Transplant Recipients Remain Vulnerable to COVID-19 After Vaccination

Nancy A. Melville

May 13, 2021

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Dr Brian Boyarsky

Solid organ transplant recipients who receive two doses of the mRNA SARS-CoV-2 vaccine show detectable antibody responses that are higher than the levels observed after 1 dose, but the levels are still notably lower than those seen in people who are not immunocompromised, new research indicates.

"It is highly concerning that only a little over half the population developed antibodies to the vaccine because we know in healthy people, it's nearly 100%," lead author Brian Boyarsky, MD, PhD, a research follow in the Department of Surgery at Johns Hopkins University School of Medicine, in Baltimore, Maryland, told Medscape Medical News.

"The take-home message from this is that transplant recipients and certain other immunocompromised people should not assume immunity after vaccination."

The study was published online May 5 in JAMA.

Immunocompromised Patients Excluded From COVID-19 Vaccine Trials

Evaluation of the effects of the SARS-CoV-2 vaccine in solid organ transplant recipients is especially important given that they and other immunocompromised people were generally excluded from COVID-19 vaccine trials.

"In general, transplant recipients have a slightly blunted response to vaccination, but this was a novel mRNA platform, so we just didn't know how these vaccines would work in these patients," Boyarsky explained.

In a previous study, Boyarsky and his team found that most solid organ transplant recipients failed to show appreciable antibody responses to the first dose of the vaccine.

To investigate responses after the second dose, the researchers evaluated data on 658 transplant recipients from across the United States who received two doses of the Pfizer or Moderna SARS-CoV-2 mRNA vaccine between December 2020 and March 2021.

Participants included 396 from the previous study of the first dose.

At a median of 21 days following the first dose, antibodies were detectable in 15% of participants.

After a median of 29 days following the second dose, only 54% of participants had detectable antibodies.

In a further dissection of the results after two doses among all 658 patients, only 15% had measurable antibody responses after dose 1 as well as dose 2, 46% had no antibody response after either dose 1 or dose 2, and 39% who had no antibody response after dose 1 did show a response after dose 2.

Type of Immunosuppression Impacts Response to Vaccine

Among 473 of the patients receiving immunosuppressive treatment with antimetabolites, only 8% had an antibody response after dose 1 and dose 2; 57% had no antibody response after either dose 1 or 2, and 35% had no antibody response after dose 1 but did show a response after dose 2.

Of 185 patients who were not treated with antimetabolites, the results were better, with 32% having a response after both doses, 18% with no response after dose 1 or 2, and 50% with no response after dose 1 but antibodies after dose 2.

Despite the fact that immunocompromised people tend to have lower responses to vaccines in general, the degree of the reduced effect among patients overall was unexpected, Boyarsky told Medscape Medical News.

"What surprised us was the magnitude of the decreased immunogenicity in these patients," he said.

"To us, this means that clearly there's some interplay between the transplant immunosuppression and perhaps the underlying diseases or comorbidities that the patients have that renders these vaccines less immunogenic in our populations."

With kidney transplant representing most transplant recipients across the United States, these patients were slightly over-represented in the study, Boyarsky noted.

"However, the results were more related to the immunosuppressive regimen than the type of transplanted organ," he emphasized.

Potential options for improving antibody responses could be the addition of a booster shot or the potential modification of immunosuppressive regimens in some cases.

"That's something that would have to be done in a very careful manner because these immunosuppressive drugs obviously are very important for the transplant recipients to...prevent their bodies from rejecting the organs," Boyarsky explained.

He underscored, however, that the findings do not necessarily suggest that transplant patients get no protection from the vaccines, and, considering their higher risk of serious effects from COVID-19, patients should nevertheless be vaccinated.

"Just because we're not detecting robust antibody responses to vaccination doesn't mean that there aren't other cells at play in the immune system, for example T cells or memory B cells, that may contribute to some level of immunity or protection from severe disease. We also recommend family members and social networks of transplant recipients also absolutely get vaccinated to help protect the most vulnerable members of society."

Boyarsky has reported no relevant financial relationships.

JAMA. Published online May 5, 2021. Full text

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