Long term effect of COVID-19 on brain metabolism and connectivity

Aims: After 3 years from the beginning of SARS-CoV-2 pandemic, a substantial proportion of affected patients still present at least one symptom after infection. Given that: magnetic resonance imaging studies up to two years after COVID-19 reported changes in white matter (WM) microstructure and in functional connectivity; WM associates with glutamate and N-acetyl-aspartate levels in BD; the link between cognitive impairment and WM integrity, the aim of the study was to investigate metabolites associations with alterations in structural and functional brain connectivity and cognition in 64 COVID-19 survivors and 33 healthy controls (HC). Methods: We compared WM microstructure and metabolites levels between individuals recovering from COVID-19 and HCs. Then, we investigated the associations between WM and glutamate and N-acetyl-aspartate in the two groups. Results: Patients showed: higher levels of glutamate and NAA compared to HCs with a positive effect on cognitive complaints; higher fractional anisotropy (FA), and lower radial (RD) and mean diffusivity (MD); glutamate and N-acetyl-aspartate significant positive associations with FA, and a negative one with MD and RD. FA levels moderated the relation between the glutamate and cognitive deficits. Finally, N-acetyl-aspartate associated with higher rs-FC between VOI and the posterior cingulate gyrus in individuals recovering from COVID-19. Conclusions: Our findings suggest that a process of brain repair and remyelination, as suggested by higher levels of glutamate and N-acetyl-aspartate and by higher measures of WM microstructure, may occur after SARS‑CoV‑2 infection which may help the recovery from long COVID-19 symptoms such as cognitive impairment.