Get in the exercise studio. Get back in shape.
This is what patients suffering from long COVID have to hear when they speak of the intense fatigue that comes over them after a brief bout of exercise.
The symptoms of exhaustion, or post-exertional malaise, as it’s known as, are typical of chronic COVID as well as complicated illnesses such as ME/CFS, or chronic fatigue syndrome.
The idea that exercising can benefit patients has proved difficult to dispel despite the evidence to suggest that this isn’t just a case of deconditioning that patients could overcome through working through discomfort.
“I do not think the message is strong enough” declares David Putrino Director of Rehabilitation Innovation at Mount Sinai Health System. “It is evident that this isn’t the typical response to exercising.”
The research that was published this month within Nature Communications adds weightto this assertion.
In taking biopsies of long COVID patients prior to and after exercising, researchers in the Netherlands came up with a stunning illustration of the widespread abnormalities that have occurred in the muscles that could be the reason for this extreme response to physical activity.
Among the most striking findings were clear signs that the cellular power plants, the mitochondria are in decline and the tissue is is starving for energy.
“We discovered this quickly and it’s extremely significant,” says Braeden Charlton who is one of the research’s co-authors of the study at Vrije University in Amsterdam.
The samples of tissue from lengthy COVID patients also showed severe muscle damage, a sluggish immune response, as well as an increase in microclots.
“This is a real condition,” says Charlton. “We observe this in virtually all the parameters we test.”
The results of tests on exercise show a cellular energy system that has gone awry
A majority of people experience delayed-onset muscle soreness when they have an intense workout, however post-exercise malaise is an entirely distinct beast altogether.
“It’s more than just soreness” claims Charlton. “For most people, it’s a complete crippling for a couple of days to weeks.”
Although the symptoms can vary, the most prevalent tend to be muscle aches as well as an increase in fatigue and cognitive issues often known as “brain fog” which lasts for as long as one week following physical exertion.
Study was conducted in the Vrije as well as Amsterdam UMC Health Center evaluated 25 individuals suffering from chronic COVID with healthy control subjects who were completely recovered from COVID-19 and were free of any symptoms. Both groups were required to exercise for approximately 10 hours on stationary bicycle before gradually achieving their highest aerobic capacity.
Researchers performed numerous blood draws and gathered two muscle biopsies of their thighs one week prior to exercising and the day following.
“Their basis was compromised and fell even further with maximum exercise” Charlton says. Charlton.
As was evident in other studies of COVID that were long The issue wasn’t due to how their heart or lungs functioned. It was something else that caused it to be difficult for the muscle to soak oxygen into 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
More tests provided more clues
The blood’s metabolic enzymes that contribute in energy-producing capacity were significantly reduced in COVID patients. They also began producing lactate, which is a fuel that acts as a “last choice” in cells more quickly when exercising than healthy individuals which is yet another indicator that their energy system had gone off the rails.
“The mitochondria operate at a very low capacity when compared with healthy individuals,” says Charlton.
All in all, the findings suggest that mitochondrial dysfunction is a factor in the long-term COVID symptoms such as fatigue and post-exertional malaise says Dr. David Systrom, a physician at Harvard Medical School and Brigham and Women’s Hospital.
“They were able to connect symptoms to biological changes” the researcher says. “I was awed by that.”
In his own studies, Systrom has discovered evidence of an abnormal uptake of oxygen by the muscles of the skeletal system during peak exercise, both in long COVID and ME/CFS patients. This suggests that there is a problem with mitochondrial oxygen supply.
However research from the Dutch study suggests that there could be “intrinsic malfunction” of mitochondria’s capacity to create energy, says the researcher.
Systrom suggests that both of these could be occurring in patients with COVID who have a long duration. “There could be two sides of the range,” he says. “That’s an area that future research will need to consider.”
Biopsies reveal clear evidence of muscle injury
The story doesn’t stop with mitochondria, neither does it end.
The muscle biopsies that were taken following the test of exercise revealed additional alarming events.
“They are likely to suffer much more muscle injury than a healthy individual would,” says Charlton. “And because their max capacity is lower and they are more susceptible to damage occurring earlier .”
