REALITIES AND SILVER LININGS:COVID-19 TWO YEARS ON

REALITIES ANDSILVER LININGS:COVID-19 TWO YEARS ON

BY ELIZABETH GAMILLO

Since the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic on March 11, 2020, approximately 6.3 million people worldwide have died. Experts estimate that 15 million more people died in 2020 and 2021 than normal. Nearly 70 percent of those excess deaths were concentrated in ten countries: Brazil, Egypt, India, Indonesia, Mexico, Peru, Russia, South Africa, Turkey, and the United States. The United States alone surpassed one million reported deaths to COVID-19 in May 2022, and the virus is currently the leading cause of death in the U. S. In Wisconsin, there were over 13,000 confirmed deaths from COVID-19 by early June.

As the pandemic moves into its third year, more variants evolve and change how experts think about how vaccines hold up against new variants and when boosters are needed.

The pandemic has underscored our need for public health experts and agencies, produced new approaches and insights on vaccine technology, and highlighted the need for accurate information from both health and civic leaders. The pandemic has also put a spotlight on other issues like racial disparities in health care and food access, political divisions, domestic violence, and concerns for children's development under stressful conditions. Three public health experts in Wisconsin provide illuminating insights as they share their experiences working on COVID-related research. From refining the nation's COVID-19 vaccine policies, understanding the epidemiology and pathogenesis of the SARS-CoV-2 virus (the source of COVID-19), to providing insights on how children will adapt to these challenging times, these experts share their wisdom and give a vision of how life will continue.

Dr. Jonathan Temte, Associate Dean for Public Health and Community Engagement at the UW School of Medicine and Public Health, reflected on the pandemic through the lenses of his experience serving on the U. S. Advisory Committee on Immunization Practices from 2008-2015, being the first family physician to serve as chair of that group, and currently chairing the Wisconsin Council on Immunization Practices. During the first years of the pandemic, Dr. Temte was involved with the COVID-19 response on the UW–Madison campus and at the state and national levels and offered insights on how SARS-CoV-2 spread in Wisconsin.

To understand how a virus-like SARS-CoV-2 can spread and how experts can track illness, Dr. Temte takes us to his backyard in Oregon, Wisconsin, which overlooks two schools, Prairie View Elementary and Netherwood Knoll Elementary school. Dr. Temte and his team have been collecting data on children with respiratory infections and their families at these schools and the rest of the Oregon School District (OSD) in Wisconsin as part of a project called the Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS). The study, published in Influenza and Other Respiratory Viruses in October 2021, was funded by the Centers for Disease Control and Prevention (CDC) and used student absenteeism to look at how various respiratory viruses, such as colds and flus, spread in classrooms. The study tracked influenza cases between 2014 and 2020 and was used to detect and recognize outbreaks early on. When students were absent from school, their parents were asked to call the absentee line and report any cold or flu-like symptoms. From there, parents could opt-in for a home visit where researchers would collect a nasal swab of the child and then test for influenza.

In mid-March 2020, millions of American students were sent home after orders like Wisconsin's Safer At Home Order were enacted across the nation. “Over the course of one week, 50 million children across the United States were sent home, and schools closed because of this new virus that was emerging and circulating. In the Oregon School District, March 16 was the first day of closure. By the end of that week across the country, virtually all kids were home,” Dr. Temte says. After students were sent home, influenza cases tracked by absenteeism went down because the students were not at school. But using the same absenteeism method, Dr. Temte could track COVID-19 cases and understand how they emerged within the Oregon School District community.

Yassine Khalfall

The first case of COVID-19 was detected in an adult woman in Wisconsin on January 29, 2020, and the first pediatric case was detected on March 8, 2020. One isolated case of a child with SARS-coV-2 was seen on March 13, 2020, in the Oregon School District. While the student was at home, the child's mother came down with symptoms a day after the child tested positive for the virus, and the child's father had symptom onset after ten days. Dr. Temte explains that the mother ran a home daycare and continued to work while she was sick without any personal protective equipment. “So, in a microcosm, this is where the bomb went off. And if you can think of this happening thousands of times across the country with these small-scale episodes, [you can see how] it just accelerated this virus into our communities,” Dr. Temte says.

