Long COVID can destroy your ability to exercise. Now we know why.

For many people with long COVID, a major symptom is difficulty with exercising, because when these patients push past their limits it can lead to a devastating cycle of fatigue that boosts the risk of worsening their condition.

These issues with exercise, which is known as post-exertional malaise (PEM), are also the defining symptoms of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS).

Now a new study, published in the journal Nature Communications, provides an explanation for this feeling of exhaustion, suggesting that patients with long COVID experience a range of changes in their body after exercising, including widespread muscle damage, changes in muscle composition, and disrupted energy metabolism.

This study “actually shows the damage” to the body that is being caused by post-exertional malaise, says Lucinda Bateman, a physician at the Bateman Horne Center, who specializes in treating patients with ME/CFS and long COVID. As Bateman notes, this includes showing “the inflammation, the damage, the scarring, the clots,” which are all found in the muscles of long COVID patients. Researchers also found differences in the activity of the mitochondria—the body’s microscopic energy factories—following exercise.

The suggested response to PEM: pace yourself.

Post-exertional malaise triggered by exercise test

In the study, researchers recruited 25 long COVID patients. These patients were all young—average age, 41—with no other pre-existing conditions, and were all experiencing a significant reduction in their work and social life due to long COVID.

They had to have post-exertional malaise to participate in the study, says Rob Wüst, an exercise physiologist at Vrije University Amsterdam and a co-author of the study.

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Participants underwent a cardiopulmonary exercise test in which they were asked to exercise until they were exhausted, which then triggered a bout of post-exertional malaise.

To characterize the changes their bodies were going through, researchers drew blood and performed a muscle biopsy one week before the exercise test and one day after. The results from these tests were then compared to the results from 21 healthy patients, who were matched for age and gender.

“Normally we know from all the other chronic diseases that exercise is good for you, that exercise is medicine,” Wüst says. “However, these patients do get worse.”

Changes to the body’s energy systems

The worsening of symptoms after exercise was such a unique phenomenon that Wüst and his colleagues wanted to understand what was happening in long COVID patients.

Key changes they discovered were differences in the body’s ability to generate energy compared to healthy patients. This included lower levels of oxidative phosphorylation—a biochemical process that yields ATP, a molecule that the body uses for energy. They also observed that after exercise there was a decrease in the activity of mitochondria, cellular power stations that manufacture the ATP molecules.

“Their mitochondrial function is impaired rapidly upon exercise,” Wüst says. “This can make them go into a vicious cycle, because every time they overexert themselves, they get a crash in their mitochondrial function and their metabolism.”

The impact on the body’s ability to manufacture energy are also echoed by the results from experiments where patients with post-exertional malaise performed two exercise tests—24 hours apart—in which they were asked to exercise until exhausted.

During the exercise test on the second day, patients with post-exertional malaise showed an impaired ability to manufacture energy and reached a point of exhaustion much sooner and with far less exercise than on the first day. For people without post-exertional malaise, they can do very similar amounts of exercise on both days before they reach exhaustion.

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The point at which the body shifts from using oxygen for energy to anaerobic metabolism—a biochemical process in the cell that produces less energy and is less efficient—is when people will “hit the wall” in terms of what they can do, as there is only a very small amount of energy left for the body to use.

For trained athletes, hitting the “wall” can come at the end of a marathon. For people with post-exertional malaise, hitting the “wall” can happen doing everyday activities, such as going for a walk around the block, taking a shower, or doing housework.

Your anaerobic threshold determines how much activity you can do before crashing from exhaustion, says Todd Davenport, a researcher at the University of the Pacific, whose research focuses on post-exertional malaise. You don’t function above your anaerobic threshold for very long or very well, he adds.

(For some long COVID patients, exercise is bad medicine)

This change to how the body uses energy is unique to patients with post-exertional malaise. For patients with other conditions that make it hard to exercise—such as heart failure, chronic obstructive pulmonary disease, or cystic fibrosis—exercise is still beneficial and there is no over-exertion-induced change in how their body makes energy.

Changes to muscle fiber composition

Another key difference that Wüst and his collaborators found were changes to the muscle composition of long COVID patients. These individuals had a higher proportion of fast-twitch muscle fibers compared to healthy patients.

Fast-twitch muscle fibers are used for quick, explosive movements, such as lifting heavy objects or sprinting, while slow-twitch muscle fibers are used for slower, steadier activity, such as walking or endurance running.

“We know that it is difficult to change fiber types in people, and that it doesn’t happen with inactivity,” Wüst says. “Something else is changing the fiber types.”

Although they don’t know what is driving this change, it may help explain some of the fatigue that patients are experiencing. “[Fast-twitch muscle fibers] use energy quicker, and therefore they fatigue quicker,” Wüst says.

Changes to the body’s ability to recover

In addition to the changes in the body’s ability to use energy, and the composition of muscle fibers, Wüst and his collaborators also found evidence of muscle damage.

In a healthy person, “muscles get torn down and built up, that’s how you get better after you exercise,” says Maureen Hanson, a molecular biologist at Cornell University, whose research focuses on understanding post-exertional malaise in long COVID and ME/CFS patients. “The healthy person has a response to the exercise, and that response is different than the response of the ME/CFS patient.”

In a number of studies carried out by Hanson and her collaborators, long COVID and ME/CFS patients show an impaired ability to recover from exercise. In a healthy person, the muscle damage caused by exercise will start getting repaired, causing them to get stronger in the process. In a person with post-exertional malaise, this repair process doesn’t work properly, leading to accumulated damage.

Evidence of this impaired exercise recovery was also seen in muscle tissue of long COVID patients in the Nature Communications study—signs of muscle scarring, inflammation, and blood clots, both before and after the exercise. “We saw a lot of muscle damage, and signs that there has been damage in the past,” Wüst says.

This damage is thought to be the result of multiple bouts of post-exertional malaise, which is then compounded by an impaired ability to recover.

“Often when we see people, they are in a slow rolling crash, it’s these constant waves of post-exertional malaise,” says Davenport, noting that for many patients with long COVID or ME/CFS, overexertion can happen while carrying out their daily activities, whether it’s going to the grocery store or brushing their teeth.

For patients with post-exertional malaise, this study affirms the importance of staying within their energy limits to minimize crashes, a strategy that is commonly referred to as pacing. “You want to minimize the severity and duration of post-exertional malaise,” Bateman says.