Longitudinal relationships between changes in post-COVID mental fatigue and neuropsychiatric symptoms across distinct recovery trajectories

Inflammopharmacology. 2025 Aug 11. doi: 10.1007/s10787-025-01860-5. Online ahead of print.

ABSTRACT

BACKGROUND: Persistent fatigue, often accompanied by neuropsychiatric symptoms (e.g., cognitive impairment, sleep disorders, depression, anxiety, and PTSD), commonly referred to as “long COVID”. Fatigue is multidimensional, comprising physical, psychological, and situational components. However, the relationships between these fatigue dimensions and co-occurring neuropsychiatric symptoms remain unclear. This study aimed to (1) examine the time-varying characteristics of post-COVID fatigue and (2) determine whether specific fatigue dimensions uniquely affect neuropsychiatric symptoms in long COVID.

METHODS: We analyzed neuropsychiatric assessments from 233 individuals at 1 and 3 months post-infection using Canonical Correlation Analysis (CCA). Participants were categorized into four groups based on fatigue recovery trajectories: persistent fatigue, alleviated fatigue, new-onset fatigue, and no fatigue. Longitudinal CCA assessed relationships between changes in fatigue dimensions and cognitive impairments (memory, executive function) and psychiatric symptoms (anxiety, depression, PTSD, and sleep disturbances) from the acute to chronic phase.

RESULTS: Physical fatigue was dominant in the acute phase, while mental fatigue became more prominent at 3 months. Across both phases, all fatigue dimensions were strongly associated with depression, anxiety, PTSD, and sleep disturbances, with mental fatigue showing the strongest impact (canonical loadings: ρ = – 0.875 at 1 month; ρ = – 0.914 at 3 months). In the persistent fatigue group, mental fatigue was closely linked to anxiety, depression, and cognitive impairments, including recognition and short-term recall (ρ = – 0.677). No significant longitudinal associations were observed in the alleviated, new-onset, or no-fatigue groups.

CONCLUSIONS: Mental fatigue plays a central role in the chronic phase of recovery, significantly impacting cognitive and psychiatric health in individuals with persistent fatigue. Targeted interventions addressing mental fatigue are essential for improving long COVID outcomes.

PMID:40789995 | DOI:10.1007/s10787-025-01860-5