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The complex situation for immunocompromised people and COVID-19 vaccines

  • Science
  • Coronavirus Coverage

Studies suggest the available shots don’t provide enough protection, leaving more than nine million Americans with compromised immune systems stuck in a waiting game.

Published June 16, 2021

13 min read

When Margaret Collins, a 43-year-old geologist from Fort Worth, Texas, got her first dose of the Moderna vaccine January 6, she came home and cried.

“I was finally getting the shot,” she says. “I saw it as a step back to the life that I loved.”

A self-described extrovert, Collins became a hermit during the pandemic. She and her husband rarely stepped outside, and never without a mask. Her caution is warranted because she suffers from a generalized autoimmune disorder that includes hepatitis, psoriatic arthritis, vitiligo, and type 1 diabetes. Collins is also particularly vulnerable to COVID-19 because she received a donated pancreas and kidney in 2014 and takes three medications to suppress her immune system so her body doesn’t reject those organs. Yet, vaccines work by harnessing the capability of a fully competent immune system.

Since the FDA authorized the first COVID-19 vaccine, people with compromised immune systems have lived in limbo, waiting to find out whether, or how much, vaccination might protect them. The vaccine clinical trials excluded nearly all immune-compromised people because including them might interfere with determining vaccine effectiveness for the general population. But that’s left this group with little data on what vaccination means for them. Now studies are trickling in.

“We’re starting to learn some of the things we don’t know, whereas before, it was a bunch of we don’t know what we don’t know,” says Peter Martin, a hematologist and oncologist at Weill Cornell Medicine in New York City.

It’s difficult to gauge the number of immune-compromised people in the U.S. One study estimates that 2.8 percent of people with private insurance take immune-suppressing drugs—about nine million Americans. But that doesn’t include Medicare or Medicaid patients, who are more likely to have some conditions requiring immunosuppression, says study author Beth Wallace, a rheumatologist at University of Michigan Medicine. It also doesn’t include people with immune-compromising conditions who aren’t taking immune-suppressing medications.

From the very beginning of the pandemic Collins worried how her body would respond to the vaccine. But when she later read a study of organ transplant recipients that found low antibody levels after the first mRNA vaccine dose, she panicked.

Even though she had been vaccinated and wore a mask, she thought “How safe was I? It really scared me.”

A follow-up study that found about half of transplant recipients responded to the vaccine offered her little comfort. “That’s essentially the flip of a coin,” Collins says. But a small study published Monday offers a flicker of hope.

After two doses of mRNA vaccine, 30 transplant recipients with no or low antibodies got a third shot, though not necessarily of the same vaccine they received first. The six people with low antibody levels subsequently developed higher levels, and a quarter of the others, who had never responded to the COVID-19 vaccine, developed antibody levels thought to be high enough to prevent COVID-19 after the third dose.

But this study has substantial limitations: It’s very small and involves a grab bag of different vaccine combinations. Further, the Food and Drug Administration has not authorized a third dose, and the Centers for Disease Control and Prevention currently advises against it. The authors concluded that their findings suggest the need for more studies to test third doses in people without fully functioning immune systems.

A diverse population

Immune-compromised people fall into two broad categories: Either they have an underlying condition that weakens their immune system, such as people with leukemia, uncontrolled HIV, or a rare genetic disease, or they have an underlying condition requiring immune-suppressing therapy, such as organ transplant recipients and people with rheumatic diseases (inflammatory, autoimmune conditions) or some cancers. A few conditions, such as chronic lymphocytic leukemia and lupus, fall into both categories.

Factors that might affect someone’s response to a vaccine include the medication they’re taking and what it does, how long they’ve been taking it, their specific disease, and their history of infection. For organ transplant recipients, the time since their transplant may also matter.

“That’s why it’s really important for people who have these immune-suppressed conditions to talk to an expert about their specific situation, because there is such a great amount of variability,” says Aaron Richter

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