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Functional olfactory impairment and fatigue in post-COVID-19 syndrome including ME/CFS - a longitudinal prospective observational study.
Meyer-Arndt, Lil, Pierchalla, Greta, Mödl, Lukas et al. · Brain, behavior, & immunity - health · 2025 · DOI
Quick Summary
This study followed 45 long-COVID patients over 28 months to understand the connection between smell problems and fatigue, including those who developed ME/CFS. Researchers tested how well patients could smell (detecting scent strength, telling scents apart, and identifying them) and measured their fatigue, thinking ability, and physical strength. Most patients' smell improved over time, but problems with identifying specific smells lasted the longest, and patients with better smell discrimination at the start tended to feel better and function better after 20 months.
Why It Matters
This research identifies olfactory identification as a potentially persistent marker of post-COVID neurological dysfunction and suggests it may correlate with long-term cognitive and functional outcomes. For ME/CFS patients, understanding that smell problems reflect central nervous system processing difficulties could validate this overlooked symptom and potentially guide early intervention strategies based on olfactory function patterns.
Observed Findings
- All 45 patients showed improvement in overall olfactory function and returned to normosmia by 20 months post-COVID, regardless of PCS or PCS-ME/CFS diagnosis.
- Odor threshold was the most severely affected olfactory measure initially, while odor identification remained the most persistently impaired component over the 28-month follow-up.
- Better odor discrimination at baseline correlated with improved daily functioning and health-related quality of life after 20 months, suggesting a prognostic relationship.
- Olfactory performance showed stronger correlations with cognitive, physical, and mental outcomes in the PCS group compared to the PCS-ME/CFS group.
- Persisting impairment in odor identification appears to reflect ongoing central nervous system processing difficulties rather than peripheral olfactory loss.
Inferred Conclusions
- Odor identification deficits may serve as a biomarker of persistent central nervous system dysfunction in post-COVID-19 syndrome, potentially with prognostic value for long-term cognitive outcomes.
- The different time-courses of recovery for odor threshold versus identification suggest distinct pathophysiological mechanisms, with identification impairment reflecting more persistent central processing disruption.
- Early olfactory improvements, particularly in discrimination ability, may predict better overall functional and cognitive recovery in post-COVID patients.
- Shared underlying mechanisms likely connect olfactory dysfunction to cognitive and physical impairment in both PCS and PCS-ME/CFS phenotypes, though the strength of these associations may differ between groups.
What This Study Does Not Prove
This study demonstrates correlation between olfactory dysfunction and cognitive/physical impairment but does not prove causation or identify the underlying mechanism. The findings apply primarily to mild-to-moderate cases and cannot establish whether olfactory testing would be a reliable diagnostic tool for ME/CFS across all severity levels or different patient populations. Additionally, improvement in smell does not prove that the same central processing deficits resolve in other domains.
Tags
Symptom:Cognitive DysfunctionFatigue
Biomarker:Neuroimaging
Phenotype:Infection-TriggeredLong COVID Overlap
Method Flag:No ControlsSmall SampleMixed Cohort