Cerebrovascular recovery drives restoration of neurometabolite levels after mild COVID-19

SARS-CoV-2 infection can trigger broad acute-stage endothelial dysfunction that is often followed by neurocognitive post-acute sequelae (PASC) chronically. It is thus of interest to evaluate long-term post-infection cerebrovascular function dynamics and their effects of neuronal health. Using functional magnetic resonance imaging (fMRI), we examined cerebrovascular reactivity (CVR) magnitude and delay across a broad post-infection timeline (3-59 months) in 69 participants who previously had mild cases of COVID-19. We also assessed the relationships between CVR and neurometabolite markers of neuronal health using magnetic resonance spectroscopy (MRS) in the thalamic region and the corona radiata. Increasing time since infection (TSI) was associated with shorter CVR delay in global gray (GM) and white matter (WM), with no effects of TSI on CVR magnitude. Parcellation of the GM revealed TSI-dependent decreases in CVR delays in nine of the 10 examined GM regions. CVR delay was inversely related to total choline (tCho), creatine (tCr), and N-acetylaspartate (tNAA) levels in the thalamic region, but not in the corona radiata. The results suggest slower cerebrovascular reactivity follows mild COVID-19 and eventually resolves spontaneously, albeit on a protracted timeline. Further, improved levels of tCho, tCr, and tNAA in the GM are associated with this functional cerebrovascular recovery.