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Inflammatory predictors of Post-COVID fatigue
A Nuber-Champier1,2, G Breville2,3, P Voruz1,4
1Clinical and Experimental Neuropsychology Laboratory, Faculty of Psychology, University of Geneva, Geneva, Switzerland.
Brain, Behavior, & Immunity - Health
|October 10, 2025
Summary
Acute immune responses, including elevated interleukin-1 receptor antagonist (IL-1RA), interferon-gamma (IFNγ), and tumor necrosis factor-alpha (TNFα), predict long-term fatigue in post-COVID syndrome patients. This inflammation impacts physical, total, and cognitive fatigue dimensions.
Area of Science:
- Immunology
- Virology
- Neurology
Background:
- Post-COVID syndrome frequently involves persistent fatigue, impacting quality of life.
- The biological underpinnings of fatigue after SARS-CoV-2 infection are not fully understood.
- Immune system activation during acute infection may influence long-term sequelae.
Purpose of the Study:
- To investigate if immune responses during acute SARS-CoV-2 infection predict fatigue dimensions.
- To identify specific immune markers associated with chronic fatigue 6-9 months post-infection.
- To explore the relationship between acute inflammation and different types of post-COVID fatigue.
Main Methods:
- Serum immune markers (IL-1RA, IFNγ, TNFα) and monocyte percentage were analyzed from 54 hospitalized COVID-19 patients.
- Chronic fatigue dimensions (physical, cognitive, total) were assessed 6-9 months post-infection.
- General linear mixed models were used to associate acute immune markers with fatigue outcomes.
Main Results:
- Elevated levels of IL-1RA, IFNγ, TNFα, and monocyte percentage during acute infection predicted increased physical and total fatigue.
- Higher TNFα levels were significantly correlated with reduced awareness of cognitive fatigue (r = -0.40, p = 0.019).
- Specific inflammatory markers during acute COVID-19 are linked to persistent fatigue symptoms.
Conclusions:
- Acute phase immune responses, particularly inflammatory markers, play a significant role in the development of chronic fatigue post-COVID.
- Targeting acute inflammation may be a potential strategy for mitigating long-term fatigue in post-COVID syndrome.
- Further research is needed to elucidate the precise mechanisms linking acute immunity to persistent fatigue.
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