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LONG COVID PUZZLE PIECES ARE FALLING INTO PLACE  
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Ziyad Al-Aly
July 18, 2024
The Conversation
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_ Important progress is being made in understanding the pathways by
which long COVID wreaks havoc on the body. Studies suggest that an
abnormal immune response may underlie long COVID. Removing these
antibodies may hold promise as a treatment. _

Long term covid-19, by Sandra Lopez-Leon, Talia Wegman-Ostrosky,
Instituto Nacional de Cancerología: Instituto Nacional de
Cancerologia. Carol Perelman, National Autonomous University of
Mexico: Universidad Nacional Autonoma de Mexico. Rosalinda Sepulveda,
Harvard University

 

Since 2020, the condition known as long COVID-19 has become a
widespread disability
[[link removed]]
affecting the health and quality of life of millions of people across
the globe and costing economies billions of dollars in reduced
productivity of employees and an overall drop in the work force
[[link removed]].

The intense scientific effort that long COVID sparked has resulted in
more than 24,000 scientific publications
[[link removed]],
making it the most researched health condition in any four years of
recorded human history.

Long COVID
[[link removed]]
is a term that describes the constellation of long-term health effects
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caused by infection with the SARS-CoV-2 virus. These range from
persistent respiratory symptoms, such as shortness of breath, to
debilitating fatigue or brain fog that limits people’s ability to
work, and conditions such as heart failure and diabetes, which are
known to last a lifetime.

I am a physician scientist, and I have been deeply immersed in
studying long COVID since the early days of the pandemic. I have
testified before the U.S. Senate as an expert witness on long COVID
[[link removed]],
have published extensively on it
[[link removed]] and was
named as one of Time’s 100 most influential people in health in 2024
[[link removed]] for my research in this area.

Over the first half of 2024, a flurry of reports
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and scientific papers [[link removed]] on long
COVID added clarity to this complex condition. These include, in
particular, insights into how COVID-19 can still wreak havoc in many
organs years after the initial viral infection, as well as emerging
evidence on viral persistence and immune dysfunction that last for
months or years after initial infection.

[Computer-generated image of coronavirus inside lungs surrounded by
multiple copies of the virus.]
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Early on in the pandemic, the SARS-CoV-2 virus seemed to be primarily
wreaking havoc on the lungs. But researchers quickly realized that it
was affecting many organs in the body. Uma Shankar sharma/Moment via
Getty Images
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How long COVID affects the body

A new study that my colleagues and I published in the New England
Journal of Medicine on July 17, 2024, shows that the risk of long
COVID declined [[link removed]] over the course
of the pandemic. In 2020, when the ancestral strain of SARS-CoV-2 was
dominant and vaccines were not available, about 10.4% of adults who
got COVID-19 developed long COVID. By early 2022, when the omicron
family of variants predominated, that rate declined to 7.7% among
unvaccinated adults and 3.5% of vaccinated adults. In other words,
unvaccinated people were more than twice as likely to develop long
COVID.

While researchers like me do not yet have concrete numbers for the
current rate in mid-2024 due to the time it takes for long COVID cases
to be reflected in the data, the flow of new patients into long COVID
clinics has been on par with 2022.

We found that the decline was the result of two key drivers:
availability of vaccines and changes in the characteristics of the
virus – which made the virus less prone to cause severe acute
infections and may have reduced its ability to persist in the human
body long enough to cause chronic disease.

Despite the decline in risk of developing long COVID, even a 3.5% risk
is substantial. New and repeat COVID-19 infections translate into
millions of new long COVID cases that add to an already staggering
number of people suffering from this condition.

Estimates for the first year of the pandemic suggests that at least 65
million people [[link removed]] globally
have had long COVID. Along with a group of other leading scientists,
my team will soon publish updated estimates of the global burden of
long COVID and its impact on the global economy through 2023.

In addition, a major new report by the National Academies of Sciences
Engineering and Medicine details all the health effects that
constitute long COVID
[[link removed]].
The report was commissioned by the Social Security Administration to
understand the implications of long COVID on its disability benefits.

