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Preventing SARS-CoV-2 infection in immunocompromised people hasn't gotten any easier as the pandemic trundles on into its fifth year.

The monoclonal antibody tixagevimab-cilgavimab (Evusheld) has long gone by the wayside for pre-exposure prophylaxis and no replacements are on the horizon. Other prevention strategies among the general population, such as mask-wearing, have all but disappeared.

Vaccination against SARS-CoV-2 is now the key prevention strategy for this vulnerable population, and people who are immunocompromised should still get COVID boosters -- but, given that they are less likely to generate an adequate immune response to the vaccines, the question is: how often?

"We really have a very confusing, complex black box of problems," Catherine Diefenbach, MD, a hematologist-oncologist at NYU Langone Health in New York City, told 番茄社区app. "Different people are immunocompromised in different ways. You have people with autoimmune disease who are compromised. You have people with organ transplants who are compromised. You have the elderly who are immunocompromised, and you have malignancy patients who are immune compromised."

The most vulnerable among the immunosuppressed are people receiving treatment for cancer, especially with B-cell-depleting therapies, those who have received organ transplants who must remain on immunosuppressive medications indefinitely, and people living with HIV. People who must take medications like steroids or methotrexate to manage autoimmune conditions are also at risk for more severe disease from SARS-CoV-2 infection.

Keep It Simple

Of three clinicians who treat moderately to severely immunocompromised patients and spoke with 番茄社区app, all of them offered a similar recommendation: people who are immunocompromised should get a COVID vaccine about every 6 months, with the caveat that intervals between vaccine doses should be tailored to individual patient needs.

"We know that immunity drifts down, wanes over time," said Camille Kotton, MD, an infectious disease specialist at Massachusetts General Hospital in Boston. "So it seems like a good idea to keep boosting [every 6 months] and keep immunity as high as possible. Unfortunately, vaccines are still not as protective against severe disease as we would like in the immunocompromised, but it's certainly much better to be vaccinated than not."

Dorry Segev, MD, PhD, a transplant surgeon at NYU Langone Health, told 番茄社区app that "every 6 months is probably reasonable for most people who are immunocompromised."

However, he occasionally takes a more individualized approach, depending on the patient's exposure to high-risk situations, such as those who anticipate being in crowded situations or have a good chance of being exposed to others with COVID. "Maybe that person would consider getting boosted every 3 months," he said.

Diefenbach noted that for people with compromised immunity, she would recommend getting boosted "no more than every 6 months." Immunity from the vaccines tends to peak at 3 to 4 months, and then drops off, she added, and multiple vaccinations have not been shown to be more beneficial, indicating that more frequent vaccination is probably unnecessary.

What if the patient gets COVID and recovers? Should they stay on the every-6-months schedule? "You can wait 3 months to get another dose of vaccine" after infection, Kotton said of her approach. "There it is ... don't make it complicated."

Checking Antibody Levels, Neutralization Assays Not Recommended

Segev said that in the early days of the pandemic, "there was a time where I felt that checking antibody levels was really important" for immunocompromised patients, "and that we could use those to guide, on an individual level, when it's time for a booster -- who needed three doses, who needed four doses."

However, those days are gone. Antibody levels are, in general, not considered useful anymore because of the fact that most people now have some level of antibodies to the SARS-CoV-2 virus, either from natural infection or vaccination, and neutralizing antibody assays are not recommended to assess vaccine response, he said.

One overlooked problem, Kotton pointed out, is that immunocompromised people are typically excluded from vaccination trials, and as a result, "we don't know how to best protect them."

She said that although the CDC recommends against checking antibody titers in clinical practice, the FDA accepts immunobridging data that rely on neutralizing antibody titers as markers for how well COVID vaccines work. "There's mixed messaging," she noted, regarding whether such testing is useful or not.

Individuals who are immunocompromised are not a small group. A recent showed that an estimated 6.6% of U.S. adults reported that they were immunocompromised -- over double the oft-cited percentage of 2.7% to 3%. This percentage may have increased in recent years due to wider use of immunosuppressive therapies or a general increase in awareness of conditions.

What Does the CDC Say?

A found that, as of Aug. 6, 2022, only 41% of immunocompromised individuals enrolled in a large U.S. integrated delivery network had received four doses of mRNA COVID vaccine, and only 1% had received the recommended five doses.

Vaccine hesitancy wasn't at play, the authors concluded. Rather, they posited that the complexity of COVID vaccine recommendations for immunocompromised individuals had probably "caused confusion among both the lay and medical communities" about when they should be receiving boosters.

In a nutshell, the CDC has stuck to in people who are moderately to severely immunocompromised. According to their recommendations, everyone ages 6 months and older who is moderately or severely immunocompromised should get at least one dose of a 2023-2024 updated COVID vaccine, but depending on the number of doses previously received, they may need more than that one dose of updated vaccine.

Notably, the CDC also advises that people who are immunocompromised and 65 and older who received one dose of any updated 2023-2024 COVID vaccine should receive one additional dose of the vaccine at least 2 months after the previous updated dose.

Roy Chemaly, MD, MPH, an infectious disease specialist at the University of Texas MD Anderson Cancer Center in Houston, told 番茄社区app that, anecdotally, he has not seen vaccine hesitancy or fatigue among immunocompromised patients.

"I think patients want to get vaccinated, but unless it is recommended by their physician, they may not think about it," he said. "So we need to remind our providers that they need to still keep reiterating the value of vaccines."

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