“In every viral
infection, you get autoantibodies, and this has been known for decades,” said
Dr. Shiv Pillai, an immunologist at Harvard Medical School.
Many years from now,
scientists may record a higher incidence of autoimmune diseases in those who
had severe COVID, he said, but that is not a foregone conclusion: “There may be
many, many other factors that have to be fulfilled for someone to get the
disease.”
Why only some people
develop autoimmune conditions is unclear, but the answer is likely to involve
dozens of genes and an environmental catalyst.
Lupus is preceded by
high levels of autoantibodies more than 10 years before disease onset, but many
relatives of patients with lupus who have a similar genetic background never
develop the disease.
“The most likely
explanation is that you have all these risk factors, you have all these things
ready to go, and there’s a final trigger,” said Dr. Iñaki Sanz, an immunologist
at Emory University.
To conclusively link a
virus to an autoimmune condition, rigorous studies would need to follow a large
number of people over many years. The best example of such a study is the one
that tied the Epstein-Barr virus to multiple sclerosis.
EBV, a member of the
herpesvirus family, infects nearly everyone at some point. Once in the body, it
persists forever; the virus can be reactivated by conditions including stress
and hormonal changes. (Reactivation of EBV is another of the four risk factors
for long COVID.)
To probe its
association with multiple sclerosis, Ascherio and his colleagues conducted what
they call an “experiment of nature” — a long-term study of more than 10 million
active-duty soldiers in the U.S. military.
Between 1993 and 2013,
the researchers collected 62 million serum samples from this racially diverse
group. Those who were infected with EBV had a 32-fold increase in the risk of
multiple sclerosis, compared with those who did not have the virus, the
scientists found. They did not observe similar relationships with other
viruses.
Fewer than 1 million
Americans have multiple sclerosis, suggesting that other factors must also be
involved. Still, researchers are now enthusiastic about the idea of a vaccine
against EBV to prevent multiple sclerosis. (No vaccines against EBV are
currently available, although some are in clinical trials.)
Studies from other
teams support the association between EBV and multiple sclerosis. Danish
researchers followed more than 25,000 people with mononucleosis over decades
and found that it doubled their odds of developing multiple sclerosis.
And a study published
last year offered a possible explanation: EBV mimics a human protein,
potentially misdirecting antibodies made against the virus.
About 1 in 4 people
with multiple sclerosis has these antibodies, “providing the basis for how EBV
could evoke an autoimmune reaction that would cause multiple sclerosis,” said
Dr. William Robinson, an expert in autoimmune diseases at Stanford University
who led the study.
This sort of molecular
mimicry is one path to autoimmunity. But in other cases, the body might never
fully clear a pathogen after infection, and the persistence of the virus —
whether live virus or just remnants — might keep the body in a state of immune
high alert, eventually leading to autoimmunity.
Both possibilities
suggest treatments. In some small number of people, antiviral drugs and
vaccination can ease the symptoms of long COVID, hinting that live virus may be
the source. Henrich is conducting a study looking at monoclonal antibodies at
high doses that would soak up errant viral fragments lingering in the body.
“If the viral proteins
are causing an auto-reactive process, then by getting rid of those viral
proteins, it might actually improve overall health,” Henrich said.
For Wynn, there is no
relief in sight. She has tried a plethora of medications, including treatments
for rheumatoid arthritis, but so far has not responded to them.
“It’s been a long and
tedious process,” Wynn said. “And I will tell you, from a mental perspective,
it has been absolutely draining.” READ MORE