It concludes that long COVID is a complex chronic condition that can
result in more than 200 health effects across multiple body systems.
These include new onset or worsening:

* heart disease [[link removed]]
* neurologic problems [[link removed]]
such as cognitive impairment
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strokes and dysautonomia
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This is a category of disorders that affect the body’s autonomic
nervous system
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– nerves that regulate most of the body’s vital mechanisms such as
blood pressure, heart rate and temperature.
* post-exertional malaise
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a state of severe exhaustion that may happen after even minor activity
— often leaving the patient unable to function for hours, days or
weeks
* gastrointestinal disorders
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* kidney disease [[link removed]]
* metabolic disorders such as diabetes
[[link removed](22)00044-4] and hyperlipidemia
[[link removed](22)00355-2], or a rise in bad
cholesterol
* immune dysfunction [[link removed]]

Long COVID can affect people across the lifespan from children to
older adults and across race and ethnicity and baseline health status.
Importantly, more than 90% of people with long COVID
[[link removed]] had mild COVID-19
infections.

The National Academies report also concluded that long COVID can
result in the inability to return to work or school; poor quality of
life; diminished ability to perform activities of daily living; and
decreased physical and cognitive function for months or years after
the initial infection.

The report points out that many health effects of long COVID, such as
post-exertional malaise and chronic fatigue, cognitive impairment and
autonomic dysfunction, are not currently captured in the Social
Security Administration’s Listing of Impairments
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yet may significantly affect an individual’s ability to participate
in work or school.

Many people experience long COVID symptoms for years following initial
infection.

A long road ahead

What’s more, health problems resulting from COVID-19 can last years
after the initial infection.

A large study published in early 2024 showed that even people who had
a mild SARS-CoV-2 infection still experienced new health problems
[[link removed]] related to COVID-19 in
the third year after the initial infection.

Such findings parallel other research showing that the virus persists
[[link removed](24)00171-3] in various organ
systems for months or years after COVID-19 infection. And research is
showing that immune responses to the infection are still evident two
to three years [[link removed]] after a
mild infection. Together, these studies may explain why a SARS-CoV-2
infection years ago could still cause new health problems long after
the initial infection.

Important progress is also being made in understanding the pathways by
which long COVID wreaks havoc on the body. Two preliminary studies
from the U.S. [[link removed]] and the
Netherlands [[link removed]] show that when
researchers transfer auto-antibodies – antibodies generated by a
person’s immune system that are directed at their own tissues and
organs – from people with long COVID into healthy mice, the animals
start to experience long COVID-like symptoms such as muscle weakness
and poor balance.

These studies suggest that an abnormal immune response thought to be
responsible for the generation of these auto-antibodies may underlie
long COVID and that removing these auto-antibodies
[[link removed]] may hold promise as
potential treatments.

An ongoing threat

Despite overwhelming evidence of the wide-ranging risks of COVID-19, a
great deal of messaging suggests that it is no longer a threat to the
public. Although there is no empirical evidence to back this up, this
misinformation has permeated the public narrative.

The data, however, tells a different story.

COVID-19 infections
[[link removed]] continue
to outnumber flu cases [[link removed]] and
lead to more hospitalization
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leads to more serious long-term health problems
[[link removed](23)00684-9]. Trivializing COVID-19
as an inconsequential cold or equating it with the flu
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does not align with reality.[The Conversation]

_Ziyad Al-Aly
[[link removed]], Chief of
Research and Development, VA St. Louis Health Care System. Clinical
Epidemiologist, Washington University in St. Louis
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This article is republished from The Conversation
[[link removed]] under a Creative Commons license. Read
the original article
[[link removed]].

_The Conversation is a nonprofit, independent news organization
dedicated to unlocking the knowledge of experts for the public good._

_Get fact-based journalism written by experts in your inbox each
morning with  a Conversation newsletter
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* Long Covid
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* COVID-19
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* Medicine
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* immune system
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* Science
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