According to Dr. Temte's data, during the 2020-2021 school year, when students went back to face-to-face instruction, absenteeism peaked at 90 daily average absences due to COVID-19. By the 2021-2022 school year, the highest peak in the data was an average of 240 daily absences due to COVID-19. More interestingly, the data saw the highest peak in cases after the holiday break in winter. In December 2021, the B.1.1.529 virus, or Omicron variant of SARS-CoV-2, became the predominant variant in the United States. Soon after, national COVID-19 cases peaked at their highest recorded levels.

After reviewing the data collected over the start of the pandemic, Dr. Temte and his team found that COVID-19 emerged in small Wisconsin communities, that it was easily transmitted at home, both children and adults were affected by the virus, and school closures had a profound effect on the spread of all respiratory viruses. His team found that while influenza tends to go away during winter and spring school breaks, COVID-19 thrived and accelerated at these times. Their analysis also found that masks and social distancing were effective for preventing the spread of SARS-CoV-2 but not so much for the more common rhinoviruses. Monitoring systems like Dr. Temte's provide the ability to promptly detect developing health situations so that preventative measures can be taken. His method also enables health experts to assess the timing and intensity of outbreaks.

Two years into the pandemic, experts have seen the rise of SARS-Cov-2 variants, like Delta and Omicron, and its subvariants, which are challenging the recent protective measures taken against the virus. Dr. Nasia Safdar, an infectious disease physician, and researcher at the University of Wisconsin School of Medicine and Public Health, walks us through how the epidemiology of the pandemic has evolved over the past two years. “Part of what has been challenging about this pandemic has been keeping up with the variants as they evolve because it's much more than simply knowing what's circulating and how severe it is,” she says. “There are certain treatments that only work for some variants and don't work with others.”

As the pandemic moves into its third year, more variants are evolving and changing how experts are thinking about how vaccines will hold up against the new strains, and when boosters will be needed. A study published by the CDC in the Morbidity and Mortality Weekly Report (MMWR) in August 2021 studied the effectiveness of mRNA COVID-19 vaccines in preventing SARS-CoV-2 infections of frontline workers between December 2020 and August 2021, both before and during the time the Delta variant (B.1.617.2) was predominant. The study found that before the variant was predominant, the vaccine was 91 percent effective at preventing SARS-CoV-2 infection of frontline workers. After the Delta variant became predominant, the number dropped to 66 percent effectiveness, although this may have been due to the passage of time since vaccine. “Now, in the world of vaccination protection, that is still very well worth getting,” Dr. Safdar says. She points out that although more breakthrough infections were reported during this time, few hospitalizations and fatalities were reported.

Fusion Medical Animation

When the Omicron variant appeared, the CDC found in a study that vaccines’ effectiveness against Omicron in symptomatic adults rose to about 68 percent after an mRNA booster. Protection did wane after 2 to 4 months, and the effectiveness dropped to 63 percent.

“A vaccine effectiveness of 63 means that 40% of vaccinated people may have some evidence of symptomatic infection, so it's not surprising that we see as many breakthrough infections as we have been. The goal now has really been to prevent hospitalizations and complications,” Dr. Safdar explains.

It is essential to compare Delta and Omicron variants because Omicron arose when immunity was increasing in the population due to vaccines and prior infections with COVID-19. With subvariants continuing to appear, we can better understand the epidemiology and the best measures to control the spread and protect people. While data has shown vaccines are effective, fewer than half of people in the U.S. who have received the COVID-19 vaccine have also received a booster shot, and more than 20 percent of U.S. residents have not received any COVID-19 vaccine. These numbers are alarming since variation in immunity means SARS-CoV-2 can continue to spread and possibly mutate into more variants.

“We are going to need revaccination. There's a waning of immunity from vaccines, and there are escape variants. This is just a fact of life,” says Dr. Temte. “There's going to be vaccine hesitancy and avoidance, and there are going to be people who will never vaccinate, unfortunately, and they may be the venues for creating new variants because of higher transmission.”

Currently, a subvariant of Omicron dubbed BA.2 is the most predominant variant, due to its increased transmissibility. Compared to its ancestral strain found in Wuhan, BA.2 has 28 unique genetic changes with four on the spike protein, which is the target for immune cells and vaccines.

Compared to two years ago, we have a better understanding of the population’s development of antibodies to COVID-19, a measure of seroprevalence. Between vaccines and infections from COVID-19, very few people have had zero exposure to SARS-CoV-2. CDC found, looking at data from September 2021 to February 2022, that about 60 percent of people in the U.S. have seroprevalence, meaning they caught SARS-CoV-2 at one point, or were vaccinated, and now have antibodies against the virus. “The silver lining is the fact that there are vaccines available and that they have been very effective. At least we're talking about trying to come back to a sense of normalcy,” Dr. Safdar says.

