Evidence Atlas

Post-Exertional Malaise in Post-COVID-19 Syndrome: A Shift in the Frequency Across Pandemic Phases. — ME/CFS Atlas

E2 ModerateCohortPEM not requiredObservationalPeer-reviewed

Standard · 3 min

Post-Exertional Malaise in Post-COVID-19 Syndrome: A Shift in the Frequency Across Pandemic Phases.

Ghali, Alaa, Lavigne, Christian, Ghali, Maria et al. · Journal of clinical medicine · 2026 · DOI

Quick Summary

A French hospital study observed that post-COVID patients infected in 2020–2021 reported post-exertional malaise (PEM) more often than those infected later, and that PEM was associated with higher fatigue levels. By analogy, this may be relevant to ME/CFS patients, though the study examined post-COVID populations and the reasons for these differences remain uncertain—they could reflect changes in the virus, vaccination, immunity, or other unmeasured factors.

Why It Matters

Post-exertional malaise is a cardinal feature of ME/CFS, and observing its prevalence and associations in a large post-COVID cohort provides an epidemiological reference point by analogy for understanding PEM phenotypes across post-infectious conditions. The link between PEM and severity of fatigue reinforces the clinical importance of screening for PEM in post-infectious fatigue populations, potentially including ME/CFS specialist settings.

Observed Findings

Post-exertional malaise was observed in 26.4% (58/220) of post-COVID patients in this cohort.
PEM was significantly associated with earlier COVID-19 infection during 2020/2021 compared to later pandemic waves (OR 5.68, 95% CI 1.66–19.45, p=0.006).
PEM was significantly associated with higher fatigue severity (OR 2.07, 95% CI 1.22–3.50, p=0.007).
The frequency of PEM appeared to decline across successive pandemic phases, with earlier waves reporting higher rates than later waves.

Inferred Conclusions

The authors suggest that differences in viral characteristics (such as the emergence of the Omicron variant) may explain the lower frequency of PEM in later infection waves.
Alternatively, they propose that increasing vaccination coverage or accumulating post-infectious immunity in later cohorts could account for the temporal pattern.
The observed association between PEM and fatigue severity supports systematic screening for PEM in post-COVID patients.

Remaining Questions

What specific viral or immunological properties of early pandemic strains versus Omicron might explain differences in PEM frequency?
Do vaccination status, prior infection history, and immune markers independently predict PEM risk, and how do these factors interact?

What This Study Does Not Prove

This study does not establish causation between infection timing, viral variant, or fatigue severity and PEM—it only identifies associations in a single retrospective cohort. It does not demonstrate that the Omicron variant, vaccination, or immunity changes actually caused the observed temporal shift in PEM frequency; alternative unmeasured factors may account for the pattern. Findings in post-COVID patients do not directly confirm mechanisms or epidemiology in primary ME/CFS.

Topics

Long COVID Overlap Post-Exertional Malaise

Metadata

DOI: 10.3390/jcm15082948
PMID: 42074751
Evidence level: Single-study or moderate support from human research
Last updated: 5 May 2026

Explore further

Explore Long COVID Overlap →Explore Post-Exertional Malaise →Browse all studies →

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 →

Cite this study

The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.

Primary citation

Ghali, Alaa, Lavigne, Christian, Ghali, Maria, & Lacombe, Valentin (2026). Post-Exertional Malaise in Post-COVID-19 Syndrome: A Shift in the Frequency Across Pandemic Phases.. Journal of clinical medicine. https://doi.org/10.3390/jcm15082948

BibTeX

@article{mecfsatlas-ghali-2026-post-exertional,
  author  = {Ghali, Alaa and Lavigne, Christian and Ghali, Maria and Lacombe, Valentin},
  title   = {Post-Exertional Malaise in Post-COVID-19 Syndrome: A Shift in the Frequency Across Pandemic Phases.},
  journal = {Journal of clinical medicine},
  year    = {2026},
  doi     = {10.3390/jcm15082948},
  note    = {PubMed: 42074751},
  url     = {https://www.mecfsatlas.com/evidence/ghali-2026-post-exertional},
}

Atlas snapshot reference

ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-05. https://www.mecfsatlas.com/evidence/ghali-2026-post-exertional

Contribute

Private, reviewed by a human. Not a public comment thread.

Report an error Suggest a source Ask a follow-up Request a guide