Trump's Covid-19 Treatment Seeks to Boost Immune Response
06 October 2020 - 2:25AM
Dow Jones News
By Anna Wilde Mathews
The experimental infusion doctors have given to President Trump
seeks to counter a problem affecting many older Covid-19 patients:
an ineffective immune response.
Among other treatments, Mr. Trump has taken a drug cocktail from
Regeneron Pharmaceuticals Inc. that hasn't been approved for broad
use but aims to jump-start an immune defense by supplying
antibodies to help fight the coronavirus that causes Covid-19. The
company says its results suggest the infusion can help people
infected with the coronavirus who haven't yet produced their own
antibodies.
The approach makes sense in elderly patients, whose bodies are
often less able to fight off pathogens, said Janko Nikolich-Zugich,
an immunologist and gerontologist who is a professor at the
University of Arizona. "You don't control the virus as quickly as
you should" with older patients, he said.
A growing body of research points to the immune system as a key
reason why the elderly are so susceptible to serious cases of
Covid-19. As a person ages, the system undergoes
"immunosenescence," gradually losing its ability to mount a
response to infection as robustly as it once did. The complicated
mechanisms of the immune system don't work together as well,
leading to a slower and less-powerful defense.
In addition to his age, 74, Mr. Trump's weight also may raise
concerns about his immunity, as obesity has been tied to impaired
response. And a study published in the journal Nature this August
also highlighted the possibility that older men, in particular,
might tend to mount a less-robust immune response to the virus.
About 80% of deaths in the U.S. have been among those 65 and
older, and about 31% of deaths are among people aged at least 85
years, according to death-certificate data from the Centers for
Disease Control and Prevention. This is partly because the elderly
are often frailer, and they also have higher rates of conditions
such as heart disease and diabetes that are risk factors for severe
impact from Covid-19.
But their immune systems are another important factor,
researchers say. "When you challenge a body with a virus or a
vaccine, there's just not the vigorous response," said Cari Levy, a
geriatrician who is a professor at the University of Colorado.
Older people often produce fewer, and less-effective,
antibodies. These y-shaped proteins are supposed to bind to
invading pathogens, neutralizing them and signaling to the body to
destroy them.
"It's slower, it's unreliable -- you probably don't make as
many" antibodies, said Peter Chin-Hong, a professor of medicine at
the University of California, San Francisco. The hope is that
treatments like Regeneron's experimental cocktail might help fill
that gap early in the infection process, potentially slowing the
initial spread of the virus.
Elderly immune systems also often have problems generating the
powerful soldiers known as T-cells, which supply a main line of
defense against invaders. Production of these cells, from a gland
in the chest known as the thymus, drops sharply over the course of
a person's life. They can also lose some of their function.
One recent study suggests that older men have a harder time
getting their T-cells into action. New research published this
August in Nature looked at 98 patients infected with the
coronavirus and found evidence that the immune response varied by
gender.
"Especially men of older age were very impaired with respect to
T-cell activation," said Akiko Iwasaki, a professor of
immunobiology at Yale University who led the study. Those men who
had the least T-cell response tended to have worse Covid-19
outcomes, she said.
There is no treatment currently available that would help with
Covid-19 patients' T-cells, she said. Potentially a future vaccine
might do this, but vaccines are often less effective in older
patients.
But even as vital parts of an elderly person's immune system are
performing sluggishly, another response can cause trouble by firing
up too much. As the body fails to contain the virus quickly, the
immune system may produce too many of a type of protein called
cytokines. These can damage blood vessels and allow fluid to seep
into the lungs.
It isn't clear why this "cytokine storm" effect is triggered in
some patients but not others. But elderly people tend to have a
higher level of inflammation, and cytokines, said Amber Mueller, a
molecular biologist who is a postdoctoral research fellow at
Harvard Medical School.
This greater baseline level of inflammation is one reason the
soldier T-cells are less effective, and it sets the stage for the
dangerous overproduction of cytokines, she said.
President Trump remained hospitalized early Monday, after
doctors offered conflicting signals about how he is faring with
Covid-19. The president sought to project confidence and vigor over
the weekend.
--Jon Kamp contributed to this article.
Write to Anna Wilde Mathews at anna.mathews@wsj.com
(END) Dow Jones Newswires
October 05, 2020 11:10 ET (15:10 GMT)
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