A
bone-marrow plasma cell (artificially coloured). Such cells, which
produce antibodies, linger for months in the bodies of people who have
recovered from COVID-19.Credit: Dr Gopal Murti/Science Photo Library
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 defence. 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) hide away in bones, trickling out antibodies for decades.
“A
plasma cell is our life history, in terms of the pathogens we’ve been
exposed to,” says Ali Ellebedy, a B-cell immunologist at Washington
University in St. Louis, Missouri, who led the study, published in Nature on 24 May.
Researchers presumed that SARS-CoV-2 infection would trigger
the development of BMPCs — nearly all viral infections do — but there
have been signs that severe COVID-19 might disrupt the cells’ formation2. Some early COVID-19 immunity studies also stoked worries, when they found that antibody levels plunged not long after recovery3.
Ellebedy’s
team tracked antibody production in 77 people who had recovered from
mostly mild cases of COVID-19. As expected, SARS-CoV-2 antibodies
plummeted in the four months after infection. But this decline slowed,
and up to 11 months after infection, the researchers could still detect
antibodies that recognized the SARS-CoV-2 spike protein.
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.”
doi: https://doi.org/10.1038/d41586-021-01442-9
Correction 27 May 2021: An earlier version of this article gave the wrong number of bone-marrow samples. This has now been corrected.
Turner, J. S. et al. Nature https://doi.org/10.1038/s41586-021-03647-4 (2021).
Kaneko, N. et al. Cell 183, 143–157 (2020).
Long, Q.-X. et al. Nature Med. 26, 1200–1204 (2020).
Ellebedy, A. et al. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-310773/v1 (2021).