Immunocompromised and Getting the COVID-19 Vaccine

COVID-19 vaccination is safe, and everyone should take advantage of whatever level of protection it offers, experts agree. However, when your immune system is compromised, the vaccine may not work as well.

People with weakened immune systems due to certain types of cancer treatment and transplant regimens face reduced vaccine effectiveness. But they may still reap some benefit from COVID-19 vaccination, emerging studies show. For these patients, it's important to discuss vaccination details with their doctors and continue to use infection-prevention measures like masks.

In addition, those with autoimmune diseases like rheumatoid arthritis should consult with their doctors about vaccination timing and extra precautions. The Centers for Disease Control and Prevention and medical associations like the American College of Rheumatology provide more guidance.

The most encouraging news is that two large groups -- older adults and pregnant women -- are responding extremely well to COVID-19 vaccination. Although age and pregnancy may weaken the immune system somewhat in general, they don't seem to hamper vaccine effectiveness.

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Cancer Survivors

Patients with active cancer and those on cancer treatment are a high-priority vaccination group, according to recommendations from the National Comprehensive Cancer Network's COVID-19 vaccine committee. Vaccination will not affect their cancer treatment.

However, those receiving certain aggressive cancer treatments, such as undergoing stem cell transplants or CAR-T therapy, should delay vaccination while their immune systems are the most suppressed, according to the National Cancer Institute's Cancer Currents blog.

"COVID-19 vaccines are not live viruses," says Dr. Ghady Haidar, director of research, bone marrow transplant and hematological malignancy infectious diseases at University of Pittsburgh School of Medicine in Pennsylvania. Therefore, he says, people who are immunocompromised because of their cancer or treatment are safe in that regard.

Instead, Haidar says, vaccine effectiveness is the big concern, for instance with patients with hematologic malignancies: cancer of the blood, bone marrow or lymph nodes.

"They're not going to work as well, which is something that we suspected just because of what we know about other vaccines in immunocompromised patients," he says. "And common sense indicates that if your immune system is weak, you're just not going to respond to an intervention which is meant to trigger your immune system."

In a study by Haidar and colleagues, among 67 patients with hematologic cancers who completed the two-vaccine series for COVID-19, nearly half (46%) did not produce antibodies and were considered vaccine nonresponders. Patients with chronic lymphocytic leukemia -- the most common type of blood cancer in adults -- had the least response, with only about one-quarter (23%) with detectable antibodies, in the preprint study released online April 7.

"The key point here is that this is totally different from the signal we saw in healthy volunteers, in which 100% developed antibodies after receiving their COVID-19 vaccines," Haidar says.

Although vaccination is still recommended, timing nuances come into play with different groups of immunocompromised patients, he notes. Medical societies around specific diseases have offered provisional recommendations to address timing.

It's possible that vaccinated people who are immunocompromised yet still come down with COVID-19 may have less severe illness than they otherwise would have. "That's the hope -- that it'll soften the blow," Haidar says.

With clearly less protection from COVID-19 after vaccination, "We're advising everyone who's immunocompromised to please continue masking and social distancing, regardless of the vaccine," Haidar says. "And just make sure that everyone in your bubble is vaccinated so that you can reduce your risk of developing COVID-19 as much as possible."

Transplant Patients

"At this point -- for all immunocompromised people -- we want them to get vaccinated," says Dr. Kathleen Mullane, an infectious disease physician specializing in immunocompromised patients with University of Chicago Medicine. "But we want to make sure when they get vaccinated they get the best response."

Transplant patients must take powerful drugs that suppress the immune system to reduce the risk of graft rejection -- the body's immune system attacking the donor organs or cells. The type of transplant they're getting -- a solid organ such as a heart or lung transplant versus a liquid transplant like a stem cell transplant -- is another factor to consider.

"Usually, we will wait on our solid organ transplant patients for a least three months," Mullane says. "That's because when they get their transplants, they get a ton of immunosuppression, or high doses of immunosuppression in the operating room and early on after the transplant to prevent rejection. Then, that slowly wears off and we moderate their doses based on how the organ is functioning itself."

Stem cell transplant patients require additional caution as treatment wipes out their bone marrow, which plays an important role in the immune system. The standard wait for COVID-19 vaccination is about six months, Mullane says.

Graft-versus-host-disease can occur if the donor bone marrow or stem cells attack the patient from within. Some patients get extremely sick with severe GVHD and require even more treatment to suppress the immune system.

"When they have graft-versus-host disease they end up being on a lot more steroids," Mullane says. And, unfortunately, she says, some patients may have a relapse of their leukemia or other cancer. "If something like that happens, then we would hold off on the vaccines until we knew their immune system was in a little bit better shape."

Once transplant patients receive the COVID-19 vaccine, their response is reduced compared with that of healthy people. "Depending on the studies that you're looking at, none to maybe 25% to 30% of people will have an immune response to the first dose" with the COVID-19 vaccine, Mullane says. "Then it goes up a little bit after the second dose -- up to maybe 50% of what we would expect in someone who's not immunocompromised."

