While the CDC now says people fully vaccinated against COVID-19 are safe to forgo their masks, an estimated 3 percent to 4 percent of Americans are living with immunocompromising conditions that may inhibit their ability to respond to the shots, leaving many uncertain about how they should approach the CDC's eased guidance.
Some experts, including CDC Director Rochelle Walensky, MD, have said COVID-19 vaccines may not be as protective for those with chronic health conditions.
At the same time, a wide range of conditions fall under the immunocompromised designation.
"Immunocompromised is just a huge bucket, and I think there's a big difference between people that are mildly immune-compromised, and people that are severely immune-compromised," said Jennifer Lighter, MD, hospital epidemiologist at New York City-based NYU Langone Health. "I'm pretty confident that the vaccines seem protective for people that are mildly immunocompromised. It's highly likely that they will get some protection from the vaccines," she told Becker's.
Those who may be severely immunocompromised include transplant recipients and people with certain cancers, with recent studies underlining their constant vulnerability to COVID-19 infection despite vaccination.
One such study found that among 658 organ transplant recipients who were fully vaccinated against COVID-19, 46 percent didn't demonstrate any antibody response. Even those who did have an antibody response had weaker responses compared to people with standard immune systems, the findings showed.
In a separate study, which is undergoing peer review, 46 percent of 67 patients with hematologic malignancies, or cancers that affect the blood, bone marrow or lymph nodes, did not produce antibodies a few weeks after receiving their second dose of the vaccine, according to an analysis led by researchers at the University of Pittsburgh School of Medicine and UPMC Hillman Cancer Center.
The same study, led by Mounzer Agha, MD, hematologist at UPMC Hillman Cancer Center, found that among 13 patients with chronic lymphocytic leukemia included in the analysis, just three produced measurable antibodies in the weeks after being fully vaccinated. That was particularly unexpected because those patients did not have symptomatic cancer.
"They're just being followed for smoldering disease, and they do not require therapy," Dr. Agha told Becker's. "So one would have expected them to mount an immune response [to the vaccine] and they did not."
While CDC officials have suggested fully vaccinated people with suppressed immune systems consult their physicians on how to navigate the updated guidance, the agency hasn't yet offered specific recommendations for the group.
In the absence of concrete guidelines, how should immunocompromised people who've been fully vaccinated interpret the guidance? The current evidence is enough to recommend remaining cautious, experts say.
"It's just prudent that people who are severely immunocompromised still be careful," Dr. Lighter said. "Don't attend crowded indoor activities, consider still wearing the mask even if vaccinated, try to surround yourself only with people that are vaccinated. It just is logical."
If a person is unsure whether they're mildly or severely immunocompromised, they should check with their clinician, she added.
Beyond that, there may be potential value in antibody testing after vaccination among immunocompromised patients, the physicians said. Currently, the FDA recommends against using antibody tests as a measurement of immunity after receiving the COVID-19 vaccine among the general public.
"I think the situation for immune-compromised patients and for blood cancer patients in particular is different because when they are receiving the vaccine, they are assuming they are immune while they are, in fact, still vulnerable to the infection and they have to continue to be careful," Dr. Agha said.
While they may add additional insight into a person's immune response, antibody test results shouldn't be a primary determinant on how immunocompromised patients should proceed, the physicians explained.
"Even if someone has a low antibody response, that doesn't mean they're not protected because there's so many immune cells that are important to fighting off COVID-19 that get stimulated with vaccination that are more than just antibody," Dr. Lighter said. "You have your T-cells, your memory B cells, your toll-like receptor cells. There are just many immune cells that respond to vaccination, so measuring antibodies is just a small piece of that."
In the same vein, results that show a high antibody response could give someone a false sense of security.
Additionally, the most common antibody test targets the N protein, which would not trigger a positive result after vaccination or infection.
"A lot of people don't realize they need to get an antibody test that targets the S protein. It is the S protein that would be positive after vaccination or infection," Dr. Lighter said. "I think there's a lot of confusion and that that should be specified."
For some cancer patients, depending on severity and stage of disease, pausing treatment is a way to allow their immune systems to best respond to the vaccine, Dr. Agha said.
"We have this discussion practically every visit because we have to decide if they are in need of active therapy," Dr. Agha explained. "And if they are, we have to do what's best for their disease, but if their disease is in a state where they can be allowed some time off from being treated and not compromise their immune system further, we tend to let them have a break from the treatment. That has to be judged on a case by case basis."
Among immunocompromised patients who don't mount an antibody response after receiving their final vaccine dose, administering a booster shot is another area to explore, as there's been a few anecdotal cases demonstrating a third booster injection increased antibody levels, Dr. Agha said.
"We need to run a clinical trial, and I would love to see that happening," he said.