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Graded exercise therapy for individuals with Long COVID syndrome and postexertional malaise: Pro et Contra

A significant number of individuals with the postacute phase of COVID-19 exhibit neurological sequelae that include autonomic imbalance and exercise intolerance. The autonomic imbalance observed in individuals with long COVID syndrome significantly overlaps with dysautonomia syndrome observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In their recent articles, several authors have discussed the clinical management of autonomic dysfunction and graded exercise therapy for individuals diagnosed with long COVID syndrome. 

Previous studies suggested that neurorehabilitation and multimodal therapy can be delivered in outpatient and inpatient settings. Occupational therapy was recommended as a cornerstone of rehabilitation in individuals with post-COVID syndrome. Diem L. and coworkers suggested that patients with long COVID should use therapies that have proven successful in patients with multiple sclerosis, such as energy management education. They also recommended pacing, which establishes the optimal and individual balance between rest and activation periods (physical, cognitive, and emotional). This energy conservation strategy is known as the “Principle of Three Ps”, namely, prioritization, planning, and pause in everyday activities.

One systematic review of graduated exercise therapy found that patients with chronic fatigue syndrome experienced a reduction in fatigue and an improvement in sleep and physical function after completing graduated exercise therapy. Therefore, some authors have recommended that physical activity should be adapted to individual limitations to avoid severe post-exertional malaise. Diem L. et al. The Role of Neurorehabilitation in Post-COVID-19 Syndrome. Clin. Transl. Neurosci. 2023, 7, 13. https://doi.org/10.3390/ctn7020013  recent paper by Fedorowski et al. recommended graded exercise therapy in patients with post-exertional malaise based on the PACE trial. This trial reported positive outcomes of graded exercise and cognitive behavioral therapy in patients with ME/CFS. (Fedorowski et al. Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden. Nat. Rev.Cardiol  https://doi.org/10.1038/s41569-023-00962-3

In their article, Diem L. et al. stated that the NICE guidelines do not recommend graduated exercise therapy due to the evidence gathered from patient surveys and qualitative studies, indicating its ineffectiveness and detrimental effects. This decision has drawn strong criticism.

A group of authors from the Netherlands, Austria, Germany, and the United States also discussed the clinical management of cardiovascular autonomic dysfunction in patients with long COVID syndrome and expressed disagreement with the recommendations for graded exercise therapy for individuals with long COVID syndrome who suffer from postexertional malaise. Van Rhijn-Brouwer et al. stated that up to 85% of patients with long COVID syndrome can have a combination of postexertional malaise and cardiovascular autonomic dysfunction. They also pointed out that research that used modern, more accurate diagnostic criteria for postexertional malaise showed that exercise-based therapies frequently result in detrimental health outcomes for patients with ME/CFS.

Van Rhijn-Brouwer et al. emphasized that patients with long COVID syndrome should be classified according to the presence of postexertional malaise. They stated that graded exercise therapy should be avoided in individuals with long COVID and postexertional malaise. To support their views, the authors cited a previous cross-sectional study which demonstrated that 75% of 477 participants diagnosed with long COVID reported a worsening of symptoms and functional capacity after exercise therapy. They added that the recommendations in the article by Fedorowski et al. can be followed only in individuals with long COVID without postexertional malaise, and with ongoing surveillance for the emergence of postexertional malaise. 

Van Rhijn-Brouwer et al. concluded that individuals with long COVID and postexertional malaise should be supported in maintaining their daily activities within their available fund of energy. These patients should be managed by employing other nonpharmacological and pharmacological interventions outlined in the article by Fedorowski et al.

This article was published in Nature Review Cardiology.

Journal Reference

van Rhijn-Brouwer, F.C.CC., Hellemons, M., Stingl, M. et al. Graded exercise therapy should not be recommended for patients with post-exertional malaise. Nat Rev Cardiol (2024). (Open Access) https://doi.org/10.1038/s41569-024-00992-5

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