From xxxxxx <[email protected]>
Subject What Causes Long COVID? We Have Some Answers.
Date August 6, 2022 12:35 AM
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[Long COVID-19 and other chronic respiratory conditions after
viral infections may stem from an overactive immune response in the
lungs ]
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Harish Narasimhan
August 4, 2022
The Conversation
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_ Long COVID-19 and other chronic respiratory conditions after viral
infections may stem from an overactive immune response in the lungs _

Leukemia treatment - immune system T-cells (center) binding to beads
which cause the cells to divide, Microbe World (CC BY-NC-SA 2.0)


Viruses that cause respiratory diseases like the flu and COVID-19 can
lead to mild to severe symptoms within the first few weeks of
infection. These symptoms typically resolve within a few more weeks,
sometimes with the help of treatment if severe. However, some people
go on to experience persistent symptoms that last several months to
years. Why and how respiratory diseases can develop into chronic
conditions like long COVID-19
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are still unclear.

I am a doctoral student
[[link removed]] working
in the Sun Lab [[link removed]] at the
University of Virginia. We study how the immune system sometimes goes
awry after fighting off viral infections. We also develop ways to
target the immune system to prevent further complications without
weakening its ability to protect against future infections. Our
recently published review [[link removed]]
of the research in this area found that it is becoming clearer that it
might not be an active viral infection causing long COVID-19 and
similar conditions, but an overactive immune system.

Long COVID-19 patients can experience persistent respiratory,
cognitive and neurological symptoms.

The lungs in health and disease

Keeping your immune system dormant when there isn’t an active
infection is essential for your lungs to be able to function

Your respiratory tract is in constant contact with your external
environment, sampling around 5 to 8 liters (1.3 to 2 gallons) of air
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– and the toxins and microorganisms in it – every minute. Despite
continuous exposure to potential pathogens and harmful substances,
your body has evolved to keep the immune system dormant in the lungs
[[link removed]]. In fact,
allergies and conditions such as asthma are byproducts of an
overactive immune system
[[link removed]]. These excessive
immune responses can cause your airways to constrict and make it
difficult to breathe. Some severe cases may require treatment to
suppress the immune system.

During an active infection, however, the immune system is absolutely
essential. When viruses infect your respiratory tract, immune cells
are recruited to your lungs to fight off the infection. Although these
cells are crucial to eliminate the virus from your body, their
activity often results in collateral damage to your lung tissue. After
the virus is removed, your body dampens your immune system
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chance to recover.

An overactive immune system, as in the case of asthma, can damage the

Over the past decade, researchers have identified a variety of
specialized stem cells in the lungs
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damaged tissue. These stem cells can turn into almost all the
different types of cells in the lungs depending on the signals they
receive from their surrounding environment. Recent
[[link removed]] studies
[[link removed]] have highlighted
[[link removed]] the prominent role the
immune system plays in providing signals that facilitate lung
recovery. But these signals can produce more than one effect. They can
not only activate stem cells, but also perpetuate damaging
inflammatory processes in the lung. Therefore, your body tightly
regulates when, where and how strongly these signals are made in order
to prevent further damage.

While the reasons are still unclear, some people are unable to turn
off their immune system after infection and continue to produce
tissue-damaging molecules [[link removed]]
long after [[link removed]] the virus has
been flushed out. This not only further damages the lungs, but also
interferes with regeneration via the lung’s resident stem cells.
This phenomenon can result in chronic disease, as seen in several
respiratory viral infections including COVID-19
[[link removed]], Middle East
Respiratory Syndrome (MERS) [[link removed]],
respiratory syncytial virus (RSV)
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The immune system’s role in chronic disease

In our review, my colleagues and I found that many different types of
immune cells [[link removed]] are involved
in the development of chronic disease after respiratory viral
infections, including long COVID-19.

Scientists so far have identified one particular type of immune cells,
killer T cells [[link removed]], as
potential contributors to chronic disease. Also known as cytotoxic or
CD8+ T cells, they specialize in killing infected cells either by
interacting directly with them or by producing damaging molecules
called cytokines.

Killer T cells are essential to curbing the virus from spreading in
the body during an active infection. But their persistence in the
lungs after the infection has resolved is linked to extended reduced
respiratory function [[link removed]].
Moreover, animal studies have shown that removing killer T cells from
the lungs [[link removed]] after infection
may improve lung function and tissue repair.

A legion of immune cells work together to remove invading pathogens.

Another type of immune cells called monocytes are also involved in
fighting respiratory infections, serving among the first responders by
producing virus- and tissue-damaging cytokines. Research has found
that these cells also continue to accumulate
[[link removed]] in the lungs of long
COVID-19 patients and promote a pro-inflammatory environment that can
cause further damage.

Understanding the immunological mechanisms underlying long COVID-19 is
the first step to addressing a quickly worsening public health problem
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Identifying the subtle differences in how the same immune cells that
protect you during an active infection can later become harmful could
lead to earlier diagnosis of long COVID-19. Moreover, based on our
findings, my team and I believe treatments that target the immune
system could be an effective approach to manage long COVID-19
symptoms. We believe that this strategy may turn out to be useful not
only for COVID-19, but also for other respiratory viral infections
that lead to chronic disease as well.[The Conversation]

Harish Narasimhan
[[link removed]], PhD
Candidate in Immunology, _University of Virginia
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This article is republished from The Conversation
[[link removed]] under a Creative Commons license. Read
the original article
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* Science
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* biology
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* vaccines
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* viruses
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* COVID-19
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