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October 18, 2021

Vaccines can't fully protect the immunocompromised. Will they ever be safe against Covid-19?

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    Several studies suggest many immunocompromised people are not adequately protected after being vaccinated against Covid-19—but monoclonal antibody treatments may be an effective alternative to help immunocompromised people build immunity.

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    The immunocompromised are among the most vulnerable to Covid-19

    An estimated 3.6 million immunocompromised Americans with a wide range of conditions, including organ transplants, autoimmune disorders, and cancer, are at an increased risk from Covid-19, Slate reports. For example, a study published in CDC's Emerging Infectious Diseases found that immunocompromised patients may experience longer cases of Covid-19 if they are infected.

    "What happens for some of these immunocompromised folks is that they can't really fight off this new virus that hits them, and so, they end up having the infection for a longer period of time," Brad Pollock, the associate dean for public health sciences at the University of California, Davis, said. "In this case, quite a long period of time. There was evidence of viral replication going on for many, many weeks."

    In addition, Covid-19 vaccines may produce mixed results in immunocompromised people, with some having a reduced or no immune response after vaccination, Slate reports.

    For example, three small studies from the Bambino Gesu Hospital in Rome found that an average of 30% of immunocompromised patients did not develop immunity to the coronavirus after vaccination. While the remaining 70% were able to produce an immune response, particularly after a second dose, the response was lower compared to that of healthy people and varied among the participants.

    A separate pair of studies published in JAMA found that only half of kidney transplant recipients produced an antibody response after a second dose of an mRNA vaccine. And a small study of 12 transplant patients who received Johnson & Johnson's Covid-19 vaccine found that only two produced antibodies.

    Because of this, many immunocompromised patients remain vulnerable to Covid-19 even after vaccination. According to a study in the journal Transplantation, transplant recipients are 82 times more likely to get a breakthrough infection and 485 times more likely to be hospitalized or die from Covid-19.

    Additional vaccination is recommended, but it may not be enough

    Currently, CDC and the World Health Organization (WHO) recommend immunocompromised people receive an additional dose of a Covid-19 vaccine to further bolster their immunity and prevent breakthrough infections.

    WHO's Strategic Advisory Group of Experts on Immunization said additional doses should be administered "as part of an extended primary series since these individuals are less likely to respond adequately to vaccination following a standard primary vaccine series and are at high risk of severe Covid-19 disease."

    However, some research suggests that an additional vaccine dose may still not be enough to produce immunity in some immunocompromised patients. For example, two separate studies found that only a third of transplant recipients produced antibodies in response to a third dose after failing to do so after a second shot.

    According to Dorry Segev, director of the Epidemiology Research Group in Organ Transplantation at Johns Hopkins University, at least 1 million immunocompromised people will need further protection against Covid-19 than just the vaccines.

    Although healthy vaccinated people will largely be protected even if they do get infected, "many immunocompromised people will have to put their entire lives on hold again, or risk death," Segev said.

    Antibody treatments might help the immunocompromised build immunity

    According to Slate, a promising potential alternative to vaccines to provide a degree of immunity to immunocompromised patients is monoclonal antibody treatments.

    Antibody treatments are often used to treat Covid-19, but they can also be used to prevent infection in immunocompromised people after they have been exposed to the coronavirus, Slate reports. According to Lindsay Ryan, a physician at the San Francisco VA Medical Center, monoclonal antibodies stand in for the ones immunocompromised people are not able to produce on their own after being vaccinated.

    In a study of immunocompromised patients who had a Covid-infected household member and no evidence of a past or current coronavirus infection, Regeneron's antibody treatment reduced the risk of symptomatic infection by 81%.

    Antibody treatments may also soon be used as routine prevention for immunocompromised people, not just after exposure, Slate reports. AstraZeneca earlier this month applied for emergency use authorization of a long-acting antibody drug to prevent Covid-19 in high-risk populations. The drug was 77% effective against symptomatic infection among high-risk participants, and researchers hope it will offer protection for up to a year after being administered.

    However, Emily Blumberg, the director of transplant infectious diseases at the University of Pennsylvania's Perelman School of Medicine, said logistical issues may make it harder for immunocompromised patients to access antibody treatments. In particular, sites where the treatment can be administered are limited, and immunocompromised people will need to receive the treatment separately from Covid-19 patients.

    In addition, the federal government has taken over distribution of monoclonal antibodies to prevent shortages following a surge in demand—primarily from unvaccinated Covid-19 patients. According to Slate, this has made it harder for immunocompromised patients to access the treatment.

    "It's terrible that the immunosuppressed, who are vulnerable and desperate and doing anything they possibly can to seek protection, would be denied the only protective avenue that they have because people are refusing the vaccine, acting recklessly, getting infections, and then soaking up the monoclonal antibodies," Segev said. "That's a disappointing thought for me." (Requarth, Slate, 10/12; Ryan, Slate, 10/12; De La Cruz, KCRA 3, 10/5; Parodi, Reuters, 10/4; Nebehay/Farge, Reuters, 10/11)

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