Perivascular spaces in neuropsychiatric post-COVID syndrome

Neuropsychiatric symptoms, such as executive dysfunction, fatigue, and depression, are common and disabling in post-COVID syndrome, often hindering daily activities and work. While the exact mechanisms remain unclear, recent studies suggest SARS-CoV-2 may damage the blood-brain barrier (BBB), contributing to these symptoms. If BBB dysfunction is central, structural changes may occur in neighbouring areas, such as in perivascular spaces (PVS). In this study, we measured PVS volumes in 80 participants, both with and without neuropsychiatric post-COVID syndrome, to assess whether PVS enlargement was associated with the syndrome and its duration. We used data from the post-COVID Brain project , a study designed to investigate differences in brain morphology, cognitive function, and overall neurological health between post-COVID patients and healthy controls. The study included 50 neuropsychiatric post-COVID patients and 30 age- and gender-matched healthy controls. We semi-automatically quantified PVS in the basal ganglia (BG ROI) and centrum semiovale (CSO ROI) and leveraged linear regression to test whether neuropsychiatric post-COVID syndrome and its duration were associated with fractional PVS volumes. We adjusted all models for age, sex, years of education, body-mass-index, and cardiovascular disease history. In the full sample, the difference in fractional PVS volumes between individuals with and without neuropsychiatric post-COVID syndrome increased with age (BG: β _{Age × Post-COVID?} = 0.49 ( SE 0.21), Z = 2.34, P = 0.022; CSO: β _{Age × Post-COVID?} = 0.45 ( SE 0.22), Z = 2.05, P = 0.044). In individuals with a neuropsychiatric post-COVID syndrome, longer duration of the neuropsychiatric symptoms was associated with larger fractional PVS volumes (BG: β _{Post-COVID duration} = 0.27 ( SE 0.12), Z = 2.20, P = 0.034; CSO: β _{Post-COVID duration} = 0.30 ( SE 0.13), Z = 2.28, P = 0.028). The presence and duration of neuropsychiatric post-COVID syndrome in humans relate to the extent of enlargement of PVS in the brain.