Five-Year Study Tracks Brain Function and Cognitive Shifts After COVID-19

Hospitalized COVID-19 survivors exhibited persistent cognitive impairment, sleep disturbances, and functional brain alterations five years after recovery, according to a longitudinal investigation assessing patients over an extended post-infection trajectory. The findings address long-term uncertainties regarding how cognitive performance and underlying neural dynamics evolve well beyond the acute phase and initial recovery periods.

The single-center longitudinal study evaluated 14 hospitalized COVID-19 survivors across three follow-up intervals: one year (V1), two years (V2), and five years (V5) following recovery. Researchers compared these patients to a cohort of 20 healthy controls (HCs) using both neuropsychological testing batteries and resting-state functional magnetic resonance imaging (fMRI). The neuroimaging analysis focused on specific indices of brain activity and network topology, including the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and network small-worldness (σ).

At the five-year mark, assessments demonstrated measurable behavioral and clinical differences between the recovering cohort and healthy participants. Compared to the healthy controls, survivors at V5 experienced poorer sleep quality, indicated by significantly higher scores on the Pittsburgh Sleep Quality Index (PSQI). The survivor cohort also recorded lower scores on memory and attention tasks, specifically the Logical Memory (LM) test and the backward Digit Span (BDS) assessment.

Neuroimaging comparisons identified corresponding functional alterations in the brains of survivors at five years. Relative to healthy controls, survivors at V5 exhibited increased ALFF in the right supramarginal gyrus (SMG.R), decreased ALFF in the right precuneus, and decreased ReHo in the left middle frontal gyrus. Statistical analyses showed that each of these regional alterations was significantly associated with reduced cognitive function and poor sleep quality, with all reported findings maintaining statistical significance under corrected thresholds (all corrected P < 0.05).

Longitudinal monitoring across the three follow-up visits revealed fluctuating trajectories in clinical metrics and neural measures. Patient PSQI scores decreased from V1 to V2, reflecting an interval change in sleep quality. Concurrently, physical functioning scores on the 36-Item Short-Form Health Survey (SF-PF) increased from V1 to V2, and SF-Vitality (VT) scores increased at V2 relative to both the initial one-year and five-year visits.

Neural dynamics also shifted over the five-year observation period. Between V1 and V2, ALFF decreased in the right precentral gyrus, whereas ALFF in the right supramarginal gyrus increased at V5 compared to V2. Network small-worldness (σ) exhibited a biphasic pattern, decreasing at V2 before increasing at V5, where the measure correlated negatively with backward Digit Span scores. The authors concluded that these combined observations provide neuroimaging evidence for persistent long-term neuropsychiatric sequelae five years post-COVID-19.

Subject of Research: Five-year longitudinal assessment of brain function and cognition after COVID-19 recovery

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

Article References: Yang, J.-J., Cao, S.-R., Zhou, X.-L., Huang, S.-H., Yao, J.-Q., Zhang, L.-J., Xu, X.-J., Zeng, Y.-L., Lin, X., Huang, B., Wang, J.-H., Yang, D.-H., & Liu, J. (2026). Dynamic changes in cognition and brain function over a five-year follow-up after COVID-19 recovery: a longitudinal fMRI study. BMC Medicine. https://doi.org/10.1186/s12916-026-05379-6

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05379-6

Keywords: COVID-19, brain function, cognition, fMRI, sleep quality, neuroimaging, longitudinal study, small-worldness, Dynamic, changes, brain, function