Clinical and Laboratory Characteristics of Fatigue-Dominant Long-COVID Subjects: A Cross-Sectional Study.
Lee, Jin-Seok, Choi, Yujin, Joung, Jin-Yong et al. · The American journal of medicine · 2025 · DOI
Quick Summary
This study looked at 100 people with long COVID who experience significant ongoing fatigue, similar to ME/CFS. Researchers measured fatigue levels and checked blood levels of cortisol (a stress hormone) and other immune markers. They found that people with lower cortisol levels reported worse fatigue and lower quality of life, suggesting a possible connection between this hormone and fatigue severity.
Why It Matters
Long COVID and ME/CFS share core symptoms including fatigue and postexertional malaise, making long COVID research valuable for understanding ME/CFS pathophysiology. This study provides early biomarker insights—particularly regarding cortisol dysfunction—that may help clinicians recognize and potentially treat fatigue-dominant presentations in both conditions. These findings could inform future mechanistic studies exploring neuroendocrine abnormalities in post-viral fatigue syndromes.
Observed Findings
Severe fatigue was observed across all fatigue assessment scales in the cohort (100 subjects with mKCFQ11 >60).
Lower cortisol levels were associated with reduced quality of life (positive correlation between cortisol and SF-36 scores).
Cortisol correlation with mental fatigue was more pronounced than with physical fatigue.
No significant differences in fatigue severity were observed based on sex, post-COVID duration, or age.
Inferred Conclusions
Cortisol dysfunction may be a relevant biomarker in fatigue-dominant long COVID presentations.
Mental fatigue components may be more closely linked to neuroendocrine dysfunction than physical fatigue.
Characterization of long COVID fatigue provides reference data applicable to understanding ME/CFS pathophysiology.
Fatigue severity in long COVID appears largely independent of demographic factors and post-infection timing.
Remaining Questions
Does low cortisol directly cause fatigue, or is it a consequence of chronic fatigue and illness? Can cortisol-targeted interventions improve fatigue symptoms in long COVID or ME/CFS?
What This Study Does Not Prove
This cross-sectional snapshot cannot establish whether low cortisol causes fatigue or results from it—correlation does not prove causation. The study does not assess whether these cortisol patterns are unique to long COVID or shared with other fatigue conditions, nor does it demonstrate that cortisol manipulation would improve fatigue symptoms. Single time-point measurement cannot capture dynamic changes or establish whether findings persist over time.