at the highest levels of our government countermanding our best public health officials. We
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know this epidemic can be put under control, other countries have done it. We are doing the opposite.” Haseltine was referring to a Monday White House press conference call in which actual senior White House officials spoke on the record but “on background,” meaning their names are known only to the people on the call, expressed support for a document that recommends herd immunity: On a call convened Monday by the White House, two senior administration officials, both speaking anonymously because they were not authorized to give their names, cited an October 4 petition titled The Great Barrington Declaration, which argues against lockdowns and calls for a reopening of businesses and schools. “Current lockdown policies are producing devastating effects on short and long-term public health,” the declaration states, adding, “The most compassionate approach that balances the risks and benefits of reaching herd immunity, is to allow those who are at minimal risk of death to live their lives normally to build up immunity to the virus through natural infection, while better protecting those who are at highest risk. We call this Focused Protection.” Trump himself has also alluded to herd immunity in the past, which he habitually calls “herd mentality.” Watch the clip above via CNN. The link to this article can be found here: Doc Rips White House Embrace Of ‘Herd Immunity’ To CNN: ‘Another Word For Mass Murder’
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"Herd Immunity Is Another Word For Mass Murder," Expert Says CNN | October 14, 2020 | Interview
William Haseltine, Chair and President of ACCESS Health International, said he is " extremely concerned that the President is being advised by people who speak of herd immunity." “Herd immunity is another word for mass murder. That is exactly what it is," Haseltine said on CNN’s “New Day” on Wednesday. Haseltine went on to say that if the virus is allowed to spread, as the Trump Administration is allegedly advocating, “we are looking at two to six million Americans dead – not just this year but every year.” “This is an unmitigated disaster for our country – to have people at the highest levels of our government countermanding our best public health officials,” Haseltine said. “We know this epidemic can be put under control. Other countries have done it. We are doing the opposite.” Some background: A study recently published in The Lancet has shown that less than 10% of the US population has been exposed to Covid-19. In order to essentially create a herd of protection around other people, 60% to 70% of the population would have to become infected, Dr. Sanjay Gupta said later on New Day. "We know that with around 10% of the country that's become infected, 216,000 people have died, roughly. So, just do the math there," he said. The link to this article can be found here: "Herd immunity is another word for mass murder," expert says
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U.S. Health Experts Warn Against 'Herd Immunity' Policy To Fight COVID-19 CGTN | October 17, 2020 | Interview
A number of U.S. public health officials have warned against the Trump administration's support for scientists who are pushing against lockdowns to fight the coronavirus, while also pushing for "herd immunity" against the virus. Dr. Anthony Fauci, America's top infectious disease expert, called the White House's herd immunity proposal "total nonsense." The idea "misses the basic point that we're all connected," former director of the U.S. Centers for Disease Control and Prevention Dr. Thomas Frieden told CNN. He added that the best way to achieve widespread immunity will be through a vaccine. William Haseltine, chair and president of ACCESS Health International, said on CNN's "New Day" on Wednesday that "herd immunity is another word for mass murder." He said if the "herd immunity" strategy is to be implemented and let the pandemic run its course, "we are looking at two to six million Americans dead – not just this year but every year." "This is an unmitigated disaster for our country – to have people at the highest levels of our government countermanding our best public health officials," Haseltine said. "We know this epidemic can be put under control. Other countries have done it. We are doing the opposite." The World Health Organization is also pushing against using herd immunity as a strategy against the COVID-19 crisis, calling such a move "simply unethical." The link to this article can be found here: U.S. health experts warn against 'herd immunity' policy to fight COVID-19
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Suite Talk: Dr. William A. Haseltine, Chairman And President, Access Health International
Westchester & Fairfield County Business Journals | October 18, 2020 | Interview
Dr. William A. Haseltine is one of the nation’s most prominent scientists who is celebrated for his groundbreaking work on cancer research, HIV/AIDS and the human genome. A former professor at Harvard Medical School and Harvard School of Public Health, he founded more than a dozen biotechnology companies, including Human Genome Sciences, and is chairman and president of Access Health International, a global health think tank. In the wake of the Covid-19 pandemic, Haseltine authored two books: “A Family Guide to Covid: Questions and Answers for Parents, Grandparents and Children” and “A Covid Back to School Guide.” In this edition of Suite Talk, Business Journal Senior Enterprise Editor Phil Hall speaks with Haseltine on the current race to create a vaccine to fight Covid-19. The speed in getting a Covid vaccine prepared is astonishingly fast. But is that good science or is that good politics? “Let’s hope it’s good science. There is a serious effort to develop a vaccine around the world by many countries. The techniques that are being used are sound. The trials, I believe, are suspect. They were designed, it seemed to me, for rapid approval rather than to really test the hypothesis that these vaccines work. You want a vaccine to prevent infection, prevent serious illness, and prevent death. Those were not the primary endpoints of any of the vaccine trials – rather, out of a very large group of people, they were going to make both their preliminary and final decisions based on infected people who were vaccinated as compared to infected people who weren’t vaccinated, and what the symptoms that they contracted after infection were. And when you read through for almost all of the trials that were described, what those criteria were, they were could be very mild symptoms – a cough, a low fever, or a headache.
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And if there were more of those events in the unvaccinated then the vaccinated, you would call that a success. That isn’t a real trial that would make a difference to most people. Most people are interested in not being infected, stopping the transmission, and certainly not dying. In some of the trials, those were secondary endpoints but not required. Now, on top of that, the numbers of people were very small. In some cases – in all cases, I think – less than 50 or 60. And even for the major trial, for final approval, it was only less than 200. That isn’t a serious number where you’re considering vaccinating hundreds of millions, if not billions, of people. In addition, there was no long waiting period between the end of the vaccine and the observation of long-term adverse effects. So, immediately as that data was available, the vaccine could be approved for emergency use authorization and for other purposes. To me, it suggests that they weren’t really focusing on safety.” You mention millions or billions of people – how is this vaccine going be manufactured so quickly for so many people? “When you’re using a new technology, and even an old technology you’re trying to scale up, it can take you a minimum of a couple of years to get it right. How do we know they’re getting it right? When I developed drugs and vaccines, we had to do the full manufacturing – the full dress-rehearsal – for what it was going to be like three times and get the same result. We had to do stability studies for six months to a year before we could have our products approved. None of that is possible.” I’ve seen several polls where many people are saying they would not take a vaccine if it does become available. Are we running the risk of this vaccine being science’s version of the Edsel, where they’re putting out a product that nobody wants? “We’re not quite there. I think the issues are being partially addressed by the FDA in the U.S. right now, which is at least one of some of the patients in the unvaccinated group have to get seriously ill and compare that to none of the patients of the vaccinated group. And there has to be a two-month period to observe for potential effects. That’s a little bit of an improvement and isn’t much, but it’s something that we have to acknowledge. In terms of public acceptance, you’re not going to get a whole scientific world to endorse a vaccine that has gone through this 2550
meager of a clinical trial – it just isn’t going to happen because the true answer is that we will not know how effective or how safe it is. I wouldn’t take that vaccine, but some of my fellow scientists would take the vaccine. So, I think that if the scientific community is somewhat divided on the issue, there is likely to be serious questioning in the public.” Is the focus on vaccines and drug cures the right approach in fighting the pandemic? “The emphasis on vaccines, secondarily on drugs, as compared to public health measures to control this pandemic is very badly misplaced. In the U.S., we have basically done very little to control the pandemic – we’re the worst in the world. We know this pandemic can be brought to close to zero, in a population of 1.4 billion people, within three months, using only public health measures. But there is some allergy to discussing China in this country. China did not do it because it was a totalitarian government. It did it because it used public health measures that everybody endorses: isolation of those who are exposed for 14 days. That’s reasonable. To dismiss it as ‘I don’t want to live under a totalitarian government’ is a non-sequitur. You don’t have to be in a totalitarian government to do normal public health measures that everybody would recommend. We just didn’t do them, nor did most countries in the world.” What’s going to be happening with Covid-19 when the cold wintry weather comes and flu season is in full swing? “What we’ve seen with coronaviruses and influenza is they have very sharp, seasonal peaks in temperate climates – that means anything that’s not tropical. And that means that come midNovember through February, there are very strong peaks. One thing we’ve had a little bit of heads-up for is the flu season in South America this year. For their winter, it did not exist – it basically was wiped out by whatever medicines people were taking. Now, they weren’t good enough to stop Covid but they certainly reduced flu. It looks like Covid is more transmissible than flu, from those that very broad picture.” The link to this article can be found here: Suite Talk: Dr. William A. Haseltine, Chairman And President, Access Health International
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What Fans Of ‘Herd Immunity’ Don’t Tell You NY Times | October 19, 2020 | Article
No matter their politics, people nearly always listen to those who say what they want to hear. Hence, it is no surprise that the White House and several governors are now paying close attention to the “Great Barrington Declaration,” a proposal written by a group of well-credentialed scientists who want to shift Covid-19 policy toward achieving herd immunity — the point at which enough people have become immune to the virus that its spread becomes unlikely. They would do this by allowing “those who are at minimal risk of death to live their lives normally.” This, they say, will allow people “to build up immunity to the virus through natural infection, while better protecting those who are at highest risk. We call this Focused Protection.” These academics are clearly a distinct minority. Most of their public health colleagues have condemned their proposal as unworkable and unethical — even as amounting to “mass murder,” as William Haseltine, a former Harvard Medical School professor who now heads a global health foundation, put it to CNN last week. But who is right? The link to this article can be found here: What Fans Of ‘Herd Immunity’ Don’t Tell You
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Feds To Let 15,000 Worship On National Mall—Masks Be Damned Daily Beast | October 21, 2020 | Article
For weeks, Sean Feucht has presided over thousands of maskless worshippers experiencing the “joy of salvation” even as America grapples with the terror of the coronavirus pandemic. From California to Nashville, the evangelical leader has defied public health experts and local officials with his “Let Us Worship” tour— leaving behind fear of superspreader contagion in already hard-hit areas. Now Feucht’s grand finale is set for this weekend at the National Mall in Washington, D.C. And federal officials appear to be doing absolutely nothing to stop Feucht and his (expected) 15,000 guests, with the National Park Service approving an application to hold a “demonstration or special event” without mention of any guidelines to mitigate COVID-19 exposure. “It’s disgraceful,” Lawrence Gostin, a professor of global health law at Georgetown University who advises the World Health Organization, told The Daily Beast on Tuesday. “It violates D.C.’s COVID-19 plan and it’s almost certainly going to lead to a superspreader event—and cause many new cases, hospitalization, and even death. It violates virtually every principle to mitigate this pandemic.” That the rally was slated to be held some 1,200 yards from the White House, which played host to a likely superspreader event at the Rose Garden last month, pointed to a federal government seemingly content to let the pandemic run wild, experts said. But it’s D.C. residents and leaders, who have long lacked meaningful federal representation, who are caught in the most immediate epidemiological crosshairs. Because the prayer event is at the National Mall, it is regulated by the National Park Service, and not city officials. …
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Dr. William Haseltine, a former Harvard Medical School professor known for his work on HIV and president of the global health think tank ACCESS Health International, believes it’s only a matter of time before we see these events confirmed as superspreaders. “They’re reckless,” Haseltine said, adding that Feucht was “putting people in danger.” “Unfortunately, even our leaders are not following public health recommendations, so it’s not impossible to see how this permit was granted,” he said. "But let’s be clear, there is no way to host an event like this without putting people in danger.” The link to this article can be found here: Feds to Let 15,000 Worship on National Mall—Masks Be Damned
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Drive? Fly? Stay home? The Hard Decisions Behind Pandemic Holiday Gatherings Boston Globe | October 24, 2020 | Article
Public health experts are warning Americans to avoid travel because of COVID-19, at a time when many people are desperately missing relatives and tired of COVID-19 restrictions. In the 1950s, Perry Como planted an idea into the heads of millions that “(There’s No Place Like) Home for the Holidays.” But 64 years after his melodic declaration that “If you want to be happy in a million ways / For the holidays you can’t beat home sweet home,” the singer’s cheery perspective is sounding downright dated — and reckless. This year, the nation’s top infectious disease specialist, directly contradicting the crooner’s sweet sentiment, told people to avoid travel — much to the disappointment of millions of Americans who are both suffering from COVID-19 fatigue and desperately missing relatives they haven’t seen in months. But with the number of coronavirus cases rising steeply as the long-predicted fall surge arrives with a vengeance, many doctors are warning that even the most careful travelers should step back a moment before finalizing plans. “The advice I’ve given my patients is that this is the year to be thinking hard about visiting your family,” said Julita Mir, an internist and infectious disease specialist at the nonprofit Community Care Cooperative. “Put it into perspective. Weigh the value against the potential consequences. Even with the best of intentions, traveling to see mom or grandma could be the worst thing you could do. Maybe the best thing you could do is to come up with an alternative celebration.” … “I think flying is very dangerous,” said William Haseltine, a scientist, author, and philanthropist who is perhaps best known for his work researching HIV and AIDS. He has already written two books on coronavirus, “A Family Guide to COVID” and “A COVID Back to School Guide.” “I tell people to only fly if they 2555
have to. I know there are people who would tell you it’s not so dangerous, but there are real, documented cases of people catching COVID on flights.” Haseltine said another danger with flying is traversing the airport, particularly the TSA checkpoint. In July, it was revealed that more than 1,000 TSA agents had tested positive for COVID-19. “They’re touching bags all day, they don’t change their gloves very often, and they reach in and touch your personal belongings,” he said. “The answer is to carry as little as possible and wipe down all of your personal belongings with gloves on.” Despite his wary view of flying, Haseltine said he would choose to take a plane over taking a long car ride with multiple hotel stops along the way. While flying, Haseltine said he would wear an N95 mask, goggles, and gloves. He’s also a proponent of plastic face shields, worn with a mask, both on a flight or in places where you’ll be in close proximity to others. “There’s good evidence that doctors and nurses who wear face shields in addition to masks reduced their chance of infection to close to zero,” he said. “I don’t think people understand exactly why, but there’s some theories. One is that you don’t touch your face as much. Another theory is that with a shield you’re not going to get infected through your eyes. It’s good for daily use, but very important to have when you travel.” The link to this article can be found here: Drive? Fly? Stay home? The hard decisions behind pandemic holiday gatherings
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Scientists Debate How Much To Lower The Bar On COVID-19 Vaccine Potential NBC News | October 28, 2020 | Article
The White House and many Americans have pinned their hopes for defeating the Covid-19 pandemic on a vaccine's being developed at "warp speed." But some scientific experts warn they're all expecting too much, too soon. "Everyone thinks Covid-19 will go away with a vaccine," said William Haseltine, chair and president of Access Health International, a foundation that advocates for affordable care. Ongoing clinical trials are primarily designed to show whether Covid-19 vaccine candidates prevent any symptoms of the disease — which could be as minor as a sore throat or a cough. But the trials, which will study 30,000 to 60,000 volunteers, will be too brief and too small to prove that the vaccines will prevent what people fear most — being hospitalized or dying — by the time the first vaccine makers file for emergency use authorization, which is expected to occur later this year, Haseltine said.OCT. 26, 202001:32 The United States should hold out for an optimal vaccine, with more proven capabilities, Haseltine said. Others say the crushing toll of the pandemic — which has killed at least 225,000 people in the U.S. — demands that the country accept the best vaccine it can achieve within the next few months, even if significant questions remain after its release. The link to this article can be found here: Scientists Debate How Much To Lower The Bar On COVID-19 Vaccine Potential
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November 2020
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Why A Top Infectious-Disease Expert Says It's Too Soon To Celebrate Pfizer's Coronavirus Vaccine Business Insider | November 9, 2020 | Article
On Monday, Pfizer marked a milestone in society's fight against the coronavirus pandemic, announcing its experimental vaccine was highly effective at preventing COVID-19 in a 43,538-person study. The $220 billion drugmaker said a two-dose regimen of its shot was found to be more than 90% effective in preventing COVID-19, based on 94 cases of the disease observed in the large-scale trial. But even with the good news, there are caveats and unanswered questions for Pfizer and its German partner BioNTech. William Haseltine, a longtime biotech executive and infectiousdisease expert, told Business Insider he wanted to see the underlying data to support the efficacy claim. Haseltine has previously criticized other front-runners in the race for a coronavirus vaccine, namely Moderna, for touting study results in news releases before releasing detailed data. With Pfizer's release on Monday, however, Haseltine said there wasn't any data in the release. The analysis was based on 94 cases of COVID-19 among study participants, but Pfizer didn't share an exact breakdown of how many got sick from getting Pfizer's vaccine versus the placebo. The release also didn't specify how many of the cases were severe or mild or if different age groups had varying levels of protection. Beyond saying there have been no serious safety concerns, Pfizer didn't provide any details on the safety profile, such as the frequency and severity of typical side effects. CEO Albert Bourla said in a statement the company would share additional efficacy and safety data "in the coming weeks." "This is science by public pronouncement," Haseltine said. Haseltine is a former Harvard medical professor who founded two research centers focused on HIV/AIDS and cancer at the school. 2559
The virology and infectious-disease expert is now the chairman and president of Access Health International, a nonprofit healthcare think tank. He has also founded and led several biotech companies, including Human Genome Sciences, which was eventually bought by GlaxoSmithKline for $3 billion. During the pandemic, he has advocated the US to embrace an expansive testing strategy, previously saying the country's response was overly reliant on a vaccine. "It is very welcome news that the vaccine has a measurable effect," Haseltine said, adding there was still much to learn about Pfizer's shot. "There are many, many outstanding questions which are left unanswered," he added. Most of the questions have to do with the limitations of the study. The trial was designed to see if there were fewer cases of symptomatic COVID-19, the disease caused by the coronavirus, in people getting the vaccine rather than placebo. It brings up one crucial distinction that could have a major influence on the pandemic response: Does this vaccine prevent infection as well as disease? Pfizer's trial, and the ongoing studies of other leading coronavirus-vaccine developers, aren't regularly testing volunteers to gauge asymptomatic infections. That may mean vaccinated people could still become asymptomatic carriers and unknowingly spread the virus to others. "That's a major point that I don't think most people appreciate," Haseltine said. "It doesn't mean an end to the epidemic." Haseltine also raised the question of if the vaccine reduces serious disease and ultimately affects the number of hospitalizations and deaths. Again, the study's findings are limited by its main goal, which did not distinguish between a mildly ill COVID-19 patient — maybe someone with a minor fever and cough for a few days — and someone who is critically ill. Finally, Pfizer's news release made no mention of if the vaccine appeared as effective in different subgroups, such as older people, who are more susceptible to the worst outcomes of the virus.
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The link to this article can be found here: Why A Top InfectiousDisease Expert Says It's Too Soon To Celebrate Pfizer's Coronavirus Vaccine
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Pfizer's Covid-19 vaccine promising, but many questions remain NBC News | November 9, 2020 | Article
Even with early promising results from Pfizer's Covid-19 vaccine trial, significant challenges and unanswered questions remain before average Americans can get a shot. Pfizer's vaccine is a new type of technology that's never been used in mass human vaccination before and experts caution that much remains unknown about its safety, how long it might work and who might benefit most. Full coverage of the coronavirus outbreak Pfizer's phase 3 clinical trial began in late July and has enrolled more than 43,000 study participants. Some received the actual vaccine, while other received a placebo. Vaccine trials rely on a certain number of infections to occur. If more infections are reported among study participants who received the placebo than the actual vaccine, it's a good signal of efficacy. On Monday, the U.S. pharmaceutical giant Pfizer and its German partner, BioNTech SE, said that early analysis show that the Covid-19 vaccine is more than 90 percent effective at preventing symptomatic illness. …. Dr. William Haseltine, an infectious diseases expert and president of ACCESS Health International, agreed with that assessment. He predicted that if the vaccine indeed is proven safe and effective, it may work more like the flu shot. "It's not necessarily going to protect you from infection, and it may not work for everyone," Haseltine said Monday on MSNBC. "But it should be useful for many people. And it should moderate the severity of disease." The link to this article can be found here: Pfizer's Covid-19 vaccine promising, but many questions remain
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Abortion Reversal’ Evangelist Enlists in the COVID Wars Daily Beast | November 12, 2020 | Article
Dr. George Delgado, the man best known for claiming women could reverse their abortions, has now set his sights on a new mission that is just as scientifically dubious: helping churches fight public health restrictions during a global pandemic. Delgado, a 58-year-old family medicine physician from San Diego, California, became a hero of the anti-abortion movement for inventing a protocol he calls “abortion pill reversal.” The procedure is meant to stop the effects of a medication abortion midway through, by giving the patient an injection of progesterone after they take the first of two pills that trigger a medication abortion. It is a tantalizing idea for religious conservatives, who have spent years fighting the rise of inexpensive, readily available abortion pills—but one that is almost entirely unproven. … Dr. William Haseltine, a former Harvard professor and pioneer in HIV/AIDS research, denounced these claims as “completely bogus.” “He has no ... idea what the spiritual cost is,” Haseltine said. “To me, the spiritual harm is having your friends and family die.” “Having your mother die is going to be spiritually beneficial to you? Having your child hospitalized and maybe die is spiritually beneficial for you?” he added. “I don’t think so.” … And attempting to reach herd immunity, Haseltine said, would mean tolerating between 2 and 6 million American deaths across this past year and the next 12 months. “Is that what they want?” he asked. “I call that the equivalent of mass murder.” The link to this article can be found here: Abortion Reversal’ Evangelist Enlists in the COVID Wars
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In an Attempt to Keep Schools Open, Some Parents Are Refusing to Test their Kids for COVID-19 Parents | November 13, 2020 | Article
Some Utah parents are reportedly endangering the health of others by refusing to test their children for COVID-19. Experts weigh in on the "mom code" and explain why testing and contact tracing are necessary to control the pandemic. Many families have coronavirus fatigue after practicing pandemic protocols for eight months, but some parents are reportedly refusing to test their children for COVID-19 in order to artificially keep the number of cases low and avoid closing the schools. Proponents of the so-called "mom code" encourage parents to keep their children at home if they have symptoms, but not to test them. Parents share messages on Facebook groups in Utah's Davis, Salt Lake, and Washington counties, which all have high positivity rates of COVID-19 infections. "I [personally] think getting tested is selfish," posted one Utah parent, according to Salt Lake City's KUTV. "Because of the fact that they contact trace everyone so one person leads to 30 people that have to quarantine or worse, programs like athletics etc. are shut down … Stop the testing. Stop the contact tracing." …. "Societies need to shift to make it possible for kids and their families who've been exposed to the virus to stay home safely," says William Haseltine, Ph.D., scientist and author of A Covid Back to School Guide. "This requires community support and a system that allows families to isolate for the necessary length of time, without risk to their jobs, income, and livelihoods." The link to this article can be found here: In an Attempt to Keep Schools Open, Some Parents Are Refusing to Test their Kids for COVID-19
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December 2020
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HIV lessons for covid-19
El Pais | December 1, 2020 | Article
World leaders in the fight against AIDS review what they have learned in four decades and call for putting science, political leadership and individual responsibility at the center of the response to pandemics The human immunodeficiency virus (HIV) and SARS-CoV-2 are almost nothing alike, but the response to the COVID-19 pandemic has a lot to learn from four decades of AIDS efforts. Not only in research and development (R&D), but also in communication, human behavior, equity and implementation of programs to prevent, detect and treat infection on a global scale. Above all, with a view to avoiding upcoming waves of great impact and preparing the deployment of vaccines. Investigate Tomorrow's Epidemics Today Decades of research on issues that have nothing to do with a coronavirus have taken decades for prototype covid-19 vaccines to be developed in just a few months. So says William Hasseltine, founder of Harvard University's HIV and Cancer Research Units, who led the effort to sequence the HIV genome in the 1980s “HIV research has been absolutely vital to COVID-19: it has bequeathed many of the scientists who now lead R&D on the new virus along with the infrastructure to conduct research and clinical trials. In turn, the first effective drugs against AIDS were drugs that had been rejected for cancer, "says Hasseltine who, coincidentally, was one of the first people to save his life thanks to another innovation, penicillin, in 1945. Hasseltine gives an example: in the past decade, drugs against SARS and MERS were being developed that could also have worked against SARS-CoV-2, but when the alarm was passed, the funds were withdrawn and the initiative was left up in the air. . "The lesson is that you should never let your guard down when it comes 2566
to funding antiviral research," says the scientist and also founder of a dozen biotech companies. Hasseltine agrees, but also stresses individual responsibility for the common good. “The science has been stellar for both HIV and COVID-19, but it is not enough. Political leadership and social solidarity are needed to control these pandemics, ”he says. "Individual freedom is important, but it has limits: when in the middle of a pandemic we say that we have the right not to wear a mask and go to the pub every night, we are exceeding these limits." In a globalized world, this means that the virus not only continues to be transmitted between neighbors, but between countries, many of them with fragile health systems already before the arrival of covid-19. The link to this article can be found here: HIV lessons for covid-19
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January 2021
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Simpler guidelines may speed rollout healthline | January 13, 2021 | Article
More than 29 million doses have been distributed by the federal government, and about only 10.2 million people have received their first dose, according to the CDC’s COVID Data Tracker. The delay in the rollout comes as the country continues to set new COVID-19 records — averaging more than 248,000 new infections a day over the past week, along with more than 3,200 COVID-19 deaths a day, according to CNN. Dr. Robert Amler, dean of the School of Health Sciences and Practice at New York Medical College and a former chief medical officer at the CDC’s Agency for Toxic Substances and Disease Registry, says the Trump administration’s new guidelines are a step in the right direction. “Fewer people will have to hold back until their priority group is called,” he said. “There will be less frustration, so more people will plan to get vaccinated.” William A. Haseltine, PhD, a former professor at Harvard Medical School and Harvard School of Public Health, and founder of nonprofit ACCESS Health International, thinks having lesscomplicated guidelines can also help speed up vaccinations. “The simplest rule is if you’re of a certain age, you’re eligible to get the vaccine,” he said, “and you continually lower the age groups.” However, he says that by taking into account comorbidities in people under 65 years old, the new guidelines complicate matters. Several conditions are linked to a higher risk of severe COVID19, including diabetes, chronic lung or heart disease, high blood pressure, and cancer. But so is obesity, which would make over 42 percent of adults eligible to be vaccinated. “The moment you open it up to include any kind of complexity, it’s going to be confusing and misinterpreted,” Haseltine said. Amler agreed that simpler is better. 2569
“The more restrictive approach — with many different categories, unclear distinctions, and guidelines that keep changing — hasn’t worked well so far,” he said. He added that “open vaccination with fewer priority distinctions” will be even more important as people begin to come back for their second dose. While Azar said the rollout will be aided by the “consistent pace of [vaccine] production,” Haseltine warned that manufacturing has not been the main cause of the lag in vaccinations. Instead, it’s disorganization and lack of resources at the local level. “Each locality is doing what they can with their limited resource to address those issues,” he said. “But they’re serious issues that haven’t been resolved yet.” The link to this article can be found here: Simpler guidelines may speed rollout
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As new Covid vaccines near U.S. debut, here’s what you need to know about the shots CNBC | January 29, 2021 | Article
Help is on the way. This week, two companies released more news on their Covid19 vaccines as they prepare to seek regulatory clearance, flashing signs of hope that the U.S. could soon have more weapons against the pandemic. But with fresh reasons to be hopeful also came signals of caution, as the not-yet-authorized vaccines appeared to be less effective against some rapidly spreading strains of the virus. Biotech firm Novavax said Thursday that its vaccine was more than 89% effective in protecting against the disease in its phase three clinical trial conducted in the United Kingdom. And Johnson & Johnson added Friday that its single-dose shot was 66% effective overall in protecting against Covid-19. The introduction of two more vaccines could significantly bolster the world’s arsenal of tools to drive back the virus and bring the pandemic to an end. And while J&J’s vaccine appears to be significantly less effective in preventing disease than Moderna’s and Pfizer-BioNTech’s, officials said it’s still effective enough to prove useful and the fact that it only requires one shot is a clear advantage. With more vaccines entering the fray, here’s what you need to know as you prepare to get your shot: 1. Who’s eligible to get vaccinated? Pfizer’s vaccine has been authorized by the Food and Drug Administration for use in people age 16 and older, while Moderna’s vaccine has been authorized for people 18 and up. J&J’s vaccine hasn’t been authorized yet. The company is expected to submit an application for emergency use authorization to the U.S. agency next week. The FDA review process is expected to take a few weeks, and the vaccine could be distributed across the U.S. as early as next month. Meanwhile, it’s unknown when the Novavax vaccine will be authorized for use in the U.S. Its phase three trial, the results of 2571
which were published Thursday, was conducted in the United Kingdom, and it’s unclear if that will be enough for U.S. authorization. The company began a late-stage trial with 30,000 people in the U.S. and Mexico in late December. With supply so constrained, states are rationing doses to those deemed most vulnerable and essential to society. While there is federal guidance on who should get the shots first, many states are charting their own course. But with the slower-than-expected rollout, the federal government urged states to open up eligibility to everyone 65 and older. 2. When will supply increase? More than 48.4 million doses of vaccine have been distributed in the U.S. so far, according to data from the Centers for Disease Control and Prevention. Considering the two currently authorized vaccines are two-dose regimens, the U.S. would need more than 660 million shots to inoculate the entire public with the currently available vaccines. Earlier this week, President Joe Biden announced plans to purchase an additional 200 million doses of the vaccines, including 100 million from Moderna and 100 million from Pfizer. That would bring total U.S. supply of those two vaccines to 600 million doses, but the companies are still working to ramp up the pace of production. Pfizer has said it will deliver 120 million doses, and Moderna has promised 100 million by April. The introduction next month of J&J’s one-shot vaccine could ramp up supply in the U.S., which has ordered 100 million doses from J&J to be delivered by the end of June. Novavax has agreed to deliver 100 million doses of its vaccine to the U.S. if it’s authorized. 3. Are the vaccines effective against new variants? Manufacturers and the U.S. government are studying how effective the current vaccines are against new variants of the virus. One variant in particular, the B.1.351 strain that’s become dominant in South Africa, is causing concern among health officials. The global trials of the Novavax and J&J vaccines give some indication about how those vaccines will hold up against new strains. Novavax said its vaccine proved just 49% effective among 44 Covid19 cases in South Africa, where 90% of the cases were associated with the troubling new variant. And J&J said its vaccine was 57% effective in the South African arm of its trial. 2572
Dr. Paul Offit, a member of the FDA’s Vaccines and Related Biological Products Advisory Committee, told CNBC the new strains are not a huge problem yet, but it’s important for drugmakers to prepare for the possibility that the virus could mutate enough to evade the protection of the current vaccines. “Prepare for it. Sequence these viruses. Get ready just in case a variant emerges which is resistant” to the vaccine, he said. Both Pfizer and Moderna have already said they’re working on a booster shot for their vaccines that will hold up better against the B.1.351 strain. 4. Are some shots better than others? The first two vaccines authorized in the U.S. set a lofty standard for the others to follow. Pfizer’s data showed that its vaccine was 94% effective in preventing the disease, while Moderna’s read out at 95% efficacy. J&J said its vaccine was 72% effective in preventing the disease in the U.S., but added that it was 85% effective in preventing people from becoming severely ill with Covid-19. White House health advisor Dr. Anthony Fauci noted later Friday that the most important finding of the J&J vaccine data is that the single shot may keep people out of hospitals and prevent severe illness. “The first thing people do is compare a 72% efficacy with the previously reported in other trials of 94% to 95%. That is true,” Fauci said at a White House press briefing Friday, adding that the more important figure to look at is the 85% efficacy in preventing severe sickness. “The most important thing — more important than whether you prevent someone from getting aches and a sore throat — is preventing people” from getting severe disease, Fauci had said earlier on a call with reporters. “That will alleviate so much of the stress and human suffering and death in this epidemic.” But with supply limited and appointments hard to come by, public health specialists are urging people to accept whichever vaccine is available to them, rather than wait for their vaccine of choice. “I don’t think in a public health crisis, we should be picking,” said Dr. Carlos del Rio, a professor at Emory University School of Medicine. “I think in a public health crisis, you take what there is.” 5. What can you do in the meantime? 2573
As supply of vaccine doses ramps up and new players enter the fray, many Americans still won’t be able to get a shot for months. Health officials are urging people to take steps to drive down the level of spread, in the meantime, to prevent more new strains of the virus from emerging. Viruses are like nature’s artificial intelligence, William Haseltine, president of the think tank ACCESS Health International and a former Harvard Medical School professor, told CNBC. As the virus spreads, it makes huge numbers of copies of itself, and each version is a little different from the one before it. Those copies allow the virus to adapt to its environment. As they spread, they can learn how to penetrate into humans better and make themselves more transmissible, like the variants of concern first reported in the U.K., South Africa and Brazil. That’s part of the reason why global health experts have pushed for people to dent Covid-19′s spread through public health measures, such as social distancing, washing hands and wearing a face mask. That would give the virus fewer opportunities to mutate, and it would buy time until a vaccine can be rolled out. “What this virus is telling us is if we don’t control it through public health, we’re sunk for a couple more years and maybe for a much longer time. That is a big message,” Haseltine said. “Don’t rely on the vaccines, don’t rely on the drugs. This virus can outwit them.” Dr. Jay Butler, the CDC’s deputy director for infectious diseases, said on Friday that current modeling suggests that 70% to 75% of people would need to be vaccinated for the population to reach herd immunity. However, if a faster spreading virus were to become the dominant strain, it would likely push that percentage to as high as 85%, he said. “Looking down the road, I think it emphasizes again the importance of ongoing work in community mitigation, as well as the importance of using the vaccines that we have available now and in the near future,” Butler said on a conference call organized by the Infectious Diseases Society of America. The link to this article can be found here: As new Covid vaccines near U.S. debut, here’s what you need to know about the shots
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February 2021
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Moral Injury: Pandemic's Fallout for Healthcare Workers Medscape | February 2, 2021 | Article
Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center. In his 17 years as a doctor, Matthew Heinz, MD, had never gotten a telephone call like the one from his hospital in Tucson, Arizona. Late one night in December, a hospital supervisor called to tell him that five COVID patients were in distress. All of them needed a higher level of care, four of them urgently. But only one bed was available for the level of care they needed. "You pick," she told Heinz. "It's something I have never anticipated having to do," he says in retrospect. "I was never, ever called upon to make such an important decision so quickly. I was frustrated, and it's heartbreaking. But you don't have time to dwell on that. I had to sit there and think about...who would be first, second.... No, I thought, this is not what I signed up for." While burnout is often used to describe the effects of all this ongoing stress among healthcare workers battling the pandemic, mental health experts have recently begun to say that a better description is moral trauma — and that this moral trauma is so longlasting and pervasive, it actually becomes moral injury. Originally used to describe what soldiers experience in wartime, moral injury in healthcare began to be applied to healthcare even before the pandemic, says Wendy Dean, MD, a psychiatrist and the president and co-founder of Moral Injury of Healthcare, a nonprofit devoted to reframing clinician distress as moral injury — and to work to improve the source of it, which she and others say is the healthcare system itself. Moral trauma is different than the trauma, for instance, from a car accident, says William A. Haseltine, PhD, chair and president of ACCESS Health International, a global health think tank. "Moral 2576
trauma is seeing something that's wrong. Moral trauma has a special dimension. It affects your sense of right and wrong." When healthcare providers have to launch a "crisis standard" of care, deciding on how to distribute healthcare resources based on things like how many productive years a patient likely has left, or the extent of sickness, "that's deeply traumatic," he says. "That could happen in an earthquake, a tidal wave." But having to make these decisions during the COVID pandemic is even worse, he says, than during natural disasters because "COVID was preventable by government action." Making those standard-of-care decisions in natural disasters doesn't lead to moral injury for healthcare providers, Haseltine says. But "moral injury comes from knowing you are making that decision in a situation where it didn't have to happen. That is deeply traumatic." In a viewpoint published last year, Haseltine proposed this solution to aid the recovery from the pandemic's moral trauma: "We need collective action to return our government to a disciplined plan based on science to control the pandemic. We know with certainty it can be done with the tools at hand." No miracle is needed, he stresses, but "only resolve, that of our government to do what is right, and if not, by we the people to make sure they do!" The link to this article can be found here: Moral Injury: Pandemic's Fallout for Healthcare Workers
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Experts split on delaying COVID-19 vaccine second doses. Here's why CNN Philippines | February 3, 2021 | Article
"We get down the list faster if we do all those first doses," Marc Lipsitch, professor of epidemiology at the Harvard T.H. Chan School of Public Health, told CNN on Monday. "My view is that the weight of the evidence suggests that we would probably save more lives by delaying second doses than by insisting on the schedule that was tested in the trials," he said. Yet not all experts agree that changing dosing schedules is a good idea. "We have two problems with that. The first -- they may not get fully protected and that might accelerate the rate of variants taking over and causing us much more trouble in the future," William Haseltine, chair and president of the global think tank ACCESS Health International, said during an appearance on CNN's New Day on Monday. "Secondly, we really don't know if delaying the second dose for a long time is going to give you the same degree of protection," he said. In other words, there's not much research as Covid-19 vaccines were developed only recently. Meanwhile, as debates around delaying second doses continue in the United States, so do a slow vaccine rollout, more Covid-19 deaths and the spread of newly identified coronavirus variants that appear to be more transmissible. The link to this article can be found here: Experts split on delaying COVID-19 vaccine second doses. Here's why
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"Pathogen porn": Two papers about a New York coronavirus strain spark a scientific war of words Salon | February 26, 2021 | Article
One of the greatest ongoing pandemic concerns is how the SARS-CoV-2 coronavirus, which causes the disease, frequently mutates. Some of these mutations have become household names: there's B.1.1.7, which originated in the United Kingdom and is more transmissible than usual strains of the novel coronavirus. The 501Y.V2 strain, which originated in South Africa, raised alarm last month after a paper revealed that many people who contracted other coronavirus strains did not have antibodies which protected them from the new one. Then there was a hybrid coronavirus that scientists announced earlier this month had been discovered in California; this one combined B.1.1.7 with a different coronavirus strain. Now there is a mutant version of the novel coronavirus in New York City called B.1.526, according to a pair of studies produced by Caltech and Columbia University. Neither of them has been published in a scientific journal or been vetted through the peer review process, which means scientists do not have definitive information about if and/or how the new strain will pose a greater risk to human health. What we know for sure is that B.1.526 is a hybrid of two mutations: One mutation, E484K, is believed to help the viruses beat the vaccines; another mutation, S477N, scientists theorize has an effect on how tightly the virus binds itself to cells. "The Caltech paper by [computational biologist Anthony] West is better," Dr. William Haseltine, the chair and president of the global health think tank Access Health International and a biologist famous for his work in confronting the HIV/AIDS epidemic, wrote to Salon. Haseltine says that the CalTech group reported on two variants in New York City and the Columbia group only reported on one. 2579
Still, Haseltine calls the discovery a "big deal," and said that observations suggest the new variants are more transmissible, more likely to infect young children, more virulent and can avoid antibodies both produced by the body and induced by vaccines. The link to this article can be found here: "Pathogen porn": Two papers about a New York coronavirus strain spark a scientific war of words
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The Heat: One scientist’s fight against disease & Racism against Asian-Americans America CGTN | February 26, 2021 | Video
As a scientist and businessman, William Haseltine has created 10 different companies that have produced a range of products – from medicines to combat cancer, AIDS, lupus and diabetes, to protections against bioterrorism. If that weren’t enough, he founded ACCESS Health International, a nonprofit think tank and foundation focused on expanding access to health care. He covers all that and more in his new autobiography – “My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19.” •
William Haseltine is the Chair & President ACCESS Health International
The link to this video can be found here: The Heat: One scientist’s fight against disease & Racism against Asian-Americans
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April 2021
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Trump-Touted Drug Lives On as Covid Therapy Despite Trial Flops Bloomberg | April 1, 2021 | Article
Hydroxychloroquine, the antimalarial drug that former President Donald Trump touted as a “game changer” in the fight against Covid-19, is still being prescribed by physicians in the U.S. though it has proven to be ineffective against the virus in clinical trials. Concern is growing that patients are at risk of harm because physicians continue to prescribe hydroxychloroquine over other potentially life-saving Covid treatments. In June, the Food and Drug Administration revoked the emergency use authorization for hydroxychloroquine “in light of ongoing serious cardiac adverse events and other serious side effects.” The potential benefits of the drug no longer outweigh the known and potential risks for the authorized use, the agency said in a statement. “I would say if it’s not malpractice then it’s certainly close,” said William Haseltine, a former Harvard Medical School professor and a pioneering HIV researcher who now chairs Access Health International, a health equity think tank. “It’s unfortunate. The patients that are receiving [hydroxychloroquine] are not receiving benefit. It’s not particularly toxic, although it is toxic in some cases for people with heart problems -- so it could harm those people.” The link to this article can be found here: Trump-Touted Drug Lives On as Covid Therapy Despite Trial Flops
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Months after recovering from COVID-19, millions may suffer from "brain or psychiatric disorders" Salon | April 8, 2021 | Article
An astonishing study found that roughly one out of three COVID-19 survivors were diagnosed with either a brain or psychiatric disorder within six months of contracting COVID-19. The shockingly high proportion of brain and psychiatric disorders in COVID-19 patients suggests that 10 million Americans (out of the 30 million who have contracted COVID-19) could suffer mental health repercussions in the coming years. That prophesies an impending social crisis for which American society is unprepared. In an article published in the journal The Lancet Psychiatry, researchers revealed that out of more than 230,000 COVID-19 patients (most of them from the United States), approximately one out of three (33.6%) developed either neurological or psychiatric issues. That number rose to 38.7% for patients who were hospitalized, 46.4% for those who had to be admitted to an intensive treatment unit and 62.3% for those who were diagnosed with encephalopathy (a term that refers to any disease which alters the structure or function of your brain). Although the researchers were unable to determine how COVID-19 leads to many of these conditions, they established that the most common psychiatric conditions linked to a COVID-19 diagnosis were anxiety and depression. There were also statistically significant cases of strokes, dementia and other neurological conditions, although these were more rare. "These results are worrying and suggest COVID-19 is associated with a higher rate of long term psychological and neurological complications than have been observed in other respiratory diseases such as influenza," Dr. Russell Medford, Chairman of the Center for Global Health Innovation and Global Health Crisis Coordination Center, told Salon by email. "In order to develop effective 2584
therapeutic, behavioral and public health interventions, this study emphasizes the urgent need for additional scientific and medical research to gain a better understanding of the underlying pathophysiological mechanisms of COVID-19 that may impact brain function and human behavior." Dr. Georges Benjamin, executive director of the American Public Health Association, wrote to Salon that scientists already know that "this virus causes significant impairments to several bodily organs beyond the lungs. These commonly include the heart kidneys, blood system and brain. The exact mechanisms are not well understood but are under intensive study." When it comes to neurological effects, it had already been established that these ranged "from targeted functions like temporary but prolonged loss of taste and smell to prolonged episodes of headaches, debilitating physical fatigue or muscle weakness and difficulty with thinking clearly (brain fog)." He added that survivors would need supportive care going forward and pointed out that "there are some studies looking at the use of monoclonal antibodies to see if they can halt or reverse some of the neurological symptoms. Scattered reports of improvements after vaccination have also been reported but these are not conclusive." "There are two separate issues: One is psychiatric and one is neurological," Dr. William Haseltine, a biologist renowned for his work in confronting the HIV/AIDS epidemic, for fighting anthrax, and for advancing our knowledge of the human genome, told Salon. After noting that the new paper focuses more on psychological issues than neurological ones, Haseltine observed that scientists have already learned that COVID-19 can hurt your brain. "It isn't necessarily infection of the brain, but it is disturbance of the blood flow to the brain and the inflammation in the veins and arteries that serve the brain that leads to neurological damage," Haseltine explained. "There is considerable evidence that that occurs." He said that in addition to that, scientists know that "COVID-19 causes a lot of blood clots. It's almost equivalent to what happens to the heart-lung machine. And that is, it sends up a lot of micro clots into multiple organs. The most important one for us in this case is the brain. And you get a lot of micro-clotting in the brain for people who've had severe and serious COVID-19." He said 2585
that this is typical not just for SARS-CoV-2, the virus which causes COVID-19, but with many other viruses as well. The link to this article can be found here: Months after recovering from COVID-19, millions may suffer from "brain or psychiatric disorders"
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What’s Actually Safer? Flying Commercial or Taking a Private Jet? Fodor’s Travel | April 19, 2021 | Article
Are chartered flights poised to become the rideshare of the sky? We all know that feeling. The agony of endless airport security lines and crowded waiting areas. Waves of tension permeating the air as a flight agent announces the plane’s late departure. The possibility of a missing bag, an annoying seatmate, or even worse– unpredictable catastrophes. In this pandemic travel era, we have the additional concern of potentially contracting COVID-19, which has now morphed into COVID-21, a more contagious and infectious strain that is spreading to various parts of the world. Despite that, air travel demand for the spring and summer months is rapidly rising. Which got me thinking: with the increase in popularity of semi-private, chartered flights, are they really that much safer than flying commercial? Aero, a new luxury travel service that in February debuted its first flight route from Los Angeles to Aspen, recently invited me to evaluate this for myself. I hadn’t been on a plane since March 2020, when I returned home from Switzerland the day before the European travel ban took effect. I was nervous but also curious–as demand increases and prices become more affordable, are these airlines poised to become the Ubers and Lyfts of the sky? …. Dr. William Haseltine, the chair and president of ACCESS Health International and an internationally recognized expert on the COVID pandemic, emphasizes that private flights are much safer than commercial ones. “It’s a very different experience because with a private flight you don’t have an airport check-in line. In addition, most airports are not designed to keep a six-foot distance. There are also a number of things that can happen when you’re not in a controlled environment.” So all of the transactions that you undergo at airports through commercial flying–at check-in, boarding,
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customs, and immigration–multiplies potential contact with other people. …. But Dr. Haseltine asserts that the most dangerous aspect of flying, whether private or commercial, is being in a confined space and breathing the same air as everyone else. “Regardless of what the airlines tell you, I do not believe that they have adequate air circulation or ventilation,” he says. Dr. Haseltine also emphasized that COVID-19 is not the same as COVID-21. “COVID-21 is far more infectious and much more dangerous than COVID-19. It takes a lot less virus to infect you, and it can make you much sicker, and you have an increased probability of falling seriously ill and dying,” he says. If you do have plans to fly in the near future, what are the best ways to protect yourself? Dr. Haseltine recommends an essential supplement to a face mask–a face shield. “A face shield is really important because the virus gets into your eyes,” he says. Another precaution is wearing gloves and changing them as often as you would wash your hands. And if possible, bring your own food and drink on the plane. The link to this article can be found here: What’s Actually Safer? Flying Commercial or Taking a Private Jet?
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India's 'double mutation' covid virus variant is worrying the world Mint | April 19, 2021 | Articles
With India’s daily tally of Covid-19 infections surging by records, public health experts worry that a new -- possibly more virulent -- coronavirus variant could be racing through the crowded nation of more than 1.3 billion people. The new variant, which has a so-called double mutation, is thought to be fueling India’s deadlier new wave of cases that has made it the world’s second worst-hit country, surpassing Brazil again, and has already begun to overwhelm its hospitals and crematoriums. India has reported more than 14.5 million Covid cases so far and more than 175,600 fatalities. …. “The B.1.617 variant has all the hallmarks of a very dangerous virus," William A. Haseltine, a former professor at Harvard Medical School wrote in Forbes on April 12. “We must do all that is possible to identify its spread and to contain it." The link to this article can be found here: India's 'double mutation' covid virus variant is worrying the world
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GLOBAL TRAVELER: Six vaccinated medical experts reveal their summer travel plans CNBC | April 22, 2021 | Article
The U.S. Centers for Disease Control and Prevention cleared vaccinated Americans to travel again, but some immunized travelers remain on the fence about making summer plans. Is it finally safe to fly? What about visiting unvaccinated relatives or traveling with young children? CNBC Global Traveler asked medical professionals — all of whom are involved in treating or researching Covid-19 — to share their travel plans this summer. Here are their responses, in their words. ….. Only from one home to the other — by car “I am not traveling this summer, except to travel by car from our place in New York City to our home in the country. Under normal circumstances, we would travel extensively, including abroad. But this year, we will spend most of our time in our country home, since it is much easier to avoid close contact than it is in the city or when traveling afar.” “When we do have to come into the city, we will do so by car. And when we arrive, we will avoid public transit, crowded venues and indoor activities.” This is not yet the time to let up…. William Haseltine PRESIDENT, ACCESS HEALTH INTERNATIONAL “Being vaccinated didn’t change my behavior or my summer travel plans. There are new variants … emerging with regularity, and the vaccines will not be equally effective against them all. Because of this, I and all those in my immediate family are taking the same precautions after vaccination as we did before we were vaccinated. That includes avoiding unnecessary travel.” “When we do need to go into public places, like to the post office or the grocery store, we wear N95 masks and a face shield, a 2590
combination that has proven effective even in indoor healthcare settings of significantly cutting down the risk of infection.” “If some members of our extended family are required to travel over the summer, we’ll be asking them not to visit us until at least two weeks post travel — that includes the adults that are vaccinated and the children who are not.” “This is not yet the time to let up on the public health measures that can help us control the pandemic.” —William Haseltine, former professor at Harvard Medical School and current president of Access Health International; author of “Variants! The Shape-Shifting Challenge of COVID-19” The link to this article can be found here: GLOBAL TRAVELER: Six vaccinated medical experts reveal their summer travel plans
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Vaccine Hoarding May Backfire on Rich Nations as India Reels Bloomberg | April 27, 2021 | Article
For months, developed economies have hoarded Covid-19 vaccines and the raw materials needed to make them. Now, they’re being forced to act as an explosive outbreak in India raises the risk of new virus mutations that could threaten the wider world. Under mounting criticism for dominating vaccine resources, the U.S. said this week that it will help India by sending items needed to manufacture vaccines as part of an aid package. European countries are also pledging help as new cases in the South Asian country smash world records. President Joe Biden’s administration is separately vowing to share its stockpile of AstraZeneca Plc vaccines -- which the U.S. hasn’t even approved for use -- and meeting with drug companies about boosting supply and waiving intellectual property protections on Covid-19 shots, a shift India and South Africa have been pushing for. The moves show a growing realization that the vaccine nationalism many wealthy nations have embraced has the potential to backfire, prolonging the global pandemic. While those countries have been cornering supplies of the first vaccines for their worldleading rollouts, places like India have run short, allowing the virus to run wild. Some scientists have linked the nation of 1.3 billion people’s second wave to a more virulent strain, with the out-ofcontrol outbreak providing a petri dish for further mutations to evolve that could challenge the vaccines now being distributed from the U.K. to Israel. ….. “I fear there may be more trouble coming,” said William Haseltine, a former Harvard Medical School professor and HIV researcher who now chairs think tank Access Health International. “There are already second and possibly third generation variant of the B.1.617 circulating in India. These may be more dangerous than is the B.1.617 variant itself.” 2592
The link to this article can be found here: Vaccine Hoarding May Backfire on Rich Nations as India Reels
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May 2021
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Will summer see a ‘travel window’ before fall infections rise? Here’s what medical experts say CNBC | May 5, 2021 | article
For some homebound travelers yearning for a vacation, the question isn’t whether to book a vacation this year, but when. Enthusiasm for travel is at its highest point in a year, with 87% of American travelers expected to take a trip this summer, according to a survey conducted last week by travel market research company Destination Analysts. But is the summer the best time to travel this year, or is it prudent to wait? Medical professionals present several scenarios of how the rest of 2021 may play out. …. 4. The chance of another summer surge William Haseltine, former professor at Harvard Medical School and author of “Variants! The Shape-Shifting Challenge of COVID19,” said there is a risk of another summer surge, and traveling during the summer will only exacerbate the problem. “The more people choose to travel as an escape from the very real pandemic stress and fatigue, the more we risk another surge of cases this summer,” he said. Haseltine said many people hope warm summer weather will bring a decrease in Covid cases, due to the seasonality of other coronaviruses and influenza viruses. But as it turns out, this virus is “far less seasonal than many expected it to be,” he said. “If you look back at 2020 and the early part of 2021, you’ll see that there have been fall surges and winter surges, as one might expect, but there have also been spring surges and summer surges.” While the virus that causes Covid-19 is expected to become seasonal at some point, the UN World Meteorological Organization
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highlighted in a report that “there is no evidence” that this year will be different from 2020. The link to this article can be found here: Will summer see a ‘travel window’ before fall infections rise? Here’s what medical experts say
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What Does a Future Without Herd Immunity Look Like? NYT | May 20, 2021 | article
For many months after the coronavirus locked the world into a strange and fearsome new reality, herd immunity was billed as the key to our escape. Vaccinate enough of the population, the theory went — between 60 percent and 70 percent, it was estimated — and the virus would no longer be able to spread widely. But recently, the tantalizing promise of a clean exit from the pandemic has receded. “There is widespread consensus among scientists and public health experts,” The Times’s Apoorva Mandavilli wrote two weeks ago, “that the herd immunity threshold is not attainable — at least not in the foreseeable future, and perhaps not ever.” How did herd immunity come to be seen as a remote possibility, and what does a future without it look like? Here’s what people are saying. *** “Much like what has been proposed with influenza, we must develop Covid risk assessment tools that can identify the viral properties of dominant strains — how transmissible they may be or how resistant they are to current drugs or vaccines — to help us align our public health response with the level of risk,” William A. Haseltine, the founder of Harvard’s cancer and H.I.V./AIDS research departments, wrote in Scientific American in February. “Otherwise, we’ll be setting ourselves up for failure once more.” The link to this article can be found here: What Does a Future Without Herd Immunity Look Like? Mixing two different vaccine doses might actually strengthen COVID-19 immunity, not hurt it Salon | May 23, 2021 | article In mid-April, the New York Post ran a story about a worried patient who suffered a vaccine mix-up. "Man accidentally gets one Moderna and one Pfizer COVID vaccine," the headline read. 2597
Both the Moderna and the Pfizer coronavirus vaccines, which are being distributed in the United States, require two separate shots to be complete; the Moderna vaccine is delivered in two injections spaced 28 days apart, while for Pfizer, the difference is 21 days. *** "It appears as if they're at least as good or better," Dr. William Haseltine, chair and president of the global health think tank Access Health International, told Salon. "You're presenting the immune system with something it has seen before, but in a slightly different version, and that can make a positive difference." At the very least, it appears that someone who mixes vaccines does not have to be worried. As Haseltine noted, "almost everybody has received mixtures of vaccines over time, both for influenza and for many other diseases." The link to this article can be found here: Mixing two different vaccine doses might actually strengthen COVID-19 immunity, not hurt it
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What’s the difference between full FDA approval for a vaccine and emergency use authorization? Dallas Morning News | May 27, 2021 | Article
Over the last several months, federal regulators have given the green light to three vaccines to fight COVID-19. And though researchers say the Pfizer-BioNTech, Moderna and Johnson & Johnson shots are safe and effective, they don’t yet have full approval from the U.S. Food and Drug Administration. Instead, the agency has issued an emergency use authorization for each of the vaccines, a type of approval that’s used in public health emergencies. So what’s the difference between full FDA approval and an emergency use authorization? Here’s what you need to know. *** When could the current vaccines get full approval? For example, companies may be asked to submit more comprehensive data on how long the vaccines provide protection, whether people will need annual booster shots, how well the vaccines are likely to protect against emerging variants and how well they prevent transmission of the virus, said William Haseltine, president of the nonprofit think tank ACCESS Health International and an infectious disease expert. The link to this article can be found here: What’s the difference between full FDA approval for a vaccine and emergency use authorization?
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July 2021
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England’s Covid unlocking is threat to world, say 1,200 scientists The Guardian | July 16, 2021 | Article
International experts say ‘unethical experiment’ could allow vaccine-resistant variants to develop. Boris Johnson’s plan to lift virtually all of England’s pandemic restrictions on Monday is a threat to the world and provides fertile ground for the emergence of vaccine-resistant variants, international experts say. Britain’s position as a global transport hub would mean any new variant here would rapidly spread around the world, scientists and physicians warned at an emergency summit. They also expressed grave concerns about Downing Street’s plans. Government advisers in New Zealand, Israel and Italy were among those who sounded alarm bells about the policy, while more than 1,200 scientists backed a letter to the Lancet journal warning the strategy could allow vaccine-resistant variants to develop. *** “What I fear is that some of the worst impulses in many of our states will follow the UK example,” said Dr William Haseltine, a former Harvard Medical School researcher and a pioneering Aids researcher who chairs Access Health International, a New Yorkbased thinktank. The full article can be found here: England’s Covid unlocking is threat to world, say 1,200 scientists Scientists round on UK over plan to end COVID curbs Al Jazeera | July 16, 2021 | Article The UK government’s plan to scrap day-to-day pandemic restrictions in England next week is reckless and has no basis in science, international experts have warned, with one arguing it amounts to premeditated murder. Prime Minister Boris Johnson said this week it was “highly probable” the worst of the coronavirus pandemic was over as he
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pressed ahead with Monday’s reopening, despite the Delta variant spreading out of control. *** “I’ve written that I believe that the strategy of herd immunity is actually murderous,” US scientist William Haseltine said after an emergency discussion among experts about the UK plan. The full article can be found here: Scientists round on UK over plan to end COVID curbs
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UK govt plan to end virus orders queried as cases top 50,000 Associated Press | July 16, 2021 | Article
LONDON (AP) — The U.K. recorded more than 50,000 new coronavirus cases for the first time in six months Friday amid a warning from the British government’s top medical adviser that the number of people hospitalized with COVID-19 could hit “quite scary” levels within weeks. Government figures showed another 51,870 confirmed lab cases, the highest daily number since mid- January. Infections have surged in recent weeks, mainly among unvaccinated younger people, as a result of the far more contagious delta variant and the continued easing of lockdown restrictions. Despite the increase, the British government plans Monday to lift all remaining legal restrictions on social contact in England and to ditch social distancing guidelines as well as the legal requirement for people to wear masks in most indoor settings, including shops, trains, buses and subways. *** One of the co-signatories to Friday’s statement, Dr. William A. Haseltine of the New York-based think tank Access Health International, went further, describing the seeming strategy of herd immunity as “murderous” and “unconscionable.” The full article can be found here. England’s lifting of Covid lockdowns is a danger to the entire world, experts warn CNBC | July 16, 2021 | Article KEY POINTS • Gathering at a virtual summit on Friday, leading scientists and government advisors from all over the world warned that Britain was heading for disaster by removing most of its remaining restrictions on Monday. • The event came as more than 1,200 scientists backed a letter to the Lancet medical journal, in which U.K. Prime Minister 2603
Boris Johnson’s plans were dubbed “dangerous and premature.” LONDON — Global scientists have criticized the U.K. government’s plans to ease almost all Covid-19 restrictions, calling it unethical and dangerous for the entire planet. Gathering at a virtual summit on Friday, leading scientists and government advisors from all over the world warned that Britain was heading for disaster by removing most of its remaining restrictions on Monday. *** 1. William Haseltine, a U.S. virologist and chair and president of ACCESS Health International, told the panel at Friday’s summit that the world had “always looked to the U.K. for great, sensible policies.” 2. Haseltine slammed so-called herd immunity strategies — where populations are allowed to build up natural immunity to an illness through exposure to it — as “murderous.” 3. “I think that’s a word we should use, because that is what it is. It is knowledge that you are doing something that will result in thousands, and in some cases tens of thousands of people dying,” he said. “It is disaster as policy, it’s been clear that that’s been the case for some time, and to continue to espouse that policy is unconscionable.” 4. Haseltine also noted that vaccines alone would not bring an end to the pandemic. “Even if you are fully vaccinated, you must follow serious efforts and control to try to eliminate, not just mitigate, the problem. Policies that open up the country in the midst of a growing wave of infections are counterproductive in the most extreme,” he warned. The full article can be found here. Will we ever find COVID-19's 'Patient Zero?' LiveScience | July 27, 2021 | Article Chinese officials have rejected a World Health Organization proposal to investigate the origins of the novel coronavirus that causes COVID-19, raising new questions about whether the world will ever learn when, where and how the coronavirus (SARS-CoV2) made the leap into humans.
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China objected to the WHO plan last week because this phase of the investigation left open the possibility that the virus escaped as the result of a laboratory accident, NPR reported. Without Chinese cooperation, scientists will face frustrating gaps in the data that may keep them from identifying the moment the pandemic began. However, the virus itself does hold clues to its own origin. In the coronavirus's genetic blueprint is a history of where it came from and how long it took to cause the outbreak that led to a global catastrophe. *** However, comparing the bat viruses to the human virus can be illuminating. Bats are a lot like humans, said William Haseltine, the president of ACCESS Health International and a former professor at Harvard Medical School, where he studied HIV and the human genome. Like humans, bats have long life spans, travel over long distances and then cluster together in close contact. This pattern of behavior may partly explain why coronaviruses that evolve in bats tend to find fertile ground in humans. "A bat has a chance to be infected many times in its lifetime, so these viruses have got to survive in a long-lived mammal that has many defenses against them," Haseltine said. The full article can be found here.
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August 2021
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The war against COVID-19 was fought with weapons developed to battle HIV Salon | August 19, 2021 | Article
Harvard immunologist Dr. Bruce Walker first heard whispers of the coming pandemic while teaching a course on HIV to MIT undergraduates in South Africa. One of his students, who had recently returned from visiting family in the Chinese city of Wuhan, recounted the state of affairs in grisly detail. As the student relayed, she had been "getting text messages from her parents saying that something really drastic is going on there," Walker recalled to Salon. *** Dr. William Haseltine, a biologist renowned for his work in confronting the HIV/AIDS epidemic, as well as the chair and president of the global health think tank Access Health International, noted that "a number of different technologies were pioneered in efforts to develop HIV vaccines." "In addition," he added, "national and international vaccine clinical trial networks were constructed and operational. All were important for rapid development, testing and analysis of the safety and efficacy of COVID vaccines." "Just as cancer research facilitated rapid understanding of HIV, HIV has facilitated rapid progress on COVID-19 and finding treatments for COVID-19," Haseltine told Salon. As he explained, Richard Nixon made the fateful decision as president to fund anticancer programs that explored the possibility of the disease being caused by a virus. Years of ensuing research eventually helped scientists figure out how to treat victims of HIV, the virus behind the AIDS epidemic. "The result was very rapid progress," Haseltine explained. Notably, Dr. Anthony Fauci, President Joe Biden's chief medical adviser, spent much of his career researching HIV. The full article can be read online here.
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'Draconian measures' needed vs virus – expert The Manila Times | August 22, 2021 | Article
"DRACONIAN measures" such as intense lockdowns, rigorous contact tracing, testing, isolation and increased public health measures will have to be enforced for the Philippines to control the spread of the coronavirus disease 2019 (Covid-19), an infectious disease specialist and author told The Manila Times in an exclusive interview. Dr. William Haseltine, currently the chairman of Access Health International and who has worked on the development of treatments for HIV/AIDS and cancer, said the Philippines has the chance to become the next "New Zealand" which set up stringent border control and "ruthless" lockdowns. *** The full article can be read online here.
