COVID-19 Vaccines Signal Light After Dark Days

Dec. 22, 2020

In order to end this pandemic, we must end the spread of the virus. The misguided assumption that herd immunity could be accomplished by allowing life to return to normal has become a national catastrophe, resulting in more deaths than U.S. combat deaths in World War II, the most deadly conflict in our history. The rational, scientific approach to end the pandemic is to develop protective vaccines that can be distributed globally. The rapid development of these vaccines, with only 11 months separating the publication of the SARS-CoV-2 genomic sequence from widespread vaccine distribution, might be the most impressive scientific achievement in modern history. Over the past 2 weeks, 2 COVID-19 vaccines have received emergency use authorization (EUA) in the U.S. Initial doses of the Pfizer vaccine were given on Dec. 14, 2020 to health care workers at medical centers throughout the United States. With the Dec. 18 EUA for the Moderna vaccine, its distribution begins the week of Dec. 21. The data upon which the initial 2 EUAs are based suggest that these vaccines have favorable safety profiles and are highly effective in preventing COVID-19. For health care providers and our most vulnerable populations, protection against COVID-19 disease is approximately 6 weeks away from each individual’s initial injection. 

However, this promising news should be balanced against the current status of the COVID-19 pandemic in the U.S. Despite consistent public health warnings to avoid travel and large gatherings over the Thanksgiving holidays, many people decided that the sense of security and normalcy that family holiday gatherings provide was worth the risk. These individual decisions have resulted in an unrelenting surge in daily U.S. COVID-19 case counts, which are currently topping 200,000 each day — by far, both the highest case number of any nation in the world, and the highest at any time during our national pandemic. As we approach the darkest days of the year, we are faced with the devastating consequences of this surge, with 110,000 hospitalized nationally, a daily death toll topping 3,000 and care providers who may soon have to decide who will receive care in overwhelmed critical care units. Physically and mentally exhausted healthcare providers, many in tears, pleading with people to follow public health guidance have become a fixture on the evening national news broadcasts. 

The Unanswered Questions About COVID-19 Vaccines With EUAs

Although the vaccine development process has been a magnificent accomplishment thus far, humanity has never faced the task of vaccinating the global population in as brief a time as possible. Shortages in essential supplies, such as personal protective equipment (PPE) and testing reagents, are a continuing challenge during this pandemic. The mRNA vaccine technology used by Pfizer and Moderna has never been used at the scale that will be needed. What manufacturing, distribution and administration problems will be encountered? Will there be shortages of supplies needed for vaccine manufacture, such as vials to package the vaccine, shipping containers or dry ice necessary for maintaining cold chain during shipments or syringes? 

Once vaccines safely arrive, the logistics of prioritizing vaccinations for each population, administering the vaccine and then tracking each individual to assure that they receive their second vaccine dose at the right time are unprecedented. Importantly, special protocols need to be established to administer these vaccines to individuals with a history of severe allergic reactions. What will the unintentional consequences on other vaccine programs be, if any? As we wait our turn to receive the vaccine, “patience” is the watchword.  

Immunity following natural infection elicits both secretory IgA and IgG antibody response. Secretory IgA is central to providing the mucosal immunity that prevents SARS-CoV-2 from initiating infection in the nasopharynx. Because all of the COVID-19 vaccines currently in clinical trials are given intramuscularly, they will elicit an IgG response only. Although this will likely protect from lung infection, the vaccines may not provide sterilizing immunity in the upper respiratory tract. The preliminary data from the Moderna and Pfizer vaccines shows protection from clinical disease, but their effects on interruption of viral transmission have not yet been evaluated. Further studies are needed to determine this.

We do not yet know the durability of immunity provided by these 2 vaccines. We will learn more as the initial clinical trials proceed to their long-term endpoints at 2 years. Will boosters be necessary, as they are with other vaccines? 

How will the vaccines impact pregnant women? Because a significant number of healthcare workers are women of child-bearing age and may be in the first trimester of pregnancy when they are vaccinated, we may begin to learn more from this initial vaccinated cohort. Observational studies, such as pregnancy registries, will be set up to monitor safety with EUA use of these 2 vaccines. The several dozen pregnancies and birth outcomes that occurred during the conduct of the Pfizer and Moderna Phase 3 trials are being followed closely. 

