Key findings guide clinical recommendations regarding exercise, respiratory training, and cognitive therapy., Don L. Goldenberg, MD,

Despite the marked decline in cases of COVID-19 during the past few years, there continues to be an enormous toll globally from the chronic medical symptoms that have persisted long after the initial SARS-CoV-2 infection. This has been termed Long COVID, characterized by its multiple chronic symptoms, most notably exhaustion, muscle pain, and cognitive, sleep, and mood disturbances. These symptoms cannot be explained by another disease or well-defined organ damage.

At least 65 million people worldwide have long COVID. Five percent (5%) of the general population currently report such persistent symptoms, and in three-quarters of this population, these chronic symptoms have lasted more than 1 year.¹

How best to rehabilitate these patients whose multiple symptoms have persisted for months to years and continue to interfere with their lives has been a major focus of research. Herein, I review some of the key study findings to help guide care.

Define and Separate Long COVID Patient Cohorts

Initial reports of post-COVID outcomes and rehabilitation included hospitalized patients who had pulmonary or other organ damage and others who met criteria for post-ICU syndrome. For example, a systematic review of COVID rehabilitation clinical practice guidelines² did not differentiate such patients from what most investigators consider to be long COVID, characterized by Phillips and Williams in 2021: “Long COVID is not a condition for which there are currently accepted objective diagnostic tests or biomarkers. It is not blood clots, myocarditis, multisystem inflammatory disease, pneumonia, or any number of well-characterized conditions caused by COVID-19.”³

It is recommended that rehabilitation interventions in long COVID not lump together all patients with chronic symptoms but rather distinguish those with cardiac or pulmonary damage. Exercise tolerance testing and pulmonary function tests should be taken before and tracked during rehabilitation, although the vast majority of studies in non-hospitalized patients with long COVID have revealed no major pulmonary or cardiac abnormalities.^4,5 Dysfunctional breathing, deconditioning, and chronotropic incompetence are important contributors to long COVID exercise intolerance.⁵

Positive Results of Physical Exercise-Based Rehabilitation

In 1,000 non-hospitalized patients with long COVID, exercise rehabilitation programs were well-tolerated, enhanced aerobic fitness and physical function, and relieved symptoms of dyspnea, fatigue, and depression.⁶ Two systematic reviews and a meta-analysis concluded that exercise-based rehabilitation is effective and well-tolerated in individuals with long COVID.^7,8 In the first review, exercise and respiratory training in long COVID improved functional capacity, dyspnea, and quality of life, with a high probability of improvement compared with the current standard care.⁷

The second systematic review of 24 trials comprising 3,695 patients with long COVID concluded that intermittent aerobic exercise and a program of integrated physical and mental health rehabilitation were effective in improving long COVID symptoms and quality of life.⁸

A separate online supervised long COVID rehabilitation program utilized carefully prescribed incremental exercise, referred to as pacing, with cognitive behavioral therapy.⁹ There was substantial improvement in long COVID symptoms and no episodes of exacerbations of post-exertional malaise (PEM).

Key Findings from Long COVID Rehabilitation Studies

• Differentiate patients with organ damage or post-ICU syndrome.^2,3
• Exercise tolerance tests and pulmonary function tests should be routinely checked prior to and during rehabilitation, but most individuals with long COVID have no major cardiac or pulmonary abnormalities.^4,5
• Incremental exercise training, termed pacing, has been safe and effective in long COVID, and is often best integrated with strength training and cognitive behavioral training.^6-9
• There continues to be concern about exercise exacerbating post-exertional malaise (PEM), which needs to be carefully assessed.^10,11

Clinical Cautions

An absence of exercise-induced PEM exacerbation may help to balance out the media and popular press warning against exercise for individuals with long COVID, as reported by one journalist, “Just about any form of physical, mental, or emotional exertion – in some cases, activities no more intense than answering emails, folding laundry, or digesting a particularly rare steak – can spark a debilitating wave of symptoms called a crash that may take weeks or months to abate.”¹⁰ Much of this exercise concern relates to the overlap of long COVID with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS),¹² and the concern that even slowly incremental exercise (pacing) exacerbates ME/CFS.

Despite the positive results of exercise as part of long COVID rehabilitation, the potential of exercise-induced exacerbation of post-exertional malaise (PEM) needs to be addressed with additional rehabilitation trials, as recent reviews have emphasized.^7-9 Deconditioning alone is not the whole answer as long COVID exercise intolerance and focal muscle and nerve dysfunction have been linked to PEM.

“Any rehabilitation program evaluation should include the current severity and stage of long COVID, patient sex, training modalities, and results that are analyzed with standardized methods.”

An individualized long COVID rehabilitation approach is required, with careful attention to PEM. Any rehabilitation program evaluation should include the current severity and stage of long COVID, patient sex, training modalities (content, length, duration, intensity, frequency), and results need to be analyzed with standardized methods.¹¹

Possibly the most persuasive messages about the importance of exercise and activity in long COVID include a report that linked pre-pandemic inactivity to an increased risk of long COVID and increased the odds of a poor outcome,¹³ and another report that higher levels of physical activity reduced mental and neurological symptoms in the 2 years after COVID-19 infection in young women.¹⁴ We can now safely say that carefully prescribed incremental exercise, integrated with respiratory training, education, and cognitive therapy, is recommended for long COVID rehabilitation.