For some long COVID patients, exercise is bad medicine

​They used to run marathons. Now, taking a shower is exhausting. But for these patients—who have one of the most debilitating symptoms of long COVID—hope may be on the horizon.

When Jessica Lambert was seen at a Chicago long COVID clinic in May 2021 after months of debilitating symptoms, a physical therapist told the formerly active, 37-year-old she was out of shape and started her on an exercise program. Lambert left the sessions exhausted, a fatigue beyond anything she’d ever felt after weightlifting and cycling. The next day she would wake up feeling worse. Forty-eight hours after therapy, her symptoms peaked, with a fever, deep muscle pain, nausea, and a migraine.

“I couldn’t get out of bed, except to move to the couch,” she says. “I’d stay there for the next four or five or six days and start climbing out of it just in time for my next appointment.” After two and a half months of weekly physical therapy sessions and a trip to visit her mother, she spent four months bedridden. Eventually, following a second bout of COVID, she could no longer walk at all.

Lambert didn’t know it, but she was experiencing post-exertional malaise, or PEM, one of the most mysterious and debilitating symptoms of long COVID. Defined as the significant worsening of symptoms or the development of new ones following even minor physical, mental, or emotional exertion, a PEM “crash” can take days, weeks, or months to recover from, and some people claim they never do. Almost 80 percent of an estimated 16 million adult long COVID patients in the U.S. say they are limited in their day-to-day function, a quarter of them significantly. About half have had to reduce work hours, and as many as four million long COVID patients in the U.S. are out of work altogether.

“People come in and tell me, I used to work out. I used to run. I used to love my job as the vice president of my company. And now I can’t do any of that,” says Mark VanNess, a researcher with the Workwell Foundation, which studies PEM in long COVID and other related chronic illnesses. “These are not people that want to stay home and collect disability. They’re forced to.”

In one study, about 75 percent of the almost 500 long COVID patients surveyed said physical activity made their symptoms worse, while less than one percent saw improvement. Still, in long COVID patients like Lambert, PEM is often ascribed to deconditioning—the effects of being inactive—that can be treated with exercise. But the narrative of deconditioning is slowly starting to change. “You used to run marathons and after a three-week viral infection you’re somehow unable to walk across one side of your apartment to the other? That’s not deconditioning,” says David Putrino, the director of rehabilitation innovation for the Mount Sinai health system in New York.

As doctors struggle to treat the approximately 65 million people worldwide with long COVID, PEM has ignited a debate about the role of physical activity in rehabilitation: Exercise is generally considered a universal medicine, but can it make some long COVID patients worse?

What is PEM?

For decades, PEM has been a hallmark symptom of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), a little-understood illness usually manifesting after a viral infection. About half of long COVID patients meet the criteria for ME/CFS. “When we started seeing long COVID, we thought, This looks pretty darn familiar,” says Brayden Yellman, a physician who treats ME/CFS and long COVID patients at the Bateman Horne Center in Utah. People with ME/CFS rate lower on quality-of-life measures than those with cancer, stroke, and multiple sclerosis—in large part because of PEM.

How PEM presents varies widely. A shower can leave some confined to bed for days. A short visit with friends can cause flu-like symptoms and trouble speaking. Watching a movie can lead to migraines and light sensitivity. Most of the afflicted describe a profound fatigue that can feel like a conscious coma, where they are unable to move or talk. “I’ve had patients say to me, If the house was on fire, I’m not sure I’d be able to get out,” Yellman says.

Because the onset of PEM is often delayed by 24 to 72 hours after exertion, patients may appear functional one day, then crash the next, making it hard to track. And, since there is no official diagnostic code for PEM, its prevalence in long COVID patients is difficult to determine via electronic health records, where it can appear as exercise intolerance or fatigue, two related but different symptoms. Patient surveys suggest that the percentage of COVID long haulers experiencing some form of PEM may be more than 90 percent.

In ME/CFS, PEM has historically been dismissed or downplayed as a combination of deconditioning and a psychological fear of exercise. Physicians prescribed graded exercise—therapy in which the intensity of physical activity is increased incrementally—and while some studies show it had a positive effect, between half and three-quarters of patients reported it made them worse. Eventually, many of the studies were criticized or independently discredited, and both the U.S. and U.K. governments removed graded exercise from ME/CFS official treatment guidelines. Still, exercise is commonly prescribed to long COVID patients: half of the current 388 international long COVID clinical trials are focused on rehabilitation, many involving exercise.

Biological causes of PEM

A growing trove of research shows that PEM has physiological underpinnings. In cardiopulmonary exercise tests spaced 24 hours apart designed to trigger PEM, researchers find that while active people, sedentary people, and even people with conditions like heart disease and cystic fibrosis perform generally the same from one day to the next, people with ME/CFS do worse on the second test. Other studies find that ME/CFS patients show decline on cognitive tests post-exercise while healthy people perform better. The studies also show these patients are missing certain metabolites in their urine, which suggests their bodies aren’t performing the necessary functions to recover.

