Resolving SARS-Cov-2 tropism and COVID19 pathology in the brain

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SUMMARY Coronavirus disease 2019 (COVID19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a global pandemic, causing overwhelming morbidity and mortality. While the main manifestations of COVID19 relate to problems with respiration, emerging studies recognize the presence of neurological complications in a number of patients, so far primarily related to cerebrovascular disease as reported by our group and others. Urgent high-resolution molecular studies are needed to understand better how the SARS-Cov-2 coronavirus targets the brain and whether its effects on the cerebral vasculature are through direct infection, secondary systemic coagulopathy, or a combination of both, which carries specific implications for future risk stratification and treatment in vulnerable individuals. The purpose of this one-year supplement is to urgently elucidate the cell-type specific tropism of the SARS-CoV-2 virus in primary COVID19 autopsy brain tissue using complementary single cell transcriptomic and histological analysis tools already established by our team, and to elucidate further the cellular and molecular associations between viral infectivity, co-expression of ACE2 and other putative viral receptor targets, and central nervous system pathology related to cerebrovascular disease, other pathophysiological manifestations of COVID19, and pre- existent co-morbidities. A better understanding of COVID19 pathophysiology in the brain through this and other studies will inform clinicians of more effective and personalized treatment protocols for patients infected with SARS-Cov-2 who may be predisposed to having neurological complications.