Cancer patients. Organ transplant recipients. Individuals with HIV. Those with autoimmune or chronic inflammatory conditions such as lupus, multiple sclerosis and rheumatoid arthritis.
But even though the coronavirus vaccines authorized for emergency use by the Food and Drug Administration are considered safe for people with compromised immune systems, they may not work as well, or at all, for some Americans. Even those who do make antibodies have expressed concern about them waning, particularly as the highly transmissible delta variant has become the dominant strain in the United States. Indeed, a small study in Israel showed that about 40 percent of the 152 breakthrough infections that resulted in hospitalization were in people with compromised immune systems.
That’s why public health authorities have been working to understand more about vaccine effectiveness within the immunocompromised community and how to protect the most vulnerable. In fact, the Centers for Disease Control and Prevention now recommends a third dose of the two-dose messenger RNA vaccines — Pfizer-BioNTech and Moderna — for people who are moderately to severely immunocompromised.
I’m immunocompromised. Will the vaccines work for me?
No one knows yet for certain, and it will probably depend on a number of factors — the individuals, the illnesses and which immune-suppressing treatments are involved in their care.
U.S. clinical trials did not specifically study the effectiveness of the coronavirus vaccines in people with compromised immune systems, so there is not yet conclusive data to show how they will ultimately respond. But early research seems to suggest it will be a mixed bag — that although some immunocompromised individuals may make antibodies, others may not. And for those who do, it is not known whether the antibodies will be effective at neutralizing SARS-CoV-2, what level of antibody will be needed to protect against infection or how long the antibodies will last.
Many of these questions remain unanswered for the general population, as well.
Ghady Haidar, an infectious-diseases physician at the University of Pittsburgh Medical Center who specializes in organ transplant recipients, said he and his team studied immune responses in blood-cancer patients who received both doses of one of the mRNA vaccines and discovered that 46 percent of them did not produce any antibodies against covid-19. Haidar has since led a subsequent study showing that the vaccine-induced antibodies varied depending on the type of underlying immune system issue.
“These were expected results, as disappointing as it is,” Haidar said of the findings.
Similarly, a research letter that was published in JAMA found that 46 percent of 658 transplant patients did not mount an antibody response after completing either the Pfizer or Moderna vaccine series. And some research suggests that some treatments may impact immune responses. One preprint showed that patients with chronic renal insufficiency who were on hemodialysis had less vaccine-induced immunity.
Haidar said each flu season, he urges his cancer and transplant patients to get the flu shot, telling them that although it’s “probably not going to work as well as with someone with a healthy immune system, it might soften the blow.”
“My hope is the same will hold true for covid-19,” he said.
All of that said, some early studies are showing that, for some patients, the vaccines are producing antibodies.
In fact, a study out of Mount Sinai’s and New York University’s medical schools documented detectable antibodies in inflammatory bowel-disease patients who received at least one dose of either the Pfizer or Moderna vaccines.
Charlotte Cunningham-Rundles, an immunologist at the Icahn School of Medicine at Mount Sinai who was not involved in the previously mentioned study, said she has also seen an immune response in some of her patients after coronavirus infection and vaccination. Cunningham-Rundles treats many patients with congenital immune-system deficiencies.
However, she said, a “big caveat” to her observations is whether the detected antibodies are capable of fighting infection and for how long they will be able to do the job.
These are reasons why the Food and Drug Administration amended its emergency use authorizations to include a third mRNA dose for immunocompromised individuals. The CDC now recommends that people who are moderately to severely immunocompromised — including those being treated for certain cancers, those who have received an organ transplant and those who have chronic medical conditions that can weaken immune responses — get a third shot at least 28 days after completing the initial two-dose mRNA series.
There is no need to get a prescription. Those who are immunocompromised simply have to attest that they have compromised immune systems.
