Exercise training in long COVID: the EXER-COVID trial

Post-COVID-19 syndrome, also referred to as long COVID is a multisystemic condition characterized by fatigue, headaches, attention deficits, low energy, functional impairment, sleep disturbance, and dyspnea. While the underlying mechanisms of long COVID remain unclear, several hypotheses have been proposed, including persisting viral reservoirs, immune dysregulation, alterations in the host microbiome, autoimmunity, and endothelial dysfunction. Treatments such as vaccinations, pharmacotherapy, nutritional support, rehabilitation, and physical exercise have been shown to improve symptoms.

It appears reasonable to cautiously incorporate exercise into rehabilitation protocols, with careful adjustments to intensity based on each patient’s symptoms and abilities. We hypothesized that nonhospitalized patients with long COVID would benefit from structured exercise. In a randomized cross-over trial, we assessed the effects of a 6-week personalized PRT intervention, with a 5-day washout period between arms on cardiopulmonary fitness, muscular strength, long COVID symptoms, QoL, and emotional distress.

These findings indicate that the PRT program yields both physical and mental benefits. While our results do not offer insights into the optimal duration of exercise programs, the data provide strong support for the use of this nonpharmacological intervention in real-world settings. The absence of functional or exercise tolerance outcomes does limit the interpretability of these results. Yet, prior evidence has shown that improvements in muscle strength may lead to enhanced functional capacity in individuals recovering from post-COVID-19 syndrome. Furthermore, our exploratory analysis identified a correlation between baseline Ferritin, a well-known inflammation marker, and improvements in peak V? O2. This suggests that clinical improvements may, at least in part, be mediated by reductions in inflammation. Further mechanistic studies are needed to confirm these findings.

Robinson Ramírez-Vélez, Julio Oteiza, Gaizka Legarra-Gorgo?on, Sergio Oscoz-Ochandorena, Nora García-Alonso, Yesenia García-Alonso, María Correa-Rodríguez, Adrian Soto-Mota, Mikel Izquierdo, Exercise training in long COVID: the EXER-COVID trial, European Heart Journal, 2024;, ehae721, https://doi.org/10.1093/eurheartj/ehae721

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European Society of Cardiology American College of Cardiology Cardiology Consultants of Philadelphia Navarrabiomed. Centro de Investigación Biomédica. UPNA NUP