On a recent conference call with medical experts from the country, a conversation around Covid-19 vaccine boosters reflected the incredible tension the topic holds.
One infectious disease physician passionately implored many of us to put the brakes on the rush to authorize booster doses, even for immunocompromised patients, citing a lack of data and concerns about safety. Another respected vaccine researcher expressed the opposite viewpoint, saying that we are past the time for discussing booster shots and that we should have been giving third shots months ago.
This intellectual debate might be moot in a matter of days, as the Food and Drug Administration is expected to authorize third doses of mRNA vaccines, or “booster” shots, most likely for selected populations. But as the country remains in the grips of a fourth wave with a variant of the coronavirus that has surprised many health experts, it is worth highlighting what we do and do not know about immunity and vaccine boosters.
What is immunity, anyway?
The human body has an incredibly elegant way of responding to biological signals to turn on its natural immune response. When you get a Covid-19 injection, your innate immunity kicks in within hours. These are different kinds of cells in the blood that rush to the site of the injection to start the body’s defenses. It is why your arm might feel sore after a vaccination.
Days later, your adaptive immunity starts to ramp up — these are very specific B and T cells, or antibodies, that work with one another to target the coronavirus spike protein. Think of your adaptive immunity as a very specific and diverse response that can remember past infections or exposures; this is the part we are counting on for Covid-19. The vaccine helps to prime your adaptive immunity so that if the real coronavirus is introduced, your body will remember and send antibodies and other cells quickly to help fight the infection.
Some conditions do not allow the body to produce a robust immune response: certain cancers, HIV/AIDS, autoimmune diseases and the use of certain medications. Some medications, such as prednisone, which is commonly used for many conditions in moderate doses, including asthma, result in a tenfold reduction in antibodies compared to people who do not take prednisone. Together, these patients are about 2.8 percent of the population, and they are generally referred to as “immunocompromised.”
At a recent Centers for Disease Control and Prevention Advisory Committee meeting, staff members and other experts presented data that patients with conditions that compromise immunity are more likely to get severely ill from Covid-19 and to have lower levels of antibodies to the virus, especially the delta variant. According to growing research, there is also a higher risk for prolonged infection and shedding, which could mean that immunocompromised patients who are infected have the virus in their bodies longer and in turn could infect other people past the current 10-day time frame. We also know that our immune system is less responsive as we age, beginning in our sixth decade. All of these factors also lead to the potential for breakthrough infections that result in hospitalization and death.
What is a Covid-19 vaccine booster?
The idea behind a booster is not new with vaccines; boosters are recommended for several vaccines, including the diphtheria, tetanus and pertussis vaccines (also known as Tdap). The idea behind a booster is to re-expose the body to the outside biologic threat (in this case, the coronavirus spike protein) to increase its natural immunity. The tetanus booster is recommended every 10 years because we know that the body’s adaptive immunity, referred to earlier, decreases over time.
The goal of increasing immunity is not intellectual. It is to prevent disease and serious effects of disease. With Covid-19, the goal of a booster or any other additional doses would be to optimize immunity to ensure maximum protection against serious illness or death. The Covid-19 boosters being considered by the FDA would be the exact same formulation as the first and second doses of the mRNA vaccines developed by Pfizer/BioNTech and Moderna.
Both companies have conducted trials to support the use of boosters, noting that third doses prompted spikes in levels of “neutralizing” antibodies when administered several months after second doses. Of note, Johnson & Johnson does not have a booster, but it is in trial with a second dose of its vaccine. About 12.8 million people in the U.S. have received the Johnson & Johnson vaccine, and hopefully any booster guidance will include these people.
So, who should get a booster?
It feels like an incredibly First World problem to discuss boosters when half the world still needs to get any vaccine, but a growing body of data supports boosters, especially for particular populations.
Several countries, including Israel, France and Germany, have already made plans for booster shots in older patients, health care workers and people with certain chronic conditions. Given the mounting evidence, it seems as if there should be little debate that immunocompromised patients are likely to need boosters, as well as patients over a certain age. But the debate is fierce, as noted in my conference call conversations. While it is true that immune response is not equivalent, it is not clear whether boosters will remedy the situation and whether third doses will lead to prevention of serious disease and death. Booster doses might increase antibody levels, but we do not know what level is adequate to lead to protection, and even if we did, we do not have the ability to check every person’s levels before or after vaccination. The pace of a pandemic with the threat of variants that have taken many public health professionals by surprise has resulted in a crisis in confidence and communication. As the FDA advances access to boosters, it will be critical to have a conversation with your physician or other health care professional. There are potential risks, and it is worth discussing your situation before jumping to the conclusion that more vaccine is ideal. Even with the booster, many patients will still need to wear masks and act is if they are unvaccinated because of the possibility that a third shot (or even a fourth) might not be enough. At a minimum, people over age 65, immunocompromised patients and patients taking certain medications should ask their physicians about booster doses. Health care and other essential workers who were vaccinated early and are still at high risk because of their occupations, from grocery store personnel to law enforcement officers, should also be considered for booster doses, but data have been a bit more limited in terms of timing and criteria for them. The political vitriol around simple messages about vaccines and masks has made the conversation about boosters even more complicated. The FDA’s announcement about boosters should not undermine confidence in the vaccines. Vaccines work. Masks, ventilation and distance work. In the global fight against a tiny virus, we need all the defenses possible. Boosters should be acknowledged for what they are: one piece of this defense.
Dr. Kavita Patel
Dr. Kavita Patel is a teaching professor of medicine, Division of Hospital Medicine, at Stanford University and a board-certified internal medicine physician. She served in the Obama administration as director of policy for the Office of Intergovernmental Affairs and Public Engagement in the White House. Her area of expertise is around the intersection of health policy, clinical medicine and innovation. She also spends time advising venture capital and is a medical contributor for NBC News. 