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September 2021
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Researcher says COVID variant R.1 is ‘something really to watch’ 11 Alive, Atlanta | September 22, 2021 | Interview
ATLANTA — Out of all the COVID variants emerging, the one called R.1 got into a nursing home in Eastern Kentucky this past March -- a nursing home where almost all of the residents were vaccinated. That R.1 COVID variant, carried into the facility by an infected health care worker, was able to infect one-fourth of the vaccinated residents. The same variant is here in Georgia. *** “That’s the first warning, that there was a virus that spreads through a fully vaccinated population,” said William Haseltine, Ph.D., a COVID-19 researcher and a former Harvard Medical School professor. “This particular one, one that can penetrate vaccine defenses in nursing homes, gives you cause for concern,” he said, calling the variant “something really to watch.” In that Kentucky nursing home, one of the vaccinated patients died, and two of the unvaccinated patients died. R.1 has since spread to all but three states, with more than 2,200 cases nationwide. In Georgia, there are fewer than 100 R.1 cases, according to the Georgia Department of Public Health. Dr. Haseltine, who wrote in Forbes this week that R.1 can lead to “increased resistance to antibodies,” told 11Alive on Wednesday that there are now more than 10,000 R.1 cases worldwide. The full article can be read online here.
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October 2021
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Top Covid experts privately urge Biden admin to scale back booster campaign Politico | October 6, 2021 | Article
A vocal contingent of prominent doctors and scientists is pressing the Biden administration to scrap its plans to provide booster shots to all previously vaccinated adults, according to five people familiar with the matter. Several of these outside experts, including some who advised President Joe Biden’s transition team, objected to the administration’s approach during a private, off-the-record call last week with federal health officials. Current U.S. data on vaccine performance does not justify using boosters widely to reduce the risk of breakthrough infections and slow the virus’ spread, the experts said. *** A former Harvard Medical School professor and founder of the university's cancer and HIV/AIDS research departments, William Haseltine, said those who oppose a broad booster rollout are “pitting their hopes against the unknown.” “If you don’t have a high level of antibodies and you are relying on [immune cell] memory, it isn’t going to stop you from getting sick. It may prevent you from dying, but it won’t stop transmission,” Haseltine said. “They are guessing about how well memory will protect you. It is something they will come to regret. If you are in a situation like we’re in now, is it better to prepare for the worst or prepare for the best?”
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November 2021
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A prominent virologist warns COVID-19 pill could unleash dangerous mutants. Others see little cause for alarm Science | November 7, 2021 | Article
The first oral antiviral for treating COVID-19, Merck & Co.’s molnupiravir, received approval from the U.K. Medicines and Healthcare products Regulatory Agency on 4 November. But the approval, for people at high risk of severe disease, comes as a prominent virologist has suggested using molnupiravir could do far more harm than good, potentially unleashing new, deadlier variants of SARS-CoV-2. Other virologists say the concern is worth tracking but is largely hypothetical, for now. “I don’t think we are in the position of withholding a lifesaving drug for a risk that may or may not happen,” says Aris Katzourakis, a viral evolution expert at the University of Oxford. *** Now, William Haseltine, a virologist formerly at Harvard University known for his work on HIV and the human genome project, suggests that by inducing viral mutations, molnupiravir could spur the rise of new viral variants more dangerous than today’s. “You are putting a drug into circulation that is a potent mutagen at a time when we are deeply concerned about new variants,” says Haseltine, who outlined his concern Monday in a Forbes blog post. “I can’t imagine doing anything more dangerous.” He notes that patients who are prescribed antibiotics and other drugs often don’t complete a prescribed medication course, a practice that can allow resistant germs to survive and spread. If COVID-19 patients feel better after a couple of days and stop taking molnupiravir, Haseltine worries viral mutants will survive and possibly spread to others. “If I were trying to create a new and more dangerous virus in humans, I would feed a subclinical dose [of molnupiravir] to people infected,” Haseltine says.
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This article originally appeared in Science, and can be read online here: A prominent virologist warns COVID-19 pill could unleash dangerous mutants. Others see little cause for alarm
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A COVID pill from Merck called Molnupiravir is narrowly backed by FDA for future use, but there are risks MassLive | November 30, 2021 | Article
The Food and Drug Administration backed the first drug that Americans could take in the future to combat COVID-19 from the comfort of their own home Tuesday. The COVID-19 pill from Merck called molnupiravir was narrowly backed by advisors at the FDA setting the stage for a likely authorization of the first drug that Americans could take at home to treat the virus. *** “Molnupiravir works by tricking the virus into using the drug for replication, then inserting errors into the virus’ genetic code once replication is underway,” wrote William A. Haseltine in Forbes Magazine. “When enough copying errors occur, the virus is essentially killed off, unable to replicate any further.” Haseltine questions the effectiveness of the drug in fighting the COVID-19 virus. He states that missing from the official statements issued by UK regulators and pharmaceutical companies is any mention whatsoever of the potential mutagenic effects of molnupiravir on the virus itself. This article originally appeared on MassLive, and can be read online here: A COVID pill from Merck called Molnupiravir is narrowly backed by FDA for future use, but there are risks
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December 2021
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Scientists puzzle over Omicron’s origins as variant spreads Financial Times | December 10, 2021 | Article
Reports of a heavily mutated coronavirus variant first surfaced in late November after a flurry of baffling genomes was uploaded to a global database. Omicron, as it came to be known, was traced back to a disparate set of cases: university students in South Africa’s capital Pretoria, a diplomatic mission in Botswana and a South African traveller in a Hong Kong quarantine hotel. As health officials worldwide try to contain the rapid spread of the variant, which has been detected in more than 50 countries on six continents, scientists continue to puzzle over its origins. *** Another theory about how Omicron emerged in southern Africa has been advanced by William Haseltine, a virologist who has speculated that mutations could have been caused by Merck’s Covid-19 antiviral pill. He noted that South Africa was among the locations chosen for clinical trials of the drug molnupiravir, which began in October 2020. [...] UK and EU regulators have already authorised molnupiravir for emergency use but some scientists, including Haseltine, have warned that its mutagenic properties could, under certain circumstances, create more dangerous variants. These concerns were also raised by external experts at a US Food and Drug Administration meeting last week. “That is a very heavily mutated virus and that is the kind of pattern you see with molnupiravir,” Haseltine told the Financial Times. “And the timing is right. I’m not saying it happened, but it could have happened.” This article originally appeared in the Financial Times, and can be read online here: Scientists puzzle over Omicron’s origins as variant spreads 2618
The U.S. Faces Another Covid Christmas as Omicron Fuels a Rise in Cases New York Times | December 20, 2021 | Article
With the holiday travel season already underway, new coronavirus cases are surging in the United States, prompting governors and mayors to once again wrestle with how far to go to combat the virus as federal officials said that Omicron has become by far the dominant form of new virus cases in the country. In New York State, reports of new cases shot up more than 80 percent over two weeks. In Washington, D.C., where the mayor reinstated an indoor mask mandate on Monday, more than three times as many infections are being identified each day as at the start of December. In Boston, another place where cases are surging, Mayor Michelle Wu on Monday announced proof-of-vaccination requirements for certain indoor spaces like gyms and restaurants — but notably did not order any places to shut down. *** “We’re in deep trouble,” said William Haseltine, a virologist and former Harvard Medical School professor who is president of Access Health International, a nonprofit global health think tank. He urged Americans to cancel holiday party and travel plans, work from home and avoid public transportation if possible, and go out only when absolutely necessary — and then wear a mask. “We should have learned our lesson, but we grossly underestimated this virus and were unprepared for Covid coming back in a newly transmissible and virulent form,” he said. “And we’re going to pay the price.”
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'Drug cocktail' may be needed as COVID variants attack immune system on multiple fronts Milwaukee Journal Sentinel | December 23, 2021 | Article
Variants of the virus that causes COVID-19 have developed key mutations that not only enable it to latch onto human cells more tightly, but also delay our body's immune response, according to a new study published Thursday in the journal Nature. The virus' skill in delaying our immune response, but not stopping it altogether, may explain why the immune system roars to life in the overreaction that kills many COVID-19 patients. That deadly overreaction is known as a cytokine storm. Scientists across the globe have focused on mutations in the coronavirus' spike protein, the mechanism that allows it to invade cells. However, mutations in other proteins suggest researchers are fighting a battle on multiple fronts, and may be best off developing cocktails involving two or more drugs. *** Although the idea of developing drug cocktails to treat COVID19 is controversial, it is supported by William Haseltine, a former professor at Harvard Medical School known for his groundbreaking work that led to treatments for HIV. "There are many functions in this virus that we need to attack," Haseltine said. "Nevan's work shows, 'Hey guys, there's a whole world outside the spike protein.'" … "People are asking, 'Will it get weaker?' They should be asking how much more dangerous it can get, and the answer is much more," Haseltine said.
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"Sick madness": The public reacts to the CDC's decision to cut COVID-19 self-isolation time in half Salon | December 28, 2021 | Article
Prior to this week, those who tested positive for COVID-19 were urged by government officials to isolate themselves for 10 days. That changed on Monday, when the Centers for Disease Control and Prevention (CDC) cut the quarantining recommendation in half, instead urging infected Americans to avoid interpersonal contact for five days. The reasoning behind these modifications are rooted in economics perhaps more than science. Dr. Anthony Fauci — director of the National Institute of Allergy and Infectious Diseases and one of President Biden's chief science advisers — recently told CNN's Jim Acosta that "we want to get people back to the jobs, particularly the essential jobs, to keep society running smoothly." *** Dr. William Haseltine, who chairs a global health think tank called Access Health International, criticized the CDC's decision — but made it clear to Salon that he does not view this as a political issue and "a matter of the left or the right." Haseltine, who has received international recognition as an expert in fighting the HIV/AIDS epidemic, emphasized the body of medical research about COVID-19 and infectiousness. "I have pointed out repeatedly that countries that are best at containing the pandemic have a mandatory isolation policy of anybody who is exposed for two weeks — anybody who is exposed, much less infected," Haseltine told Salon. "If you're infected, you are isolated for a minimum of two weeks and sometimes three weeks. So we are exceptional, and I think this is a grave mistake because the data that I've seen suggests that people who are either exposed or infected may be continually infectious for at least two weeks and possibly three. This is a serious mistake." 2621
Haseltine added that he does not "pretend to know what is motivating" the CDC's decision "other than for hospitals to get the hospital workers back to work. I don't think it has anything to do with whether you're a capitalist or not capitalist society. It's getting hospital workers back to work. And I think it's a particularly dangerous thing for them personally, because they may suffer health consequences, and they still may be infectious for their patients and their families. So I think it's a big mistake." This article originally appeared on Salon, and can be read online here: "Sick madness": The public reacts to the CDC's decision to cut COVID19 self-isolation time in half
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Is Omicron Just Covid “Evolving to Become the Common Cold”? Eudaimonia & Co. | December 28, 2021 | Article
Is Omicron just Covid evolving to become the common cold? Right about now, you’re hearing that from a dozen places or more. Here, here, here, here, and here. But is it true? Or is it just a myth? I want to share with what science — actual science — has to say. You can form your own conclusions. I am not going to take a “side.” If you’re the kind of person who wants to pick sides, then you are politicising science, and in my estimation, you are a fool. Please go where fools go. Read pundits at the New York Times, who fly into a rage every time I write things like this, and call me names, instead of engaging with the science. I am not on any side. I am only here to try and think through the science. That is all I am going to do, and you can join me if you want to learn something, too. If not, please don’t read this, and go away. Let’s begin at the beginning. *** Here’s what Dr William Haseltine, doctor, PhD, and former professor at Harvard Medical School, has to say in his new book, Variants. He is perhaps the single smartest mind on this topic, and I’m going to show you why. “The existing literature on coronaviruses already tells us they can recombine…in fact, this process is likely how SARS-CoV-2 came to be born, in the ant-eating mammals knowns as pangolins. There are unpublished reports that recombination among SARS-CoV-2 variants occurs.” “Give the high prevalence of both SARS-COV-2 and other cold-causing viruses at this time, I suspect all the events above have either already occurred or inevitably will.” Did you get that? Dr Haseltine seems to have predicted Omicron. Now that’s shockingly smart. Haseltine figured out something that affected the entire world, as far as I can tell, first. 2623
Where will the next variant come from, and what will it be like? So where does the man when who predicted Omicron think the virus will go? He’s monitoring immunocompromised patients. Because they are where new variants appear to emerge, something like — and I hate to say this, but there is no other way to put it — petri dishes for mutation and recombination. “In some instances of Covid infection, lingering symptoms may last for months, often in immunocompromised individuals. This allows the virus to effectively adapt within a single patient over time, resulting in potent mutations to the Spike protein and larger genome, particularly in cases when the patient receives any sort of antiviral drug. Here we examine one such case of a 72-year-old patient who was infected continuously for two months, as detailed by Truffot et al.” You should read that article — it’s published in Forbes, of all places. It’s very detailed, and you’ll come away with a much, much better understanding of the science — and the stakes. Here’s whatDr Haseltine goes on to say.
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Social Media Below, I include a collection of my COVID-related social media posts, published on Twitter, LinkedIn, and on Facebook.
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January 2020
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January 28, 2020 I recently returned from Wuhan where I chaired the 9th USChina Health Summit. Now, as I observe the unfolding of the coronavirus epidemic, I look to the lessons from the SARS and MERS epidemics in 2003 and 2012, respectively and ask why we are not more prepared globally for another deadly coronavirus outbreak. As we see the numbers of confirmed cases continue to rise, I wish to say that to be forewarned is to be forearmed--and we must arm ourselves against this new threat, and not allow ignorance, denial, and complacency stand in the way of human health. Over the coming weeks I will be observing and offering my thoughts on this unfolding situation. January 29, 2020 The numbers of confirmed cases of the coronavirus are on the rise, not just in China, but in the US as well. Wuhan is the major transportation hub in China, bigger than New York in both population and size. And as cases are being evaluated in New York City, it’s worth noting that we are, like they were, woefully unprepared. When President Donald Trump says potential spread in the United States is “totally under control,” he’s wrong. https://www.nytimes.com/2020/01/27/world/asia/chinacoronavirus.html January 30, 2020 With past epidemics, lives have been lost due to our inability to coordinate and execute a proactive response. We must take these lessons and be prepared with plans of attack in this new coronavirus outbreak before it’s too late. https://www.scientificamerican.com/article/experts-warn-ofpossible-sustained-global-spread-of-new-coronavirus/ January 31, 2020 I’d like to offer a few tips on ways you can protect yourself and to help slow the spread of the new coronavirus: Take certain precautions, such as avoiding crowds. Wash your hands often with soap. Avoid face touching, a bad habit that occurs on average a few times each hour and accumulates over the course of a day. Wear 2627
gloves and swipe surfaces with sterile cleaning wipes when taking public transport. Use nasal spray or a bit of petroleum jelly to maintain resistance to infection while traveling.
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February 2020
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February 1, 2020 How is this coronavirus outbreak different from SARS and MERS? For one, we’re living in a different time, and the world has changed over the past two decades. Now, for example, six times as many people are flying in and out of China on a daily basis than they were just 7 years ago, and that potentially impacts the speed of transmission. For more on what makes this coronavirus outbreak different, read my recent post on Forbes. https://www.forbes.com/sites/williamhaseltine/2020/01/28/what -makes-this-coronavirus-differentand-what-we-can-do-aboutit/#7f10fff16e8f February 2, 2020 The WHO has declared a global health emergency following the spread of the coronavirus to more than a dozen other countries. We are dealing with a deadly virus that can spread quickly. Read more below about the US response to the coronavirus outbreak. https://www.usatoday.com/story/news/health/2020/01/29/coron avirus-wuhan-china-outbreak-united-states-cdc-preparedvaccine/4599870002/ February 3, 2020 We now have witnessed three deadly coronavirus outbreaks in humans within 17 years. We can and must develop, test and stockpile combinations of drugs that can protect us against what is certain to be another coronavirus outbreak. https://blogs.scientificamerican.com/observations/want-toprevent-another-coronavirus-epidemic/ February 4, 2020 After SARS and MERS, we should have created and stockpiled an anti-coronavirus drug, which we did not do. Instead of treating those outbreaks as anomalies, we should have treated them as trends, and this current coronavirus outbreak is a lesson for us, one on which we should take decisive action. https://www.jsonline.com/story/news/2020/01/28/top-healthofficial-blames-lack-preparation-spread-virus/4599529002/ 2630
February 5, 2020 I have a very specific ask of the US government, which is to include the coronavirus on the list of organisms for which we have bio-preparation. It's not on there. It should be. https://www.thenational.ae/uae/health/world-should-have-beenmore-prepared-for-coronavirus-says-us-scientist-william-haseltine1.973049 February 6, 2020 Earlier this week I spoke on Fox Business about the coronavirus outbreak and what steps we can take in the US to be prepared in the event of a future epidemic. https://video.foxbusiness.com/v/6129868354001/#sp=showclips February 7, 2020 After SARS and MERS, the United States had the opportunity to stop this latest coronavirus outbreak from ever happening. But we dropped the ball. I now urge the U.S. government to take swift and serious measures to be prepared before the next (and possibly even more deadly) coronavirus outbreak. https://www.forbes.com/sites/williamhaseltine/2020/02/04/es calate-federal-action-against-the-coronavirus-before-its-too-late/ February 8, 2020 As research and trials begin for treatment solutions to the new coronavirus outbreak, it’s important that we also keep our eyes on the future so that we are more prepared when the next virus strikes. https://www.nytimes.com/2020/02/06/health/coronavirustreatments.html?0p19G=0038 February 9, 2020 The world needs an anti coronavirus drug as soon as possible— and there is something the United States government can do right now to achieve that. https://www.forbes.com/sites/williamhaseltine/2020/01/31/if -the-us-government-does-this-we-could-have-an-anticoronavirus-drug-within-months/ 2631
February 15, 2020 The WHO has just named the new coronavirus epidemic COVID-19. I think that the name could be improved to emphasize the continuity between this outbreak, and SARS and MERS. In my article on Forbes I discuss how something as simple as a name could help prevent this health event from slipping from collective memory. https://www.forbes.com/sites/williamhaseltine/2020/02/07/s olving-the-coronavirus-identity-crisis-a-strategy-forprevention/#24f94a915666 February 17, 2020 The line between panic and preparedness can feel perilously thin in the thick of any epidemic. We’re seeing that right now with the new coronavirus outbreak. Fortunately, there are steps each of us can take to calm the fear. https://www.psychologytoday.com/us/blog/honor-theaging/202002/why-are-we-so-fearful-the-new-coronavirus February 19, 2020 Nature is teaching us a heavy lesson with this latest coronavirus outbreak. We didn’t heed the warnings of SARS and MERS, and I fear that our global community risks paying an unimaginable price if we ignore nature this third time. Read more in my op-ed in the Washington Post. https://www.washingtonpost.com/opinions/2020/02/18/scien tists-warned-about-coronavirus-years-got-nowhere-heres-how-fixthat/ February 20, 2020 I am in Rwanda visiting Partners in Health and the University of Global Health Equity. In Kigali, I visited the Genocide Museum. Standing over the graves of 250,000 citizens is a stark reminder of the consequence of politicians who inflame division for their own personal gain. February 25, 2020 The U.S. health system is unprepared for a pandemic: Our hospital-centric system isn’t equipped to handle such a crisis. Read 2632
my op-ed in the LA Times about the three things we can do to be prepared for the next big outbreak. https://www.latimes.com/opinion/story/2020-02-24/op-edu-s-hospitals-are-unprepared-for-the-spread-of-coronavirus-hereswhat-they-need-to-do
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March 2020
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March 2, 2020 I had the opportunity to talk with Nicholas Kristof about the coronavirus and immediate steps I think our government would be wise to take, which he shared in his most recent article in the NYT. You can read his full perspective here. https://www.nytimes.com/2020/02/29/opinion/sunday/coro navirus-outbreak.html March 3, 2020 Clear, concise and credible public health communications are imperative in this time of crisis. Here you can read some of my thoughts on what we each can do to weaken the impact of this virus as it continues to spread. https://www.foxnews.com/opinion/dr-william-haseltine-4coronavirus-prevention-steps-we-can-all-take March 4, 2020 I recently had the pleasure of speaking with Ira Pastor, the founder of Bioquark and host of the ideaXme podcast. We covered a wide variety of topics, from optimal aging to value-based care for older patients. You can listen to the interview here. https://radioideaxme.com/2020/01/24/dr-william-haseltine/ March 6, 2020 Earlier this week, I spoke with Bloomberg TV about the novel coronavirus. One issue we discuss is how the low numbers of tests we are able to perform here in the U.S. is allowing for enormous gaps in terms of reducing community transmission. I also reiterate the importance of preparedness for the next time an epidemic arises. https://www.bloomberg.com/news/videos/2020-0305/nature-is-there-ready-to-pounce-says-access-healthinternational-video March 9, 2020 Last week, I spoke with Bloomberg TV about the novel coronavirus. One issue we discuss is how the low numbers of tests we are able to perform here in the U.S. is allowing for enormous 2635
gaps in terms of reducing community transmission. I also reiterate the importance of preparedness for the next time an epidemic arises. https://www.bloomberg.com/news/videos/2020-0305/nature-is-there-ready-to-pounce-says-access-healthinternational-video March 10, 2020 The WHO has compiled a report about what we know so far about the novel coronavirus. It is an important document. This article describes some of the simple--and also dramatic--steps the government of China has taken to contain and slow transmission, all well worth noting. https://www.motherjones.com/politics/2020/03/who-reportchina-constructed-new-hospitals-in-days-and-other-lessons-fromtheir-response-to-the-coronavirus/ What measures should healthcare providers take today to protect themselves and their patients? Please join me for a live discussion about the ongoing outbreak of the novel coronavirus and COVID19 where I will be sharing my thoughts on this and other implications of the outbreak, as well as critical next steps in our global response. The conversation will be led by Tech Care for All Senior Vice President of Global Health, Pam Bolton. http://ow.ly/sjx850yF7Ud March 13, 2020 I mention in this article that diseases such as the coronavirus are as much a natural disaster as earthquakes and hurricanes. While we can't prevent natural disasters, we certainly can prepare for them-that includes creating and stockpiling antiviral drugs so we are ready for the next time. Right now, we are over a year away from a vaccine. Treatment solutions could come faster. https://www.newsweek.com/coronavirus-vaccine-treatmentantiviral-speed-COVID-19-1491292 March 14, 2020 In everything from lack of clear communication to flawed testing kits, the U.S. response to the potential dangers of the coronavirus infection has been inadequate and confused. Because of this, we are 2636
finding ourselves at much greater risk than we need to be. We can-and must--do better. https://www.forbes.com/sites/williamhaseltine/2020/03/09/c oronavirus-mismanagement-is-costing-americanlives/#77883b873913 March 15, 2020 We very likely have all the tools needed to develop combinations of drugs right now that will cure those infected with coronavirus, and protect those who are not. https://www.ibtimes.com/could-widespread-coronavirustesting-make-things-worse-prevention-seen-key-2934480 March 16, 2020 Our national response to COVID-19 all but ignores the social workers and caregivers in our nursing homes and long-term care centers who are caring for our elders, the ones most vulnerable to this crisis. To redress our oversight, we must work immediately to integrate social workers and long-term care providers into our overall response to the outbreak. https://www.foxnews.com/opinion/william-haseltine-socialworkers-coronavirus March 19, 2020 The COVID-19 infection may have started in China but it is now an American problem. No new cases were reported in China yesterday. This infection can be controlled without antiviral drugs and vaccines! March 20, 2020 I see four possible scenarios for how the coronavirus pandemic will end. The highest likelihood, I think, is that a treatment option will become available, hopefully within the next few months. Read more here about all four paths this pandemic might take. https://www.thedailybeast.com/four-ways-experts-saycoronavirus-nightmare-could-end March 21, 2020 2637
New York is making progress in getting the necessary equipment for coronavirus testing. Contact tracing is absolutely critical, and has been a problem here in the U.S. until very recently. Now I am very happy to see we’re starting to ramp up that level of testing. https://video.foxbusiness.com/v/6141511756001/#sp=showclips March 23, 2020 I recently spoke on the new Coronavirus Daily podcast from KTLA about how the U.S. is doing in our efforts to slow the spread of COVID-19, and what each of us can do to help. https://art19.com/shows/coronavirusdaily/episodes/9c861ba0-b0cd-491e-a6fb-43247954ffa2 March 24, 2020 As we face a growing new epidemic, let us not forget 3 other major epidemics: tuberculosis, malaria, HIV/AIDS. Today on World TB Day, let us honor the 4,000 people who die each day from this preventable & curable disease. It’s time for leaders to accelerate TB response worldwide. This is an excellent summary of the consequences of action and inaction in the time of COVID-19. https://medium.com/@tomaspueyo/coronavirus-the-hammerand-the-dance-be9337092b56 March 25, 2020 If you have a cold, you won’t have a fever (that’s why we call it a cold). Here are some other tips to help you distinguish between cold, flu, and coronavirus, and what to do if you think you might be infected. https://people.com/health/how-to-tell-between-coronavirusflu-cold/ A recent report of a controlled clinical trial from China shows no change in the health outcomes of hospitalized COVID-19 30 patients treated with or without hydroxychloroquine. http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003 /43f8625d4dc74e42bbcf24795de1c77c.pdf
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The measures the US is taking to control COVID-19 are far inferior to what was done in China according to @JNBPage in @WSJ - http://ow.ly/BS5R50yVDV2. For more details see an interview quarantine of an American in Shanghai https://accessh.org/interview-with-an-american-quarantinedin-china-for-COVID-19/ Two months of lockdown in Hubei province in China has been lifted, although Wuhan remains under quarantine until April 8. This is an important moment, and testament to the effectiveness of containment measures. https://www.huffpost.com/entry/hubei-lockdown-liftedchinacoronavirus_n_5e79b92dc5b63c3b64969f2e?ncid=engmodushpmg 00000006 March 26, 2020 How will the coronavirus pandemic end, and how soon? As I see it, there are four possible ways. https://www.foxnews.com/opinion/dr-william-haseltinehere-is-how-coronavirus-pandemic-could-end-maybe-soonerthan-we-expect I had the opportunity to talk with Joe Scarborough and Mika Brzezinski on Morning Joe about the steps China has taken to curb the spread of the coronavirus, and what we could be doing here in the U.S. to slow this epidemic. https://www.msnbc.com/morning-joe/watch/doctorrecommends-strict-measures-to-curb-coronavirus-in-u-s81229893860 March 27, 2020 An American friend of mine and his wife spent 11 days in controlled quarantine in Shanghai. Their story highlights steps we need to take in the United States to prepare ourselves for the inevitable onslaught of new cases of the coronavirus. https://www.forbes.com/sites/williamhaseltine/2020/03/20/w ondering-what-a-coronavirus-quarantine-is-reallylike/#35dd884a1f84
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For anyone who would like to learn more and understand the details of the last coronavirus epidemic, MERS-CoV I strongly recommend this article in The Lancet https://www.thelancet.com/journals/lancet/article/PIIS01406736(19)33221-0/fulltext?dgcid=raven_jbs_etoc_email To understand the true magnitude of the COVID-19 pandemic we will need to have a rapid, reliable, and inexpensive way to determine who is infected. Fortunately, we can develop these tests and many are already in development now https://www.statnews.com/2020/03/27/serological-testsreveal-immune-coronavirus/ March 28, 2020 As coronavirus cases in the US continue to climb, it is deadly advice for the White House to suggest that it is safe for people who have been exposed to the virus to return to work only wearing a mask. https://www.thedailybeast.com/potential-white-house-cdcreturn-to-work-guidance-deadly-deadly-advice-expertsays?source=articles&via=rss March 29, 2020 I am very optimistic that we are going to be able to tackle the coronavirus epidemic with drugs--to both prevent and treat the infection. Watch the full interview with Stephanie Ruhle at MSNBC. https://www.msnbc.com/stephanie-ruhle/watch/nytscientists-identify-69-drugs-to-test-against-virus-81103941523 March 30, 2020 Results from a small clinical trial show that hydroxychloroquine is not effective for treating people suffering from COVID-19. Read more here about the study and the implications of the findings. https://www.forbes.com/sites/williamhaseltine/2020/03/25/h ydroxychloroquine-is-ineffective-in-treatment-of-patientshospitalized-with-COVID-19-according-to-small-controlled-trialfrom-shanghai/#6460f6e26092 March 31, 2020 2640
Asia took steps in the early weeks of the coronavirus pandemic that have had a positive effect on the spread of the virus. Here are some of the key lessons learned. https://www.bbc.com/news/world-asia-51970379 Interested in knowing what a coronavirus quarantine is really like? I invite you to visit a new series of interviews I am posting at @Medium. The first is an interview with a friend who was forced into quarantine in China. https://medium.com/@williamahaseltine/what-a-coronavirusquarantine-is-really-like-reflections-on-COVID-78dcb32034eb
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April 2020
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April 2, 2020 My latest piece on Medium highlights news from a friend and physician in India on conditions in the country around COVID-19 #COVID19 #india #coronavirus https://medium.com/@williamahaseltine/bracing-ourselvesfor-an-explosion-of-cases-in-india-reflections-on-COVIDd3581eaa2d2d Vaccines must be tested extensively before administered to the public. It’s a highly expensive process. Listen to the discussion I had with Chicago radio's Roe Conn about how we create vaccines and what we might expect in developing a vaccine for COVID-19. https://wgnradio.com/health/COVID-19-the-search-for-avaccine/ Wrong sided thinking by the UK government on COVID-19 – including one expert who advocated for a “nice big epidemic” to generate herd immunity. That thinking led to an uncontrolled epidemic in the UK to which they are now just beginning to confront. https://www.thelancet.com/journals/lancet/article/PIIS01406736(20)30669-3/fulltext April 3, 2020 Knowing that hydroxychloroquine is ineffective against COVID-19 leads us to ask some important questions about what to do next. This is a follow up to an earlier piece I published in Forbes about the outcome of the controlled clinical trial in China. https://www.forbes.com/sites/williamhaseltine/2020/03/25/st udy-shows-hydroxy-chloroquine-is-ineffective-against-COVID19---so-what-now/#745fb375409b Our sewage may be the best early warning sign for COVID-19. Infectious diseases like SARS-CoV-2 are excreted in urine and feces...analyzing wastewater can give cities a warning sign if the virus has arrived or recurs https://www.nature.com/articles/d41586-020-00973-x I spoke with @Salon about how vaccines are developed and why making one for COVID-19 can be challenging. Read a transcript of our talk here. #COVID19 #vaccine #coronavirus 2643
https://www.salon.com/2020/03/29/how-to-make-acoronavirus-vaccine/ April 4, 2020 An important article highlighting how unproven drugs for COVID-19 like chloroquine, azithromycin, and lopinavir-ritonavir shouldn’t be administered as a last resort without knowing whether the potential benefits will outweigh the harm. https://jamanetwork.com/journals/jama/fullarticle/2763802 When someone is diagnosed with COVID-19 all of the people they were in contact with over the previous days should be contacted and quarantined to prevent further infection. What happened in Arizona instead was unacceptable. https://www.azcentral.com/story/news/local/arizonahealth/2020/03/26/pima-county-not-contacted-tucson-bridgetournament-with-coronavirus-patient/2891695001/ April 5, 2020 This simple message from Bill Gates is worth reading and rereading. If our federal government continues as is, we will suffer increased death and the destruction of our economy. Every day of inaction means more weeks of suffering and economic damage. https://www.washingtonpost.com/opinions/bill-gates-hereshow-to-make-up-for-lost-time-on-COVID19/2020/03/31/ab5c3cf2-738c-11ea-85cb8670579b863d_story.html Falls send ~3M people to the emergency room each year. People 65 years+ are particularly at risk. This article suggests doctors ask older patients about falls in the past year to identify those at high risk. It also presents exercises that can help. https://www.nejm.org/doi/full/10.1056/NEJMcp1903252 April 6, 2020 It’s difficult for people living in rural America to access vital mental-health services, because their counties often don’t have a psychiatrist or a psychologist. This has led to a public health crisis. #nphw2020
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https://www.theatlantic.com/video/index/603127/mentalhealth-rural/ I recently spoke on Fox News about how our understanding of SARS-CoV-2 changes week to week as we study the effects in of infected people. It may be more contagious than we thought, and we still don’t know how long our bodies are immune after infection. https://uk.news.yahoo.com/dr-haseltine-says-COVID-19200434098.html?guccounter=1&guce_referrer=aHR0cHM6Ly90 LmNvL1luWEtETDZnZ1Y_YW1wPTE&guce_referrer_sig=AQ AAAA_0fRaZmFP9zapeuDQfBeHXZCgHUwzqHuEQmKeagL3 0SooDsMiQRKqJz0cKjqPXMvpSgg43tWhpaWPdmNTMYnypEyI3O2j fkbKkTVOKFxwXblxYYCU4ocvDvmVWaPGtCnPiou4ne7L81 Vwxt1K8eLWxCLH8nhvfmwmfTAInj7h This Monday marks the beginning of National Public Health Week here in the United States, and this annual event may be more important this year than ever. I will be sharing a series of relevant articles to help raise awareness. #healthforall #nphw2020 http://www.nphw.org/nphw-2020 One group we are overlooking in coverage of #COVID19 are the geriatricians who care for our elders. Here, one talks about her concerns for patients, how she is providing care, and her fears of bringing the virus home to her family https://medium.com/@williamahaseltine/geriatricians-maybe-few-in-number-but-play-outsized-roles-against-COVID-19reflections-on-COVID-8e5c127db4fb April 7, 2020 Today, on World Health Day, we honor all our Nurses and Midwives for the vital role they play. During this difficult time, your efforts are more important than ever. Thank you for your tireless work to improve the health and wellbeing of all. https://www.who.int/news-room/campaigns/world-healthday/world-health-day-2020 In this panel discussion on CGTN, I joined Dr. Lewis Kaplan, President of the Society of Critical Care Medicine, and Nathan King CGTN’s White House Correspondent, to discuss the coronavirus pandemic and what we could be doing differently here in the US. 2645
https://america.cgtn.com/2020/03/31/the-heat-COVID-19impact-on-spain-and-u-s April 8, 2020 Is this epidemic the BIG one? The biggest devastation from this pandemic is as a result of human action and inaction rather than from anything intrinsic to the virus itself. https://www.forbes.com/sites/williamhaseltine/2020/03/31/is -this-coronavirus-epidemic-the-big-one/#d6614695c782 With a shortage of personal protective gear for healthcare workers, some hospitals are asking doctors and nurses to reuse masks. While in some cases reuse may be safe, it is essential that such practices be controlled and approved rather than fly-by-night. https://news.yahoo.com/docs-buck-bosses-beg-cuomo084456179.html Please see this excellent report on COVID vulnerability of the 50 most populous US cities. Most are in Florida and the Rust Belt and reflect age and social determinants of health. Vital for predicting where to locate resources. https://socialprogress.blog/2020/04/03/COVID-19vulnerability-mapping-for-the-uss-500-largest-cities/ This report from Germany raises the possibility that as part of post COVID-19 "back to normal" we may issue COVID Antibody Passports for work, shopping and social interactions. https://www.washingtonpost.com/world/europeanpoliticians-are-making-big-promises-about-antibody-passports-thescience-is-still-catching-up/2020/04/07/3c228b20-7887-11eaa311-adb1344719a9_story.html The COVID-19 death toll likely includes many who died because overwhelmed health systems prevented them from receiving care for chronic diseases. We must pay attention to those with serious chronic disease, including those with cognitive dysfunction. https://www.economist.com/graphicdetail/2020/04/03/COVID-19s-death-toll-appears-higher-thanofficial-figures-suggest?utm_campaign=coronavirus-specialedition&utm_medium=newsletter&utm_source=salesforcemarketing-cloud&utm_term=2020-04-04&utm_content=articlelink-2 2646
This paints a clear picture of the consequences of our failure to institute early lockdowns and how lockdowns help. Think of Northern Italy as New York, Central Italy as Chicago, and Southern Italy as the midwest, and south (except Florida and Louisiana). https://www.nytimes.com/interactive/2020/04/05/world/eur ope/italy-coronavirus-lockdown-reopen.html?smid=em-share Massachusetts will launch an aggressive contract tracing initiative against COVID-19. Good news, but disappointing that this is the only effort in the US to date. https://www.project-syndicate.org/commentary/united-statesCOVID-testing-contact-tracing-by-william-a-haseltine-2020-03 April 9, 2020 A fascinating perspective on the economic impact of this outbreak from a friend and former adviser to Kissinger, Scowcroft and Brzezinski. https://link.medium.com/eKjPo0KTx5 #COVID19 #coronavirus #economy Of the many things that occupy my thinking about our response to the novel coronavirus, contact tracing is at the top of my list. This is something we should be doing now to get the spread under control. Read more about how other countries used this method in my article published on Project Syndicate. https://www.project-syndicate.org/commentary/united-statesCOVID-testing-contact-tracing-by-william-a-haseltine-2020-03 Don’t count on summer to save us from #COVID19. SARS and MERS persisted in Singapore and the Arabia, both famous for very hot, and in Singapore, humid weather. The National Academy of Sciences suggests this is likely to be the case for COVID-19. https://www.washingtonpost.com/weather/2020/04/08/coro navirus-unlikely-diminish-with-warm-weather-nationalacademies-sciences-panel-finds/ COVID-19 is exposing the health disparities in black America. This article asks an important question—what now? https://www.forbes.com/sites/lisafitzpatrick/2020/04/08/coro navirus-has-exposed-the-world-to-health-disparities-in-blackamerica-so-what-now/#3b11e27721ca
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Important lessons on what we can learn from Asia to handle the outbreak: Take it seriously, Act quickly, Test, Trace and Isolate, Keep your distance, Keep informed, and Individual attitudes matter. https://www.bbc.com/news/world-asia-51970379 April 10, 2020 Reflections on COVID-19 from a friend in Europe whose story reflects the experiences many of us share in the face of this disease https://link.medium.com/TDjuX9gpz5 I spoke with Ernie Manouse on the public radio show Houston Matters about the coronavirus and steps we can take to stop the virus. https://www.houstonpublicmedia.org/articles/shows/houstonmatters/2020/04/01/365863/special-edition-dr-william-haseltinedietrich-von-biedenfeld-april-1-2020/?utm_source=rss-houstonmatters-article&utm_medium=link&utm_campaign=hpm-rss-link In times of plague people grasp at straws to keep afloat. Sometimes those straws are a dangerous illusion, as with this COVID-19 BCG story. An unproven and likely false belief that you are protected may lead to reckless exposure. https://naturemicrobiologycommunity.nature.com/channels/2549 -coronaviruses-past-present-and-future/posts/64892-universal-bcgvaccination-and-protection-against-COVID-19-critique-of-anecological-study A look inside a Hong Kong coronavirus quarantine camp where people at risk of COVID-19 are housed, whether or not they have symptoms. https://www.cnn.com/2020/04/09/homepage2/hong-kongcoronavirus-quarantine-diary-intl-hnk/index.html April 11, 2020 There are now two ways to test for COVID-19: one that measures the actual virus, and one that measures the body’s reaction to the virus. The finger prick antibody test will change the landscape of COVID-19 testing as we know it. https://www.forbes.com/sites/williamhaseltine/2020/04/06/h ow-antibody-tests-can-be-used-to-fight-COVID19/#6c62aaa13904
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Taking hydroxychloroquine for COVID-19 may have serious — even life threatening — consequences. It is not something to take unless a doctor prescribes it. https://www.salon.com/2020/04/07/top-biologist-to-foxnews-host-dana-perino-unproven-drug-treatment-hyped-bytrump-is-a-quack-cure/ April 12, 2020 Our ACCESS Health team in China have put together a very informative summary of the innovative digital solutions that China used to contain the spread of the coronavirus. China's approach holds important lessons for other countries. Read more: https://accessh.org/digital-solutions-to-manage-and-containdisease-outbreaks/ Our best option to end the coronavirus pandemic in the least amount of time is to accelerate the development of drugs that treat and prevent infection. We must ensure these drugs do not get stalled the same way R&D for SARS and MERS drugs did. https://www.forbes.com/sites/williamhaseltine/2020/04/03/w hy-dont-we-have-a-coronavirus-drug-yet-and-how-we-can-getone-as-soon-as-possible/#78872f40489e It is the responsibility of our nation’s leadership to prepare and educate the public when a global crisis is unfolding. It is the national government’s responsibility to ensure cohesive and consistent messaging and to provide direction. https://www.salon.com/2020/04/07/trump-lashes-out-at-foxnews-reporter-you-should-say-great-job-instead-of-being-sohorrid/ Anecdotal accounts of the use of HCQ as a therapeutic for COVID-19 are not equivalent to having results from clinical trials. It should not be used off-label: There is risk of heart attack, among other things. https://www.youtube.com/watch?v=0Gld-Mw7760 April 13, 2020 This article describes the experience of a rural Virginia hospital that is using remote patient management to deal with a shortage of critical-care physicians. As the U.S. population ages, the need for these types of technologies will likely increase. 2649
https://www.modernhealthcare.com/caredelivery/telemedicine-helps-rural-hospitals-meet-intensivistshortage?utm_source=email&utm_campaign=THUB6&utm_conte nt=12202019 This is the account of two cases of young children at risk of COVID-19 in two countries. The difference between the response at the ER department in the United States compared to that in Singapore exemplifies the difficulties we are facing here in the US. https://www.psychologytoday.com/us/blog/best-practices-inhealth/202004/troubling-tale-two-children-in-the-time-COVID19 The US now leads the world in the number of people infected and dead from SARS-CoV-2. Our crowded cities, and social inequities create the prime condition for the devastating spread of the disease, compounded by shortsighted and self-serving leadership. https://www.nytimes.com/2020/04/11/us/politics/coronaviru s-trump-response.html?smid=em-share South Korea reports that 91 patients thought cleared of the virus tested positive, suggesting reinfection. Similar cases in China. Whether this is reinfection or reactivation of the original virus is a critical question. https://www.theguardian.com/world/2020/apr/11/wholooks-into-report-of-COVID-patients-testing-positive-afternegative-tests It is surprising that those who know they will receive paychecks while in self-isolation during the health emergency lockdown are more likely to comply than those who know they will not be paid or are uncertain that they will. See this study from Israel ow.ly/UV4g50zcLSm The impact of COVID-19 is beginning to appear in the world of artistic imagination. The initial question and the jumping off point for many is: What have others done when faced with similar tragedy? See this New York Times piece. https://www.nytimes.com/2020/04/08/t-magazine/artcoronavirus.html?smid=em-share
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April 14, 2020 This article reveals how the very wealthy in the United States are able to respond to the coronavirus pandemic, including escaping to remote vacation homes. https://edition.cnn.com/2020/04/05/opinions/coronaviruswealthy-false-security-vicky-wardopinion/index.html?fbclid=IwAR3VgTMYjXfjK5A8HNzRRDO lFof7XkwuvogPexQcp_gQLpYC-SwCW6PGIYM We were close to a COVID-19 cure. This 2003 @nytimes piece on an anti-SARS drug shows how it could also work against SARSCoV-2. What happened? Companies didn't see a financial interest to bring it to market and the government didn't fill the gap. A true loss. https://www.nytimes.com/2003/05/14/world/experimentaldrug-may-fight-sars-researchers-say.html What will World War III look like? According to senior US diplomat and economist Robert Hormats, now we know. It looks like, and is, COVID-19. As in World War II we need to engage our full economic, financial and scientific resources to win this war. https://thehill.com/opinion/national-security/492409-worldwar-iii-isnt-what-the-strategists-thought-it-would-be People are beginning to explore the long term social consequences of COVID-19. Will cities retain the central role in modern life? Will remote work be the norm? Will innovation suffer from less frequent informal face to face meetings? A view from Boston. https://www.bostonglobe.com/2020/04/11/business/citiesage-coronavirus-after/ With each passing day, the coronavirus outbreak is exposing the widening gap between rich and poor. This article includes a note from a friend in the Philippines who reminds us of the suffering face by the poorest among us. https://medium.com/@williamahaseltine/how-coronavirushits-the-poorest-among-us-reflections-on-COVID-from-thephilippines-f0c6319ae58e The evidence is mounting that not only is hydroxychloroquine ineffective as a treatment for COVID-19, it is dangerous. Read about what we’re learning about the dangers of this antimalarial in the treatment of COVID-19. 2651
ow.ly/VFRw50ze3kE April 15, 2020 This is the story of two friends of mine who were working on drugs to fight coronaviruses after the SARS and MERS outbreaks. Lack of interest and funding ended their pioneering work. Let’s not make the same mistake again. https://www.forbes.com/sites/williamhaseltine/2020/04/06/o pportunity-lost-avoiding-further-missteps-with-COVID-19-andfuture-biothreats/#7374947c28b7 Testing and contact-tracing will be critical to our ability to phase out our current social distancing measures. Read more here for perspectives on criteria for the American people to be—and feel— safe to return to public life. https://www.thedailybeast.com/coronavirus-lockdown-willend-eventually-heres-how-it-might-playout?source=articles&via=rss Are companies living up to their pledge to protect employees? Peter Goodman says no in his thoughtful @nytimes story today: https://www.nytimes.com/2020/04/13/business/businessroundtable-coronavirus.html What is it like to lose the sense of smell and taste to COVID-19? Read Maura Judkis' description in the Washington Post https://www.washingtonpost.com/lifestyle/style/what-its-like-tosuffer-from-the-coronaviruss-weirdestsymptom/2020/04/13/68e0adc4-7853-11ea-a130df573469f094_story.html COVID-19 devastates the lives of both the infected and uninfected. The consequences for the poor in all countries is doubly severe. See this excellent summary in the Washington Post by Ishaan Tharoor. https://www.washingtonpost.com/world/2020/04/15/pande mic-is-ravaging-worlds-poor-even-if-theyre-untouched-by-virus/ Benjamin Rome, M.D. and Jerry Avorn, M.D. warn of the danger to COVID-19 patients of the use of chloroquine drugs. They also argue that there will be long-term harm to the public interest unless we ensure that the drugs we take are safe and effective. https://www.nejm.org/doi/full/10.1056/NEJMp2009457 2652
April 16, 2020 We all know testing is central to our ability to control COVID19. Yet cost is prohibitive, not only in the United States, but globally. Here are three things we can do to control the cost of testing. https://www.forbes.com/sites/williamhaseltine/2020/04/08/p ricing-and-profiteering-from-COVID-19-tests/#8fdb4f51ccbc Please join me and @BrookingsInst USC-Brookings Schaeffer Initiative for Health Policy Director Paul Ginsburg for a discussion on short- and long-term approaches to the COVID-19 pandemic. Tomorrow at 2:45ET. #COVID19response Register here: https://www.brookings.edu/events/webinar-a-short-and-longterm-approach-to-COVID-19/?preview_id=799922 Important insight into disease surveillance from Alex Pentland - how we could have predicted COVID-19 and what we should do to protect ourselves from future pandemics. https://medium.com/@williamahaseltine/what-did-we-knowwhen-did-we-know-it-and-what-are-we-doing-about-it-nowreflections-on-COVID-eae5dd0e6208 In this comprehensive and thoughtful piece in The Atlantic, Ed Young explores what comes next following this global pandemic. What will we do about the virus? Will we live in a world of whacka-mole until a vaccine is created? https://www.theatlantic.com/health/archive/2020/03/howwill-coronavirus-end/608719/ April 17, 2020 If we are able to develop a vaccine for this novel coronavirus to manage the pandemic, it’s unknown how long immunity would last. Why? It has to do with how the body protects itself from invading organisms. https://blogs.scientificamerican.com/observations/can-wereally-develop-a-safe-effective-coronavirus-vaccine/ There is still time to register for my webinar with the USCBrookings Schaeffer Initiative for Health Policy on the short- and long-term approaches to the COVID-19 pandemic. Today at 2:45ET. Register here:
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https://www.brookings.edu/events/webinar-a-short-and-longterm-approach-to-COVID-19/?preview_id=799922 Helen Branswell of STAT hosted a live video chat with Tom Frieden, former director of CDC and current CEO of Resolve to Save Lives. They discussed what it might take to start to safely emerge from the current containment strategy. https://www.statnews.com/2020/04/13/video-chatconversation-on-the-coronavirus-with-tom-frieden/ A controlled trial in France of the use of hydroxychloroquine for patients hospitalized for COVID found no benefit of the drug, and also that it caused dangerous heart rhythm abnormalities https://t.co/Z6ukf6BImJ?amp=1 During this time of heightened public concern, it is possible to conduct high quality clinical trials, and do so quickly, as we proved with HIV/AIDS. https://www.thelancet.com/pdfs/journals/lancet/PIIS01406736(20)30894-1.pdf April 18, 2020 Internal, unpublished reports from a small uncontrolled trial of rem desivir shows shortened hospitalization for some. Hopeful, but far from conclusive. Results from larger controlled trials already in progress should give a more accurate picture https://www.statnews.com/2020/04/16/early-peek-at-dataon-gilead-coronavirus-drug-suggests-patients-are-responding-totreatment/ Robert Hormats served under five different U.S. presidential administrations, working on our international economic strategy. He recently shared with me his unique insight on the complexities of the COVID induced economic crisis. https://medium.com/@williamahaseltine/the-economicimpact-of-the-outbreak-reflections-on-COVID-1f0cbbe0329e This important story by Cathy O’Neill shows that the decline of COVID-19 is not as rapid as we projected. Why might this death and disease pattern differ from that of Wuhan, where the curve had a sharp rise, short peak, and equally rapid decline? https://www.bloomberg.com/opinion/articles/2020-0416/coronavirus-this-isn-t-the-flattened-curve-we-were-promised 2654
April 19, 2020 Everyday our healthcare workers take risks to save lives, endangering their own. 19% of those infected with COVID-19 are healthcare workers, a stark reminder of the risks they face both for themselves and their families. https://www.forbes.com/sites/williamhaseltine/2020/04/15/1 9-of-people-infected-with-COVID-in-the-us-are-healthcareprofessionals-almost-three-quarters-of-them-arewomen/#44f16b6f588e April 20, 2020 A decade or more of low interest rates & slow growth is ahead. Opportunities will shrink. Investment in infrastructure will vanish. Resources for the elderly will contract. The challenge is how to manage the consequences and maintain free & open societies. https://www.washingtonpost.com/uspolicy/2020/04/18/record-government-corporate-debt-risktipping-point-after-pandemic-passes/ Kidney failure affects a large fraction of those with severe COVID-19 and must now be added to the growing litany of complications from the disease. We now add dialysis machines and fluids to the list of acute medical equipment shortages. https://www.nytimes.com/2020/04/18/health/kidneydialysis-coronavirus.html?smid=em-share Germany's COVID-19 surveillance program will test 15,000 people monthly for antibodies to coronaviruses, including SARSCoV-2. The results will give a sense of how many are infected. Here's how Germany's experience differs from France, Italy and Spain. https://www.nytimes.com/2020/04/18/world/europe/withbroad-random-tests-for-antibodies-germany-seeks-path-out-oflockdown.html?smid=em-share There will be no quick return to our previous lives, according to nearly two dozen experts. But there is hope for managing the scourge now and in the long term. https://www.nytimes.com/2020/04/18/health/coronavirusamerica-future.html?smid=em-share
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A relatively unbiased look at true COVID-19 infection rates in NYC. @NEJM reports that 15% of pregnant women tested positive. Using this as a representative sample means between 2.7-3.6 million of the 18.8m ppl in greater New York metro area are infected ow.ly/J8LU50zjlky South Korea reports that up to 2% of recovered COVID-19 patients test positive again and must be isolated for a second time, otherwise they could infect those around them. I recommend weekly tests until we understand the phenomenon of re-emergence in far greater detail. April 21, 2020 Please find a thoughtful piece in the Washington Post on the danger of assuming that COVID-19, if left unchecked, will not devastate rural communities in America. https://www.washingtonpost.com/opinions/rural-areas-thinktheyre-the-coronavirus-exception-theyrenot/2020/04/16/d488b800-8028-11ea-80131b6da0e4a2b7_story.html Avoidable deaths from causes other than COVID-19 are rising. In World Class, I describe NYU Langone's network of community based outpatient clinics. Outpatient clinics may be the long term solution we need for COVID and other problems plaguing medical care. https://www.nytimes.com/2020/04/20/health/treatmentdelays-coronavirus.html?smid=em-share 15% of women admitted to the hospital in NYC to deliver their babies have tested positive for COVID-19. If that represents the infection rate of NYC as a whole, it means many more people are infected than current estimates are showing. https://www.forbes.com/sites/williamhaseltine/2020/04/20/n ew-study-suggests-that-were-underestimating-COVID-19-casesby-the-millions/#228115e72e40 Arizona is a stark example of how lack of testing is an obstacle to states safely reopening and softening social distancing measures. Arizona needs 22,000 tests a week to have crystal clear data to guide their decision, vastly more than the 51,000 tests performed in total since the beginning of March. 2656
https://www.azcentral.com/story/news/local/arizona/2020/04 /20/lack-COVID-19-testing-arizona-miles-away-safelyreopening-expert-says/5147720002/ April 22 , 2020 As antibody tests ramp up, and studies point to possible hot-spots containing a higher percentage of people showing resistance to COVID-19 than the percentage of people who tested positive for the virus, it’s tempting to think that your particularly bad flu or cold back in November or December was COVID-19. Most likely, it wasn’t. https://www.thedailybeast.com/was-it-coronavirus-when-ihad-a-cold-in-november-or-december?source=articles&via=rss The US Veterans Administration reports no benefit and higher death rates for hospitalized COVID-19 patients treated with hydroxychloroquine as compared to controls. ow.ly/UEpg50zlztf Unique insight into the economic impact of COVID-19 from a friend and senior economic advisor under five previous Presidential administrations. https://medium.com/@williamahaseltine/a-closer-look-at-theeconomic-impact-reflections-on-COVID-5b81b93ae495 Evidence of the true number of direct & indirect deaths from COVID-19. Some are due to undetected COVID infections. Many others are the result of untreated life threatening illness, either due to inadequate health care capacity or fear of hospitalization. https://www.nytimes.com/interactive/2020/04/21/world/cor onavirus-missing-deaths.html?smid=em-share Managing anxiety in the COVID crisis is essential for long term wellbeing. Please see these simple recommendations by @katy_milkman in the Washington Post. https://www.washingtonpost.com/health/anxiety-is-highbecause-of-coronavirus-heres-how-you-can-feelbetter/2020/04/17/3e13fe20-7e61-11ea-80131b6da0e4a2b7_story.html April 23, 2020 We need guidelines for doctor’s offices and hospitals so that people with non-COVID illnesses can receive treatment. Creating 2657
policies for patient testing, wearing of personal protective equipment and facility cleaning would move us in the right direction. https://www.forbes.com/sites/williamhaseltine/2020/04/21/t he-new-normal-for-hospital-care/#154b6b216443 We need guidelines for doctor’s offices and hospitals so that people with non-COVID illnesses, both chronic and acute, can receive treatment. Creating and implementing clear policies for patient testing, wearing of personal protective equipment, and facility cleaning would move us in the right direction. Read more in my article about what it will take to get our healthcare system back to a place where non-COVID patients can seek care. https://www.forbes.com/sites/williamhaseltine/2020/04/21/t he-new-normal-for-hospital-care/#4ac4731f6443
April 24, 2020 The most significant, positive news to date for the treatment and prevention of COVID-19. A group of Chinese scientists have reportedly isolated two human monoclonal antibodies with the potential to treat and to prevent SARS-CoV-2 infections. https://www.forbes.com/sites/williamhaseltine/2020/04/23/p romising-new-drugs-to-treat-and-prevent-COVID19/#5dbd341545bf There are four things that make us vulnerable to the spread of viruses, with deadly effects. Modern medicine is our weapon against the force of Mother Nature. https://www.forbes.com/sites/williamhaseltine/2020/04/21/w hy-COVID-natures-code-cracking-machineintelligence/#1d0ce7236685 Two hospitals--NYU Langone and Rush in Chicago--have put in a concerted effort over the past few years to reduce in-hospital death rates. Their progress is translating into higher survival rates of patients with COVID-19. Read more about the death rate differences between these hospitals and others. https://www.forbes.com/sites/williamhaseltine/2020/04/23/in -some-hospitals-surviving-COVID-is-almost-twice-aslikely/#39a125c9155e 2658
What is the path forward to ensure we have enough testing in place to safely reopen our schools and businesses? Given that we’ll be needing over 5 million tests per day in June, and 20 million per day in July, I call on our government to create a program to develop necessary instruments and materials. https://www.forbes.com/sites/williamhaseltine/2020/04/23/h ow-many-tests-do-we-really-need/#25739b353243 David Ignatius writes a thoughtful piece in the Washington Post about how technology could help us through the pandemic, and explores the challenges with implementation here in the U.S. https://www.washingtonpost.com/opinions/how-to-avoid-apandemic-patriot-act/2020/04/21/61932346-83f5-11ea-a3ebe9fc93160703_story.html Fox News has a public responsibility to inform their viewers that they made a mistake by advocating the use of hydroxychloroquine. It’s not a crime to make a mistake, but they do need to correct it. Read more about the coverage of this drug over the past weeks. https://www.washingtonpost.com/lifestyle/media/fox-newshosts-go-mum-on-hydroxychloroquine-the-COVID-19-drugthey-spent-weeks-promoting/2020/04/22/eeaf90c2-84ac-11eaae26-989cfce1c7c7_story.html Sylvester Odion Akhaine discusses COVID studies and potential remedies to pursue in Nigeria. https://guardian.ng/opinion/coronavirus-diary-part-3/ April 25, 2020 What is the economic impact of COVID? We all want to understand what is happening and what we might expect over the next three months to a year. My recent conversation with Robert Hormats, a senior US diplomat and economist, sheds some light. https://medium.com/@williamahaseltine/a-closer-look-at-theeconomic-impact-reflections-on-COVID-5b81b93ae495 April 26, 2020 With disease surveillance, these are the questions that haunt me: What can we know, when can we know it, and what can we do with what we know? In this article recently published on Forbes, I share the lessons of lengthy conversations I have had with people 2659
whose job it is to collect and analyze data that helps us answer these questions. https://www.forbes.com/sites/williamhaseltine/2020/04/22/w hat-did-we-know-and-when-did-we-know-it-disease-surveillancepast-present-and-future/#72a107f964a3 April 27, 2020 As discussions heat up about employers reopening their doors before our public health infrastructure is in place to keep workers safe, here are some tips to protect yourself and the people around you. http://ow.ly/x2MI50zpKhF As businesses explore reopening their doors without strong national guidelines, it is vital that owners and managers lead the way in taking steps to prevent a further outbreak. I share some things leaders can do to build trust among staff and customers. https://www.psychologytoday.com/us/blog/best-practices-inhealth/202004/how-business-leaders-can-respond-COVID-19 I spoke with the Fox News about my concerns about use of hydroxychloroquine as a treatment for COVID-19 as well as three things we should have in place in order to safely move out of quarantine. https://www.foxnews.com/opinion/coronavirus-reopeningamerica-william-haseltine April 28, 2020 I am encouraged by the progress that Sinovac, a Beijing based biotech company, has made in creating and testing a vaccine candidate for the SARS-CoV-2 virus. They are starting human trials. Read more about the results from the non-human primate trials. https://www.forbes.com/sites/williamhaseltine/2020/04/25/avaccine-candidate-protects-non-human-primates-from-sars-cov-2infection/#2fd8cf127b00 Arizona continues to fall short on testing capacity as the cases in the state rise dramatically. Although they have increased testing in the past week, the state should be able to process 100,000 tests per month before considering reopening the economy. https://thehill.com/homenews/state-watch/494527-arizonahas-worst-day-yet-with-coronavirus 2660
What would it take for Americans to take the steps necessary to get the spread of this coronavirus under control? I spoke with Ernie Manouse of Houston Matters about this, as well as the economic hardships people are experiencing. https://www.houstonpublicmedia.org/articles/shows/houstonmatters/2020/04/24/368009/special-edition-dr-william-haseltineapril-24-2020/ I am 100% confident that we will develop drugs to treat people who are infected with COVID-19. Early funding will make all the difference. https://karmaimpact.com/early-funding-key-to-finding-drugsthat-will-fight-COVID-19/ We need to diversify supply chains for critical pharmaceutical products including rebuilding national capacities for the production of drugs such as antibiotics. An added concern: antibiotic resistant superbugs for which new antibiotics are needed. https://www.statnews.com/2020/04/28/china-has-near-totalcontrol-of-the-worlds-antibiotic-supply-is-america-at-risk-as-aresult/ https://www.nytimes.com/2020/04/27/health/coronavirussymptoms-cdc.html?smid=em-share NYC's death rate is 6x more than expected based on data for this time of year. Many, but not all, are due to uncounted COVID-19. Unattended serious illness and stress related deaths (incl suicide) account for the rest. Similarly high rates are reported in global COVID hot spots. April 29, 2020 A Wuhan study shows SARS-CoV-2 RNA in tiny exhaled particles that may remain in the air for hours. It is unknown whether these tiny particles can infect another person but the finding reinforces the importance of PPE & the isolation of all those exposed. https://www.nature.com/articles/s41586-020-2271-3 The case fatality rate (death of those with symptoms) & infection fatality rates (those infected with and without symptoms) of SARSCoV-2 is much more lethal than the average annual flu and more lethal than the 1957-1958 outbreak, the deadliest since 1920. 2661
https://www.washingtonpost.com/health/antibody-testssupport-whats-been-obvious-COVID-19-is-much-more-lethalthan-flu/2020/04/28/2fc215d8-87f7-11ea-ac8afe9b8088e101_story.html We always knew air travel was a good way to catch a cold. Now, we know why. What are airlines, aircraft manufacturers, and regulators doing to keep us safe? Not enough!! https://www.washingtonpost.com/local/trafficandcommuting/ scientists-think-they-know-ways-to-combat-viruses-on-airplanestheyre-too-late-for-this-pandemic/2020/04/20/83279318-76ab11ea-87da-77a8136c1a6d_story.html April 30, 2020 Caution is warranted regarding the excitement about the use of Remdesivir to speed the recovery of COVID-19 patients. The peerreviewed study in the Lancet shows Remdesivir is not only ineffective, but may in fact be harmful. https://www.thelancet.com/journals/lancet/article/PIIS01406736(20)31022-9/fulltext More hopeful progress in COVID-19 research has been made by a group of Chinese scientists. They report the isolation of two human monoclonal antibodies with the potential to treat and to prevent SARS-CoV-2 infections https://www.forbes.com/sites/williamhaseltine/2020/04/23/p romising-new-drugs-to-treat-and-prevent-COVID19/#548fcba45bf5 Test, trace, and self-isolate are the primary principles that a bipartisan public health group included in their letter to congress on Monday. Read about their proposal and what Americans must do to continue slowing the spread of this pandemic. https://www.forbes.com/sites/williamhaseltine/2020/04/29/aletter-to-congress-four-principles-for-a-safe-economicreopening/#35897b55bc61 We need our health care facilities to be positioned to care for people who are not afflicted with COVID-19. However, many hospitals need an infusion of money in order to serve the nonCOVID needs of their communities. Read more about why it is so urgent: 2662
https://thehill.com/opinion/healthcare/495509-an-urgentneed-to-reopen-medical-care-for-all?rnd=1588272465