While the vaccines against COVID-19 do not have a 100 percent efficacy rate, they have proven to prevent severe illness from COVID-19 and its new variants. The CDC has published data showing that mRNA booster shots provide significant protection against hospitalization from Omicron and reduce the risk of having to go to the emergency room or an urgent care clinic.

Promega Corporation, a biotechnology company headquartered in Dane County, is working on conducting and providing products for serological or antibody tests that can reveal when and if an individual had a past SARS-CoV-2 infection and if the person has anti-SARS-CoV-2 antibodies. Readily available serology tests can help provide screening of large populations to understand the adaptive immune response to the virus. Sensitive serology tests that detect antibodies against SARS-CoV-2 are vital to vaccine development efforts and to understanding if someone is safe from reinfection. Promega’s test dubbed Lumit™ has a post-symptom onset sensitivity of 93.5 percent, according to Sara Mann, Promega’s Vice President of Commercial Excellence.

The COVID-19 pandemic has highlighted and increased disparities within already struggling communities. In the United States, over 80 million family units, while navigating the pandemic, are also facing challenges such as changes in employment, poverty, homelessness, loss of social support, transitioning to online schooling, juggling work and childcare responsibilities, and increased anxiety and depression. The U.S. Census Bureau's experimental Household Pulse Survey, a survey that measures household experiences during the coronavirus pandemic, found that about 11.8 million children live in households that missed a mortgage or rent payment or sought a deferment. The survey also found that about 3.9 million children experienced COVID-19-related food shortages in 2020. All these issues have the potential to negatively impact developing children and the interactions they may have in their homes.

Dr. Dipesh Navsaria, a pediatrician and associate professor of pediatrics at the School of Medicine and Public Health and a clinical associate professor of Human Development and Family Studies at the School of Human Ecology at the University of Wisconsin-Madison, explains that when parents get the support they need, they can provide the safe, stable, and nurturing relationships that enable their children to develop and thrive despite the added stressors of the pandemic.

In the first three years of life, a child's brain architecture is shaped by the engagements, responses, and emotions derived from human relationships formed during this time. Positive, stimulating, and nurturing relationships are needed to ensure the child develops the vital connections for emotional security, social well-being, and resilience. A concept called Early Relational Health (ERH) has emerged recently addressing the importance of foundational relationships in the healthy development of children. This concept is now being linked to fields like public health services, child welfare, family support services, and pediatric health care.

If children’s need for positive and nurturing relationships are not met, and they are in an environment of constant stress caused by situations like homelessness, racial discrimination, child abuse, and parental substance abuse, they experience toxic stress. Toxic stress can alter the brain architecture and negatively affect children’s emotional health, behavior, physical health, and academic performance later in life.

If children have the support and nurturing they need from adults and learn how to self-regulate their emotions, they are more likely to effectively deal with stress. “One thing that's important about how we think about this pandemic’s impact is that when children are with their families, and their families are able to reasonably attend to their needs, children have this great ability to respond to adversity,” says Dr. Navsaria. He adds that while children need help to cope with toxic stress, parents need support too, steps that will reduce the external sources of stress on their families, and strengthen their core life skills.

Families need access to a stable and sufficient income, nutritious food, and policies that address structural factors that systematically disadvantage people of color. The basic needs of families must be met first so adults can nurture their children. “You can't attend to the higher-order stuff about your life and your career and your happiness if you're worried about safety, shelter, food, things like that. So families need to have their basic needs met. And how can we do this? It's through the programs we set up, the policies we enact, and the advice that we might give,” Dr. Navsaria says.

In May 2020, a survey published at the Center for the Study of Social Policy (CSSP) called the Early Relational Health Survey: What We're Learning From the Field found that when study participants, who work in various sectors representing the early childhood field, were asked what policies or practices would change if the importance of forming healthy early relationships were fully recognized in their field, the most frequently noted policy and practice changes included universal paid family leave, a transformation of child healthcare, and expanded parent education.

