Immune system mounts a lasting defense after recovery from COVID-19, researchers find
Rockefeller
University
A new Rockefeller study offers an encouraging answer, suggesting that those who recover from COVID-19 are protected against the virus for at least six months, and likely much longer.
The
findings, published in Nature, provide the strongest evidence yet
that the immune system "remembers" the virus and, remarkably,
continues to improve the quality of antibodies even after the infection has
waned. Antibodies produced months after the infection showed increased ability
to block SARS-CoV-2, as well as its mutated versions such as the South African
variant.
The
researchers found that these improved antibodies are produced by immune cells
that have kept evolving, apparently due to a continued exposure to the remnants
of the virus hidden in the gut tissue.
Based
on these findings, researchers suspect that when the recovered patient next
encounters the virus, the response would be both faster and more effective,
preventing re-infection.
"This is really exciting news. The type of immune response we see here could potentially provide protection for quite some time, by enabling the body to mount a rapid and effective response to the virus upon re-exposure," says Michel C. Nussenzweig, the Zanvil A. Cohn and Ralph M. Steinman Professor and head of the Laboratory of Molecular Immunology, whose team has been tracking and characterizing antibody response in Covid-19 patients since the early days of the pandemic in New York.
Long-lasting
memory
Antibodies,
which the body creates in response to infection, linger in the blood plasma for
several weeks or months, but their levels significantly drop with time. The
immune system has a more efficient way of dealing with pathogens: instead of
producing antibodies all the time, it creates memory B cells that recognize the
pathogen, and can quickly unleash a new round of antibodies when they encounter
it a second time.
But how well this memory works depends on the pathogen. To understand the case with SARS-CoV-2, Nussenzweig and his colleagues studied the antibody responses of 87 individuals at two timepoints: one month after infection, and then again six months later.
As expected, they found that although antibodies were still
detectable by the six-month point, their numbers had markedly decreased. Lab
experiments showed that the ability of the participants' plasma samples to
neutralize the virus was reduced by five-fold.
In
contrast, the patients' memory B cells, specifically those that produce
antibodies against SARS-CoV-2, did not decline in number, and even slightly
increased in some cases. "The overall numbers of memory B cells that
produced antibodies attacking the Achilles' heel of the virus, known as the
receptor-binding domain, stayed the same," says Christian Gaebler, a
physician and immunologist in Nussenzweig's lab. "That's good news because
those are the ones that you need if you encounter the virus again."
Viral
stowaways
A
closer look at the memory B cells revealed something surprising: these cells
had gone through numerous rounds of mutation even after the infection resolved,
and as a result the antibodies they produced were much more effective than the
originals. Subsequent lab experiments showed this new set of antibodies were
better able to latch on tightly to the virus and could recognize even mutated
versions of it.
"We
were surprised to see the memory B cells had kept evolving during this
time," Nussenzweig says. "That often happens in chronic infections,
like HIV or herpes, where the virus lingers in the body. But we weren't
expecting to see it with SARS-CoV-2, which is thought to leave the body after
infection has resolved."
SARS-CoV-2
replicates in certain cells in the lungs, upper throat, and small intestine,
and residual viral particles hiding within these tissues could be driving the
evolution of memory cells. To look into this hypothesis, the researchers have
teamed up with Saurabh Mehandru, a former Rockefeller scientist and currently a
physician at Mount Sinai Hospital, who has been examining biopsies of
intestinal tissue from people who had recovered from COVID-19 on average three
months earlier.
In
seven of the 14 individuals studied, tests showed the presence of SARS-CoV-2's
genetic material and its proteins in the cells that line the intestines. The
researchers don't know whether these viral left-overs are still infectious or
are simply the remains of dead viruses.
The
team plans to study more people to better understand what role the viral
stowaways may play in both the progression of the disease and in immunity.
