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For patients with long COVID, an 8-week online rehabilitation program with weekly supervised group exercise and psychological support sessions improved health-related quality of life, the randomized REGAIN trial showed.

Among nearly 600 patients, those participating in the rehab program experienced improvements in health-related quality of life at 3 months compared with those who had a single online session with a practitioner, as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) preference (PROPr) score (adjusted mean difference 0.03, 95% CI 0.01-0.05, P=0.02), reported Gordon McGregor, PhD, of University Hospitals Coventry and Warwickshire NHS Trust in England, and colleagues in .

This was driven primarily by greater improvements in the PROMIS subscores for depression (adjusted mean difference 1.39, 95% CI 0.06-2.71, P=0.04), fatigue (2.50, 95% CI 1.19-3.81, P<0.001), and pain interference (1.80, 95% CI 0.50-3.11, P=0.01).

The PROMIS-PROPr score ranges from -0.022 to 1.0, where 0 indicates a health state equivalent to death and 1.0 indicates perfect health.

The effects were sustained at 12 months (adjusted mean difference 0.03, 95% CI 0.01-0.06, P=0.02). When comparing overall heath to 3 months prior, a higher proportion of the intervention group (17% vs 8%) reported feeling "much better now."

"At about 3 months, and more importantly, at 12 months, there was a meaningful difference between the intervention group and the control group in their quality of life," McGregor told MedPage Today. "And equally important, there was no harm."

According to the authors, the underlying pathophysiology of long COVID is still not clear, its symptoms are diverse, and medical treatments are, so far, limited. In other long-term conditions, they wrote, physical and mental health rehabilitation have improved breathlessness, fatigue, and quality of life. "No high-quality definitive evidence exists as to the potential benefits or harms of physical and mental health rehabilitation interventions," they noted.

However, such interventions have been the subject of some controversy. In an , Rana S. Hinman, PhD, of the University of Melbourne in Australia, and Chris G. Maher, PhD, DMedSc, of the University of Sydney, wrote that long COVID "affects numerous organ systems and is associated with increased risk of developing myalgic encephalomyelitis. Post-exertional malaise features in both conditions, raising concerns about the safety of exercise."

Still, they pointed out that the , which excluded those with contraindication to exercise training, "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.

From January 2021 to July 2022, McGregor and colleagues used the National Health Services' Digital "Digi-Trials" mailout to recruit patients, and patients could also self-refer. The researchers conducted eligibility phone calls to ask prospective participants about substantial lasting effects they attributed to their COVID-19 hospitalization. Exclusion criteria included contraindication to exercise, severe mental health problems that would prevent engagement with study procedures, and being enrolled in a clinical trial already.

They included a total of 585 adults ages 26 to 86 who had been discharged from the hospital 3 or more months previously and reported ongoing substantial COVID-related physical and/or mental health conditions. Mean age of participants was 56, and 52% were women. Mean time from hospital discharge was 323 days.

Participants in the control group had a 30-minute one-to-one consultation with a trained practitioner, and also received a booklet with COVID recovery information and advice. The intervention was an 8-week, online home-based group rehabilitation program, which included a 1-hour one-to-one consultation with a REGAIN practitioner, weekly practitioner-led group exercise sessions, and six hour-long live group psychological support sessions.

The researchers recorded 21 serious adverse events, and one was determined to be possibly related to the trial intervention (syncope with vomiting 24 hours after a live exercise session). Two adverse events (not serious), including knee pain during an exercise session and severe anxiety before an exercise session, were definitely related, and two were probably related (anxiety before a live exercise session and headache during a live exercise session).

"No instances of post-exertional symptom exacerbation were identified during weekly monitoring," McGregor and team noted.

Limitations acknowledged by the authors included an inability to mask patients and practitioners to treatment, no established threshold for a clinically meaningful PROPr score, and a lack of ethnic and racial diversity.

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