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Does COVID lead to lasting antibody protection? Answer lies in bone marrow, WashU study finds

The key to figuring out whether COVID-19 leads to long-lasting antibody protection lies in bone marrow, according to researchers at WashU

ST. LOUIS — Long after recovering from mild cases of COVID-19, people still have immune cells in their body releasing antibodies against the virus, and those cells could last for a lifetime, according to a study from Washington University School of Medicine.

The study, published in the journal Nature on Monday, suggests mild cases of COVID-19 leave those infected with lasting antibody protection and repeated illness is 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. But that’s a misinterpretation of the data,” said senior author Ali Ellebedy, PhD, who's an associate professor of pathology and immunology, of medicine and of molecular microbiology. “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.”

When a person experiences a viral infection, antibody-producing immune cells rapidly multiply and circulate in the blood, which drive antibody levels sky high. Once the infection resolves, most of those cells die off and blood antibody levels drop.

A small amount of those cells, called long-lived plasma cells, migrate to the bone marrow, where they will secrete low levels of antibodies into the bloodstream to help guard against the virus. The key to figuring out whether COVID-19 leads to long-lasting antibody protection lies in the bone marrow, WashU stated in a news release

A team of researchers had already enrolled 77 people who were giving blood samples at three-month intervals starting about a month after the initial infection. Most of the participants had mild cases and six people had been hospitalized.

The team obtained bone marrow from 18 participants seven or eight months after their initial infections. Five of them came back four months later and provided a second bone marrow sample, the release stated. Researchers also obtained bone marrow from 11 people who had never had the virus, for comparison.

As they expected, antibody levels in the blood from the COVID-19 participants dropped quickly in the first few months after the infection, with some antibodies detectable 11 months after. Fifteen of the 19 bone marrow samples from people who had the virus contained antibody-producing cells. Those cells could still be found four months later in the five people who provided a second sample.

“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 indefinitely.”

Researchers also are speculating that people who had COVID-19 but never had symptoms could also be left with long-lasting immunity. It is yet to be investigated if people who had severe symptoms would be protected against a future encounter with the virus.

“It could go either way,” said Jackson Turner, PhD, who's an instructor in pathology and 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 reinfection.”

The WashU research team is now studying whether vaccination also induces long-lived antibody producing cells.

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