How do fatigue, cognitive dysfunction, activity and role functioning, and mental health inter-relate in adults with post-COVID-19 syndrome? A structural equation model analysis

Abstract

Purpose: Post-COVID-19 Syndrome (PCS) is associated with persistent fatigue and cognitive symptoms that may disrupt daily functioning and mental health. This study examined interrelationships among fatigue, cognitive function, activity and role functioning, and mental health in individuals with PCS. Methods: We analyzed cross-sectional data from 535 adults in the Quebec Action for Post-COVID (QAPC) cohort who self-identified as experiencing PCS symptoms. Structural Equation Modelling was used to estimate associations among fatigue, self-reported cognitive concerns, cognitive performance, and two latent constructs: activity and role functioning and mental health. Models were adjusted for age, sex, education, race, alcohol use, prior mental health history, and vaccination status. Results: Fatigue showed association with mental health (standardized regression coefficient, β_std = 0.44, p < 0.001), primarily through a direct path (β_std = 0.42) and a smaller indirect path via self-reported cognitive concerns (β_std = 0.10). Fatigue was also associated with reduced activity and role functioning (β_std = − 0.79), which did not mediate its link to mental health. Self-reported cognitive concerns were independently associated with poorer mental health (β_std = 0.19). Cognitive performance was positively associated with activity and role functioning (β_std = 0.11) but not with mental health. Covariates, including older age, Caucasian ethnicity, and vaccination, were linked to more favourable outcomes. Conclusion: Fatigue and self-reported cognitive concerns were associated with mental health symptoms in PCS. These findings highlight the value of symptom cluster–based screening to inform referral pathways for cognitive, psychological, and functional support. Longitudinal research is needed to clarify temporal ordering.