‘A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise.’
📖 (4 Jan 2024 ~ Nature: Communications) Muscle abnormalities worsen after post-exertional malaise in long COVID ➤
© 2024 Nature.
❦ Overview ~ ‘A discovery in the muscles of long COVID patients may explain exercise troubles’
By Will Stone / NPR (9 Jan 2024)
‘By taking biopsies from long COVID patients before and after exercising, scientists in the Netherlands constructed a startling picture of widespread abnormalities in muscle tissue that may explain this severe reaction to physical activity.
Among the most striking findings were clear signs that the cellular power plants, the mitochondria, are compromised and the tissue starved for energy.
“We saw this immediately and it’s very profound,” says Braeden Charlton, one of the study’s authors at Amsterdam’s Vrije University.
The tissue samples from long COVID patients also revealed severe muscle damage, a disturbed immune response, and a build-up of microclots.
“This is a very real disease,” says Charlton. “We see this at basically every parameter that we measure.”
While symptoms vary, the most common tend to be muscle pain, an increase in fatigue, and cognitive problems, usually referred to as ‘brain fog’, that last up to a week after physical exertion.
As seen in other long COVID studies, the problem wasn’t related to how their lungs or heart were functioning. Instead, something was making it hard for the muscle to take up the oxygen in the blood.
Using a technique called respirometry, the Dutch researchers oversupplied oxygen to the muscle tissue and found evidence the mitochondria weren’t functioning properly.
Taken together, the results support the hypothesis that mitochondrial dysfunction plays a role in long COVID symptoms like fatigue and post-exertional malaise.
The story doesn’t end with mitochondria, either.
The muscle biopsies taken after the exercise test revealed other troubling events.
“They end up having a lot more muscle damage than a healthy person would have,” says Charlton. “And because their maximal capacity is now also lower, they have that damage happening at a sooner point.”
A close look at the muscle tissue showed long COVID patients had more atrophy – shrinking of the fibers – than the healthy controls.
There were also “immense amounts” of cell death, or ‘necrosis’, which happens when immune cells infiltrate and degrade the tissue, he says. The data hints at some kind of altered immune response to exercise in post-exertional malaise.
“It’s not just the functionality of their muscles, but the way that their immune system is receiving that exercise signal,” says Charlton.
The tissue-level analysis of defects in the muscle is “striking” and may help explain the pain, fatigue and weakness that patients experience.
The deep dive into muscle tissue also turned up another increasingly familiar character in long COVID pathology – microclots.
The researchers found these were heavily elevated in those with symptoms – a feature that only got worse following exercise.
In the Dutch study, there wasn’t evidence that microclots were blocking the tiny blood vessels, which was one hypothesis. Instead, they were lodged in the tissue.
In this scenario, the microclots could reflect the extent of damage to the lining of the blood vessels, which would also impair the delivery of oxygen to the muscle tissue.
The role of exercise in treating post-exertional malaise remains “intensely controversial,” says Harvard’s Dr. David Systrom, who has studied exercise in the context of other complex chronic illnesses like ME/CFS.
“Post-exertional malaise is a unique symptom in these disorders and is not a feature of deconditioning,” he says. “You cannot simply ask these patients to go to the gym and fix the problem.”
Long COVID is itself an umbrella term that encompasses a wide range of symptoms that may have different underlying causes.
Systrom says it’s possible a subset of these patients may benefit more than others from gradual exercise, especially after successful medical treatment has been first established.
In their study, Charlton says they looked at other research to verify that what they observed did not stem from physical inactivity. He also notes that the long COVID patients who were enrolled were not bedridden and had an average of 4,000 steps a day.
Putrino at Mount Sinai considers the study a much-needed wake-up call for the broader medical field – clear evidence of a biological basis for the energy crash and onslaught of symptoms that patients with long COVID and similar conditions experience.
“As opposed to what’s been sold to patients over the last few decades, that symptoms such as extreme fatigue and exertional malaise are psychological or physical conditioning issues,” he says.
“Physical exertion does harm to the bodies of people with these illnesses.”
His general guidance is to avoid exercise if you have post-exertional malaise and instead practice “energy conservation.”
Whereas the aim of exercise is to improve cardiovascular fitness – something he might recommend to patients who’re recovering after severe pneumonia – this type of rehabilitation is done at a much lower intensity and duration, and it takes into account post-exertional malaise.
“We need to step out of this erroneous mindset of no pain, no gain,” he says.’
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📖 (9 Jan 2024 ~ NPR / National Public Radio) A discovery in the muscles of long COVID patients may explain exercise troubles ➤
© 2024 NPR / National Public Radio.
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