Interhemispheric structural connectivity alterations and hierarchical connectome gradient reorganization following SARS-CoV-2 infection

Neurological sequelae of SARS-CoV-2 infection extend beyond the acute phase, yet the structural basis of network-level brain changes across disease severity remains poorly understood. We investigated structural brain connectivity and connectome gradient organization in adults with polymerase chain reaction-confirmed coronavirus disease 2019 (COVID-19), stratified into non-hospitalized and hospitalized groups, alongside a comparison group with non-COVID respiratory infection, using 3T diffusion-weighted magnetic resonance imaging. Network-Based Statistics was used to identify subnetworks of altered structural connectivity, and connectome gradients were derived separately for each hemisphere using diffusion map embedding and compared across groups within seven canonical resting-state networks. Network-Based Statistics identified a predominantly interhemispheric subnetwork differing across the three groups, linking left-hemispheric control and salience regions to right hemisphere sensory and association areas, with a related subnetwork distinguishing hospitalized participants from the comparison group. Connectome gradient analysis revealed group-related differences in connectivity-derived embedding positions within sensorimotor and dorsal attention networks, more pronounced among hospitalized participants. These findings suggest that SARS-CoV-2 infection is associated with severity-related interhemispheric structural connectivity differences and altered hierarchical connectome organization, particularly within sensorimotor and dorsal attentional systems. Given the cross-sectional design, modest sample size, and absence of behavioral data, these findings should be considered exploratory and do not establish anatomical fiber loss, causal mechanisms, or predictive clinical value; instead, they provide a structural framework to guide future studies of neurological outcomes after COVID-19.