Research by David Systrom, a physician at Brigham and Women’s hospital in Boston, might provide a hint as to why. When ME/CFS patients and those with long COVID exercise, Systrom discovered their veins were not moving blood to the heart efficiently, or “priming the pump.” He also found problems with oxygen exchange by the exercising muscle. Through skin biopsies, he sees nerve damage in most patients he tests. “It’s not what we’d expect in pure deconditioning,” Systrom says.

Systrom’s work points to a dysfunctional autonomic nervous system, which controls functions like breathing and circulation, and moves blood and oxygen through the body during and after exercise. He also theorizes that the mitochondria—the parts of our cells that make energy—might not harness oxygen correctly. This all impairs the body’s ability to recover.

Does exercise lead to decline?

The concept of long-term decline after pushing through exertion is well-known amongst providers who treat ME/CFS, and now long COVID.

“Repeated crashes of PEM are like an injury,” Yellman says. “If you stub your toe really hard on the door, you need to let it heal before you put your shoe back on. If you stub it every day, there’s going to be scarring and the toenail isn’t going to grow back.”

The answer, according to physicians familiar with PEM, is pacing—managing daily activities through periods of exertion and rest. It’s critical, Yellman says, to break what he calls “the push-crash cycle,” by learning to recognize energy limits and resting accordingly, which for some people can take months or even years. “I’ve never met a couch potato with this illness,” he says. “A type A personality is honestly a risk factor.”

Clayton Powers, a physical therapist with the University of Utah, first learned about PEM five years ago, while treating patients with postural orthostatic tachycardia syndrome (POTS), a type of autonomic nervous system dysfunction also common in long COVID that can be helped by a form of graded exercise. But he noticed many of his patients weren’t improving with his exercise prescriptions.

He changed his tactics, focusing instead on using heart rate monitors, education, and lifestyle modifications to help patients avoid PEM. “The amount of improvement switching from exercise to focusing more on pacing and energy conservation was drastic,” he says.

With a growing awareness of cases like Lambert’s, patients, advocacy organizations, clinicians, and researchers are pushing back against the National Institutes of Health’s $1.15 billion RECOVER project’s proposed exercise trial for long COVID. Duke University’s Clinical Research Institute, which is coordinating the study, says it’s aimed at combating exercise intolerance, fatigue, and other long COVID symptoms. In an emailed statement, the institute noted that “exercise is not recommended” for those experiencing PEM and claims researchers will carefully monitor for PEM and adapt the program accordingly, but does not explicitly say whether participants with PEM would be excluded.

Even if the trial successfully screens for PEM, advocates suggest that government funds for the five planned clinical trials might be better spent on testing pharmacological treatments that could help more long COVID patients and others with post-viral illness.

Is all exercise equal?

With long COVID encompassing about 200 symptoms, some patients may benefit from exercise. But doctors must know how to carefully screen patients before prescribing an exercise regimen. It’s part of why advocates are now petitioning the Centers for Disease Control and Prevention to create an official diagnostic code for PEM, hoping it will drive recognition, provide a way to track it, and give patients and providers clear guidance on treatments.

The U.S. ME/CFS clinician coalition is against exercise, Yellman says. “But the real answer is, it’s still good for you, if you can avoid PEM.” Yellman, Systrom, and other physicians who treat ME/CFS and long COVID emphasize that they don’t recommend any exercise until, after a combination of medication, treating comorbidities, and pacing, a patient can consistently perform daily activities without triggering PEM. Even then, what they prescribe is far less strenuous than what most people consider traditional exercise.

“If exercise is medicine, you should treat it like medicine,” Putrino says. “You should understand what the contraindications are, who might have adverse effects of the medicine, and how to dose the medicine effectively for each person.”

Putrino and his colleagues developed a specialized rehabilitation program to help some long COVID patients reboot their autonomic nervous systems. In it, patients slowly progress through a series of gentle movements while lying down and doing breathing exercises that promote their “rest and digest” response. Then they move to sitting and upright exercises over the course of a few months. But, unlike graded exercise that encourages patients to push through discomfort, the program is scaled back to about 30 percent of the previous effort at the first sign of PEM, and some people won’t progress past a certain level. Still, according to Putrino, after three months, most participants see fatigue halve and activity tolerance double.

The therapists in Jessica Lambert’s in-patient rehabilitation program employed a similar strategy to help her regain her ability to walk.

“They would start off with me laying down in bed, lifting one leg at a time, then resting,” she says. She eventually progressed to seated activities, like wheelchair yoga, that focused on her ability to better care for herself. Now she’s in physical therapy doing recumbent exercises, and the therapists pull back if she experiences PEM. In a year, she’s gone from being in a wheelchair to being able to walk slowly around the block. “It’s small,” she says, “but it feels huge.”

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