Extra COVID-19 Vaccine Could Help Immunocompromised People

Laird Harrison

July 08, 2021

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People whose immune systems are compromised by therapy or disease may benefit from additional doses of vaccines against SARS-CoV-2, researchers say.

In a study involving 101 people with solid-organ transplants, there was a significant boost in antibodies after the patients received third doses of the Pfizer vaccine, said Nassim Kamar, MD, PhD, a professor of nephrology at Toulouse University Hospital, in Toulouse, France.

None of the transplant patients had antibodies against the virus before their first dose of the vaccine, and only 4% produced antibodies after the first dose. That proportion rose to 40% after the second dose and to 68% after the third dose.

The effect is so strong that Kamar and his colleagues at Toulouse University Hospital routinely administer three doses of mRNA vaccines to patients with solid-organ transplant without testing them for antibodies.

"When we observed that the second dose was not sufficient to have an immune response, the Francophone Society of Transplantation asked the National Health Authority to allow the third dose," he told Medscape Medical News.

That agency on April 11 approved third doses of mRNA vaccines not only for people with solid-organ transplants but also for those with recent bone marrow transplants, those undergoing dialysis, and those with autoimmune diseases who were receiving strong immunosuppressive treatment, such as anti-CD20 or antimetabolites. Contrary to their procedure for people with solid-organ transplants, clinicians at the Toulouse University Hospital test these patients for antibodies and only administer third doses of vaccine to those who test negative or have very low titers.

The Toulouse University Hospital findings, published on June 23 as a letter to the editor of The New England Journal of Medicine, come as other researchers document more and more categories of patients whose responses to the vaccines typically fall short.

A study at the University of Pittsburgh School of Medicine, in Pittsburgh, Pennsylvania, that was published as a preprint on MedRxiv compared people with various health conditions to healthy healthcare workers. People with HIV who were taking antivirals against that virus responded almost as well as the healthcare workers, said John Mellors, MD, chief of infectious diseases. But people whose immune systems were compromised for other reasons fared less well.

"The areas of concern are hematological malignancy and solid-organ transplants, with the most nonresponsive groups being those who have had lung transplantation," he told Medscape Medical News.

For patients with liver disease, mixed news came from the International Liver Congress (ILC) 2021 annual meeting.

In a study involving patients with liver disease who had received the Pfizer vaccine at Hadassah University Medical Center, in Jerusalem, Israel, antibody titers were lower in patients who had received liver transplants or who had advanced liver fibrosis, as reported by Medscape Medical News.

A multicenter study in China that was presented at the ILC meeting and that was also published in the Journal of Hepatology, provided a more optimistic picture. Among patients with nonalcoholic fatty liver disease who were immunized against SARS-CoV-2 with the Sinopharm vaccine, 95.5% had neutralizing antibodies; the median neutralizing antibody titer was 32.

In the Toulouse University Hospital study, for the 40 patients who were seropositive after the second dose, antibody titers increased from 36 before the third dose to 2676 a month after the third dose, a statistically significant result (P < .001).

For patients whose immune systems are compromised for reasons other than having received a transplant, clinicians at the Toulouse University Hospital use a titer of 14 as the threshold below which they administer a third dose of mRNA vaccines. But Kamar acknowledged that the threshold is arbitrary and that the assays for antibodies with different vaccines in different populations can't be compared head to head.

"We can't tell you simply on the basis of the amount of antibody in your laboratory report how protected you are," agreed William Schaffner, MD, professor of infectious diseases at Vanderbilt University Medical Center, in Nashville, Tennessee, who is also a spokesperson for the Infectious Diseases Society of America.

Not enough research has been done to establish that relationship, and results vary from one laboratory to another, he said.

That doesn't mean that antibody tests don't help, Schaffner said. On the basis of views of other experts he has consulted, Schaffner recommends that people who are immunocompromised undergo an antibody test. If the test is positive — meaning they have some antibodies to SARS-CoV-2, however low the titers — patients can take fewer precautions than before they were vaccinated.

But they should still be more cautious than people with healthy immune systems, he said, and added, "Would I be going to large indoor gatherings without a mask? No. Would I be outside without a mask? Yes. Would I gather with three other people who are vaccinated to play a game of bridge? Yes. You have to titrate things a little and use some common sense."

If the results are negative, such patients may still be protected. Much research remains to be done on T-cell immunity, a second line of defense against the virus. And the current assays often produce false negative results. But to be on the safe side, people with this result should assume that their vaccine is not protecting them, Schaffner said.

That suggestion contradicts the US Food and Drug Administration (FDA), which issued a recommendation on May 19 against using antibody tests to check the effectiveness of SARS-CoV-2 vaccination.

The studies so far suggest that vaccines are safe for people whose immune systems are compromised, Schaffner and Kamar agreed. Kamar is aware of only two case reports of transplant patients rejecting their transplants after vaccination. One of these was his own patient, and the rejection occurred after her second dose. She has not needed dialysis, although her kidney function was impaired.

But the FDA has not approved additional doses of SARS-CoV-2 vaccine to treat patients who are immunocompromised, and Kamar has not heard of any other national regulatory agencies that have.

In the United States, it may be difficult for anyone to obtain a third dose of vaccine outside of a clinical trial, Schaffner said, because vaccinators are likely to check databases and deny vaccination to anyone who has already received the recommended number.

Kamar, Mellors, and Schaffner have disclosed no relevant financial relationships.

International Liver Congress (ILC) 2021: Abstract PO-2688. Presented June 22, 2021.

N Engl J Med. Published online June 23, 2021. Full text

Laird Harrison writes about science, health, and culture. His work has appeared in magazines, newspapers, and online publications. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at lairdharrison.com or follow him on Twitter: @LairdH.

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