Mild cases of COVID-19 give enduring antibody, shows study

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• Source: Washington University School of Medicine


• Date: 24 May,2021

Months after recovering from mild cases of COVID-19, people still possess 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 of the while.

The findings, published May 24 in the journal Nature, imply that moderate 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. 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.”

Ali Ellebedy, PhD, Study Senior Author and Associate Professor of Pathology & Immunology, of Medicine and of Molecular Microbiology

During a viral disease, antibody-producing immune cells rapidly multiply and circulate in the bloodstream, forcing antibody levels sky-high. When 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 into the bone marrow and settle in, in which they always secrete low levels of antibodies into the bloodstream to help protect against another experience with the virus.

The key to figuring out if COVID-19 leads to long-lasting antibody protection, Ellebedy realized, lies in the bone marrow. To find out whether individuals who have recovered from mild cases of COVID-19 harbor long-lived plasma cells which produce antibodies specifically targeted to SARS-CoV-2, the virus which causes COVID-19, Ellebedy teamed up with co-author Iskra Pusic, MD, an associate professor of medicine.

The team already had enrolled 77 participants that 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 hospitalized.

With Pusic’s help, Ellebedy and colleagues obtained bone marrow from 18 of the participants seven or eight months following their first 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 individuals who had never had COVID-19.

As anticipated, 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 a few antibodies detectable even 11 months following infection. Further, 15 of the 19 bone marrow samples from people who’d had COVID-19 contained antibody-producing cells specifically targeting the virus that causes COVID-19. Such cells could nevertheless be discovered four months later in the five individuals who came back to offer a second bone-marrow sample. None of the 11 individuals who had never had COVID-19 had such antibody-producing cells in their bone marrow.

“Individuals with mild cases of COVID-19 clear the virus from their bodies two to three weeks after infection, so there would not be a virus forcing an active immune response seven or 11 months following infection,” Ellebedy said. “These cells are not dividing. They have been doing that ever since the disease resolved, and they’ll keep on doing that indefinitely.”

People who were infected and never had symptoms also may be left with long-term immunity, the researchers speculated. However, it’s yet to be investigated whether those who suffered more acute 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 significant role in acute COVID-19, and too much inflammation can lead to defective immune responses. But on the other hand, the reason people get really sick is often because they have a lot of virus in their bodies, and having a lot of virus around can result in a good immune reaction. So it’s not clear. We need to replicate the analysis in people with moderate to severe infections to understand whether they are likely to be protected from reinfection.”

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