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May 1, 2020 We have known for quite some time that on airplanes, viruses are transmitted not only on surfaces, but also through the air. What have airlines done to prevent this? Precious little. Now’s the time. https://www.forbes.com/sites/williamhaseltine/2020/04/29/re ducing-the-risk-of-in-flight-COVID-19transmission/#37bade3d4111 Please see this excellent @nytimes summary of the issues and opportunities facing COVID-19 vaccine development. The graphics are superb! The only issue it does not address is the availability of populations at high risk for infection. https://www.nytimes.com/interactive/2020/04/30/opinion/c oronavirus-COVID-vaccine.html?smid=em-share May 2, 2020 The excitement about the NIH’s study of Remdesivir may be premature. The conclusions were released prior to peer review, and without the data behind the results. I urge caution as we move to find treatments during this crisis. https://www.forbes.com/sites/williamhaseltine/2020/04/30/u rging-caution-on-remdesivir/#18cc47ac6a6f Remdesivir has been approved in the US for treatment in COVID-19 patients. This is premature, and therefore concerning. https://www.forbes.com/sites/williamhaseltine/2020/05/01/re mdesivir-a-non-antiviral-antiviral-drug/#4d4cec9254fc May 3, 2020 Tune into my interview on The Heat where we discuss promising research for treatment and prevention of COVID. https://america.cgtn.com/2020/04/30/the-heat-COVID-19research-and-medical-response May 4, 2020 This article addresses a fundamental question: Why COVID-19 strikes some populations more than others. My answer: effective government action, personal behavior, and timing. 2665
https://www.nytimes.com/2020/05/03/world/asia/coronaviru s-spread-where-why.html?smid=em-share A glimpse of what reopening looks like for universities: Few new infections, testing and vigorous contact tracing in place, mandatory controlled isolation, and regular temperature checks in all public places. If infections rise, they will shut down again. ow.ly/ZY0n50zwpQ7 Changing the endpoint in a clinical trial is suspect, especially when it has such profound social and economic impacts on a company & economy. Missing is a key piece of evidence: Did remdesivir reduce viral load or not? It did not do so in the Hubei study. https://www.washingtonpost.com/business/2020/05/01/gover nment-researchers-changed-metric-measure-coronavirus-drugremdesivir-during-clinical-trial/ May 5, 2020 My latest piece on Medium is a reflection on COVID-19 after a walk through Central Park on the weekend. https://medium.com/@williamahaseltine/a-walk-with-death964ff5e0bf81 The level of containment of COVID infections in the United States is insufficient to avoid a second and bigger wave of deadly cases in the fall, which coincides with the flu season. Until we have a medical breakthrough, we must prepare for the worst. https://www.project-syndicate.org/commentary/americafacing-second-wave-of-COVID19-by-william-a-haseltine-2020-05 NYU Shanghai has reopened after meeting the criteria for safely doing so. Here’s the list of requirements they have met. If new cases begin to rise, they will implement stronger measures. https://www.forbes.com/sites/williamhaseltine/2020/05/04/re sponsible-reopening-a-lesson-from-nyu-shanghai/#25514ca73ced Unfortunately, antibody tests are not a clear indicator of your immunity to COVID. As we begin to reopen our economy, we need clear guidelines in every place of business so workers and customers are protected. Here I offer a few ideas. https://www.forbes.com/sites/williamhaseltine/2020/05/04/C OVID-immunity-how-protected-are-you/#6ba1dd57125a 2666
May 6, 2020 I strongly recommend this excellent article of the biology of SARS-C0V-2 and diseases it causes. The virus is placed in context of other members of the coronavirus family. Knowns and unknowns the disease are clearly outlined. https://t.co/7EPR6hRU1E?amp=1 This article describes a vigorous attempt to stamp out COVID in China and prevent new infections with prolonged border closings. The story asks at what cost to the economy? It might also ask about alternative costs in lives lost. https://www.economist.com/china/2020/04/30/china-plansto-crush-new-COVID-outbreaks-with-tough-measures May 8, 2020 For those my age, this is the third pandemic we have faced. Polio and AIDS took millions of lives before we could develop a solution to bring them under control. We could have been prepared for this one, but were not. Let’s not make the same mistake again. https://www.forbes.com/sites/williamhaseltine/2020/05/08/p utting-COVID-19-behind-us-a-research-agenda-to-prepare-forthe-next-pandemic/#42d2aa0161a3 As states, counties and cities consider lifting COVID-19 restrictions they do so without clear guidelines. The risk is high of continued spread of the virus as a consequence of poorly coordinated and controlled reopening. https://www.modernhealthcare.com/government/expertsworry-cdc-sidelined-coronavirus-response May 11, 2020 A recent article in @NEJMfinds no difference in the rate of intubation and death of severely ill COVID-19 patients with or without treatment with hydroxychloroquine. http://ow.ly/BKpH50zD6gZ May 12. 2020 Very encouraging results from a study in Hong Kong. Patients who received the test drug cocktail recovered more quickly than the control group, and viral loads in the body went down. 2667
https://www.forbes.com/sites/williamhaseltine/2020/05/11/sc ientists-see-progress-in-treatment-of-COVID-19/#143546795a38 Something is deeply wrong with the way the preliminary results from the remdesivir NIAID trial were rolled out. We have yet to see the full results from the trial, and yet licensing is moving forward. https://www.forbes.com/sites/williamhaseltine/2020/05/11/w hy-havent-we-seen-the-data-on-remdesivir/#3365eefa7e93 I have been outspoken from the beginning about the administration’s slow response to early warnings about the novel coronavirus. https://www.salon.com/2020/05/08/kellyanne-conwaycriticizes-anti-trump-group-co-founded-by-husband-neverachieved-what-i-achieved/ NYC will begin widespread antibody testing, and this will give us insight into where the virus has been, and how widespread. It is very important that people who test positive keep in mind that they are not invincible. https://www.thedailybeast.com/new-yorks-antibody-testingspree-could-be-a-game-changer?source=articles&via=rss May 13, 2020 Emergency room doctors and nurses face difficult decisions every day, and the hype around remdesivir is clouding their ability to know which treatments work against COVID. It’s essential that our frontline healthcare workers have clear data—not hope alone. https://www.forbes.com/sites/williamhaseltine/2020/05/11/w hich-COVID-19-antivirals-actually-work/#69e85be068c6 We need to be able to test for the active virus, for antibodies, and for antigens. These tests need to be cheap, easy to administer, and the results need to be fast. Fortunately, they are on the way. https://www.forbes.com/sites/williamhaseltine/2020/05/12/ra pid-accessible-affordable-ubiquitous-tests-for-sars-cov-2-are-onthe-way/#60299bcefe55 May 14, 2020 Too many of us were sounding the warning bells for over a decade about a potential pandemic such as the one we’re facing right now. Had we developed and stockpiled drugs after SARS and MERS, we could have contained the death toll to just a small few. 2668
https://www.forbes.com/sites/williamhaseltine/2020/05/12/w hy-werent-we-ready-for-the-coronavirus/#50ddc0c48510 According to the WHO, there are very early studies of treatments that are limiting the severity or the length of COVID19. This is hopeful. However, we do not have anything that can stop the virus. https://www.salon.com/2020/05/12/who-says-somemedicines-can-shorten-duration-of-COVID-19-buthydroxychloroquine-is-ineffective/ May 15, 2020 Studies of COVID-19 are revealing that it closely resembles the virus that caused the first SARS outbreak in 2002, which originated in bats. The more we understand about the genetic make up of SARS-CoV-2 the closer we are to finding its origins in nature. https://www.forbes.com/sites/williamhaseltine/2020/05/13/o ne-step-closer-to-understanding-the-origin-of-sars-cov2/#2b4f46711180 Please join me and Reuters Global Managing Editor Alessandra Galloni as we discuss COVID-19, the race for a vaccine, and the pandemic’s impact on the future of public health. Register for this virtual live event below. https://reutersnewsmakerdrhaseltine.splashthat.com/ May 16, 2020 Pediatric multisystem inflammatory syndrome includes these critical symptoms (high fever of 102-103 degrees, abdominal pain, diarrhea, and a rash (localized or whole body). This new syndrome is the latest expression of COVID-19 in young people. https://www.forbes.com/sites/williamhaseltine/2020/05/14/C OVID-19-among-children/#4c6212f975d4 The common cold spreads through the air with a cough or a sneeze. The virus that causes COVID-19 can be spread through the air through merely talking. https://www.salon.com/2020/05/14/merely-talkingnormally-may-spread-the-coronavirus/ Please join me and Reuters Global Managing Editor Alessandra Galloni as we discuss COVID-19, the race for a vaccine, and the 2669
pandemic’s impact on the future of public health. Register for this virtual live event below https://reutersnewsmakerdrhaseltine.splashthat.com/ May 17, 2020 Treatments are improving for patients with COVID-19 as we test and learn more about what works and what doesn’t. Anticoagulant drugs are making an impact--more people are surviving when given blood thinners. https://www.forbes.com/sites/williamhaseltine/2020/05/14/p rogress-and-possibilities-for-treating-COVID-19/#6dc4501d7f55 Some say the virus may be with us for 4-5 years or longer. But there is a difference btw a virus persisting in the population and a lethal pandemic. I am reasonably sure we can control the epidemic by behavioral change or pharmaceutical intervention. https://www.salon.com/2020/05/14/what-if-the-pandemicnever-ends-the-who-thinks-its-possible/ May 18, 2020 Please join me and Reuters Global Managing Editor Alessandra Galloni as we discuss COVID-19, the race for a vaccine, and the pandemic’s impact on the future of public health. Register for this virtual live event below. https://reutersnewsmakerdrhaseltine.splashthat.com/ Just as it is impossible for us to control tsunamis and earthquakes, our ability to subdue contagious outbreaks is limited. But we can take steps to be prepared for future biological emergencies. We must respond now, beyond politicization. https://www.project-syndicate.org/onpoint/what-aids-taughtus-about-fighting-pandemics-by-william-a-haseltine-2020-05 Please find an up to date summary of drug treatment options for COVID-19. This is a rapidly evolving field. Detailed answers to many of your questions can be found herein. This report is an authoritative summary of what we know and, what we don’t know. https://jamanetwork.com/journals/jama/fullarticle/2764727 Can COVID be transmitted by dirty water? Probably. Live SARS-CoV-2 was found in the feces of some infected people. No surprise as we knew this previously with SARS - people in the same 2670
hotel as a SARS-infected person were infected through leaking sewer gas. https://jamanetwork.com/journals/jama/fullarticle/2762997 Can mothers transmit SARS-CoV-19 to a fetus? Perhaps yes. A study finds IgM antibodies in infants, which aren't known to cross the placental barrier. This raises the possibility of mother to fetus transmission. More research needed https://jamanetwork.com/journals/jama/fullarticle/2763854 May 19, 2020 Two private companies announced this week that their vaccine candidates worked to protect rhesus monkeys from COVID-19. Results were varied, with only one of the two showing no virus recovered from the vaccinated animals. https://www.forbes.com/sites/williamhaseltine/2020/05/16/di d-the-oxford-COVID-vaccine-work-in-monkeys-notreally/#6d4b1b113c71 Some children and adolescents with COVID-19 are exhibiting unusual symptoms late in the course of the disease, such as skin rashes, reddening of the toes and fingers, shortness of breath, fever, diarrhea, muscle aches and fatigue. https://www.forbes.com/sites/williamhaseltine/2020/05/18/m is-c-a-new-name-for-COVID-kawasakitoxic-shock-in-youngpeople/#3aab96504357 May 20, 2020 STARTING SOON: Pls join me and Reuters Global Managing Editor Alessandra Galloni as we discuss COVID-19, the race for a vaccine, and the pandemic’s impact on the future of public health. Register now for this virtual live event below. https://reutersnewsmakerdrhaseltine.splashthat.com/ It is possible to eliminate COVID without effective drugs or vaccines. This is how they did it in Wuhan, China. https://jamanetwork.com/journals/jama/fullarticle/2764658 Please see a business editor for the LA Times who is even more skeptical than me regarding the Moderna announcement. https://www.latimes.com/business/story/2020-0519/moderna-vaccine-share-price-coronavirus-COVID-19 2671
Healthcare systems around the country are in deep economic trouble. New CMS rules regarding payments for COVID will exacerbate the problem. https://www.modernhealthcare.com/payment/providerscould-bear-brunt-state-COVID-19-medicaid-cuts The story in STAT reinforces the need to take extraordinary measures to protect the elderly from infections that are devastating elder care homes. It is time to replace elder care homes with care at home. https://www.washingtonpost.com/health/elderly-COVID-19patients-on-ventilators-usually-do-not-survive-new-york-hospitalsreport/2020/05/19/ba20e822-99f8-11ea-89fd28fb313d1886_story.html Please see this obvious conflict of interest at the top of the FDA which, in my opinion, is not resolved by the recusals. Resignation of one or both is in order. https://www.statnews.com/2020/05/19/conflict-of-interestfda-recusal-operation-warp-speed/ Another important story on Moderna and the search for a coronavirus vaccine. https://www.bostonglobe.com/2020/05/19/business/hopeCOVID-19-vaccine-attracts-investors-cambridgebiotech/?s_campaign=breakingnews:newsletter May 21, 2020 See Tom Freidman’s excellent op-ed. Will shouting down a hurricane lessen its force? https://www.nytimes.com/2020/05/19/opinion/trumpcoronavirus.html?smid=em-share My Forbes article on viruses as code cracking machines follows the same themes of viruses and Nature. https://www.forbes.com/sites/williamhaseltine/2020/04/21/w hy-COVID-natures-code-cracking-machineintelligence/#65055c106685 Yesterday I spoke with Reuters Global Managing Editor Alessandra Galloni about COVID-19. I also took questions from the global audience. This is the video recording of our discussion.http:// https://www.reuters.com/livevideo?id=Paj8 2672
How China handles sporadic COVID eruptions tells us a lot about what a prolonged post pandemic world will look like— renewed lockdowns and closed business. All countries will face episodic disruptions, the only question is at what scale. https://www.nytimes.com/2020/05/21/world/asia/coronaviru s-china-lockdown.html?smid=em-share This piece shows the main cause of the disproportionately high infection and death rates in NYC are due to poor living conditions. They compare high rates in poor districts here to migrant workers in Singapore & suggest a redesign of urban spaces. https://www.wired.com/story/how-does-a-virus-spread-incities-its-a-problem-ofscale/?utm_brand=wired&utm_campaign=onsiteshare&utm_medium=email&utm_source=onsite-share May 22, 2020 Trust in science is being undermined as companies rush to announce breakthroughs without sharing the data behind their findings. Despite the need to find solutions to this pandemic, we cannot give up our standards in the scientific and medical community. https://www.washingtonpost.com/opinions/2020/05/19/rush -share-good-news-COVID-19-drugs-is-undermining-science/ A report from Shanghai shows that despite differences in the genome of 2 SARS-CoV-2 strains, the disease caused by infection was the same. The health of patients before infection was the major determinant of the severity of symptoms not the virus variant. https://www.genomeweb.com/infectious-disease/host-factorsinfluence-COVID-19-severity-more-viral-genetic-variation-studyfinds The best approach to the pandemic is to manage the disease through careful tracing of infections and strict isolation measures whenever it starts spreading. https://www.theguardian.com/world/2020/may/21/globalreport-coronavirus-vaccine-us-scientist-cases-5-million The US has pledged funding for the COVID vaccine out of Oxford despite the weakness it shows in actually killing the virus. https://www.bloomberg.com/news/articles/2020-0521/astrazeneca-gets-1-billion-from-u-s-to-make-oxford-vaccine 2673
Preparation is key as we look towards a possible second wave of the virus in the fall. Countries must work to contain the disease, not count on the possibility of a vaccine being developed. https://www.theguardian.com/us-news/2020/may/21/firstthing-us-has-three-months-to-prepare-for-second-COVID-19wave-say-scientists We still have a long way to go in this pandemic, and we can’t count on a vaccine. The tools we should be relying on to control the spread are careful tracing of infections and strict isolation measures. https://www.nbcnews.com/news/morning-briefing/globalCOVID-19-cases-top-5-million-trump-s-factory-n1211891 Why am I skeptical about a vaccine coming to the rescue in this COVID pandemic? Because vaccines developed previously for other types of coronavirus failed to protect mucous membranes in the nose where the virus typically enters the body. https://www.reuters.com/article/us-health-coronavirushaseltine-newsmake/top-hiv-scientist-says-he-wouldnt-count-ona-vaccine-for-coronavirus-soon-idUSKBN22W34T May 23, 2020 There is justified skepticism over the quality and the timing of the Moderna announcement. See this summary from STAT. https://www.statnews.com/2020/05/19/vaccine-experts-saymoderna-didnt-produce-data-critical-to-assessing-COVID-19vaccine/ May 24, 2020 Actions in an epidemic result in enormous differences to health and economy. I fear the US has fallen short. We are paying in lost lives and a severely damaged economy. I see a new “lost generation" saddled with enormous debt and a poor job market. https://www.nytimes.com/2020/05/20/us/coronavirusdistancing-deaths.html?smid=em-share
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May 26, 2020 The fear and sadness expressed so eloquently here, in this article about having a loved one in a nursing home in the time of COVID, is shared around the world. https://www.nytimes.com/2020/05/25/opinion/nursinghome-coronavirus.html?smid=em-share This @nytimes column elaborates on the dangers of what I call “publication by press release.” https://www.nytimes.com/2020/05/23/health/coronavirusvaccine-moderna.html?referringSource=articleShare Social distancing limits the spread of infectious diseases, including influenza. The study cited here shows that this year’s influenza pandemic was prematurely cut short, very likely the cause of social distancing measures related to COVID-19. https://www.nature.com/articles/d41586-020-01538-8 How well do we learn the lesson of past pandemics? Not well it appears. Recent trauma we remember, but that memory recedes rapidly with time. Desire for the normal may be a drive more powerful than the will to do the inconvenient to survive. https://www.citylab.com/life/2020/05/behavior-changepandemic-handshakes-crowds/611164/ Remdesivir is being heralded as a miracle drug. States are setting up lotteries and task forces to determine which patients get access to the supply. But from what we know today, the drug has a relatively minor effect only for those with moderate COVID-19. https://theintercept.com/2020/05/26/coronavirus-gileandremdesivir-treatment/ The NIH has released the data from the Remdesivir trial and it remains unclear whether or not the drug actually saves lives. In this article I share thoughts on some key aspects of the full data set. https://www.forbes.com/sites/williamhaseltine/2020/05/26/re mdesivir-revealed-what-the-finally-released-data-tellsus/#7ffafd672800 Moving too fast into human trials for the coronavirus vaccine is dangerous. We cannot afford not to do these trials the right way-too many lives are at stake. https://www.nbcnews.com/nightly-news/video/u-s-gives-1billion-boost-to-oxford-coronavirus-vaccine-effort-83761221840 2675
Wash your hands. Clean and disinfect surfaces. Even though we’re learning that the probability of picking up the coronavirus from surfaces might be somewhat lower than we originally thought, it’s not impossible, so don’t change your behavior. https://www.salon.com/2020/05/25/cdc-revises-itsguidelines-on-surface-contact-prompting-an-outbreak-ofmisleading-headlines/ May 27, 2020 While I am in favor of government support of broad vaccine research and development, I have many concerns about taxpayer dollars being given to corporations with robust finances. https://www.forbes.com/sites/williamhaseltine/2020/05/26/it s-too-early-for-the-us-government-to-place-risky-billion-dollarbets-on-COVID-vaccines/#29fbf71a7280 The coronavirus vaccines in development are not working the way people often think of vaccines: They do not protect you completely from getting sick. Wolf Blitzer and I discuss the prospects and process of creating a vaccine. https://grabien.com/getmedia.php?id=924037&key=44bda499 4b587741e9990f13882fbd81 A new COVID-19 vaccine is being developed in China. In the first, small human study, it caused no serious side effects and recipients developed antibodies. I agree with the authors that further human studies are worth pursuing. https://www.forbes.com/sites/williamhaseltine/2020/05/22/e arly-study-of-COVID-19-vaccine-developed-in-china-seesmixed-results/#297462c477dd A study of hydroxychloroquine and azithromycin alone or together showed no benefit for COVID-19 patients. Given this and other studies, continued use of these drugs to prevent or treat COVID-19 is unethical and should be discontinued. https://www.thelancet.com/pdfs/journals/lancet/PIIS01406736(20)31180-6.pdf It is very difficult to prevent COVID transmission at work. Until the incidence of infection is lowered and controlled, many manpower intensive and customer facing businesses will struggle to resume operations safely without driving more infections. 2676
https://www.washingtonpost.com/business/2020/05/25/meat -industry-is-trying-get-back-normal-workers-are-still-getting-sickshortages-may-get-worse/ May 28, 2020 As the population of older people in the U.S. increases, we’re seeing a decline in people trained to care for them. We’re now in catch-up mode. To reverse the decline, we need to understand the root causes of the geriatrician shortage. http://viewer.zmags.com/publication/154922a2# May 29, 2020 A new study shows us that in the noses of children, the virus that causes COVID-19 has fewer places to attach itself than in the noses of adults. https://www.forbes.com/sites/williamhaseltine/2020/05/27/at tachment-sites-for-the-COVID-19-virus-are-less-abundant-inchildren-than-adults/#323defd5bcf2 The medical and scientific community—and especially those developing vaccines—have a responsibility to be transparent. The release of information about vaccine trials without data creates a false impression about progress that may or may not exist. https://www.cbc.ca/radio/thecurrent/the-current-for-may27-2020-1.5586338/without-data-press-releases-of-COVID-19vaccine-findings-create-false-impression-of-progress-expert1.5586899 In a recent @AAPSComms series, we explore testing and analytical approaches to COVID-19. We talk about what’s making a rapid response possible, repurposing drugs, and maintaining business continuity and global supply chains in a pandemic. Free for members. https://www.pathlms.com/aaps/courses/17752 May 30, 2020 We are learning how the body’s immune system responds to SARS-CoV-2. It’s unusual, and explains why some people are showing very low antibodies after infection as well as why some people’s health declines extremely rapidly after infection. 2677
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June 1, 2020 We know what it takes to stop COVID-19 dead in its tracks by looking at examples from other countries. The trouble is, we aren’t doing it. https://www.forbes.com/sites/williamhaseltine/2020/05/28/1 00000-dead-and-countless-wounded/#55cff32549a6 The question is not WHEN will we have a vaccine, but IF we will. On top of that, there’s the challenge of the public accepting the vaccine--and if more than 10% of the population refuses it, the vaccine won’t protect our most vulnerable. https://www.forbes.com/sites/williamhaseltine/2020/05/28/c onfronting-barriers-to-COVID-19-vaccineacceptance/#284abd484882 It is unrealistic that we will have a vaccine by October. https://www.sciencemag.org/news/2020/05/doubts-greet-12billion-bet-united-states-coronavirus-vaccine-october Please take note of this woman’s experience. Research has already shown what she has experienced first hand: Hydroxychloroquine doesn’t protect you against COVID-19. https://www.salon.com/2020/05/21/longtimehydroxychloroquine-user-contracts-COVID-19/ A vaccine for COVID-19 may never be developed. Back in 1986, I said the same thing about the prospects for an HIV/AIDS vaccine. I was booed off the stage for saying that in front of an audience of scientists. But we still don’t have a vaccine for AIDS. https://blogs.thomsonreuters.com/answerson/reutersnewsmakers-dr-william-haseltine/ What can we do about this pandemic that has killed over 100,000 in the US? We start with doing what we know works: (1) aggressive social distancing (2) widespread testing (3) contact tracing (4) mandatory 14-day isolation for those exposed. https://www.latimes.com/opinion/story/2020-05-26/op-edwill-memorial-day-2020-be-remembered-as-the-holiday-whenCOVID-19-got-the-upper-hand A moving story about the death of one young woman, age 15, from COVID-19. An important read especially for those who think youth is a shield from the disease. 2680
https://www.washingtonpost.com/local/daryana-dyson-ateen-who-loved-music-and-wanted-to-become-a-cosmetologistdies-of-complications-of-COVID-19/2020/05/29/4488412ea02d-11ea-b5c9-570a91917d8d_story.html In war we count the dead, wounded, and those with long term disabilities. For COVID we should do the same, with hospitalized counted as wounded. But we don't. No one knows how many have been hospitalized or have long term damage. https://www.washingtonpost.com/health/could-COVID-19cause-long-term-chronic-fatigue-and-illness-in-somepatients/2020/05/29/bcd5edb2-a02c-11ea-b5c9570a91917d8d_story.html June 2, 2020 COVID-19 has had a devastating effect on America's mental wellbeing. We need to change the way our healthcare systems treats and manages mental illnesses to mitigate more devastation from the outbreak. https://www.statnews.com/2020/05/29/COVID-19-changeapproach-mental-illness/ June 3, 2020 In the rush to create a vaccine for COVID-19, we must be careful to fully understand what each vaccine does and doesn’t do, as well as what harm it might cause to otherwise healthy adults and children. https://www.forbes.com/sites/williamhaseltine/2020/06/02/C OVID-in-kids-a-reason-to-be-wary-of-COVIDvaccines/#787ca93d2027 We now understand that children who are presenting symptoms similar to Kawasaki syndrome have something different: MIS-C (Multisystem Inflammatory Syndrome—Children). The Lancet recently published a study detailing the difference between these illnesses. https://www.forbes.com/sites/williamhaseltine/2020/06/01/C OVID-19-in-children-a-detailed-study-of-10-italianchildren/#70628c297200 Please see this important story on the US withdrawal from the World Health Organization. 2681
https://www.forbes.com/sites/madhukarpai/2020/06/03/uswithdrawal-from-who-sad-for-global-health-and-bad-foramerica/#34f2ddac1327 June 4, 2020 The steps China has taken to protect its population through testing and tracking is truly impressive. The US, on the other hand, is failing. https://www.forbes.com/sites/williamhaseltine/2020/06/03/t wo-weeks-and-ten-million-COVID-tests-inwuhan/#734328356080 Hydroxychloroquine does not prevent COVID-19, or slow disease progression. It also doesn't help recovery of the seriously ill. It does, however, increase the risk of heart disease and death. Why politicians and talking heads still push it is unfathomable. https://www.wired.com/story/major-hydroxychloroquinetrial-shows-no-prevention-benefits/?utm_source=onsiteshare&utm_medium=email&utm_campaign=onsiteshare&utm_brand=wired Another poor decision restricting Chinese students from study in the US. The US & China are near parity in our technical & scientific know-how. We stand to gain as much if not more from the wealth of well educated Chinese students and post-Docs. https://www.nytimes.com/2020/05/28/us/politics/chinahong-kong-trump-student-visas.html?smid=em-share As long as COVID infection rates are high in one country, travel between countries can put an entire nation at risk. When 12 passengers tested positive on arrival in Greece from Qatar, Greece rightly quarantined the whole plane, including the air crew. https://www.theguardian.com/world/2020/jun/03/COVID19-greece-quarantines-all-passengers-from-qatar-flight June 5, 2020 From the onset of the coronavirus outbreak, Sweden has been lax in its protective measures, refusing to implement stay at home orders or to enforce social distancing. Now, their per capita death rate from COVID-19 is among the highest in the world. https://www.forbes.com/sites/williamhaseltine/2020/06/04/awarning-from-sweden/#23fe90b54c56 2682
June 9, 2020 Intelligence agencies have excellent open source tools to detect anomalous events that signal a disease outbreak. Some propose an official alliance between the WHO & intel agencies, but I prefer to equip the WHO with open source intel capabilities itself. https://www.newsweek.com/prevent-next-pandemic-globalspy-agencies-must-join-forces-who-opinion-1508513 COVID-19 has erased the boundaries between health system providers, public health, and public and private Life. See these thoughts from Health Affairs. https://www.healthaffairs.org/do/10.1377/hblog20200604.821 30/full/ June 10, 2020 Every day we learn more about COVID-19: How it is transmitted, who is most susceptible, and how it affects our bodies. Recent data brings our attention to the role someone’s blood type plays as well as in one’s physiological response to the disease. https://www.forbes.com/sites/williamhaseltine/2020/06/10/t he-role-of-blood-type-in-COVID-19-infection-and-respiratoryfailure/#6015228c307e COVID-19 is not a mild cold. It is debilitating. Survivors continue to suffer: Some have lungs that will never breathe easy, others foggy brains and paralyzed limbs, failing kidneys, or hearts that swell and veins that burst. We need to hear their stories. https://www.forbes.com/sites/williamhaseltine/2020/06/10/w ounded-in-action-from-COVID-19/#328563002bde The rush to test the COVID-19 vaccine in humans is unethical because it is extremely unlikely that all vaccine candidates will work in all trials. Volunteers may be permanently harmed. https://www.project-syndicate.org/commentary/COVID19vaccine-trials-innecessary-uninfomative-unethical-by-william-ahaseltine-2020-06 June 15, 2020 COVID-19 affects more than just those infected. Many services aren't available for other types of care. Most severely impacted are
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the young, who are missing routine checkups & vaccinations. Health systems must maintain routine care even during outbreaks. https://www.nytimes.com/2020/06/14/health/coronavirusvaccines-measles.html?smid=em-share Some good news today. A new study shows some high blood pressure medications are unlikely to worsen COVID symptoms. But people with high blood pressure are still at high risk for severe COVID and should minimize risks of infection. https://www.washingtonpost.com/health/high-bloodpressure-drugs-apparently-dont-add-to-COVID-19-danger-asearlier-feared/2020/06/12/22432df6-a9a9-11ea-94d2d7bc43b26bf9_story.html I am pleased to see this FDA action in the face of what may have been political pressure to do otherwise. We all count on our regulatory agencies to keep us safe. Last week France took similar measures. Hopefully countries like India & Brazil will follow. https://www.statnews.com/2020/06/15/fda-revokeshydroxychloroquine/ June 16, 2020 Recent evidence suggests that the SARS-CoV-2 virus has mutated. The dominant strain today is now capable of infecting more human cells, but it remains unclear whether this mutation is more lethal. https://edition.cnn.com/2020/06/12/opinions/coronavirusmutation-increased-infectivity-haseltine/index.html June 17, 2020 We are learning that COVID-19 discriminates against those who it sickens and kills, disproportionately affecting people according to their ethnicity and whether or not they have any pre-existing diseases. https://www.forbes.com/sites/williamhaseltine/2020/06/16/anew-cdc-report-shows-COVID-disproportionately-affects-thosewith-underlying-disease-and-disadvantagedminorities/#1a40bbf34d72 If your air travel is optional, my advice is to stay home. https://www.forbes.com/sites/williamhaseltine/2020/06/16/tr aveling-by-air-in-the-time-of-covi/#796465404277 2684
This is an excellent analysis of what the office workspace might look like as the epidemic continues and we continue to work! https://www.huffingtonpost.co.uk/entry/future-of-theworkplace-COVID19_uk_5ee255c1c5b6c846accb15f8?utm_campaign=share_email&n cid=other_email_o63gt2jcad4 COVID vaccine challenge studies move closer to reality in the US. I believe these to be unnecessary and unethical. If they are not condemned by the US & UK, what will stop other countries? Can courts issue global injunctions? https://www.washingtonpost.com/health/2020/06/15/volunt eers-sign-up-put-their-lives-line-coronavirus-vaccine/ June 18, 2020 It is encouraging to hear that the steroid Dexamethasone reduced the death rate of patients with COVID-19. We don’t have the data to review, but these reports give hope. https://www.forbes.com/sites/williamhaseltine/2020/06/16/d examethasone-reduces-mortality-in-seriously-ill-COVID-19patients-and-so-do-other-treatments/#3d2f60c1a3e4 On Bloomberg Business Week I shared thoughts about the latest spike in cases in Florida and other US states, the lack of strong leadership, and my new book “A Family Guide to COVID” (due out next week). https://www.bloomberg.com/news/audio/2020-0616/confusion-over-antibody-tests-podcast Drugs and other approaches are making an impact on people who fall ill from the coronavirus, which is very encouraging. We discuss those tools, and also vaccines, on The Close on Bloomberg TV. https://www.bloomberg.com/news/videos/2020-06-16/90chance-for-effective-COVID-19-drugs-within-year-dr-haseltinevideo June 19, 2020 With Sinovac’s latest announcement about the results of their vaccine trial for COVID-19, we have no peer-reviewed data. Data transparency should be the rule, not the exception, for public announcements. This is a troubling trend. 2685
https://www.forbes.com/sites/williamhaseltine/2020/06/17/m ore-publication-by-press-release-this-time-from-sinovac-on-aCOVID-vaccine/#67fa3d67c2e7 Yes we should re-open, but carefully, as in East Asia. See this excellent description from an LA Times correspondent in Singapore. https://enewspaper.latimes.com/infinity/article_share.aspx?gui d=f6310737-0073-4abf-8119-edd70a0d6d04 An excellent interview with a Japanese economist on how to climb out of the recession. Japanese have had the experience of living through very tough economic times - the 80s & dot com bubbles & impact of SARS, tsunami, COVID - yet they are still afloat. https://www.newyorker.com/news/q-and-a/how-to-shortenthe-american-recession?utm_source=onsiteshare&utm_medium=email&utm_campaign=onsiteshare&utm_brand=the-new-yorker June 20, 2020 This details my worst fears of a fast-tracked COVID vaccine. We can't know the safety or efficacy of a vaccine by year's end. A failed vaccine will cause harm and undermine public confidence. Talk to your congressional rep to ensure a COVID vaccine is safe. https://www.washingtonpost.com/health/2020/06/17/trumpcoronavirus-vaccine/ June 21, 2020 New research suggests that children may be less susceptible to SARS-CoV-2, although there are many confounding variables from the study. Correct understanding of this will have policy implications, such as school openings. https://www.forbes.com/sites/williamhaseltine/2020/06/17/ar e-children-less-easily-infected-by-sars-cov-2-maybe-yes-andmaybe-no/#77fea4063284 June 22, 2020 The barely perceptible impact of COVID-19 on unemployment in Japan highlights what putting workers first really means. https://www.nytimes.com/2020/06/20/business/japanunemployment.html?smid=em-share 2686
This is a sad story of unnecessary lives lost due to poor readership, poor governance and poor public health infrastructure, not to mention economic wreckage. https://www.statnews.com/2020/06/19/faster-responseprevented-most-us-COVID-19-deaths/ This story in the Washington Post personalizing the devastating impact of COVID-19 healthcare professionals. Many died unnecessarily due to lack of personal protection. They gave their lives to save others. https://www.washingtonpost.com/graphics/2020/health/healt hcare-workers-death-coronavirus/ June 23, 2020 Countries are opening up, and we have lessons around the world of what works, and what doesn’t. One thing we know for sure: We have tools on hand to ensure a successful reopening. The question is, will we employ them? https://www.forbes.com/sites/williamhaseltine/2020/06/19/s uccessful-reopening-its-not-what-you-think/#703caae25d98 We are learning more about the immunity response to COVID19. This recent study has profound implications for the pursuit of a vaccine. https://www.forbes.com/sites/williamhaseltine/2020/06/19/i mmunity-to-COVID-19-infection-may-fade-quickly/ Since the start of the pandemic, my children, grandchildren and many of my friends have been coming to me with question after question about COVID-19. Why have our lives changed? Are my children in danger? Will there be a vaccine or a cure and if so, when? When will our lives return to normal? That’s why I wrote this book. It is my attempt to answer these questions honestly and with compassion. As our understanding of COVID-19 evolves, so will this book. You can get it online for $1.99 and you’ll have access to the newest editions at no extra charge. www.accessh.org/COVIDfamilyguide June 24, 2020 Wearing a mask can lead to a 40% reduction in new COVID cases per day, so why won’t most Americans wear one? 2687
https://www.forbes.com/sites/williamhaseltine/2020/06/19/w hy-wearing-a-face-mask-is-the-sanest-thing-you-can-do/ This chart tells it all. We must do better to contain COVID. It can be done without a lockdown but in takes leadership, governance, efficient centralized public health action, and each person choosing to protect themselves and their loved ones. https://www.washingtonpost.com/world/2020/06/23/countri es-around-world-scramble-contain-coronavirus-flare-ups-us-statesremain-open/ There are new efforts to protect companies and insurers from liability should workers contract COVID-19 on the job. Protecting business that neglect safe practices may endanger working men and women. Protecting insurance companies may bankrupt them. https://www.modernhealthcare.com/payment/trumpadministration-says-insurers-hook-back-work-COVID-19-tests June 25, 2020 Information about how COVID-19 affects pregnant women and their unborn children has been inconsistent and inconclusive. We need more data. https://www.forbes.com/sites/williamhaseltine/2020/06/22/p rotecting-pregnant-women-from-COVID-19/ As much as we all hope for a vaccine to put a rapid end to the pandemic, there are risks that come with a fast-tracked vaccine delivered end of this year, not the least of which are the risks related to the safety of the vaccine itself. https://www.scientificamerican.com/article/the-risks-ofrushing-a-COVID-19-vaccine/?previewid=C5F6B7EC-E3544497-A244F69BB97647B8 SARS-CoV-2 can spread via the eye, by inhalation, via sewagecontaminated water & possibly via sewer gas (oral/fecal). The CDC now recommends goggles & face masks for medical personnel. I recommend the same for air travel and prolonged indoor encounters. https://www.cdc.gov/coronavirus/2019-ncov/hcp/guidancerisk-assesment-hcp.html June 26, 2020 Very promising progress is being made with monoclonal antibodies to treat and prevent COVID-19. This study is a tour de 2688
force not only for the clarity and completeness of the results but also for the speed with which all the many steps were accomplished. http://www.forbes.com/sites/williamhaseltine/2020/06/23/pr ogress-in-monoclonal-antibodies-for-the-treatment-andprevention-of-COVID-19/ The U.S. is finally beginning to scale up its testing efforts for COVID-19. With pool testing, twenty samples are tested at once. If one is positive, all twenty are tested to find those that are actually infected. This strategy has proved successful in Wuhan, Beijing, and other cities in China. https://www.washingtonpost.com/news/powerpost/paloma/t he-health-202/2020/06/26/the-health-202-the-trumpadministration-is-eyeing-a-new-testing-strategy-for-coronavirusanthony-fauci-says/5ef4f629602ff1080718f308/ June 27, 2020 Three strains of SARS-CoV-2 are circulating in Chicago. The study of their origins, and the differing rates of infection between the three, gives some insight into why some cities and countries may have been more easily able to contain the outbreak than others. https://www.forbes.com/sites/williamhaseltine/2020/06/22/atale-of-four-cities-wuhan-seattle-new-yorkchicago/#54764d25c050 June 28, 2020 Humans can pass the coronavirus to animals. Whether or not we should worry about animals passing it back to humans is an area for detailed surveillance. https://www.forbes.com/sites/williamhaseltine/2020/06/23/C OVID-19-ping-pong-animal-to-human-human-to-animal-animalto-human-transmission-how-great-a-danger/#74831cd22f49 June 29, 2020 Please read this investigation by the Washington Post. A case study in mismanagement of a public health crisis. We need an effective national Public Health Service.
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https://www.washingtonpost.com/health/how-arizona-lostcontrol-of-the-epidemic/2020/06/25/f692a5a8-b658-11ea-aca5ebb63d27e1ff_story.html The Harvard Gazette asked many of its most distinguished faculty to write a short piece on how COVID-19 is changing the world, ranging from foreign policy to the workplace. Read these thought provoking comments here. https://www.hks.harvard.edu/faculty-research/policytopics/public-leadership-management/how-COVID-19-haschanged-publicpolicy?utm_source=SilverpopMailing&utm_medium=email&utm_ campaign=Daily%20Gazette%2020200629%20(1 NPR looked at efforts to control COVID in Florida & California. Some California cities acted early and did well, others acted later and are still suffering. In Florida, the governor prohibited the implementation of policies. The state is paying the price. https://www.revealnews.org/article/how-a-national-healthcrisis-fell-on-the-backs-of-local-leaders/ Robinson Myer & Alexis Madrigal make a bold attempt at understanding the underlying causes of the rise in new COVID cases in the South, Southwest and West of the US. Deliberate policy choices and irresponsible personal behavior are driving the catastrophe. https://www.theatlantic.com/science/archive/2020/06/second -coronavirus-surge-here/613522/ To those of you interested in the macroeconomic effects of COVID-19, this Brookings study is for you. Warning. The news is not good. https://www.brookings.edu/research/global-macroeconomicscenarios-of-the-COVID-19-pandemic/?preview_id=859460 We all are tempted by a July 4 BBQ with friends. It can be done safely but you must know your community & the infection rate. That can help you estimate risk. If it is very high, don’t even think about a BBQ, even with close friends. And no matter what stay outdoors, not inside! https://www.nytimes.com/2020/06/26/dining/socialdistance-bbq-recipes.html?smid=em-share
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June 30, 2020 China has taken a bold and risky move by approving a vaccine of unknown safety and efficacy for its military. If it works they will be heroes. If it is harmful they will be villains. Let’s hope other countries do not follow this dangerous example. https://www.nytimes.com/reuters/2020/06/29/world/asia/29 reuters-health-coronavirus-china-vaccine.html?smid=em-share Our understanding of COVID-19 is changing everyday and it is important we stay aware and informed. A Family Guide to COVID is a compilation of questions and answers that I have been compiling from my own children, grandchildren, friends and family. It is my goal to share with you the most current knowledge of this disease as our understanding of it unfolds. This is a living book meaning that my team and I will be continuously updating it with new information. Gain free access to each new edition of the book by downloading it here: www.accessh.org/COVIDfamilyguide
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July 1, 2020 Over $3,000 for remdesivir? This is an outrageous price for a drug that has shown virtually no benefits for patients with COVID19. It is time for governments to push back. https://www.forbes.com/sites/williamhaseltine/2020/06/29/t he-other-shoe-drops-gileads-outrageous-pricing-ofremdesivir/#4aa7cc648d1f July 2, 2020 I predict with confidence that by this time next year, cocktails of anti-viral drugs will be approved for use that effectively treat SARSCoV-2 infections. https://www.forbes.com/sites/williamhaseltine/2020/06/29/w ere-making-exciting-progress-in-developing-COVID-19drugs/#43b79182fbd4 July 3, 2020 The impact of the pandemic is negatively affecting women’s emotional, mental, physical, and reproductive health. This survey asked women about their desire to have children, their sense of safety, and their confidence in being able to take care of their kids. Responses are telling, and sadly show that the effects of COVID are reinforcing disparities already in place--we must do more to help. https://www.forbes.com/sites/williamhaseltine/2020/06/30/w omens-health-and-the-ripple-effect-of-the-COVID-19pandemic/#1f86fa536de6 July 4, 2020 As a medical scientist, I have had many people in my life, young and old, come to me with critical questions about COVID-19. Why have our lives changed? Are my children in danger? When will this be over? Will there be a vaccine or a cure and if so, when? When will our lives return to normal? I attempt to answer these questions in A Family Guide to COVID with honesty, clarity and compassion. A Family Guide to COVID is written especially for those who are faced with the difficult task of not only protecting themselves, but of protecting their families, their children, their spouses, and their 2693
parents. Download the book www.accessh.org/COVIDfamilyguide
for
free
here:
July 5, 2020 Economists, psychologists & historians agree: the long term economic impact of COVID-19 is not promising. Here are three articles that highlight the scope of the impact (1 of 3). https://www.theatlantic.com/politics/archive/2020/05/lifeafter-coronavirus-china-denmark-southkorea/611011/?utm_source=atl&utm_medium=email&utm_camp aign=share The psychology of a generation of young adults whose expectations have changed fundamentally, dislocations in supply chains, globalization, and mountains of government debt will slow global economic growth for decades (article 2 of 3). https://www.washingtonpost.com/business/2020/07/05/coro navirus-pandemic-trust-government These reports all tell the same story albeit from diverse viewpoints. Our questions are how do we plan for our own future, that of our grown children and how do we help our grandchildren live in this altered world (article 3 of 3). https://www.washingtonpost.com/business/2020/07/02/cboeconomic-outlook/ COVID-19 is about to inflict another great hardship on people across the country. The dramatic increase in infections means that economic pain in the United States will continue for much longer than anticipated. https://www.bloomberg.com/news/articles/2020-0701/black-renters-in-boston-face-highest-eviction-risk A heartbreaking story, one I fear is common to many countries with no voice to speak to the world. https://www.washingtonpost.com/world/2020/07/02/wefeel-absolutely-abandoned-how-pandemic-russia-tankedeconomy-plunged-families-into-crisis/ In the absence of strong central government, the responsibility falls to state governors to set policy. If governors won't lead, local authorities must do the job, though some governors are restricting the ability of mayors to do what they think is best. 2694
https://www.bloomberg.com/news/articles/2020-07-01/howstates-co-opted-local-power-during-coronavirus How will we educate our youth? July is the month that parents, teachers, mayors, and governors must begin to answer this question. Here is the answer from Harvard and some other universities. It is NOT business as usual. https://www.harvardmagazine.com/2020/07/harvard-allows40-percent-of-undergraduates-return-fall-semester Please see this short interview I gave as part of a series on COVID-19 healthcare leaders and innovation. https://www.linkedin.com/posts/erik-ilyayevb9795084_healthcareinnovation-COVID-healthcareleadersactivity-6685924178152980480-CHk3 COVID-19 is rapidly changing the way we live and our philosophy of life. The effects will be long lasting, possibly generational. See this thoughtful article in the Boston Globe. https://www.bostonglobe.com/2020/07/05/nation/if-i-dienow-have-i-lived-life-i-wanted/?s_campaign=8315 July 8, 2020 Deep brain damage in 4 out of 4 SARS-C0V-2 infected children. The lesions can cause loss of speech and coordination and mental confusion. Other viral infections (HIV, rotavirus, influenza) can sometimes cause similar damage. Those with symptoms get MRIs. https://jamanetwork.com/journals/jamaneurology/fullarticle/2 767979 Since the start of the COVID-19 pandemic, I have been asked many questions: When will this be over? Will there be a vaccine or a cure and if so, when? When will our lives return to normal? I’m a medical scientist with children and grandchildren, and I do my best to answer their questions, even with the answers changing from day to day as we learn more about this virus. My new bestselling book, A Family Guide to COVID, is a practical tool to help families navigate life during this confusing time. It will be updated with new information as we learn new things to help you and your loved ones stay safe. Gain free access to the ebook, and to each new edition, from our website. You can also order it from Amazon. www.accessh.org/COVIDfamilyguide 2695
https://www.amazon.com/Family-Guide-COVID-WilliamHaseltine-ebook/dp/B08C95DPQM/ July 9, 2020 Even if our path to a COVID vaccine is much longer and harder than we currently estimate (which I fully expect), the science is promising for drugs to keep those most vulnerable from becoming infected and, potentially, treat those already ill. While we wait, we must use what we know for certain will work today -- masks, physical distancing and quarantine -- to reduce lives lost unnecessarily. https://www.cnn.com/2020/07/08/opinions/COVID-19treatment-reason-for-hope-haseltine/index.html Wearable technology to help with early detection of COVID19 has its flaws. However, if it helps us catch even a small percentage of cases before symptoms become full-blown, we should pursue it. https://www.forbes.com/sites/williamhaseltine/2020/07/09/is -wearable-technology-the-savior-weve-been-waitingfor/#1961fa823817 July 10, 2020 Parents are already thinking about fall school. Many panic when they realize that there is no uniform standard for public schools and are uncertain whether or not it is safe for their children, including high school students, to return to class. https://www.huffpost.com/entry/teachers-parents-schoolsreopening-bad-newscoronavirus_l_5f061f44c5b6480493ca9645?utm_campaign=share_e mail&ncid=other_email_o63gt2jcad4 A sad story on the effects of COVID-19 on child nutrition and health in the United States. Programs to assist those seriously affected by the pandemic do not reach all those in need. https://www.huffpost.com/entry/14-million-children-goinghungrycoronavirus_n_5f07777cc5b6480493cd5e87?ncid=engmodushpmg 00000006 We look to the CDC for clear, credible information to guide our response to disease outbreaks. Today, they are sidelined. States 2696
and local communities are left to decide policies according to the priorities of local leaders. https://www.washingtonpost.com/health/trump-sidelinespublic-health-advisers-in-growing-rift-over-coronavirusresponse/2020/07/09/ad803218-c12a-11ea-9fddb7ac6b051dc8_story.html Pregnancy may increase risk of SARS-CoV-2 infection and subsequent illness. The risk to the fetus is uncertain. Another study found SARS-CoV-2 in umbilical cord blood suggesting the potential for in utero maternal-child transmission. https://www.cdc.gov/mmwr/volumes/69/wr/mm6925a1.htm July 11, 2020 The NBA announced that 16 of its players have tested positive for COVID-19, and 40 Major League Baseball players are infected. Even with precautions in place, sports are inherently high risk events. Is it too soon to be restarting? https://www.forbes.com/sites/williamhaseltine/2020/07/10/is -it-too-soon-to-restart-sports/#514d729c1823 July 12, 2020 Are you attempting to make sense of all the mixed information and advice available about life in the time of COVID-19? Has it been hard for you to know what you can do to protect your family? In my newest, bestselling book, A Family Guide to COVID, my team and I have been collecting common questions which I attempt to answer honestly and with compassion. This book is a living project--I will update the answers as we get new information about this virus, and how to keep you and your loved ones safe.Download the book for free here: https://lnkd.in/gi2T9qd Also available on Amazon: https://lnkd.in/d8MvWGN July 13, 2020 An excellent reference for the probability of transmission -- it is 20 times higher indoors compared to outdoors, yet transmission may still occurs outdoors in close proximity to another. https://www.medrxiv.org/content/10.1101/2020.02.28.20029 272v2 2697
Insight into school reopenings. Note the risk to high school students & Israel's cautionary tale. The successes all have 1 commonality: the level of infections were very low when schools reopened, not surging like in the US today. https://www.washingtonpost.com/world/europe/schoolsreopening-coronavirus/2020/07/10/865fb3e6-c122-11ea-890868a2b9eae9e0_story.html July 14, 2020 We can stop this coronavirus dead in its tracks by wearing masks, not by hoping for herd immunity. Studies are showing that the body’s protective immune response isn’t preventing people from being reinfected. https://www.cnn.com/2020/07/13/opinions/herd-immunityCOVID-19-uncomfortable-reality-haseltine/index.html Peter Orszag's predictions on economic recovery. He writes in Bloomberg News that the COVID “fear factor” has and will retard economic recovery, regardless of the pace of pandemic control (which at present is poor in most countries). https://www.bloomberg.com/opinion/articles/2020-0713/COVID-fear-will-keep-the-world-in-a-slump July 15, 2020 Houston Matters interviewed me about my newest book, A Family Guide to COVID. We also talk about the importance of strong and compassionate leadership in a time of crisis, how to navigate the confusing and upsetting information circulating, and some of my background in science. https://www.houstonpublicmedia.org/articles/shows/houstonmatters/2020/07/13/377899/special-edition-scientist-dr-williamhaseltine-july-13-2020/?utm_source=rss-houston-mattersarticle&utm_medium=link&utm_campaign=hpm-rss-link A clear warning of what may be our future. Let’s all work together to do what must be done. https://www.nytimes.com/2020/07/14/opinion/coronavirusshutdown.html?smid=em-share COVID data is available by zip code in many states. That, and the zip codes of those who you associate with at work or school, 2698
may be the most relevant information you need to know your risk— rather than your age and underlying health status. https://www.bostonglobe.com/2020/06/25/nation/graphicswhere-coronavirus-is-spikingus/?s_campaign=breakingnews:newsletter July 16, 2020 This is a MUST READ interview with Ken Frazier, CEO of Merck, summarizing his thought on COVID vaccine development and race in America. His perspectives are unique and profound. This is a voice that must be heard. https://hbswk.hbs.edu/item/merckceo-ken-frazier-speaks-about-a-COVID-cure-racism-and-whyleaders-need-to-walk-the-talk July 18, 2020 In this podcast, I speak with Dr. Azizzadeh about vaccines, therapeutic treatment and what we can learn from the HIV crisis. https://podcasts.apple.com/us/podcast/coronavirus-updatewith-dr-william-haseltine/id1510060367?i=1000485184838 July 19, 2020 Vaccine development is complex, and especially so with SARSCoV-2 due to how this virus interacts with the human immune system. Yet forward progress is being made, as Moderna’s announcement on Tuesday indicates. Positive as the trial results are, there remains much uncertainty about whether a vaccine will work at all against COVID-19, which I explain in detail here. https://www.forbes.com/sites/williamhaseltine/2020/07/16/w hat-does-disappearing-immunity-to-COVID-19-mean-for-avaccine/#35ad745149ed How do I care for someone who is sick with COVID? If possible, they should be isolated in a hotel room or another location where they can recover. If it does fall to you to take care of someone sick with COVID, the chances you will be infected are extremely high. If they’ve consulted a health provider themselves, or if you’ve consulted a health provider for them (e.g. for your child), you’ll need to help them follow any instructions given and pick up any medications prescribed, in addition to suggested over-the-counter 2699
medicines. Make sure they’re consuming a lot of fluids, getting a lot of rest, and staying away from pets if you have any. Learn more practical ways to deal with COVID-19 in your life with my book, A Family Guide to COVID. In it, I attempt to answer the most common questions with honesty and compassion, updating the answers as our understanding of this virus unfolds. Download the book for free here: www.accessh.org/COVIDfamilyguide Also available on Amazon: https://www.amazon.com/FamilyGuide-COVID-William-Haseltine-ebook/dp/B08C95DPQM/ July 20, 2020 Retreating from WHO in the middle of a pandemic dishonors and endangers healthcare workers at home and around the globe. http://ow.ly/y44Y50AD7wA Behavior at bars is one of the reasons many states are closing them. The chart in this article shows the % of people seeking tests who are positive. Any fraction above 2-3% is worrisome. Above 5% is scary. Above 20% is a harbinger of very grave trouble. https://www.cbc.ca/news/health/coronavirus-canada-barsreopening-1.5652671 Please see this insightful analysis comparing the mentality of the French government and leadership during the phony war (the period between the German invasion of Poland and the conquest of France) and that of the US facing COVID-19. https://www.foreignaffairs.com/articles/united-states/202007-20/strange-defeat-united-states Why, in midsummer 2020, is COVID-19 still raging across the US when it was so quick to leave other parts of the world? The answer is clear: the US containment strategy has lacked leadership, governance and social solidarity. https://www.thinkglobalhealth.org/article/midsummer-seasonnot-coronavirus With eight COVID-19 vaccine candidates already in human trials and almost 180 more in the wings, how are we to understand what each new finding means for our children, our jobs, our economies, and a world in crisis? We can begin by listening for a moment to Ken Frazier, CEO of Merck, a company that has brought numerous life-saving vaccines to market. 2700
https://www.forbes.com/sites/williamhaseltine/2020/07/20/akey-to-understanding-the-race-for-a-COVID-19vaccine/#50e1dffc7fcb July 21, 2020 Earlier this week I spoke with CNN’s Don Lemon on the risk of letting children return to school in the fall when we are still attempting to contain COVID-19. https://www.cnn.com/videos/us/2020/07/21/missouri-govkids-return-to-school-sot-haseltine-ctn-vpx.cnn July 22, 2020 Some people with COVID-19 have alarmingly low blood oxygen levels which can cause shortness of breath, chest pain, confusion and a rapid heartbeat. But early in the disease, it may not be obvious that your oxygen level is low, which can put you at risk. Fortunately, you can test your own oxygen levels at home with a pulse oximeter. https://www.youtube.com/watch?v=ST-j95fdsYg Dating has become extra challenging during this pandemic. It may feel awkward wearing a mask and keeping your distance when you are meeting someone new, but it is important to remain cautious. https://www.youtube.com/watch?v=efTHqk5euGE Ever since COVID-19 first began to spread, the question of how many people are infected with the disease has remained difficult to answer. Official case counts, it is widely acknowledged, represent only the tip of the iceberg—a gap in our knowledge even more felt today, now that the virus is ten times as transmissible as earlier strains. Recent studies suggest that COVID-19 might be more far spread than previously thought and further verify that social inequalities are a factor in infection rates. To put a stop to this pandemic, we need to intensify our focus on reducing infections in marginalized and low-income populations. https://www.forbes.com/sites/williamhaseltine/2020/07/22/C OVID-19-might-be-far-more-widespread-than-we-think-hereswhat-we-can-do-about-it/#6d865d6a3d53
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July 23, 2020 Recent studies suggest that COVID-19 might be more widespread than previously thought. They also show that social inequalities are a factor in infection rates. To put a stop to this pandemic, we need to focus on reducing infections in marginalized and low-income populations. https://www.forbes.com/sites/williamhaseltine/2020/07/22/C OVID-19-might-be-far-more-widespread-than-we-think-hereswhat-we-can-do-about-it/#6d865d6a3d53 This article shows why existing trials of new COVID drugs/vaccines fail to meet the fundamental criteria to determine how effective they will be. Those developing new therapies must be rigorous in their approach so we know what works and how well it works. https://jamanetwork.com/journals/jama/fullarticle/2765696?ut m_source=undefined&utm_campaign=contentshareicons&utm_content=article_engagement&utm_medium=soci al&utm_term=072220#.XxjIQG_2Dy4.email How do I know if I should remove my parent or spouse or grandparent from their nursing home? The only answer I can offer to this difficult question is: it depends. Both the CDC and AARP have cautioned against moving older adults out of nursing homes and long term care facilities since the process could unnecessarily expose them to infection. Even so, the decision should ultimately be made on a case by case basis by the resident and their loved ones. Do you have more questions about COVID-19? Download my book, A Family Guide to COVID to get answers to common questions about the evolving pandemic from me and my team at ACCESS Health International. Download the book for free here: www.accessh.org/COVIDfamilyguide Also available on Amazon: https://www.amazon.com/FamilyGuide-COVID-William-Haseltine-ebook/dp/B08C95DPQM/ July 24, 2020 Historically, two conflicting trends have shaped how France manages public health crises. But in the face of COVID-19, they 2702
were able to reach a resolution. This fascinating article contains many lessons for those countries willing to learn. https://www.thelancet.com/journals/lancet/article/PIIS01406736(20)315993/fulltext?dgcid=raven_jbs_etoc_email#.XxrAXjdVNj8.email COVID-19 is unlikely to be the last pandemic in this century. What are the most successful features of China’s response to COVID-19 that may assist other countries now and in the future? https://www.thelancet.com/journals/lancet/article/PIIS01406736(20)316378/fulltext?dgcid=raven_jbs_etoc_email#.Xxq_imnRsDU.email July 25, 2020 While many aspects of COVID-19—from its symptoms to its duration to its short- and long-term aftereffects—remain difficult to pin down, we now have enough data to identify four broad stages of infection that can guide us going forward. https://www.forbes.com/sites/williamhaseltine/2020/07/24/t he-complex-pathogenesis-of-COVID-19/#667dfc272c33 July 26, 2020 If I’m pregnant, what can I do to protect myself and my baby throughout my pregnancy? More than ever, it is important for you to seek out and keep up your prenatal care plan. Talk to a health provider about creating an appointment schedule and care routines that are right for you and your baby. In addition to observing more general safety guidelines like social distancing and frequent handwashing, you will need to make an extra effort to limit physical exposure to others, especially strangers. I answer more questions about pregnancy in the time of COVID in my new book, A Family Guide to COVID. Download the book for free here: www.accessh.org/COVIDfamilyguide Also available on Amazon: https://www.amazon.com/FamilyGuide-COVID-William-Haseltine-ebook/dp/B08C95DPQM/ July 27, 2020 2703
It's time to end COVID profiteering. Publication by press release & selectively leaked “data” to support insider stock sales and corporate fundraising is nothing more than pandemic profiteering. What we see today for anti-COVID vaccines we will see tomorrow for companies touting antiviral COVID drugs. https://www.nytimes.com/2020/07/25/business/coronavirusvaccine-profits-vaxart.html?smid=em-share There are 4 predictable and preventable COVID epidemics. The most difficult to contain is among poor working-class minorities who must work. Social programs (guaranteed income) are needed to counter this trend around the country. This is the aspect of COVID-19 that I fear we will be the slowest to confront. https://www.washingtonpost.com/opinions/2020/07/22/howcalifornia-went-coronavirus-success-story-disaster-how-it-canregain-control/ July 28, 2020 I spoke with James Shaw on his Positively Dad podcast about the “back to school” season in the era of coronavirus. We cover some of the critical issues to consider as parents wrestle with the difficult decision of sending kids to school this fall. https://positivelydad.com/podcast/back-to-school/ July 29, 2020 India is stepping up testing protocols: An inexpensive and fast antigen test identifies at least half of people infected, and those who test negative get the more sensitive (and more expensive) test. This helps identify those who weren’t presenting enough virus to show up as negative in the antigen test. This is a model to watch. https://www.forbes.com/sites/williamhaseltine/2020/07/28/in dia-approves-antigen-test-to-speed-detection-and-management-ofsars-cov-2-infections/#1d455de54626 This article highlights the seriousness and the complexity of the COVID-19 epidemic in the United States. It is not one response but a series of well thought out coordinated actions needed to control what are now multiple epidemics. https://www.nytimes.com/2020/07/29/health/coronavirusfuture-america.html?smid=em-share 2704
A new CDC report explores improved services to underserved minorities—Native Americans, Blacks, and Hispanics—such as improved data collection, testing, contact tracing, quarantine, isolation, and treatments. https://www.modernhealthcare.com/safety-quality/us-agencyvows-steps-address-COVID-19-inequalities This article highlights the need to strengthen our primary healthcare system: increasing investment in primary care above 5%, strengthening supportive technologies & telehealth, opening data silos, & using prospective payments for primary care services https://www.modernhealthcare.com/opinioneditorial/COVID-19-exposes-flaws-our-primary-care-system July 30, 2020 For those who would like an “inside baseball” discussion of COVID-19 vaccine prospects, please see this recent Nature Magazine analysis. https://www.nature.com/articles/d41586-020-02174-y Please see this well informed and thoughtful review in @latimes of what we may expect from the first generation of COVID-19 vaccines. http://enewspaper.latimes.com/infinity/article_share.aspx?guid =9e602b67-7579-40ff-a035-2ec71029f27b Young people may be driving the very high numbers of seniors infected in the sunbelt. Many in their twenties live in households with grandparents and other adults. Even though the young do not suffer obvious symptoms they may infect others who may fall ill and sometimes die. https://www.washingtonpost.com/health/youngpeople-are-infecting-older-family-members-in-sharedhomes/2020/07/28/b8cdc810-cd0a-11ea-b0e3d55bda07d66a_story.html July 31, 2020 This study gave rise to the headlines saying students can safely return to college if tested every 2 days. The authors actually wrote: "symptom-based screening alone was not sufficient to contain an outbreak [safe reopenings] may require screening every 2 days, uncompromising vigilance, and continuous attention to good prevention practices." 2705
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August 3, 2020 Whatever we're doing here to control COVID isn't working. This piece highlights the urgent need to reset national & regional efforts. The recommendations are also valid for countries where the virus is raging or on the upsurge, like Europe and much of Asia. https://www.washingtonpost.com/health/coronavirus-threatrises-across-us-we-just-have-to-assume-the-monster-iseverywhere/2020/08/01/cdb505e0-d1d8-11ea-8c5561e7fa5e82ab_story.html Some call SARS-CoV-2 the China virus for its origins but it's now a plague of the Americas. All the hotspots, except for South Africa and India, are in the Americas. Almost twice as many people in the US have died of COVID as have been infected in China. The number of newly diagnosed on July 31: 66,364 USA, 45 China. https://www.nytimes.com/interactive/2020/us/coronavirusus-cases.html?smid=em-share This story helps people estimate the risk of COVID at schools. In my new COVID Back To School Guide, I discuss risk hierarchy: 1. What is our risk of becoming infected? 2. What is our risk of severe illness? 3. Is my school doing enough to protect students? https://www.nytimes.com/interactive/2020/07/31/us/corona virus-school-reopening-risk.html?smid=em-share August 4, 2020 How do I know if my child is infected with the COVID virus? If your child has developed cold symptoms and you think it might be COVID, call a doctor, preferably one who already knows your child’s medical history. Schedule a telehealth visit if possible so your child can be examined without leaving your home. Make sure the child is resting and getting enough fluids. For the most up-to-date list of COVID symptoms, visit the U.S. Centers for Disease Control and Prevention Website. For more current information about how to deal with COVID19, especially if you are caring for children or grandparents, check out my living book, A Family Guide to COVID. Download the second edition for free here: www.accessh.org/COVIDfamilyguide
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Also available on Amazon: https://www.amazon.com/FamilyGuide-COVID-William-Haseltine-ebook/dp/B08C95DPQM/ August 6, 2020 Can dangerous blood clots form in people with no or mild symptoms? Yes. Young adults as well as older people have been admitted to the hospital for heart attacks and stroke as a result of infection. They may not know they are infected until they are tested in the hospital. My bestselling book, A Family Guide to COVID, addresses common questions which I attempt to answer honestly and with compassion. This book is a living project—we just released the second edition with updated answers based on the evolving information we have about this virus and how to keep you and your loved ones safe. Download the second edition for free here: www.accessh.org/COVIDfamilyguide Also available on Amazon: https://www.amazon.com/FamilyGuide-COVID-William-Haseltine-ebook/dp/B08C95DPQM/ Children may be one of the most significant drivers of the pandemic. Although they may not experience many, or any, symptoms, they have 10-100 times the amount of the virus in their system, and so are as or even more contagious than adults when sick. https://www.forbes.com/sites/williamhaseltine/2020/07/31/n ew-evidence-suggests-young-children-spread-COVID-19-moreefficiently-than-adults/#dd728dc19fdc August 7, 2020 In this piece, one of our ACCESS Health interns in Italy shares her experience of traveling in Europe during the coronavirus outbreak. https://medium.com/@williamahaseltine/travel-from-milanto-arles-reflections-on-COVID-44c7a4ad6a09 A summary of @drsanjaygupta’s Interview of Anthony Fauci as Part of the Harvard Chan School of Public Health’s COVID series. https://news.harvard.edu/gazette/story/2020/08/there-are-5easy-steps-to-tame-COVID-19-says-fauci/ Parents are wondering whether or not to send their kids back to school. This isn’t an easy decision. Our new book, A COVID Back to School Guide, offers some framework for making this decision. 2709
