The persistent fatigue experienced by patients with long COVID-19 may have a biological cause, according to a study.

Researchers from Amsterdam University Medical Center (UMC) and Vrije Universiteit Amsterdam (VU) in the Netherlands, discovered that mitochondria -- the powerhouse of a cell -- in muscles produce less energy in long patients than in healthy patients.

"We're seeing clear changes in the muscles in these patients," said Michele van Vugt, Professor of Internal Medicine at Amsterdam UMC.

The study, published in the journal Nature Communications, included 25 long COVID patients and 21 healthy controls. They were asked to cycle for 15 minutes.

This cycling test caused a long-term worsening of symptoms in people with long COVID-19, called post-exertional malaise (PEM).

Extreme fatigue occurs after physical, cognitive, or emotional exertion beyond an unknown, individual threshold.

The researchers looked at the blood and muscle tissue one week before the cycling test and one day after.

"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," said Rob Wust, Assistant Professor at the Department of Human Movement Sciences at the VU University.

"So, the cause of the fatigue is 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," Michele van Vugt added.

One of the theories about COVID-19 is that coronavirus particles may remain in the body of people who have had the coronavirus.

"We don't see any indications of this in the muscles at the moment," Van Vugt said.

The researchers also saw that the heart and lungs functioned well in the patients. This means that the long-lasting effect on a patient's fitness is not caused by abnormalities in the heart or lungs.

The study also found that exercising is not always good for patients with long COVID-19.

"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 or riding an electric bike is good for maintaining some physical condition. Remember that every patient has a different limit," said Brent Appelman, researcher at Amsterdam UMC.

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