By Jan E. Patterson, MD, MS, MACP

COVID-19 in 2021:

Vaccine Progress and Challenges

By Jan E. Patterson, MD, MS, MACP

Just a year ago, we were headed into a summer surge of COVID-19 hospitalizations and deaths. As we cared for sick patients and saw continued increases in hospitalizations and deaths, we worked to increase testing, improve public health measures and discover what therapies worked best. We could hardly envision that an even worse winter surge was coming, in which we would exceed 500,000 U.S. deaths from COVID-19. It was also hard to imagine that by the year’s end, we would have effective vaccines against COVID-19, but vaccination of health care workers began in December. Even better, the vaccines were more efficacious than we could have imagined.

In clinical studies, mRNA vaccines (Pfizer/BioNTech, Moderna) were 94-95% effective against symptomatic disease and even more effective against hospitalizations and death. Real-world data after the FDA Emergency Use Authorization (EUA) has confirmed 94% effectiveness against symptomatic disease of the mRNA vaccines after two doses in health care workers, and efficacy in the general population appears to be similar. The single dose, replication-deficient adenovirus vector Johnson & Johnson/Janssen (J&J) vaccine was 66% effective against COVID infection in clinical studies. Most real-world efficacy data is for the mRNA vaccines, and real-world data on the J&J vaccine is still being evaluated. Evidence is also accumulating that each of the FDA-authorized vaccines provide significant protection against asymptomatic infection. For all of these vaccines, the most protection was achieved two weeks after the final vaccination dose.

Effectiveness of a single dose of mRNA vaccine estimated from realworld data is 70-80% in health care workers. Long term data regarding mRNA vaccine single dose efficacy is unknown, and based on current data, people should receive two doses of the mRNA vaccine to obtain the most benefit from vaccination.

Vaccine breakthrough cases have occurred, including some cases of hospitalizations and deaths, but these are very rare. The CDC recently reported 0.001% breakthrough cases among 100 million people vaccinated and most of these cases did not result in hospitalization or death. Review is still ongoing to see who may be most at risk of breakthrough cases, but it is likely to be elderly or immunosuppressed persons.

The safety record of the vaccines has also been good. Common side effects are typically within two days of the vaccine and include sore arm, headache, fatigue and less commonly, chills and fever. Reactogenic side effects such as chills and fever are more common after the second dose and in those < 55 years old. The Moderna vaccine can have a benign delayed local reaction at the site of injection 8-10 days after the vaccine, occurring in <1% of people.

A side effect to be aware of for mRNA vaccines is anaphylaxis, which occurs in about 4 per 1 million persons vaccinated, and has been treated successfully at vaccine sites during the post-vaccine observation period. This occurs more commonly in women and those with a history of allergic reactions. If a severe reaction occurs within four hours of the first dose of the mRNA vaccine, the second dose should not be given. While the cause of these severe reactions is not known with certainty, polyethylene glycol (PEG) is a constituent of mRNA vaccines and is a known potential allergen. Those with a history of PEG allergy should avoid mRNA vaccines. The J&J vaccine does not contain PEG, but contains polysorbate which has potential cross-reactivity. For persons with a history of polysorbate allergy, consider an Allergy/Immunology consult or contact the CDC Clinical Immunization Safety Assessment Center for guidance.

The detection of rare blood clots after the J&J vaccine demonstrates successful post-EUA surveillance with the Vaccine Adverse Event Reporting System (vaers.hhs.gov). The distinctive Thrombosis with Thrombocytopenia Syndrome (TTS) consists of a blood clot in an unusual location, such as the brain, in combination with thrombocytopenia, occurring within two weeks of the J&J vaccination. Women and those < 60 years old are at higher risk of this complication. An impor-

tant finding is that heparin antibodies are present in this condition, so other anticoagulants must be used for treatment of these clots.

Current recommendations are that persons who have already had COVID should still be vaccinated. The degree of natural immunity after vaccination varies, and reinfection can occur. There is not a recommended minimum interval for the vaccine after infection, but reinfection is uncommon before 90 days. Persons with COVID should defer vaccination at least until recovery from acute illness and criteria for discontinuing isolation is met.

