Two-day cardiopulmonary exercise testing in long COVID post-exertional malaise diagnosis.
Gattoni, Chiara, Abbasi, Asghar, Ferguson, Carrie et al. · Respiratory physiology & neurobiology · 2025 · DOI
Quick Summary
This study tested whether Long COVID patients experience a measurable drop in exercise capacity after 24 hours, which would suggest their bodies aren't recovering properly from exercise. Researchers had 15 Long COVID patients do exercise tests on two consecutive days and found no significant difference in performance between day 1 and day 2. Surprisingly, this was true even though 80% of patients reported post-exertional malaise (PEM) symptoms over the previous six months.
Why It Matters
This study directly addresses a core feature of ME/CFS and Long COVID—post-exertional malaise—and uses objective exercise testing to investigate its mechanism. Understanding whether PEM involves measurable physiological changes on repeat testing is crucial for developing targeted treatments and validating diagnostic criteria for these conditions.
Observed Findings
80% of Long COVID patients reported post-exertional malaise symptoms on the modified DePaul Symptom Questionnaire
40% of patients showed aerobic deconditioning on day 1 CPET (V̇O₂peak <80% predicted)
No statistically significant differences were found between day 1 and day 2 CPET responses for V̇O₂peak, GET, WRpeak, or perceived effort ratings
Lung function testing was normal across all participants
Mean participant age was 53 years with a BMI of 32.2 kg/m²
Inferred Conclusions
PEM symptoms in Long COVID patients are not associated with measurable impairment in cardiopulmonary exercise capacity recovery within a 24-hour period
The mechanism underlying PEM in Long COVID may involve physiological processes not detected by standard CPET measures between days
Aerobic deconditioning is present in a subset of Long COVID patients but does not appear to worsen acutely between consecutive exercise tests
Remaining Questions
Does PEM involve physiological impairment beyond 24 hours post-exercise, or at other physiological levels not measured by standard CPET?
What mechanisms drive PEM symptoms if exercise capacity itself is not reduced on day 2—could these involve autonomic, metabolic, or immunological factors?
What This Study Does Not Prove
This study does not prove that PEM has no physiological basis; rather, it suggests the mechanism may not involve reduced aerobic exercise capacity recovery within 24 hours. The findings do not rule out other physiological explanations for PEM, such as delayed symptoms beyond 24 hours, autonomic dysfunction, or metabolic impairments not captured by standard CPET measures. A negative finding with a small sample size cannot definitively exclude differences that might appear in larger or more sensitive studies.