Physiological reportsSep 2, 2025

Exercise limits in long COVID and chronic fatigue syndrome/myalgic encephalitis involve similar body mechanisms

Long Covid Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

Long COVID and CFS/ME may share impaired skeletal muscle oxygen diffusion as a driver of exercise intolerance.

Evidence

An invasive cardiopulmonary exercise study in 15 PASC patients, 11 CFS/ME patients, and 11 controls found reduced peak oxygen consumption in both patient groups, with skeletal muscle oxygen diffusion the most impaired parameter and simulated normalization improving peak oxygen uptake by 66% in PASC and 34.7% in CFS/ME.

Caveat

This was a very small mechanistic physiology study with simulated intervention effects, so it cannot show that correcting muscle oxygen diffusion will improve symptoms in broader patient populations.

Simplified

Post-acute sequelae of SARS-CoV-2 (PASC or "long COVID") and chronic fatigue syndrome/myalgic encephalitis (CFS/ME) share symptoms such as exertional dyspnea. We used exercise oxygen pathway analysis, comprising six parameters of oxygen transport and utilization, to identify limiting mechanisms in both conditions. Invasive cardiopulmonary exercise testing was performed on 15 PASC patients, 11 CFS/ME patients, and 11 controls. We evaluated the contributions of alveolar ventilation (V̇a), lung diffusion capacity (D), cardiac output (Q̇), skeletal muscle diffusion capacity (D), hemoglobin (Hb), and mitochondrial oxidative phosphorylation (V) to peak oxygen consumption (V̇O). To simulate targeted interventions, each variable was sequentially normalized to assess its impact on V̇O. V̇Owas significantly reduced in both PASC and CFS/ME compared to controls. Skeletal muscle Odiffusion (D) was the most impaired parameter in both patient groups (p = 0.01). Correcting Dalone improved V̇Oby 66% in PASC (p = 0.008) and 34.7% in CFS/ME (p = 0.06), suggesting a dominant role for peripheral Oextraction in exercise limitation. Impaired skeletal muscle oxygen diffusion (D) is a shared mechanism of exercise intolerance in PASC and CFS/ME and may represent a therapeutic target. However, our findings are limited by small sample size. L M max2peak2peak2peak2M M2 2M

Full Text

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Funding

Competing interests

Dr. Rischard reports no direct conflicts related to this manuscript. His general disclosures include consulting relationships with Acceleron/Merck and United Therapeutics. He receives research support from the NIH, NHLBI, Ismed, United Therapeutics, Bayer, Merck, Janssen, Keros, and Aerovate. Dr. Levine has a financial interest in Corinthian Reference Labs and CND Life Sciences.

PubMed

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Exercise limits in long COVID and chronic fatigue syndrome/myalgic encephalitis involve similar body mechanisms

Abstract

Full Text

Funding

Competing interests

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