www.accessh.org/COVIDfamilyguide August 9, 2020 How much virus does a cough or sneeze release into the environment? When someone sick with COVID coughs, about 3,000 virus-laden droplets fly out of their mouth at a speed of 50 miles per hour. When they sneeze, ten times as many droplets are released at four times the speed. The droplets themselves can contain hundreds of millions of virus particles that, once unleashed, flood their surrounding environment. This is why wearing a mask and covering your mouth and nose when you cough and sneeze is no small matter. In my bestselling book, A Family Guide to COVID, I answer common questions about COVID-19 as honestly and compassionately as I can. And, I update the answers as I receive new information. Download the second edition of the book for free here: www.accessh.org/COVIDfamilyguide Also available on Amazon: https://www.amazon.com/FamilyGuide-COVID-William-Haseltine-ebook/dp/B08C95DPQM/ August 11, 2020 Please see this excellent firsthand account of an American -- and father to two small children -- who taught at Sichuan University in Chengdu, China during the epidemic. Many Americans abroad are puzzled and deeply distressed by the US pandemic response. https://www.newyorker.com/magazine/2020/08/17/howchina-controlled-the-coronavirus?utm_source=onsiteshare&utm_medium=email&utm_campaign=onsiteshare&utm_brand=the-new-yorker Please see this summary of an insightful interview with Anthony Fauci conducted by medical correspondent Sanjay Gupta as part of the Harvard T.H. Chan School of Public Health's COVID Series. https://news.harvard.edu/gazette/story/2020/08/there-are-5easy-steps-to-tame-COVID-19-says-fauci/ August 12, 2020 Is it easy to catch the disease from objects? Technically, yes. If droplets containing the SARS-2 virus end up on a doorknob, railing, 2710
countertop, phone, toilet, or any number of other surfaces, they could stay there for hours or even days.28 How long they survive depends on the type of material and other extraneous circumstances, like the weather. Transmission through objects, however, is not the main way the virus spreads.29 The main way is through close contact with people who have it.In my living book, A Family Guide to COVID I answer the most critical COVID questions of the day. You can download subsequent editions freely, so you can be certain to have the most up to date information about this pandemic as it unfolds. Download the second edition of the book for free here: www.accessh.org/COVIDfamilyguide Also available on Amazon: https://www.amazon.com/FamilyGuide-COVID-William-Haseltine-ebook/dp/B08C95DPQM/ August 15, 2020 A low-income, Latino high school student who lives in a COVID-19 hotspot penned an op-ed for the New York Times detailing his frustrations and concerns with premature school reopenings. It's well worth the read. ttps://www.nytimes.com/2020/08/13/opinion/COVIDschool-reopening-student.html This article gives a clear overview of all the vaccines currently in development around the world, showing the different types and how much progress has been made with each. The graphics are superb! https://www.washingtonpost.com/graphics/2020/health/CO VID-vaccine-update-coronavirus/ It will cost an additional $1.77M per school district to safely reopen. This chart shows the breakdown. In our new book, A COVID Back to School Guide, we discuss the many considerations parents and administrations are wrestling with in the very difficult question of reopening schools. www.accessh.org/COVIDfamilyguide August 16, 2020 Let’s use what we’re learning with the spread of COVID cases in the bubble of Major League Soccer and other sports despite the levels of caution being taken to protect players and staff. The same could happen when we reopen schools. Our children’s and 2711
communities’ health and wellbeing should come first. https://www.forbes.com/sites/williamhaseltine/2020/08/14/what -restarting-sports-and-reopening-schools-have-incommon/#1809b778ae38 August 17, 2020 The purpose of population testing is to limit contagion-transmission is too soft a word. We need population-based testing with fast, inexpensive tests. PCR is testing with the intent to manage those with active infection and to treat, not control contagion. https://www.nytimes.com/2020/08/15/us/coronavirustesting-decrease.html?smid=em-share Low wage workers are among the most affected by COVID, driving infections in many parts of the US and the world. But these workers can't just stop working & traveling, as many work to eat. Infection of any group is a risk for all. Ignoring their plight perpetuates the personal, economic, & psychological damage of the pandemic. https://www.latimes.com/california/story/2020-0815/coronavirus-workers-retaliation-claims The technology exists to allow every US citizen to use a rapid home test to determine if they or their children are contagious. This @TheAtlantic essay outlines the technologies that can make that a reality. https://www.theatlantic.com/health/archive/2020/08/howto-test-every-american-for-COVID-19-everyday/615217/?utm_source=atl&utm_medium=email&utm_campaig n=share This is what can happen if we are able to reduce the number of contagious people in a community. There may still be contagions at schools when they reopen in New York as some parts of Manhattan have a much higher COVID-19 incidence than others. https://www.bostonglobe.com/2020/08/16/nation/beatingback-COVID-19-new-york-emerges-leader/?s_campaign=8315 August 18, 2020 Case in point for the danger of in-person college in an orange zone-- can not be done safely! Neither can back to work under most circumstances. 2712
https://www.washingtonpost.com/local/education/unc-chapelhill-coronavirus-cluster/2020/08/17/8ebce060-e0ab-11ea-8181606e603bb1c4_story.html See this story on the pending reform of the British Public Health System because of its failures. Alas, there is no immediate prospect for reform of the US public health system which has fared very much worse. https://www.telegraph.co.uk/politics/2020/08/15/hancockaxes-failing-public-health-england/ New findings show high incidence of cardiac abnormalities in COVID infected asymptomatic people. Other studies showed twothirds of asymptomatic people had ground glass lung opacities and declines in athletic performance. Asymptomatic no longer means “without evidence of bodily harm". ttps://www.forbes.com/sites/robertglatter/2020/08/17/COVI D-19-can-cause-heart-damageeven-if-you-areasymptomatic/#681810dd6cef August 19, 2020 Parents are struggling with the decision about whether or not to send their children back to school. In our new book, we offer a framework for decision-making. One consideration is: How good is the contact tracing in your area? We go into more detail about what contact tracing is and how to find out about it in your area in A COVID Back to School Guide. ww.accessh.org/COVIDfamilyguide August 21, 2020 How can schools for young children reopen safely? The answer to this question varies from place to place, and even from school district to school district. Only when the level of new cases in a community is either very low—less than ten cases per day for a large city—should schools reopen. Many people think that children aren’t easily infected, which isn’t actually the case. Young children may not fall ill as often as adults, but that doesn’t mean they can’t become very sick or spread the disease far and wide. Plus, kids older than the age of 10 have the same chance of being infected as young adults. If you are a parent concerned about school starting this fall, download A COVID Back to School Guide. It contains answers to 2713
the most common questions about COVID and is updated as our understanding of this virus grows. Download the book for free here: www.accessh.org/COVIDfamilyguide August 24, 2020 Rapid and inexpensive testing that can be done at home could help us contain the spread of COVID-19--and the technology already exists. Now we need to invest in it. https://www.forbes.com/sites/williamhaseltine/2020/08/17/c heap-daily-home-tests-are-the-first-step-to-containing-thepandemic/#2ea252d94ad4 The humid air inside gyms and locker rooms, which can hold the virus from people’s exhales for as long as 3 hours, may not be a safe environment for working out. Try some of these alternatives to stay healthy during the pandemic. https://www.psychologytoday.com/us/blog/best-practices-inhealth/202008/will-reopening-gyms-improve-our-wellbeing-orput-it-risk In his personal essay @Sammy_Roth shares wise words on managing emotions during difficult times while continuing the work needed to improve our situation “It is not your responsibility to finish the work of perfecting the world, but you are not free to desist from it either.” https://www.latimes.com/environment/newsletter/2020-0820/boiling-point-california-broiling-burning-boiling-point If the threat of COVID to the lungs is not enough to worry you (two-thirds with asymptomatic infections have ground glass abnormalities in at least one lung and almost all hospitalized have residual lung fibrosis) these images of vaping induced lung disease are. Help friends & children STOP VAPING immediately. ttps://www.thelancet.com/journals/lancet/article/PIIS01406736(20)31755-4/fulltext?dgcid=raven_jbs_etoc_email August 26, 2020 This candid interview with Bill Gates is well worth watching for his discussion of drugs and vaccines in the pipeline, thoughts on the timing of the end of the pandemic, the muzzling of the CDC and NIH by the government, the craziness of Fox News and more. 2714
https://www.wired.com/story/bill-gates-on-COVID-most-ustests-are-completely-garbage/?utm_source=onsiteshare&utm_medium=email&utm_campaign=onsiteshare&utm_brand=wired One of the biggest challenges we have is in describing the magnitude of short, medium, and long term culture change in the US and globally as a result of COVID. Here is an unexpected dimension of cultural change. https://www.ft.com/content/596e49d9-1283-47b3-a7711c0beebd7df5 A key antibody test reference. The focus is on using these tests to detect contagious individuals. They aren't well-suited to detect those currently contagious as antibodies often appear after one is no longer infectious. But tests can help manage later stages of COVID19. https://www.idsociety.org/practice-guideline/COVID-19guideline-serology/ Many of us wonder what life will be like after COVID-19. According to this Forbes story, if you were happy with your life preCOVID-19, you are likely to be happy with your post-COVID-19 life too! Is the converse also true? https://www.forbes.com/sites/mariellaattard/2020/08/22/ifyou-were-satisfied-with-your-life-before-youll-probably-bounceback/#8624dd76bd3f August 28, 2020 Please see this regarding the FDA emergency use authorization of convalescent plasma for treatment of COVID-19, The data show no beneficial effect for most. The significance of the reported improvement of the small fraction of patients who began in-hospital treatment within three days of first symptoms is uncertain as there was no control group with which to compare the data. https://www.nytimes.com/2020/08/24/health/fda-bloodplasma.html August 29, 2020 A COVID Back to School Guide: Parents and students today are faced with an agonizing decision-send kids back into the classroom in the midst of a pandemic or keep them at home, straining the 2715
emotional bandwidth of families that have already been pushed to the limit during lockdown. Read this e-book by William A. Haseltine available on Amazon: https://amzn.to/3baTsbZ August 31, 2020 If the federal government decides to fast track vaccines to market, what would be the damage? The most immediate and obvious answer is that vaccines would be untested, unproven, and potentially harmful. The longer and more frightening outcome could be the public’s loss of trust in vaccines. https://www.forbes.com/sites/williamhaseltine/2020/08/27/d eregulating-COVID-19-treatment-sets-dangerous-precedent-forvaccine-approval/#63961dde7486 In the first two weeks of August, 75,000 new COVID cases were diagnosed in children. This comes as school districts around the country are faced with the decision about reopening. As it turns out, six in ten voters oppose reopening K-12 schools in their states, while as many as 81% urge the prioritization of health among students and faculty over the economy. https://www.forbes.com/sites/williamhaseltine/2020/08/21/w hy-most-voters-oppose-schools-reopening/#1b1282031822 Please join me tomorrow as I talk about the long term impact of COVID-19 on brain health as part of the Aspen Brain Institute’s virtual Expert Series. I will be joined by Dr. Doren Madley Pinnell. 6pm ET. Please register now for free: https://bit.ly/ABI-Experts
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September 2020
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September 1, 2020 Mandatory school and workplace wastewater testing must be coupled with mandatory reporting of all COVID-19 test results. Doing so will bring us one step closer to understanding the risks COVID-19 poses to our places of work and learning. https://www.forbes.com/sites/joshuacohen/2020/09/01/predi cting-a-COVID-19-outbreak-with-wastewateranalysis/#f520ffa18dc6 September 2, 2020 What went wrong with the U.S. – China relations? Should and can they be made right again, and how? Since 2011, the U.S.China Health Summit has been working to promote win-win collaboration in the health and healthcare space. Please join us at 9pm ET for an important discussion on collaboration between these two great nations. Register here: https://us02web.zoom.us/webinar/register/WN_O6t41uWSQou XzhJVTND3jg Here Jasmyn Ward, a writer, offers a personal testament to the compounded loss in this troubled time— loss from COVID and the continued, almost daily, reminder of injustice in America. https://www.vanityfair.com/culture/2020/08/jesmyn-wardon-husbands-death-and-grief-during-COVID?utm_source=onsiteshare&utm_medium=email&utm_campaign=onsiteshare&utm_brand=vanity-fair Spain shifted responsibility for their COVID response to the provinces which may explain why Spain is doing much worse than other European countries. While most are seeing a resurgence in cases, it is not as severe as Spain’s. Time will tell if European countries who retain central control will fare as badly. https://www.ft.com/content/947d94aa-abdd-456d-85bc363d64520869 Track the coronavirus pandemic in Massachusetts to its roots and you find a story driven by heroics, ingenuity, error, pain, and a hard question: How could a state famous for health care excellence have suffered such a vast loss of human life? https://apps.bostonglobe.com/metro/graphics/2020/05/coron avirus-tale/ 2718
An excellent summary of the social-psychic impact of COVID19 on parents. The piece highlights an important aspect of the pandemic: the moral trauma and PTSD people living through it experience. https://www.aljazeera.com/indepth/features/postpartumdepression-survivors-pandemic-parenting-200601140348340.html PCR based COVID testing in the US now focuses on the worried and the ill. We should focus instead on those who may be contagious. I estimate that we miss 90% of those who are actively contagious. A rapid, simple, salvia based and assisted isolation is the answer to COVID control, American style. https://www.nytimes.com/2020/08/29/health/coronavirustesting.html?smid=em-share A disturbing trend in the US with a rapid increase in COVID infections, hospitalizations, & deaths in kids. This comes amid new reports that very young children have a lower case morbidity and mortality rate than older children or adults. While this may be true, we must remember that young children are not immune to this disease. https://www.nytimes.com/interactive/2020/08/31/us/corona virus-cases-children.html?smid=em-share Here Jasmyn Ward, a writer, offers a personal testament to the compounded loss in this troubled time— loss from COVID and the continued, almost daily, reminder of injustice in America. http://ow.ly/dRqK50BgbMn September 3, 2020 Catching asymptomatic spreaders of COVID-19 is a crucial tool for slowing the spread of the pandemic. It is unclear why, then, the CDC has released new guidelines that excludes testing for anyone who has come into contact with a known carrier of the disease. With the reopening of schools and businesses, this new guideline will accelerate the spread. https://www.forbes.com/sites/williamhaseltine/2020/08/31/n ew-cdc-guidelines-decrease-testing-for-those-who-need-itmost/#148131626515
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September 4, 2020 Today at 9pm ET, I will be the keynote speaker for a special webinar: U.S. vs China: Confrontation vs Collaboration. Since 2011, the U.S.-China Health Summit has been working to promote win-win collaboration in the health and healthcare space, and in this webinar, we will be discussing what went wrong with the U.S. – China relations, and whether they can be made right again. Please join us for this important discussion. Register Now: https://us02web.zoom.us/webinar/register/WN_O6t41uWSQ ouXzhJVTND3jg September 5, 2020 There is a strategy for containing COVID-19 that would bring an end to the pandemic in the United States without a vaccine or drug therapy. It is cost-effective, compatible with American values, and needs only two to three months to take effect. Read more here: https://dailyclout.io/containing-COVID-american-style/ September 8, 2020 Please see this discussion in @washingtonpost on the long term social effects of COVID -19 on the housing market in the United States. Will the effect be similar in European countries that are seeing a resurgence in COVID cases? https://www.washingtonpost.com/opinions/the-housingmarket-is-roaring-now-here-are-the-worries-thatreveals/2020/09/04/6e62f058-eedd-11ea-b4bc3a2098fc73d4_story.html College re-openings are the source of increasing infections among students and local communities as well. College students in many areas resist school rules and advice and continue to socially mix. In this respect, they mimic the broader American population. https://www.nytimes.com/interactive/2020/us/COVIDcollege-cases-tracker.html?smid=em-share A short interlude with five gorgeous violin exercises. You will feel renewed, refreshed and hopefully remember that beauty is a much a part of human nature as self-interest. https://www.nytimes.com/2020/09/02/arts/music/fiveminutes-classical-music-violin.html?smid=em-share 2720
September 9, 2020 Digital technology can empower disease control measures and fulfill unmet needs of patients, doctors, and the public. Read our latest report with @RockefellerFdn to understand how digital solutions have helped to control spread of #COVID19 in China. https://www.rockefellerfoundation.org/report/tackling-COVID19-pandemic-through-integrating-digital-technology-and-publichealth Digital technologies play an instrumental role in the fight against #COVID19. From fast response, epidemiological studies, to longterm management, we looked at the role digital technology played in the fight with #COVID19 in their latest report, with the support of @RockefellerFdn https://www.rockefellerfoundation.org/report/tacklingCOVID-19-pandemic-through-integrating-digital-technologyand-public-health This is a good summary by Carl Zimmer in @nytimes describing some of the different types of COVID-19 vaccines under development as well as some of their advantages and disadvantages compared to those in advanced clinical trials. https://www.nytimes.com/2020/08/27/health/COVID-19vaccines.html?smid=em-share @WSJ published its analysis of the effect of COVID-19 on the banking system. The charts show the effects are profound. The health of the banking system is one measure of the health of the economy. The indications are worrying. https://www.wsj.com/articles/the-coronavirus-is-doing-weirdthings-to-the-banking-industry-11598779800 Unfortunately, as predicted, low-quality care and sloppy procedures in most nursing homes created an avoidable catastrophe. Without dramatic action, a second wave will likely wreak equal devastation. Federal regulatory guidelines are badly needed to save the lives of this older generation. https://www.nytimes.com/2020/09/05/opinion/sunday/coronavi rus-nursing-homes-deaths.html?smid=em-share This article highlights how knowing your risk depends upon knowing how likely you are to encounter a contagious person as you go about your daily activities. My book A COVID Guide to 2721
Back to School gives guidance on how to access the infection rates in your zip code and county. http://ow.ly/RZIU50BmhPo September 10, 2020 Relying on herd immunity to solve the COVID-19 crisis would result in a catastrophic death toll: 2- 7 Million more people could die with many more left with life long health complications. https://dailyclout.io/herd-immunity-a-reckless-andineffective-strategy/ Providing inexpensive, at-home testing and financial assistance to people who self-isolate following a positive test result would cost the nation only $55B and could end the epidemic here in the U.S. within 2-3 months. https://us.cnn.com/2020/09/04/opinions/how-we-cancontain-COVID-19-without-a-vaccine-hasletine/index.html The COVID Back To School Guide answers the most pressing question facing parents and students today—is it safe to go back to school? Like the Family Guide, the Back To School Guide will be updated as our understanding of the disease and the nature of the outbreak changes. The first edition of the book is focused primarily on public schools serving students from kindergarten to grade 12. https://accessh.org/COVIDfamilyguide/#backtoschool September 11, 2020 Approving treatments for emergency use for COVID-19 patients is important, but it’s critical that we not rush these approvals, only for the treatments to fail. In this article I outline steps that the FDA and others could take to improve the success rate. It’s essential we do this for the sake of the public’s trust in the medical field. https://www.forbes.com/sites/williamhaseltine/2020/09/09/t he-case-for-safer-emergency-use-authorizations/#534847307271 A new CDC report highlights why COVID-19 continues to spread. It is our social behavior, simply being in the presence of others, that spreads the virus. The analysis of risk hierarchy is very helpful. http://ow.ly/Fh8a50BonUy
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September 12, 2020 Drug company AstraZeneca's suspension of its COVID-19 vaccine clinical trials is a sign that any vaccine, rushed to approval, may prove dangerous to healthy individuals. Here’s what we know: https://www.forbes.com/sites/williamhaseltine/2020/09/09/w hy-astrazenecas-move-to-pause-their-vaccine-trialmatters/#6c39a46758e3 September 13, 2020 This article makes clear the complexities of premature approval of a product like convalescent plasma which is, at best, a stop-gap measure. Emergency Use Authorization will make it much harder to test products such as hyperimmune IgG or anti-SARS-CoV-2 monoclonal antibodies. http://ow.ly/dtp750Bqk4W We often demonize our enemies, as seen in our response to COVID. Arthur Amman, a veteran of our eternal struggle with dangerous microbes, projects himself into the "mind” of our viral opponents, exploring their needs and the natural forces that drive them. His conversation with 3 viruses, influenza, SARS-C0V-2, and HIV, are lessons in virology and of our relation to the natural world. http://ow.ly/FgUw50BqkpR September 14, 2020 AstraZeneca must reveal what stopped their COVID vaccine trail and clarify the reasoning behind restarting it. They say "patient confidentiality" prevents them but they can reveal salient details while maintaining confidentiality. This is the second instance of what appears to be a rare malady, transverse myelitis, in vaccinated individuals. http://ow.ly/bIk550Bqkzr Infected ≠ Infectious. Testing To Diagnose ≠ Testing To Contain An Outbreak. Antigen testing is maximally sensitive when people are maximally infectious. The enthusiasm for saliva-based rapid tests often excludes the use of very inexpensive home-based tests, followed by assisted home isolation. http://ow.ly/tcrJ50BqkEP
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The pharma companies working on a COVID vaccine with $$ from the US and other countries have failed in their pledge for transparency. We must hold them to account, if not by the government action, by consumer and investor pressure. This is too important to let them hide behind a screen of confidentiality. http://ow.ly/P1hS50BqkLH Digital technology can help governments to make better decisions in the face of public health emergencies. We worked with @RockefellerFdn and analyzed what communities need to do to leverage AI, 5G, and the internet of things to track and contain the spread of #COVID19. https://www.rockefellerfoundation.org/report/tackling-COVID19-pandemic-through-integrating-digital-technology-and-publichealth A disturbing @FT story about vaccine availability. The largest vaccine supplier in the world estimates that if a safe and effective vaccine is approved it will be 2024 before there are enough doses to stop the pandemic. My conclusion, redoubling public health COVID control efforts now! http://ow.ly/Vv8x50BrCQk This @nytimes story partly explains why COVID-19 is so devastating to the elderly. The immune system functions much differently in older people, contributing to several different pathologies. http://ow.ly/zTMR50BrCD0 As we age, the immune system begins to shift into a heightened state of alert, dialing up inflammation and running out of certain immune cells. September 15, 2020 I have a proposed strategy to contain the spread of COVID-19 months faster than relying on a future vaccine. It would involve providing regular at home testing (for fifty cents each) so that people can check themselves for the virus before symptoms occur. If they test positive, they self isolate regardless of if they have symptoms. This is achievable. https://www.forbes.com/sites/williamhaseltine/2020/09/11/adefense-of-self-testing-and-supported-self-isolation/#352c450c4feb
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September 16, 2020 This story in Forbes on the University of Illinois is identifying and isolating those who are potentially contagious by the use of universal frequent short turn around COVID tests and implications for similar control measures throughout the US. http://ow.ly/FSTd50BrE6i https://www.forbes.com/sites/williamhaseltine/2020/09/15/t he-university-of-illinoiss-COVID-19-control-shows-that-masstesting-is-the-answer/#1f7bf4ec2fd6 I'm often asked whether the US has done all it could to control COVID-19. My answer is that COVID can be contained without a vaccine or drug, but we haven't done it. China, which had a similarly sized outbreak now has near zero new infections. ACCESS Health & the @RockefellerFdn explored how they did it with the use of digital technologies. http://ow.ly/mxzv50BrDNf Digital technology can empower disease control measures and fulfill unmet needs of patients, doctors, and the public. Read our latest report with @RockefellerFdn to understand how digital solutions have helped to control spread of #COVID19 in China. http://ow.ly/itOr50BrEuz September 17, 2020 See, in comic book form, how the US pandemic response falters in comparison with South Korea’s. Sometimes pictures speak louder than words. https://www.insider.com/comic-how-united-states-lostcontrol-of-coronavirus-pandemic-2020-9 Had a great conversation on @CareDotCom’s Equal Parts podcast about what parents should know about #COVID19. I discussed my two ebooks, “A Family Guide to COVID” & “A Back to School COVID Guide," how to assess your family's hierarchy of risk, and more. https://workplace.care.com/podcast-advice-froman-expert-what-parents-need-to-know-about-COVID-19 Europe is starting to lock down again due to a resurgence of COVID-19. In France, large gatherings of family and friends have become massive vectors of infection. In Spain, bars and a vibrant nightlife are likely the cause. A warning for us all. https://www.bbc.com/news/world-europe-54189575 2725
Digital technologies play an instrumental role in the fight against #COVID19. From fast response, epidemiological studies, to longterm management, we looked at the role digital technology played in the fight with #COVID19 in their latest report, with the support of @RockefellerFdn https://www.rockefellerfoundation.org/report/tacklingCOVID-19-pandemic-through-integrating-digital-technologyand-public-health September 18, 2020 In this discussion with Ernie Manouse, we discuss realistic expectations for an effective COVID vaccine, how the U.S. can put COVID in the rear-view mirror (even without a vaccine), and what to expect on a global scale as we enter flu season. www.houstonpublicmedia.org/articles/shows/townsquare/2020/09/14/381807/town-square-vaccines-and-theglobal-COVID-map-sept-14-2020/?utm_source=rss-town-squarearticle&utm_medium=link&utm_campaign=hpm-rss-link September 19, 2020 In this discussion with Ernie Manouse, we discuss realistic expectations for an effective COVID vaccine, how the U.S. can put COVID in the rear-view mirror (even without a vaccine), and what to expect on a global scale as we enter flu season. www.houstonpublicmedia.org/articles/shows/townsquare/2020/09/14/381807/town-square-vaccines-and-theglobal-COVID-map-sept-14-2020/?utm_source=rss-town-squarearticle&utm_medium=link&utm_campaign=hpm-rss-link September 21, 2020 Any proposal to use herd immunity to end the coronavirus pandemic is misguided at best, as it would result in millions of lives lost. Not only that, but studies of coronavirus immunity (such as with the common cold) suggests that the human body may not stay immune for long, meaning people could become reinfected. If that is the case, our strategies for containment must be reconsidered. Learn more here:
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https://edition.cnn.com/2020/09/18/opinions/reinfectionCOVID-19-prevention-herd-immunity-haseltine/index.html September 22, 2020 The opaque veil of vaccine approval must be lifted during this time of crisis. These trials must be more transparent in their development of a drug that will be administered to millions. https://www.forbes.com/sites/williamhaseltine/2020/09/16/p aused-astrazeneca-trials-emphasize-need-for-vaccinetransparency/#693af6982bdb We cannot expect natural immunity to protect us from COVID. Studies in Kenya, Hong Kong, and the U.S. suggest it is possible to be reinfected with COVID-19 mere months after having it the first time. Read more about what we’re learning: https://www.forbes.com/sites/williamhaseltine/2020/09/18/w hy-we-cant-rely-on-natural-immunity-to-protect-us-fromCOVID-19/#1873897e1ff2 Several lessons from the long battle with HIV suggest what may lie ahead as we fight COVID-19: Vaccines are never a guarantee (but treatments can be our most important weapon); human behavior plays a vital role; and it is critical to build on knowledge and tools gained fighting earlier outbreaks—a strategy only possible if we continue funding research in between pandemics: https://www.scientificamerican.com/article/lessons-from-aids-forthe-COVID-19-pandemic September 23, 2020 It seems these Pharma companies are racing towards a finish line that may not guarantee a successful outcome for COVID-19 vaccines. Moderna, Pfizer, AstraZeneca, and Johnson & Johnson have published their trial protocols and it boggles the mind that they do not emphasize the most important ramifications of COVID-19 that people are most interested in preventing: overall infection, hospitalization, and death. Learn more about the problems with these vaccine protocols: https://www.forbes.com/sites/williamhaseltine/2020/09/23/C OVID-19-vaccine-protocols-reveal-that-trials-are-designed-tosucceed/#437335652479 2727
September 24, 2020 The protocols for the COVID-19 vaccine trials just released by Modern and Pfizer are outrageous: They seem to have been designed to ensure the greatest possible success, which could overstate the vaccine's effectiveness, with a timeline driven more by politics than public health. The lives of millions of people are at risk. We can and should demand better. https://www.washingtonpost.com/opinions/2020/09/22/bew are-COVID-19-vaccine-trials-designed-succeed-start/ Andrew Dunn of Business Insider spoke with me and four other experts in vaccine research, virology, and infectious diseases about the safety of the coronavirus vaccines that are currently in development. As I’ve said before, we have reason to be concerned. https://www.businessinsider.com/the-ultimate-guide-tointerpreting-phase-3-coronavirus-vaccine-results-2020-9 September 25, 2020 Each of us naturally focuses on what is happening to us and our countries. It is often worthwhile to look at others to understand ourselves and what can happen and sometimes is happening closer to home. https://www.nytimes.com/2020/09/23/world/americas/mexicocoronavirus-COVID-iztapalapa.html?smid=em-share Please see this brilliant reporting of COVID transmission in an Iowa community. A situation like this could happen anywhere, most likely these days at a Trump indoor rally, a school, a crowded office, an airplane, a rave, a frat party, or a bar. https://www.washingtonpost.com/graphics/2020/national/genetic -science-coronavirus-outbreak-iowa/ Seven months into the pandemic, Trump’s testing plan enters its second wave of failure https://www.washingtonpost.com/opinions/2020/09/23/sevenmonths-into-pandemic-trumps-testing-plan-enters-its-secondwave-failure/?tid=ss_tw Yet another misstep on the part of the CDC. Airborne transmission of COVID-19 occurs. The CDC needs to set the record straight. 2728
https://www.washingtonpost.com/opinions/2020/09/22/yesairborne-transmission-is-happening-cdc-needs-set-recordstraight/?tid=ss_tw See this excellent @FinancialTimes summary of COVID-19 related vaccines, what they are, how and where they are being tested, and excellent graphics on the criteria for approval. https://www.ft.com/content/e5012891-58da-4a4f-8a05182adf3ba0e2 September 28, 2020 FREE e-books that offer guidance about COVID-19 for Parents and students today who are straining the emotional bandwidth of families that have already been pushed to the limit during lockdown. https://accessh.org/COVIDfamilyguide/COVID-back-toschool-read-book/ Advice from @nytimes on limiting colds indoors applies to COVID as SARS-CoV-2 is a cold virus that kills between 0.1% and 5% of those infected. Who are the 0.1%? Young people in Africa & India who are routinely exposed to a plethora of infectious diseases and who've probably developed tolerance to septic shock. https://www.nytimes.com/2020/09/27/health/coronavirustransmission-indoors.html?smid=em-s This @FortuneMagazine on fading trust in the FDA shows clear evidence of meddling and White House interference in CDC and FDA policies. https://fortune.com/2020/09/24/fda-COVIDvaccine-trump-meddling/ New daily cases of COVID are on the rise in Italy. But the government's willingness to implement strict measures has kept Italy's tally of new infections lower than other countries in the region. The country is offering harsh lessons to the rest of us on what is needed to keep another wave of infections at bay. https://www.ft.com/content/6831be3e-2711-4ea3-8f62daa82cf9ca11 September 29, 2020 This meta-analysis of SARS-CoV-2 transmission shows children 20 and under are about half as susceptible to infection and children under 10 are less susceptible to infection than those over 2729
14. One thing it doesn't tell us is whether children transmit infection any differently than adults. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2771 181 September 30, 2020 This Scientific American article is FREE for 7 days: Lessons from the long battle with HIV suggest what may lie ahead as we fight COVID-19: Vaccines are never a guarantee (but treatments can be our most important weapon); human behavior plays a vital role; and it is critical to build on knowledge and tools gained fighting earlier outbreaks—a strategy only possible if we continue funding research in between pandemics. https://www.scientificamerican.com/article/lessons-from-aids-forthe-COVID-19-pandemic One repercussion of COVID-19 is its effect on working mothers. Women are leaving the workforce at three times the rate of men because of child care demands. A disturbing downward trend in gender equality in the workplace. https://knowledge.wharton.upenn.edu/article/how-thepandemic-is-affecting-working-mothers/ Be wary of your pets. Dogs and cats can be infected with SARS-CoV-2 and may be able to transmit the virus. Knowing this, it's possible the intermediary between bats and humans might have been a pet cat or dog. It raises the question: will our pets become reservoirs of future SARS-CoV-2 outbreaks. https://www.nytimes.com/2020/09/29/science/cats-coronavirusimmunity.html?smid=em-share
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October 1, 2020 Confidence in vaccines is more sensitive than that for drugs. Vaccines are given to the healthy, whereas drugs are to help those who are already sick. For COVID, confidence requires radical transparency https://www.nature.com/articles/d41586-02002738-y An interesting read from @JoshuaPCohen1 on protections for those with pre-existing conditions if the ACA is overturned. https://www.forbes.com/sites/joshuacohen/2020/10/01/supreme -court-decision-on-aca-may-threaten-protections-for-those-withpre-existing-conditions/#4f0db1f94521 October 2, 2020 No nationwide public health intervention will ever go according to plan, but so far, we have had no plan at all to contain the coronavirus from spreading. I suggest at home rapid testing and selfisolation for anyone who tests positive, with financial assistance for those who cannot work while at home. Some argue this won’t work--read more about why I think it will. https://www.forbes.com/sites/williamhaseltine/2020/09/30/t o-contain-COVID-19-combine-mass-testing-with-social-andeconomic-assistance/ October 5, 2020 In July, @RockefellerFdn updated their national testing and tracing plan to recommend 30 mil tests per week by November. Though testing numbers here have always been unclear, we are likely far from that target: https://www.rockefellerfoundation.org/national-COVID-19testing-and-tracing-action-plan/ The federal gov't has abandoned its duty to put in place a coordinated national plan for COVID-19 testing. The state by state strategy that is being patched together in the absence of such a plan holds risks for us all https://www.statnews.com/2020/10/01/national-COVID-19testing-strategy-not-state-by-state-patchwork/ Remnick's reflections in @NewYorker show how his own selfdestructive COVID behavior destroys us all, heightening the chances of lethal outbreaks countrwide but also the divisions 2732
between us. https://www.newyorker.com/magazine/2020/10/12/thecoronavirus-and-the-threat-within-the-whitehouse?utm_source=twitter&utm_medium=social&utm_campaign =onsite-share&utm_brand=the-new-yorker&utm_socialtype=earned Reports on Trump’s condition have been heavy on reassurances but light on clinical details, making it difficult to determine whether these therapies are intended to improve worsening symptoms or placate a panicked president. In this article I outline the reasons and effects of the various treatments reportedly administered. https://www.forbes.com/sites/williamhaseltine/2020/10/04/al l-the-presidents-medicines/#428a2eb51f54 There is no telling yet which way Trump's illness will turn nor how he might spin the outcome for political purposes. No matter the direction of his disease or his judgement, there is one thing every American should be acutely aware of: this virus knows no bounds. https://www.thedailybeast.com/trumps-coronavirushospitalization-is-his-last-best-chance-to-tell-the-truth-about-thevirus October 6, 2020 Trump joins Boris Johnson, Prime Minister of the UK, and Brazil's President Jair Bolosonaro, as a handful of leaders who’ve contracted COVID-19. Why not China’s President Xi or Russia’s Putin? Read more about why it was inevitable that Trump became infected, and what steps must be taken to protect our nation going forward. https://www.forbes.com/sites/williamhaseltine/2020/10/03/t he-encounter-was-inevitable-trump-meets-thecoronavirus/#1b29d9817a1c An excellent @NewYorker piece about Wuhan, where COVID-19 is said to have begun. The city is back to normal, save for frequent COVID checks & quarantine of all entering from abroad. Schools, businesses, and theaters are open & masks are as common as before the epidemic. https://www.newyorker.com/magazine/2020/10/12/nine-daysin-wuhan-the-ground-zero-of-the-coronaviruspandemic?utm_source=onsite2733
share&utm_medium=email&utm_campaign=onsiteshare&utm_brand=the-new-yorker October 7, 2020 The HIV/AIDS epidemic has taught us lessons that translate to the current COVID-19 pandemic. Yet there are critical differences in the extent to which public health measures can successfully contain the spread of these two viruses. I hope leaders might take to heart some of what we have learned, particularly in regions of the world in which COVID-19 still roams almost freely. https://www.forbes.com/sites/williamhaseltine/2020/10/05/t he-difference-between-COVID-19-and-hivaids/#65f9f84234f6 Twitter Six months into our COVID-19 response, the challenges faced by the healthcare industry remain vast. Yet we continue to adapt. This article offers six strategies for moving forward based on what we've learned so far. https://www.modernhealthcare.com/transformation/lessonslearned-more-six-months-us-response-COVID-19 Facebook and LinkedIn Six months into our COVID-19 response, the challenges faced by the healthcare industry remain vast. Yet we continue to adapt, absorbing knowledge in the thick of crisis that we can retain and apply in the future. This article offers six strategies, assembled by experts based on what we've learned so far, that the industry can use to move forward: 1) Know your supply chain 2) Rethink staffing 3) Keep employees mentally healthy 4) Bolster infection prevention 5) Extend reach into the community 6) Get creative with technology https://www.modernhealthcare.com/transformation/lessonslearned-more-six-months-us-response-COVID-19 Trump’s distortions continue to cost lives. In this excellent @nytimes op-ed, Michelle Goldberg explains “how thoroughly this administration has been infected by its own disinformation.” https://www.nytimes.com/2020/10/05/opinion/trumpcoronavirus-white-house.html 2734
Will the FDA approve an Emergency Use Authorization (EUA) for a #COVID19 vaccine? This brief history of EUAs argues that the risks outweigh the benefits. http://www.bioethics.net/2020/10/emergency-use-authorizationfor-COVID-19-vaccines-lessons-from-the-past/ October 8, 2020 At a time when we most need faith in and support of our public health leaders, both are eroding. Fast-tracking approvals for treatments and vaccines is inflicting serious damage. Let me be perfectly clear: There is no magical cure that will bring the pandemic to a rapid end. Any suggestion of a vaccine or quick-fix treatment by the end of this year is magical thinking, and magical thinking will not end the nation’s suffering. The way to end this pandemic quickly is through the forceful implementation of sound public health principles—principles that public health agencies should have been vigorously enforcing from the start. https://www.thinkglobalhealth.org/article/eroding-faithpublic-health-leaders There is evidence for PTSD in the era of COVID, for both individuals and in society as a whole. Rates of depression and suicide are high, and the degree of moral trauma that many are experiencing in the loss of trust in our leadership, is, in my estimation, creating an additional crisis, severe enough to be given a name: I’m calling it CVSTD (COVID-19-related Traumatic Stress Disorder). https://www.psychologytoday.com/us/blog/best-practices-inhealth/202010/COVID-19-traumatic-stress-disorder October 9, 2020 Herd immunity is not a solution and should never be a strategy for combating COVID-19. For anyone holding up Sweden’s choice to forego lockdown and mask-wearing as an example, it’s important to remember their strategy backfired and they now have one of the highest fatality rates in the world. If we in the U.S. simply stand back and wait for “herd immunity” then we can expect over 6.5M people to die. https://www.project-syndicate.org/commentary/trump-herdimmunity-strategy-will-not-defeat-COVID19-by-william-ahaseltine-2020-10 2735
Earlier this week, I wrote in detail about the White House rejecting the guidelines set by our public agencies for vaccine approvals. Since this writing, those agencies are pushing back (and I write about that as well) but if you’d like to learn more about this battle, start here. https://www.forbes.com/sites/williamhaseltine/2020/10/06/w hite-house-continues-to-choose-political-gain-over-publichealth/#3e7c7a421bf9 The FDA and the CDC are pushing back against the White House in a time when we most need those public agencies to be independent from political pressure. https://www.forbes.com/sites/williamhaseltine/2020/10/08/fe deral-health-agencies-push-back-against-politicalinterference/#45f88ed24c05 The final report from @theNASciences a plan that HHS and state, tribal, local, and territorial authorities should adopt to roll out a potential COVID-19 vaccine fairly and equitably. Read the plan here https://www.nap.edu/catalog/25917/framework-forequitable-allocation-of-COVID-19-vaccine Birx warns the rise in COVID cases in the Northeast is very different than the rise in cases in the spring. In March & April COVID was primarily being spread at workplaces. Now, workplaces are safer. But the virus is spreading quickly at social gatherings, where family & friends let down their guard, take off their masks, and stand too close. https://www.modernhealthcare.com/policy/birx-warnsabout-very-different-coronavirus-spread October 10, 2020 Studies show that 20% of people infected with COVID don’t have symptoms, and are spreading the disease. We are also learning that people who are sick sometimes don’t realize they have COVID because they don’t recognize the signs. This is problematic for the same reason. https://www.healthline.com/health-news/20-percent-ofpeople-with-COVID-19-are-asymptomatic-but-can-spread-thedisease#The-bottom-line
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October 12, 2020 For the first time, Dr. Haseltine tells his life story—which is still unfolding—in My Lifelong Fight Against Disease, including facing devastating public health crises such as the COVID-19 pandemic, and highlighting exhilarating moments of medical discovery. Stay tuned to purchase your copy! October 14, 2020 For those curious as to why bats are a source of such troubling infections (Ebola, SARS, MERS, COVID-19), this article is a thoughtful exploration of the question. The take-home message: COVID-19 is by far NOT the last of pandemics of bat origin coming soon to a world near you! https://science.sciencemag.org/content/370/6513/172 The @JAMA_current estimate of the long term cost of COVID19 in the US may surprise you. Other countries contained the epidemic with sound public health measures. All of us should have by now lost patience with the US response and demanded federal action to end the pandemic. https://jamanetwork.com/journals/jama/fullarticle/2771764 COVID-19 is widening existing gender inequalities. When schools & daycares close, women are primarily the ones to step in and care for children, risking their career and income. Before the pandemic, women already held lower ranking jobs and earned less money than men. How much further behind will women be when the pandemic ends? https://www.nytimes.com/2020/09/26/world/COVID-womenchildcare-equality.html?smid=em-share October 15, 2020 The COVID trends in Europe are sending us a clear message: Relax COVID restrictions and die. No European country has imposed strict control measures like China. Relaxing restrictions on social gatherings and mask-wearing have predictable consequences. When will we learn that short term pain means long term gain! https://www.wsj.com/articles/europe-overtakes-u-s-in-newcases-of-COVID-as-restrictions-tighten-11602669748
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Would that Scienceville were real. @washingtonpost describes the power of genome sequencing to track COVID transmission & tailor control measures. In the UK scientist have determined the virus sequence of 12% of all diagnosed cases as compared to 0.4% in the US. Total genome sequencing can tell us who gave the infection to whom. https://www.washingtonpost.com/graphics/2020/health/coronavi rus-genetic-code/ Drug inspectors uncovered serious quality control problems at an Eli Lilly plant that is ramping up to manufacture COVID-19 drugs. Trump wants to make these drugs available now, but who guarantees the quality of COVID drugs and vaccines and ensures they don't do more harm than good? https://www.reuters.com/article/us-health-coronavirus-lillyexclusive/exclusive-fda-faults-quality-control-at-lilly-plantmaking-trump-touted-COVID-drug-idUSKBN26Y30C With no end to the pandemic in sight, @nytimes reminds us that we need to start getting back to routine medical care -- especially important for parents and caregivers who may ignore vague symptoms like headaches and depression that could be a sign of what I call CVTSD -- COVID-19 Traumatic Stress Disorder. https://www.nytimes.com/2020/10/14/parenting/pandemicvirus-stress-symptoms.html?smid=em-share October 16, 2020 The recent pause in the Johnson & Johnson and Eli Lilly COVID-19 vaccine trials should give all of us pause. We have been given limited information as to the specifics, and we deserve to know the details. Read more for what we might deduce: https://www.forbes.com/sites/williamhaseltine/2020/10/14/w hat-the-pause-in-the-johnson--johnson-and-eli-lilly-COVIDdrug-trials-may-mean/#253026736c90 COMING SOON! The COVID Commentaries contain a collection of my writings, research and interviews on COVID-19. This is a Living eBook, updated regularly with new information on the disease and our response as it unfolds. It is organized into four parts, spread across six volumes
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October 19, 2020 The impact of COVID-19 is directly related to the burden of disease in various populations. America's poor carried a high burden of disease before the pandemic, compared to other countries. COVID-19 has made it catastrophically worse. https://www.wired.com/story/the-pre-existing-conditions-ofthe-coronaviruspandemic/?utm_source=twitter&utm_medium=social&utm_camp aign=onsite-share&utm_brand=wired&utm_social-type=earned Red states continue to resist efforts to enforce public health control measures to contain COVID-19. The science is clear, so why no action -- ignorance, cowardice, or destructive intent?Whatever the reason the result will be increaed death and illness https://www.washingtonpost.com/national/as-coronaviruscases-rise-red-state-governors-resist-measures-to-slow-the-spreadpreach-personal-responsibility/2020/10/18/bb95176e-0fc3-11ebb1e8-16b59b92b36d_story.html Mental illness can increase a person's risk of death by COVID19. This @JAMA_current article highlights the need for those living with mental health conditions to take additional prevention and treatment precautions. And a reminder that we must design targeted interventions for those with mental illness, as well as for nursing homes. https://jamanetwork.com/journals/jamanetworkopen/fullarticl e/2771037 Another important @JAMA_current article, this one a thoughtful review of the issues surrounding an early introduction of a COVID vaccine under emergency use authorization. It highlights many uncertainties regarding efficacy and safety and is a reminder of how appallingly China and Russia acted by rushing to approve a vaccine. https://jamanetwork.com/journals/jama/fullarticle/2772138 This meta analysis of the effectiveness of a set of widely used antiviral drugs to treat COVID-19 reveals no consistent effect on duration of illness or mortality mortality. Gilead, the company promoting remdesivir disputes the findings based on their own trial results. I hope this helps end premature EUAs that prevent definitive controlled trials of COVID drugs from being completed 2739
https://www.medrxiv.org/content/10.1101/2020.10.15.20209 817v1 See this well reasoned discussion in @STATnews of the perils of ”herd immunity” policies to control COVID-19. We cannot rely on magical thinking: Herd immunity is not a plan https://www.statnews.com/2020/10/16/we-cannot-rely-onmagical-thinking-herd-immunity-is-not-a-plan/ The economic damage caused by SARS-CoV-2 won't be fully understood until well after the pandemic ends. In the meantime, two eminent economists have estimated the cost in the United States alone at $16 trillion. The cost to Europe is likely comparable. https://jamanetwork.com/journals/jama/fullarticle/2771764 1.9 million years of life have been lost during the COVID pandemic. It's an important marker -- if someone should have lived to 80 but died at 50, that's 30 years lost. Now, younger people account for the vast majority (65%) of years of life lost to COVID in the US. This is especially painful, now that the majority of those infected are those that are young. https://www.modernhealthcare.com/patient-care/19-millionyears-life-have-been-lost-during-pandemic October 20, 2020 Antibodies to SARS-CoV-2 decrease rapidly after infection, especially those to the main neutralizing region of the spike protein. In vitro neutralizing antibodies also decrease, meaning reinfection and antibody-dependent disease enhancement is possible. The authors suggest measuring neutralizing antibodies before using convalescent anti-sera or hyperimmune IgG. https://mbio.asm.org/content/11/5/e02590-20 We are learning more each day about how to diagnose and treat COVID-19. Most recently we’ve discovered that people who get the most seriously ill from the coronavirus infection have a compromised interferon response. Essentially, the immune system’s warning signals are down. Read more about how this impacts the severity of the ensuing disease: https://www.clinicalomics.com/topics/patientcare/coronavirus/compromised-type-i-interferon-responsecommon-among-severe-COVID-19-patients/ 2740
As I said recently on CNN, it is unworkable and unethical to adopt a “herd immunity” approach to the coronavirus epidemic. This NYT op-ed by John M. Barry, professor at the Tulane University School of Public Health and Tropical Medicine and author of “The Great Influenza: The Story of the Deadliest Pandemic in History,” does a good job of laying out the cautions of adapting a herd immunity approach. https://www.nytimes.com/2020/10/19/opinion/coronavirusherd-immunity.html I recently spoke with Business Journal Senior Enterprise Editor Phil Hall about the race to develop a COVID vaccine as well as the coming flu season, and our nation’s misguided emphasis on treatments rather than public health measures to contain the spread of the coronavirus. https://westfaironline.com/129194/suite-talk-dr-william-ahaseltine-chairman-and-president-access-health-international/ If the "herd immunity" strategy is to be implemented and we let the pandemic run its course, we are looking at two to six million Americans dead – not just this year but every year. https://newsus.cgtn.com/news/2020-10-17/Health-expertsWhite-House-views-on-herd-immunity-to-fight-COVID-19UElrdBDgNG/index.html October 21, 2020 For the first time, Dr. Haseltine tells his life story—in My Lifelong Fight Against Disease, including facing devastating public health crises such as the COVID-19 pandemic, and highlighting exhilarating moments of medical discovery. https://www.amazon.com/dp/B08LL5T2ZW After a lifetime spent in science, medicine and pursuing better public health, Dr. William A. Haseltine is once again battling a new and still somewhat unknown disease, COVID-19. His opinions on the course of the pandemic are sought regularly by major broadcast news networks and print media. His COVID-related writing has been published in the Washington Post, Los Angeles Times, Project Syndicate, CNN, Forbes and Psychology Today. Volume One: https://www.amazon.com/COVID-CommentariesChronicle-Plague-I2741
ebook/dp/B08LK734XC/ref=sr_1_1?dchild=1&keywords=COVI D+commentaries&qid=1603302579&sr=8-1 Hospitalized patients with COVID-19 in the Veterans Health Administration had more than five times higher risk for in-hospital death and increased risk for 17 respiratory and nonrespiratory complications than did hospitalized patients with influenza. https://www.cdc.gov/mmwr/volumes/69/wr/mm6942e3.htm#:~ :text=Hospitalized%20patients%20with%20COVID%2D19,did%20 hospitalized%20patients%20with%20influenza. We knew that in most countries excess deaths, over and above what is expected, are much larger than normal. What is surprising about the current report is how many excess deaths are among the young, more than 25% over what is expected. This report highlights the under-recognized threat of COVID to all age groups, especially those 25-45 years old . https://www.washingtonpost.com/health/coronavirus-excessdeaths/2020/10/20/1e1d77c6-12e1-11eb-ba42ec6a580836ed_story.html October 22, 2020 The cost of our nation’s failure to respond to the COVID crisis is hundreds of thousands of lives lost and more than $16 trillion and rising. Many of the issues plaguing our response are due to the governance and structure of how we address public health issues here in the US. https://www.forbes.com/sites/williamhaseltine/2020/10/14/t he-need-for-an-effective-national-public-health-service-how-uspublic-health-failed-you-and-me/#315057d11318 An independent committee is meeting today to evaluate the FDA's approach to a COVID vaccine and its accelerated timeline to completion. One item to discuss: what will happen if the FDA issues an EUA for a vaccine before trials are complete? Will it effectively end the trials early as it did for treatments like remdesivir, later proven to have little to no impact on the disease? https://www.washingtonpost.com/politics/2020/10/22/health -202-emergency-approval-coronavirus-vaccine-could-undermineefforts-keep-researchingit/?utm_campaign=wp_the_health_202&utm_medium=email&ut m_source=newsletter&wpisrc=nl_health202 2742
A shame that it took infection and illness for @GovChristie to see the truth. Admitting his mistakes took courage. Would that other leaders follow his path. "It was a serious failure for me, as a public figure, to go maskless at the White House. ...I am lucky to be alive." https://www.wsj.com/articles/i-should-have-worn-a-mask11603315968 The pros, cons, and limitations of lockdowns. We have COVID-19 fatigue because we still have COVID in our midst. About one-fifth of humanity has no such fatigue because their countries are essentially free of disease (China, Taiwan, New Zealand). Lockdowns can work when well-implemented and coupled with continued vigilance. https://www.washingtonpost.com//world/2020/10/22/secon d-lockdown-ireland-europecoronavirus/?utm_campaign=wp_todays_worldview&utm_mediu m=email&utm_source=newsletter&wpisrc=nl_todayworld&cartaurl=https%3A%2F%2Fs2.washingtonpost.com%2Fcar-lntr%2F2c44349%2F5f9102c89d2fda0efb5114e1%2F596a9c6bae7e8a 0ef340b8c3%2F10%2F83%2F2a2819295f08f700b7488be6add4f1ff Yet another example of political interference in medical and scientific efforts to contain, control, and eliminate COVID-19 in a safe and timely manner. How many more people must die before this administration realizes that the pandemic will not respond to political persuasion? https://www.politico.com/news/2020/10/22/azar-plansoust-hahn-fda-431139 We have underfunded public health for years, and the result is that the US population has a higher prevalence of chronic illnesses and shorter lives. COVID is simply exposing the failure of our public health infrastructure to maintain people’s well-being. https://www.forbes.com/sites/williamhaseltine/2020/10/21/u nderfunding-public-health-harms-americans-beyond-COVID19/#6880f786419c We now have more reason than ever for our concerns about the government fast tracking approvals for COVID-19 treatments. Eli Lilly, a pharmaceutical company developing treatments that President Trump wants authorized immediately, has been cited by the FDA for falsifying records.
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https://www.forbes.com/sites/williamhaseltine/2020/10/20/el i-lilly-plant-set-to-manufacture-COVID-19-therapy-cited-forbreaching-fda-regulations/#5980d6b8527b October 23, 2020 15,000 people are expected to gather in D.C. this weekend for a worship event--which has been permitted by public officials.There is no way to host an event like this without putting people in danger. https://www.thedailybeast.com/sean-feuchts-let-us-worshipevent-approved-for-national-mall-and-feds-are-doingnothing?ref=home Remdesivir and hydroxychloroquine, and two other drugs, are proving to be ineffective. In a study covering 30 countries with over 11,000 patients, interim results show that patients prescribed any of these drugs were no more likely to survive or have shorter hospital stays. https://www.forbes.com/sites/williamhaseltine/2020/10/20/m assive-COVID-19-drug-trial-underscores-the-importance-ofcontrolled-clinical-studies/#4e80e2be1681 People in Europe started to slowly let down their guard in August, and now they are paying the price with skyrocketing cases. The spike was avoidable. https://dailyclout.io/daily-clout-exclusive-renowned-scientistdr-haseltine-hiv-treatment-pioneer-on-how-we-made-europesavoidable-second-wave-unavoidable/ October 24, 2020 Available on Amazon NOW! After a lifetime spent in science, medicine and pursuing better public health, Dr. William A. Haseltine is once again battling a new and still somewhat unknown disease, COVID-19. His opinions on the course of the pandemic are sought regularly by major broadcast news networks and print media. His COVID-related writing has been published in the Washington Post, Los Angeles Times, Project Syndicate, CNN, Forbes and Psychology Today. https://www.amazon.com/COVID-CommentariesChronicle-Plague-Iebook/dp/B08LK734XC/ref=sr_1_1?dchild=1&keywords=COVI D+commentaries&qid=1603302579&sr=8-1 2744
October 25, 2020 Available NOW: Dr. William Haseltine’s Autobiography For the first time, Dr. Haseltine tells his life story—which is still unfolding—in My Lifelong Fight Against Disease, including facing devastating public health crises such as the COVID-19 pandemic, and highlighting exhilarating moments of medical discovery. https://www.amazon.com/dp/B08LL5T2ZW I spoke with Carol Massar and Paul Sweeney on Bloomberg Business Week about our efforts to prevent the spread of the coronavirus and what we can expect ahead of us. It’s grim. https://www.bloomberg.com/news/audio/2020-10-21/whitehouse-nearing-deadline-for-fiscal-stimulus-podcast Why don't we all have COVID-19 tests in our medicine cabinets yet? From the President on down, most of the official leadership has been deeply misguided. They have focused first on treatment and not on prevention. https://www.cnn.com/2020/10/21/health/COVID-19treatment-progress-wellness/index.html What we really need from a COVID-19 vaccine isn’t a broad reduction in mild cases, but mitigation of serious illness and death. Read here about the primary outcomes of the FDA’s recent meeting with an advisory panel of experts and laypeople. https://www.forbes.com/sites/williamhaseltine/2020/10/23/t hree-takeaways-from-major-fda-advisory-meeting-on-COVID-19vaccines/ Rushing a vaccine to market while ignoring serious side effects is not safe for the general public, much less for individuals participating in the trials. Safety, not a need for speed, must absolutely come first and foremost, and in the context of vaccine trials that means taking each pause or hold as seriously as needed. https://www.forbes.com/sites/williamhaseltine/2020/10/22/m ore-troubling-events-in-the-rush-to-find-COVID-19vaccine/#44ac10b9440b As cold weather here approaches, it remains to be seen whether or not we in America can control the coronavirus pandemic. I spoke with CBS News radio about what we need to do to curb the spread (our segment is 20 minutes into the broadcast). https://www.radio.com/knx1070/podcasts/knx-in-depth809/knx-in-depth-should-be-a-gonzo-final-presidential-debate2745
southwest-the-latest-airline-to-bring-back-the-dreaded-middleseat-doctors-are-getting-much-better-at-treating-COVID348444088 Vaccines are very delicate and therefore difficult to transport. Air cargo companies are concerned that they are not prepared to help with vaccine distribution, in part because they don’t have sufficient numbers of cold cargo containers. Read here about this and other challenges in mass-distribution of a vaccine. https://www.forbes.com/sites/williamhaseltine/2020/10/22/v accine-transporters-feel-unprepared-for-the-distributive-effortahead/#22ba088b5102 After some hard life lessons, I have learned not to engage in public discussion with people who put forward harmful approaches to public health crises. Such is the case now with the deadly suggestion by the White House that herd immunity is a solution to the coronavirus pandemic. https://www.psychologytoday.com/us/blog/best-practices-inhealth/202010/false-equivalency-in-public-health-dialogue October 26, 2020 Here Nick Kristof elegantly summarizes many of the themes in our recent commentary on the COVID-19 pandemic in the US and worldwide. To fight the pandemic we need good leadership, good governance, social solidarity, and great science. We have great science but score poorly on all others. https://www.nytimes.com/2020/10/22/opinion/sunday/coronavi rus-united-states.html .@thewanreport asks an important question. 10 months into the pandemic, where are the rapid at-home COVID tests? We have the technology & we know the tests will help, so why aren't companies seeking FDA approval and why isn't the FDA doing more to identify opportunities? https://www.washingtonpost.com/health/2020/10/24/corona virus-home-tests/ Arguments rage over the balance between COVID protection measures and maintaining the economy. China’s shows us that protecting the economy means doing whatever necessary to control COVID. Leaders in Europe and the Americas have been unwilling to sacrifice short term pain for long term gain. 2746
https://www.economist.com/china/2020/10/24/in-a-worldmired-in-recession-china-manages-a-v-shaped-recovery @TheEconomist discusses herd immunity as if it were an argument based on reason, not political and economic expediency. Public health measures alone can control the epidemic. The absence of this proven alternative in the article is utterly baffling. https://www.economist.com/science-andtechnology/2020/10/21/should-COVID-be-left-to-spreadamong-the-young-and-healthy The EU may approve a COVID vaccine even if it is effective in less than half of people taking it, a lower threshold than the FDA which will likely expect at least 50% effectiveness. A mediocre shot may further erode public trust in vaccines & still not stop the pandemic. https://www.wsj.com/articles/european-unionwouldapplylower-threshold-in-assessing-COVID-19-vaccine11603649465 The failure to hold Trump accountable for one of the worst instances of civilian mass deaths in U.S. history stands among the greatest failures of American media. https://www.washingtonpost.com/opinions/2020/10/26/medianever-held-trump-responsible-mass-atrocity/ October 27, 2020 An office dedicated to vaccine safety was shuttered by the Trump administration last year and merged with another program. The move means we have no single government body coordinating and monitoring the safety of the COVID vaccine trials happening now. https://www.nytimes.com/2020/10/23/health/COVIDvaccine-safety.html?smid=tw-share A new surge of COVID hospitalizations threatens to swamp health systems across US and Europe. Deaths will soon rise. Why are East Asian nations doing so much better than us? We could do as well as them with universal frequent family testing and paid family isolation. https://www.nytimes.com/2020/10/26/us/a-surge-inhospitalizations-is-straining-some-us-health-care-facilities.html This wide-ranging analysis shows that banning large gatherings, closing schools, and restricting the number of people who can 2747
congregate to ten or less determines whether or not the epidemic is controlled or not. https://www.thelancet.com/journals/laninf/article/PIIS14733099(20)30785-4/fulltext#seccestitle80 Posted directly from VuMedi to Twitter and LInkedIn What can we expect from the COVID-19 vaccines currently under development? #COVID19 #COVID19vaccine What Would COVID-19 Vaccine Do? What Are the Vaccine Trials Measuring? Which Requirements Need to Be Met for FDA Approval? An average treatment of Remdesivir costs between $2,340 and $3,120 depending on the patient’s insurance. The expense is high, considering that studies show that the drug has limited effect on the course of disease. https://www.forbes.com/sites/williamhaseltine/2020/10/26/d espite-conflicting-evidence-fda-approvesremdesivir/#52a4511246ad Federal bodies must levy their governing powers to stop COVID-19 and create a national public health system for the future. This piece is the third in my series analyzing public health infrastructure in the U.S. https://www.forbes.com/sites/williamhaseltine/2020/10/26/re structuring-the-federal-response-to-a-pandemic/#45d11a6c5c50 Available now! “This gripping autobiography is at once a study in the development of a scientific mind infused with humanist commitment and a candid revelation of a complex and manysided personality." —Leo J. O'Donovan, S.J. President Emeritus, Georgetown University https://www.amazon.com/dp/B08LL5T2ZW October 28, 2020 A rise in drug use over the course of the pandemic is a sign that people are suffering mentally and struggling to manage stress and anxiety. It's also a sign that CVTSD -- COVID-19 Traumatic Stress Disorder -- is very real. Two stories that highlight the issue (1/2): https://jamanetwork.com/journals/jama/fullarticle/2770987?g uestAccessKey=5fbb9b8f-2ad8-420e-b50e4c05984b5aaf&utm_source=silverchair&utm_medium=email&utm 2748
_campaign=article_alertjama&utm_content=etoc&utm_term=102720 A rise in drug use over the course of the pandemic is a sign that people are suffering mentally and struggling to manage stress and anxiety. It's also a sign that CVTSD -- COVID-19 Traumatic Stress Disorder -- is very real. Two stories that highlight the issue (2/2): https://jamanetwork.com/journals/jama/fullarticle/2770986?guest AccessKey=b31e24aa-7a0b-409d-bd3ce17a58a048cb&utm_source=silverchair&utm_medium=email&ut m_campaign=article_alertjama&utm_content=etoc&utm_term=102720 Experts are worried about what happens when pandemic depression meets seasonal depression. COVID-19 has affected so many stressors that its effects will be felt long after the outbreak is gone. What I call CVTSD -- COVID-19 Traumatic Stress Disorder https://www.washingtonpost.com/lifestyle/wellness/seasonaldepression-COVID-help/2020/10/26/5d93bbe2-1479-11ebba42-ec6a580836ed_story.html?tid=ss_tw Domestic violence is a symptom of CVTSD-COVID Traumatic Stress Disorder. While domestic violence crimes are officially down, experts say the #s are underreported since during the pandemic since victims are focused on meeting basic needs instead of stopping abuse. https://www.washingtonpost.com/lifestyle/wellness/seasonaldepression-COVID-help/2020/10/26/5d93bbe2-1479-11ebba42-ec6a580836ed_story.html?tid=ss_tw Even Putin now believes masks are necessary. Once can only hope that Trump will now follow the lead of the man he seemingly so admires. https://www.nytimes.com/live/2020/10/27/world/COVID19-coronavirus-updates/russia-imposes-a-nationwide-maskmandate-as-its-foreign-minister-sergey-lavrov-heads-intoquarantine October 29, 2020 People in Europe and the US seem unwilling to save their own lives and those of others. Such is not the case in East/Southeast Asia. Why is a sense of personal and social responsibility so weak in the West? Are we spoiled by 60 yrs of peace and prosperity? 2749
https://www.nytimes.com/2020/10/27/world/protesters-initaly-and-spain-clash-with-police-as-they-call-for-freedom-fromvirus-restrictions.html From infection to ICU treatment, COVID-19 exposed disparities by race/ethnicity, immigration status, income and wealth. The disparities include preexisting disease vulnerability, effectiveness of public health efforts, and the availability and intensity of medical care. https://www.healthaffairs.org/do/10.1377/hblog20201023.55778/ full/ Trump and Bolsonaro: Two Peas in a Pod. Their Pod came close to killing them and is now killing hundreds of thousands of their fellow citizens. In times of plague, leadership matters. https://www.nytimes.com/2020/10/27/world/trumpbolsonaro-coronavirus-latin-america.html?smid=em-share This is what a well run COVID Control Program looks like. One day we may hope to emulate their success. https://www.washingtonpost.com/world/asia_pacific/chinakashgar-xinjiang-coronavirus-outbreak/2020/10/26/6db14e6e1748-11eb-8bda814ca56e138b_story.html?utm_campaign=wp_todays_worldview& utm_medium=email&utm_source=newsletter&wpisrc=nl_todayw orld&carta-url=https%3A%2F%2Fs2.washingtonpost.com%2Fcarlntr%2F2c5a605%2F5f979a389d2fda0efb553109%2F596a9c6bae7e8a 0ef340b8c3%2F31%2F68%2F2a2819295f08f700b7488be6add4f1ff via @washingtonpost A COVID vaccine will be no quick fix to end the pandemic-it likely won't prevent infection and may only help curb mild symptoms of the disease. If one is proven safe & approved, consider it another tool to use with other public health measures, not a silver bullet in itself. https://www.modernhealthcare.com/safetyquality/scientists-warn-americans-are-expecting-too-much-vaccine Fading immunity of COVID-19 has wide-ranging implications. Here in the first of this series, I discuss what we know from antibody test results of people months after they tested positive for the virus.