A close examination of the muscle tissue revealed that long COVID patients had greater atrophy, which means shrinking of the fibers as compared to healthy subjects. Additionally, there were “immense quantities” in the death of cells also known as “necrosis,” which happens when immune cells invade and break down the tissue he explains.
The data suggests that there is an altered immune response to exercise post-exertional malaise.
“It’s not just about the function in their muscle, but also the method by which their immune system receives the signal from exercise,” says Charlton.
The analysis of tissue-level defects within the muscle is “striking” and could help to explain the fatigue, pain and apathy that patients feel According to Akiko Iwasaki. an immunobiology professor at Yale University, who was not part of the study.
The discovery that T cells, an element that make up the body’s immune arsenalwere infiltrating the muscles of patients with COVID for a long time also attracted Iwasaki’s attention, signalling “an an autoimmune reaction within the muscles cells.”
“In muscles that are healthy there are not many T cells,” she says.
Microclots can cause major complications for blood vessels
Deep dives into the muscle revealed a second common occurrence in COVID pathology: microclots.
Researchers found that these were significantly elevated in people suffering from symptoms, an issue that only became worse with exercise.
Researchers from South Africa have zeroed on on microclots which are able to carry “trapped inflammation molecules” as a sign of vasculature issues in patients.
According to the Dutch research, it was found that there was no evidence of microclots blocking blood vessels in the tiny blood vessels that was a possible explanation. In reality, the microclots were encased within the tissue.
This discovery could be huge, according to Resia Pretorius, Professor of physiology of Stellenbosch University in South Africa and who was not involved in the current study.
“That implies that the microclots could be able to have travelled across the damaged vasculature and into muscles,” She says. “What is a bit scary, but likely to be very important, is the possibility that this could be occurring in other tissues, too.”
In this situation the microclots might indicate the extent of the injury to the lining of blood vessels. This would hinder the delivery of oxygen to muscles.
If the vasculature has been “totally destroyed,” Pretorius says the “mitochondria will be severely impaired,” although more work is needed before drawing a final conclusion.
The root causes of prolonged COVID remain unclear but one popular theory suggests that an ongoing chronic infection may be causing the repercussions.
The researchers investigated this idea. They discovered evidence of viral proteins from SARS-CoV-2 within the muscle tissue, however there was no distinction between the COVID long group and the untreated controls and they concluded that these are leftovers of viral infection which don’t necessarily correlate with the post-exercise malaise.
Experts warn that exercise could “harm” and that other methods are recommended
The role played by exercise in treating post-exertional malaise continues to be “intensely debated,” says Harvard’s Systrom who has studied exercise in relation to other chronic diseases with complex features, like ME/CFS.
“Post-exertional malaise is an uncommon manifestation of these disorders, and is not a sign that is deconditioned,” Dr. A.J. says. “You are not able to simply ask the patients to visit the gym to fix the issue.”
Long COVID itself is an umbrella term which covers many symptoms that could be caused by different reasons.
Systrom believes that certain patients will be more benefited than others from exercise gradually particularly after a the effectiveness of treatment is first proven.
In the study, Charlton says they looked at research from other studies to confirm that the findings was not due to physical inactivity. Charlton also points out that the long COVID patients that were included were not bedridden and walked on average 4,000 walked a day.
Putrino in Mount Sinai considers the study as a crucial wake-up call to the wider medical field -there is a clear proof of a biological cause for the energy loss and the adolescent symptoms patients suffering from long-term COVID and similar ailments suffer.
“As as opposed to what’s offered to patients in the last decade that symptoms like extreme fatigue and malaise from exertion are physical or psychological problems,” he says. “Physical physical exertion can cause harm to the bodies of people suffering from these diseases. “
The most common advice given to not exercising if you suffer from post-exercise fatigue and instead focus on “energy conserving.”
In his clinic, Putrino prescribes what’s referred to as ” autonomic rehabilitation” for these patients.
The goal of exercising is to increase the fitness of your heart — something that he could suggest to patients recuperating from severe pneumonia this kind of rehabilitation takes place with less amount and length, as well as considers post-exercise fatigue.
“We have to get rid from this false belief that no loss, just pain,” he states.
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