A new study finds that nearly a year after recovering from COVID-19, the body’s bone marrow plasma cells (BMPCs) still make active antibodies against the virus. The findings, published in Nature from researchers at Washington University School of Medicine in St. Louis, appears to suggest that antibody production does not wane over time to the point of offering no protection.
Some studies have reported that anti-SARS-CoV-2 serum antibodies decay rapidly in the first few months after infection, raising concerns that long-lived BMPCs may not be generated and that over time they will no longer contribute to humoral immunity through antibody production against this virus.
In this study, the research team showed that in COVID-19 patients who experienced mild infections (n=77), serum anti-SARS-CoV-2 spike (S) antibodies decline rapidly in the first 4 months after infection and then more gradually over the following 7 months, remaining detectable at least 11 months after infection. Their study shows that SARS-CoV-2 infection induces a robust antigen-specific, long-lived humoral immune response.
“It’s normal for antibody levels to go down after acute infection, but they don’t go down to zero; they plateau,” said senior author Ali Ellebedy, PhD, an associate professor of pathology & immunology, of medicine and of molecular microbiology. “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.”
After infection, a small population of plasma cells migrate to the bone marrow where they continue to secrete low levels of antibodies into the bloodstream to help guard re-infection with the virus.
The team studied participants who were giving blood samples at three-month intervals starting about a month after initial COVID-19 infection. Most participants had had mild cases of COVID-19; only six had been hospitalized. Bone marrow was obtained from 18 volunteers about eight months after infection; five provided a second bone marrow sample after another four months. Controls bone marrow was also studied from 11 people who had never had COVID-19.
Consistently, circulating resting memory B cells directed against the S protein were detected in the convalescent individuals Fifteen of the 19 bone marrow samples from people who had had COVID-19 contained BMPCs 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 indefinitely.”
The research team is now studying whether vaccination also induces long-lived antibody-producing cells.