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https://www.forbes.com/sites/williamhaseltine/2020/10/28/n ew-study-offers-more-evidence-that-immunity-to-COVID-19fades-quickly/ Eli Lilly has halted trials for an antiviral drug that was intended to speed recovery and prevent further progression of COVID-19 in hospitalized volunteers. Read more here for analysis of the decision by the NIH to end the trial. https://www.forbes.com/sites/williamhaseltine/2020/10/28/el i-lilly-stops-antibody-trial-in-hospitalized-COVID-19patients/#1a41403a5c1a The move to fund and expedite human vaccine challenges in the U.K. has more to do with political expediency than scientific necessity, and frankly, is unethical. The U.S. is considering a human challenge trials as well -- it’s not too late to stop this from happening. https://www.thinkglobalhealth.org/article/britains-moralbankruptcy-over-COVID-19-vaccines October 30, 2020 The risk of infection of essential workers in customer facing jobs is high. The study highlights the risk and also what I call CVTSD, COVID related traumatic stress disorder with increases in anxiety, depression, substance abuse, and intrafamily violence. https://oem.bmj.com/content/early/2020/10/11/oemed2020106774?utm_source=STAT%20Newsletters&utm_campaign=86f7 e1f88bMR_COPY_01&utm_medium=email&utm_term=0_8cab1d7961 -86f7e1f88b-151227717 Taiwan has gone 200 days-more than 6 months-without a single locally transmitted case of COVID-19. This article calls them the envy of the world but the truth is every country could achieve this through masks, social distancing, quarantine & isolation. https://www.bloomberg.com/news/articles/2020-10-29/thisplace-hasn-t-had-a-local-coronavirus-case-in-200-days October 31, 2020 The COVID Commentaries contain a collection of my writings, research and interviews on COVID-19. This is a Living eBook, updated regularly with new information on the disease and our 2751
response as it unfolds. It is organized into four parts, spread across six volumes: https://www.amazon.com/COVID-CommentariesChronicle-Plague-Iebook/dp/B08LK734XC/ref=sr_1_1?dchild=1&keywords=COVI D+commentaries&qid=1603302579&sr=8-1
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November 1, 2020 The FDA will not be inspecting the facilities where vaccines for COVID-19 are being manufactured. This poses questions and raises concerns. Vaccines improperly manufactured are a significant public health problem. https://www.forbes.com/sites/williamhaseltine/2020/10/29/fd a-will-not-inspect-vaccine-production-plants/#39438c494616 The immunological complexities of the SARS-CoV-2 virus must be taken into account while we attempt to create goals and timelines for a COVID-19 vaccine. Read more here about the sizable gulf between what we know about the virus and what we are doing to protect ourselves from the virus. https://www.forbes.com/sites/williamhaseltine/2020/10/30/n ew-research-on-flu-vaccines-sheds-light-on-COVID-19vaccines/?sh=e2b9d933aeef November 2, 2020 Dr Daniel Salmon & @drJoshS make a powerful case for postapproval safety and efficacy monitoring of COVID vaccines, based on the H1N1 vaccine program model. We must prepare now to inspire the confidence necessary for a successful vaccination program. https://www.statnews.com/2020/10/29/lessons-h1n1monitoring-COVID-19-vaccine-safety/ @apoorva_nyc implies that persistence of SARS-CoV-2 T-cells leads to long-lasting protection. This is incorrect. Coronaviruses return to infect the same person year in and year out. The safe bet is that SARS-CoV-2 is the same. The article indirectly supports herd immunity & is a disservice to @nytimes readers https://www.nytimes.com/2020/10/27/health/coronavirusantibodies-studies.html?smid=em-share GW Bush reminds us what presidential leadership looks like in a pandemic. He embraces public health, medical science and the US's role as a global leader. He does not shirk from using the full power of the federal govt to fight disease. Leadership matters. Today our country bleeds.
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https://www.cnn.com/2005/HEALTH/conditions/11/01/bush.tr anscript/ FDA regulation of COVID lab tests is lax. Lax oversight leads to inaccurate results and failure to identify those infected. This is a serious safety hazard for those tested and their contacts. To ensure your test results are accurate go to high-quality medical centers for tests https://www.statnews.com/2020/11/02/hhs-relaxedoversight-of-problematic-COVID19-tests-despite-being-told-ofaccuracy-concerns/ UK scientists are speculating that COVID-19 may become endemic, with or without a vaccine. I agree. COVID vaccines have the potential to be as effective as flu vaccines. They may limit the severity of disease in some but not eliminate annual waves of winter COVID-19 infections. https://www.huffingtonpost.co.uk/entry/COVID-19endemic-pandemicepidemic_uk_5f99a2abc5b6aab57a0eb788?utm_campaign=share_e mail&ncid=other_email_o63gt2jcad4 November 3, 2020 NOW on Amazon! For the first time, Dr. Haseltine tells his life story—in his autobiography—”My Lifelong Fight Against Disease”, where he accounts the devastating public health crises such as the COVID-19 pandemic, and highlights exhilarating moments of medical discovery. https://www.amazon.com/dp/B08LL5T2ZW This story describes what life as a senior state level public health official is like in the time of COVID in a red state. https://www.newyorker.com/news/us-journal/how-americacan-avoid-dual-cataclysms?utm_source=onsiteshare&utm_medium=email&utm_campaign=onsiteshare&utm_brand=the-new-yorker November 4, 2020 This week, parents in New York City are having to make a difficult decision about their kids’ education: Choose in-person learning now, or wait until next year. 2755
https://www.forbes.com/sites/williamhaseltine/2020/11/02/n ew-york-city-limits-the-chances-for-in-person-learning-forstudents/?sh=568494ac5693 Some people develop COVID-19 and become severely ill, while others do not. Why? This article explains what we’re learning about the role of autoantibodies with this disease. (An autoantibody response is when your immune system targets YOU instead of the invading virus.) https://www.forbes.com/sites/williamhaseltine/2020/11/03/w hat-are-autoantibodies-the-latest-risk-factor-for-severe-COVID19/?sh=fdbcf0261aa2 As much as families want to gather for the holidays, the risks are high and the consequences dire. If travel is a must, I offer my tips here for staying safe. https://www.bostonglobe.com/2020/10/24/lifestyle/drivefly-stay-home-hard-decisions-behind-pandemic-holidaygatherings/ November 5, 2020 Health workers known as "travelers" brave deplorable safety conditions to fill staffing shortages in health systems across the country. We must protect our heroes on the frontlines, not expose them to unnecessary risks. https://www.modernhealthcare.com/safety/this-worth-my-lifetraveling-health-workers-decry-COVID-care-conditions November 6, 2020 This past week, the U.S. set a new record for COVID-19 infections: Almost 100,000 new cases every single day. The real number of new infections is likely much higher—far closer to a million. A new study in the Lancet confirms what I’ve long thought to be true: Multiply whatever number of new COVID-19 infections in your community by ten--that is likely the true number of new infections. https://www.forbes.com/sites/williamhaseltine/2020/11/04/e very-day-one-million-americans-likelyinfected/?sh=27a7845d6456 COVID-19 is killing over 700 people each day here in the U.S. and it is within our power to do something about it. If we implement 2756
public health measures such as closing schools and banning large public events, in conjunction with mask wearing, we can significantly impact the spread of this virus. Read here about the study published in the Lancet. https://www.forbes.com/sites/williamhaseltine/2020/11/05/la ncet-study-concludes-that-public-health-interventions-reduceviral-transmission/?sh=702f7ccf1a9e What do the massive mink SARS-CoV-2 infections mean for us? It means the pandemic is more likely to become endemic, with domestic and feral animals becoming significant reservoirs. The virus may also mutate possibly increasing their pathogenicity in humans. https://www.statnews.com/2020/11/05/spread-of-mutatedcoronavirus-in-danish-mink-hits-all-the-scary-buttons-but-fearsmay-be-overblown/ A triple epidemic of COVID-19, obesity, and diabetes. Poverty drives both obesity and diabetes. In this region, rich in natural resources, generations of government dysfunction drives poverty. https://www.thelancet.com/journals/lancet/article/PIIS01406736(20)32328-X/fulltext Purchase your copy of COVID Commentaries- Volume One here: https://www.amazon.com/COVID-CommentariesChronicle-Plague-Iebook/dp/B08LK734XC/ref=sr_1_1?dchild=1&keywords=COVI D+commentaries&qid=1603302579&sr=8-1 November 9, 2020 TWITTER ONLY: Some worry about lack of reporting on results from rapid COVID-19 tests. If we provide financial incentives for people who test positive--$$ that could help them stay home from work to isolate safely--we could gather the data and stop the spread of disease. https://www.statnews.com/2020/11/05/rapid-COVID-19tests-hidden-public-health-hazard/ LINKEDIN & FACEBOOK ONLY: I believe the fear of nonreporting of home test results is greatly exaggerated as it was for HIV/AIDS home tests which the FDA held off on approving for 25 years. Today we miss an estimated 90% of those symptomatically infected. We can’t do much worse than that. My plan to pay 2757
households $500 a day to home isolate for two weeks if one member is infected will provide a positive incentive to dramatically increase the fraction of those identified and isolated. https://www.statnews.com/2020/11/05/rapid-COVID-19tests-hidden-public-health-hazard/ Former governors Dirk Kempthorne (R) and @DevalPatrick (D) call on public officials to heed the call of the people and work together on an orderly plan for COVID-19 vaccines. A recent poll shows Americans want a safe and effective vaccine, based on science, distributed fairly. https://www.statnews.com/2020/11/02/heed-will-of-thepeople-COVID-19-vaccines/ The FDA authorized the first neutralizing antibody test for COVID-19 but rightly warns patients not to assume a positive result means they are immune, or have any level of immunity. Immunity to COVID-19 is temporary at best. No one should ease personal protection measures. https://www.fda.gov/news-events/pressannouncements/coronavirus-COVID-19-update-fda-authorizesfirst-test-detects-neutralizing-antibodies-recentor?fbclid=IwAR3VA46Ew9WCCC-2o7-KdA_nLJcgAvacLpwb8bkxlEDNjbwJ68KDx3rT0k Misinformation regarding COVID-19 is rampant. Please see this story in @sciam summarizing and addressing some of the most dangerous myths https://www.scientificamerican.com/article/nine-COVID-19myths-that-just-wont-go-away/ Daily COVID-19 infections are rising in all but three states, with the biggest surge in the Midwest & Southwest. In Nebraska hospitalizations have doubled. In Colorado, they're as high as in April. Large groups of ppl at the polls may push numbers even higher https://www.modernhealthcare.com/safety-quality/virushospitalizations-surge-pandemic-shadows-us-election I am worried about the safety, efficacy, manufacturing quality, distribution, and administration of anti-COVID-19 vaccines. Read more here about STAT’s must-read overview of some of what the public needs to know regarding vaccine development, what and information has been withheld. https://www.forbes.com/sites/williamhaseltine/2020/11/06/amore-transparent-and-trusted-COVID-vaccine/?sh=64e9e94a5b65 2758
13.7 million kids and adults in the U.S. are obese, and this puts them at a higher risk of more serious illness from COVID-19. https://www.forbes.com/sites/williamhaseltine/2020/11/06/h ow-obesity-puts-you-at-risk-for-COVID-19/?sh=5c2bc27d1c34 Children DO get COVID. This week alone, over 60,000 kids were diagnosed, and over 850,000 in the U.S. have had COVID-19 since the pandemic started. They account for 11% of total cases. https://www.forbes.com/sites/williamhaseltine/2020/11/09/o ne-tenth-of-americans-infected-by-COVID-19-are-children/ A large CDC study of 400,000 women confirms that pregnant women are at higher risk for severe COVID-19 and death. This study also confirms racial and ethnic disparities, showing women of color are at increased risk, regardless of whether they are pregnant. https://www.forbes.com/sites/williamhaseltine/2020/11/09/p regnant-women-are-at-higher-risk-for-severe-COVID-19-anddeath/ November 10, 2020 My purpose is to make sure I use whatever energies and intelligence I have to alleviate suffering from disease for as many people as possible. That has been my guide star. My career has not been just about science. The paradigm was using science to improve human health. Read more in Haseltine’s latest Autobiography: https://www.amazon.com/dp/B08LL5T2ZW I spoke with Dave Ross of Seattle Morning News about the coronavirus and my thoughts for how we can end the pandemic without a vaccine. https://omny.fm/shows/ross-files-with-dave-ross/dr-williamhaseltine-we-dont-need-a-vaccine-to-end November 11, 2020 Pandemic parenting stress is real. Adults, on average, have increased the amount of alcohol they consume since the pandemic. But women with children increased their drinking more than any other group, likely due to the added stress of parenting. https://www.washingtonpost.com/lifestyle/2020/11/09/paren ts-alcohol-consumption-COVID/ 2759
TWITTER: These are truly horrifying numbers. A new report finds that people in Texas prisons are testing positive for COVID at a rate 490% higher than for the state of Texas as a whole and at least 231 people - staff and prisoners - have died in Texas prisons to date.https://repositories.lib.utexas.edu/handle/2152/83635 LINKEDIN/FACEBOOK: These are truly horrifying numbers. A new report finds that people in Texas prisons are testing positive for COVID at a rate 490% higher than for the state of Texas as a whole and at least 231 people - staff and prisoners - have died in Texas prisons to date. Some of the key findings: - 80% of people who died from COVID-19 in county jails in Texas were pretrial and not convicted of a crime. - 58% of the people who died from COVID in Texas prisons were eligible for parole at the time of their death. - Nine people died in prison who were approved for parole but not yet released - Over 80% of people who died from COVID in Texas prisons were over age 55. https://repositories.lib.utexas.edu/handle/2152/83635 November 12, 2020 Hundreds of thousands of healthcare workers have contracted COVID-19and thousands have died, according to a new survey. The U.S. reported the highest number of infections out of 37 countries. The numbers are shocking but likely an undercount of the true number infected. https://www.medscape.com/viewarticle/940701 The Pfizer vaccine's cold chain requirements mean low income & rural areas in the US and abroad will likely not get the drug. Most health systems, save for large city centers, aren't prepared to vaccinate large numbers of people with vaccines that require special equipment, procedures or monitoring. https://www.statnews.com/2020/11/11/rural-hospitals-cantafford-freezers-to-store-pfizer-COVID19-vaccine/ A new study finds 20% of those diagnosed with COVID-19 go on to develop some form of mental illness within 90 days. Anxiety, depression and insomnia were the most common mental health 2760
problems cited. A sign of COVID-19's effect on the brain and the mind. https://www.reuters.com/article/us-health-coronavirusmental-illness-idUSKBN27P34L Underlying all scientific progress are decades of research, sustained government funding, bold entrepreneurs, and remarkable intellects, like my friend Robert Langer, a driving force for the RNA technology described here. Learn the origins of the technology offering hope to our world. https://www.statnews.com/2020/11/10/the-story-of-mrna-howa-once-dismissed-idea-became-a-leading-technology-in-theCOVID-vaccine-race/ TWITTER: COVID vaccine protection is likely due to primary immune response & not long-term immune memory. Observed protection must be due to short term antibodies, not a memory response. There must have been a short interval between 2nd dose of vaccine & infection. Memory is best tested 6mo-1yr post vaccine. https://www.forbes.com/sites/judystone/2020/11/10/pfizersCOVID-19-vaccine-results-look-exciting-but-come-with-bigwarnings/?sh=596377521bc8 LINKEDIN & FACEBOOK: Most vaccines rely on long-term memory B and T cells for efficacy long after the vaccine is administered. The immediate T and B cell responses fade. It is immune memory that allows the body to mount a rapid response to infection in those vaccinated. In the case of accelerated vaccine approval, we do not know if the vaccines generate long-term memory. The time between the last vaccine administration and infection is very short, possibly weeks and certainly no longer than a month or two. Whatever protection the vaccine offers is very likely due to the primary immune response to the virus, that is antibodies present as the result of recent vaccination, and not to immune memory. Immune memory is best tested six months to a year after vaccination. The Pfizer vaccine and other vaccines may well elicit memory responses, harbingers of long term protection, but we certainly do not know that from these results. https://www.forbes.com/sites/judystone/2020/11/10/pfizersCOVID-19-vaccine-results-look-exciting-but-come-with-bigwarnings/?sh=596377521bc8 2761
35 years since we discovered HIV, and we still don’t have a vaccine. But we now have the promise of the next best thing: Two long-acting prevention drugs that could effectively end the pandemic. https://www.forbes.com/sites/williamhaseltine/2020/11/10/lo ng-lasting-hiv-drugs-hold-lessons-for-us-all/?sh=77cf56c82962 A very small study under peer review is pointing us in a promising direction for preventing transmission of COVID-19: Nasal spray. https://www.forbes.com/sites/williamhaseltine/2020/11/10/t his-nasal-spray-could-be-the-breakthrough-we-need-to-endCOVID-19/?sh=34a5fcb84132 Coronavirus has been discovered on frozen food packaging, posing concerns for food handling and transportation facilities and workers. https://www.forbes.com/sites/williamhaseltine/2020/11/09/ar e-frozen-foods-a-risk-for-COVID-19-infection-possibly/ I have many questions about Pfizer’s announcement that they have a vaccine that is 90% effective. Read more about my concerns here: https://www.businessinsider.com/infectious-disease-experton-waiting-on-pfizers-vaccine-data-2020-11 https://www.williamhaseltine.com/a-love-of-science/ November 16, 2020 In 1960 I was a sophomore in high school. Here is my friend, Jeffrey Besser, in front of our science fair project. Our experiments demonstrated how bacteria from my throat created boils in rats and how antibiotics cured them. In this article I share some of what it is about science that inspires and drives me to this day. You can also check out my new autobiography, available on Amazon. https://www.williamhaseltine.com/a-love-of-science/ Inequitable policies in our health, criminal justice, education, housing and employment systems, have created the conditions for COVID-19 to harm communities of color disproportionately, not to mention that non-whites are more likely to become infected and suffer from more severe illness than their white counterparts. In this article I highlight the disparities and suggest short and long-term measures we can take to address inequity. 2762
https://dailyclout.io/COVID-19-has-laid-bare-the-inequitiesin-our-health-system-what-are-we-going-to-do-about-it/ Antiviral drugs such as monoclonal antibodies offer hope for COVID-19 patients if administered in the early stages of infection. These offer hope for ending the pandemic by summer, if we move quickly and do two critical things. Read more about those here: https://www.forbes.com/sites/williamhaseltine/2020/11/13/aray-of-hope-for-treatment-of-COVID-19/?sh=171b318a1d88 I completely disagree with Dr. George Delgado: It is far more spiritually devastating to lose a family member to COVID than it would be to limit the size of your wedding. https://www.thedailybeast.com/abortion-reversal-dr-georgedelgado-inventor-enlists-in-the-COVID-wars?ref=scroll I spoke with Ernie Manouse on Town Square about the Pfizer vaccine and what we can understand about how it works. As I told him on the show, this vaccine makes me more hopeful today than I was yesterday. https://www.houstonpublicmedia.org/articles/shows/townsquare/2020/11/10/385954/a-new-vaccine-against-COVID-andhealth-experts-answer-your-questions/ Pfizer’s vaccine should be useful for many people--it should moderate the severity of the disease. https://www.nbcnews.com/health/health-news/pfizer-sCOVID-19-vaccine-promising-many-questions-remain-n1247102 November 17, 2020 This story shows the power of celebrity and notoriety in public perception. We have argued for months that reinfection is likely. Now that Boris Johnson is at risk, the message is being heard. https://www.huffingtonpost.co.uk/entry/can-you-catch-COVID19twice_uk_5f4761f3c5b64f17e138cab4?utm_campaign=share_email &ncid=other_email_o63gt2jcad4 I suggest that we take the good news about Moderna’s vaccine with a healthy dose of caution. Given what we know about distribution challenges, and what we don’t know about the vaccine’s safety, we can’t rely on a vaccine alone to protect ourselves. The one sure way to contain this virus remains: Wear a mask and social distance, get tested, and isolate when infected. 2763
https://www.forbes.com/sites/williamhaseltine/2020/11/16/anote-of-caution-on-modernas-promising-COVID-19-vaccinenews/?sh=73ef0c44532d At-home testing for COVID-19 could save lives. Let’s take some of the hard lessons we learned with the 25-year ban on at-home HIV testing and apply them to this current coronavirus pandemic, and not repeat the past. https://www.statnews.com/2020/11/16/build-COVID-19home-testing-plan-on-reason-not-speculation-or-politics/ COVID-19 is a community problem. As this article highlights, some parents are failing to consider how their decision not to test for the virus impacts the wider population. At the same time, what are families to do when they get a positive result? Our society has a responsibility to support them. https://www.parents.com/health/coronavirus/in-an-attemptto-keep-schools-open-some-parents-are-refusing-to-test-theirkids-for-COVID-19/?=234234 November 18, 2020 Our healthcare workers are putting themselves at risk every day, and in the past three months, their rate of infection has doubled in the U.S. alone. To date, almost 800 American healthcare workers have died from COVID-19. We all need to work together to slow the spread of this disease to protect our most essential front-line workers. https://www.forbes.com/sites/williamhaseltine/2020/11/17/t he-infection-of-hundreds-of-thousands-of-healthcare-workersworldwide-poses-a-threat-to-national-healthsystems/?sh=4d1c031d3499 I spoke with Kathleen Hays and Haidi Stroud-Watts on "Bloomberg Daybreak” about the COVID vaccines: What we know, what we don’t, and what we can expect about effectiveness. https://www.bloomberg.com/news/videos/2020-1116/vaccine-to-reach-most-people-by-mid-2021-says-accesshealth-international-president-video Everyone is struggling to cope with isolation and loneliness from our extended coronavirus pandemic. Don’t let Thanksgiving be a time to ignore guidelines--now more than ever it is important to stay home and stay safe. 2764
https://www.forbes.com/sites/williamhaseltine/2020/11/17/d o-not-ignore-COVID-19-safety-this-thanksgiving/ “That is a big distinction. What is important for you and what is important for your fellow human? What do you need? What do they need? Science as a discipline is agnostic. It is a tool. How do you direct that tool? For me, this has always come from understanding human need.” Read more in Haseltine’s latest Autobiography: https://www.amazon.com/dp/B08LL5T2ZW November 19, 2020 Sweden has six times the death rates of other Scandinavian Countries and no better economic results. Sound public policy makes a difference in people’s health and lives. Swedish hubris, stubbornness and exceptionalism have resulted in a heavy burden of needless death. https://www.washingtonpost.com//world/2020/11/18/swedencoronavirus-surgepolicy/?utm_campaign=wp_todays_worldview&utm_medium=em ail&utm_source=newsletter&wpisrc=nl_todayworld&cartaurl=https%3A%2F%2Fs2.washingtonpost.com%2Fcar-lntr%2F2cd0ff4%2F5fb4a9579d2fda0efb6bcdee%2F596a9c6bae7e8a0 ef340b8c3%2F10%2F87%2F2a2819295f08f700b7488be6add4f1ff November 20, 2020 Once a COVID-19 vaccine is approved, regulatory agencies must enforce long-term safety and monitoring procedures. Without adequate follow-up, we risk the safety of hundreds of millions. https://www.forbes.com/sites/williamhaseltine/2020/11/20/t o-guarantee-safety-of-COVID-19-vaccines-prioritize-long-termstudies/?sh=33d9a6dbf27e If Americans got tested every 1-3 days and self-isolated with a positive result, we could reduce COVID-19 transmission by 80%. Yet this at-home test, now on the market, doesn’t quite get us there. Read my article for more about how at-home testing could truly make an impact. https://www.forbes.com/sites/williamhaseltine/2020/11/19/w e-finally-have-rapid-at-home-COVID-19-tests-what-happensnow/?sh=3a0aeddd42c4 2765
November 21, 2020 Available NOW on Amazon: https://www.amazon.com/COVID-CommentariesChronicle-Plague-Iebook/dp/B08LK734XC/ref=sr_1_1?dchild=1&keywords=COVI D+commentaries&qid=1603302579&sr=8-1 November 23, 2020 There is a troubling lack of information on the impact of COVID-19 on our military’s preparedness of forces at air, land, and sea. We need the military to be more forthcoming about how it is controlling the virus in its ranks. https://www.forbes.com/sites/williamhaseltine/2020/11/20/h ow-is-COVID-19-impacting-the-preparedness-of-the-usmilitary/?sh=1ed807e91677 As we mark one year since the discovery of COVID-19, and hold out hope for returning to a normal world, I have my doubts. There is reason to believe that COVID-19 will become endemic, meaning once infected, you can become reinfected. https://www.forbes.com/sites/williamhaseltine/2020/11/20/C OVID-19-reinfection-is-possible-and-should-inform-pandemicpriorities-moving-forward Tune in to @modrnhealthcr interview with the CEO of @nationwidekids to learn about the mental health crisis facing children and teens and how providers are responding -- a symptom of the COVID crisis and what I have termed CVTSD, COVID-19 Traumatic Stress Disorder. https://www.modernhealthcare.com/the-checkup?utm_source=mhcheetah&utm_medium=webform&utm_campaign=The-CheckUp . @JamesFallows on the negligent homicide of thousands of Americans "Terms like 'negligence' and 'manslaughter' and, yes, 'homicide' are useful right now. They give us a way of assessing the horror a government is visiting upon its people" https://www.theatlantic.com/ideas/archive/2020/11/this-istrumpsfault/617159/?utm_source=twitter&utm_medium=social&utm_ca mpaign=share 2766
A negative COVID test doesn't give you the go ahead to socialize freely. A test is just a snapshot in time, it doesn't guarantee you're not infected or you won't be infectious tomorrow. To protect those around you, you still need to wear a mask, distance, and avoid indoor settings https://www.nytimes.com/2020/11/21/upshot/coronavirus-testthanksgiving-plans.html?smid=em-share Faced with the reality that the Pfizer COVID-19 vaccine won't be widely available anytime soon, India is turning to candidates like Russia's Sputnik-V and the Oxford vaccine to fill the void. https://timesofindia.indiatimes.com/india/india-pins-hopes-onlocally-tested-COVID-19-vaccines-given-pfizerconstraints/articleshow/79266351.cms Evidence suggests that about one in five infected people will experience no symptoms. That doesn't mean they have a stronger immune response. https://www.nature.com/articles/d41586-020-03141-3 COVID has had a disproportionate effect on women, from job losses to the risks of infection, since women make up much of the healthcare workforce. Lockdowns caused lapses in maternity care and an increase in domestic abuse. This threatens women’s opportunities now & in the future. https://www.projectsyndicate.org/commentary/COVID-long-term-costs-for-womenand-girls-by-pinelopi-koujianou-goldberg-2020-11 The heaviest burden of COVID-19, like much else, falls on minorities, the poor and the disadvantaged in all parts of America, as illustrated by this story of COVID in Massachusetts. https://www.bostonglobe.com/2020/11/20/metro/coronavirussurge-made-worse-by-inequity/ We are a forward looking species. See these thoughts on the future of the COVID-19 pandemic. My view: it may end for some before it ends for many! https://www.bostonglobe.com/2020/11/21/nation/end-is-sightexperts-express-optimism-about-COVID-19-pandemic-comingclose/ Lombardy has world-class medical facilities but was overwhelmed by COVID-19 - a consequence of entrusting a public healthcare system to the private sector while failing to coordinate their services. This highlights the need for strong public 2767
health infrastructure & education. https://www.nytimes.com/2020/11/19/business/lombardy-italycoronavirus-doctors.html?smid=em-share November 24, 2020 Despite the breadth of damage COVID-19 has already wrought, we are only beginning to glimpse what its long term toll might be. There is no doubt though that the impact of the pandemic will be massive, indelibly imprinting and changing the behaviors of our rising generations. Read more in my COVID Commentaries Vol. 1... https://www.amazon.com/COVID-CommentariesChronicle-Plague-Iebook/dp/B08LK734XC/ref=sr_1_1?dchild=1&keywords=COVI D+commentaries&qid=1603302579&sr=8-1 On this Health Matters podcast, Ned Hoke and I had a wide ranging discussion about my background in science as well as the current coronavirus pandemic. https://podcasts.apple.com/us/podcast/11-20-20-authorwilliam-haseltime-a-family-guide-toCOVID/id1347605924?i=1000499637598 The Chinese government has determined that approximately 5% of COVID-19 cases have an incubation period longer than the 14 days that are currently informing our quarantine guidelines. While we don’t have much data yet about this, right now, it doesn’t hurt to be extra cautious to protect yourself and your loved ones. https://www.forbes.com/sites/williamhaseltine/2020/11/23/d ont-assume-a-14-day-quarantine-is-enough/?sh=59c3fe1b721e With Thanksgiving fast approaching, please take extra precautions about air travel. I share these tales of contagion on plane flights--including one that led to 60 cases--with the hope that we don’t see these scenes repeated this holiday season. https://www.forbes.com/sites/williamhaseltine/2020/11/23/o ne-man-one-plane-seven-infections-and-counting-a-cautionarytale-for-all-those-planning-air-travel/ More reason to be cautious over the Thanksgiving holidays. Data show hospitalized COVID-19 patients are surviving at higher rates, but a surge in new cases -- as is happening across the country today -- could roll back these gains. 2768
https://www.statnews.com/2020/11/23/hospitalized-COVID-19patients-surviving-at-higher-rates-but-surge-could-roll-back-gains/ Patterns of devastation as a new wave of infections sweeps the US: losses among racial and ethnic minorities remain disproportionately large. Black Americans were 37% more likely to die than Whites; Asians 53%; Native Americans and Alaskan Natives, 26%; & Hispanics 16% https://www.washingtonpost.com/graphics/2020/health/COVID -race-mortality-rate/ November 25, 2020 A new mural at University of Texas at Arlington’s North Texas Genome Center -- which processes campus COVID-19 tests -depicts colorful portraits of individuals wearing masks. My sister Florence is the medical director there and a passionate supporter of the arts. https://www.uta.edu/news/newsreleases/2020/11/19/seirmural?fbclid=IwAR2CoygPqUdeXaMvqhYTTmFF4lQcGUkUIP kq9VRDtUbVpkuT32hEtRaErms A new study of COVID antibodies from July-September found that prevalence ranged from just 1% to 23%. This means most Americans have not been infected. But even those who have should still be cautious. Immunity wanes and everyone should still wear masks & remain socially distant. https://jamanetwork.com/journals/jamainternalmedicine/fullarticl e/10.1001/jamainternmed.2020.7976?utm_source=STAT+Newsle tters&utm_campaign=fa6bcbf6f6MR_COPY_01&utm_medium=email&utm_term=0_8cab1d7961 -fa6bcbf6f6-151227717 As a potential COVID vaccine becomes reality, we need to think more about vaccine acceptance. @MIAMIBIZDEAN explains 4 factors that will influence whether people get vaccinated: perceived risk, perceived effectiveness, perceived convenience, and perceived fairness. https://www.miamiherald.com/opinion/oped/article247378524.html There's highly unequal access to COVID testing & quick results. Many clinics promise immediate testing and instant results but at a cost. Some charge $150 or more. Many also pay the cost of time off work. Very low cost, self-administered home tests could make an 2769
important difference. https://www.modernhealthcare.com/safetyquality/inequality-baked-virus-testing-access-cases-surge Survival rates for serious COVID-19 have not improved since the summer. The new drugs are either not working or are not deployed properly. https://www.washingtonpost.com/politics/2020/11/24/health202-coronavirus-survival-rates-united-states-havent-improvedsince-summer/ Experts warn the toxic mix of isolation and economic devastation could generate a wave of suicides, but these dire predictions have resulted in little action. A CDC study shows that COVID-19 has affected the mental health of those age 18-24, with 1 in 4 contemplating suicide. https://www.washingtonpost.com/health/2020/11/23/COVIDpandemic-risesuicides/?utm_campaign=wp_the_health_202&utm_medium=ema il&utm_source=newsletter&wpisrc=nl_health202 Hundreds who died in NYC in the COVID surge in the spring are still in storage in freezer trucks. Officials are unable to track down some relatives and families who are reached can't afford to collect the bodies. Another sad consequence of our gov't not controlling COVID-19. https://www.wsj.com/articles/nyc-deadstay-in-freezer-trucks-set-up-during-spring-COVID-19-surge11606050000 November 26, 2020 Testing can make a difference if there are enough tests. They are inexpensive. They are fast. They are convenient (self administered home tests are best). The technology exists but we don’t use it!!! https://www.bostonglobe.com/2020/11/23/business/COVID19-testing-mass-is-far-short-levels-needed-stop-spread/ Despite the WHO recommending against the use of the antiviral remdesivir for COVID-19 patients, some doctors continue to back the drug as a possible cure. The WHO says there's no evidence to suggest it improves survival or other health outcomes. https://www.reuters.com/article/health-coronavirus-idsaguidelines/u-s-infectious-disease-group-backs-gileads-remdesivirfor-COVID-19-treatment-idUSL1N2I916W 2770
Who receives a COVID vaccine first? Health workers treating COVID patients, essential workers, the elderly & high risk. But who qualifies as an essential worker? Are elderly in nursing homes too fragile? Does high risk include the 35% of Americans who are obese? https://www.statnews.com/2020/11/23/essential-workers-likelyto-get-earlier-access-to-COVID-19-vaccine/ November 27, 2020 I went into science to help humanity. You can learn more about my journey in my new autobiography: My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19. Available on Amazon: https://www.amazon.com/dp/B08LL5T2ZW Hospitals in at least 25 states are critically short of nurses, doctors, and other staff as COVID-19 surges. Many of these hospitals built up stockpiles of medical equipment and protective gear, but the supplies are of little use without adequate staffing. https://www.statnews.com/2020/11/19/COVID19-hospitals-inhalf-the-states-facing-massive-staffing-shortage/ November 28, 2020 No group has been left untouched — no gender, ethnicity, age or income bracket — but some have suffered much more than others from what I have termed CVTSD, COVID-19 Traumatic Stress Disorder. Read my article in Psychology Today to learn more about how COVID-19 is affecting our mental health. https://www.psychologytoday.com/us/blog/best-practices-inhealth/202011/the-mental-health-toll-COVID-19 November 30, 2020 A major omission in Biden's COVID Task Force: a mental health expert. In a recent survey of young adults, nearly half reported significant symptoms of depression, severe enough to prompt treatment. This is 6 times higher than normal what I call COVID-19 Traumatic Stress Disorder https://www.statnews.com/2020/11/23/mental-health-expertisemissing-from-biden-COVID-19-task-force/ This story is for those of all ages that believe that death from COVID-19 is visited only on the old. Read the story of three 2771
young deaths with rage for those who encourage us to defy rational public health guidelines.https://abcnews.go.com/US/wreckedlives-families-young-adults-died-COVID-19/story?id=74148061 Steve Roach predicted a W-shaped COVID recovery. Here he makes the cause that the apparent late summer/early fall recovery was a "dead cat bounce" and that, as a service-based economy, we are in for serious economic pain until mid-summer 2021. https://www.project-syndicate.org/commentary/more-economicpain-before-COVID19-vaccine-by-stephen-s-roach-2020-11 More evidence of COVID-19 Traumatic Stress Disorder #CVTSD - 13.6% of US adults in April 2020 report serious psychological distress vs 3.9% in 2018. We have much more work to do beyond ending the spread of SARS-CoV-2. https://jamanetwork.com/journals/jama/fullarticle/2773517#:~:te xt=November%2023%2C%202020,Psychological%20Distress%20and%20COVID%2D19%E2%80%93 Related%20Stressors%20Reported%20in%20a,in%20April%20and% 20July%202020&text=Serious%20psychological%20distress%20was %20reported,2020%20vs%203.9%25%20in%202018. Even the young suffer from COVID-19 Traumatic Stress Disorder. Many young children remote learning are suffering emotionally, mentally and even physically from so many hours, often alone, in front of a computer screen - back pain, burning eyes & even a loss of interest in food. https://www.washingtonpost.com/education/2020/11/27/remote -learning-emotional-toll/?arc404=true Healthcare workers are quitting due to stress "I was experiencing what healthcare people have come to call moral injury, or a kind of PTSD, and that it was best for my health if I left." COVID-19 Traumatic Stress Disorder affects all of us but especially those on the frontlines. https://www.modernhealthcare.com/nursing/workersleaving-healthcare-prisons-over-COVID-19-stress See Jeffrey Sachs' long list of ailments in US political, institutional, and international affairs that are in desperate need of repair. He describes what needs to be done, but only hints at how it can be accomplished. https://www.projectsyndicate.org/onpoint/america-political-crisis-and-globalcooperation-by-jeffrey-d-sachs-2020-11
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Just because COVID is raging in most countries doesn't mean other diseases are taking time out. But in some countries, research and eradication programs for infectious diseases like malaria have been set back by many months, even years. https://www.who.int/teams/global-malariaprogramme/reports/world-malaria-report-2020 Why don't more Americans use contact tracing apps? A lack of trust, according to this article. These apps need more users to become more accurate, but accuracy is what begets trust in the first place. https://www.modernhealthcare.com/informationtechnology/people-weakest-link-apps-tracking-coronavirusexposure?utm_source=modern-healthcare-COVID-19coverage&utm_medium=email&utm_campaign=20201129&utm_ content=article1-headline
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December 1, 2020 The FDA, FBI & DHS are looking for phony Covid vaccines and other scams. They're working with drug companies to study the vaccine's packaging to help spot fakes and limit fraud. Since the pandemic started, millions of fake PPE products & drugs were seized https://www.modernhealthcare.com/safety-quality/bewarecovid-19-scams-vaccine-approaches-fda-approval This study shows the psychological effect of the pandemic on US adults in the spring and early summer. Things have only become worse since then, with the exception of hope for a vaccine. We should stay alert about our mental health & the mental health of those we love. #CVTSD https://jamanetwork.com/journals/jama/fullarticle/2773517#:~:te xt=November%2023%2C%202020,Psychological%20Distress%20and%20COVID%2D19%E2%80%93 Related%20Stressors%20Reported%20in%20a,in%20April%20and% 20July%202020&text=Serious%20psychological%20distress%20was %20reported,2020%20vs%203.9%25%20in%202018. There are no comprehensive studies on the pandemic and its impact on suicide rates across the globe. But emerging trends from Japan and South Korea may be an early warning of the toll on our mental health and the broad impact of Covid-19 Traumatic Stress Disorder #CVTSD https://www.washingtonpost.com/world/asia_pacific/japansuicides-pandemic-women/2020/11/28/0617e3a2-fdbd-11eab0e4-350e4e60cc91_story.html The confusion over who will receive a Covid vaccine, what the vaccine will be, and when they will receive it begins... https://www.statnews.com/2020/11/30/divisions-emerge-amongu-s-officials-over-when-first-covid-19-vaccine-doses-will-beavailable-and-for-whom/ The question: Are Americans as responsible to one another as the French and is our federal government as effective? My answer: probably not enough to ensure that what is working in France will work in the United States, even with a much better administration. https://www.nytimes.com/2020/11/30/world/europe/francecovid-schools.html?smid=em-share
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The US is finally beginning to recognize what happened to us and Covid under the Trump administration. Fine journalists are not only reporting the latest news but to integrate our collective experience and to describe the unnecessary tragic reality. 1/2 https://www.nytimes.com/2020/11/30/health/coronavirusvaccines-treatments.html?smid=em-share The US is finally beginning to recognize what happened to us and Covid under the Trump administration. Fine journalists are not only reporting the latest news but to integrate our collective experience and to describe the unnecessary tragic reality. 2/2 https://www.huffpost.com/entry/what-needs-happen-covidpandemic-over_l_5fc4448dc5b66bb88c680942 The US is not the first country to develop & test Covid-19 vaccines. Pfizer and Moderna are requesting EUAs based on tens of thousands of people. Russian & Chinese vaccine makers are basing approval on hundreds of thousands. For all, we must regret the lack of transparency on results. https://uk.reuters.com/article/healthcoronavirus-vaccine-chinaidUSKBN27R1Q1?utm_source=STAT+Newsletters&utm_campa ign=fcd62cce02stat_china_COPY_01&utm_medium=email&utm_term=0_8cab1d 7961-fcd62cce02-151227717 A thoughtful article that describes the dilemmas and questions of “real people” as they seek to understand the implications of possible Covid-19 vaccines. https://www.modernhealthcare.com/opinion-editorial/we-needbe-ready-vaccines-industry-nation Weekly testing is insufficient. It should be daily or every other day, at a minimum, to detect the contagious and to allow for early treatment which may forestall hospitalization and death. https://www.modernhealthcare.com/labor/california-urges-covid19-tests-all-hospital-staff-patients December 2, 2020 Yet another controlled clinical trial that concluded hydroxychloroquine should not be used to treat Covid-19 patients. https://jamanetwork.com/journals/jama/fullarticle/2772922 I am no lawyer, but as a vaccine maker and former CEO of a drug company myself, I can tell you that it is wrong for drug 2776
company executives to be personally profiting from stock sales in coordination with early announcements of success in their vaccine trials. This self-interested behavior is undermining the public’s trust in the safety of these vaccines. https://www.forbes.com/sites/williamhaseltine/2020/11/30/p ut-an-end-to-publication-by-proclamation-for-covidvaccines/?sh=5e65981b2672 In this Spanish publication, El Pais, I along with others discuss the relationship between HIV/AIDS and the coronavirus pandemic. https://elpais.com/planeta-futuro/2020-12-01/lecciones-delvih-para-la-covid-19.html Until we have an approved vaccine widely available (probably not until spring/summer 2021) and in the present absence of decisive federal leadership, Congress and the states must take action to stem the spread of the pandemic. https://thehill.com/opinion/healthcare/528053-congress-andthe-states-must-fix-trumps-covid-19-mistakes?rnd=1606779464 December 3, 2020 We need a Covid-19 vaccine that works worldwide, both rural and urban, in high- and low-income countries. This article dives into the differences between types of vaccines and which ones would be most practical for distribution to stem the spread of this disease affecting every nation on earth. https://www.forbes.com/sites/williamhaseltine/2020/12/02/w hy-most-countries-wont-benefit-from-moderna-and-pfizers-covid19-vaccines/?sh=3d531cc65170 China is proving to be the canary in the coal mine when it comes to rare and consequential types of Covid-19 transmission. Most recently: Contaminated freight trucks. https://www.forbes.com/sites/williamhaseltine/2020/12/03/t hese-forms-of-covid-19-transmission-may-be-rare-but-cant-beignored/?sh=7ebb23ff3ab7 9/11 claimed the lives of 3,000 Americans. The coronavirus pandemic has killed a quarter million. To protect ourselves from future attacks--this time from a virus--we would be wise to respond with the same level of concern as we did to protecting ourselves from terrorism following the 9/11 attacks. Written 2777
together with General John Allen, President of the Brookings Institution. https://www.theatlantic.com/ideas/archive/2020/12/usneeds-covid-19-commission/617242/ Dr. William Haseltine, PHD, from his autobiography, My Lifelong Fight Against Disease: From Polio and AIDS to COVID19. Available on Amazon: https://www.amazon.com/dp/B08LL5T2ZW December 4, 2020 Should residents of long-term care facilities be among the first to receive the COVID-19 vaccine? The answer is probably no. Best to wait a bit until we have more data on this age group. https://www.statnews.com/2020/12/03/cdc-advisory-panelslone-dissenter-on-why-long-term-care-residents-shouldnt-receivecovid-19-vaccine-first/ LinkedIn version -In a CDC vote on whether long-term care residents should be among the first to receive a COVID-19 vaccine, only one committee member dissented. An expert on the effects of vaccines in older adults, she raised an important concern--the absence of data that shows the leading candidates are safe and effective in this group. Even if the vaccines are safe, providing vaccinations to longterm care residents first may run the risk of undermining public confidence in vaccines in the long run. Reports of adverse health conditions that residents of long-term care facilities would have developed regardless of vaccination might lead the public to be unnecessarily fearful of the vaccine. https://www.statnews.com/2020/12/03/cdc-advisory-panelslone-dissenter-on-why-long-term-care-residents-shouldnt-receivecovid-19-vaccine-first/ 2) See this analysis of a South Korean study confirming that in restaurants, Covid-19 can be transmitted efficiently by aerosols both a) at a distance and b) over a short period of time. The details are worth reading. https://zeynep.substack.com/p/small-data-bigimplications 3) Face masks reduce Covid-19 transmission by about 45%, according to this German study. The reduction was observed just 2778
20 days after masks were made mandatory. https://www.pnas.org/content/early/2020/12/02/2015954117 4) One manufacturing misstep could result in serious health complications for anyone taking a Covid-19 drug or vaccine. That's why the FDA must inspect the plants set to manufacture them. Read the Vanity Fair investigation of these facilities for more https://www.vanityfair.com/news/2020/12/fda-covid-vaccineplant-inspectors?utm_source=onsiteshare&utm_medium=email&utm_campaign=onsiteshare&utm_brand=vanity-fair Governments must take great care to restore the public’s trust in vaccines, or this powerful tool will not be effective in helping us contain the pandemic. The recent actions by the UK sets a worrying precedent of prioritizing speed over safety, and the consequences could be devastating. https://www.forbes.com/sites/williamhaseltine/2020/12/04/u k-vaccine-approval-sets-worrying-precedent-for-worldleaders/?sh=4f30d3f86adf As Covid-19 cases, hospitalizations, and deaths are peaking in the US, the CDC has released new and relaxed guidelines for isolating after infection. This will inevitably lead to increased cases and a prolonged pandemic. Read more here about the new guidelines and why they’re problematic. https://www.forbes.com/sites/williamhaseltine/2020/12/04/m odified-cdc-guidelines-grants-covid-19-patients-discretion-toleave-quarantine-early/?sh=7e2ae9a82692 December 5, 2020 The current divide between the two political parties’ responses to Covid-19 is severely limiting our ability to both respond to the current crisis as well as prepare for future virus outbreaks or bioterrorism. General John Allen, the President of the Brookings Institution, and I wrote this piece together to urge the US Government to create a bipartisan Covid-19 commission to provide a full accounting of the country’s response to the pandemic and prepare us for the future. https://www.theatlantic.com/ideas/archive/2020/12/usneeds-covid-19-commission/617242/ 2779
December 6, 2020 Despite the breadth of damage COVID-19 has already wrought, we are only beginning to glimpse what its long term toll might be. There is no doubt though that the impact of the pandemic will be massive, indelibly imprinting and changing the behaviors of our rising generations. Read more in my COVID Commentaries Vol. 1... https://www.amazon.com/COVID-CommentariesChronicle-Plague-Iebook/dp/B08LK734XC/ref=sr_1_1?dchild=1&keywords=covid +commentaries&qid=1603302579&sr=8-1 In forgoing regulatory protocols to approve Pfizer's Covid-19 vaccine, the UK government has chosen speed over safety. If governments don't take care to restore public trust in vaccines before launching mass vaccination campaigns, they risk ridding this tool of its potency. https://www.forbes.com/sites/williamhaseltine/2020/12/04/u k-vaccine-approval-sets-worrying-precedent-for-worldleaders/?sh=4f30d3f86adf As Covid-19 cases, hospitalizations, and deaths are peaking in the US, the CDC has released new and relaxed guidelines for isolating after infection. This will inevitably lead to more cases and a prolonged pandemic. Read more here about the new guidelines and why they’re problematic. https://www.forbes.com/sites/williamhaseltine/2020/12/04/m odified-cdc-guidelines-grants-covid-19-patients-discretion-toleave-quarantine-early/?sh=7e2ae9a82692 December 8, 2020 A thoughtful review of an analysis of the tension between science, governance, and human behavior revealed by Covid-19 with an emphasis on the Nordic countries and Asia https://www.noemamag.com/a-tale-of-two-pandemics/ Efforts to integrate mental health & social services in home and primary care settings are especially relevant to dealing with the sequelae of the pandemic and Covid-19 Related Traumatic Stress Disorder #CVTSD: anxiety, depression, domestic violence, opioid addiction & suicide. https://www.nap.edu/read/25927/chapter/1 2780
Confirmed efficient aerosol Covid-19 transmission at a distance for a short time in a restaurant. The details are worth reading. https://zeynep.substack.com/p/small-data-big-implications Face masks reduce Covid transmission by 45% "20 days after becoming mandatory face masks have reduced the number of new infections by around 45%. As economic costs are close to 0 compared to other public health measures, masks seem to be a cost-effective means to combat COVID" https://www.pnas.org/content/early/2020/12/02/2015954117 How has it come to this again? New Mexico will soon allow hospitals to move to crisis standards, which lets them to ration care depending on a patient’s likelihood of survival. A doctor's nightmare, but with limited ICU capacity for Covid-19 care, there may be no other choice. https://www.washingtonpost.com/national/new-mexicohospitals-covid-crisis/2020/12/04/3d06e2d2-3675-11eb-b59cadb7153d10c2_story.html LinkedIn and Facebook: We are just beginning to get hints of the series of issues that will complicate vaccine distribution and uptake. The issues with vaccines will mimic many of the problems we encountered with testing. Most of these issues stem from local rather than national control of public health measures. What is certain is that vaccine accessibility will vary dramatically from state to state, county to county, city to city, and from town to town. Inequities in health service accessibility will be amplified. https://www.washingtonpost.com/politics/2020/12/03/health202-states-need-distribute-coronavirus-vaccines-they-struggledwith-past-immunization-efforts/? Twitter: Hints of complications to come for Covid vaccine distribution and uptake. They mimic many of the problems we encountered with testing, with states determining their own rollout. Vaccine accessibility will vary dramatically by state, city and county amplifying inequities. https://www.washingtonpost.com/politics/2020/12/03/health202-states-need-distribute-coronavirus-vaccines-they-struggledwith-past-immunizationefforts/?utm_campaign=wp_the_health_202&utm_medium=email &utm_source=newsletter&wpisrc=nl_health202
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The pressure on families through Covid-19 is relentless. Working parents have strained their budgets since spring to pay for school and day-care substitutes — and there’s no end in sight. As is often the case, lower income and single parent families suffer the most. https://www.thelily.com/the-cost-of-child-care-wasalready-astronomical-in-the-pandemic-its-terrifying/ This vaccine Q&A misses an important question: If I'm vaccinated should I still wear a mask? My answer: Yes. Vaccines may only prevent symptoms, not infection, which means those vaccinated may still spread the virus. Everyone should wear masks & distance until infection rates drop https://www.nytimes.com/2020/12/07/us/coronavirustoday.html Vaccines may be widely available this summer, but Covid-19 is spreading like wildfire today. Basic precautions like masks, social distancing, and handwashing will lead to fewer infections and deaths immediately, meaning a quicker end to the pandemic. https://www.nytimes.com/2020/12/08/briefing/vaccine-dongable-your-tuesday-briefing.html December 9, 2020 After a tough year, recommendations for tough conversations over the holidays and declining invitations to family gatherings. Be grateful for the invitation and honest about declining because of Covid-19. “You have to be OK with people not understanding” https://www.bostonglobe.com/2020/12/06/nation/how-canyou-say-no-family-during-holidays-with-kindness-experts-urge/ Four things to stay healthy and sane this winter: Get your flu shot. Figure out a fitness routine and stick to it. Consider a Vitamin D supplement. Monitor your mental health and improve your mental wellbeing through meditation, talk therapy or even daily gratitude lists. https://www.gq.com/story/four-things-for-covidwinter Please see what could be a long-awaited breakthrough for repair of deleterious inherited genetic variants using CRISPR technology. In this case, promising preliminary results for inherited red blood cell disorders. This report may mark the beginning of a new era of genomic medicine. https://www.statnews.com/2020/12/05/preliminary-but-nothing2782
short-of-great-new-data-on-crispr-treatment-for-blood-diseasessuggest-cure-is-possible/ If we want to retain the gains and livelihoods we’ve made as a species, we must recognize and mitigate the losses we’ve wrought on the natural world. Here I discuss the findings and recommendations from a new report published in the Lancet Countdown about the connection between human health and planetary health, including the role of the Covid-19 pandemic. https://www.forbes.com/sites/williamhaseltine/?sh=701a1f365 088 December 10, 2020 The oceans are now yielding new classes of antibiotics at an ever-increasing rate thanks to genomics and metabolomics https://science.sciencemag.org/content/370/6519/974#:~:text=A %20polycyclic%20molecule%20dubbed%20turbinmicin,Candida%2 0auris%20and%20Aspergillus%20fumigatus. Why hasn't Zika disease caused as much devastation in Africa, its continent of origin, as it has in the Americas? The answer, according to this new study, is in part due to the mosquitoes that transmit the virus and how they differ across regions. https://science.sciencemag.org/content/370/6519/991 December 11, 2020 One of the key dangers of rushing out a Covid-19 vaccine is the lack of quality control. Due to manufacturing issues related to the concentration of vaccine used in clinical trials, AstraZeneca and Sanofi-GSK have slipped up and may never recover. https://www.statnews.com/2020/12/11/sanofi-suffers-majorsetback-in-development-of-a-covid-19-vaccine/ The city vs. country debate is as old as time yet still relevant, though of course the views expressed in this article are those of a NYC-based paper. Evidence suggests that in a time of plague, nowhere is safe. https://www.nytimes.com/2020/12/07/well/live/coronaviruscities-safe.html?smid=em-share Many states are seeing spikes in new cases this week that can be traced back to Thanksgiving festivities. If one day of the year is 2783
enough to make a dent, who knows what impact several weeks of winter travel and holidays will have. https://thehill.com/policy/healthcare/529271-first-signs-ofthanksgiving-covid-19-wave-emerge “We spend way too much money at the end of the process – health care services – and starve the beginning of the process – basic research and disease prevention.” In my autobiography, I talk about how I have dedicated my life to medical research as well as to affordable health care. You can read an excerpt on my website. (Note: This picture of President Bill Clinton with an AIDS patient in 1993 was taken shortly after he pledged to take the AIDS epidemic seriously and end it worldwide.) https://www.williamhaseltine.com/everyone-deserves-accessto-high-quality-affordable-healthcare/ December 12, 2020 Cancer in adolescents and young adults is on the rise. Between 1973 and 2015 cancer diagnosis increased 30%. Read more here about how we might start to understand what’s behind this alarming upward trend. https://www.forbes.com/sites/williamhaseltine/2020/12/09/c ancer-rates-are-on-the-rise-in-adolescents-and-young-adults-newstudy-shows/?sh=49769f123b7b Between 65-70% of the population must be vaccinated against Covid-19 for us to achieve herd immunity. While a vaccine will help, we must continue enforcing other public health measures or risk backsliding https://www.forbes.com/sites/williamhaseltine/2020/12/11/t he-trouble-with-covid-19-vaccines-and-herdimmunity/?sh=4db8547739a7 December 13, 2020 We don’t know yet whether vaccinated people can still catch and spread Covid-19. Until that data is available, we must proceed with caution. That means continuing to social distance, wear masks, and avoid travel. https://www.forbes.com/sites/williamhaseltine/2020/12/11/h ow-will-a-covid-19-vaccine-impact-travel/ 2784
COVID-19 has demonstrated that our health systems are weak and easily fractured. Read my article in Think Global Health about how government investment in healthcare systems is an investment in the economy. https://www.thinkglobalhealth.org/article/covid-19investment-our-economy December 14, 2020 It will take several months for the newly approved vaccine to curb the spread of Covd-19. Rapid testing is what can give us the momentum we need to outmaneuver the virus in the meantime. https://www.forbes.com/sites/williamhaseltine/2020/12/11/e ven-with-a-vaccine-we-still-need-rapid-tests-to-end-covid19/?sh=2693d6f23031 The decision of how, where, to whom and in what order to administer a Covid-19 vaccine will vary from state to state & by jurisdictions within states, maybe even from town to town. I predict confusion and anger, similar but more intense than what happened withCovid-19 testing. https://www.nationalgeographic.com/science/2020/12/who-isreally-first-in-line-coronavirus-vaccine-states-not-guaranteed/ Twitter: I spoke with @mattbish on Covid-19, science & policymaking. Science moved faster than ever to find drugs, diagnostics, and other tools to end this disease. But a vaccine won't stop it overnight. We need public health tools to end it: masks, distancing, testing & isolation https://drivingchange.org/sciencepolicymaking-and-the-pandemic-qa-with-bill-haseltine/ LinkedIn/Facebook: I spoke with @mattbish for his Driving Change podcast about Covid-19, science and policymaking. Many see science today as the superpower that will save us from this disease. Our scientists have shown remarkable success, first identifying the virus faster than we thought possible then finding drugs, diagnostics, and other tools to deal with this disease. But a vaccine or any other drug isn't going to stop this pandemic overnight. To end it, we have to put our trust in science and public health -- mask wearing, social distancing, and mass testing and isolation. https://drivingchange.org/science-policymakingand-the-pandemic-qa-with-bill-haseltine/ 2785
Vaccine distribution correlates roughly with the adult population in each state. A notable is exception is the difference between CA (relatively more) and NY (relatively less). Note the excellent graphic of Covid-19 infection rates, hospitalizations & deaths by state & territory https://www.nytimes.com/interactive/2020/12/11/us/covid-19vaccine-doses.html?smid=em-share Young adults may not usually suffer serious Covid-19 consequences but their behavior may cause death and injury to their communities. Some colleges and universities do not enforce rigorous testing and isolation, leading to outbreaks, but they are more the exception than the rule. https://www.nytimes.com/2020/12/12/us/covid-collegesnursing-homes.html?smid=em-share This personal account of a visit to France shows what an effective lockdown feels like. France reduced the infection rate by almost 20x within a month using these techniques. The US has not enforced similar measures. No wonder why we lead the world in cases and deaths per capita. https://www.nytimes.com/2020/12/10/us/france-lockdowncompare-new-york.html?smid=em-share There have been several issues with Covid-19 vaccines (eg. AstraZeneca's concentration & Sanofi's dilution issues). Now, concerns about vaccines & drugs manufactured in India. Given the speed of approval, there are similar concerns for drugs & vaccines in other countries as well https://www.statnews.com/2020/12/11/drug-regulator-indiafailed-pandemic-stress/ When we think of climate change, our thoughts do not turn naturally to the healthcare industry. These stories argue that it should. Healthcare makes up a significant part of GNP & produces copious carbon, paper, & plastic waste. We can and must do better. https://www.healthaffairs.org/toc/hlthaff/39/12 Health care workers and minorities in the UK are far more likely to succumb to serious disease if infected by SARS-CoV-2 than others. Health care workers are seven times more likely and minorities 3-5 times. https://www.medrxiv.org/content/10.1101/2020.05.22.20109892 v2 2786
An accounting of impact of Covid-19 on our mental health and the grief that will weigh on Americans for many years to come. I have called this Covid-19 Traumatic Stress Disorder, a collective suffering #CVTSD https://www.statnews.com/2020/12/09/drive-by-burials-andfacetime-farewells-grief-in-the-covid-era-will-weigh-on-theamerican-psyche-for-years-tocome/?utm_source=STAT+Newsletters&utm_campaign=a0ff0969 47MR_COPY_01&utm_medium=email&utm_term=0_8cab1d7961 -a0ff096947-151227717 This spectacular chart on the efficacy of the Pfizer vaccine warms the heart of every drug & vaccine researcher. It definitely works in the population tested. Now onto studies of duration, long-term efficacy, & reduction in transmission as well as disease. https://www.statnews.com/2020/12/08/fda-scientists-endorsehighly-effective-pfizer-biontech-covid-19-vaccine-ahead-of-keypanel/ The initial press reports of the data from the large scale Pfizer trial are positive and impressive. We await details to confirm this data from published manuscripts such as the one AstraZeneca published today in the Lancet. https://www.washingtonpost.com/graphics/2020/health/pfizervaccine-trial-results/ LINKEDIN and FACEBOOK: The FDA press release announcing the EUA for the Pfizer/BioNTech Covid-19 vaccine outlines what they did, why they did it, what the conditions of approval mean, and what the company must do to provide data on the vaccine's safety as it is rolled out to millions of Americans. It is a great day for humanity and for science. It took only weeks to identify the virus that was the cause of a new infectious disease. Within a month, the detailed makeup of the virus & genetic sequence was shared publicly. In less than two months, scientists and pharmaceutical companies around the world began developing and testing the vaccines. Results were shared "hot of the press" in record time, an unprecedented release of early data, assuring that progress in one country was useful for all. The governments of several countries deployed massive resources to
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support the tests of the efficacy and safety of these vaccines in record time. We have every right to be proud of what our US scientists and institutions have done to bring this vaccine forward. At the same time, we recognize that the pandemic affects every nation and people and that collectively we have used our intelligence and technology to bring hope to the world that an end is in sight. A great day for humanity and for science. https://www.fda.gov/news-events/press-announcements/fdatakes-key-action-fight-against-covid-19-issuing-emergency-useauthorization-first-covid-19 TWITTER: The EUA authorization for a Covid-19 vaccine represented a great day for humanity and science. It took us just weeks to identify the virus. A month to understand its genetic sequence. Then within two months were were developing vaccines with support from several countries. December 15, 2020 I spoke with NHK World's Catherine Kobayashi about the Pfizer vaccine and the course of the pandemic in the US last week. https://www3.nhk.or.jp/nhkworld/en/news/videos/20201210 092322784/ The Covid-19 pandemic demonstrates the enormous impact that one infectious disease can have on all other aspects of our health. Immunizations are down this year, while incidents of polio, Malaria, HIV, and TB are up, and we are seeing other significant yet indirect health consequences. https://www.forbes.com/sites/williamhaseltine/2020/12/14/t he-covid-19-pandemic-is-threatening-decades-of-progress-inglobal-health/?sh=239c2b795425 TWITTER: The Covid-19 pandemic demonstrates the enormous impact that one infectious disease can have on all other aspects of our health. Immunizations are down this year, while incidents of polio, Malaria, HIV, and TB are up. https://www.forbes.com/sites/williamhaseltine/2020/12/14/t he-covid-19-pandemic-is-threatening-decades-of-progress-inglobal-health/?sh=239c2b795425 I welcomed the opportunity to join the virtual Jaipur Literature Festival this year to talk about the coronavirus. 2788