Health experts said it is a common practice to give immunocompromised patients additional doses or higher doses of a vaccine to try to generate a stronger immune response, and research has shown that such patients can develop increased antibodies after a third shot of the coronavirus vaccines. A paper published in the New England Journal of Medicine found that organ transplant recipients who took both doses of the Moderna vaccine had “substantially higher immunogenicity” — meaning an effective immune response — after a third shot.
As with most vaccines, it is hard to say exactly how much more protection the extra coronavirus shot will provide as it will vary from patient to patient. But the third dose is likely to give many a boost, said Monica Gandhi, an infectious-disease expert who works with HIV patients at the University of California at San Francisco.
That said, antibodies don’t tell the whole story, Gandhi said.
In a healthy immune system, the coronavirus vaccines prime the immune system to recognize the spike protein — the proteins found on the surface of the coronavirus — by producing antibodies and memory cells. These memory cells, which are white blood cells, are known as memory B cells and protective T cells. And when the immune system later detects coronavirus in the body, the immune system stimulates these memory cells to respond — B cells start making more antibodies, while T cells work to attack and kill the virus.
In immunocompromised individuals who make at least some antibodies from the vaccines, memory B cells can still serve as the blueprint to produce more antibodies when needed, but even those who do not make antibodies at all may still benefit from protective T cells, Gandhi said.
“Antibodies are only one part of our protective armor against covid-19 after vaccines,” she said.
So how will I know whether the vaccine has done its job?
There’s no way to know for sure.
Yes, there are antibody tests. But the tests vary in the types of antibodies they detect, and even when they do detect antibodies, it’s not that informative, because experts do not yet know the level of antibody needed for protection against the coronavirus.
That’s why health authorities and many medical experts agree antibody testing for assessing immunity post-vaccination is not recommended. “And it really doesn’t change the makeup of what you’re going to do next,” said Gauri Varadhachary, a professor of gastrointestinal oncology at MD Anderson Cancer Center.
Haidar, at the University of Pittsburgh, acknowledged that “it’s frustrating for people.”
“I know patients want to be tested, and there are doctors who are also testing their patients. I get it — I do,” he said. “But the issue then becomes: ‘Well, what do we do now?’”
“I worry that if immunocompromised people are antibody positive, they might be infused with a false sense of overconfidence. And if they’re antibody negative, what do you do? I know that many patients are panicking when they realize that the vaccine ‘did not take,’” he added.
Without being able to offer more to immunocompromised patients right now, Haidar said, “I personally think that, for now, we should restrict post-vaccine antibody monitoring to studies, so that we can understand this better.” But, he said, assuming health authorities change their recommendation down the line, “we can certainly change our practices then.”
What more can I do to protect myself against the virus?
Health experts agree that most immunocompromised people should still get vaccinated, because, to recap, many may make protective antibodies, though some may need a third shot. And others may still achieve protection from the cellular side of the immune system as it is revved up by the vaccine.
It may also be necessary to work with treating physicians to balance the timing of the shots with any immune-suppressing treatments such as chemotherapy or other medications for underlying illnesses.
But even after vaccination, health experts said, those with immune system deficiencies should still be cautious — continuing with frequent hand-washing, mask-wearing, social distancing and also choosing the types of gatherings that are the safest for them, particularly in areas that have higher transmission rates.
For those who are exposed to the virus, there are laboratory-designed monoclonal antibodies, which have been used to treat patients with active covid-19 infections. But one manufacturer, Regeneron, recently announced that it has received FDA authorization to be used prophylactically in people who have been exposed and are at high risk of developing a severe covid-19 infection, including those who “are not expected to mount an adequate response to vaccination.”
Still, it’s not all about what immunocompromised patients can do to protect themselves from covid-19; it’s also about those around them.
“Every vaccine that goes into the arm of someone — anyone — is more protection for these people who aren’t able to build a full response to vaccination,” said Erin Longbrake, a neurologist at Yale New Haven Hospital who specializes in neuro-immune diseases. “So as many healthy people who get vaccinated, that’s one fewer person who can pass covid on to these more vulnerable people.
“Everyone needs to get vaccinated, so we can protect those who can’t protect themselves.”