E2 ModerateModerate confidencePEM not requiredObservationalPeer-reviewedMachine draft
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Cardio-Respiratory Fitness and Fatigue in Post-COVID-19 Syndrome-A Three-Year Update.
Cherneva, Radostina, Cherneva, Zheyna, Youroukova, Vania et al. · Biomedicines · 2025 · DOI
Quick Summary
More than two years after COVID-19 infection, about a quarter of people still experience persistent symptoms including fatigue, breathing problems, and reduced ability to exercise. Researchers tested how well patients' hearts and lungs worked during exercise and found that those with moderate-to-severe symptoms had noticeably reduced fitness levels and felt more exhausted even when not working as hard as their test results showed they should be.
Why It Matters
This study demonstrates persistent cardio-respiratory dysfunction in long-term post-COVID-19 patients, paralleling pathophysiological findings in ME/CFS including reduced aerobic capacity and exaggerated perceived exertion relative to actual workload. The three-year follow-up provides crucial data on the chronic trajectory of post-COVID-19 syndrome and supports the hypothesis that some patients develop exercise intolerance with measurable physiological abnormalities similar to ME/CFS.
Observed Findings
Moderate-severe PCS patients experienced significantly higher symptom burden during CPET (73.6%) compared to mild (24.8%) and asymptomatic (17.4%) groups.
Peak VO₂ was reduced in moderate-severe PCS (24.13 ± 6.1 mL/min/kg) versus mild (26.73 ± 5.9) and asymptomatic (27.01 ± 6.3) subjects.
Over half of moderate-severe PCS patients (51.8%) failed to reach anaerobic threshold during exercise testing.
Perceived exertion did not correlate with actual workload, heart rate, or breathing rate in symptomatic subjects.
Approximately 24% of the general COVID-19 cohort retained persistent symptoms more than 30 months post-infection.
Inferred Conclusions
Long-term post-COVID-19 syndrome persists in a substantial minority of infected individuals and is characterized by reduced cardio-respiratory fitness and pathological dissociation between perceived and actual physiological effort.
A third of long-term PCS patients exhibit objectively measurable aerobic metabolism impairment that is independent of symptom severity perception.
The symptom burden and physiological abnormalities in moderate-severe PCS suggest a genuine organic basis for exercise intolerance rather than purely psychological limitation.
Remaining Questions
What mechanisms underlie the dissociation between perceived exertion and objective physiological parameters in PCS patients—is this a central nervous system issue, metabolic defect, or autonomic dysfunction?
What This Study Does Not Prove
This study cannot establish causation or identify the specific mechanisms underlying the cardio-respiratory impairment, nor does it confirm post-exertional malaise (PEM), which is central to ME/CFS diagnosis. The cross-sectional design prevents determination of whether dysfunction is improving or worsening over time. The study also does not compare PCS directly to ME/CFS patients or establish whether PCS and ME/CFS share identical pathophysiology.
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 →