Charlton et al. (2026)
- Authors: Braeden T. Charlton, Kasper Janssen, David M. Systrom, David Putrino, Rob C.I. Wüst
- Institutes: Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, DeSportarts, Sports and Exercise Medicine Clinic, Utrecht, The Netherlands, Department of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA, Cohen Center for Recovery from Complex Chronic Illness, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Publisher: British Journal of Sports Medicine
- Link: DOI
Summary
This paper challenges the long-standing clinical assumption that exercise intolerance in Long COVID and ME/CFS is simply a result of physical inactivity. By distinguishing between cardiac deconditioning and the unique physiological impairments of post-exertional malaise, the authors advocate for a safer, patient-centered approach to rehabilitation. This shift is crucial for protecting patients from the harm often caused by standardized exercise programs that ignore the underlying cellular and vascular pathology.
What was researched?
The researchers investigated whether the cardiac alterations and exercise intolerance observed in Long COVID patients are caused by physical deconditioning or by distinct pathological mechanisms related to post-exertional malaise (PEM).
Why was it researched?
Historically, medical guidelines have often attributed fatigue and low exercise capacity in post-viral syndromes to ‘deconditioning,’ leading to recommendations for graded exercise that can be harmful. This study aimed to clarify the pathophysiology to ensure that clinical management strategies align with biological evidence rather than outdated assumptions.
How was it researched?
The authors synthesized physiological data from invasive cardiopulmonary exercise testing (iCPET) and studies on mitochondrial and endothelial function. They compared typical patterns of deconditioning with the specific abnormalities seen in Long COVID and ME/CFS patients, such as preload failure and impaired oxygen extraction.
What has been found?
The study found that cardiac abnormalities in these patients, including preload failure and inflammation-mediated scarring, are largely independent of physical inactivity. To manage symptoms, the authors highlight the potential benefits of targeted pharmacotherapy such as low-dose naltrexone 💊, beta-blockers 💊, and pyridostigmine 💊.
Discussion
The authors argue that traditional cardiac rehabilitation models are inappropriate for patients with PEM because they fail to account for cellular-level dysfunction. They emphasize the need to distinguish between ‘normal’ deconditioning and the active disease processes that cause symptoms to worsen after exertion.
Conclusion & Future Work
The paper concludes that management for Long COVID must be individually tailored and guided by exercise physiology to avoid triggering PEM. Future research and clinical practice should prioritize pacing and the stabilization of cellular health over traditional aerobic training.