Long COVID Symptoms Improve With Outpatient Intervention

Self-reported physical function was better for long COVID patients after a brief outpatient program based on cognitive and behavioral therapy, a pragmatic trial in Norway showed.

Scores on the Short-Form Health Survey 36 Physical Function Subscale (SF-36-PFS) — a 100-point scale with higher scores reflecting better physical functioning — improved in the intervention group compared with usual care (difference 9.2 points, 95% CI 4.3-14.2, Pd = 0.43), reported Tom Farmen Nerli, MD, of Vestfold Hospital Trust in Tønsberg, Norway, and co-authors.

The between-group difference was nearly identical at long-term follow-up (12 months after enrollment), indicating a sustained effect, Nerli and colleagues wrote in JAMA Network Open.

Most other measures of functional capability and symptom scores showed more improvement in the intervention group. Adverse events in the intervention group were fewer compared with usual care.

“Patients can recover from post-COVID condition,” Nerli said. “This intervention is effective and safe. The treatment is brief, but giving patients an explanation they can relate to — an explanation for their symptoms — is important,” he told MedPage Today.

For over a decade, Nerli and his team have treated other patients with persistent physical symptoms — mainly, fatigue and pain — with this intervention.

“For us, it is essential to foster a belief that the body has the potential to adapt, and that a positive adaption towards a normal health state requires an active pursuit of physical and mental tasks that are individualized, suitable, feasible, and enjoyable,” he said. “We differ a lot from others with our way of working, but our experience over years has made us confident.”

The findings add to an emerging body of evidence suggesting that cognitive behavior therapy (CBT) and rehabilitation can improve long COVID symptoms and functioning, noted Trudie Chalder, PhD, MSc, of King’s College London in England. In the Netherlands, for example, CBT improved symptoms in long COVID patients with severe fatigue.

“Over the past few decades, substantial evidence has amassed for the efficacy of CBT for symptoms in the context of somatic conditions, including chronic fatigue syndrome,” Chalder wrote in an accompanying editorial.

“Cognitive behavior therapy is not only positively associated with immune parameters, such as proinflammatory cytokines and immune cell counts, in patients with physical health conditions but also outperforms pharmacologic treatments, such as infliximab [Remicade], in that the effects last longer,” she observed.

Long COVID includes fluctuating symptoms like postexertional malaise, fatigue, brain fog, or other manifestations that persist for at least 3 months after SARS-CoV-2 infection. Recent CDC data have suggested that 6.4% of U.S. adults have long COVID, with about one in five reporting major limitations in performing daily activities.

In their trial, Nerli and co-authors randomized 314 patients with mild to moderate long COVID to a rehabilitation program or usual care at a single referral center in Norway. They followed up with participants after treatment completion and 12 months after enrollment, collecting data from February 2022 to April 2024.

Overall, 231 people completed an SF-36-PFS evaluation, which was the primary endpoint. Primary outcome data were analyzed on an intention-to-treat basis.

Participants had a mean age of 43 years, and 72% were women. Fatigue, cognitive difficulties, and postexertional malaise were the most prevalent long COVID symptoms.

The rehabilitation program involved two to eight outpatient visits with about 2 to 6 weeks between them with the overall aim of restoring physical function. The intervention involved physicians and physiotherapists and was grounded in the cognitive activation theory of stress, which states that any stressful event necessitates an adaptive response.

“Cognitive factors, such as subconscious expectancies, are key determinants of the degree and duration of the adaptive response and are themselves shaped by individual learning history,” Nerli and colleagues noted.

Nine people in the intervention group reported lower physical function from baseline to the primary outcome, compared with 25 people in the usual care group. Fourteen people in the intervention group reported an increase in postexertional malaise from baseline to the primary outcome, compared with 31 people who received usual care.

Study limitations included the single-center design of the trial and its lack of blinding. Objective measures of physical and social function — such as steps per day or work attendance — were not reported in the study.

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