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Solve-funded Grantee Strengthens Connection Between ME/CFS and Long Covid Exercise Intolerance

Solve M.E. funded Dr. David M. Systrom at Brigham and Women’s Hospital in 2017 to study exercise intolerance in ME/CFS. Six years later, his findings have redefined our understanding of the exertion problems people with ME/CFS and related conditions like Long Covid face. The first-ever trial to directly test a promising treatment called Mestinon is also underway. 

What Dr. Systrom did:

Dr. David M. Systrom has long been at the forefront of using exercise testing for diagnostic and research applications. His clinic at Brigham and Women’s Hospital (BWH) uses invasive cardiopulmonary exercise testing (iCPET) to study patients with unexplained shortness of breath (dyspnea) or inability to exercise. The iCPET collects traditional CPET information plus a more comprehensive evaluation of breathing, heart function, and gas exchange at rest and while on an upright bike. 

In 2017, Solve M.E. and an anonymous donor initiated a ME/CFS Research Fund at BWH to bring iCPET to ME/CFS research. In a dedicated study of 160 ME/CFS patients, the research team found nearly half of patients were unable to supply sufficient oxygen to the muscles from the blood. Some patients in this group had signs of dysfunctional mitochondria (the energy powerhouses in our cells) while others exhibited hyperventilation, causing a reduction in available oxygen. The team also found a reduction of blood volume returning to the heart from blood vessels (called preload failure) in 15% of patients.

A new review paper in Chest from Dr. Systrom and colleagues details evidence from hundreds of exercise tests that suggests similar processes are producing ME/CFS and Long Covid symptoms; specifically dysregulated blood flow, hyperventilation, mitochondrial dysfunction, and small fiber neuropathy (damaged nerve fibers). The findings are similar to connective tissue diseases, POTS, and Long Covid studies that have uncovered patterns of disrupted blood flow and oxygen delivery problems in patients. 

While deconditioning, or a decline in physical functioning that results from lack of activity, has often been cited as an explanation of exercise intolerance, these results argue against this explanation since deconditioning is not associated with the physiologic changes observed in this new study.

These research efforts have opened up new, impactful ways to understand ME/CFS and related illnesses, implicating pathways that may be meaningful targets for treatments. In fact, the iCPET findings have already led to treatment trials of a drug called Mestinon, which might improve blood flow back to the heart, breathing, and oxygen uptake in the muscles.

SOURCE: Joseph P, Singh I, Oliveira R, Capone CA, Mullen MP, Cook DB, Stovall MC, Squires J, Madsen K, Waxman AB, Systrom DM, Exercise Pathophysiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-Acute Sequelae of SARS-CoV-2: More in Common Than Not?, CHEST (2023), doi: https://doi.org/10.1016/j.chest.2023.03.049 

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