Circadian rhythm disruption in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for the post-acute sequelae of COVID-19. — ME/CFS Atlas
Circadian rhythm disruption in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for the post-acute sequelae of COVID-19.
McCarthy, Michael J · Brain, behavior, & immunity - health · 2022 · DOI
Quick Summary
This review examines whether disrupted body clocks (circadian rhythms) contribute to ME/CFS symptoms like fatigue, sleep problems, and cognitive difficulties. The authors focus on a specific immune molecule called TGFB that may interfere with the body's natural daily rhythms. They suggest that COVID-19 infections may cause similar circadian disruptions, potentially explaining why some people develop long COVID symptoms that resemble ME/CFS.
Why It Matters
This study bridges emerging chronobiology research with ME/CFS pathophysiology at a critical moment, as long COVID increases public awareness of ME/CFS-like conditions. Understanding circadian rhythm disruption as a potential mechanism could lead to new diagnostic markers and targeted therapies (such as chronotherapeutic interventions) for both ME/CFS and PASC. The focus on TGFB as a testable molecular bridge between circadian function and ME/CFS symptoms offers a concrete research direction.
Observed Findings
ME/CFS is characterized by persistent fatigue, exercise intolerance, sleep disturbance, autonomic dysfunction, and cognitive problems
Circadian rhythm abnormalities have been examined in ME/CFS for decades, but older studies lacked modern molecular methods
SARS-CoV-2 and related coronavirus infections cause persistent changes in TGFB signaling
Previous coronavirus outbreaks (pre-COVID) were associated with ME/CFS-like syndromes
TGFB has known roles in regulating circadian rhythms, particularly in peripheral organ systems
Inferred Conclusions
Disrupted TGFB signaling may be a common mechanism linking viral infections, circadian rhythm dysregulation, and ME/CFS symptoms
Modern molecular chronobiology methods and advancing biomarker research justify renewed investigation of circadian dysfunction in ME/CFS
Circadian rhythm considerations may offer new therapeutic targets and improved understanding of PASC and long COVID
The overlap between ME/CFS and long COVID suggests shared circadian-immune mechanisms triggered by viral infection
Remaining Questions
Does TGFB dysfunction directly cause circadian rhythm disruption in ME/CFS, or is it one of multiple contributing factors?
What This Study Does Not Prove
This review does not establish that circadian rhythm disruption is the primary cause of ME/CFS, nor does it provide new experimental evidence proving TGFB dysfunction drives ME/CFS symptoms. The authors explicitly acknowledge that existing evidence remains inconclusive and that correlation between circadian abnormalities and ME/CFS does not confirm causation. This is a conceptual framework rather than a definitive mechanistic proof.
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 →