Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome.
Paul, Bindu D, Lemle, Marian D, Komaroff, Anthony L et al. · Proceedings of the National Academy of Sciences of the United States of America · 2021 · DOI
Quick Summary
This review examines how COVID-19 and ME/CFS may share similar biological problems, particularly an imbalance in how the body handles harmful molecules called free radicals. Both conditions appear to involve problems with inflammation, energy production in cells, and a slowed metabolism. While this research shows these biological abnormalities exist in both illnesses, more studies are needed to understand exactly how they work together and how to treat them.
Why It Matters
This review provides scientific validation that ME/CFS and long COVID-19 involve measurable biological abnormalities rather than being purely psychological conditions. Understanding these shared mechanisms could accelerate development of treatments applicable to both illnesses and help clinicians recognize long COVID-19 as potentially part of the ME/CFS disease spectrum.
Observed Findings
People with acute COVID-19 and ME/CFS show measurable redox imbalance (altered oxidative stress markers)
Both conditions demonstrate systemic and neuroinflammation with abnormal cytokine patterns
Cells in both conditions show impaired ability to produce sufficient ATP (energy currency)
Both illnesses are associated with a hypometabolic state (slowed overall metabolic rate)
These biological abnormalities also appear in other neurological diseases, suggesting shared pathophysiological mechanisms
Inferred Conclusions
Redox imbalance, inflammation, energy metabolism deficits, and hypometabolism are interconnected phenomena in ME/CFS and acute COVID-19 that may drive symptom severity
Long COVID-19 shares phenotypic features with ME/CFS and may involve overlapping molecular pathology requiring similar investigation
Identifying these molecular mechanisms provides targets for developing novel therapeutics for both post-infectious conditions
The bidirectional relationships among these biological abnormalities suggest treating one pathway may have cascading effects on others
Remaining Questions
Do these same biological abnormalities characterize long COVID-19 patients, and to what degree?
What This Study Does Not Prove
This review does not prove that redox imbalance directly causes ME/CFS or long COVID-19—it documents associations that may be correlational. It also does not establish that all ME/CFS cases involve identical biological mechanisms, nor does it provide evidence that current treatments targeting these pathways will be effective in patients.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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