https://youtu.be/lEEn63yUPa8 I spoke with Matthew Bishop on his podcast, Driving Change, about the coronavirus, the anti-vax movement, lessons we’ve learned from working to solve the HIV/AIDS epidemic, and my hopes that through my career and telling the story in my new autobiography that I am opening doors for young people to enter into science and medicine. https://drivingchange.org/science-policymaking-and-thepandemic-qa-with-bill-haseltine/ TWITTER: I spoke with @mattbish on his podcast, Driving Change, about the coronavirus, the anti-vax movement, lessons we’ve learned from working to solve the HIV/AIDS epidemic, and my hopes that through my career and telling the story in my new autobiography https://drivingchange.org/science-policymaking-and-thepandemic-qa-with-bill-haseltine/ December 16, 2020 Signed and hardcover copies of My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19 will be available starting tomorrow Thursday, December 17. Available here: https://www.amazon.com/dp/B08LL5T2ZW The FDA has approved the first fully at home self administered test for Covid-19, available over the counter sometime in January for around $30. This is great news and a first step to very low cost ($0.50 or less I hope) universally available self administered home tests https://www.fda.gov/news-events/pressannouncements/coronavirus-covid-19-update-fda-authorizesantigen-test-first-over-counter-fully-homediagnostic#:~:text=Today%2C%20the%20U.S.%20Food%20and,a %20surface%20with%20reactive%20molecules. TWITTER: The FDA has approved the first fully at home self administered test for Covid-19, available over the counter sometime in January for around $30. This is great news and a first step to very low cost ($0.50 or less I hope) universally available self administered home tests https://www.npr.org/sections/healthshots/2020/12/15/946692950/fda-authorizes-first-homecoronavirus-test-that-doesnt-require-a-prescription 2789
Human culture and disease are closely intertwined. As Zika moved from Africa to South America, the Caribbean, and onto the US, it became more dangerous as our carrier mosquitoes inject more virus per bite than African ones. A complex tale of human culture influencing disease. https://science.sciencemag.org/content/370/6519/991 Data submitted by Pfizer/BioNTech & Moderna to the FDA suggests that the two vaccines are comparable. They are both highly effective but induce unpleasant though tolerable reactions. The one concerning side effect in both is maybe Bell’s Palsy, a painful facial nerve malady. https://www.nytimes.com/2020/12/15/health/covid-modernavaccine.html TWITTER: Data submitted by Pfizer/BioNTech & Moderna to the FDA suggests that the two vaccines are comparable. They are both highly effective but induce unpleasant though tolerable reactions. The one concerning side effect in both is maybe Bell’s Palsy, a painful facial nerve malady. https://www.nytimes.com/2020/12/15/health/covid-modernavaccine.html A variant of SARS-CoV-2 is raising concerns that it might be more transmissible, or virulent or both. The answer is unknown. See this link for an extensive discussion of the topic. www.sciencemediacentre.org/tag/covid-19 The decision of how, where, to whom and in what order to administer a Covid-19 vaccine will vary from state to state & by jurisdictions within states, maybe even from town to town. I fear there may be confusion and anger, similar but more intense than what happened with testing. https://www.nationalgeographic.com/science/2020/12/who-isreally-first-in-line-coronavirus-vaccine-states-not-guaranteed/ December 17, 2020 Signed and hardcover copies of My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19 are available now https://www.amazon.com/dp/B08LL5T2ZW Vaccines are the best tools we have for preventing disease. If effective, they protect you no matter what. I spoke with Cristina 2790
Manzano of IE University about vaccines for Covid-19 and other diseases, as well as the broader lessons this pandemic is teaching us. https://www.ie.edu/insights/articles/viruses-not-only-killpeople-they-kill-economies/ While all Californians are suffering from a frightening rise in cases, Covid-19 is hitting some populations at much higher rates than others. Read my latest piece for Forbes to learn why, and what we can do about it. https://www.forbes.com/sites/williamhaseltine/2020/12/17/w hy-covid-19-is-overwhelming-california/?sh=4e2cc6c5192b December 18, 2020 Over 100 million people are expected to fall into extreme poverty due to the devastation of Covid-19. They'll be living on less than $1.90 per day. If wealthy nations don't help developing countries, they'll fall even further behind in their sustainability goals. https://www.forbes.com/sites/williamhaseltine/2020/12/16/c ovid-19-is-preventing-sustainable-investment-in-developingnations/?sh=74e8faad34e9 My memory is organized around meaning, how a piece of information fits into an overall picture. This all serves as the guide for what I should be doing, helping me understand the world. I recently published my autobiography, and this is an excerpt about how we gather--and use--knowledge. https://www.williamhaseltine.com/the-knowledge-puzzle/ Good news: A new and accurate at-home Covid-19 test has been approved by the FDA. Bad news: it’s too expensive. This test would be far more effective at curbing the spread of the virus if it were fifty cents or less. https://www.forbes.com/sites/williamhaseltine/2020/12/17/c ovid-19-home-tests-should-be-much-cheaper/?sh=4b405588795f A Biogen conference held in Feb may be responsible for as many as 250,000+ Covid-19 infections. This begs the question: how many explosive outbreaks in the US are the result of super spreading maskless political rallies and White House events? https://www.nytimes.com/2020/12/11/us/biogen-conferencecovid-spread.html 2791
How long does it take for immunity to develop once you’ve been vaccinated against Covid-19? See this HuffPost article for a nuanced answer. https://www.huffpost.com/entry/how-longbefore-coronavirus-vaccineworks_l_5fd6c66fc5b6218b42ea3760?utm_campaign=share_email &ncid=other_email_o63gt2jcad4&guccounter=1 So much for Swedish exceptionalism. Now the US is the outlier. In the time of HIV/AIDS, the slogan was “Silence Equals Death.” Today the slogan should be “Exceptionalism Equals Death.” https://www.nytimes.com/2020/12/15/world/europe/swedencoronavirus-restrictions.html?smid=em-share These charts show the devastating economic effects of Covid19. Conclusion: Population health is inextricably tied to national security and economic well-being. Failing to control Covid-19, as China did, has eroded the US position in the global economy. https://www.nytimes.com/interactive/2020/12/17/business/e conomy/economic-indicator-charts-measures.html?smid=em-share HuffPost summarized where you are most likely to be exposed to Covid-19 -- your home, social gatherings, gyms and fitness studios, religious gatherings, restaurants and bars, certain workplaces, and stores and shops. https://www.huffpost.com/entry/most-common-places-covidspreading_l_5fd778cec5b62f31c1ff042b This story describes the extreme regional and local differences that impact Covid-19 public health measures. What happens in one town or county does not stay there. A case-in-point for a national containment strategy that provides uniform guidance for all. https://www.bostonglobe.com/2020/12/17/business/differentcities-different-rules-regional-rollback-thats-all-over-map/ December 19, 2020 Andorra is a great example of the kind of impact we can have on the spread of the virus. For months they've had widespread Covid-19 testing, including a new round of free home tests available just in time for the holidays. https://www.forbes.com/sites/williamhaseltine/2020/12/18/t he-mouse-that-roared-what-the-us-can-learn-from-andorra-aboutcovid-19-testing/?sh=223ae11e2124
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A clear-eyed summary of some of the issues we will encounter in global Covid-19 vaccine distribution, but leaves out two critical factors: 1) whether the vaccines protect against infection and transmission, and 2) duration of protection https://www.thelancet.com/journals/lancet/article/PIIS01406736(20)32713-6/fulltext Twitter Many hospitals are so overwhelmed with severely ill Covid-19 patients that many are being turned away. This level of triage is akin to times of war. @theNAMedicine has outlined ethical principles that can govern decision making in these desperate times. https://nam.edu/112920-crisis-standards-of-care-resources/ LinkedIn Many hospitals are so overwhelmed with severely ill Covid-19 patients that many are being turned away. This level of triage is akin to times of war. In past months I have warned that if we did not enforce public health measures to control the pandemic and build surge capacity, we were looking at a future of Crises Standard of Care—only to have my warnings dismissed as alarmist. If we had acted to contain the epidemic by public health measures, as other countries have, or even if we had added surge capacity via temporary hospital beds buildouts, which we are entirely capable of doing, we would not have reached our current crisis, whereby hospitals are forced to choose who may live and who will die without care. Now is the time to take forceful nationwide measures to curb the pandemic. Unless we do so, we are on track to lose another 350,000 Americans to Covid-19. What’s more, the disease will surge through the economy like a wrecking ball, blighting the hopes of young and old alike for a brighter and more prosperous future. Vaccines alone cannot avert our present disaster. The National Academy of Medicine has outlined ethical principles that can govern decision making in these desperate times. https://nam.edu/national-organizations-call-for-action-toimplement-crisis-standards-of-care-during-covid-19-surge/
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December 20, 2020 When this pandemic is finally over, as it no doubt will be one day, my hope is that my Commentaries will provide the historical perspective to help us reckon with mistakes we have made, especially in the United States, and provide insights into how we might better contain the next contagion and reduce the number of lives ultimately, needlessly lost. Available now: https://www.amazon.com/COVIDCommentaries-Chronicle-Plague-I-ebook/ December 23, 2020 A large number of people fled high density cities in the early months of Covid-19. Here I examine a recent paper by the NYU Stern School of Business covering reports of widespread urban flight. Data suggests that who is moving out -- and why -- may not be due to fear of the disease itself. Read More: https://www.forbes.com/sites/williamhaseltine/2020/12/21/urban -flight-due-to-covid-19-is-temporary-notpermanent/?sh=7b07d2514cd5 In this webinar I provide timely answers to common questions about the Covid-19 vaccine, including what we know about the possibility of reinfection, herd vs. vaccine immunity, the distribution timelines, possible vaccine side effects, and more https://www.youtube.com/watch?v=iSX_j_d82w&feature=youtu.be December 24, 2020 An excerpt from my autobiography, available now: https://www.amazon.com/dp/B08LL5T2ZW A new variant of Covid-19 has appeared in the UK, resulting in closed borders and restrictions. I spoke with Laura Lynch about how viruses mutate, why, and what we might expect about the coronavirus going forward. https://www.cbc.ca/listen/live-radio/1-63-thecurrent/clip/15815784-u.k.-facing-variant-covid-19-risk-no-dealbrexit-looms
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December 25, 2020 “To do science at the very highest levels is a true art form, not a technical exercise. You realize as you work that what you are focusing on is part of a much bigger global picture. My objectives were to put down important bricks to increase our understanding of the natural world, particularly our own bodies, to make a difference for humanity now. My work in HIV/AIDS and Human Genome Sciences for me was the apotheosis of both.” An excerpt from my autobiography: https://www.amplifypublishing.com/product/my-lifelong-fightagainst-disease-from-polio-and-aids-to-covid-19/ December 26, 2020 The COVID Commentaries is a collection of Dr. Haseltine’s writings, research and interviews on COVID-19. It is a Living eBook, updated regularly with new information as it unfolds. When a reader purchases a copy of the book, either in print or online, you will receive a special passcode that will give you online access to every subsequent edition of the book, as it is released. Purchase your copy today: https://www.amazon.com/COVIDCommentaries-Chronicle-Plague-I-ebook/dp/B08LK734XC As countries begin easing Covid-19 lockdowns, transparency in decision making is crucial. A recent article published in the Lancet compares nine countries' current approaches and provides insight into five requirements that countries should fulfill before lifting lockdowns. Read More here: https://www.forbes.com/sites/williamhaseltine/2020/12/21/when -implementing-or-easing-restrictions-for-covid-19-transparency-isparamount/?sh=783685183c93 December 27, 2020 Read more in my autobiography, My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19 here: https://www.amazon.com/dp/B08LL5T2ZW Early studies of Moderna vaccine effectiveness have shown sustained antibody counts greatly differ between 18-55 year olds and the 56-70+ age group. These patterns may be the first of many
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indicators that Covid-19 vaccines don’t last as long as we would hope. Read More: https://www.forbes.com/sites/williamhaseltine/2020/12/22/t he-moderna-vaccines-antibodies-may-not-last-as-long-as-wehoped/?sh=b63ee7445674 December 28, 2020 The UK and SA variants have shown us the virus can adapt much more rapidly than anticipated to evade pharmaceutical control measures. Public health measures remain the best protection: masks, face shields, gloves, and social distancing. https://www.statnews.com/2020/12/21/looming-questions-newvariant-coronavirus/ The new strain (B.1.1.7) may outsmart vaccines. Normally, SARS-CoV-2 has one or two variations per month, but the new variant has had 17 mutations. Mutations will affect us biologically and we must adjust our future vaccine strategies accordingly. https://edition.cnn.com/2020/12/24/opinions/coronavirusvariant-what-weve-learned-haseltine/index.html See these questions and answers to some of the most frequently asked questions regarding the Covid-19 vaccines. Many of the questions simply require time and observation to answer. We'll know more about these vaccines in the coming months. https://www.huffingtonpost.co.uk/entry/getting-the-vaccinedoesnt-necessarily-stop-you-spreading-covid-19-toothers_uk_5fe307b8c5b66809cb2eca66 The new strain (B.1.1.7) may only be present in the UK, but it does not mean that North America is safe. Given the US hosts the world's largest population of infected people, it would be surprising if we didn't have similar variants. https://www.cbc.ca/radio/thecurrent/the-current-for-dec-232020-1.5852837/even-if-new-variant-of-covid-19-isn-t-in-northamerica-we-might-have-made-our-own-expert-1.5852976 The Year in COVID podcast focuses on how a novel virus that began as a marketplace sickness became the worst health crisis in American history. Here, we talk about the timeline of this pandemic, the lessons we have learned and our current progress. Link: https://www.houstonpublicmedia.org/articles/shows/townsquare/2020/12/23/388472/the-year-in-covid/ 2796
The WHO has initiated investigations of the origins of Covid19. The data from China now suggest that the infection began sometime in September or October outside of Wuhan. Come December, Covid-19 made it to other Chinese cities and then everywhere else. https://www.aljazeera.com/news/2020/12/28/china-covid-19 While the Moderna and Pfizer Covid-19 vaccines are groundbreaking, they may not be of much benefit to most countries with limited resources. We must look at logistically feasible and cost-effective alternatives to mRNA vaccines. https://www.lemonde.fr/idees/article/2020/12/24/covid-19-laplupart-des-pays-avaient-besoin-d-un-vaccin-que-l-on-aurait-puproduire-stocker-et-administrer-simplement-et-a-bascout_6064387_3232.html This video prepared by the WSJ is an excellent summary of medium to long-term cognitive dysfunction due to Covid-19. One definitive cause is Covid-19 related macro and mini-strokes caused by blood clots induced by the infection. https://www.wsj.com/video/suspected-bomber-died-in-nashvilleexplosion-police-say/5F792357-DA36-4118-A104C3C3A53221C5.html December 29, 2020 The neglected art of autopsy has contributed critical insights into Covid-19 pathogenesis, leading to improved treatments. We should revive routine autopsies to understand chronic and infectious diseases as a step toward better medical management. https://www.usnews.com/news/health-news/articles/2020-1224/the-autopsy-a-fading-practice-revealed-secrets-of-covid-19 Routine genomic sequence analysis in the UK & South Africa identified the new SARS-CoV-2 variants. Whether we have our own variants here is unknown because we haven't done enough genomic sequencing. We need to ramp up these sequencing efforts dramatically. https://www.nytimes.com/2020/12/22/opinion/coronavirus-ukstrain.html Despite evidence that the Lilly & Regeneron monoclonal antibody drugs prevent infection and stave off serious disease if administered early, the current supply of these medications exceeds 2797
demand, in the face of the now raging pandemic. https://www.nytimes.com/2020/12/23/health/covid-antibodytreatment.html This analysis in Science is a timely review of the safety measures needed to assure the safety of new vaccines. These observations are relevant to evaluation of Covid-19 vaccines intended for use in billions of people around the world. https://science.sciencemag.org/content/370/6522/1274 A new South African variant of SARS-CoV-2 (501.V2), independent from the UK one, increases contagiousness for adults and children. It also evades inactivation by several monoclonal antibodies and higher concentrations are found in those infected. https://www.businessinsider.co.za/what-we-know-about-thenew-strain-of-the-coronavirus-2020-12 If the U.S. already has Covid-19 variants that are more contagious and dangerous, we wouldn't know. The US lags behind in surveillance by genome sequence analysis. We must use our skills and technology to increase genome sequence surveillance immediately.https://newrepublic.com/article/160743/us-alreadycovid-variant-wouldnt-know We don't know much about the transmission of Covid-19 from mother to fetus. How severe is fetoplacental Covid-19 infection? Can antibodies be transmitted from the mother if she had developed them? This article sets out to discern those answers: https://pubmed.ncbi.nlm.nih.gov/33351086/ Critical Covid vaccine questions remain. How long will immunity last? Will a vaccine reduce transmission & contagion? Will we require frequent revaccination? Infection rates are higher than ever. We must now intensify, not relax, use of masks & distancing. https://www.statnews.com/2020/12/22/beware-thedanger-of-vaccine-euphoria/ December 30, 2020 The UK variant is here in the USA (as expected). Next up, I predict that we will discover our home grown variants with similar properties. Without a change in Covid-19 strategy, we will continue to pay a steep price in lost lives. https://apnews.com/article/public-health-united-kingdom-jared2798
polis-coronavirus-pandemic-denver755cd6f5e9189b1890f34f625d6a37f8 "Policy makers must determine to which, if any, populations mandates should apply. Vaccine mandates could be imposed in multiple sectors, each with their own legal and ethical considerations." https://jamanetwork.com/journals/jama/fullarticle/2774712?utm_ source=undefined&utm_campaign=contentshareicons&utm_content=article_engagement&utm_medium=soci al&utm_term=122920 As vaccine distribution takes centerstage, Israel is leading the way in vaccinations per capita. Many are focused on how the United States will manage to vaccinate the nation, but Israel, Bahrain, and the United Kingdom lead the way as of yet. https://www.timesofisrael.com/nearly-100000-vaccinated-sundayas-health-ministry-expands-vaccination-drive/ A new education project allows children of financiallystruggling families to use empty schools as a supervised space for online learning. Affluent families run similar environments at home. The equity hubs, as discussed here, level the playing field. https://www.washingtonpost.com/local/education/pandemiclearning-pod-montgomery-county/2020/12/25/9216f7c4-2de911eb-860d-f7999599cbc2_story.html Does the new variant of COVID-19 affect people who are already infected? Does it infect children more easily? Does it spread quicker? Is the new variant more transmissible? NPR explains how worried we should be about the new UK variant. https://www.npr.org/sections/goatsandsoda/2020/12/24/9501446 67/how-worried-should-we-be-about-the-new-u-k-coronavirusvariant Covid-19 has left those in nursing homes socially isolated and emotionally disregarded. This vignette describes the lonely life the pandemic has forced upon thousands living in assisted-living facilities. https://enewspaper.latimes.com/infinity/article_share.aspx?guid=4 6844cac-43e0-4887-a7da-5560fbe0a2da South Korea is the most recent example of the need to continue to use effective public health measures even if the pandemic in your country seems controlled. Relaxation of such 2799
measures results in a rapid resurgence of infection. https://www.bloomberg.com/news/articles/2020-12-26/afterearly-success-s-korea-sleepwalks-into-virus-crisis What caused the surge of new infections in California, Tennessee, and elsewhere? If it's the more transmissible Covid variant from the UK or homegrown variants, we must study the UK variant as it will help us provide an immediate and powerful response. https://cmmid.github.io/topics/covid19/uk-novelvariant.html#:~:text=We%20estimate%20that%20VOC%20202012 ,of%20disease%20than%20preexisting%20variants December 31, 2020 The UK variant of SARS-CoV-2 was detected in France as well as several other countries. The South African variant is now present in the UK. As of yet, there are no reports of the variants in the US, but time will tell if that remains the case. https://www.npr.org/2020/12/25/950351681/french-officialsannounce-first-confirmed-case-of-new-coronavirus-variant Covid-19 first began to spread in the United States in nursing homes. Since then, caregivers at these facilities have among the highest death rates among frontline healthcare workers. These workers must be aided and protected. https://enewspaper.latimes.com/infinity/article_share.aspx?guid=d bfb0168-bc42-42ac-bf39-c5cdca2f288a Please see this thoughtful analysis of the US Supreme Court's series of rulings regarding the power of the state to regulate attendance at religious services in times of plague. https://www.nejm.org/doi/full/10.1056/NEJMp2034280#:~:text =On%20November%2025%2C%202020%2C%20as,ability%20to% 20control%20that%20pandemic.&text=Cuomo%2C1%20the%20C ourt%20temporarily,New%20York%20Governor%20Andrew%20 Cuomo Until recently, it seemed as if Africa might be spared the worst of Covid-19 in terms of infection and consequent disease. That seems to be ending, resulting from relaxing public health measures and possibly a new more transmissible virus strain. https://www.nytimes.com/2020/12/26/world/africa/africacoronavirus-pandemic.html?smid=em-share 2800
Covid-19 Highlights persistent economic and social inequalities and inequities in many countries. Foreign Affairs Luis Alberto Morena describes how Covid-19 highlights “Latin America’s Lost Decades” and applies to many countries in Africa and Asia. https://www.foreignaffairs.com/articles/south-america/2020-1208/latin-americas-lost-decades The speed at which the Covid-19 vaccines were developed is miraculous, but that may result in unintended consequences like allergic reactions. The NYTimes describes a doctor, who has a shellfish allergy, reporting a severe reaction to Moderna's vaccine. https://www.nytimes.com/2020/12/25/health/Covid-modernavaccine-allergies.html?smid=em-share China led the world in the development and deployment of the first Covid-19 vaccines. Millions, if not billions, of people outside the US and Europe will receive the Chinese vaccine. We must know the safety and efficacy data as soon as possible. https://science.sciencemag.org/content/370/6522/1263 As European nations eased restrictions following the first wave of he Covid-19 pandemic, infections surged. It seems that some countries may have underdetected Covid-19 cases during the easing period. This paper describes such underdetection in France: https://www.nature.com/articles/s41586-020-03095-6#articleinfo Understanding the differences between acute and severe cases of Covid-19 can be the difference between life and death for a sick family member. Take the time to learn about this disease to know more about how patients with severe Covid-19 are managed. https://www.nejm.org/doi/full/10.1056/NEJMcp2009575
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January 4, 2021 In Britain and South Africa, where new variants of the Covid19 virus have been identified, case counts are surging sharply. This chart says it all. https://www.nytimes.com/2021/01/04/briefing/trumpelection-raffensperger-julian-assange-costume.html Long-term care residents make up about 5% of Covid-19 cases and 40% of Covid-19 deaths in the US. Read this shocking story to learn why. https://www.nytimes.com/2020/12/31/opinion/sunday/covid -nursinghomes.html?action=click&module=Opinion&pgtype=Homepage Has the UK’s B117 variant been present in the US since fall of last year? If so, this analysis suggests, we can expect it to become the dominant strain in coming months. https://www.theguardian.com/world/2021/jan/01/nowcoronavirus-variant-us-since-october Rwanda may have more limited resources compared to the US, but so far they’re doing a better job at controlling Covid-19. The reason? A decentralized, equitable health system. https://www.project-syndicate.org/onpoint/rwanda-model-ofpublic-health-lessons-from-covid-by-agnes-binagwaho-202012?barrier=accesspaylog Very few facilities are capable of offering monoclonal antibody treatments for Covid-19. For many, the expense and relatively short duration of protection are reason enough to pass on this otherwise groundbreaking therapy. https://www.washingtonpost.com/health/2020/12/31/covidmonoclonal-antibodies-unused/ Please see this thoughtful story in The Atlantic on the UK variant. As we move into 2021, we must modify our attitudes and behaviors around Covid-19 -- first by replacing complacency with vigilance. https://www.theatlantic.com/science/archive/2020/12/virusmutation-catastrophe/617531/ See this NYT article for a clear description of the AstraZeneca Covid-19 vaccine and a useful primer on vaccines in general. The graphics are superb. 2803
https://www.nytimes.com/interactive/2020/health/oxfordastrazeneca-covid-19-vaccine.html?smid=em-share In the years following the 2002-3 SARS epidemic, US and Chinese public health officials had a fruitful dialogue on how to control future pandemics. Today, China is nearly Covid-free, and the US anything but. Can we learn from our mistakes? https://www.nytimes.com/2021/01/04/business/chinacovid19-freedom.html January 6, 2021 The only way to permanently contain Covid-19 is to ensure everyone in the world is vaccinated. Which means, easily transported, lower cost vaccines must be available to distribute to the 650 million people worldwide living in extreme poverty. https://www.forbes.com/sites/williamhaseltine/2021/01/05/v accines-need-to-be-cheap-and-accessibleworldwide/?sh=1ff598c122f7 As the new year begins, focus your energy on the work that you love, that you can make the most significant impact in, that you can look back and be proud of your accomplishments. Read More: https://www.williamhaseltine.com/self-understanding-canyield-a-great-global-impact/ January 7, 2021 Over 8% of military personnel have had a confirmed case of Covid-19, compared to 15% of Americans. The DoD has learned from its early mistakes and the military’s efforts to quarantine and standardize mask use have drastically improved which we can all use as a blueprint going forward. https://www.forbes.com/sites/williamhaseltine/2021/12/31/h ow-the-us-military-is-handling-covid-19-and-what-we-can-learnfrom-their-experience/?sh=4b1865ec75ff As you embark on a career in science, begin by asking what contribution you want to make. Science is one discipline whereby insights of one person can improve the condition of all. I recently published my autobiography, and this is an excerpt on how I've chosen to use science throughout my life to assist humanity. 2804
https://www.williamhaseltine.com/science-is-a-key-tounderstanding-human-need/ The number of health workers sick with Covid-19 in California is so high it imperils the quality of care given to patients. Such shortages were predicted in "war game” scenarios in 2003-6 following the SARS outbreak. https://www.latimes.com/california/story/2021-01-06/covid19-surge-infecting-la-healthcare-workers-in-huge-numbers This article shows how the UK variant of the Covid-19 virus is beating even strict control measures. We must remain vigilant of what happens in the UK and South Africa -- they may be a harbinger of what’s to come for the rest of the world. https://nyti.ms/3op7bly Until we have a better understanding of the impact of the new SARS-CoV-2 variants, my recommendation is that all countries require testing prior to international travel and mandatory isolation upon arrival. https://www.sciencedirect.com/science/article/pii/S24682667203 02632 January 8, 2021 Both the UK and South African SARS-CoV-2 variants have rapidly spread to over 34 countries and there is a sizable chance that more variants are waiting to be discovered. We need plans if any of these variants become vaccine resistant. https://www.forbes.com/sites/williamhaseltine/2021/01/06/n ew-covid-19-variants-in-one-country-pose-a-threat-to-allcountries/ With a limited supply of Covid-19 vaccines, many countries seem intent on diluting or delaying the second dose of the vaccine. Doing this could lead to a large population with low antibody titers, which is the ideal condition for vaccine resistance, and will most likely prolong the pandemic indefinitely. https://www.forbes.com/sites/williamhaseltine/2021/01/06/t he-risks-of-delaying-or-diluting-covid-19vaccines/?sh=659bf6123ad5 Vaccine nationalism will prolong this pandemic -- to the detriment of us all, not just low- and middle-income countries. 2805
Wealthy countries need to do their part to aid global vaccination efforts like COVAX. https://www.project-syndicate.org/commentary/covaxvaccine-access-for-developing-and-emerging-economies-by-ngoziokonjo-iweala-2021-01 This writeup in the Washington Post does a good job of summarizing the findings and implications of the JAMA paper in my last post. More evidence that public health measures like mask wearing are critical to ending the Covid-19 pandemic. https://www.washingtonpost.com/science/2021/01/07/covidasymptomatic-spread/ The principles of this call for a common approach to Covid-19 control across Europe are sound and simply expressed. The implicit question is: can the West achieve levels of containment equivalent to those of China? https://www.thelancet.com/journals/lancet/article/PIIS01406736(20)32625-8/fulltext Mass vaccination shouldn’t come at the expense of mass testing. We need to equip health facilities with adequate resources and prevent health workers from getting sick to have capacity for both. https://www.bostonglobe.com/2021/01/07/nation/virus-testingremains-challenge-it-could-get-worse-taxed-health-care-providersjuggle-vaccine-rollout/ TWITTER: Researchers used an analytical model to compare the rate of Covid-19 transmission of people who don’t have symptoms to people who do. Their findings? Across multiple scenarios, asymptomatic people were estimated to cause more than half of all transmission. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2 774707#:~:text=If%20more%20than%2030%25%20of,median%20t ime%20of%20symptom%20onset LINKEDIN/FB: Researchers used an analytical model to compare the rate of Covid-19 transmission of people who don’t have symptoms to people who do. What did they find? The results, now published in JAMA, show that across multiple scenarios, asymptomatic people were estimated to cause more than half of all transmission. “The findings of this study,” the authors wrote, “suggest that the identification
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and isolation of persons with symptomatic COVID-19 alone will not control the ongoing spread of SARS-CoV-2.” That’s why providing low-cost, widespread Covid-19 testing to all, not just people who are worried they might be or get sick, is so important. There is far more to this pandemic than meets the eye, and always has been. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2 774707#:~:text=If%20more%20than%2030%25%20of,median%20t ime%20of%20symptom%20onset January 9, 2021 I joined Carol Massar and Tim Stenovec on the Bloomberg Businessweek (@business) podcast to discuss the coronavirus variants--both their potency and potential impacts of mutations on our current vaccine, as well as the importance of national and global public health planning regarding infectious diseases going forward. https://www.bloomberg.com/news/audio/2021-0105/georgia-runoff-elections-for-u-s-senate-heating-up-podcast As the new coronavirus mutations raise questions and alarms about how this mutation will affect our plans for ultimately containing the pandemic, I offer insight here into how virus mutations are an essential component of all life on earth. It is important to understand the mechanisms behind virus mutations and what that means for humanity. https://www.forbes.com/sites/williamhaseltine/2021/01/06/h ow-the-covid-19-virus-changes/?sh=3e883003a084 January 11, 2021 One of the most pressing questions is whether new SARSCoV-2 variants, like we’ve seen in the UK and South Africa, will impact the efficacy of Covid-19 vaccines. In this article, I offer insight and analysis on the recent study by Pfizer and two other, not-yet-peer-reviewed, papers on how we might anticipate these virus mutations to respond to the current vaccines. https://www.forbes.com/sites/williamhaseltine/2021/01/08/h ow-to-decipher-the-new-pfizer-study-on-vaccines-andvariants/?sh=3a66f13242b3 2807
As the novel coronavirus mutates, there is a chance that new strains will be vaccine-resistant. To stay ahead, we should be doing regular genome sequencing, yet only 0.3% of samples have been sequenced in the U.S., ranking us 43rd among countries using this technique to analyze the structure of the virus as it changes. https://www.forbes.com/sites/williamhaseltine/2021/01/08/g enome-sequencing-in-the-united-states-or-lack-thereof/ January 12, 2021 “Ultimately though, the combination of the loftiest goals and the hardest worker achieve the greatest success. Take a moment to think about your work ethic, whether it can be improved, and if yes, do so. Were everyone to maximize their work ethic, there may be a brighter future around the corner.” I recently published my autobiography, and this is an excerpt on how working hard will help you achieve your goals. ttps://www.williamhaseltine.com/give-your-goals-everythingyou-have/ January 13, 2021 Convalescent plasma is reported to help some with Covid-19 if administered early. This study found severe Covid-19 patients were unaided by plasma. Antibody and plasma treatments may work for immunosuppressed people until an effective Covid drug is found. https://www.reuters.com/article/us-health-coronavirusplasma/trial-of-covid-19-blood-plasma-finds-no-benefit-inseverely-ill-patients-idUSKBN29G1JZ January 14, 2021 As new SARS-Cov-2 variants arise, certain mutations could make vaccines less effective. To protect ourselves from being crushed by the incoming tide, we need to speed up vaccine rollout and expand our efforts to sequence new variants. Now is the time to think long term, and be prepared. https://www.forbes.com/sites/williamhaseltine/2021/01/13/h ow-new-covid-19-variants-might-impactvaccines/?sh=3d0bd08c5b42
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On behalf of the partnership from Access Health, @FHI360, Koe Koe Tech, and Networks Strategies for Health, we would like to invite you to join our upcoming Prince Mahidol Award Conference (PMAC) webinar on Online COVID-19 Misinformation in Asia: Patterns, Tools, and Paths Forward. Come join our panelists to discuss patterns and drivers of misinformation in the Asia region, what are the efforts to monitor and combat COVID-19 misinformation, and what are the challenges and risks related to the balance of free speech and protection from harm. Mark your calendar and see you on 20 January 2021 at 7pm., Bangkok time. Register now at https://pmac2021.com/sideMeeting/detail/13 Vendors on the dark net are touting Covid-19 vaccines with price tags of up to $1,000 for a dose of an unspecified product that is likely to be fake. These fake vaccines could be dangerous and should not be purchased. https://www.timesofisrael.com/darknet-vendors-tout-likely-fake-covid-19-vaccines-as-prices-soarresearchers/ As mutant variations of SARS-CoV-2 work their way through the population, it's valuable to understand how and why mutations take place. This short video by STAT explains this process succinctly and simply. https://www.statnews.com/2021/01/14/how-coronavirusmutates/ Hope springs eternal. I have observed natural population immunity for cold-causing coronavirus does not exist. They reoccur seasonally along with influenza. Vaccination may not mean population immunity for Covid-19 anymore than it does for the flu. https://www.modernhealthcare.com/supply-chain/us-trackherd-immunitysummer?_ptid=%7Bjcx%7DH4sIAAAAAAAAAFWQwW6CQBC G32XPaHakAnIjSrFNU2MVtL1t1wksLguyixibvrtgbRvnNvN9fy YzX4SJHfGJeRFaLwHtx2xSMVSTAS2Tz3Z5yf7DGcvzUc5tbOe46nCWqDieDXC7Y xuYjdeLaLojoYn5I0Rpbpq4FHXQAayHNCuRqYETdWESiiYN 8acp8D1XT7gf2Gdle0ai0oygzM639jL1ft4uknA6RIZ07-MKZu0CLm1l_Di3UEITxPvZGzJf8sYbVgytyUJPzw4vVr8DifdQ5n RcVEqjTxVSOlRY5Cix_1OLi9hH1WxWHvyHPni6q_0HaGD5 Mh2EN30s0ajXWQojId2rW832wk8cEB6trUoePvC3i-efd2809
AQAA&CSAuthResp=1%3A%3A900204%3A1389%3A24%3Asuc cess%3A0EE8431FC21E65B456A76136096F35A0 January 15, 2021 I spoke with Healthline about vaccine access by age group and how less-complicated guidelines could speed up the vaccination process. https://www.healthline.com/health-news/cdc-now-sayseveryone-over-65-should-get-access-to-covid-19-vaccine Thanks to hand washing, mask-wearing, and social distancing, fewer people became infected with common illnesses in 2020. What does this mean for the years ahead? Once restrictions are lifted, endemic respiratory illnesses and the flu could see a heavy return. Lasting effects from our year spent in isolation. https://www.forbes.com/sites/williamhaseltine/2021/01/14/w hen-society-returns-to-normal-post-pandemic-common-viruseswill-return-in-droves/?sh=5edd5ae77e99 Thursday, January 21 at 5pm EST please join me via Zoom to discuss my recently published autobiography with Dr. Margaret Hamburg: Roosevelt House is pleased to present a live Zoom discussion of the timely and inspirational memoir, My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19 by renowned scientist, entrepreneur, healthcare expert, and author Dr. William A. Haseltine. In this deeply relevant story, Dr. Haseltine tells for the first time the riveting tale of his extraordinary life and career. He will be in conversation with former Commissioner of the Food and Drug Administration Dr. Margaret Hamburg. RSVP Here: https://community.hunter.cuny.edu/roosevelthouse-pages/my-lifelong-fight-against-disease-from-polio-andaids-to-covid-19-01-21-21?srctid=1&erid=13506276&trid=7de2ffea-df79-4737-b021d5d7aa490e54 Here I discuss two preprint studies that are lending insight into how SARS-Cov-2 variants may be responsible for people becoming reinfected with Covid-19. We have a great deal to learn about the immunology of this virus.
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https://www.forbes.com/sites/williamhaseltine/2021/01/14/n ew-covid-19-variants-reshape-our-understanding-ofreinfection/?sh=c9b8bb629663 A recent Ohio State University study says there are SARSCoV-2 variants in the US. Troubling news, as these mutations could be vaccine resistant and have increased transmissibility. Our best defense is a good offense, meaning detect and prevent circulation of variants through wider research, increased public health measures, and continuous vaccinations. https://www.forbes.com/sites/williamhaseltine/2021/01/14/re searchers-identify-new-covid-19-variant-inohio/?sh=2838f7f6cd41 January 16, 2021 “Haseltines fought in every American war from the French and Indian War (1754-1763) to Korea (1950-1953). Dad himself was a military scientist in the Cold War against the Soviet Union. In the 19th century, Haseltine engineers helped construct the Erie Canal, then moved west, settling along the west coast of Lake Michigan in Ripon, Wisconsin. That is where my father grew up.” This is an excerpt from my recently published autobiography, available here: https://www.amazon.com/dp/B08LL5T2ZW I will be speaking on Wednesday at 8:30am EST in the NATHEALTH Thought Leadership Series about COVID-19 vaccine R&D, which has escalated at an exceptional scale over the past year. This is an interactive session and you can register for this webinar below: http://bit.ly/TheFutureofBiotech January 18, 2021 Please join me Thursday, January 21 at 5pm EST via Zoom for a discussion with Dr. Margaret Hamburg, former Commissioner of the Food and Drug Administration Dr. Margaret Hamburg. We will be discussing my new memoir, My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19. RSVP Here: https://community.hunter.cuny.edu/roosevelt-house-pages/mylifelong-fight-against-disease-from-polio-and-aids-to-covid-19-0121-21-?srctid=1&erid=13506276&trid=7de2ffea-df79-4737-b021d5d7aa490e54 2811
January 19, 2021 On behalf of the partnership from Access Health, @FHI360, Koe Koe Tech, and Networks Strategies for Health, I invite you to join our upcoming webinar on Online COVID-19 Misinformation in Asia: Patterns, Tools, and Paths Forward. We will discuss patterns and drivers of misinformation in the Asia region, the efforts to monitor and combat COVID-19 misinformation, and the challenges and risks related to the balance of free speech and protection from harm. Register now at https://pmac2021.com/sideMeeting/detail/13 I will be speaking tomorrow at 8:30am EST in the NATHEALTH Thought Leadership Series about COVID-19 vaccine R&D, which has escalated at an exceptional scale over the past year. This is an interactive session starting soon! http://bit.ly/TheFutureofBiotech Facebook Live: https://m.facebook.com/nathealthindia/live SARS-CoV-2 variants could make it difficult to control the pandemic. Experiments described in a preprint paper from the Weizmann Institute of Science suggest that naturally occurring variants have not yet reached peak infectivity. Here, I explain the science and discuss its implications. https://www.forbes.com/sites/williamhaseltine/2021/01/16/cansars-cov-2-become-even-more-troublesome-than-the-uk-and-south-africanvariants/?sh=26ae52d73895 A recent story in the NYTs on China’s handling of the coronavirus outbreak is like so many stories that miss an important fact: China has controlled Covid-19 better than almost any other nation. How? By applying what we learned following SARS. It is an embarrassment and a tragedy that we have not done the same. https://www.forbes.com/sites/williamhaseltine/2021/01/14/w hy-america-should-look-to-china-to-contain-covid19/?sh=213b4943501f I recently spoke with NDTV about what coronavirus variations mean for the future. Covid-19 is not going away anytime soon, and to make progress against the pandemic, we need strong leadership, social solidarity, and improved public health standards. https://www.ndtv.com/video/news/coronavirus-facts-vsmyths/there-will-be-no-quick-fix-for-coronavirus-us-scientist571930 2812
Cases of Covid-19 stemming from the more infectious UK variant of SARS-CoV-2 (B117) are slowly increasing in the US. The CDC believes it could be the dominant strain in the US by March, further complicating the pandemic for Americans. https://www.statnews.com/2021/01/15/covid19-b117variant-cdc/ The Affordable Care Act provided millions of young people with insurance they previously lacked. This study in Health Affairs concludes that these young people with ACA coverage are more likely to seek HPV vaccination; insurance drives vaccination. https://www.healthaffairs.org/doi/10.1377/hlthaff.2014.1302 For those who not enjoy the brain-tickling sensation of a Covid-19 test nasal swab, this article will come welcome news. Saliva will do just fine. PCR accuracy for saliva is equal to that of a nasopharyngeal swab. https://jamanetwork.com/journals/jamainternalmedicine/fullar ticle/2775397?guestaccesskey=8058e841-bc18-4398-a25154087a84297f&utm_source=silverchair&utm_medium=email&ut m_campaign=article_alertjamainternalmedicine&utm_content=olf&utm_term=011521#247 544805 In a Fox News op-ed Tom Frieden, former CDC chief, outlines the 5 things we need to do to keep the Covid-19 death toll in the US below 1 million. These measures include wearing masks, as well as stepping up vaccination, treatment, and testing. https://www.foxnews.com/opinion/vaccines-coronavirusdeaths-tom-fireden Reporting at its best is art that informs. Covid control works in China and it doesn’t in Italy. The following articles explain why. The detail of human lives described in the pieces are macroscopic, the conclusions shattering. https://www.washingtonpost.com/world/europe/italy-coviduk-variant/2021/01/16/0732bd24-544e-11eb-acc592d2819a1ccb_story.html https://www.economist.com/china/2021/01/16/many-inchina-are-strikingly-accepting-of-harsh-virus-controls While schools remain open and cases remain high in the US, European schools are contemplating closures again. Growing concerns over new infectious strains and research of children as 2813
Covid-19 spreaders is forcing some in Europe to close school doors. https://www.wsj.com/articles/europes-schools-are-closingagain-on-concerns-they-spread-covid-19-11610805601 This is an excellent report of the discovery, significance, and possible future of SARS-CoV-2 variants. See my six-part series on variants in Forbes to learn more about how Covid-19 variants develop and spread. https://www.nytimes.com/2021/01/16/world/europe/ukcoronavirus-variant.html A cave in Thailand home to millions of bats is an international tourist destination, but now it is being inspected by scientists for possible links to SARS-CoV-2 or other emerging viral agents. https://www.nytimes.com/2021/01/17/world/asia/thailandbats-coronavirus.html Different trial populations for a vaccine could yield variable efficacy reports. This thoughtful analysis dives into the efficacy of the Sinovac Covid-19 vaccine and the factors that could impact the numbers. https://www.reuters.com/article/health-coronavirus-sinovacexplainer-int/explainer-whats-behind-varying-efficacy-data-forsinovacs-covid-19-vaccine-idUSKBN29J0M1 Please see this NYT opinion essay on why public messaging regarding Covid-19 vaccination should be relentlessly optimistic. I agree we should be hopeful for the vaccines' success, but remaining critical of the vaccine rollout is vital to improve. https://www.nytimes.com/2021/01/18/briefing/donaldtrump-pardon-phil-spector-coronavirus-deaths.html This story illustrates the power of robust and comprehensive medical management systems. Does Pfizer need information it cannot obtain from the US, the UK, or elsewhere the vaccine is deployed? We should all have the information Pfizer needs. https://www.modernhealthcare.com/informationtechnology/israel-trades-pfizer-doses-medical-data-vaccineblitz#:~:text=After%20sprinting%20ahead%20in%20the,hard%2Dt o%2Dget%20vaccine. Low-paid gig workers could be avoiding tests because the cost of not working is too great. We need cheap, self-administered
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rapid tests paired with government compensation for those who have to self-isolate in case of a positive result. https://www.theguardian.com/society/2021/jan/16/low-paidshun-covid-tests-cost-of-self-isolating-toohigh?CMP=share_btn_link After 400,000 Covid-19 deaths, it is clear that the US could have avoided much of this strife. A fractured response to testing and economic closures paired with Covid-19 misinformation from government officials doomed the country from the start. https://www.nytimes.com/2021/01/17/us/covid-deaths2020.html?smid=em-share This article provides an excellent overview of Covid-19 variants. As more infectious strains are discovered, it turns out Covid-19 has been mutating all along. How do these mutations affect vaccines and immunity? Only time will tell. https://www.statnews.com/2021/01/19/coronavirus-variantstransmissibility-disease-reinfection/ A summary of new data from South Africa shows that antibodies in half of the people previously infected with SARSCoV-2 failed to neutralize the South African variant virus. This suggests that they may no longer be protected from re-infection. https://www.nicd.ac.za/can-i-be-re-infected-with-the-newvariant-if-ive-had-covid19/#:~:text=People%20who%20have%20recovered%20from,%2D 6%20months%2C%20maybe%20longer. January 20, 2021 Thank you @MaryWoolleyRA for the kind words about my recently published autobiography, My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19. Available here: https://www.amazon.com/dp/B08LL5T2ZW Vaccine distribution in the US has been inefficient and ineffective, and our tracking system isn’t centralized, making it difficult to know who has had their shots, and who hasn’t. One solution? A national registry to track vaccination records. Australia, among other countries, have done this with good effect--the incoming administration would be wise to look to their example. https://thehill.com/opinion/healthcare/534629-the-us-mustdevelop-a-national-vaccine-registry?rnd=1610901516 2815
Vaccine's are growing more available in wealthy countries, but low to middle-income countries may not receive their vaccines quite so soon. We may face a global "vaccine apartheid" as the wealthy become vaccinated and the poorer countries don't. https://www.foreignaffairs.com/articles/world/2021-0119/wealthy-countries-should-share-vaccine-doses-it-too-late The following NYT interactive breaks down the composition of the B.1.1.7 SARS-CoV-2 variant and explains how this version is different from variants we've seen thus far. The graphics are welldone and the explanations simplify a complex topic. https://www.nytimes.com/interactive/2021/health/coronaviru s-mutations-B117-variant.html January 21, 2021 Today at 5pm EST, please join me via Zoom with Dr. Margaret Hamburg to discuss my recently published autobiography, My Lifelong Fight Against Disease. You can RSVP here: https://community.hunter.cuny.edu/roosevelt-housepages/my-lifelong-fight-against-disease-from-polio-and-aids-tocovid-19-01-21-21-?srctid=1&erid=13506276&trid=7de2ffeadf79-4737-b021-d5d7aa490e54 You can order a copy of my autobiography here: https://www.amazon.com/dp/B08LL5T2ZW January 23, 2021 Looking at the long history of seasonal human coronaviruses suggests the immunity we develop against SARS-CoV-2 might be short-lived. This combined with widespread emergence of variants means future generations of Covid-19 vaccines will need to be modified every year. https://www.forbes.com/sites/williamhaseltine/2021/01/21/fo r-insight-on-new-covid-19-variants-look-to-natural-history-ofcoronaviruses/?sh=285f4b2530e1 In October last year, 76% of Manaus, Brazil had been infected with Covid-19. In recent weeks, the city has seen another surge. Manaus’s second outbreak is a warning for anyone who still believes population immunity will take the edge off this disease.
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https://www.forbes.com/sites/williamhaseltine/2021/01/22/t his-devastating-covid-19-outbreak-in-brazil-is-a-warning-for-therest-of-the-world/?sh=4529397138d7 With great relief, we welcome President Biden's inauguration and his administration's Covid-19 recovery and economic stimulus plan. But will his plans be enough? Here I outline several additional ways the new administration could assist in fighting the current pandemic. https://www.forbes.com/sites/williamhaseltine/2021/01/21/biden s-covid-19-plan-is-a-welcome-relief---but-it-needs-to-gofurther/?sh=62c2521757c6 Without an increase in Covid-19 vaccine production and distribution, billions of people won’t be vaccinated in 2021-mostly in low-income countries. Economic powerhouses like the US and EU should sponsor mass investment in vaccine distribution in poorer nations to help prevent a long-term extension to the pandemic. https://www.forbes.com/sites/williamhaseltine/2021/01/21/bi llions-in-low-income-nations-will-not-receive-their-vaccineanytime-soon/?sh=e18804e6208b January 25, 2021 My self-recognition fuels my drive, and I have much more to give in the years to come. Based on some of the stories in my autobiography, this short piece is a reflection on a fundamental perspective that has underpinned my choices throughout my career in science. I hope that it may serve as a contemplation for young people as they embark on their ambitions. https://www.williamhaseltine.com/self-recognition-isthe-greatest-admiration/ I recently shared my perspective on development and distribution of the Covid-19 vaccine and on some missteps we’ve taken, explained the science behind viral mutations, and took questions on related topics during the NatHealth Thought Leadership Series. https://www.youtube.com/watch?v=q9pN0pmRfo&feature=youtu.be I joined Matt Galloway on CBC’s The Current to discuss our new administration’s plan for controlling the pandemic. To date, 2817
divisions over COVID have been more political than medical, and while you can't change public perceptions immediately, persistent, patient messaging with good leadership from the top down will have an impact over time. https://www.cbc.ca/radio/thecurrent/the-current-for-jan-202021-1.5880191/these-americans-express-optimism-biden-canturn-the-tide-on-pandemic-1.5880805 When you purchase a copy of the book, either in print or online, you will receive a special passcode that will give you online access to every subsequent edition of the book, as it is released. Purchase your copy today: https://www.amazon.com/COVIDCommentaries-Chronicle-Plague-I-ebook/dp/B08LK734XC We have learned over many years of tracking the flu that it recurs in patterns, enabling us to plan interventions. The science behind the evolution of the influenza virus provides insight for what we might expect with SARS-CoV-2. We must prepare for emergent and future variations. https://www.forbes.com/sites/williamhaseltine/2021/01/21/w hy-patterns-in-covid-19-variation-could-resemble-seasonal-flu/ The two studies below show that IgM and IgA responses to SARS-CoV-2 infection are short-lived, whereas IgG responses last longer, several months these studies. Long-term studies are required to understand immune responses to all Covid-19 vaccines. https://directorsblog.nih.gov/2020/10/20/two-studies-showcovid-19-antibodies-persist-for-months/ LINKEDIN: The two studies below show that IgM and IgA responses to SARS-CoV-2 infection are short-lived, whereas IgG responses last longer, several months these studies. Long-term studies are required to understand immune responses to all Covid-19 vaccines. The short duration of IgM and IgA response leaves open the possibility of reinfection at mucosal surfaces by SARS-CoV-2 these two classes of antibodies protect the mucous membranes of the nasopharynx from viral infections. https://directorsblog.nih.gov/2020/10/20/two-studies-showcovid-19-antibodies-persist-for-months/ The Question and Answer commentary below by NPR is a thoughtful reminder of what we know and don't know about Covid-19 vaccines. As distribution expands, understanding the implications of vaccination will create a safer world for all. 2818
https://www.npr.org/sections/healthshots/2021/01/18/957322501/3-questions-and-the-emerginganswers-about-covid-19-vaccine-protection LINKEDIN: The Question and Answer commentary below by NPR is a thoughtful reminder of what we know and don't know about Covid-19 vaccines. Please note my answers to the following questions. First, can someone who has been vaccinated still spread the disease? WH Answer: Not yet known but preliminary data from Israel indicate whereas the vaccine protects many from illness up to 70% may still be infected. NO data yet on reducing transmission. Second, will the vaccine remain effective as the virus itself evolves? WH Answer: Current vaccines may protect some, but not all variants (preliminary laboratory evidence suggests that the vaccines may protect against the UK B.1.1.17 variant but the South African 501.V2 variant) And third, how long will the vaccine's protection last? WH Answer: Unknown. Much more research is needed. The half life of infection of mRNA vaccines (Moderna) for Ebola, Zika and RSV is short about 3 months. Preliminary data suggestive same for the Covid-19 Moderna vaccine. https://www.npr.org/sections/healthshots/2021/01/18/957322501/3-questions-and-the-emerginganswers-about-covid-19-vaccine-protection As new strains of SARS-CoV-2 work their way through the US population, we all must keep a watchful eye. With every infection comes the chance of mutation, which could mean a more infectious, deadlier, or vaccine-evading virus. https://www.usatoday.com/story/news/health/2021/01/22/c ovid-new-virus-mutations-but-vaccines-fightoutbreak/4216815001/ A recent JAMA study indicates that combination treatment with bamlanivimab and etesevimab reduced SARS-CoV-2 viral load in patients with mild to moderate COVID-19, but not when using bamlanivimab on its own. More research should be done on these therapies. https://jamanetwork.com/journals/jama/fullarticle/2775647 2819
LINKEDIN: A recent JAMA study indicates that combination treatment with monoclonal antibody therapies bamlanivimab and etesevimab reduced, but did not eliminate SARS-CoV-2 viral load in patients with mild to moderate COVID-19. When used on its own, bamlanivimab did not reduce viral load in comparison to the control group. More research should be done on these therapies in combination as their success could prevent eliminate symptoms for thousands, if not millions of patients. https://jamanetwork.com/journals/jama/fullarticle/2775647 It's welcome news that Moderna is beginning to develop vaccines designed for the UK and South African variants. There is cautious optimism that these will succeed against these and perhaps other variants as they arise. Time will tell if optimism prevails. https://www.cnbc.com/2021/01/25/covid-vaccine-modernaworking-on-covid-booster-shots-for-south-africanstrain.html?__source=sharebar|email&par=sharebar January 26, 2021 Much uncertainty remains around how new Covid-19 variants will shape the year ahead. Here I explain two studies that add depth and nuance to our understanding. The takeaway? While viral variation is not inherently disastrous, it could be if we don’t adequately anticipate and address its consequences. https://www.forbes.com/sites/williamhaseltine/2021/01/25/atale-of-two-viruses/?sh=7b1817b66949 One cause of severe Covid-19 reaction may be antibodies that attack the body instead of the invading pathogen. Studying these autoantibodies may open doors for future understanding of the virus and help us to develop more effective treatments. https://www.forbes.com/sites/williamhaseltine/2021/01/26/a utoantibodies-may-be-the-driver-behind-severe-covid-19reactions/?sh=7e5d72251249 January 27, 2021 At their core, scientists are just interested in the world around them, and they want to know more. Science is an innate part of existence. As a young person, I chose medical science as a way to help humanity. Now, many years later, I hope to inspire and encourage other young people to pursue science as a career path. 2820
https://www.williamhaseltine.com/science-as-a-career-path/ Richard Horton, Editor of the Lancet, analyzes the UK's Covid-19 struggles. Among these are refusal to institute timely public health measures. The US, with new leadership has an opportunity to learn from these mistakes with masks, Covid testing, etc. https://www.aljazeera.com/news/2021/1/11/uk-covid-crisisqa-with-the-lancets-richard-horton Mental health in the US and worldwide is degrading under the stress of lockdown and pandemic hardship. Health Affairs presents five emergency public health measures the new Congress should take to combat the failing mental health of the population. https://www.healthaffairs.org/do/10.1377/hblog20210122.959 001/full/ January 28, 2021 Covid variants infecting people who have been vaccinated, or reinfecting those who have already had Covid-19, is a hot topic. Here, I examine results from two studies, suggesting that antibody neutralizing activity decreases over time and that SARS-CoV-2 has potential to evade immune responses. https://www.forbes.com/sites/williamhaseltine/2021/01/28/sa rs-cov-2-immunity-a-moving-target/?sh=30965887337d January 29, 2021 Making up only 6% of the world's population, Mexico and the US now accounts for more than a quarter of all Covid-19 related deaths. Our neighbors to the South are overwhelmed by crowded ICUs, lack of ventilators, and low testing levels. https://www.nytimes.com/live/2021/01/28/world/covid-19coronavirus?campaign_id=9&emc=edit_nn_20210128&instance_id =26537&nl=themorning&regi_id=66679615&segment_id=50580&te=1&user_id= f06871ca0427fabf3a1cb840c5d998ba#mexico-coronavirus-deaths
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January 30, 2021 Read more in my autobiography, My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19 here: https://www.amazon.com/dp/B08LL5T2ZW
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February 1, 2021 A new federal public health order requires masks to be worn on trains, buses, and airplanes. A good move, but a year too late. Added face shields would reduce risk even further in crowded public areas. Regardless, this is a step in the right direction. https://www.washingtonpost.com/local/trafficandcommuting/ cdc-issues-sweeping-mask-mandate-for-planes-publictransportation-in-us/2021/01/30/db31f364-6197-11eb-906107abcc1f9229_story.html Nearly 50% of all new Covid-19 cases in southern California in January are attributable to the new SARS-CoV-2 homegrown variant: CAL.20C. It appears to be far more infectious than previous strains has already begun to spread to other states and countries. https://news.sky.com/story/covid-19-new-variant-blamedfor-surge-in-coronavirus-deaths-in-los-angeles-12204020 February 2, 2021 President Biden’s elevation of the Office of Science and Technology to a Cabinet-level agency is a bold move, and sends a positive message about the importance of science, which is critical for our national security. https://dailyclout.io/opinion-a-great-moment-for-science/ I spoke with Catherine Kobayashi from NHK World about President Biden and his team’s coronavirus strategy and also shared my concerns about the new, more transmissible variants emerging. https://www3.nhk.or.jp/nhkworld/en/news/videos/20210129 092831900/ The need for effective therapies to treat severe Covid-19 has never been greater, as related hospitalizations and deaths are at an all time high. Eli Lilly’s new antibody therapy, now in trials, proves effective at reducing viral load in patients. https://www.forbes.com/sites/williamhaseltine/2021/01/29/el i-lillys-latest-combination-antibody-therapy-yields-strongeffectiveness-against-covid-19/?sh=3168e6861700 Two vaccine candidates have joined the fight, Novavax and Johnson & Johnson. Particularly interesting is their data showing moderate efficacy against the UK and South African variants.
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https://www.forbes.com/sites/williamhaseltine/2021/02/01/n ovavax-and-johnson--johnsons-vaccines-are-less-effective-againstthe-uk-and-south-african-variants/?sh=76e74b8068e4 February 3, 2021 Scientists are filled with passion; driven by finding answers and dedicated to discovering new knowledge. This short piece is part of a series showcasing some of the stories that are included in my autobiography: My Lifelong Fight Against Disease. Read More: https://www.williamhaseltine.com/scientists-are-more-soartists-than-technicians/ The relatively steep drop in new Covid-19 cases in the US, along with the vaccine rollout, has renewed the debate over population (herd) immunity. In this article, I discuss how our understanding of how influenza and seasonal cold viruses behave might help us predict the course of the pandemic over the next 11 months. https://www.forbes.com/sites/williamhaseltine/2021/02/01/w ill-population-herd-immunity-to-covid-19-be-permanent-orseasonal/?sh=4f23b3bb6fb1 Biden’s ban on non-US travelers arriving from only certain countries will likely be ineffective against the spread of SARSCoV-2 variants. Instead, I propose we impose strict restrictions on all inbound travel: Require multiple negative tests and mandatory isolation upon arrival, measures that ought to be taken globally. TWITTER: To prevent the spread of SARS-CoV-2 variants, I propose that instead of banning non-US travelers from only certain countries, we impose strict restrictions on all inbound travel. I suggest just a few measures here that ought to be taken up globally. https://www.forbes.com/sites/williamhaseltine/2021/02/03/tr avel-bans-wont-stop-the-spread-of-new-variants---travelrestrictions-might/?sh=129f8aa645ab The rate at which new variants have been appearing over the last few months is alarming. Here I explain the science behind the recent variant found in Southern California, and the implications for vaccines and the trajectory of the pandemic.
