Dynamic changes in cognition and brain function over a five-year follow-up after COVID-19 recovery: a longitudinal fMRI study

Abstract Background Long-term trajectories of brain function and cognition after COVID-19 remain unclear beyond early recovery. Methods We conducted a single-center longitudinal study of 14 hospitalized COVID-19 survivors assessed at 1 (V1), 2 (V2), and 5 (V5) years post-recovery, alongside 20 healthy controls (HCs). Participants underwent resting-state fMRI and neuropsychological assessments. The imaging indices analyzed included ALFF, ReHo, and small-worldness. Results Compared to HCs, survivors at V5 exhibited poorer sleep and cognitive performance, as reflected by higher Pittsburgh Sleep Quality Index (PSQI) scores and lower Logical Memory (LM) and backward Digit Span (BDS) scores. Compared to HCs, survivors at V5 also showed increased ALFF in the right supramarginal gyrus (SMG.R), decreased ALFF in the right precuneus, and decreased ReHo in the left middle frontal gyrus—all of which were significantly associated with reduced cognitive function and poor sleep quality. Longitudinally, PSQI scores decreased from V1 to V2; 36‑Item Short‑Form Health Survey physical functioning (SF‑PF) scores increased from V1 to V2; and SF‑Vitality (VT) scores increased at V2 relative to both V1 and V5. For neural dynamics, ALFF decreased in the right precentral gyrus at V2 (vs. that at V1), but increased in the SMG.R at V5 (vs. that at V2). Additionally, small‑worldness (σ) decreased at V2 and subsequently increased at V5. Notably, this σ value at V5 correlated negatively with BDS scores. All reported findings remained statistically significant (all corrected P < 0.05). Conclusions Five years after recovery, survivors exhibited persistent cognitive impairment, sleep disturbances, and functional brain alterations, providing neuroimaging evidence for the long-term neuropsychiatric sequelae of COVID-19.