At this time, the FDA recommends against the routine use of antibody testing for detection of vaccine antibody response. Many FDAauthorized antibody tests detect nucleoproteins that are the result of natural infection and not spike protein, which is what vaccines are directed against. Even with tests detecting spike protein antibodies, studies continue regarding the amount of antibodies that are protective against infection. Commercially available antibody tests do not detect neutralizing antibodies.

The need and timing for booster doses have not been established, but it is likely that a booster will be advised around the end of the year. The vaccines currently authorized by the FDA appear to have efficacy against variants of concern, although responses may be diminished for some variants. As the virus continues to spread in areas around the globe, the development of new variants is concerning.

Early studies in immunosuppressed persons indicate that they may have less antibody response. Depending on the results of ongoing studies, earlier boosters in this population may be warranted, but as of this writing, this is not yet recommended.

The adenovirus vector Oxford/Astra-Zeneca vaccine, used widely in the United Kingdom and some other countries, is not yet FDA-authorized in the U.S. and has also been noted to be associated with TTS. In addition, studies show there are concerns with efficacy against the South African variant. Clinical trials with Novavax, a recombinant protein plus adjuvant vaccine, appear very promising, but FDA authorization is not expected until later this summer.

Influenza was virtually nonexistent this past winter season, but without masking and distancing next winter, it is expected to return. A combination of flu/COVID vaccine could be desirable, and Novavax has announced promising preclinical data with a combination vaccine. Clinical trials with this combination vaccine are expected to begin before the end of the year.

The U.S. is on course to achieve the Biden administration’s goal of 70% of adults receiving at least one dose of vaccine by July 4, 2021. By the third week in May, over 60% of adults have received one dose. Around 40% of the total U.S. population is fully vaccinated. Several states have achieved at least one dose to 70% of their adult population. See the CDC COVID Data Tracker for updated numbers.

At the time of this writing, more than 50% of Texans 12 years of age and older have received at least one dose of vaccine. Bexar County has exceeded 1 million doses given and the majority of seniors have been vaccinated. Among the total Bexar County population, more than half have received at least one dose and over 40% are fully vaccinated. See the COVID-19 page at sanantonio.gov for the most upto-date information from Metro Health.

This is encouraging news, and yet the pace of vaccination in the U.S. has slowed. Strategy has shifted from mass vaccination to mobile vaccination, pharmacies and physician offices to make vaccination more convenient. Vaccine hesitancy is more common in rural areas, and vaccination rates also vary a great deal by state. Most hesitancy is related to concerns about side effects. Surveys continue to show that a person’s most trusted source of information about vaccines is their personal health care provider, so physician discussions with their individual patients about the vaccine are key. Vaccination rates high enough to achieve herd immunity in all geographic areas of the U.S. may be elusive, however, and we may have to be prepared for another increase in cases next winter, since coronaviruses are typically a fall/winter seasonal virus.

Countries leading the world in vaccination rates include Israel, United Arab Emirates, Bahrain, Chile and the UK. Clinical study results of the efficacy and safety of vaccines used in many other areas of the world, such as Sinovac/Coronavac (inactivated virus technology; China) and Sputnik V (adenovirus vector technology; Russia) are not as well-known, and real-world data will be telling.

While vaccination rates in the U.S. are encouraging, the battle against COVID-19 is still fierce in most parts of the world. The current situation in India is an example. In the month of May, India reported more COVID-19 deaths in a single day than any other country during the pandemic.

The efficacy of vaccines authorized in the U.S. and the speed with which they became available is phenomenal and we are indeed fortunate to have had the government’s support, innovative technology, scientific expertise and willing study volunteers to achieve such success. Because the virus knows no borders, however, we are not safe until we are all safe, and the U.S. can play an important role in controlling COVID-19 worldwide by making its plentiful supply of vaccines available to other countries.

Jan E. Patterson, MD, MS, MACP is a Professor of Medicine/Infectious Diseases at the Lozano Long School of Medicine. She has more than 30 years of experience in infection prevention and has been involved in the COVID-19 response for the South Texas Regional Advisory Council, UT Health, University Health and Metro Health. She is a member of the Bexar County Medical Society.