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Cause of fatigue in long Covid patients has finally been revealed

Researchers at the Amsterdam University Medical Center have made a significant discovery regarding the persistent fatigue experienced by long Covid patients. 

The experts have identified a biological cause for this debilitating symptom: reduced energy production by mitochondria in muscle cells.

Focus of the study 

The study participants, including 25 long Covid patients and 21 healthy controls, were subjected to a 15-minute cycling test. 

The test resulted in a prolonged worsening of symptoms in the long-Covid group, known as post-exertional malaise (PEM). This exacerbation of fatigue occurs after physical, cognitive, or emotional exertion, beyond an individual’s tolerance.

Muscle tissue changes

“We’re seeing clear changes in the muscles in these patients,” said Professor Michèle van Vugt. These changes were evident in blood and muscle tissue analyses conducted one week before and one day after the cycling test.

“We saw various abnormalities in the muscle tissue of the patients. At the cellular level, we saw that the mitochondria of the muscle, also known as the energy factories of the cell, function less well and that they produce less energy,” explained Professor Rob Wüst.

Critical insights

“So, the cause of the fatigue is really biological. 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,” said Professor van Vugt.  

One of the theories about long Covid is that coronavirus particles may linger in the body. “We don’t see any indications of this in the muscles at the moment,” said Van Vugt. 

Furthermore, heart and lung functions appeared normal in the patients, indicating that the persistent fatigue is not due to abnormalities in these organs.

Implications for treatment 

The findings have significant implications for managing the symptoms of persistent Covid. The results suggest that intense exercise is not always good for patients with long Covid. 

“A low exercise capacity is one of the hallmark signs of long Covid, associated with a substantial burden for daily life,” wrote the researchers. “The ventilatory and central cardiovascular system did not limit exercise capacity in long Covid patients, but our results confirm previous suggestions of a peripheral impairment in skeletal muscle metabolism in long Covid patients.”

Advice for patients  

Brent Appelman, a researcher at Amsterdam UMC, advises patients to exercise within their own limits. “In concrete terms, we advise these patients to guard their physical limits and not to exceed them.” 

“Think of light exertion that does not lead to worsening of the complaints. Walking is good, or riding an electric bike, to maintain some physical condition. Keep in mind that every patient has a different limit,” said Appelman. 

“Because symptoms can worsen after physical exertion, some classic forms of rehabilitation and physiotherapy are counterproductive for the recovery of these patients,” added Professor van Vugt. 

Understanding long Covid

An estimated one in eight patients develop long Covid, also known as post-Covid syndrome (PCS). A major study involving nearly 10,000 Americans found that long Covid can affect almost every tissue and organ in the body, with symptoms like fatigue, brain fog, dizziness, and gastrointestinal issues. 

Notably, long COVID was more prevalent and severe in those infected before the 2021 Omicron variant. Researchers also identified 12 symptoms that most distinguish long Covid cases, including post-exertional malaise and issues with sexual desire or capacity.

Further research has proposed several mechanisms for long Covid pathogenesis, including immune dysregulation, microbiota disruption, autoimmunity, clotting and endothelial abnormality, and dysfunctional neurological signaling. 

Studies have observed alterations in immune cells, such as T cells and B cells, in individuals with long Covid, as well as elevated levels of certain cytokines. Elevated levels of autoantibodies have also been found in long Covid patients.

The study is published in the journal Nature Communications.

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