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https://www.forbes.com/sites/williamhaseltine/2021/02/03/c oncerns-grow-over-the-newly-discovered-southern-californiacovid-19-variant/?sh=4f48742197a6 GSK is working with CureVac to help manufacture its Covid19 vaccine, as well as develop a new vaccine geared towards variants. The aim is to develop one vaccine that would neutralize multiple variants and that would be available in 2022. https://www.statnews.com/2021/02/03/gsk-joins-forceswith-curevac-to-manufacture-its-covid-19-vaccine-and-todevelop-another/ Thanks to physical distancing and masks, doctors see fewer cases of a polio-like condition in children. It turns out, public health measures do reduce spread of dangerous pathogens. Now we just need to ramp up efforts to control Covid-19. https://www.statnews.com/2021/02/04/doctors-see-fewercases-afm-polio-like-condition-children/ A recent study in the Journal of the National Cancer Institute noted that in addition to those suffering from cancer, cancer recoverees are at a higher risk of severe Covid-19, as are those with heart disease, diabetes, and other chronic diseases. https://academic.oup.com/jnci/advancearticle/doi/10.1093/jnci/djab012/6123751?searchresult=1&utm_s ource=STAT+Newsletters&utm_campaign=720b235bf1MR_COPY_14&utm_medium=email&utm_term=0_8cab1d7961 -720b235bf1-151227717#skipNav Rates of mental health conditions, suicide attempts, overdoses, domestic violence, and child abuse were all higher from March to October of 2020 than in the same period of 2019. The pandemic is fueling mental health issues that need to be addressed. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2 775991?utm_source=STAT+Newsletters&utm_campaign=720b23 5bf1MR_COPY_14&utm_medium=email&utm_term=0_8cab1d7961 -720b235bf1-151227717#skip-to-navigation When a reader purchases a copy of the book, either in print or online, you will receive a special passcode that will give you online access to every subsequent edition of the book, as it is released. Purchase your copy today: https://www.amazon.com/COVIDCommentaries-Chronicle-Plague-I-ebook/dp/B08LK734XC 2826
February 5, 2021 From January 8th to February 14th, cases of UK and SA variants in France grew from 3.3% to 14% of all cases. These more infectious variants may soon make similar inroads in countries around the world. Stricter public health regulations would slow them down. https://www.ft.com/content/c0670182-549c-3bb7-8794891bcd0f1d16 Some countries are extending the time between vaccine doses to administer more first-round shots. The data suggests one dose only yields around 50-60% efficacy. Withholding second doses could derail global vaccination efforts and extend the pandemic. https://www.nature.com/articles/s41591-021-012615?utm_source=STAT+Newsletters&utm_campaign=c9b7cade7fEMAIL_CAMPAIGN_2021_02_04_09_50&utm_medium=email &utm_term=0_8cab1d7961-c9b7cade7f-151227717#article-info This optimistic opinion column describes trying to manage Covid-19 down to the way we handle the flu: seasonal waves treated by vaccines. Covid-19 is 10 times deadlier, so unless we want hundreds of thousands dead per year, we need to do better. https://www.washingtonpost.com/opinions/2021/02/04/covi d-vaccine-trial-results-hospitalization/ Current rates in the UK could mean every citizen vaccinated by summer. This would slow UK's transmissions, but lower vaccine efficacy against the UK variant and the presence of other immune-resistant variants means the pandemic may return in a later wave. https://www.nytimes.com/interactive/2021/02/04/world/eur ope/covid-vaccine-uk-rate.html?smid=emOverworked and burnt-out, healthcare workers are exhausted after months of crowded ICUs and Covid-19 hospitalizations. The government's lack of attention to health care workers' mental health is another shortfall of the federal response to the pandemic. https://www.nytimes.com/2021/02/04/health/health-careworkers-burned-out-quitting.html?smid=em-share
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February 8, 2021 Federal government planning on some Americans having access to rapid at-home covid-19 tests by Summer. This is far too slow and not universal. Every American should have access to at-home tests for remarkably cheap or free out-of-pocket costs. https://www.medscape.com/viewarticle/945405?src=rss February 10, 2021 I joined the Morning Show on Chicago WGN9 to talk about Covid-19 variants. We discussed how viruses like the flu and colds come back each year, and the ways this disease is similar. https://wgntv.com/video/infectious-disease-expert-williamhaseltine-discusses-covid-19-variant-concerns/6272303/ As I told CNBC, the virus that causes Covid-19 is sending us a big message with how it is changing: If we don’t control it through public health, we may be facing a longer battle, more like what we see with the flu. https://www.cnbc.com/2021/01/29/covid-vaccine-whatyou-need-to-know-about-shots-nearing-us-debut.html We don’t know the full effect of delaying a second dose of the Covid-19 vaccine. CNN summarized the opinions of some infectious disease experts on whether a not delaying the second shot is a good idea. https://cnnphilippines.com/world/2021/2/3/COVID-19second-doses-debate.html February 11, 2021 This examination of moral injury is an important contribution to our understanding of the effects of the pandemic on healthcare providers. Doctors and nurses are having to decide who gets care, and who doesn’t, and that’s deeply traumatic. Read more here (login required). https://www.medscape.com/viewarticle/945128 I had the great privilege of speaking about my life in science with my friend and colleague, former Commissioner of the FDA, Dr. Margaret Hamburg, hosted by the Roosevelt House of Hunter College. We covered significant historical scientific events, science education, the politicization of science, and more. Watch it here. 2828
http://www.roosevelthouse.hunter.cuny.edu/events/drwilliam-haseltine-lifelong-fight-disease-polio-aids-covid-19/ I joined Mark Masselli and Margaret Flinter of Conversations on Health to discuss the growing number of new variants, their potential to evade the current vaccines and the importance of more widespread genomic testing to understand their impact on Covidrelated illness. https://www.chcradio.com/episode/William-Haseltine/566 Learn from Bhutan. There is a way to eliminate the virus from a country. Bhutan is now the Sixth country to have done so. Read and wonder what life would have been like if we had taken this pandemic with the seriousness it deserves. https://www.theatlantic.com/international/archive/2021/02/c oronavirus-pandemic-bhutan/617976/ Firearm violence was up in 2020 compared to previous years. A global pandemic forcing billions indoors paired with national recognition of systematic racism may be some of the sparks behind the rise. This study evaluates the links between these events. https://jamanetwork.com/journals/jama/fullarticle/2776537 Layering masks and improving their fit increases protection for you and others. This NYT article and accompanying video demonstrate how proper mask-wearing reduces transmission risk by more than 90%. https://www.nytimes.com/2021/02/10/world/double-maskprotection-cdc.html Prior infection with cold-causing coronavirus does not protect you from Covid-19. What was obvious is now confirmed. Everyone has had coronavirus colds many times, usually at least once every year or every other year, including those who've had Covid-19. https://www.nytimes.com/2021/02/10/health/coronaviruscolds-immunity.html?smid=em-share February 12, 2021 As we now know, new variants are a serious cause for concern. Here, I examine several studies on parallel mutations of SARSCoV-2 in immunocompromised patients. Further analysis of persistent infections in these patients could give us valuable insights used to improve drugs, diagnostics, and vaccines. 2829
https://www.forbes.com/sites/williamhaseltine/2021/02/11/c ovid-19-could-end-up-like-the-flu-or-worse/?sh=3abb5a997796 As the world moves into the second year of the Covid-19 pandemic, SARS-CoV-2 variants are now the fundamental issue at the root of many of our questions — Will the vaccines work? Will we need new shots each year? Will the pandemic end or can we expect a renewed surge of Covid-19 cases every year, like we see with the flu? In Variants! Dr. Haseltine turns his focus to SARS-CoV-2, providing a general overview of how the virus is evolving, how the variants may have emerged, and what these changes may mean for the course of the pandemic. Available here: www.williamhaseltine.com Treating Covid-19 patients very early on in their hospitalization with prophylactic anticoagulation may decrease risk of death according to this bmj study. Treatment must be early in the infection—24 hours in this study—to make a substantial impact. https://www.bmj.com/content/372/bmj.n311 Covid-19 uprooted normal life and has justifiably prompted depressive symptoms in people worldwide. These signs are likely common in many and recognizable by the majority. Don't ignore your mental health in these trying times and seek help if necessary. https://www.huffpost.com/entry/signs-depression-dont-feelsad_l_6022e901c5b6173dd2fa1630?utm_campaign=share_email&n cid=other_email_o63gt2jcad4 This article by the Lancet not only analyzes the short-term effects of school closures on children, but also the long-term sociopsychological impacts on them. Health and education are directly linked and the longer the pandemic, the greater the impact. https://www.thelancet.com/journals/lancet/article/PIIS01406736(21)00142-2/fulltext Sweden attempted to approach Covid-19 by attempting population immunity as quickly as possible. Deaths and hospitalizations are now disproportionately high. Why did Sweden make the deadly blunder? Have they learned what they must now do? https://www.thelancet.com/journals/lancet/article/PIIS01406736(20)32750-1/fulltext 2830
This BBC story informs us that vaccines prevent disease, not infection and onward transmission of the infection to others. Until we have more vaccine data, assume you can be infected and infect others even you have been vaccinated. https://www.bbc.com/future/article/20210203-whyvaccinated-people-may-still-be-able-to-spread-covid19?ocid=ww.social.link.email February 14, 2021 As the science evolves, so too will the book itself. Variants! is a Living eBook, updated regularly with new information as it unfolds. When a reader purchases a copy of the book, either in print or online, they will receive a special passcode that will give them online access to every subsequent edition of the book, as it is released. Buy your copy this week! www.williamhaseltine.com February 16, 2021 I have spent a lifetime studying viruses and their ability to adapt and flourish within an ever-changing environment. In Variants! I turn my focus to SARS-CoV-2, providing a general overview of how the virus is evolving, how the variants may have emerged, and what these changes may mean for the course of the pandemic. Available now: https://www.amazon.com/dp/B08WKPXCKD/ref=sr_1_1?crid= 2WLQRMEZ901VG&dchild=1&keywords=william+haseltine+v ariant&qid=1613263780&sprefix=haseltine+variants%2Caps%2C1 59&sr=8-1 February 17, 2021 Within the first days of his term, President Biden has followed through on his promise to get to work fighting COVID-19. His actions, although important, could be bolstered. Here, I outline 5 ways the new administration could build on Biden’s early executive orders. https://www.thinkglobalhealth.org/article/weighing-bidensfirst-executive-orders-address-covid-19 I have previously discussed the importance of studying viral variants that arise in immunosuppressed patients. Here, I describe 2831
observations of a 45-year old infected man in Boston. The findings shed light on the variations of SARS-CoV-2 that may blindside us down the road. https://www.forbes.com/sites/williamhaseltine/2021/02/16/p ersistently-infected-covid-19-patients-a-potential-source-for-newvariants/?sh=59a88c27208a This thoughtful piece explores what to do about vaccine hesitancy among long-term care workers but applies to all of us. It is no surprise that the first step is to understand the fear and address it directly. It takes time, sensitivity and trust. https://www.washingtonpost.com/outlook/nursing-home-skipvaccine/2021/02/12/4d31d17a-6bfa-11eb-9f803d7646ce1bc0_story.html These stories of young people in Europe struggling with despair as a result of lockdowns and the pandemic echo the stories we have heard at home as well. We should focus as seriously on the mental health pandemic unfolding as we do Covid-19 itself. https://www.nytimes.com/2021/02/14/world/europe/youthmental-health-covid.html?smid=em-share This new study finds that the UK variant, B.1.1.7 has reached US shores. What’s more, it’s confirmed to have an increased transmission rate of 35-45%. Though national case counts are falling, we must remain vigilant or risk another surge. https://www.medrxiv.org/content/10.1101/2021.02.06.21251159 v1 In addition to ushering in waves of isolation and financial hardship, the pandemic has seen overdose deaths reach new heights, in Colorado increasing by 20% from the previous year. A true tragedy. https://www.statnews.com/2021/02/16/aspandemic-ushered-in-isolation-financial-hardship-overdose-deathsreached-new-heights/ How dangerous are the new Covid-19 variants? We now have evidence of a man in France who fell critically ill after being reinfected by the South Africa variant--not a good sign. https://www.washingtonpost.com/world/2021/02/13/reinfect ion-south-africa-variant/ A mutation called Q677P has made a splash in the US, where it has appeared in at least 7 new Covid-19 variants. Why it hasn’t taken hold in other countries is, at least for now, unclear. 2832
https://www.medrxiv.org/content/10.1101/2021.02.12.21251658 v2 TWITTER: The story of the new Covid-19 variants is unfolding with breathtaking speed. Those who wish to follow along should look into my new book Variants!, now available on Amazon. https://jamanetwork.com/journals/jama/fullarticle/2776542?utm_ source=undefined&utm_campaign=contentshareicons&utm_content=article_engagement&utm_medium=soci al&utm_term=021421 LINKEDIN: The story of the new Covid-19 variants is unfolding with breathtaking speed. Those who wish to follow along should look into my new book Variants!, now available on Amazon. The book will be updated at no charge to keep pace with the rapidly changing landscape of new isolates and their implications for vaccines and reinfection. https://jamanetwork.com/journals/jama/fullarticle/2776542?ut m_source=undefined&utm_campaign=contentshareicons&utm_content=article_engagement&utm_medium=soci al&utm_term=021421 Cases of Covid linked syndrome in children are rising and a higher percentage are critically ill. I believe this may be related to the new and more serious variants and should inform the reopening of schools. https://www.nytimes.com/2021/02/16/health/covid-childreninflammatory-syndrome.html Hardcover Available Now on Amazon: https://www.amazon.com/gp/product/B08LL5T2ZW/ref=dbs_a _def_rwt_bibl_vppi_i1 February 19, 2021 In this article, I examine a study of an immunocompromised patient from Pittsburgh. This case makes one thing clear: If we don’t pay attention to mutations across the entire breadth of the SARS-CoV-2 genome, we risk missing a piece of the puzzle that could prove to be significant in future variants. https://www.forbes.com/sites/williamhaseltine/2021/02/17/t his-region-of-the-covid-19-virus-is-one-we-cantignore/?sh=376073a96786 2833
In this continuation of my series on variants and random mutation, I explore a study from the Lancet that continues to prove the theory of parallel evolution. It is critical that we analyze all the data we have to guide our future response to this virus because it is highly likely that Covid-19 will become a seasonal phenomenon, just like influenza. https://www.forbes.com/sites/williamhaseltine/2021/02/18/h ow-one-covid-19-patients-infection-foreshadowed-the-rise-ofnew-variants/?sh=1abc34191efb This week, the UK government confirmed they are moving forward with a human challenge trial – infecting 90 healthy volunteers with Covid-19. I question the reasoning behind this trial when we will have real comparison data to work with in the near future from the millions of people already being vaccinated. https://www.forbes.com/sites/williamhaseltine/2021/02/19/u k-approves-human-challenge-trials-for-covid-19-but-at-whatcost/?sh=6e070de7642b New SARS-CoV-2 variants have now become the dominant strain in the UK, South Africa, and South America, and we are approaching a similar outcome in the US. We still do not know if the vaccine will protect against any or all of these emerging variants, which is very dangerous as many states are loosening Covid-19 restrictions. https://www.forbes.com/sites/williamhaseltine/2021/02/17/ra pid-spread-of-variants-across-europe-is-a-dire-warning-for-the-us February 20, 2021 Available now: https://www.amazon.com/Variants-ShapeShifting-Challenge-COVID-19Haseltine/dp/0578860856/ref=sr_1_2?dchild=1&keywords=varian t+haseltine&qid=1613660552&sr=8-2 February 23, 2021 The U.S. needs to act fast to stop a potential rapid rise in Covid-19 cases stemming from new variants. In this article, I outline the public health measures that need to be taken to protect ourselves against these new variants based on what we currently know. 2834
https://www.forbes.com/sites/williamhaseltine/2021/02/19/v ariants-could-cause-a-rapid-rise-in-covid-19-cases-in-the-usunless-we-implement-these-public-healthmeasures/?sh=3794e61d7ec0 This winter, new variants of SARS-CoV-2 have taken the world by storm. Here, I explain the science behind the recent appearance of what researchers are calling the 677 variants, which for now seems confined to the US alone. https://www.forbes.com/sites/williamhaseltine/2021/02/19/w hat-are-the-677-mutations-new-covid-19-variants-found-in-theus/?sh=5d95a7f754ae People infected with B.1.1.7 (the UK Variant) could be more contagious for longer times, according to a Harvard study of the NBA. As new variants account for more Covid-19 cases each day, we must adjust our public health policy accordingly. https://www.forbes.com/sites/williamhaseltine/2021/02/19/n ba-study-reveals-the-uk-variant-may-last-longer-in-humanhosts/?sh=1b315a022fcb The US recently hit its lowest number of daily new Covid cases but I believe the disease will return each year, in waves like the flu. We need to make the sacrifices now in order to come close to near zero infections which would allow us to trace and track new infections. https://www.forbes.com/sites/williamhaseltine/2021/02/22/b eware-the-next-wave-what-to-expect-from-covid19/?sh=7d54b09d277b How will children be affected by the new variants? Leaders should proceed with caution. While many saw a recent study of daycare centers in France as positive news that might lead to schools re-opening, it is too early to make such claims. https://www.forbes.com/sites/williamhaseltine/2021/02/22/w hat-to-make-of-covid-19-infections-in-french-daycarecenters/?sh=7c5f9c2a34a6 In this article in Clinical OMICs Magazine, I discuss one of the ways we could control the virus’s spread at relatively little cost: The US Government could manufacture and distribute hundreds of millions of rapid at home tests. Read more about my proposal on page 46: https://www.clinicalomics.com/magazine/clinicalomics-magazine-volume-8-issue-no-1/ 2835
On March 3rd, 7pm EST I will be joining Professor Wee Joo Chng from the National University Cancer Institute, Singapore to talk about my work on cancer, HIV/AIDS, and genomics. Register now for the Zoom webinar here: http://bit.ly/w_haseltine February 24, 2021 In my latest blog, I talk about the importance of interest in STEM careers and my hope for encouraging young people to pursue science as a career path. Read More: https://www.williamhaseltine.com/the-chance-to-change-theworld/ In considering granting full approval for Covid vaccines (which are currently under emergency approval), I suggest that the FDA request access to crucial data that will help us understand more about the efficacy of these vaccines. In this article I also propose they require data to be made widely available, which could greatly increase public trust. https://thehill.com/opinion/healthcare/539901-questions-thefda-must-ask-drug-makers-as-it-considers-full-covid19?rnd=1614018858 As we continue vaccination efforts worldwide, variants are emerging that may make some of those vaccines less effective. Here, I explain the mutations of a new SARS-CoV-2 variant from Japan. Our frontline defense has to remain public health measures. https://www.forbes.com/sites/williamhaseltine/2021/02/22/n ew-sars-cov-2-variant-discovered-in-japan-nearly-identical-todangerous-brazilian-variant/?sh=3a2529567fa8 We have quickly learned that the incubation time for some of these new, rapidly spreading variants is longer than the original SARS-CoV-2 Wuhan strain. Due to this information, I am urging the CDC to err on the side of caution and extend the quarantine period to three weeks. https://www.forbes.com/sites/williamhaseltine/2021/02/22/t he-spread-of-new-variants-calls-for-extending-quarantineguidelines/ On Monday, I joined Charles Adler on his Town Hall radio show to discuss the dangers of newly emerging, highly 2836
transmissible, variants and answered listener questions about the vaccine and its efficacy against SARS-CoV-2 variants. https://omny.fm/shows/charles-adler-tonight/covid-19vaccine-s-global-approval-process-and-eff February 25, 2021 A recent study published in Nature compares immune responses of vaccinated participants with people who were naturally infected with SARS-CoV-2. The study confirmed that antibodies fade over time, and questions remain about how the immune system will respond to variants. https://www.forbes.com/sites/williamhaseltine/2021/02/24/pf izerbiontech-and-moderna-mrna-covid-19-vaccines-closelymimic-the-immune-response-of-natural-sars-cov-2infections/?sh=f9006759ab6d In this article, I answer some key questions about SARS-CoV2 variants as they pertain to the immunity provided by vaccines. Insights from fellow scientists help explain how and when we should update the vaccine and what the approval process may look like. https://dailyclout.io/opinion-how-to-redesign-covid-19vaccines-so-they-protect-against-variants/ Here, I explain the mutations of the Nigerian variant (B.1.525) which, like many new variants, appears to be more transmissible and potentially vaccine resistant. Understanding the implications of this and other variants is crucial for the future of the pandemic and vaccine design. https://www.forbes.com/sites/williamhaseltine/2021/02/24/n ew-nigerian-variant-continues-the-trend-of-dangerous-strainsthreatening-covid-19-progress/?sh=1091cceb4140
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March 1, 2021 A recent preprint study of patients previously infected by Covid-19 who received one dose of the vaccine has shown promising results. Neutralizing antibodies increased 1000-fold, meaning, if you have already been infected, receiving the vaccine may provide even more protection than those who have not been. https://www.forbes.com/sites/williamhaseltine/2021/02/25/if -i-had-covid-19-should-i-still-get-vaccinated-absolutely/ Here, I examine a new variant which was first identified in a newborn in a Washington DC pediatric hospital. This outbreak, in addition to a surge in both Italy and Israel youth cases, is making us keenly aware of the threat new variants represent. https://www.forbes.com/sites/williamhaseltine/2021/02/25/identi fication-of-a-novel-covid-19-variant-cluster-isolated-from-covid19-ill-infants-in-us-capital/?sh=f04d03947d62 SARS-CoV-2 variants have emerged globally, threatening the progress made towards ending the pandemic. In this article, I explain the science behind a new variant discovered in New York. This strain is highly transmissible, reminding us to remain on guard despite vaccine-induced protection. https://www.forbes.com/sites/williamhaseltine/2021/02/26/n ew-york-finds-its-own-covid-variants-the-news-is-notgood/?sh=4f2cb5216de7 We are now seeing a steady rise in Covid-19 cases globally due to dominance of new variants. This means we must continue to wear masks, sanitize, physically distance, and the Biden administration needs to scale up genomic surveillance to have a greater understanding of how variants are spreading. https://www.forbes.com/sites/williamhaseltine/2021/02/26/c ovid-19-cases-are-rising-again-globally/?sh=2e9360df4f80 Blood thinners (anticoagulants) have been reported to reduce in-hospital deaths of patients with severe Covid-19. Here, I examine the outcome of multiple studies in which patients were given anticoagulants early on in their treatment. https://www.forbes.com/sites/williamhaseltine/2021/02/26/s hould-anticoagulants-be-used-early-or-late-in-patientshospitalized-with-covid-19-two-conflictinganswers/?sh=7c377a05d46d 2839
In Austria, students are being asked to test themselves twice a week, wear N95 masks, and attend school in two shifts. This “triple safety net” of steps to cut infection risks could become an example for the US as we consider school reopenings. https://www.forbes.com/sites/williamhaseltine/2021/02/26/se lf-testing-a-route-to-school-re-opening--the-austrianexample/?sh=6a23fbf82d58 As the science evolves, so too will the book itself. Variants! is a Living eBook, updated regularly with new information as it unfolds. When a reader purchases a copy of the book, either in print or online, they will receive a special passcode that will give them online access to every subsequent edition of the book, as it is released. Available now paperback and Kindle: https://www.amazon.com/Variants-Shape-Shifting-ChallengeCOVID-19Haseltine/dp/0578860856/ref=sr_1_2?dchild=1&keywords=varian t+haseltine&qid=1613660552&sr=8-2 March 2, 2021 Here, I explain the science behind one of the new variants circulating in Southern California (B.1.427/429). Some of these new variants have shown an enhanced ability to spread, sicken, and resist antibodies. We should maintain the utmost caution. https://www.forbes.com/sites/williamhaseltine/2021/02/27/t he-california-variant-is-more-transmissible-evokes-worsesymptoms-and-may-resist-vaccines/?sh=7922f9a4557e With the possibility of new, highly transmissible SARS-CoV-2 variants, we need increased vigilance to protect our students, their families, and our teachers. Here I review how the variants may affect the reopening of our schools. https://www.forbes.com/sites/williamhaseltine/2021/02/28/sc hools-must-reconsider-accelerating-plans-to-reopen-in-light-ofdangerous-new-covid-19-variants/ Here, I examine a study from Italy investigating the evolution of SARS-CoV-2 in the immune population. Results underscore that the virus’s extended exposure to neutralizing antibodies may yield mutations that create a resistant virus. 2840
https://www.forbes.com/sites/williamhaseltine/2021/03/01/it alian-scientists-create--live-sars-cov-2-neutralization-escapevariant/?sh=49db57b34b65 Tomorrow March 3rd, 7pm EST I will be joining Professor Wee Joo Chng from the National University Cancer Institute, Singapore to talk about my work on cancer, HIV/AIDS, and genomics. Register now for the Zoom webinar here: http://bit.ly/w_haseltine March 3, 2021 I joined Mike Walter on CGTN’s The Heat for a discussion about my autobiography and the personal and professional experiences I’ve had leading up to my work fighting the current pandemic. https://america.cgtn.com/2021/02/26/the-heat-one-scientistsfight-against-disease-racism-against-asian-americans The current pandemic has raised awareness about the importance of public health. We’ve seen many positive changes-improved hygiene, delivering care where patients need it most, and destigmatizing mental health issues. But we need to do more, especially to strengthen our health care system and address health inequalities. https://thehill.com/opinion/healthcare/541132-how-covid19-could-make-us-healthier?rnd=1614648393 A new variant has emerged in New York reminding us that we must remain vigilant and improve our efforts -- wear masks and face shields, extend self quarantine to 14-21 days minimum and, for those eligible, get the vaccine. Otherwise, we risk a repeat of the lockdown measures we faced a year ago. https://www.forbes.com/sites/williamhaseltine/2021/03/02/n ew-york-covid-19-variants-are-causing-concern/ In my latest blog, I talk about the passing down of scientific knowledge from one generation to the next. Pictured here is my first mentor, George Pimentel of UC Berkeley, who helped train me, and I in turn passed this knowledge onto my students and students of my students. https://www.williamhaseltine.com/the-science-guild/
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March 5, 2021 Two papers by Dr. Li Lanjuan of Zhejiang University, released in spring of last year, revealed the potential dangers of what we are now seeing: a rapidly mutating virus. Had we heeded these early warnings, we would not be playing catchup today. https://www.forbes.com/sites/williamhaseltine/2021/03/03/v ariants-forewarned-is-forearmed--for-those-who-listen/ My autobiography is available in paperback, ebook, and hard copy now on Amazon: https://www.amazon.com/gp/product/B08LL5T2ZW/ref=dbs_a _def_rwt_bibl_vppi_i1 March 8, 2021 Reports from Italy of a spike in cases among the very young have alarm bells ringing for school reopening in America. New variants may spread more easily among school age children. We must follow the data when making decisions to reopen schools. https://www.forbes.com/sites/williamhaseltine/2021/03/05/m ore-cause-for-concern-around-covid-19-and-schools/ I joined CGTN’s The Heat for a discussion about states loosening restrictions and the effects of new variants on the roll out of the vaccine. We also discussed the importance of global cooperation on vaccine distribution and manufacturing. https://america.cgtn.com/2021/03/04/the-heat-cautiousoptimism-in-u-s-with-vaccine-push I spoke with NHK World’s Catherina Kobayashi about the effectiveness of the Johnson & Johnson Covid vaccine, and its degree of protection against emerging variants. https://www3.nhk.or.jp/nhkworld/en/news/videos/20210305 094216546/ Of all the pandemic causing diseases of the past century, polio is the only one we’ve eradicated. Here, I explain the science behind polio vaccines and how we can use this information to combat our current pandemic. https://www.forbes.com/sites/williamhaseltine/2021/03/08/le ssons-from-the-past-and-present-for-controlling-covid-19polio/?sh=528517fa4ee1
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With the recent uptick in cases in Italy and Israel among young people being reported, schools and universities should be more aware than ever of emerging variants. In order to prevent a fourth wave, we must maintain critical safeguards and remain vigilant in our public health measures. https://dailyclout.io/opinion-covid-19-variants-and-the-safetyof-students/ March 10, 2021 At the forefront of the Covid-19 discussion is whether or not the vaccine or previous infection will protect against emerging strains. Here, I explain the good news we’re finding with our Tcell response to both the wild strain and variants of SARS-Cov-2. https://www.forbes.com/sites/williamhaseltine/2021/03/08/tcell-responses-hold-up-against-sars-cov-2-variants-studyfinds/?sh=2852e1ac3c48 Mental health professionals are working overtime guiding others through the pandemic. Many are naturally experiencing compassion fatigue. We must find ways to care for current mental health professionals and inspire others to join the profession to meet the overwhelming demand. https://www.forbes.com/sites/williamhaseltine/2021/03/09/t he-covid-syndemic-the-mental-health-crisis-of-mental-healthworkers/?sh=671c95d451c2 An excerpt from my latest blog post on the partnership between science and business in the United States. https://www.williamhaseltine.com/the-science-businesspartnership/ March 11, 2021 In this webinar by NUS Medicine International Council, I discussed the importance of academia and research in medicine and described how one medical center, NYU Langone Health, has balanced the two to great effect. My book World Class discussed this topic as well. https://www.youtube.com/watch?v=XRGcVFCu9AI Reports from Brazil and South Africa indicate that new variants are very capable of causing reinfection. What does this mean for 2843
those who have been vaccinated? The current generation of vaccines will protect you, in the short run. https://www.forbes.com/sites/williamhaseltine/2021/03/10/c ovid-19-reinfections-are-real-and-serious-all-the-more-reason-tobe-vaccinated/?sh=5dbedf912e23 I joined Susan Ryan on the Elevate Eldercare Podcast from the Green House Project to discuss my perspective on the pandemic, herd immunity, vaccines, and variants. We also discussed a vision for eldercare that prioritizes mental health AND medical health. https://www.thegreenhouseproject.org/Elevate-Eldercare Here, I examine a correspondence from the New England Journal of Medicine where variants were tested against the serum of patients who had received two doses of the Pfizer-BioNTech vaccine. The results, although promising, indicate that we need additional data and must remain vigilant. https://www.forbes.com/sites/williamhaseltine/2021/03/11/n ew-study-using-live-virus-explores-whether-pfizer-biontechvaccine-protects-against-variants/?sh=d201e8d7383f March 15, 2021 A new pancoronavirus vaccine could be in our future, which is very good news. Here I discuss two recent studies that suggest nanoparticle immunization technology may be the key to unlock a one-shot vaccine to protect against all SARS-CoV-2 variants and possibly other coronaviruses too. https://www.forbes.com/sites/williamhaseltine/2021/03/11/n ew-hope-for-a-covid-19-vaccine-that-protects-against-allvariants/?sh=32721e42259d I spoke with Shery Ahn and Haidi Stroud-Watts on Bloomberg Daybreak to discuss the vaccine distribution and the dangers of relaxing Covid measures. https://www.bloomberg.com/news/videos/2021-03-11/drhaseltine-says-it-s-too-soon-to-relax-covid-measures-video Despite the vaccine rollout and an overall decline in new cases, we are far from the end of the pandemic. The virus’ ability to mutate cannot be overlooked. We must prepare ourselves for the virus and variants to return year after year. https://www.scientificamerican.com/article/how-will-thecoronavirus-evolve/ 2844
March 17, 2021 Stress from unclear and inconsistent Covid-19 guidelines has led to divisions in families and communities, and an increase in anxiety and depressive disorders. To reduce conflicts and confusion, public health authorities should emphatically communicate guidelines. https://www.psychologytoday.com/us/blog/best-practices-inhealth/202103/clearer-covid-19-guidelines-cause-less-stress-us-all Public health officials are sending a united message: This is no time to relax! Despite the comfort provided by the vaccine roll-out, now is not the time to let down our guards and party during spring break. In this article I compare our current trend to the peaks, plateaus, and third-waves of other nations--our choices now will determine our future. https://www.forbes.com/sites/williamhaseltine/2021/03/16/thecovid-pandemic-is-not-over-the-past-may-beprologue/?sh=6394684d3c4c Here, I describe the science behind Molnupiravir, a potential new Covid-19 treatment that could reduce the severity of Covid-19 symptoms and transmission. It may also prove useful against influenza, Ebola, and other viruses. A positive advancement but one that comes with cautions around resistance. https://www.forbes.com/sites/williamhaseltine/2021/03/16/m olnupiravir-a-new-hope-for-prevention-and-treatment-of-covid19-and-other-dangerous-viruses/?sh=4620ef071200 March 18, 2021 Here I discuss the results and implications of the Novavax trials and the vaccine’s performance against variants. The vaccine has shown an impressive 86.3% efficacy against the UK variant, good news given how widespread the strain has become. https://www.forbes.com/sites/williamhaseltine/2021/03/16/n ovavax-covid-19-vaccine-performs-well-in-clinical-trials-butvariants-remain-a-threat/?sh=33b5bc5d4a7f Two recent studies show a high percentage of people who have survived Covid-19 have developed anxiety and depressive disorders. Considering the neuropsychological consequences of Covid-19, all those diagnosed should 2845
receive psychological screening and have a primary care doctor who can guide them through their recovery. https://www.psychologytoday.com/us/blog/best-practices-inhealth/202103/covid-19-survivors-risk-depression-and-otherdisorders A study shows the AstraZeneca vaccine is only 10.4% effective against the South African variant. We need to accelerate all vaccine development to protect against variants while we continue rolling out these first generation vaccines to all. https://www.forbes.com/sites/williamhaseltine/2021/03/17/as trazeneca-vaccine-fails-to-protect-against-the-south-africanvariant/?sh=9b1c6d46526e A third-generation variant has emerged, this time in the Philippines. Here I explain the genetic similarities to its predecessors, as well as new mutations in the genome. Again, we’re faced with the stark evidence of the importance of developing broad spectrum vaccines and continuing public health measures to fill the gaps. ttps://www.forbes.com/sites/williamhaseltine/2021/03/18/thi rd-generation-covid-19-variant-described-in-thephilippines/?sh=131592f873ca Twitter: A third-generation variant has emerged. Here I explain the genetic similarities to its predecessors and new mutations. Again, we’re faced with the importance of developing broad spectrum vaccines, continuing public health measures to fill the gaps. https://www.forbes.com/sites/williamhaseltine/2021/03/18/t hird-generation-covid-19-variant-described-in-thephilippines/?sh=131592f873ca March 19, 2021 Quarantines, border controls, sanitation, disinfection — these have been used over hundreds of years to ward off death. Thankfully we also have science. Here I discuss a spate of new discoveries with real promise for a second generation of vaccines and treatments against Covid-19. https://thehill.com/opinion/healthcare/543873-science-willsave-us-in-our-battle-against-covid-19?rnd=1616090709 Twitter: Quarantines, border controls, sanitation, disinfection have been used over hundreds of years to ward off death. Thankfully 2846
we also have science. Here I discuss new discoveries with promise for a 2nd generation of vaccines and treatments against Covid-19. https://thehill.com/opinion/healthcare/543873-sciencewill-save-us-in-our-battle-against-covid-19?rnd=1616090709 March 25, 2021 The recent decline in new Covid-19 infections in the US represents an opportunity to rid ourselves of the virus. But our window for this is short and the variants may throw us for a loop. https://www.project-syndicate.org/commentary/us-stillneeds-testing-contact-tracing-quarantines-by-william-a-haseltine2021-03 I joined Mark Walter on CGTN’s The Heat to discuss recent concerns about the AstraZeneca vaccine, as well as the dangers of relaxing regulations. https://america.cgtn.com/2021/03/18/the-heat-covid-19battle-third-wave-hits-europe New OSHA Covid-19 safety measures issued by the Biden administration are a step in the right direction. Unfortunately the threat of fines may not be enough incentive for companies to adopt new standards. https://www.forbes.com/sites/williamhaseltine/2021/03/22/c ontroversy-over-osha-proposals-to-create-a-covid-19-safeworkplace/?sh=586a8c1debf9 We cannot rule out the possibility that Covid-19 may be transmitted via fecal matter. Here I describe studies on how SARSCoV-2 interacts with the human gut and how it may be transmitted through human waste. We need to mount a more comprehensive response to this possible source of infection. https://www.forbes.com/sites/williamhaseltine/2021/03/22/p reventing-fecal-oral-and-fecal-aerosol-transmission-of-covid19/?sh=21fed1fd60d4 March 26, 2021 While people in Sydney are out enjoying a return to the theater and more normal life, thanks to low (only five) numbers of Covid cases in the country, other countries continue to struggle. In this article, I outline four key lessons from Australia’s Covid-19 response to the pandemic. 2847
https://www.forbes.com/sites/williamhaseltine/2021/03/24/w hat-can-we-learn-from-australias-covid-19response/?sh=645695ea3a01 On March 14 last year, there were only 700 known cases of Covid-19 in the US. But that number surged to 30,000 after people continued with their big Spring Break parties. Despite vaccines, we could see a similar pattern this year if states do not impose restrictions and people don't refrain from travel. https://www.forbes.com/sites/williamhaseltine/2021/03/25/s pring-break-could-trigger-a-national-surge-in-cases-fueled-byvariant/?sh=350ce4d362b4 March 29, 2021 Though vaccines are a useful tool to help us contain Covid-19, this wave of vaccinations will not be enough to end the pandemic. A recent modeling study shows how vaccine potency declines over time. Here, I explain the study and what it means for our vaccine strategy. https://www.forbes.com/sites/williamhaseltine/2021/03/25/m odeling-study-predicts-immune-protection-may-vary-fordifferent-covid-19-vaccines/?sh=33c50e055dd2 Our pets are not immune to Covid-19. In fact, two recent preprint studies show that new variants are even more contagious to our furry friends than the original strain. More hosts means more opportunity for the virus to evolve. We need a way to rapidly detect new strains emerging from humans and other host species. https://www.forbes.com/sites/williamhaseltine/2021/03/26/fr om-cats-and-dogs-to-minks-and-mice-covid-19-variants-areinfecting-the-ecosystem/?sh=60a148b03c3f Pre-pandemic, one in five US children lived in poverty. Covid19 school closures made matters worse, with kids missing out on both learning and meals. While the stimulus package is a big step in the right direction, we must continue to address this issue beyond the pandemic. https://www.forbes.com/sites/williamhaseltine/2021/03/27/c ovid-19-has-exacerbated-child-poverty-forcing-a-long-overduepolicy-focus/?sh=75874e94740c
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March 31, 2021 One of the biggest remaining questions about the coronavirus is degree of protection after infection. Here, I discuss a study in The Lancet looking at the duration of neutralizing antibody response in patients and what this might mean for both vaccine development and policy makers. https://www.forbes.com/sites/williamhaseltine/2021/03/30/p ersistence-of-covid-19-antibodies-varies-widely-from-person-toperson/?sh=6997a42f2191 According to the CDC, mRNA vaccines are 90% effective at preventing and spreading the infection. This is great news. But we cannot let our guard down, especially against emerging variants. https://www.forbes.com/sites/williamhaseltine/2021/03/30/m oderna-and-pfizer-vaccines-prevent-infection-as-well-as-diseasekey-questions-remain/?sh=ab1df1216882
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April 1, 2021 CDC director Rochelle Walensky fought back tears during an address, urging Americans to maintain mask mandates and social distancing. These precautions are crucial to preventing another surge, which is a definite possibility. https://www.forbes.com/sites/williamhaseltine/2021/03/31/w hy-was-cdc-director-rochelle-walensky-fighting-backtears/?sh=1f3876df35dc Another new SARS-CoV-2 variant has emerged in Belgium, B.1.214. In this article, I describe the science behind the mutative capabilities of this variant. Have we reached a point where the virus has exhausted all possible mutations? It seems unlikely. https://www.forbes.com/sites/williamhaseltine/2021/03/31/n ew-belgian-variant-illustrates-the-versatility-of-sars-cov-2-inescaping-immune-suppression/?sh=6c84b73436c7 April 2, 2021 Pfizer's successful vaccine trial among 12-15 year olds shows 100% efficacy and robust antibody responses. While we wait on its authorization and rollout to help safely reopen schools and daycares, eyes are turned to trials among younger children 6 mos to 11 yrs. https://www.forbes.com/sites/williamhaseltine/2021/04/01/pf izers-successful-covid-19-vaccine-trial-in-adolescents-brings-newhope-for-population-immunity-and-safe-school-reopenings/?sh=38e7c80a7675 Results from small clinical trials suggest Pfizer and BioNTech vaccines are 100% effective against the South African variant. It's good news. But we know this virus can mutate quickly. We'll need to adapt our vaccine strategy in response and prepare ourselves for the possibility of annual vaccines. https://www.forbes.com/sites/williamhaseltine/2021/04/01/d espite-progress-protecting-the-population-against-covid-19variants-remains-complex/?sh=29f190f16d6f April 6, 2021 It is unlikely that vaccines alone will be enough to contain the Covid-19 pandemic. We need a multifaceted approach. Enter the new oral antiviral drug from Pfizer. Still in trials, this protease 2851
inhibitor could add another crucial weapon in our armory against the pandemic. https://www.forbes.com/sites/williamhaseltine/2021/04/05/pf izers-new-oral-protease-inhibitor-could-possibly-treat-andprevent-covid-19/?sh=67b82c6e2b88 Fiona Rutherford of Bloomberg asked me what I thought regarding US physicians continuing to prescribe hydroxychloroquine despite being an ineffective treatment for Covid-19. I told her that if it’s not malpractice, it’s certainly close. https://www.bloomberg.com/news/articles/2021-0401/trump-touted-drug-lives-on-as-covid-therapy-despite-trialflops?srnd=premium April 8, 2021 The new HBO documentary, “The Last Cruise”, provides a first hand account of the passengers isolated on the Diamond Princess cruise ship when Covid-19 broke out in January 2020. Their experience is a reminder of how unprepared we were. We can only hope we are ready the next time a pandemic of this magnitude befalls us. https://www.forbes.com/sites/williamhaseltine/2021/04/06/h bo-doc-the-last-cruise-gives-insight-into-nightmarish-covid-19outbreak/?sh=297506f59a02 April 9, 2021 If we want to resume our pre-pandemic ways, we need testing. Countries that have successfully reopened relied on vaccines, rapid at home testing, and mandatory quarantines. This week, England, with its record number of cases, will begin providing everyone with free, rapid at home tests. Why can’t we? https://www.forbes.com/sites/williamhaseltine/2021/04/08/ra pid-home-testing-if-the-uk-can-do-it-why-cantwe/?sh=4ff14dfed926 April 14, 2021 A new SARS-CoV-2 variant could be the cause of an exponential increase in cases in India. Here, I explain the mutations in B.1.617, the Indian variant. The potential for trouble with this 2852
variant in the US is real and immediate. We must identify its spread and contain it. https://www.forbes.com/sites/williamhaseltine/2021/04/12/a n-indian-sars-cov-2-variant-lands-in-california-more-dangerahead/?sh=ba2666b3b290 Increased PTSD, addiction, and overdoses in the last year could be fallout from the stress of Covid-19 lockdowns. Our current health system is not equipped to treat so many new patients suffering from these types of conditions. We should be working towards more integrated healthcare to treat the whole patient, including their mental health. https://www.forbes.com/sites/williamhaseltine/2021/04/12/c ovid-19-increases-stress-and-traumatic-stress-disorders-includingdrug-abuse-and-fatal-overdoses/?sh=5f57ca5d1aa8 Here, I explain the science behind a new variant in Oregon: a mutation of the more infectious, B.1.1.7 UK variant. The appearance of this variant is troubling as it may be vaccine resistant and serves as a warning that SARS-CoV-2 is continuing to evolve. https://www.forbes.com/sites/williamhaseltine/2021/04/13/adangerous-new-covid-19-variant-detected-inoregon/?sh=7ce22e20b17e April 15, 2021 A CDC online survey indicates that people between 18-24 are the most likely to suffer mental health problems during the pandemic, including an increase in loneliness. Public education campaigns could have a huge impact on removing the stigma of loneliness and connecting young people facing these mental health issues. https://www.forbes.com/sites/williamhaseltine/2021/04/13/y oung-people-hit-hardest-by-loneliness-and-depression-duringcovid-19/ April 16, 2021 I spoke with Matthew Rozsa from Salon regarding long-term brain and psychiatric after effects in a high percentage of Covid-19 patients. It may be that the disturbance of blood flow to the brain caused by Covid-19 leads to neurological damage. 2853
https://www.salon.com/2021/04/08/months-afterrecovering-from-covid-19-millions-patients-may-suffer-brain-orpsychiatric-disorders/ I joined Anand Naidoo on the Heat to discuss inequality in access to vaccines worldwide. https://america.cgtn.com/2021/04/08/the-heat-vaccineinequality-and-brazil-battles-covid-19 A recent preprint from Israel suggests that the Pfizer/BioNTech vaccine may be less effective against some variants. Our best vaccines today are still highly effective and worthwhile to take, but the study shows we need more real-world data on their protective effect against the full array of variants. https://www.forbes.com/sites/williamhaseltine/2021/04/11/t he-pfizerbiontech-covid-19-vaccine-is-less-effective-against-thesouth-african-and-uk-variants-than-against-the-original-virusaccording-to-a-new-real-world-study-fromisrael/?sh=4a4f05535888 Thank you @erniemanouse for the great conversation! I joined Ernie on his show Town Square to share insights from my career in science, including developing the first treatments for HIV/AIDS. We also discussed Covid-19, variants, and vaccines. https://www.houstonpublicmedia.org/articles/shows/townsquare/2021/04/09/395537/a-lifelong-fight-against-disease-drwilliam-haseltine-talks-about-global-health-from-aids-to-covid19/?utm_source=rss-town-squarearticle&utm_medium=link&utm_campaign=hpm-rss-link April 20, 2021 Until the discovery of the Tanzanian variant, all SARS-CoV-2 variants of concern originated from the same ancestral virus, the B.1 strain. Here, I explain the mutations in this new variant, and the implications. https://www.forbes.com/sites/williamhaseltine/2021/04/15/n ew-tanzanian-variant-detected-in-angola-from-an-entirely-newbranch-of-sars-cov-2/?sh=4247fcc76d22 April 23, 2021 CNBC asked me and five other vaccinated medical experts for our thoughts on travel. Due to the risk of emerging variants, my 2854
immediate family and I will be taking the same precautions as before we were vaccinated. https://www.cnbc.com/2021/04/22/covid-medical-expertsshare-travel-options-for-vaccinated-people.html An End to COVID-19: Exploring Cutting-edge Science, Medicine & Public Health. Streaming live Monday, April 26 at 7:00pm ET. Presented by The Explorers Club. I will be speaking about the cutting-edge discoveries of the past year that have allowed us to weather the storm of the COVID-19 pandemic and start thinking about scenarios where the virus will be controlled. The speed and complexity of the new, life-saving science being implemented in public health measures throughout the country is unmatched in human history. However, the speed of new variants emerging throughout the world is making this a race against time. You can watch live on explorers.org, YouTube Channel, and Facebook Live! - Monday, April 26 at 7:00 pm ET April 27, 2021 Here, I describe several of the variants likely tied to the massive increase in cases of SARS-CoV-2 in India. This is a reminder that this is no time to relax. As mutations continue to be discovered, we must remain vigilant in our Covid-19 mitigation efforts. https://www.forbes.com/sites/williamhaseltine/2021/04/23/t he-recent-rise-of-indian-covid-19-cases-display-the-dangers-ofsars-cov-2-variants/?sh=6464fd397492 It wasn’t until June 2020 that gastrointestinal symptoms of SARS-CoV-2 were added to the CDC’s official list of primary symptoms, changing protocols that previously denied tests to patients experiencing diarrhea, nausea, and vomiting without fever. Here I explain some of the implications for transmission. https://www.forbes.com/sites/williamhaseltine/2021/04/23/h ow-covid-19-impacts-the-digestive-system/?sh=23268f723e21 April 30, 2021 The devastating global impact of the Covid-19 pandemic has reinforced the pressing need to make healthcare accessible and affordable to all. Fintech for health is an innovation that can help fill 2855
the gap between what governments are willing to pay for when it comes to health and what those in need are able to afford. https://www.forbes.com/sites/williamhaseltine/2021/04/29/h ow-fintech-can-help-break-the-health-povertytrap/?sh=7a6c83dc4e77 Rachel Clarke’s recent memoir, Breathtaking, is a powerful testimony of the challenges frontline health workers face. A palliative care doctor, Clarke provides an inside look into the UK NHS during the pandemic, sharing personal stories and shedding light on the fight to procure PPE for care facilities. https://www.forbes.com/sites/williamhaseltine/2021/04/26/w ritten-from-the-frontlines-of-the-pandemic-rachel-clarkesmemoir-breathtaking-is-a-must-read/?sh=51d72d8a1ca0 Gun control measures and mask-wearing mandates are unnecessarily politicized. These measures are not intended to take away freedoms, but to save lives. Countries that have been successful in eliminating Covid-19 presented a politically united, singular public health message. https://dailyclout.io/opinion-the-common-good-of-guncontrol-and-covid-control/ In initial trials, two new experimental antibody treatments demonstrate strong neutralization of the wild-type and the most common variants of SARS-CoV-2. Here I explain the virus targets for these highly engineered antibodies. Deeper analysis could lead to wide-ranging treatment and prophylactic success in the near future. https://www.forbes.com/sites/williamhaseltine/2021/04/26/n ew-antibody-therapy-and-prophylactic-shows-promise-indefending-against-sars-cov-2-variants-ofconcern/?sh=159df00671dc As I told Bloomberg, I fear there may be more trouble coming in India. As wealthier nations have held onto vaccines and manufacturing supplies, the virus has run wild in poorer nations with a slower roll-out. There are already 2nd, maybe 3rd, generation variants of the B.1.617 circulating in India which could be even more dangerous. https://www.bloombergquint.com/coronavirusoutbreak/vaccine-hoarding-set-to-backfire-on-rich-nations-asindia-reels
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May 1, 2021 SARS-CoV-2 is a shape-shifting virus, able to change parts of its infamous spike protein to avoid neutralization. However, there are some amino acids of the spike protein that are not often changed. These areas may prove to be the virus' Achilles’ heel and may be vital to both therapeutic and prophylactic antibody design, as well as next generation vaccines. https://www.forbes.com/sites/williamhaseltine/2021/04/29/a n-antibody-cocktail-to-lay-low-a-mighty-foe/?sh=1a45e45b13aa May 3, 2021 Brain fog. Encephalitis. PTSD. These and other neurological and psychological complications in recovered Covid-19 patients are prevalent enough that they should inform recommendations for care. Research to understand how neuropsychiatric Covid-19 symptoms work (and how to treat them) is also urgently needed. https://www.forbes.com/sites/williamhaseltine/2021/04/29/u nderstanding-the-neurological-and-psychological-effects-of-covid19/?sh=4a4198512090 TWITTER: Neurological and psychological complications in recovered Covid-19 patients are prevalent enough that they should inform care recommendations. Research to understand how neuropsychiatric Covid-19 symptoms work (and how to treat them) is urgently needed. https://www.forbes.com/sites/williamhaseltine/2021/04/29/u nderstanding-the-neurological-and-psychological-effects-of-covid19/?sh=4a4198512090 May 4, 2021 As the US and other countries restrict travel from India, it’s worth noting that over the course of the pandemic, reactionary travel bans have proven ineffective to prevent the spread of Covid19. In this article I review specific border control policies that work. https://www.forbes.com/sites/williamhaseltine/2021/05/03/globa l-border-control-policies-will-be-necessary-to-control-thepandemic/?sh=607384eb5728 2858
The fight to end tuberculosis by 2035, the leading cause of death from infectious disease in adults, has lost momentum over the past year. Compared to the prior year, 14 million more fell ill and 500,000 more died from TB. But we CAN end this crisis with political will and investment. https://www.forbes.com/sites/williamhaseltine/2021/05/03/c ovid-19-and-tuberculosis-a-deadly-combination---we-can-dobetter/ May 6, 2021 Indigenous populations are generally more likely to be infected by and die from Covid-19. But not in Australia. The Australian government worked closely with their indigenous communities and provided them the financial support to lead their own response. It's a blueprint we can all learn from. https://www.forbes.com/sites/williamhaseltine/2021/05/05/p rotecting-indigenous-populations-from-covid-19-the-australianexample/ A new antiviral drug combination may be the solution to India’s Covid-19 crisis. A new study shows that a cocktail of remdesivir and two hepatitis C drugs can treat the disease and prevent further spread. The same mix may also work with molnupiravir, an OTC antiviral, which could be made available quickly and cheaply to all in need. https://www.forbes.com/sites/williamhaseltine/2021/05/05/newantiviral-drug-cocktail-could-help-india-control-brutal-covid-19outbreak/?sh=3f85aa077680 Combination antibodies can help treat Covid-19 but they can sometimes be expensive to produce and challenging to deliver to the patient in time. Here, I describe another approach that uses combination nanobodies from camelids which may be more stable, more simply modified, and less expensive than traditional monoclonal antibody drugs. https://www.forbes.com/sites/williamhaseltine/2021/05/05/anew-approach-to-treat-and-prevent-covid-19/?sh=3319e93422db May 8, 2021 A big question in many of our minds is how effective vaccines are against Covid variants. Three new studies give us some early (and positive) insight: 2 real-world studies show the Pfizer-BioNTech 2859
vaccine can protect against B.1.1.7 & B.1.351, another clinical study shows a Moderna booster may protect against B.1.351 & P.1 variants. But there are still big questions still left to answer. https://www.forbes.com/sites/williamhaseltine/2021/05/06/vacci nes-vs-variants-three-new-studies-show-the-effectiveness-ofpfizer-and-moderna-vaccines/?sh=105fe69a5c33 Are you among the many Americans with travel plans this summer? CNBC asked me and other medical experts what we might expect from the virus this summer, and throughout the remainder of 2021. As I have said before, I don’t think summer travel is safe, and could lead to a surge in cases. https://www.cnbc.com/2021/05/06/is-it-safe-to-travel-thissummer-or-fall-heres-what-experts-say.html Announcement: You can hear me tell the story of my life in science, and the many world-changers I have met along the way, in the newly released audiobook of my autobiography, My Lifelong Fight Against Disease. You can download your copy here: https://www.amazon.com/My-Lifelong-Fight-AgainstDisease/dp/B0945PYNNZ/ref=tmm_aud_swatch_0?_encoding= UTF8&qid=&sr= May 10, 2021 WHO approved China’s Sinopharm’s vaccine for emergency use. I joined Anand Naidoo on CGTN’s The Heat to discuss the approval process, its potential effectiveness against variants, and the infrastructure required to distribute the shots, including implications for poorer nations gaining access. https://america.cgtn.com/2021/05/08/the-heat-china-leadsmultilateralism-talks-at-un May 11, 2021 A newly discovered monoclonal antibody, BG10-19, is highly potent against a broad range of SARS-CoV-2 variants. It neutralizes the virus by binding the receptor-binding domain of the spike protein in a closed position, and shows potential for treating and preventing Covid-19 if combined with S309 and S2H97 antibodies. https://www.forbes.com/sites/williamhaseltine/2021/05/11/newl y-discovered-antibody-neutralizes-variants-by-locking-thereceptor-binding-domain-in-a-closed-position/?sh=798f13be6861 2860
-A preprint study from Moderna shows that antibodies generated from their first generation vaccine protect from variants for only 6 months. Fortunately, their boosters demonstrate protection against B.1.351 and P.1 variants (B.1.617 was not included in the study), and I think it is safe to assume they will be fast-tracked for approval. https://www.forbes.com/sites/williamhaseltine/2021/05/11/m rna-vaccine-booster-shots-likely-required-within-six-months-toprotect-against-covid-19-variants/?sh=5bb8b59b598b May 17, 2021
You can now buy the full five volume set on Amazon here: https://www.amazon.com/dp/B08RSDZY32?searchxofy=true&bi nding=kindle_edition&qid=1621260497&sr=1-1 May 18, 2021 The search is on for neutralizing antibodies that recognize epitopes in regions outside the receptor-binding domain of the SARS-CoV-2 virus, which may be less likely to mutate. This new study shows progress, with implications for strategies to prevent new variant-associated outbreaks. https://www.forbes.com/sites/williamhaseltine/2021/05/13/anew-twist-to-antibody-cocktails-to-prevent-and-treat-covid19/?sh=59f1b47e495e -As I told Bloomberg Businessweek, we’ve recently learned that the Moderna vaccine doesn’t protect very well against two of the 2861
common SARS-CoV-2 variants after about six months. You can listen here to our discussion about boosters and more on what we’re learning about the current vaccines. https://www.bloomberg.com/news/audio/2021-05-11/tsmcstuck-in-middle-of-global-panic-over-chips-podcast -Decades of research has led to a possible new cure for “bubble baby” disease, a genetic disorder that robs patients of their immune system. In a study of 50 patients, an experimental gene therapy that takes advantage of viral vectors (which I worked on early in my career) had promising results, fully reconstituting the immune systems in all but two participants in the study. https://www.forbes.com/sites/williamhaseltine/2021/05/12/apossible-cure-for-bubble-baby-disease-and-hope-for-morediscoveries-to-come/?sh=78e5261c7141 -A new SARS-CoV-2 variant with origins likely in sub-Saharan Africa, B.1.620 was first detected circulating in Europe and is yet another reminder of the importance of global surveillance. Here I discuss what we know about its possible evolutionary path, and the mutations that make it more transmissible, infectious, and immuneevasive. https://www.forbes.com/sites/williamhaseltine/2021/05/18/athird-sars-cov-2-variant-of-interest-potentially-concern-emergesfrom-sub-saharan-africa/?sh=452bf2285e20 May 20, 2021 As we search for treatments for SARS-CoV-2, can we find measures to treat all broad classes of coronavirus unilaterally? A set of recent studies suggests that a B6 antibody combined with a camelid-derived nanobody may be one approach that could work. We should be investing in more research on this approach and others like it to help us combat Covid-19 and prepare for future pandemics. https://www.forbes.com/sites/williamhaseltine/2021/05/19/di scovery-of-a-novel-monoclonal-antibody-that-neutralizes-a-broadrange-of-coronaviruses/?sh=280e7b07516d -Public health institutions should be free of political and economic pressures. Decisions during infectious disease outbreaks 2862
should be evidence-based, and made swiftly. Sadly, this is not always the case. For examples from the Covid pandemic, look no further than Michael Lewis’s latest nonfiction book, The Premonition. https://www.forbes.com/sites/williamhaseltine/2021/05/20/p remonition-by-michael-lewis-highlights-a-longstanding-need-forstructural-reform-of-the-us-public-health-service/ May 21, 2021 The CDC’s recent mask-wearing guidance has many confused and fearful. How do we stay safe, not knowing who is vaccinated and who isn’t? My advice is to make your choices about staying masked (or not) based on the circumstances in your area. Here I offer some criteria for that decision. https://www.forbes.com/sites/williamhaseltine/2021/05/18/m aking-the-best-of-a-tough-situation-how-to-respond-to-the-cdcsnew-mask-guidance/?sh=500074e01968 May 25, 2021 Thank you to @nyt for including my perspective on the importance of developing Covid risk assessment tools to inform appropriate public health responses as the virus evolves. https://www.nytimes.com/2021/05/20/opinion/herdimmunity-covid.html ------As I told Salon, mixing doses of the Covid-19 vaccine from different manufacturers appears to be at least as good or better than two doses from the same, according to a recent study from Spain. https://www.salon.com/2021/05/23/mixing-two-differentvaccine-doses-might-actually-strengthen-covid-19-immunity-nothurt-it/ -Despite a quarter of their population already having been vaccinated, Singapore is experiencing a surge of new cases. The circumstances there, as well as similar outbreaks in Vietnam and Taiwan, should serve as warning as countries roll back restrictions. https://www.forbes.com/sites/williamhaseltine/2021/05/24/si ngapores-outbreak-highlights-a-challenging-road-ahead-for-covid19-containment/?sh=481aa79a4d81 2863
May 26, 2021 In response to the Covid-19 pandemic, scientists worldwide began sharing new ideas and data immediately and transparently. I am so encouraged by the increase in collaboration and communication, among other significant changes in the field, and here I share my observations. https://www.scientificamerican.com/article/how-covidchanged-science/ May 28, 2021 I joined @anandnaidoo on CGTN’s The Heat to discuss the vaccination progress we have made globally--overall, it’s been a remarkable success. Our panel also discussed case numbers worldwide, variants, inequalities among nations, economic impacts of Covid, and more. https://america.cgtn.com/2021/05/27/theheat-coronavirus-pandemic-more-than-1-7-billion-vaccine-dosesgiven-globally
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June 2021
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June 1, 2021 Rapid antigen testing is a preventative tool to quickly and cheaply detect the most infectious Covid-19 cases. Here, I describe a UK study indicating that, when coupled with other mitigation efforts (PCR testing, tracing, isolating), this tool could give us the upper hand against Covid-19. https://www.forbes.com/sites/williamhaseltine/2021/06/01/u nited-kingdom-data-show-population-based-rapid-antigen-testsare-a-potent-covid-control-tool/?sh=16f747f3e26a --
The COVID Commentaries: A Chronicle of a Plague, my five volume collection of writings, research, and interviews on COVID19 is now available for just five dollars for the five volume set. You can purchase it here: https://www.amazon.com/dp/B08RSDZY32?searchxofy=true&bi nding=kindle_edition&qid=1621260497&sr=1-1
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On Tuesday, June 8th at 5pm PST, I will be joining Asia Society Southern California in partnership with BioscienceLA for a discussion with Scan Health Plan President & CEO Dr. Sachin H. Jain, Illumina Chief Commercial Officer Susan Tousi on the lessons learned from the pandemic and preparations for the next one. The panel will examine how we can continue to drive innovation in healthcare, increase health equality, improve global collaboration, and address vaccine effectiveness against variants and its global rollout, among other topics. The conversation will be moderated by Asia Society Southern California Advisory Board Member Yiwen Li. @AsiaSocietyLA (Twitter, Instagram), @AsiaSocietySouthernCalifornia (Facebook, LinkedIn). Register for the event here: https://asiasociety.org/southerncalifornia/events June 3, 2021 Overall cases of Covid-19 are dropping across the US, yet the percentage of cases among children is on the rise. We urgently need comprehensive data on how Covid-19 affects children, including transmissibility and long-term effects. We must remain vigilant to protect kids. https://www.forbes.com/sites/williamhaseltine/2021/06/03/dontlet-children-be-the-casualties-of-covid-19complacency/?sh=5309f27c5982 2867
June 4, 2021
The COVID Commentaries: A Chronicle of a Plague, my five volume collection of writings, research, and interviews on COVID19 is now available for just five dollars for the five volume set. You can purchase it here: https://www.amazon.com/dp/B08RSDZY32?searchxofy=true&bi nding=kindle_edition&qid=1621260497&sr=1-1 June 5, 2021 SARS-CoV-2 is wily and elusive, and the search for drug treatments to deter it has pointed us in a promising direction. Here I describe studies recently published in Science Immunology that focus on diABZI, a small molecule drug that might prevent and treat Covid-19. https://www.forbes.com/sites/williamhaseltine/2021/06/03/n ew-drug-may-bypass-sars-cov-2-blockade-of-innate-immuneresponse/?sh=34ac089f17b5 -The pandemic is far from over. In this piece, I review the many victories we have had in our fight against SARS-CoV-2 and discuss what we can expect for prevention going forward, the many threats the virus continues to pose, and where we go from here. https://www.project-syndicate.org/onpoint/can-we-end-thepandemic-by-william-a-haseltine-202106?h=S6psB3mSyk5bTbXUFdUjxR6C97vkfN1HaAkK2CCCuv Y%3d& -2868
Our kids are suffering. Across the nation, mental health emergencies in children and teens were 24% and 31% higher respectively between March and October of 2020 compared to the prior year. Here I discuss the crisis and what we can do to help. https://www.forbes.com/sites/williamhaseltine/2021/06/04/p ediatric-mental-health-is-in-crisis/?sh=32e27749b572 -The viral protein NSP3 is showing itself to be a target for antiviral drugs. Here I describe the structure and function of nonstructural protein 3 and the discovery that a combination of Hepatitis-C antivirals along with a remdesivir metabolite hold promise for prevention and treatment of infection by SARS-CoV2. https://www.forbes.com/sites/williamhaseltine/2021/06/04/h epatitis-c-drugs-and-a-remdesivir-metabolite-as-new-anti-covid19-drugs-the-viral-protein-nsp3-emerges-as-a-newtarget/?sh=486a78be448c June 8, 2021
Today, June 8th at 5pm PST, I will be joining Asia Society Southern California in partnership with BioscienceLA for a discussion with Scan Health Plan President & CEO Dr. Sachin H. 2869
Jain, Illumina Chief Commercial Officer Susan Tousi on the lessons learned from the pandemic and preparations for the next one. The panel will examine how we can continue to drive innovation in healthcare, increase health equality, improve global collaboration, and address vaccine effectiveness against variants and its global rollout, among other topics. The conversation will be moderated by Asia Society Southern California Advisory Board Member Yiwen Li. @AsiaSocietyLA (Twitter, Instagram), @AsiaSocietySouthernCalifornia (Facebook, LinkedIn). Register for the event here: https://asiasociety.org/southerncalifornia/events --
New book alert! I wrote this youth edition of my autobiography to inspire the next generation of aspiring scientists by showing just how powerful—and accessible—a career in science can be, through my own examples. It is available now here: https://www.amazon.com/Science-As-Superpower-LifelongPossible-ebook/dp/B096N55DZ6/ June 9, 2021 Some good news for people with the rare vision disorder retinitis pigmentosa. Research in optogenetics has achieved a new milestone, and here I share some background in this approach for vision treatment and details on the breakthrough. 2870
https://www.forbes.com/sites/williamhaseltine/2021/06/08/re storing-vision-to-the-blind-regenerative-medicine-offers-newhope-for-retinitis-pigmentosa/?sh=6321d3e1607d -Most of us consider 98.5 degrees F to be our “normal” body temperature, and 100.4 degrees F to be the sign of a fever. Why? Here I explain the origins of our basis for these measurements, and why it’s so important to know your own body’s fluctuations. https://www.forbes.com/sites/williamhaseltine/2021/06/08/b aseline-temperature-dropped-over-100-years-the-importance-ofknowing-your-normal-temperature-to-detectfever/?sh=76b02f2936c6 June 10, 2021 Here in the U.S. we would be wise to pay attention to what’s happening in Australia, Singapore, China, and Taiwan. Cases there were in single digits until recently. Now they are surging. Here I describe what is happening, and the warning message it sends. https://www.forbes.com/sites/williamhaseltine/2021/06/09/t he-perils-of-covid-complacency/ -I was interviewed by Andrea Macdonald, founder of ideaXme about how Covid-19 has changed science and what the future holds. We also discuss my new book, Science as a Superpower, and the importance of inspiring young people to have an interest in science. You can watch the interview here: https://youtu.be/15jcKJHfBaw or listen to the ideaXme podcast on all popular streaming platforms. June 11, 2021 Covid-19 testing tells a story: more testing means more information on cases in a population. But testing is only one tool for containing the pandemic, and the story from Andorra offers some important lessons about testing’s role in this battle. https://www.forbes.com/sites/williamhaseltine/2021/06/10/s uccess-and-challenges-in-mass-screening-for-covid-19-controlthe-andorra-story/?sh=3a1f174b37af -I am so proud of our country. The Biden Administration’s plan to vaccinate the world is in keeping with our country’s noblest 2871
traditions. This commitment is an act of hope and a work of mercy that will safeguard all Americans alongside the wellbeing of the world. https://www.forbes.com/sites/williamhaseltine/2021/06/11/apivot-point-for-global-leadership-on-covid-19/?sh=6b2c3f1e76af June 12, 2021 Here, I talk about why I wrote my new book, Science as a Superpower. You can learn more or get your copy at scienceasasuperpower.com. https://youtu.be/Q31zpn9Pp8k June 16, 2021
Science is about asking big questions and then working hard to find the answer. – William A. Haseltine An excerpt from my latest book, Science as a Superpower: My Lifelong Fight Against Disease and the Heroes Who Made It Possible. In this book, I share my love of science with the hope of inspiring young people to pursue a life in science and someday make their own contributions to improve human life. Learn more at http://scienceasasuperpower.com/
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June 17, 2021 Good news with this step forward in precision medicine: FDA approved Lumakras as a treatment for non-small cell lung cancer. This breakthrough in cancer therapy targets the mutant protein KRAS common to many troubling tumors (85-90% of pancreatic and 40% of colorectal cancers). https://www.forbes.com/sites/williamhaseltine/2021/06/16/anew-cancer-treatment-cracking-the-kras-code/?sh=57f3abe6109b June 18, 2021 Here, I talk about the most important advice I have for any young person interested in pursuing a life in science. https://youtu.be/VrxhZlm5HGc June 20, 2021
When I was a child, my mother was often seriously ill. Her poor health filled me with fear, anxiety, and a feeling of helplessness. So, I decided I would pursue a career in science in order to fight disease and heal as many people as I could. In my new book Science as a
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June 22, 2021
I recently spoke with a 2nd grade class from St. Leo the Great School in Oakland, CA. They wrote me some wonderful letters and I want to share a few of them. Thank you for letting me speak with your class and hopefully inspire some of the students to pursue a career in science. If you would like to invite me to speak with your class please visit http://scienceasasuperpower.com/ and fill out the contact form. June 23, 2021 The devastating impact of Covid on nursing home residents has raised awareness of standards of care in long-term facilities, and an 2874
explosion of demand for at-home nursing care. Here I review shortcomings in our eldercare system and look with hope towards possible improvements. https://www.forbes.com/sites/williamhaseltine/2021/06/21/w ill-covid-19-improve-long-term-care/?sh=69e7d52c6e46 June 24, 2021
An excerpt from my latest book, Science as a Superpower: My Lifelong Fight Against Disease and the Heroes Who Made It Possible. In this book, I share my love of science with the hope of inspiring young people to pursue a life in science and someday make their own contributions to improve human life. Learn more at http://scienceasasuperpower.com/ June 26, 2021 Here, I talk about why I think young people should consider pursuing a career in science, for their own fulfillment and for the sake of humanity: https://youtu.be/NfPhqtlTap0 2875
June 28, 2021
If it weren’t for Scottish scientist, Alexander Fleming, I would’ve never written Science as a Superpower. When I was four months old, I fell very ill. Fleming had recently discovered penicillin and thankfully I was one of the lucky few able to receive the breakthrough drug, which saved my life. Learn more about my latest book and the scientists who inspired me at http://scienceasasuperpower.com/ June 29, 2021 Doctors and nurses are suffering from burnout, a problem that began long before Covid. A 2018 study found the suicide rate among physicians was twice that of the general population. Here I discuss barriers to mental health support for our healthcare workers. https://www.psychologytoday.com/us/blog/best-practices-inhealth/202106/we-need-prioritize-mental-health-healthcareworkers -Isolation from friends, economic uncertainty, fear of illness, death of close relatives--the circumstances of the pandemic has led to an increase in depression and other mental health concerns. Here
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I discuss the psychological scars from Covid, and how we might move forward. https://www.psychologytoday.com/us/blog/best-practices-inhealth/202106/how-covid-19-changes-our-understanding-mentalhealth -The Delta variant is proving to be enormously contagious: even 5-10 seconds of exposure may result in transmission. Here I discuss potential impact on the US and globally, and strategies to employ to keep this deadly variant in check. https://www.forbes.com/sites/williamhaseltine/2021/06/28/in fection-through-fleeting-contact-with-the-delta-variant-leads-tolockdowns-across-australia/?sh=f4e48d75d4ff June 30, 2021
An excerpt from my latest book, Science as a Superpower: My Lifelong Fight Against Disease and the Heroes Who Made It Possible. In this book, I share my love of science with the hope of 2877
inspiring young people to pursue a life in science and someday make their own contributions to improve human life. Learn more at http://scienceasasuperpower.com/
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July 2021
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July 2, 2021 In this video from a recent interview, I share a story about one of the scientific superheroes in my new book, Katarin Kariko, and how she changed the world through her pioneering work harnessing the power of mRNA to fight disease. https://youtu.be/EPjaIALYHyU July 6, 2021
An excerpt from my latest book, Science as a Superpower: My Lifelong Fight Against Disease and the Heroes Who Made It Possible. In this book, I share my love of science with the hope of inspiring young people to pursue a life in science and someday make their own contributions to improve human life. Learn more at http://scienceasasuperpower.com/
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July 8, 2021
Since many polio patients had respiratory issues, they needed mechanical breathing assistance. These tank chambers were built to simulate breathing and save lives. Plus, they looked like little spaceships. Learn more about my latest book and the scientists who inspired me at http://scienceasasuperpower.com/ July 10, 2021 In this video from a recent interview, I talk about what inspired me to become a scientist. https://youtu.be/gmHQmqwayBA
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July 12, 2021
An excerpt from my latest book, Science as a Superpower: My Lifelong Fight Against Disease and the Heroes Who Made It Possible. In this book, I share my love of science with the hope of inspiring young people to pursue a life in science and someday make their own contributions to improve human life. Learn more at http://scienceasasuperpower.com/ July 13, 2021 I recommend a multilayered strategy--multimodal therapy--to keep us safe in the face of the Delta variant. It is far more transmissible and appears to be more lethal. Here I discuss its impact around the world and steps countries are (and are not) taking. #multimodaltherapy https://www.forbes.com/sites/williamhaseltine/2021/07/13/t he-delta-dilemma-loosening-covid-19-controls-at-a-time-ofincreased-danger/?sh=6d1b7c682750 2882
July 14, 2021
I recently spoke with a 2nd grade class from St. Leo the Great School in Oakland, CA. They wrote me some wonderful letters and I want to share a few of them. If you would like to invite me to speak with your class please visit http://scienceasasuperpower.com/ and fill out the contact form. July 18, 2021
When you get right down to it, science is about asking big questions and then working hard to find the answer. 2883
A quote from my latest book, Science as a Superpower. In the book, I share my love of science with the hope that it will inspire young people to pursue a life in science and make their own contributions to improve human life. More at http://scienceasasuperpower.com/ July 19, 2021 One of our ACCESS Health summer interns recently toured the Wake Forest Institute for Regenerative Medicine facility, established by Dr. Anthony Atala. The tour included seeing mini-organs printed for drug testing and other new, groundbreaking treatments in development. https://www.forbes.com/sites/williamhaseltine/2021/07/13/t he-dawn-of-a-new-era-of-regenerative-medicine-tissueengineering-comes-of-age/?sh=4ba413167d11 -Pfizer’s Delta-variant booster announcement sparked an uproar. Yet, it’s important to remember that it’s the responsibility of each nation’s government to protect its citizens. Booster shots and global vaccination efforts more broadly cannot and should not be mutually exclusive. https://www.forbes.com/sites/williamhaseltine/2021/07/16/a n-argument-for-covid-19-booster-shots-to-protect-thevulnerable/?sh=19c5dba480f1 -Here I describe the mutations and characteristics of the Lambda variant. "C.37" is driving a rapid increase of Covid-19 throughout South America, Central America, and parts of the Caribbean. Each new variant provides a clue to SARS-Cov-2’s strengths and weaknesses. https://www.forbes.com/sites/williamhaseltine/2021/07/16/a-new-threat-on-the-rise-in-south-america/?sh=2b17daba3337 -If the White House asked me what more we could do to inform Americans about the dangers of Covid-19 and the importance of vaccinations, my answer would be clear: marshal the data at the most local level possible. Find local leaders, tell the local stories, make it close to home. 2884
https://thehill.com/opinion/healthcare/563605-keep-it-localhow-america-can-meet-its-vaccine-challenge?rnd=1626639214 — What characteristics would we hope for in second-generation Covid-19 vaccines? Protect against any variant, reduce viral load, elicit high levels of neutralizing antibodies are a few. Here I describe two new subunit vaccines, showing promise. https://www.forbes.com/sites/williamhaseltine/2021/07/20/n ew-studies-highlight-promising-candidates-for-second-generationcovid-19-vaccines/?sh=728cd4286c97 July 20, 2021 Here, I answer the questions of a young student about evolution https://youtu.be/k2EMrE470EA July 21, 2021 Only 54% of the UK population was fully vaccinated when they ended restrictions. A tragic error given that they, like the US have failed to mount an effective second and third line of defense. Lives will be lost and permanently destroyed by Covid-19. https://www.forbes.com/sites/williamhaseltine/2021/07/20/t he-uks-dangerous-and-deadly-gamble/?sh=717bb0ff400a -The Delta variant is sending people to the hospital, and there is an urgent need to discern which patients will need the most support. Biomarkers could help. Here I explain the findings from a recent report identifying such a marker: a small RNA fragment known as microRNA. https://www.forbes.com/sites/williamhaseltine/2021/07/21/p otential-new-biomarker-to-guide-treatment-for-severe-covid-19/ -France has taken the lead in encouraging people to get vaccinated by mandating vaccines to enter restaurants, indoor public venues, and public transpor. It seems unlikely Americans would accept such a mandate, but maybe this next wave of infections will change people’s minds. https://www.forbes.com/sites/williamhaseltine/2021/07/22/li bert-egalit-fraternit-rationalit-covid-control-frenchstyle/?sh=25e7a6cc693e 2885
July 22, 2021
Let me take you back in time to my seventh grade science fair...“The frog is very different from us on the outside but inside it looks like us,” I explained to onlookers. Learn more about my latest book and the scientists who inspired me at http://scienceasasuperpower.com/ July 24, 2021
I recently spoke with a 2nd grade class from St. Leo the Great School in Oakland, CA. They wrote me some wonderful letters and 2886
I want to share a few of them. If you would like to invite me to speak with your class please visit http://scienceasasuperpower.com/ and fill out the contact form. July 26, 2021
Surviving a close brush with death when I was a baby was a catalyst for my lifelong passion for using research, discovery, and scientific innovation to save lives. A quote from my latest book, Science as a Superpower. In the book, I share my love of science with the hope that it will inspire young people to pursue a life in science and make their own contributions to improve human life. More at http://scienceasasuperpower.com/ July 27, 2021 Dr. Summer Knight recently spoke with my team about her new book: Humanizing Healthcare. Her message is critical, especially now, emphasizing the importance of improving our healthcare model to be more compassionate & connected. I urge you to read her groundbreaking work.
