The pivotal role of central sensitization in long COVID, fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome.
Goldenberg, Don L · Expert review of neurotherapeutics · 2025 · DOI
Quick Summary
This study shows that long COVID, fibromyalgia, and ME/CFS may all share a common underlying problem called central sensitization—where the nervous system becomes overly sensitive to pain and other sensations. Rather than being caused by organ damage or infection, these conditions seem to involve how the brain and nervous system process signals. The research suggests that treating these conditions with a coordinated team approach tailored to each person may be more effective than treating them as completely separate diseases.
Why It Matters
This framework challenges the notion that ME/CFS, fibromyalgia, and long COVID are multiple unrelated diseases, potentially validating decades of patient and researcher experiences of symptom overlap. Recognizing these conditions as central sensitization syndromes may lead to more appropriate diagnostic approaches and treatment strategies tailored to nervous system dysfunction rather than searching for specific organ damage. This work could reduce diagnostic delays and improve quality of care for millions of patients.
Observed Findings
Long COVID, fibromyalgia, and ME/CFS share similar clinical presentations including pain, fatigue, cognitive dysfunction, and post-exertional malaise when organ-specific pathology is excluded.
These three conditions demonstrate similar pathophysiological features consistent with central sensitization.
Current management approaches for these conditions overlap significantly in clinical practice.
The symptoms in long COVID are not explained by persistent viral presence or organ damage in most patients.
Inferred Conclusions
Long COVID should be reclassified as a central sensitization syndrome when organ disease is excluded, rather than as a post-viral or inflammatory condition.
The three conditions (long COVID, fibromyalgia, ME/CFS) represent a single syndrome with shared nervous system dysfunction rather than distinct diseases.
Personalized, multidisciplinary primary care-led management is the optimal approach for central sensitivity syndromes.
Remaining Questions
What specific mechanisms trigger the transition from acute COVID-19 infection to persistent central sensitization in some individuals but not others?
Which validated biomarkers or diagnostic tests can reliably identify and measure central sensitization severity in these patient populations?
What This Study Does Not Prove
This review does not prove that central sensitization is the sole cause of long COVID or ME/CFS, nor does it establish the mechanisms by which viral infection triggers this sensitization. The study is a narrative literature review and does not present new primary data, mechanistic studies, or randomized controlled trials testing specific treatments. Correlation between symptom profiles does not establish causation or exclude potential biological abnormalities that may underlie central sensitization.