Blood brain barrier disruption and glutamatergic excitotoxicity in post-acute sequelae of SARS COV-2 infection cognitive impairment: potential biomarkers and a window into pathogenesis

ObjectiveTo investigate the association between blood–brain barrier permeability, brain metabolites, microstructural integrity of the white matter, and cognitive impairment (CI) in post-acute sequelae of SARS-COV-2 infection (PASC).MethodsIn this multimodal longitudinal MRI study 14 PASC participants with CI and 10 healthy controls were enrolled. All completed investigations at 3 months following acute infection (3 months ± 2 weeks SD), and 10 PASC participants completed at 12 months ± 2.22 SD weeks. The assessments included a standard neurological assessment, a cognitive screen using the brief CogState battery and multi-modal MRI derived metrics from Dynamic contrast enhanced (DCE) perfusion Imaging, Diffusion Tensor Imaging (DTI), and single voxel proton Magnetic Resonance Spectroscopy. These measures were compared between patients and controls and correlated with cognitive scores.ResultsAt baseline, and relative to controls, PASC participants had higher K-Trans and Myo-inositol, and lower levels of Glutamate/Glutamine in the frontal white matter (FWM) (p