systems, receiving the COVID-19 vaccine is no guarantee they will be protected
from the virus.
don’t provide enough protection, leaving more than nine million Americans with
compromised immune systems stuck in a waiting game
BY TARA HAELLE PUBLISHED JUNE 16,
2021
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 Richterman,
an infectious disease fellow at the University of Pennsylvania Perelman School
of Medicine, regarding how immune-compromised people can assess their infection
risk after vaccination.
Evidence so far is mixed
The wide range of conditions and drugs that weaken the immune system explain
why the response to COVID-19 vaccines is so mixed. The evidence so far shows
that transplant recipients, certain leukemia patients, and people taking a
handful of specific medications have the poorest vaccine response.
The drugs
that appear linked with the poorest response include mycophenolate (prevents
organ rejection), rituximab (treats some blood cancers and autoimmune diseases
like rheumatoid arthritis), belatacept (prevents organ rejection), and
methotrexate (treats a wide range of cancers and autoimmune diseases).
For example, the organ transplant study Collins read found only 54 percent
of 658 organ
transplant recipients had any antibodies after two doses of the
mRNA vaccine, particularly if they were taking a drug like mycophenolate. A
similar study
of 609 kidney transplant recipients found half had detectable
antibodies after mRNA vaccination, but only 5 percent of those taking
belatacept did. Transplant recipients produced even fewer antibodies in
response to the one-dose Johnson & Johnson vaccine.
Studies in people with autoimmune disease have similarly shown that vaccine
response typically depends on the specific drug they’re taking.
In a study of 404
people with rheumatic disease who had both doses of an mRNA
vaccine, almost all had detectable antibodies, but those taking rituximab or
mycophenolate had very low levels. Meanwhile, everyone taking
anti-inflammation drugs called tumor necrosis factor (TNF) inhibitors to
treat Crohn’s disease or rheumatoid or psoriatic arthritis, had strong antibody
responses.
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