Are Immunocompromised Patients Left Out by COVID Vaccines?

As more people in the United States are vaccinated against COVID, there’s concern that millions of people who are immunocompromised may not be adequately protected by the vaccines.

Several recent studies have found that antibody production in immunocompromised patients is worryingly low. One study, performed at Columbia University and NewYork-Presbyterian, found that only about half of solid organ transplant patients had detectable antibodies after SARS-CoV-2 infection. Another study, in kidney transplant recipients, found that 75% of patients had no detectable antibodies after getting fully vaccinated against the coronavirus.

Because immunocompromised patients were excluded from participating in large-scale clinical trials of the vaccines, researchers are now taking a look at how this broad group of patients—which includes cancer patients, organ transplant recipients, and people being treated for autoimmune diseases—may respond to vaccination. 

We spoke with Pawel Muranski, MD, assistant professor of medicine and of pathology & cell biology at Columbia University Vagelos College of Physicians and Surgeons and director of the Cellular Immunotherapy Lab at NewYork-Presbyterian/Columbia University Irving Medical Center, about what’s known and unknown about COVID vaccines and the immunocompromised.

Are all immunocompromised patients at greater risk of COVID and other infections? 

There is a spectrum of risk that depends on the underlying disease.

Pawel Muranski

Overall, patients with active cancer or a history of cancer treatment have a higher risk of infection because of treatments that suppress the immune system or the effects of the disease itself on immune cells. I am a hematologist/oncologist and I work primarily with patients who have blood cancers—lymphomas and leukemias—and need a bone marrow transplant. Prior to the pandemic, we had noticed that many bone marrow transplant recipients and patients with blood cancers had respiratory diseases due to ‘common cold’ coronaviruses.

For patients undergoing cancer therapy and transplant recipients, the degree of immunosuppression depends on the timing of treatment. Patients who have recently had a bone marrow transplant or solid organ transplant might have a higher risk than patients whose transplantation occurred many years ago and are now on low-dose immunosuppression or have even stopped immunosuppression and lead a relatively normal life. 

The immunosuppressive therapies used to treat patients with autoimmune disorders can also reduce response to vaccination. Some drugs, like rituximab, which directly targets B cells, may have a prolonged effect. Response to vaccination may be enhanced in patients with autoimmune diseases by temporarily reducing the dose or withdrawing immunosuppressive medication.

Are patients who don’t make antibodies to SARS-CoV-2 or the COVID vaccines completely unprotected?

It's known that some immunocompromised patients don't have a strong antibody response following influenza vaccination, so it's not really surprising that they wouldn't respond very well to SARS-CoV-2 vaccination. 

Though some studies show that immunocompromised patients do not produce many antibodies after COVID vaccination, other studies have suggested that immunocompromised people who are vaccinated have a robust T cell response. T cells [another part of the immune system] are more difficult and time-consuming to assess, so many studies stick to measuring antibodies, which is much simpler. Yet it’s not clear which component is critical for protective immunity against SARS-CoV-2. 

In our lab, we came across a few transplant recipients with a long history of immunosuppression who had some respiratory symptoms last year and tested positive for SARS-CoV-2 antibodies. We looked at their T cells and found that the patients were able to mount a very robust cellular response against the virus and against many other coronaviruses. 

We also saw some patients with autoimmune diseases who were on active immunosuppression and failed to mount an antibody response to vaccination. They also were able to demonstrate a nice T cell response, despite not having antibodies after getting vaccinated. 

These are very positive, uplifting findings and highlight the possibility that tests to measure T cell response could be used to measure immune system response after infection or vaccination against COVID-19. But the real proof of protection will have to come from studies that follow patients and measure clinical outcomes. Unfortunately, there’s no quick answer.

It also raises a bigger question about whether people in the general population are still protected if their antibody titers drop. Vaccines focus on triggering the production of antibodies that can neutralize viral particles. T cells are thought to provide broader and longer-lasting immunity than antibodies, potentially reducing the severity of infections.

If we find that people are still protected after their antibody levels decrease, it would offer more proof that there is something other than antibody response that matters.

Are there treatments to prevent severe COVID in immunocompromised patients who are infected?

Many immunocompromised patients who get COVID have prolonged disease and carry the virus with them for a long period of time. In a recent study, a monoclonal antibody cocktail was found to help hospitalized COVID patients who did not make antibodies to SARS-CoV-2, suggesting that this approach may be used to treat immunocompromised patients who are hospitalized with the infection. 

In the future, we could potentially use cellular therapies made from healthy donors to prevent infections or to treat protracted infections in immunocompromised patients.  

Cellular therapy is a ‘living drug’ made of T cells that multiply within the patient, actively seek their target, and eliminate it. Cellular therapy is different from convalescent plasma, which contains antibodies but not T cells.

Right now, our lab is developing a T cell product, which we will be testing very shortly here at NewYork-Presbyterian/Columbia University Irving Medical Center, that targets adenovirus, CMV, EBV, and BK viruses—the viruses that commonly affect bone marrow transplant recipients. These virus-specific T cells are naturally present in healthy donors and can be expanded to large numbers in the laboratory. The idea is to rapidly reconstitute the patient's protective immune repertoire soon after transplant, when they are most vulnerable to infections. The treatment could serve a patient throughout his or her entire life.

We are also thinking about adding T cells that target common respiratory viruses and SARS-CoV-2 to our mixture. Ideally, it would be given to early post-transplant patients and could also be used to treat immunosuppressed patients with prolonged COVID infections.

An alternative is to have a bank of cryo-preserved T lymphocytes from healthy donors who were exposed to or vaccinated against SARS-CoV-2. We could potentially use those cells off the shelf as a treatment for patients with severe infections who are unable to clear the infection because of an underlying immune defect.

What can immunocompromised patients do to protect themselves against COVID? 

Immunocompromised patients, particularly those who have comorbidities, should absolutely go get the vaccine. Some immunocompromised patients actually do generate antibodies and have a good immune response. But they should realize they might not have the same degree of protection from the vaccine as the general population. And that applies to many other viral infections.

Giving immunocompromised patients an extra vaccine dose, or temporarily backing off from immunosuppressive medication when possible, may be a very reasonable strategy for now, since we still don’t know whether antibody or T cell response may be more important.

In addition, all immunocompromised patients should take common-sense precautions to protect themselves against COVID, such as avoiding overcrowded areas and indoor dining, practicing hand hygiene, encouraging others around them to get vaccinated, and staying away from people with respiratory symptoms, even in the family setting. Wearing masks might also benefit vulnerable patients.