Data has shown that while the pandemic has exacerbated economic disparities, it has also created opportunities for families to engage in healthy relational activities. “Families actually spent more time reading together and having family dinner together because they were cooped up together. So, these relationally positive activities became more possible because no one was traveling, no one was out in the evenings,” Dr. Navsaria says. According to the U.S. Census Bureau's 2020, Survey of Income and Program Participation (SIPP), parents shared more dinners and read to their children more than previous years. Sixty-nine percent of parents reported reading to young children five or more times per week in 2020. In 2018, 65 percent of parents said they read to children five or more times a week, and in 2019, 64 percent was reported.

The pandemic raises not only scientific issues, but also social and political ones. When globally, enough people feel comfortable with the numbers of infections, hospitalizations, and deaths per year, the pandemic can be considered an endemic, that is, something that is not out of control but is with us all the time and has become a part of our lives. Although people will continue to get sick from COVID-19, the hope is it won’t be as disruptive or as serious as it is now. Today the average healthy person who gets COVID-19 gets an illness that is disruptive but manageable. For those who are older, immunocompromised, or at more risk, COVID-19 is still a serious illness that can land these individuals in the hospital.

“As far back as vertebrates have had lungs, we've had respiratory infections,” Dr. Temte says. “So, these are things that have been around for a long time and will continue to plague all of us.” The end of the pandemic will depend upon closing gaps in vaccination, making treatments for COVID-19 more available, and detecting mutations in the virus before they spread. Wisconsin-based technology companies have been working since the beginning of the pandemic to do just that.

At the start of the COVID-19 pandemic, molecular diagnostics company Exact Sciences, Promega Corporation, and Epic Systems worked to provide key pieces to expand COVID-19 testing in Wisconsin and help limit the virus's impact in the state. The initiative began when the CEOs of these companies reached out to the Wisconsin Department of Human Services secretary-designee Andrea Palm and Wisconsin Governor Tony Evers. In March 2020, Evers announced a public-private partnership among industry leaders, the state government, and the Wisconsin National Guard to collaborate to combat the pandemic across the state.

The Madison-based Exact Sciences and Promega Corporation made their diagnostic and biochemistry systems available for state scientists' use. While specializing as a cancer diagnostics company, Exact Sciences repurposed its equipment that looks for DNA associated with colorectal cancer to look for SARS-CoV-2 instead. Promega aided this effort by supplying reagents needed to run COVID-19 tests on Exact Sciences machines. And Epic Systems created software to transfer test results from labs to state officials and health care providers fast. Working together, Promega, Exact Sciences, and the Wisconsin-based electronic health records giant, Epic Systems, streamlined a system where accelerated, and reliable COVID-19 testing became possible. Since then, Promega has provided enough reagents and enzymes to test an estimated one billion samples for SARS-CoV-2 worldwide, Promega’s Sara Mann explains.

In March 2022, the Biden administration announced a Test-to- Treat Initiative to give more Americans access to needed COVID-19 treatments. With the initiative, individuals who test positive for COVID-19 can visit hundreds of local pharmacy-based clinics and federally qualified community health systems to receive antiviral medication. The initiative is meant to ensure that those at high risk for developing a severe case of COVID-19 can receive the treatment they need fast.

To make this process easier, Epic Systems developed software that allows healthcare providers to search for up-to-date information immediately on which pharmacies have received COVID-19 anti-viral therapies and the amount of inventory each pharmacy has. If a prescription is unavailable, Epic lets providers know before the drug is ordered.

Epic also helped set up 100 vaccination sites across the country in early 2021. And clinics and vaccination sites used Epic's software to provide over 500,000 daily vaccinations in clinical settings and mass vaccination sites. Epic also tracks COVID-19 cases and has real-time data on the state's supply of hospital beds and current hospitalization rates.

Promega Corporation is also creating snapshots of community-wide infection rates by testing wastewater samples. Those infected with SARS-CoV-2 will shed viral particles before they have any symptoms. Mann says that as a result, levels of SARS-CoV-2 in wastewater can reflect infection trends in a community and possibly predict major outbreaks seven days earlier than clinical tests can.

As the pandemic enters its third year, and the virus continues to evolve, experts in Wisconsin continue to enhance our understanding of the virus and help provide the tools we need to fight it.

Elizabeth Gamillo is a science journalist who lives in Milwaukee, Wisconsin. She is a daily correspondent for Smithsonian and has written for Science magazine as their 2018 AAAS Diverse Voices in Science Journalism Intern. She will be attending the Massachusetts Institute of Technology’s Graduate Program in Science Writing in the fall.