Mild COVID-19 induces lasting antibody protection, study finds

Mild COVID-19 induces lasting antibody protection, study finds

People who
have had mild illness develop antibody-producing cells that can last lifetime

University School of Medicine

Months after recovering from mild cases
of COVID-19, people still have immune cells in their body pumping out
antibodies against the virus that causes COVID-19, according to a study from
researchers at Washington University School of Medicine in St. Louis. Such
cells could persist for a lifetime, churning out antibodies all the while.

The findings, published May 24 in the journal Nature, suggest that
mild cases of COVID-19 leave those infected with lasting antibody protection
and that repeated bouts of illness are likely to be uncommon.

“Last fall, there were reports that antibodies wane quickly
after infection with the virus that causes COVID-19, and mainstream media
interpreted that to mean that immunity was not long-lived,” said senior
author Ali Ellebedy, PhD, an associate professor of pathology & immunology,
of medicine and of molecular microbiology. “But that’s a misinterpretation
of the data. It’s normal for antibody levels to go down after acute infection,
but they don’t go down to zero; they plateau. Here, we found antibody-producing
cells in people 11 months after first symptoms. These cells will live and
produce antibodies for the rest of people’s lives. That’s strong evidence for
long-lasting immunity.”

During a viral infection, antibody-producing immune cells
rapidly multiply and circulate in the blood, driving antibody levels sky-high.
Once the infection is resolved, most such cells die off, and blood antibody
levels drop. A small population of antibody-producing cells, called long-lived
plasma cells, migrate to the bone marrow and settle in, where they continually
secrete low levels of antibodies into the bloodstream to help guard against
another encounter with the virus.

The key to figuring out whether COVID-19 leads to long-lasting
antibody protection, Ellebedy realized, lies in the bone marrow. To find out
whether those who have recovered from mild cases of COVID-19 harbor long-lived
plasma cells that produce antibodies specifically targeted to SARS-CoV-2, the
virus that causes COVID-19, Ellebedy teamed up with co-author Iskra Pusic, MD,
an associate professor of medicine. Ellebedy already was working with
co-authors Rachel Presti, MD, PhD, an associate professor of medicine, and Jane
O’Halloran, MD, PhD, an assistant professor of medicine, on a project to track
antibody levels in blood samples from COVID-19 survivors.

The team already had enrolled 77 participants who were giving
blood samples at three-month intervals starting about a month after initial
infection. Most participants had had mild cases of COVID-19; only six had been

With Pusic’s help, Ellebedy and colleagues obtained bone marrow
from 18 of the participants seven or eight months after their initial
infections. Five of them came back four months later and provided a second bone
marrow sample. For comparison, the scientists also obtained bone marrow from 11
people who had never had COVID-19.

As expected, antibody levels in the blood of the COVID-19
participants dropped quickly in the first few months after infection and then
mostly leveled off, with some antibodies detectable even 11 months after
infection. Further, 15 of the 19 bone marrow samples from people who had had
COVID-19 contained antibody-producing cells specifically targeting the virus
that causes COVID-19. Such cells could still be found four months later in the
five people who came back to provide a second bone-marrow sample. None of the
11 people who had never had COVID-19 had such antibody-producing cells in their
bone marrow.

“People with mild cases of COVID-19 clear the virus from
their bodies two to three weeks after infection, so there would be no virus
driving an active immune response seven or 11 months after infection,”
Ellebedy said. “These cells are not dividing. They are quiescent, just
sitting in the bone marrow and secreting antibodies. They have been doing that
ever since the infection resolved, and they will continue doing that

People who were infected and never had symptoms also may be left
with long-lasting immunity, the researchers speculated. But it’s yet to be
investigated whether those who endured more severe infection would be protected
against a future bout of disease, they said.

“It could go either way,” said first author Jackson
Turner, PhD, an instructor in pathology & immunology. “Inflammation
plays a major role in severe COVID-19, and too much inflammation can lead to
defective immune responses. But on the other hand, the reason why people get
really sick is often because they have a lot of virus in their bodies, and
having a lot of virus around can lead to a good immune response. So it’s not
clear. We need to replicate the study in people with moderate to severe
infections to understand whether they are likely to be protected from

Ellebedy and colleagues now are studying whether vaccination
also induces long-lived antibody-producing cells.

Journal Reference:

  1. Jackson S. Turner, Wooseob Kim, Elizaveta Kalaidina, Charles W. Goss, Adriana M. Rauseo, Aaron J. Schmitz, Lena Hansen, Alem Haile, Michael K. Klebert, Iskra Pusic, Jane A. O’Halloran, Rachel M. Presti, Ali H. Ellebedy. SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humansNature, 2021; DOI: 10.1038/s41586-021-03647-4

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