Should You Recommend a COVID Booster to Patients?

Fully vaccinated patients are constantly inquiring about getting a COVID-19 vaccine booster. Some are already panicking, breaking the rules, and getting a third shot. While most first world countries have a centralized public health record, we do not. The states track vaccine administration, not the CDC. This means people are easily evading the system.

This begs the questions of how the U.S. should approach boosters and what providers should recommend to patients who ask about boosters.

What’s the Current Booster Landscape?

Several studies offer preliminary evidence on the benefits of boosters, especially for certain populations. A recent French study in JAMA showed that about 50% of 159 kidney transplant patients with low or no measurable antibodies after two doses of an mRNA vaccine mounted a response with a third shot, and with no serious side effects or rejection episodes. A study in the Annals of Internal Medicine also showed the benefits of a third dose in solid organ transplant patients. Pfizer data (that has not yet been peer reviewed) show antibody levels rise 11-fold in patients ages 65 to 75 after a booster.

Around the world, some countries and localities have gotten an early start on boosting. Boosters are being offered to patients over 60 years old in Israel. France is giving a booster dose to the severely immunocompromised 4 weeks after the second dose, and Hungary, Turkey, Thailand, Bahrain, and the United Arab Emirates are starting booster programs. The Mississippi Health Department is now recommending physicians consider boosters for the immunocompromised.

Who Should Get a Booster Now?

We are dealing with two segments of the population.

According to a presentation at a recent meeting of CDC’s Advisory Committee on Immunization Practices, just shy of 3% of the adult population is considered immunosuppressed. This includes people with:

• Cancer
• Organ or stem cell transplants
• HIV
• Severe primary immunodeficiencies
• Asplenia
• Advanced chronic kidney disease
• Conditions requiring immunosuppressive medications such as chemotherapy, tumor necrosis factor (TNF) blockers, certain biologics such as rituximab, and high-dose corticosteroids

These patients may have poor antibody responses to vaccination. Even though they represent about 3% of the adult population, they account for 44% of breakthrough infections requiring hospitalizations, according to one U.S. study. Here, vaccines were 59% protective against hospitalization for this group versus 91% for those without immunosuppression.

For the 97% of people who are not immunosuppressed, the initial two doses of the mRNA vaccines are highly protective for most. While some people are getting breakthrough infections, most just suffer minor symptoms. Moderna and Pfizer are also studying new formulations of the vaccines to better protect against Delta and other variants. For these reasons, there is no pressing reason to offer these patients a booster now, and measuring spike protein antibody levels in this population would only sow confusion.

There are some exceptions, however. Evidence suggests the Johnson & Johnson vaccine may be less effective against the variants, and certain localities, like San Francisco, are allowing people to boost if they received J&J. Those who received the J&J shot may want to consider getting an mRNA booster at this time and should discuss it with their doctor.

For the immunocompromised 3%, the situation is quite different. Multiple studies show these patients can mount a significant antibody response to a booster. Will this translate to a lower risk of severe infection? While we will not know for certain until outcome studies are complete, antibody titers correlate well with susceptibility to infection. An elegant New England Journal of Medicine article in July demonstrated that COVID-19 breakthrough infections in Israeli healthcare workers were less common among those with higher neutralizing and anti-spike protein antibody levels.

With the current Delta surge, we do not have the luxury of waiting for definitive studies. Until such studies determine whether boosters are effective in preventing disease in this population, we have two choices: One is to offer everyone in the immunocompromised group a booster. The World Health Organization just called for a halt on booster shots through September to “make up for a shortfall of vaccine supplies to poor countries.” The immunocompromised group, however, remains at significant disease risk despite two mRNA vaccines. A recent study showed the rate of infection in transplant patients was 82 times the general vaccinated public and the rate of serious illness was 485 times higher. A booster moratorium clearly should not apply to this group. Furthermore, the White House just announced the U.S. can both provide boosters if necessary and donate the excess supplies to poorer countries.

The second option is to measure quantitative spike protein antibodies and vaccinate those with low or undetectable antibodies. However, the FDA currently does not recommend measuring antibodies except as part of a clinical study. Although it does not measure T-cell immunity, these antibody levels are currently our best proxy and an easily measured determinant of infection risk. Patients appreciate information. If they see their antibody levels are low, they might more readily accept a booster shot now, even though a third dose is not currently authorized. Furthermore, patients with normal antibody levels can be reassured they likely have healthy humoral immunity and might opt to wait for the newer vaccines that have been bioengineered to induce a stronger immune response to the variants. We cannot simply wait around — either boosting or measuring antibodies in this at-risk population is a must.

Thinking beyond immunocompromised patients, other medical conditions — to varying degrees — pose an increased risk of hospitalization and death from COVID-19: obesity, sickle cell anemia, liver disease, advanced age, chronic lung disease, diabetes, heart conditions, stroke, and substance use disorder. Guidelines for boosters will need to be developed for each of these groups.

Robert Colton, MD, is an internist and nephrologist, founder of MDVIP, and Chairman of ClearlyDerm Dermatology.