Spatial Coefficient of Variation (sCOV) From ASL MRI Reveals Global Cerebrovascular Dysfunction in Long COVID

Long COVID is increasingly associated with persistent neurological and cognitive symptoms, yet its underlying mechanisms remain unclear. Vascular dysregulation, endothelial dysfunction, and microvascular injury have been proposed as potential contributors. Arterial spin labeling (ASL) MRI allows noninvasive quantification of cerebral blood flow (CBF) and assessment of vascular function. Previous studies have reported hypoperfusion in long COVID patients, but few have accounted for delayed arterial transit time, which can affect ASL quantification. The spatial coefficient of variation (sCOV) has been previously used as a proxy of arterial transit time, providing a noninvasive marker of global cerebrovascular function. We examined 186 adults from an Argentine cohort (145 long COVID and 41 controls), approximately 2 years postinfection. Three-dimensional pulsed ASL data were processed with ExploreASL to quantify CBF and sCOV in gray matter and lobar regions. Group comparisons were performed using multivariate models adjusted for age, sex, and white matter hyperintensity (WMH) volume. Long COVID participants showed significantly higher global gray matter sCOV compared with controls (p = 0.02), with consistent regional trends across the frontal (L: p = 0.05; R: p = 0.07), temporal (L: p = 0.05; R: p = 0.08), parietal (L: p = 0.07; R: p = 0.06), occipital (L: p = 0.08; R: p = 0.05), and insular (L: p = 0.01; R: p = 0.15) lobes after FDR correction. Mean global, lobar, and regional gray matter CBF and WMH volumes did not differ significantly between groups. Increased sCOV, reflecting delayed arterial transit and reduced vascular efficiency, indicates widespread cerebrovascular dysfunction in the absence of perfusion deficits and not associated with white matter hyperintensities. These findings provide evidence of global vascular impairment in long COVID and support sCOV as a sensitive, noninvasive biomarker of cerebrovascular health.