Perivascular spaces in neuropsychiatric post-COVID syndrome

<title>Abstract</title> <p>Persistent neuropsychiatric symptoms after COVID-19 have been found associated with neurovascular dysfunction, but their relationship with the brain’s perivascular spaces (PVS) remains unclear. We examined whether MRI-visible PVS burden differed by neuropsychiatric post-COVID syndrome status and age and was related to syndrome duration, depressive symptoms, and health-related quality of life. In this exploratory cross-sectional study, we segmented PVS on high-resolution T1-weighted MRI from 116 participants (59 with neuropsychiatric post-COVID syndrome and 57 without it). Regional PVS burden was quantified as fractional volume and count within the centrum semiovale (CSO ROI) and basal ganglia (BG ROI). Adjusted multivariable regional models examined age-by-status interactions, associations with syndrome duration among affected participants (n = 50), and status-dependent relationships with depressive symptoms and SF-36 domains. Complementary voxel-wise analyses of the spatially normalised PVS segmentation maps assessed the localisation of these effects. At younger ages, participants with and without neuropsychiatric post-COVID syndrome had similar CSO PVS burden. With increasing age, however, those with the syndrome had higher CSO PVS volume and count. Voxel-wise analysis localised these differences predominantly to juxtacortical white matter, especially that beneath the primary motor, premotor, and supplementary motor cortices. Within the syndrome group, longer syndrome duration was associated with higher CSO PVS volume. Higher PVS burden was also more strongly associated with poorer SF-36 Physical Functioning, Social Functioning, and Role Limitations due to Physical Health among individuals with the syndrome than among those without it. However, higher PVS burden was not associated with greater depressive symptom severity within the syndrome group. These findings suggest an age- and duration-related CSO PVS pattern in neuropsychiatric post-COVID syndrome, alongside possible functional correlates. Longitudinal imaging is needed to distinguish pre-existing susceptibility from changes developing during the syndrome.</p>