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Long COVID fatigue linked to malfunctioning mitochondria

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What causes fatigue after exercise in people with long COVID? Image credit: M Stone/Stocksy.
  • At least 65 million people globally have long COVID. 
  • The most common symptoms of long COVID include post-exertional malaise, cognitive impairment, brain fog, sleep problems, and fatigue, which can have a severe impact on a person’s life. 
  • Researchers are still unsure why some people develop long COVID and its symptoms while others do not.
  • Researchers from the Amsterdam University Medical Center have discovered that the fatigue experienced by those with long COVID has a physical cause. 

At least 65 million people Trusted Source The Lancet Highly respected journal, Expert written journal, Peer reviewed journal Go to source around the world have long COVID, a condition where they continue to experience COVID-19 symptoms for months after their symptoms originally start.

The most common symptoms of long COVID are fatigue, dizziness, mobility issues, sleep problems, cognitive impairment, and brain fog or inability to concentrate. 

These types of lingering symptoms can have a profound impact on a person’s life. A study published in June 2023 found more than half of people with long COVID reported their work, home, social, and private lives were severely impacted by the symptoms, with fatigue being the main problem. 

Scientists are still unsure Trusted Source National Institute on Aging Governmental authority Go to source as to why some people develop long COVID and its symptoms while others do not. 

Now researchers from the Amsterdam University Medical Center are helping to provide some answers with their new study — recently published in the journal Nature Communications Trusted Source International Journal of Obesity Peer reviewed journal Go to source — that found the fatigue experienced by those with long COVID has a physical cause. 

Impact of long COVID fatigue on life quality

Prof. Michèle van Vugt, professor of internal medicine at the Amsterdam University Medical Center and co-lead author of this study, told Medical News Today she and her colleagues decided to look for a physical cause of the tiredness experienced by people with long COVID because of the impact it has on their lives. 

“Those long COVID patients used to be like you and me totally integrated [into] society with a job, social life, and private life,” Prof. van Vugt explained. “After their COVID infection, for some of them, nothing was left because of their extreme fatigue. And this happened not only in one patient but many more — too many for only [a] psychological cause.”

Past studies report that fatigue is the most common symptom Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source reported by people who have long COVID. 

A study published in December 2023 Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source found that people with long COVID self-report persistently continuously low levels of health-related quality of life, as well as a high level of disability and declined levels of physical and mental health. 

And research published in April 2023 Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source reported that fatigue caused by long COVID may cause structural changes to the brain. 

Lowered mitochondrial function

For this study, Prof. van Vugt and her team recruited 25 people with long COVID and 21 healthy control participants. They were all asked to take a cycling test for approximately 15 minutes, that was designed to push them to maximum exertion. 

According to researchers, the cycling test caused a worsening of symptoms in the participants with long COVID, known as post-exertional malaise Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source (PEM), resulting in worsening of fatigue for up to 7 days after. 

Scientists examined blood and muscle tissue samples from all participants both one week before the cycling test and one day after. 

They found various abnormalities in the muscle tissue of the participants with long COVID, including lowered functioning of the mitochondria Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source of the muscle. Known as the “powerhouse of the cell,” mitochondria are responsible for making the energy needed to power the body’s cells. 

“So, the cause of the fatigue is really biological,” Prof. van Vugt explained. “The brain needs energy to think. Muscles need energy to move. This discovery means we can now start to research an appropriate treatment for those with long COVID.” 

Tailored exercises: Good or bad for long COVID?

Prof. van Vugt said the the research team was surprised by their study’s findings related to muscle tissue abnormalities. 

“However, we [could then] understand much better the symptoms of fatigue in the patients,” she added. 

When asked about the next steps planned for this research, Prof. van Vugt said they plan to examine whether the same muscle alterations can be found in other post-infectious patients to hopefully uncover the cause of these changes in the muscle, leading to proof of concept studies for treatment.

“Doctors should acknowledge the complaints of long COVID patients and we should advise very carefully about performing tailored exercises Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source . And as researchers, we should support our medical colleagues with our gained knowledge to support patients with their symptoms and in the meantime [try] to discover a biomarker as a diagnostic tool plus finally a treatment.”

– Prof. Michèle van Vugt

A condition that is challenging to treat

MNT also spoke with Dr. David Cutler, a board-certified family medicine physician at Providence Saint John’s Health Center in Santa Monica, CA, about this study. Dr. Cutler was not involved in the research.

Dr. Cutler commented that the topic of long COVID sparks controversy and strong emotions because it remains poorly defined, difficult to diagnose, and challenging to treat. 

“Despite scientific consensus about its existence, the lack of a definitive diagnostic test and its variable presentation continues to make many skeptical of its existence,” he explained. “As a clinician, [I find that] this [research] is helpful in reassuring long COVID sufferers that what they are experiencing is physically real, and not merely psychological.”

“Lacking a specific cure for this condition, the most important treatment physicians can provide is reassurance,” Dr. Cutler continued.

“Patients must be allowed [an] opportunity to present their symptoms to a receptive physician, they must be thoroughly evaluated to exclude other conditions, the diagnosis of long COVID should then be specifically endorsed, patients need to be informed of the generally favorable long-term prognosis, and adequate follow-up provided. This is the basis for optimal reassurance.”

– Dr. David Cutler

Regarding fatigue, Dr. Cutler said a program of graded exercise Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source to avoid worsening symptoms seems to be best. 

“However, at this point, the findings of this one study of just 25 patients does not significantly enhance our ability to treat these patients’ complaints of fatigue,” he added. “But it does help to explain their symptoms which aids in reassurance and lessens anxiety. Future research could be aimed at attempts to lessen fatigue with various regimens of exercise, nutritional support, and emotional therapy to ease the suffering of those with long COVID.” 

This article originally appeared on Medical News Today.

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