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https://www.forbes.com/sites/williamhaseltine/2021/07/23/h umanizing-healthcare-a-model-for-consumer-basedcare/?sh=66cea3031e41 -COVID-19 will not be the last pandemic this generation of Americans will experience. Our hospital systems need to be better prepared. Here I describe approaches other countries took to respond to surges, and share thoughts about what we might do now to avoid future tragedy. https://www.forbes.com/sites/williamhaseltine/2021/07/26/o verwhelmed-us-hospital-systems-a-look-into-thefuture/?sh=5f0298177c62 -Searching for the source of a virus like SARS-CoV-2 is challenging. As I mentioned to LiveScience, looking at bats can give clues. Why? Bats live long lives, travel long distances, and live close together--like us. A virus that evolves in bats can find fertile ground in humans. https://www.livescience.com/search-covid-19-origins-patientzero.html -8 years after one man's terrible car accident, he was given a voice. Speech neuroprosthesis enables Pancho to simply think the words he wants to say, and they appear on a screen. The study of this new use of regenerative medicine was recently published in the NEJM. https://www.forbes.com/sites/williamhaseltine/2021/07/27/t he-talking-man-new-advances-in-regenerativemedicine/?sh=1c7ddfea11fe July 28, 2021 I recently answered the questions of a 2nd grade class from Oakland, CA. Here, I explain how all living things get cancer...even dinosaurs! https://youtu.be/u4olVZWtmYY
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August 2021
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August 3, 2021
My new ebook, Covid Related Post Traumatic Stress Disorder (CV-PTSD): What It Is and What To Do About It, is now available on Amazon: https://www.amazon.com/gp/product/B09B9263GV/ref=dbs_a_ def_rwt_bibl_vppi_i2 https://www.amazon.com/gp/product/B09B9263GV?pf_rd_r =Q9JHGCJMDFQDNSJX648K&amp;pf_rd_p=5ae2c7f8-e0c64f35-9071-dc3240e894a8&amp;pd_rd_r=a9937c28-156e-4be5b26e040a1d783831&amp;pd_rd_w=hkTyr&amp;pd_rd_wg=KBhzq&a mp;ref_=pd_gw_unk In this book, I define and give us a name for the trauma we have experienced throughout the pandemic. I outline the shape of our shared experience and provide a roadmap to rebuild our societies. Each chapter of the book explores the effects of the pandemic on different groups. This book makes the case for CV-PTSD to be a diagnosable disorder in the classification of disease. This is the first step towards developing treatments and therapies to make them available to communities at an affordable price. Pediatric mental health is a serious concern, and COVID-19 has had a profound impact, especially on young children. I joined Donna
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Tetreault on ABC 4’s program Kids Under Construction to talk about this medical crisis and what adults can do. https://www.abc4.com/podcasts/kidsunderconstruction/kidsunder-construction-pediatric-mental-health/ August 4, 2021 To protect ourselves against this mighty virus, we must use a multimodal strategy: antivirals, vaccines, public health strategies, global cooperation on genomic surveillance, and more. Now is not the time to let down our guard. LONGER VERSION: This mighty, shape-shifting virus will not stop its attempts to evade every weapon we throw at it. Vaccines alone will not protect us, and so we must use a multimodal strategy: antivirals, vaccines, public health strategies, global cooperation on genomic surveillance, and more. Despite the tone of hope and optimism in public discourse right now, I strongly assert that now is not the time to let down our guard. https://www.washingtonpost.com/opinions/2021/08/04/becareful-about-covid-19-optimism-there-are-still-plenty-waysthings-go-wrong/
My very first independent experiments were a little more…awesome. My work bench was my bedroom desk. When a 2891
spark from a test mix ignited the main cache, my desk went up in flames instantly. Woops. Learn more about my latest book and the scientists who inspired me at http://scienceasasuperpower.com/ #authorquotes #STEM #youngadultnonfiction #bookstagram #authorsofinstagram #science #biography #autobiography #kidlit August 5, 2021 In the words of a young mother, “Imagine the burden a child would have to bear if they were to bring a life-threatening disease home to their families, from the simple act of going to school or to camp.” Kids can infect household contacts with Covid-19. Here I discuss the details of a NEJM study from July 2021 and its implications for the fall. https://www.forbes.com/sites/williamhaseltine/2021/08/04/anew-study-documents-efficient-covid-19-transmission-frominfected-children-and-adolescents-to-householdcontacts/?sh=4ab6c6b282d6 What does the future hold as SARS-CoV-2 evolves? Will it become more transmissible? More (or less) deadly? Will it evade vaccines? Here I go through four scenarios presented in a recent report from the UK. Of this I am certain: Multimodal Covid Control is a viable prospect for effective management of this pandemic. https://www.forbes.com/sites/williamhaseltine/2021/08/04/awarning-about-the-future-of-covid-19-from-the-scientificadvisory-group-for-emergencies-of-the-unitedkingdom/?sh=2a07d39c2e54 August 10, 2021 Hundreds of people at the Boston Marathon Bombing suffered perforated or ruptured ear drums. Tympanoplasty, developed in the 1950s, restores hearing, but not quite to what it used to be. Now, with regenerative medicine, doctors have an alternative. Here I describe the innovation. https://www.forbes.com/sites/williamhaseltine/2021/08/09/h ealing-ruptured-eardrums-with-a-new-3-d-printedgraft/?sh=2a1ff9203199 Suicide is the 2nd most common cause of death among college aged students. A recent study found half of college students struggle with mental health issues. Yet few seek services--largely due to 2892
stigma, but also cost and lack of staff. Here I discuss how peer counseling can help. https://www.forbes.com/sites/williamhaseltine/2021/08/09/h ow-peer-counseling-can-address-barriers-to-student-mentalhealth/?sh=46b2fe961638 The SARS-CoV-2 variant Lamda, first found in South America a year ago, is now the dominant variant in Argentina, Brazil, Chile, and Colombia. Here I describe its mutations and what we want to watch and prepare for if it gains wide circulation here in the US. https://www.forbes.com/sites/williamhaseltine/2021/08/10/it -is-time-to-pay-close-attention-to-the-lambda-variant-nowdevastating-south-america/?sh=238249eb4348 A Lancet study estimates over 1M children around the world have lost a primary caregiver to Covid-19. This is devastating. We must not overlook this vulnerable population and begin to build programs to support them. https://www.forbes.com/sites/williamhaseltine/2021/08/10/w e-must-support-the-children-orphaned-by-covid19/?sh=10eacc7e599c August 12, 2021 Over 18 months after the first documented case of Covid-19, even the most successful pandemic response strategies have fallen short. Why? How did we get here? By telling ourselves convenient truths until they were proven false. Here I unpack 12 Covid-19 myths. https://www.forbes.com/sites/williamhaseltine/2021/0 8/11/busting-12-covid-19-myths-that-couldkill/?sh=69cc29a25848 Despite having one of the highest vaccination rates in the world, Israel has had a Delta variant-driven surge. Israel is like a canary in a coal mine. Adopting a multimodal strategy, one that includes antiviral pills, is our best chance against this ever-evolving virus. https://www.forbes.com/sites/williamhaseltine/2021/0 8/11/israels-recent-surge-confirms-we-need-a-multimodalstrategy-to-fight-covid-19/?sh=1deb10195b6e B.1.621 is a new variant first detected in Colombia and recently responsible for the death of seven vaccinated nursing home residents in Belgium. Here I offer a brief tour of the potential impacts of the 2893
mutations of this variant, meriting closer observation in the coming months. https://www.forbes.com/sites/williamhaseltine/2021/0 8/12/a-new-killer-on-the-loose-b1621/?sh=53bcd1933d1f This is the first in my 15-part series on how SARS-CoV-2 delays, evades, and suppresses the immune system, and the implications for our pandemic response. This virus’s strategies are a complex tale of stealth and disguise. https://www.forbes.com/sites/williamhaseltine/2021/0 8/12/how-sars-cov-2-evades-and-suppresses-the-immunesystem-part-one/?sh=722bd6262cee While SARS and MERS caused nearly instant severe symptoms, Covid-19 has a very high asymptomatic infection rate (more than 50% of new infections). SARS-CoV-2’s selective advantage is that it can enter the body, proliferate, then exit the body before our immune system kicks in. https://www.forbes.com/sites/williamhaseltine/2021/0 8/13/how-sars-cov-2-evades-and-suppresses-the-immunesystem-part-two/?sh=5255a4b87e0e With the Delta variant spreading rapidly across the US, the onus to reinstate basic safety measures falls on government and health officials. In the meantime, we must protect ourselves and each other. In this article I provide guidance for determining your personal risk level. https://www.forbes.com/sites/williamhaseltine/2021/08/10/t he-delta-variant-a-guide-to-evaluating-personalrisk/?sh=40a0a67e61bb August 13, 2021
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I will be going live on Facebook Tuesday, August 17 at 9am PST /12pm EST with TV reporter, writer, and educator Donna Tetreault to talk about her new book Dear Me: Letters to Myself, For All of My Emotions. We will be discussing the importance of mental health awareness in young people and some of the effects Covid-19 has had on students. You can register for the event here: https://fb.me/e/QKOPElyt August 16, 2021 To understand and thwart Covid-19, we must have detailed knowledge of the SARS-CoV-2 genome and proteins. Here I explain what we know about the virus’s unique replication strategy-mRNA production specifically--and discuss implications for research into treatment and prevention. https://www.forbes.com/sites/williamhaseltine/2021/08/16/h ow-sars-cov-2-evades-and-suppresses-the-immune-system-part3/?sh=6717887486f7 Wastewater surveillance can detect a Covid-19 case 3-4 days before individual testing can. Here I explain a recent wastewater study that detected nearly 85% of symptomatic and asymptomatic cases on the US San Diego campus. Investing in this tool could help prevent future pandemics. https://www.forbes.com/sites/williamhaseltine/2021/08/16/st udy-shows-covid-19-can-be-detected-in-a-single-asymptomaticperson-through-wastewater-surveillance/?sh=58443d5b391c SARS-CoV-2 is like a serial burglar, a master of slipping in and out of hostile environments undetected. Here I elaborate on this analogy to show how the virus interacts with and suppresses our immune system, and then describe the mechanics of this key survival strategy. https://www.forbes.com/sites/williamhaseltine/2021/08/17/h ow-sars-cov-2-evades-and-suppresses-the-immune-system-part4/?sh=4dc212352bcd August 18, 2021 “When will the pandemic end?” The answer is not simple, and it evolves alongside the virus. In this piece I cover the factors involved and various scenarios, including how I think we might reign in the spread using Multimodal Covid Control. 2895
https://www.forbes.com/sites/williamhaseltine/2021/08/17/c ovid-19-no-end-in-sight/?sh=3313bc3e6e9c In this technical piece, I explain an element of the physiology of SARS-CoV-2 and other coronaviruses: the double membrane vesicle. I discuss its structure and function, the NSP3 and NSP4 nonstructural proteins, and the vesicle’s role in immune evasion. https://www.forbes.com/sites/williamhaseltine/2021/08/18/h ow-sars-cov-2-evades-and-suppresses-the-immune-system-part5/?sh=60eef8291d0a Aug 23, 2021 A recent study of 672 healthy kids (aged 3 mo - 3 yrs) showed reduced verbal, motor, and overall cognitive performance compared to children born pre-pandemic. Here I explain the study. https://www.forbes.com/sites/williamhaseltine/2021/08/19/c hildren-born-during-pandemic-show-lower-cognitivescores/?sh=57708fe24af4 August 25, 2021 Globally, over 2M bone graft procedures are performed each year. Recently a new material has been discovered that is effective for bone repair which, unlike grafts, does not require living cells or growth factors to be introduced for the bone to regenerate naturally. https://www.forbes.com/sites/williamhaseltine/2021/08/19/n anomaterial-shows-promise-for-boneregeneration/?sh=8cd736b7d840 SARS-CoV-2’s immunosuppressive pathways are one way it creates conditions favorable to its own replication and propagation. Here I explain its nonspecific and specific mechanisms: viral proteins blocking entire pathways or simply interfering with one or two cellular functions. https://www.forbes.com/sites/williamhaseltine/2021/08/24/h ow-sars-cov-2-evades-and-suppresses-the-immune-system-part7/?sh=2c8dbf3953b3 Here, I describe the role of the beginning and end of the SARSCoV-2 genome in the virus life cycle. I summarize what we know and point out what we need to know about these ends in order to develop new antiviral drugs. 2896
https://www.forbes.com/sites/williamhaseltine/2021/08/25/d ecoding-the-gordian-knots-at-the-ends-of-the-sars-cov-2genome/?sh=695a4eda1b61 Kids are suffering from depression and anxiety. Why? Research suggests lack of routine, unpredictability, decreased socialization, and other factors caused by the pandemic. We need a national and global response to support the physical and mental wellbeing of our children. https://www.forbes.com/sites/williamhaseltine/2021/08/25/d epression-and-anxiety-double-in-youth-compared-to-prepandemic/?sh=322f4cc0139f A new large-scale study demonstrates that children ages 0-3 are 40% more likely to transmit the virus to a household member than kids ages 14-17. We urgently need to protect children and those they live with as they return in person to schools. https://www.forbes.com/sites/williamhaseltine/2021/08/24/b abies-and-toddlers-are-highly-contagious-for-covid19/?sh=180d26c33e89 SARS-CoV-2 is able to evade our immune systems in a number of ways. In this piece, I explain how it conceals mRNA synthesis and the mRNAs themselves. This is relevant for our understanding of how we might develop small molecule drugs to interfere with viral activity. https://www.forbes.com/sites/williamhaseltine/2021/08/23/h ow-sars-cov-2-evades-and-suppresses-the-immune-system-part6/?sh=3270be2965e9 August 31, 2021 To develop antiviral drugs, we must understand the virus’s genome. An anomaly in the AUG-initiated 5’ uOrf may be an important clue to SARS-CoV-2 replication and pathogenesis. Here I detail the recent findings. https://www.forbes.com/sites/williamhaseltine/2021/08/30/t he-mystery-of-the-false-start-at-the-5-end-of-sars-cov2/?sh=50daaa392e16 SARS-CoV-2 prevents infected cells from signaling its neighbors, and shields them from T cell recognition and destruction. It also disrupts T cell functioning by targeting MHC-I. Here I describe these immune suppression processes of the virus. 2897
https://www.forbes.com/sites/williamhaseltine/2021/08/30/h ow-sars-cov-2-evades-and-suppresses-the-immune-system-part9/?sh=edccab8a5c59 Isolation, lack of structure, and heightened anxiety during the pandemic are possible triggers for eating disorders. A recent analysis shows a 25% increase of teen eating disorder patients since March 2020. Here I discuss this youth health crisis, including barriers to care. https://www.forbes.com/sites/williamhaseltine/2021/08/27/h ow-the-pandemic-is-fueling-eating-disorders-in-youngpeople/?sh=389fc7e42226 SARS-CoV-2 blocks expression of almost all cellular genes and proteins to favor its own messenger RNA and protein synthesis. Here I talk about viral transcription initiation, messenger RNA splicing and stability, messenger RNA export to the cytoplasm, and protein translation. https://www.forbes.com/sites/williamhaseltine/2021/08/27/h ow-sars-cov-2-evades-and-suppresses-the-immune-system-part8/?sh=3b20162e206d
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September 2021
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September 2, 2021 Close relationships, more than money or fame, are key to lifelong happiness. The pandemic has strained relationships--a recent study found that 22% of adults say they have experienced a complete breakdown of a relationship in the past year. Here I parse out the details. https://www.forbes.com/sites/williamhaseltine/2021/08/31/o ne-fifth-of-adults-report-a-relationship-breakdown-during-thepandemic/?sh=1bdea0975a42 September 7, 2021 The C.1.2 variant, first seen in South Africa, is spreading in 8 countries. It shares several mutations with other variants of concern, and has several novel mutations. Here I explain the potential effects of each mutation on replication, immune suppression, and pathogenesis. TITLE: Is This The Next Variant Of Concern— C.1.2? https://www.forbes.com/sites/williamhaseltine/2021/09/03/is -this-the-next-variant-of-concern--c12/?sh=7c0e33ed4680 Here I discuss how SARS-CoV-2 avoids ending up in the cell’s waste disposal systems. We have a fairly clear picture of how the virus inhibits autophagosomal activity, but understand less about the role SARS-CoV-2 plays in apoptosis. I discuss both processes here. TITLE: How SARS-CoV-2 Evades And Suppresses The Immune System (Part 10) https://www.forbes.com/sites/williamhaseltine/2021/09/07/h ow-sars-cov-2-evades-and-suppresses-the-immune-system-part10/?sh=5f31e668b957 September 8, 2021 I joined ABC Action News Tampa to discuss long term mental health effects from the pandemic, including CV-PTSD. https://www.abcactionnews.com/rebound/doctor-warns-ofthe-toll-this-pandemic-is-taking-on-our-mental-health-and-thehangover-is-longterm
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September 9, 2021 SARS-CoV-2 is a master at suppressing innate immunity to avoid detection. Here I discuss specific mechanisms the virus uses inside infected cells, including blockage of interferon synthesis, the role of Nsp1 inhibiting RIG-I in activating immune response, and more. https://www.forbes.com/sites/williamhaseltine/2021/09/09/howsars-cov-2-evades-and-suppresses-the-immune-system-part11/?sh=4d3f661a67cb I joined CGTN’s The Heat to discuss the ever-increasing number of Covid-19 cases globally and in the US. https://america.cgtn.com/2021/09/07/the-heat-40-millioncovid-19-cases-in-the-u-s September 10, 2021 Interferon is key to our body’s immune system. SARS-CoV-2 not only prevents synthesis of interferon, but also blocks induction of interferon type-I induced genes & proteins. https://www.forbes.com/sites/williamhaseltine/2021/09/10/h ow-sars-cov-2-evades-and-suppresses-the-immune-system-part12/?sh=4a6baeda6001 September 13, 2021 SARS-CoV-2, like the influenza virus, can engage in zoonotic volleyball. Infections from animals can make their way into humans. A recent wastewater study in NYC suggests the extreme mutations found could be attributed to evolution of the virus in animals. https://bit.ly/3AaTQmr https://www.forbes.com/sites/williamhaseltine/2021/09/13/a nimal-reservoirs-of-covid-19-may-trigger-new-rounds-of-humandisease/?sh=2a17899b1776 We need to shift our mindset to think about Covid-19 in a longterm capacity, with no single intervention having perfect results. We need a multimodal strategy of prevention and protection. https://www.forbes.com/sites/williamhaseltine/2021/09/13/t here-is-a-giant-hole-in-our-covid-control-strategy/
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September 16, 2021 A new SARS-CoV-2 variant worth careful observation has emerged. A.23.1 contains several mutations found in variants of concern, and 6 unique substitutions. Here I describe the potential effects of each mutation on replication, immune evasion, pathogenesis. https://www.forbes.com/sites/williamhaseltine/2021/09/16/asecond-east-african-variant-a231/?sh=8a730e06ed25 It’s time for the US to act. We have had a lack of coherent guidelines and mandates which has led to another record-setting number of daily cases, and we continue to fail to implement even the most basic public health measures. https://thehill.com/opinion/healthcare/572567-what-uspolicymakers-can-learn-from-the-uks-covid-19-response I joined Health Professional Radio's podcast this week to talk about the power of science and the impact young people can have on the future of science. https://healthprofessionalradio.com.au/the-power-of-science/ September 17, 2021 The FDA meets today to discuss the rollout of an additional dose of the Covid-19 vaccine. Here I explain the concept of the three dose vaccine and why the need for a “booster shot” is becoming increasingly clear. https://www.cnn.com/2021/09/14/opinions/covid-19vaccine-three-doses-haseltine/index.html With schools back in session, Covid-19 cases among kids are on the rise. We must protect our vulnerable children. Until masks, testing, quarantining, and vaccines are enforced, safety for our children is a fairy tale. https://www.forbes.com/sites/williamhaseltine/2021/09/17/ki ds--covid-what-you-need-to-know-about-schools-vaccines-andrisk/ September 20, 2021 A new Covid variant has been detected in 45 staff and residents of a Kentucky nursing home. R.1 contains a number of already
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noted and unique mutations. Here, I describe the potential effects of each on replication, immune evasion, and pathogenesis. https://www.forbes.com/sites/williamhaseltine/2021/09/20/anew-usjapan-variant-to-watch/?sh=557e10bc3509 Learning how SARS-CoV-2 evades immunity increases our opportunities to develop new ways to prevent and treat illness. Here I explain the role of immune suppression in asymptomatic transmission, cases of severe illness and death, and reinfection. https://www.forbes.com/sites/williamhaseltine/2021/09/20/p andemic-cycles-of-covid-19-sars-cov-2-immune-suppressionhelps-us-understand-repeated-cycles-of-viral-infection-andvaccine-breakthrough/?sh=52c6e731bba6 The FDA made a critical mistake in their booster ruling: Boosters for everyone over 16 years old could have helped us get ahead of the pandemic. Here I explain what we understand about how the virus suppresses immunity and why boosters are critical. https://www.forbes.com/sites/williamhaseltine/2021/09/21/amissed-opportunity-a-decision-to-regret/?sh=46a646495acc
“Trauma can be understood as a rupture in meaning-making, the way you see yourself, the way you see the world,” – David Trickey, a psychologist, and representative of the UK Trauma Council 2903
My new ebook, Covid Related Post Traumatic Stress Disorder (CV-PTSD): What It Is and What To Do About It, is now available on Amazon https://www.amazon.com/gp/product/B09B9263GV/ref=dbs_a_ def_rwt_bibl_vppi_i2 #covid19 #cvptsd #covidawareness #mentalhealth September 23, 2021 The M protein is yet another viral protein SARS-CoV-2 uses to suppress innate immunity. Here I outline how it directly inhibits MAVS as well as TBK1, a kinase critical to the phosphorylation of interferon responsive factor 3. https://www.forbes.com/sites/williamhaseltine/2021/09/22/h ow-sars-cov-2-evades-and-suppresses-the-immune-system-part13/ I recently spoke to 11 Alive News Atlanta about the R.1 variant https://www.11alive.com/article/news/health/coronavirus/r-1covid-19-variant/85-12dead4d-6317-4762-a374-60f6ca379486 September 29, 2021 Experiments from a recent study explain the emergence of so many infectious variants by showing how SARS-CoV-2 rapidly adapts to selective pressure. Here I outline the conclusions and important questions that arose from this study. https://www.forbes.com/sites/williamhaseltine/2021/09/28/asnapshot-of-sars-cov-2-evolution-observed-increase-of-infectivityin-the-covid-19-virus/?sh=1e079c942b23 A recent study shows a potentially optimistic future for those living with type 1 diabetes. Here I explain the small, implantable device researchers are working on which automatically creates insulin according to the body's needs. https://www.forbes.com/sites/williamhaseltine/2021/09/28/is-anartificial-pancreas-on-the-way/?sh=76c8ef5877da
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October 2021
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October 7 A new study has advanced our understanding of why SARSCoV-2 must deactivate interferon. Here I outline how we can use this information to assist in discovering solutions that may help Covid-19 patients who cannot fight the virus on their own. https://www.forbes.com/sites/williamhaseltine/2021/10/05/aneanderthal-gene-that-protects-us-from-covid-19-part14/?sh=5d1061703091 The identification of a coronavirus in Laotian bats that is incredibly close to SARS-CoV-2 serves as a reminder. New, more transmissible versions of COVID-19 may continue to emerge via animal coinfection and recombination events between SARS-Cov2 and other coronaviruses. https://www.forbes.com/sites/williamhaseltine/2021/10/06/o rigin-very-close-relatives-of-sars-cov-2-identified-in-laotianbats/?sh=2e7f0a557611 In this article for GEN, I explain the path that led me from assistant professor at Harvard to creating biotech businesses to help deliver drugs to patients in need. https://www.genengnews.com/commentary/making-thetransition-from-an-academic-to-a-biobusiness-entrepreneur/ Please check out this recent episode of the At Your Level podcast where I talked to the host, Ari, about why science is indeed a superpower. https://podcasts.apple.com/us/podcast/scipow/id1506825501?i=1000536991544 I joined the podcast Mental to discuss the mental health impact of the pandemic and Covid PTSD. https://podcasts.apple.com/gb/podcast/covid-ptsd-its-vital-wecan-all-receive-support-for/id1358920477?i=1000537043608 October 11 Here I explain how 9 US summer camps were able to successfully control Covid-19. The summer camp data shows us that using multiple preventative strategies is effective and could be utilized by schools, workplaces, and other congregate settings. https://www.forbes.com/sites/williamhaseltine/2021/10/07/s uccessful-multimodal-covid-control-in-summercamps/?sh=26cf87e7f8e9 2906
The chaotic Covid-19 booster rollout left many wondering if their vaccines are still protecting them. Here I outline the conditionality of current vaccines and what this means for our protection from the virus. https://www.forbes.com/sites/williamhaseltine/2021/10/08/w ill-covid-overwhelm-our-vaccines/?sh=265b9b7f7cff A new drug, molnupiravir, could ward off the most serious symptoms of Covid-19. But, it comes at a potentially high price, both in terms of actual dollars and its potential to supercharge new variants. Is it one we're willing to pay? https://www.forbes.com/sites/williamhaseltine/2021/10/08/a nti-covid-drugs-are-coming-but-at-what-cost/?sh=6d2b43a077a1 I joined Anand Naidoo on The Heat to discuss the United States’ continued battle against Covid-19, the Delta variant, and the vaccine mandate. https://america.cgtn.com/2021/10/09/heat-u-s-battles-covid19 I recently told Politico that those who oppose a broad booster rollout are pitting their hopes against the unknown. As the situation stands at present, it is better to prepare for the worst. https://www.politico.com/news/2021/10/06/biden-covidexperts-boosters-515175 October 14 A modeling study has revealed that 1 out of every 4 COVID-19 associated deaths results in a US child losing their parent or caregiver. Here I outline the details of the study and our need for a comprehensive response to support these children. https://www.forbes.com/sites/williamhaseltine/2021/10/12/c hildren-are-losing-parents-and-caregivers-to-covid-at-an-alarmingrate/?sh=6992068e612e October 18 Here I trace the mutations of SARS-CoV-2 since its original emergence in Wuhan and discuss some of the viral advantages of dominant variants. Increased transmissibility has been one of the most consistent--and dangerous--evolutions of the Alpha, Delta, and Gamma variants. 2907
https://www.forbes.com/sites/williamhaseltine/2021/10/14/c ovid-19-variation-past-present-and-future/?sh=b97239b12d2a A recent study displayed significant progress in the development of brain organoids, miniature functional organs, which have surprisingly formed rudimentary eyes. An exciting step forward for brain and eye research. https://www.forbes.com/sites/williamhaseltine/2021/10/18/is -this-petri-dish-looking-at-me/?sh=7e77cec5289e October 22 A recent study demonstrates that children can spread Covid-19 and variants as efficiently as adults. It is essential to maintain public health precautions like mask wearing, distancing, and contact tracing in schools in order to combat the virus in our communities. https://www.forbes.com/sites/williamhaseltine/2021/10/21/st udy-finds-children-to-be-vectors-of-covid-19-and-emergingvariants/?sh=5e5b6951819c The capacity to have safe, secure, real time vaccine verification is critical to any country's ability to control the course of the pandemic. Here I outline why using a blockchain ledger to generate QR codes may be the solution. https://www.forbes.com/sites/williamhaseltine/2021/10/20/bl ockchain-technology-a-practical-solution-to-vaccine-verificationsystems/?sh=5de9d3f51486 Mass rapid testing has been undervalued in the US but proven successful in other countries. Here I outline the effectiveness of these tests and discuss what the Biden administration could do to further encourage rapid testing. https://www.forbes.com/sites/williamhaseltine/2021/10/22/la teral-flow-tests-detect-most-people-at-risk-of-transmitting-covid19/?sh=68814d3d18d8 I recently joined the Bloomberg Businessweek podcast to discuss virus news and the development of the drug Molnupiravir. You can listen here: https://www.bloomberg.com/news/audio/2021-1025/facebook-in-the-spotlight-podcast October 26
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How do we try to predict the future of SARS-CoV-2? To help answer that question, I analyze the Gamma variant in Brazil. Understanding Gamma and its sublineages may shed light on the more transmissible and immune evading Delta variant. https://www.forbes.com/sites/williamhaseltine/2021/10/22/c ovid-19-variation-what-comes-next-the-amazonasexperience/?sh=7e3012c1d1bc Growing structurally sound cartilage tissue generated from stem cells is a welcome new development in regenerative medicine. Researchers published their discoveries in Nature and here I discuss their findings. https://www.forbes.com/sites/williamhaseltine/2021/10/25/h ope-for-those-aching-joints/?sh=4af0ea27861b October 29 One critical difference between who does and doesn’t suffer severe consequences from Covid-19 infection is the performance of the innate immune system. Here I examine the nucleases NSP14 and NSP15 which seem to form one of the earliest defenses. https://www.forbes.com/sites/williamhaseltine/2021/10/28/t he-role-of-nucleases-in-innate-immune-escape-part15/?sh=266f1a0f5e0e Following the virological pattern of Gamma, Delta has developed a number variants that are likely more transmissible and evasive than the original. We urge government agencies to expand efforts to understand virus variation which could allow us to further prepare for the next wave of infections. https://www.forbes.com/sites/williamhaseltine/2021/10/28/t he-growing-threat-of-the-delta-pluses-at-home-andabroad/?sh=7792cf315e8a A recent pre-print study found that tuberculosis bacteria can spread via airborne and asymptomatic transmission, similar to SARSCoV-2. We should put programs in place to begin screening and treating tuberculosis before it becomes the next big pandemic. https://www.forbes.com/sites/williamhaseltine/2021/10/28/t he-next-big-one-drug-resistant-airborne-tuberculosis/
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November 2021
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November 1 The story unfolding in Europe is a peek into our future. We may well be facing another winter of deaths the likes of which we saw last year. How could we avoid this? Stricter adherence to basic public health measures like mask wearing, regular testing, quarantining, and vaccination. https://www.forbes.com/sites/williamhaseltine/2021/10/29/a n-approaching-storm-what-to-expect-with-covid-thiswinter/?sh=332b5bf55bb1 We are potentially headed toward a world class disaster with the oral antiviral drug Molnupiravir, up for FDA review as a Covid-19 treatment for those at high risk. Here I explain how it works, and offer words of caution based on the drug's potential to supercharge SARS-CoV-2 mutations. https://www.forbes.com/sites/williamhaseltine/2021/11/01/s upercharging-new-viral-variants-the-dangers-of-molnupiravir-part1/?sh=29426d706b15 The antiviral molnupiravir’s mutagenic effects could cause cancerous tumors as well as birth defects in the unborn. Here I explain how it creates havoc with RNA polymerase, the enzyme critical for viral replication, and how it may also interfere with nucleic acids in our own healthy DNA. https://www.forbes.com/sites/williamhaseltine/2021/11/02/h arming-those-who-receive-it-the-dangers-of-molnupiravir-part2/?sh=1e3a4d971490 There is some evidence of dangerous mutations of SARS-CoV2 occurring in immunosuppressed patients suffering from long Covid. Here I discuss what we know, and urge continued surveillance of these cases so we can be prepared for what comes next. https://www.forbes.com/sites/williamhaseltine/2021/11/01/t he-urgent-need-for-increased-surveillance-of-variants-that-arisefrom-chronic-covid/?sh=1c541e4fef73 If we continue our current course, America will likely hit 1 million Covid deaths sometime in 2022. While we applaud the Biden administration’s good start in addressing the pandemic, we strongly recommend major remedial and additional measures. If they don’t act now, it may be too late to suppress the virus and save lives. 2911
https://thehill.com/opinion/healthcare/578805-defeatingdeath-from-covid-heres-a-comprehensive-strategy Physicians at NYU Langone Health have successfully transplanted a genetically engineered pig kidney to a human body. This news is an exciting step for both regenerative medicine and those on the organ transplant list. https://www.forbes.com/sites/williamhaseltine/2021/11/01/abig-step-forward-in-solving-the-organ-shortage/?sh=771dc2bd1f3a November 4 Evolution has prepared our bodies to fend off disease, both through our innate and adaptive immune systems. But nature has also gifted us with intentional reasoning, which can help us fight the virus. https://www.forbes.com/sites/williamhaseltine/2021/11/01/n ature-has-gifted-humans-with-intelligence-that-can-relegatecovid-19-if-not-a-disease-of-the-past-then-one-that-rarely-if-everis-fatal/?sh=702de9e05b67 Here I discuss a recent large scale study in Israel that has provided overwhelming evidence that three vaccine doses protect better than two. I urge the CDC to expand access to third mRNA doses for anyone over the age of 12. https://www.forbes.com/sites/williamhaseltine/2021/11/04/n ew-data-suggests-mrna-vaccines-work-best-as-a-three-doseregimen/?sh=3db974fd67f9 The UK approval of molnupiravir does not take into account the risk this drug could be to the world. Fast-tracking it for use without further data could supercharge SARS-CoV-2's ability to mutate and create new variants. https://www.forbes.com/sites/williamhaseltine/2021/11/04/u k-approval-of-molnupiravir-may-create-new-and-moredangerous-covid-19-variants/?sh=412b530466a9 November 9 Here I discuss a novel amputation technique which preserves the muscle dynamics we use to understand where our bodies are. This restored sense of awareness could make it easier for amputees to use artificial limbs. 2912
https://www.forbes.com/sites/williamhaseltine/2021/11/08/n ew-surgery-helps-preserve-better-control-and-feeling-afteramputation/?sh=6d15f71126f3 November 11 Research for restoring vision has taken a big step forward. Scientists in a recent study placed electrodes close together deep in the blind patient’s visual cortex. Compared to other similar methods studied, these low-current arrays result in the patient distinguishing higher res images with less associated risk. https://www.forbes.com/sites/williamhaseltine/2021/11/05/b rain-implants-with-the-potential-to-restore-vision-to-theblind/?sh=3454e2ec1ce9 While most studies of SARS-CoV-2 variants’ virological properties focus on the Spike protein, a recent study shows a single mutation in the N protein bolstered infectiousness by 50-fold. Analyzing the effects of mutations throughout the entire genome of this crafty foe is essential. https://www.forbes.com/sites/williamhaseltine/2021/11/09/asingle-point-mutation-in-the-nucleocapsid-protein-increasescovid-virus-infectivity-by-more-than-100times/?sh=6e4695434ba5 November 16 TITLE: Spike And Nucleocapsid Protein Mutations In Tanzanian And Ugandan Strains Of SARS-CoV-2 Demand Attention Here I analyze a paper about the A.30 strain which contains a highly mutated S protein. Further study of this mutation could provide insight into a range of potentially dangerous variations that differentiate from the Triad template. https://www.forbes.com/sites/williamhaseltine/2021/11/12/s pike-and-nucleocapsid-protein-mutations-in-tanzanian-andugandan-strains-of-sars-cov-2-demandattention/?sh=46621133489e TITLE: Unregulated Stem Cell Clinics Endanger Patients And Limit Research The number of US stem cell clinics offering unapproved therapies jumped from 600 to almost 3,000 since 2016. Here I 2913
discuss the dangers of these clinics and the impact they have on stem cell therapies being approved as official medical procedures. https://www.forbes.com/sites/williamhaseltine/2021/11/13/u nregulated-stem-cell-clinics-endanger-patients-and-limitresearch/?sh=331359b4242c TITLE: HPV Vaccine Should Be Universal For Boys And Girls, Ages 9-14 Here I discuss recent data from the UK on the effectiveness of the HPV vaccine. Hopefully this data will inspire a widespread effort to vaccinate all young men and women globally, which has the potential to save many lives. https://www.forbes.com/sites/williamhaseltine/2021/11/15/h pv-vaccine-should-be-universal-for-boys-and-girls-ages-914/?sh=32ceba3b4b95 TITLE: Epidemiology Answers Key Questions About Delta Variant Transmissibility And Lethality A recent preprint of a Delta outbreak in China shows how improving our understanding of SARS-CoV-2 can improve our efforts to stop the spread of disease if we tailor public health interventions to the unique dynamics of each variant. https://www.forbes.com/sites/williamhaseltine/2021/11/15/e pidemiology-answers-key-questions-about-delta-varianttransmissibility-and-lethality/?sh=1b34e8716b96 November 18 TITLE: Stimulating Innate Immunity Stops SARS-CoV-2 Infection A recent study identified an antiviral drug that activates the innate immune system, meaning it could prevent and treat Covid19 in humans. Here I discuss the study and the increasing relevance of innate immunity to antiviral drug development. https://www.forbes.com/sites/williamhaseltine/2021/11/17/st imulating-innate-immunity-stops-sars-cov-2infection/?sh=67a57d878d57 TITLE: Detailed Description Of A Highly Potent SARS-CoV2 Neutralizing Antibody: Bamlanivimab Monoclonal antibodies have been effective in prevention and early treatment of SARS-CoV-2. Here I describe the antibody 2914
bamlanivimab and discuss how we can use it as a blueprint to discover more treatments of this nature. https://www.forbes.com/sites/williamhaseltine/2021/11/17/d etailed-description-of-a-highly-potent-sars-cov-2-neutralizingantibody-bamlanivimab/?sh=7701623ab8e8 TITLE: Covid Ear: Virus Implicated Here I explain a new report which finds that SARS-CoV-2 may be able to infect the inner ear. It remains uncertain exactly how the virus enters the inner ear but the symptoms and subsequent damage seen in patients may potentially be due to the virus. https://www.forbes.com/sites/williamhaseltine/2021/11/18/c ovid-ear-virus-implicated/?sh=49b5ce5d4927 November 22 TITLE: Intramuscular Injection Of Monoclonal Antibodies Simplifies Covid Treatment Here I explain the trial of a monoclonal antibody that may be delivered intramuscularly which would simplify current Covid treatments. I also discuss the pros and cons compared to oral antiviral pills. https://www.forbes.com/sites/williamhaseltine/2021/11/19/in tramuscular-injection-of-monoclonal-antibodies-simplifies-covidtreatment/?sh=1b4e54118336 TITLE: Stem Cell-Derived Neurons Mimic Alzheimer’s Pathogenesis A new study could provide research into the molecular causes of Alzheimer’s. Here I describe the study and discuss how further research with this technique may help form an understanding of how to identify, prevent, and treat the illness. https://www.forbes.com/sites/williamhaseltine/2021/11/22/st em-cell-derived-neurons-mimic-alzheimerspathogenesis/?sh=74e11a064264 TITLE: Science Talk: Hope and concern for two novel Covid19 antivirals Here Roberto Patarca and myself discuss Merck and Pfizer’s oral antivirals which could help treat Covid-19 and control its spread. We outline the benefits and concerns of the two treatments with the reminder that we must also continue to rely on public health measures. 2915
https://www.straitstimes.com/world/science-talk-hope-andconcern-for-two-novel-covid-19-antivirals November 29 TITLE: Hong Kong Demonstrates Effective Use Of Covid Public Health Mitigation A recent Hong Kong study has shown us the effectiveness of public health defenses combined with medical defenses. Here I discuss the study's results and urge the US and other countries to embrace more rigorous testing, tracing, and isolation/quarantine as a Covid control policy. https://www.forbes.com/sites/williamhaseltine/2021/11/24/h ong-kong-demonstrates-effective-use-of-covid-public-healthmitigation/?sh=1bb7d0b6f86a TITLE: A New Monoclonal Antibody That Has The Potential To Neutralize All Viral Variants Here I explain the science behind a new monoclonal antibody: DH1047. This antibody targets highly conserved epitopes which may give it the ability to neutralize a larger selection of viral variants. https://www.forbes.com/sites/williamhaseltine/2021/11/24/anew-monoclonal-antibody-that-has-the-potential-to-neutralize-allviral-variants/?sh=4684759d55cb
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December 2021
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December 2 I joined Ernie Manouse on Town Square to discuss the latest pandemic situation. We discuss Omicron, boosters, and additional ways to protect yourself. https://www.houstonpublicmedia.org/articles/shows/townsquare/2021/11/30/414412/we-are-not-done-with-the-virusand-the-virus-is-not-done-with-us-says-global-health-expertabout-omicron/ https://www.masslive.com/coronavirus/2021/11/a-covid-pillfrom-merck-called-molnupiravir-is-narrowly-backed-by-fda-forfuture-use.html December 3 TITLE: Frequent Rapid Testing Is The Key To Controlling Covid-19 Transmission In Universities And In Our Communities The US has yet to embrace the power of mass rapid testing but with the Omicron variant and the rise in cases across the US it may be time. Here I discuss how we can provide mass rapid tests and utilize them to minimize the spread of the virus. https://www.forbes.com/sites/williamhaseltine/2021/12/01/fr equent-rapid-testing-is-the-key-to-controlling-covid-19transmission-in-universities-and-in-ourcommunities/?sh=7018b4ef5653 There are a number of remarkable similarities between HIV and SARS-CoV-2. Here I discuss how we can use the medical solutions developed to treat and control the spread of HIV as a roadmap to fill in the gaps where vaccine immunity for Covid-19 falters. https://www.clinicalomics.com/magazine-editions/volume-8issue-no-6-november-december-2021/can-our-success-with-hivserve-as-a-guide-for-antiviral-drug-development-for-covid-19/ TITLE: Omicron Origins Here I explore the possible origins of the Omicron variant. The advent of this variant tells us we need a systematic multimodal approach to Covid control, including public health measures, vaccines, therapeutic and prophylactic drugs, and collaborative global engagement. https://www.forbes.com/sites/williamhaseltine/2021/12/02/o micron-origins/?sh=169201b51bc1 2918
December 6 TITLE: Buckling Up for Omicron Additional layers of protection beyond vaccines are critical to combat the virus. Here I discuss wider use of monoclonal antibodies as an early treatment and for long-term prevention and protection. https://www.project-syndicate.org/commentary/belt-andsuspenders-protection-against-omicron-covid19-variants-bywilliam-a-haseltine-2021-12 December 9 TITLE: Thinning Hair? Blame The Pandemic Or Your Wandering Stem Cells Covid-19 may be to blame for your thinning hair. Here I discuss why that may be true and outline a recent study on hair loss that says perhaps stem cells leave hair follicles once they are too old. https://www.forbes.com/sites/williamhaseltine/2021/12/07/t hinning-hair-blame-the-pandemic-or-your-wandering-stemcells/?sh=4d4ffbf66409 TITLE: Brain Fog and Seizures: Is Covid-19 to Blame? Here I describe a recent report from the University of Lübeck, Germany which describes how Covid-19 works to cause several neurological symptoms. They discovered that Covid-19 patients display damage to the small blood vessels of the brain and this is caused by the main protease killing endothelial cells. http://www.forbes.com/sites/williamhaseltine/2021/12/08/br ain-fog-and-seizures-is-covid-19-to-blame/ TITLE: Omicron: The Sum Of All Fears! Here I explain how Omicron evades the neutralizing antibodies of the Pfizer vaccine, even with 3 doses. Omicron is very unlikely to be the last heavily mutated variant of concern and we must be prepared for that eventuality. https://www.forbes.com/sites/williamhaseltine/2021/12/08/o micron-the-sum-of-all-fears/?sh=77093ee15b51 TITLE: What Is The Meaning Of Omicron? Omicron is sending a warning to us all: this virus is capable of far more changes and variation than we ever thought possible. This means we can expect a barrage of variants indefinitely unless we are able to bring the virus under control, here I explain how. 2919
https://www.forbes.com/sites/williamhaseltine/2021/12/09/w hat-is-the-meaning-of-omicron/?sh=57fc125364d6 December 13 TITLE: FDA Approves Anti-SARS-CoV-2 Monoclonal Antibodies For The Vaccine Insensitive Immune Suppressed Population Here I explain a new treatment which will offer an additional option for long term protection from the virus to immunocompromised patients. This demonstrates the potential for monoclonal antibodies to be used in tandem with vaccines for the strongest possible protection. https://www.forbes.com/sites/williamhaseltine/2021/12/10/fd a-approves-anti-sars-cov-2-monoclonal-antibodies-for-thevaccine-immune-suppressed-population/?sh=2794ef0e2020 TITLE: Preliminary Study Shows Promise For Long-Term Treatment Of Diabetes Here I explain the science behind a new preliminary study which has developed a method of growing insulin-producing pancreatic cells from stem cells. The results are very promising and mark a step forward in diabetes treatment options. http://www.forbes.com/sites/williamhaseltine/2021/12/13/pr eliminary-study-shows-promise-for-long-term-treatment-ofdiabetes/ TITLE: Omicron: The Sum Of All Fears! Part 2 The Omicron variant has the potential to drive the next major wave of the pandemic. Here I discuss the mutations that occur outside the S protein of this variant. Understanding the molecular biology of the virus is crucial in finding new ways to control the pandemic. https://www.forbes.com/sites/williamhaseltine/2021/12/10/omic ron-the-sum-of-all-fears-part-2/?sh=26e8375c2223 December 20 TITLE: Clusterin: Hints Of New Hope For Aging And Alzheimer’s Here I describe a recent study where they discovered that blood transfusions from highly active mice into sedentary mice boosted 2920
brain function in the sedentary recipients. This could open new windows for the treatment of neurodegenerative diseases. https://www.forbes.com/sites/williamhaseltine/2021/12/17/cl usterin-hints-of-new-hope-for-aging-andalzheimers/?sh=79dfa86c50fd TITLE: How Omicron Evades Natural Immunity, Vaccination, And Monoclonal Antibody Treatments Epidemiologic evidence suggests that the Omicron variant is resistant to vaccines and possibly many monoclonal antibody treatments. Here I explore these concerns and what it means for the future of the pandemic. https://www.forbes.com/sites/williamhaseltine/2021/12/17/h ow-omicron-evades-natural-immunity-vaccination-andmonoclonal-antibody-treatments/?sh=1f21e75a60e0 TITLE: Non-Spike Proteins Contribute To Transmission And Virulence Of Sars-Cov-2 Here I describe a new report which prompts us to analyze the entire viral genome instead of just the S protein. As non-S protein mutations continue to crop up across different variants, this study lays the groundwork for whole-genome epistatic analysis which we would do well to build on. http://www.forbes.com/sites/williamhaseltine/2021/12/17/no n-spike-proteins-contribute-to-transmission-and-virulence-of-sarscov-2/ December 22 "We should have learned our lesson, but we grossly underestimated this virus and we're unprepared for Covid coming back in a newly transmissible and virulent form, and we’re going to pay the price." https://www.nytimes.com/2021/12/20/us/us-holidaysomicron-cases.html TITLE: Another Variant Emerges From An Immunocompromised Patient Recent studies have shown dangerous mutations can potentially develop within an immunocompromised individual. Here I explain these studies and discuss the importance of genomic surveillance of long-term immunocompromised cases to prevent further mutations. 2921
https://www.forbes.com/sites/williamhaseltine/2021/12/21/a nother-variant-emerges-from-an-immunocompromisedpatient/?sh=1166bca3671c December 27 "People are asking, 'Will it get weaker?' They should be asking how much more dangerous it can get, and the answer is much more." https://www.jsonline.com/story/news/2021/12/23/embattled -immune-system-may-need-drug-cocktail-fight-covidvariants/8994597002/ TITLE: Pfizer’s New Antiviral Drug Could Transform The Pandemic, But Challenges Still Lie Ahead The approval of Pfizer’s Paxlovid antiviral pill for Covid by the FDA could protect from severe cases and relieve some of the burden from overwhelmed hospitals. However, the drug will only succeed if there is broad access to a strong testing infrastructure. https://www.forbes.com/sites/williamhaseltine/2021/12/23/pf izers-new-antiviral-drug-could-transform-the-pandemic-butchallenges-still-lie-ahead/?sh=2b5f762d6c49 TITLE: Omicron Evades Most But Fortunately Not All Monoclonal Antibodies Most approved anti-SARS-CoV-2 antibodies have a diminished potency or are ineffective against Omicron. But, there are still a few who retain potency. Here I describe these antibodies and the treatment options which may still be viable. https://www.forbes.com/sites/williamhaseltine/2021/12/23/o micron-evades-most-but-fortunately-not-all-monoclonalantibodies/?sh=51301f7782fe December 30 "I have pointed out repeatedly that countries that are best at containing the pandemic have a mandatory isolation policy of anybody who is exposed for two weeks — anybody who is exposed, much less infected" https://www.salon.com/2021/12/28/sick-madness-the-publicreacts-to-the-cdcs-decision-to-cut-19-self-isolation-time-in-half/ TITLE: New Evidence Of Immune Suppression By SARSCoV-2 2922
Here I describe three recent studies which lead to the conclusion that SARS-CoV-2 can not only suppress the innate immune system but evolve to do so more efficiently. Additionally, I discuss the three traits that are most important in the pandemic. https://www.forbes.com/sites/williamhaseltine/2021/12/29/n ew-evidence-of-immune-suppression-by-sars-cov2/?sh=957b994e76a5 TITLE: Fight COVID-19 with lessons learned from HIV In an Op-Ed for The Hill, I discuss a combination of solutions we can use to protect ourselves from the next Omicron. We must strengthen both our public health and medical defenses utilizing tactics we have learned from events like Egypt’s rapid Hepatitis B testing and our experience fighting HIV. https://thehill.com/opinion/healthcare/587394-fight-covid19-with-the-lessons-learned-from-hiv?rnd=1640631383
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Acknowledgements
I
would first like to thank the many people who have influenced my thinking on COVID-19, from my colleagues in classrooms, laboratories and offices worldwide, to the family and friends I speak with each day. I am especially grateful to my colleagues at ACCESS Health International for their daily efforts and especially to Koloman Rath and Anna Dirksen for their support as we updated this edition of the book. I would also like to extend my thanks to Brian Stauffer, who designed the cover of this book and its companion book, My Lifelong Fight Against Disease: From Polio and AIDS to COVID-19. Finally, I thank my wife, Maria Eugenia, for her love and support and my children, stepchildren and grandchildren: Mara, Alexander, Karina, Manuela, Camila, Pedro Agustin, Enrique Matias, and Carlos Eduardo.
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