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Fatigue leads the list of persistent problems experienced by people with long Covid — which is why patients have pushed back against treatment approaches that endorse escalating levels of exercise for a condition that researchers are still trying to understand. They fear post-exertional malaise, the debilitating price to be paid for pushing their bodies too hard.

Researchers from the U.K. were well aware of those potential harms. Working with patients, they designed a trial called REGAIN to test a way to provide mental health therapy and exercise guidance to people with long Covid without making their conditions worse. Their goal was to help people manage their symptoms, improve their functioning, and reduce their distress.

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On Wednesday, they reported in BMJ that people enrolled in an online program said their health improved more than people who received standard care, which was a one-hour advice session on how to cope with such problems as fatigue, shortness of breath, brain fog, and muscle aches.

“Rehab delivered live online improves health-related quality of life for people with long Covid at three and 12 months,” study co-author Gordon McGregor, professor of clinical exercise physiology and rehabilitation at University Hospitals Coventry & Warwickshire NHS Trust, said on a call with reporters. “This is the first high-quality study to confirm the benefit and also confirm a lack of harm from rehabilitation.”

The 485 study subjects, who had been discharged three months earlier from hospital stays for Covid-19, were divided into two groups. One group of 287 people had a one-on-one session in which the general advice for coping was given. The intervention group of 298 also had an hour-long session, but it was devoted to planning an individual, self-paced approach to eight-week group sessions of psychological counseling and exercises.

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That intervention was developed with people who had long Covid, as well as with clinicians, academics, and other stakeholders involved in care of people with the condition. “It was very much led by the long Covid community,” McGregor said.

The weekly home-based sessions were online, a decision made with the large number of people who might potentially benefit from such treatment in mind. The exercises were as simple as steps and squats for some and chair-based movements for others, supervised by a trained physiotherapist or exercise physiologist, and supported by health psychologists. The goal was to help improve muscle strength and endurance, cardiovascular fitness, coordination, and balance — and to build confidence to engage in physical activity.

No special equipment was required, just body weight, and “no planks,” McGregor said — just “any kind of movement that would involve improvements in strength, balance and proprioception … to try and get people moving, more than anything.”

After three months, 17% of people in the intervention group reported on standard research questionnaires that their overall health was “much better now,” compared with 8% in the usual care group. After 12 months, depression was lower in the intervention group compared to the usual care group; cognitive function was the same.

Early on, the researchers were contacted by members of advocacy groups who expressed concerns about exercise training.The fear is that, as in another post-viral condition, myalgic encephalomyelitis or chronic fatigue syndrome, intense fatigue and worsening of other health issues after physical or mental activity will follow exertion. A clinical trial looking at exercise in RECOVER, the controversial long Covid research project from the National Institutes of Health, prompted backlash when an exercise study was announced in late 2022.

There are some caveats to keep in mind with the REGAIN study, outside experts said.

“This study focuses on a post-hospitalized group who are demographically distinct from the community-managed post-Covid patients we see much more commonly,” said Emily Fraser, a consultant in respiratory medicine at Oxford University Hospitals NHS Foundation Trust, and clinical lead of the post-Covid clinic in Oxford. She was not involved in the trial. “I think we therefore need to be careful how we extrapolate the findings to community patients.”

Matt Sydes, professor of clinical trials and methodology at University College London and also not involved in the trial, has questions. “It would be interesting to know more about the duration of symptoms participants had before joining the trial, particularly as people might look to apply the findings now to people who have been living with long Covid for a prolonged period.”

A companion editorial approved of the trial’s approach: “Regular monitoring in the REGAIN trial did not identify any episodes of post-exertional exacerbations of symptoms, providing reassurance that individualized exercise at home in online groups supervised by a trained physiotherapist or exercise physiologist is safe.”

Study co-author McGregor struck a modest tone.

“We’re not under any illusions. REGAIN is not a panacea,” he said. “We believe that these findings will assist clinicians with treatment strategies.”

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