Post-exertional malaise in Long COVID: subjective reporting versus objective assessment.
Stussman, Barbara, Camarillo, Nathan, McCrossin, Gayle et al. · Frontiers in neurology · 2025 · DOI
Quick Summary
This study looked at post-exertional malaise (PEM)—the symptom worsening that happens after activity—in people with Long COVID. Researchers asked patients about PEM symptoms and had some patients do an exercise test to see if PEM actually occurred. While 67% of patients reported having PEM symptoms, only 6% actually showed clear PEM after the exercise test. When PEM did occur in Long COVID, it was less severe than what the researchers saw in ME/CFS patients.
Why It Matters
This study addresses a critical gap in understanding PEM—distinguishing between what patients report and what clinicians can objectively measure. For ME/CFS patients and researchers, it provides important comparative data showing phenotypic differences between Long COVID and ME/CFS PEM presentations, which may guide diagnosis and treatment strategies. The findings suggest exercise testing could help personalize clinical management.
Observed Findings
67% of Long COVID patients self-reported PEM in the questionnaire cohort, but only 5.9% (2/34) demonstrated observable PEM following standardized CPET in the exercise cohort.
When PEM was observed in Long COVID after CPET, it was described as less severe and less prolonged than PEM responses in the ME/CFS comparison group.
64.7% (22/34) of Long COVID exercise cohort patients reported at least one positive theme (improved symptoms, better mood, increased function) after CPET.
Only 27% of the exercise cohort self-reported PEM at baseline, suggesting lower prevalence in this subgroup compared to the questionnaire cohort.
Inferred Conclusions
Self-reported PEM is common in Long COVID, but observable PEM triggered by standardized exercise testing is infrequent, suggesting a dissociation between subjective symptom reporting and objective post-exercise responses in this population.
Long COVID PEM phenotype may differ from ME/CFS, with less severe and prolonged responses to exercise stress, potentially indicating different underlying pathophysiological mechanisms.
Standardized exercise testing (CPET) may have clinical utility for distinguishing PEM responders from non-responders and guiding individualized activity recommendations in Long COVID management.
Remaining Questions
Why is there such a large discrepancy between self-reported PEM (67%) and objectively observed PEM (5.9%) in Long COVID, and does this reflect differences in trigger types, severity thresholds, or measurement sensitivity?
What This Study Does Not Prove
This study does not prove that PEM is absent in Long COVID or that exercise is universally safe for these patients; the 5.9% observed PEM rate reflects this small cohort under controlled conditions and may not represent real-world activity patterns. The discrepancy between self-reported (67%) and objectively observed (5.9%) PEM does not establish that subjective reports are inaccurate—it may indicate that standardized CPET does not adequately provoke individual PEM triggers. The study cannot establish causation or mechanistic explanations for PEM differences between conditions.
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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How do individual Long COVID phenotypes (cardiorespiratory, neurological, immunological) correlate with PEM presence and severity, and would subgroup analysis reveal different exercise response patterns?
What is the longitudinal course of PEM in Long COVID—does it persist, evolve, or resolve over time compared to ME/CFS?
Would exercise protocols tailored to individual symptom triggers or severity gradation produce different PEM outcomes than the standardized CPET used in this study?