April 20, 2021

The high-risk group for whom Covid-19 vaccines may not work effectively

Daily Briefing

    Though highly effective for most adults, the available coronavirus vaccines often cannot produce enough infection-fighting cells among the millions of Americans with weakened or suppressed immune systems. Here's what that means for immunocompromised people—and the alternative treatments researchers are exploring.

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    For immunocompromised, vaccines have weaker effect

    People who are immunocompromised include those who were born without a functioning immune system or with a "faulty" one, the New York Times reports. It also means those who have been immunosuppressed because of a disease or treatment for a disease—including people with blood cancers or autoimmune conditions, such as rheumatoid arthritis or lupus; or those who have received organ transplants.

    According to the Times, immunocompromised people are more likely to fall ill with Covid-19—and to remain ill for an extended amount of time, with a higher risk of death. In addition, many produce "few to no antibodies in response to a vaccine or an infection."

    For instance, one study found that of nearly 7,000 patients who had Crohn's disease and ulcertative colitis, fewer than 50% of those who were taking Remicade as treatment mounted an immune response following a coronavirus infection. Further, in follow up to that study, the researchers found that just 34% of people on the drug were protected after one dose of the Pfizer/BioNTech vaccine, and just 27% were protected after a single dose of the AstraZeneca vaccine.

    Another study found that fewer than 15% of patients who had blood or immune system cancers—and fewer than 40% of patients with solid tumors—produced antibodies after receiving a single dose of the Pfizer/BioNTech vaccine. And in a third study, researchers were not able to detect antibodies in about 46% of blood-cancer patients who had received both doses of the Pfizer/BioNTech vaccine or the Moderna one. 

    Because of this limited protection, doctors generally advise that immunocompromised patients continue to adhere strictly to other preventive measures, such as limiting their time in crowds, regular hand washing and mask wearing, and social distancing.

    "Get vaccinated, but behave as though you're not," Dorlan Kimbrough, a neurologist who treats multiple sclerosis patients at Duke University, said.

    'Everybody should try to get the vaccine'

    Despite the potentially limited efficacy of the vaccines among immunocompromised patients, doctors generally encourage this population to get vaccinated. There are no additional safety concerns for this population getting the vaccine, and even partial or limited protection can help prevent more serious infections if they do fall ill.

    "The take home message is that everybody should try to get the vaccine," Amit Verma, an oncologist at Montefiore Medical Center, said.

    That said, for those who are immunocompromised, researchers recommended thinking carefully about when to get vaccinated so as to leverage the immune function they have, The Atlantic reports.

    For instance, physicians think people who are taking the Crohn's disease drug ustekinumab, or Stelara, can continue that medication on schedule while receiving a vaccine injection, because that drug has a fairly narrow effect on the individual's immune system. But patients taking the drug rituximab, or Rituxin—used to treat conditions such as rheumatoid arthritis and certain blood cancers—should carefully schedule their vaccines around their ongoing treatment, since that drug essentially wipes out a person's antibody-producing B cells for up to six months at a time.

    According to The Atlantic, physicians also recognized that certain people—including some who have autoimmune diseases, those who have received an organ transplant, and those in the midst of chemotherapy—do not have the flexibility to postpone treatment. Those people, Chaitra Ujjani, an oncologist at the Seattle Cancer Care Alliance, said, will need to prioritize their current treatment regimens and "just get the vaccine when [they] can."

    Alternative treatments

    According to the Times, researchers are studying alternative treatments for immunocompromised patients who do not respond to the vaccines and must to wait until herd immunity is achieved.

    One such treatment is monoclonal antibody infusions, the Times reports, "mass-produced copies of antibodies obtained from people who have recovered from Covid-19."  According to the Times, several of these monoclonal antibody treatments have been authorized by FDA as treatments for Covid-19, but some are now being tested to see if they can help prevent infection as well.

    Other treatments include convalescent plasma or gamma globulin, antibodies distilled from the blood of healthy donors, according to the Times. However, a version of gamma globulin which includes coronavirus antibodies "is still months from availability," the Times reports.

    And some researchers are exploring simply increasing the doses of the already authorized vaccines, The Atlantic reports.

    For instance, Ghady Haidir, a transplant infectious-disease physician at the University of Pittsburgh, said people who do not produce sufficient antibody levels when given the hepatitis B vaccine will sometimes receive a second, three-dose series of the vaccine. And Robin Avery, of Johns Hopkins University, said older people—whose immune systems are often not as productive as those of younger people—often receive higher doses of the flu vaccine to increase the odds it will kick-start their immune cells.

    Meanwhile, researchers are also investigating how different immunocompromising drugs—such as the many different drugs that can treat multiple sclerosis—interact with the coronavirus vaccines. They hope to identify the drugs linked to weak vaccine-induced immune responses and replace them with alternative options.

    Ultimately, however, "[i]t's a clear area of unmet need," said Hala Mirza, a spokesperson for Regeneron, which has made its monoclonal antibody treatment for Covid-19 available to certain immunocompromised patients via its compassionate use program.

    Neglecting to treat this population promptly could be dangerous, The Atlantic reports. This is because it means "entire swaths" of the population remain unprotected against the virus—making it hard to stop the virus's spread—and because the virus could mutate in those who remain ill for an extended amount of time.

    "This is how some variants emerged," Ali Ellebedy, an immunologist at Washington University in St. Louis, said (Mandavilli, New York Times, 4/16; Wu, The Atlantic, 4/15).

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