HIV Specialist - March 2021 - 7

The Immune System Mounts a Lasting Defense
after Recovery from COVID-19

A

S THE NUMBER OF PEOPLE who
have fought off SARS-CoV-2 climbs
ever higher, a critical question has
grown in importance: How long will their
immunity to the novel coronavirus last? 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

SHUTTERSTOCK/ MALENKKA



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

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

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.

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HIV Specialist - March 2021

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