The introduction of COVID-19 vaccination in 2020 was a game changer. People could be protected against the virus and significantly lessen their risk of infection—particularly serious cases of disease that required hospitalization—and death. Many of us were able to breathe a sigh of relief after we were fully vaccinated.
However, one group of fully vaccinated individuals is still left in the lurch, not sure if their vaccination protects them—and if so, how much. Immunocompromised people have conditions or medical issues that weaken their immune systems and may leave them at risk of serious infection, even if vaccinated. “This is a broad term but it generally encompasses people who cannot mount the same immune response that healthy people can,” Neha Vyas, M.D., a family medicine physician at Cleveland Clinic, tells SELF. “This would include, but is not limited to, those who are undergoing treatment for cancer, those who have had an organ transplant, those who are elderly, or those who have autoimmune conditions and are taking medications which alter their immune response.”
Regardless of the cause, immunocompromised persons may remain at greater risk from COVID-19, even after vaccination, than those who are not immunocompromised. So what do we know about vaccination in this group?
1. Maximum protection via vaccination requires a robust immune response.
“Those whose immune systems are immunocompromised may not be able to generate enough of a response from the vaccine, thereby leaving them vulnerable to the COVID virus,” says Dr. Vyas.
SELF also spoke with Dorry Segev, M.D., Ph.D., professor of surgery and epidemiology and transplant surgeon at Johns Hopkins University, who has led numerous studies examining this at-risk population. He notes that for those who are immunosuppressed (taking medications that will depress their immune response) or are immunocompromised for other reasons, the problem is the same: If one is unlikely to mount an effective immune response to an infection, they may not respond effectively to a vaccine.
“For the vaccine to work, it has to activate your immune system, to develop antibodies and memory B cells and a repertoire of T cells to attack that thing that you’re being vaccinated against,” Dr. Segev explains. But if you don’t already have those functioning components of the immune system, you will be unable to mount as good of a protective response and may have a more serious reaction to an infection.
2. Ongoing studies are examining COVID-19 vaccine response in immunocompromised individuals.
Focusing primarily on solid organ transplant recipients, Dr. Segev’s group has found that many of these individuals have a poor antibody response to the COVID-19 vaccines. Only 17% of people mounted a detectable antibody response 20 days after the first mRNA vaccine dose or to the Johnson & Johnson vaccine. A second mRNA dose increased antibody response to 54% of participants.
While antibody response is only one part of vaccine-induced protection, Dr. Segev’s group also examined the incidence and severity of breakthrough infections (infections occurring in fully vaccinated individuals) in their population of immunosuppressed patients. They found that transplant patients were at a significantly increased risk of infection and serious outcomes: “If you are a fully vaccinated transplant patient, your risk of getting a breakthrough infection is 82 times higher than a fully vaccinated person from the general population, and your risk of a breakthrough infection with associated hospitalization or death is 485 times higher than a fully vaccinated person from the general population,” Dr. Segev explains. There are some caveats to keep in mind with these numbers, like the fact that the study was based on solid organ transplant recipients, so there may be differences in the response from other immunocompromised individuals. But even as estimates that require more investigation, these findings are clearly quite dramatic.
3. So far, the data suggest that COVID-19 vaccine booster shots may be helpful for immunocompromised people.
Dr. Segev led a small study which followed 30 patients who had low or no detectable antibodies after two mRNA vaccine doses (either Moderna or Pfizer-BioNTech). Researchers found that all individuals who had low antibody titers found them raised after a third dose of vaccine, and a third of those with no detectable antibodies had a detectable antibody response following the third dose.
Though the study only measured antibody response, Dr. Segev believes the results will be reasonably representative for clinical outcomes. “Definitely, with a third dose, one can increase the immune response, and the underlying biological framework is that increasing the antibody response will also increase the clinical protection,” he explains. This will be the subject of future work as researchers examine how well third doses protect against infection and severe COVID-19 disease; how long protection lasts; and whether a fourth dose would help those who still were not responsive to earlier doses of vaccines. Dr. Segev and colleagues are examining these issues as well.
“There are two major issues with immunosuppressed people right now. One is, how do we get them to the same level of immune response as the general public? And then two, if we can get them there, how long will it last?” For the latter, he notes his group has examined vaccine durability in solid organ transplant recipients after three months, “and it seems relatively strong,” but this will require additional monitoring. “We’re building the plane as we’re flying it, and one of the things we don’t have good answers for is, at what point do you reach enough protection, and what even is enough?”
Based on these and other research findings, on August 12 the U.S. Food and Drug Administration authorized a third dose of vaccine for certain immunocompromised individuals. This applies primarily to solid organ transplant recipients or those who are diagnosed with conditions “that are considered to have an equivalent level of immunocompromise.” The Centers for Disease Control and Prevention guidelines clarify that, among others, this applies to people who are “moderately to severely immunocompromised, including individuals who are undergoing chemotherapy or taking other medicines (such as high-dose corticosteroids) to suppress the immune system; have a moderate or severe primary immunodeficiency; advanced or untreated HIV infection.” The third dose should follow the second after a period of at least 28 days.
However, this guidance still leaves out people who received the single-dose Johnson & Johnson vaccine. This is largely because there is not as much data on those who received the J&J vaccine, which has been much smaller than the number of people who have received mRNA vaccines. Dr. Segev understands the frustration and hopes additional guidance for these individuals is forthcoming. “It is to me strongly compelling that if the FDA and CDC feel like a third dose of an mRNA vaccine is indicated, then very clearly an additional dose of something in people who got the J&J as their primary vaccination should be equally justified if not even more justified,” he says.
4. There’s also interest in potentially mixing and matching types of vaccines for a better immune response.
In the medical world, taking a dose of a different type of vaccine from the first dose is known as heterologous boosting. This has been tested in some other countries, generally with an initial, “priming” dose of the adenovirus vector Oxford/AstraZeneca vaccine (not currently authorized in the United States), followed by a second “booster” dose of the Pfizer-BioNTech vaccine. This would be similar to a first dose of the Johnson & Johnson vaccine, which is also an adenovirus vector vaccine, followed by an mRNA vaccine. A study examining immune response to this combination found it produced a robust immune response, but the research was not carried out in immunocompromised individuals. This needs additional testing in this population.
But the question still remains: What if a second dose (in the case of Johnson & Johnson) or third dose (in the case of mRNA vaccines) still doesn’t provide sufficient protection for immunocompromised people? Another unknown is whether pausing immunosuppressive drugs in people who are able to do so may help with a vaccine response in these cases. What Dr. Segev and other researchers want to know is if there are other factors like this that may help a person to be more responsive. However, Dr. Segev asks, “Is that riskier than it’s worth?” His team was recently awarded funding to examine some of these questions.
5. For now, it’s on all of us—immunocompromised or not—to help keep each other safe.
In one way, little has changed, even for those who aren’t immunocompromised. Dr. Vyas points out tried and true measures such as social distancing, wearing a mask, and hand washing are still important—and not just for those with immune system concerns. “Loved ones can make sure to obtain the vaccine themselves and to help those who are immunocompromised to be safe in areas where virus transmission can occur,” Dr. Vyas says. Dr. Segev agrees, noting that if everyone with a healthy immune system wore masks when needed and got vaccinated to reduce community prevalence of this virus, we could significantly curtail spread and protect the rest of us—including those who are immunocompromised.