Given the limited number of individuals in the initial clinical trials, we will learn more about rare vaccine complications only after vaccinating millions of individuals. Currently, the Centers for Disease Control and Prevention (CDC) is recommending that individuals with a history of severe allergic reactions to any component of the 2 vaccines not receive that vaccine. The EUAs require careful observational safety surveillance on vaccinees by Pfizer and Moderna. Clinical trials are also in the planning stages for children less than 16 years of age for the Pfizer vaccine and those under 18 for the Moderna vaccine.

Finally, it is likely that several additional COVID-19 vaccines will be approved. How they can each be best utilized is an open question with answers months to years away. 

Vaccine Hesitancy and Risk

 Although the EUAs for these 2 vaccines and those to follow offer great hope for developing vaccine-induced herd immunity and thus ending the pandemic, the development of herd immunity is dependent on a large percentage of the population receiving an effective COVID-19 vaccine. In the U.S., vaccination rates for childhood illnesses are between 81-93%. As a result, most of these infections are rare and occur almost exclusively in non-vaccinated individuals. Currently, only 70% of Americans surveyed would agree to take a COVID-19 vaccine. The question is whether vaccinating 70% of a population where less than 5% have been infected will result in herd immunity. The hope is that many who are now hesitant will agree to be vaccinated as we learn more about vaccine safety, especially the frequency of rare, severe reactions. 

All vaccines carry risks. Initial reports of anaphylactoid reactions in 2 health care workers in the U.K. made global news, but was not entirely surprising based on their personal medical histories, which required them to carry Epipens due to severe allergies. Recently, another individual without underlying allergies developed an anaphylactic reaction in the U.S. and required ICU admission. Because reactions are more severe with the second vaccine dose, worries about additional anaphylactoid or anaphylactic reactions are justified. However, these worries need to be put into perspective. The U.S. mortality rate for COVID-19 is currently 1.8%. By comparison, a small number of severe adverse reactions and no vaccine-related deaths have occurred in those receiving COVID-19 vaccines, with over 500,000 doses administered in the U.S. as of Dec. 20, 2020. Our current understanding is that risks associated with the COVID-19 vaccine are very small, but not zero, similar to any other vaccine. The benefit of receiving a COVID-19 vaccine so that lives are saved, children can safely return to school, families can safely gather around the table and businesses large and small can safely reopen far exceeds the risk of serious vaccine complications.

Because rare, severe vaccine reactions have long been recognized, the U.S. has developed a safety net to compensate those injured by vaccines. To ensure that litigation costs stemming from severe vaccine-related injuries would not be a disincentive for both the development and manufacturing of childhood vaccines, the Vaccine Injury Compensation Program was established in 1986, funded by a nominal excise tax on each vaccine dose. Between 1988 and 2019, this program has provided those injured by vaccines with over $3.4 billion dollars. A similar program, the Countermeasures Injury Compensation Program, was established in 2010 to protect individuals who are injured by a vaccine, medicine or device to prevent or treat an agent causing a public health emergency. This program covers COVID-19 vaccines.

What Is Next?

Public health experts emphasize daily that public health measures are still essential in fighting this pandemic. It will take 6 weeks from dose 1 for each vaccinee in the initial vaccinated cohort to develop peak immunity. Herd immunity, where more than 70% (and hopefully 80 to 90%) of the population is vaccinated, will not be here realistically until summer. Between now and then, the prevention of tens of thousands of deaths still relies on us wearing masks, social distancing and forgoing social gatherings, especially indoors. We are all tired of this, but just imagine how tired the ICU nurses are who have had to watch so many loved ones die without family near. What about our exhausted medical laboratory and public health professionals who are near the breaking point due to the never ending laboratory testing? We have a responsibility to our healthcare professionals and ourselves to follow public health guidelines, and when available, to roll up our sleeves to be vaccinated.

Author: Lynn Smiley, M.D.

Lynn Smiley, M.D.
M. Lynn Smiley, M.D. is an infectious disease physician with extensive clinical development experience with viral diseases. 

Author: Peter Gilligan, Ph.D., D(ABMM), F(AAM)

Peter Gilligan, Ph.D., D(ABMM), F(AAM)
Peter Gilligan, Ph.D., D(ABMM), F(AAM) is the former Director of the Clinical Microbiology-Immunology Laboratories at the University of North Carolina Hospitals.