McMaster researchers find talk therapy, rehabilitation likely improve long COVID symptoms

Cognitive behavioural therapy (CBT) and a program of physical and mental rehabilitation likely improve symptoms of long COVID, but the effects are modest, finds a review of the latest evidence by McMaster University researchers.

Although most patients recover from COVID-19 infection, up to 15 per cent — an estimated 65 million people globally — experience long-term health effects. Health-care providers are increasingly seeing patients with long COVID and, in the absence of trustworthy and up-to-date summaries of the evidence, patients may receive unproven, costly, and ineffective or harmful treatments.

The study, published in The BMJ on Nov. 27, 2024, shows that, compared with usual care, an online program of CBT likely reduces fatigue and improves concentration, and an online, supervised combined physical and mental rehabilitation program likely increases the proportion of patients that experience meaningful improvement or recovery, reduces symptoms of depression and improves quality of life.

Intermittent aerobic exercise is likely to improve physical function compared with continuous aerobic exercise. But the researchers found no compelling evidence to support the effectiveness of other interventions.

“Long COVID is a complex condition, presenting with symptoms like fatigue, muscle pain, and cognitive impairments. Patients with long COVID face persistent physical and mental health challenges and often feel isolated or dismissed by health-care providers. Meanwhile, providers express uncertainty about how to effectively manage long COVID. We hope the findings from our living review will guide optimal care for patients,” says Dena Zeraatkar, lead author of the study and assistant professor with McMaster University’s Department of Anesthesia.

Researchers trawled databases for trials randomizing adults with long COVID to drug or non-drug interventions, placebo or sham, or usual care. They found 24 relevant trials involving 3,695 patients investigating drugs, physical activity or rehabilitation, behavioural interventions, dietary interventions, medical devices and technologies, and combinations of physical exercise and mental health rehabilitation. The trials were of varying quality, but the researchers were able to assess their risk of bias and certainty of evidence.

“Our review identified talk therapy and physical and mental rehabilitation as the only current, evidence-based therapies for long COVID. An important area of study will be how best to engage patients in participating in such approaches, as pursuing gradual increases in function may seem counter-intuitive for many,” says Jason Busse, senior author of the study and professor with McMaster’s Department of Anesthesia.

Researchers did not find compelling evidence to support the effectiveness of other interventions, including the antidepressant vortioxetine, the antibody leronlimab, a combination of probiotics and prebiotics, the antioxidant coenzyme Q10, brain retraining, transcranial direct current stimulation, inspiratory (breathing) muscle training, hyperbaric oxygen, and a mobile education app on long COVID.

This was a rigorous review, designed with input from people with lived and living experience of long COVID, and with a focus on outcomes that are important to patients. There are, however, limitations.

“Promising interventions, such as CBT and physical and mental health rehabilitation, were only investigated in single trials, and replication in other settings is required to inform generalizability. Further, long COVID may be a heterogeneous condition, and it’s unclear whether these interventions are broadly effective across all phenotypes of long COVID,” Zeraatkar says.

These results will be updated as new evidence becomes available, researchers say.

“We hope that our review will provide trustworthy summaries of the evidence on interventions for managing long COVID. Unlike a conventional review that is only up-to-date at a single point in time, we will update this review as new evidence emerges,” Zeraatkar adds.