“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 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 hospitalized.
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. An additional person who had recovered from COVID-19 gave bone marrow separately. For comparison, the scientists also obtained bone marrow from 11 people who had never had COVID-19.
Many people who have been infected with SARS-CoV-2 will probably make antibodies against the virus for most of their lives. So suggest researchers who have identified long-lived antibody-producing cells in the bone marrow of people who have recovered from COVID-191.
The study provides evidence that immunity triggered by SARS-CoV-2 infection will be extraordinarily long-lasting. Adding to the good news, “the implications are that vaccines will have the same durable effect”, says Menno van Zelm, an immunologist at Monash University in Melbourne, Australia.
Antibodies — proteins that can recognize and help to inactivate viral particles — are a key immune defense. After a new infection, short-lived cells called plasmablasts are an early source of antibodies.
But these cells recede soon after a virus is cleared from the body, and other, longer-lasting cells make antibodies: memory B cells patrol the blood for reinfection, while bone marrow plasma cells (BMPCs) hideaway in bones, trickling out antibodies for decades.
To identify the source of the antibodies, Ellebedy’s team collected memory B cells and bone marrow from a subset of participants. Seven months after developing symptoms, most of these participants still had memory B cells that recognized SARS-CoV-2. In 15 of the 18 bone-marrow samples, the scientists found ultra-low but detectable populations of BMPCs whose formation had been triggered by the individuals’ coronavirus infections 7–8 months before. Levels of these cells were stable in all five people who gave another bone-marrow sample several months later.
“This is a very important observation,” given claims of dwindling SARS-CoV-2 antibodies, says Rafi Ahmed, an immunologist at Emory University in Atlanta, Georgia, whose team co-discovered the cells in the late 1990s. What’s not clear is what antibody levels will look like in the long term and whether they offer any protection, Ahmed adds. “We’re early in the game. We’re not looking at five years, ten years after infection.”
Ellebedy’s team has observed early signs that Pfizer’s mRNA vaccine should trigger the production of the same cells4. But the persistence of antibody production, whether elicited by vaccination or by infection, does not ensure long-lasting immunity to COVID-19. The ability of some emerging SARS-CoV-2 variants to blunt the protective effects of antibodies means that additional immunizations may be needed to restore levels, says Ellebedy. “My presumption is, we will need a booster.”