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The two-dose mRNA vaccines might be a better choice for the transplant population, Mullane says. "Looking at something like Moderna or Pfizer, where there's a boost dose after the first one, you're going to get a better response. So, where it may not be so important in someone whose immune system is in good shape, it'd be more important in these people."

In a Johns Hopkins study of following 658 solid organ transplant recipients after having both first and second dose of the COVID-19 vaccine, 15% of participants had a measurable antibody response after each dose. A significant proportion -- nearly 40% -- who had no antibody response after the first dose did develop an antibody response after the second vaccine, in the study published in the June 1 issue of JAMA.

The way that COVID-19 vaccination response is currently measured is another factor. The most commonly used tests only take part of the body's immune system activity -- antibody response -- into account.

However, "there are two arms of the immune system," Mullane points out. One is the antibody or humoral immune system. The other arm is cell-mediated immunity, in which T-cells fight cancer in different ways.

A recent study evaluated immune response in 48 lung transplant recipients who received COVID-19 vaccination before transplant. Of the 12 patients who did not have a measurable antibody response to vaccination, four patients did have significant T-cell responses.

"Some patients might therefore have clinical benefit from the vaccine despite an absent antibody response," concluded authors of the study published in May in the Journal of Heart and Lung Transplantation.

Large-scale data on people with autoimmune conditions or immune-compromising treatment is still emerging. "Whenever we do clinical trials, we do well people first, then we do kids, and pregnant ladies and people who are at risk of getting pregnant," Mullane explains. "And then we start looking at the subpopulations like cancer patients, leukemia patients and transplant patients."

With reduced vaccine effectiveness, extra precaution against COVID-19 is essential even after completing the vaccine series, Mullane also emphasizes. "We still want our transplant patients to practice safe behaviors -- stay 6 feet away from everybody, wear masks, wash their hands and not go into crowds," she says. "We're still more careful with them than the general population."

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Pregnancy

Vaccination for COVID-19 elicits immune responses in pregnant and breastfeeding women, according to a study published May 13 in JAMA. And vaccination during pregnancy appears to provide an extra benefit for babies in the womb.

Among 103 women participating the JAMA study, including 30 pregnant and 16 lactating women, all developed an immune response after receiving either of the mRNA (Pfizer or Moderna) COVID-19 vaccines, in a study led by Dr. Ai-ris Collier, a maternal-fetal medicine specialist at Beth Israel Deaconess Medical Center.

In addition, women developed two types of immune responses -- antibody and T-cell responses -- against two coronavirus variants of high concern, found researchers led by Collier as a physician-scientist in the laboratory of Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at BIDMC.

Vaccine antibodies were found to pass into infants' cord blood and breast milk. "Basically, when you get vaccinated during pregnancy, you get the passage of maternal antibodies into the fetal and newborn circulation, which may be protective," Collier says. "At this point, we don't have available vaccines for newborns. So this may be one of the only way of offering protection for newborns."

As a maternal-fetal medicine specialist, Collier is highly aware of the importance of protecting pregnant women. "Certainly in my practice, I've seen a fair amount of adverse outcomes in women who are infected with COVID-19," she says. "In thinking about the mom's health, you have to use effective strategies to prevent severe disease in the mom, which could also have adverse effects for the fetus."

Growing evidence makes the vaccination decision easier, Collier says. "Early on, there was a lot of hesitancy because of the lack of data for this vaccine in pregnancy," she says. But now the picture is clearer.

"At this stage there is great data on the safety in pregnancy, based on the first 30,000 women pregnant women in the U.S. who took it -- with no adverse effects on pregnancy loss or stillbirths, or other adverse consequences," Collier emphasizes. "That's along with our (study) and others demonstrating that the immune response is really great, and leads to higher antibody responses than even infection does."

On June 1, the National Institutes of Health's NIH Director's Blog hailed the safety and effectiveness of COVID-19 mRNA vaccines for pregnant women. Along with the BIDMC study, it highlighted a May 11 study of 84 women who were vaccinated during pregnancy and showed a "robust" response, producing effective levels of virus-neutralizing antibodies.

Older Adults

When the COVID-19 vaccine first became available in early December and supplies were still scarce, older adults were among those prioritized to receive it, because they were at higher risk of having severe disease or dying from the virus. For them, vaccination has been a huge success story.

With advanced age, the immune system naturally weakens, a phenomenon called immunosenescence. Fortunately, COVID-19 vaccination provides strong protection for older adults.

"We were overwhelmingly happy when we saw how immunogenic these COVID-19 vaccines were," in older adults, Mullane says. "To see 94% or 95% efficacy is just amazing," Mullane says. By contrast, she notes the roughly 50% efficacy that yearly flu vaccines tend typically provide.