E2 ModerateModerate confidencePEM requiredCross-SectionalPeer-reviewedReviewed
Post-exertional malaise among people with long COVID compared to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Vernon, Suzanne D, Hartle, Megan, Sullivan, Karen et al. · Work (Reading, Mass.) · 2023 · DOI
Quick Summary
This study looked at whether people with Long COVID experience post-exertional malaise (PEM)—a hallmark symptom of ME/CFS where symptoms get worse after physical or mental activity. Researchers surveyed 80 Long COVID patients and compared their experiences to 151 ME/CFS patients. Nearly all Long COVID patients reported having PEM, but the way they experienced it differed significantly from ME/CFS patients in terms of what triggered it, which symptoms appeared, and how to recover.
Why It Matters
Understanding whether Long COVID and ME/CFS share the same core pathophysiology has important implications for diagnosis, treatment protocols, and research prioritization. This study provides evidence that PEM is present in Long COVID but manifests differently, which could help clinicians recognize and appropriately manage exertional intolerance in both populations and inform whether shared versus distinct therapeutic approaches are needed.
Observed Findings
- Nearly all (79 of 80) Long COVID patients reported experiencing post-exertional malaise.
- Significant differences existed between Long COVID and ME/CFS groups in types of PEM triggers, symptom profiles during PEM episodes, and recovery/prevention strategies.
- Common features in both groups included low-to-medium physical and cognitive exertion triggers, fatigue, pain, immune symptoms, neurologic symptoms, orthostatic intolerance, and gastrointestinal symptoms during PEM.
- Rest and pacing strategies were reported by both groups as management approaches.
Inferred Conclusions
- Post-exertional malaise is a prevalent symptom in Long COVID, consistent with a key ME/CFS feature.
- Despite PEM presence in both conditions, meaningful differences in PEM presentation suggest either distinct underlying mechanisms or differences in disease maturity and patient awareness.
- The authors propose that Long COVID's recent emergence and patients' lack of familiarity with exertional intolerance may account for observed differences rather than fundamental biological distinctions.
Remaining Questions
- Do the observed differences in PEM between Long COVID and ME/CFS reflect distinct pathophysiological mechanisms or differences in disease duration and patient education?
- How do PEM characteristics in Long COVID evolve over time as patients gain familiarity with exertional intolerance?
What This Study Does Not Prove
This study does not establish that Long COVID and ME/CFS are different diseases or that their underlying biological mechanisms differ—only that reported PEM experiences differ. The cross-sectional design cannot determine causation or whether differences reflect true biological distinctions versus differences in patient education, disease duration, or recall accuracy. The findings cannot be generalized beyond patients seeking specialized care at this clinic.
Tags
Method Flag:PEM_DEFINEDSmall SampleExploratory OnlyMixed Cohort
Symptom:Post-Exertional MalaiseCognitive DysfunctionOrthostatic IntolerancePainFatigue
Phenotype:Long COVID Overlap
Metadata
- DOI
- 10.3233/WOR-220581
- PMID
- 36911963
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 7 April 2026
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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