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

SUMMARYCoronavirus disease 2019 (COVID19), caused by severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2), has emerged as a global pandemic, causing overwhelmingmorbidity and mortality. While the main manifestations of COVID19 relate to problems withrespiration, emerging studies recognize the presence of neurological complications in a numberof patients, so far primarily related to cerebrovascular disease as reported by our group andothers. Urgent high-resolution molecular studies are needed to understand better how theSARS-Cov-2 coronavirus targets the brain and whether its effects on the cerebral vasculatureare through direct infection, secondary systemic coagulopathy, or a combination of both, whichcarries 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 ofthe SARS-CoV-2 virus in primary COVID19 autopsy brain tissue using complementary singlecell transcriptomic and histological analysis tools already established by our team, and toelucidate further the cellular and molecular associations between viral infectivity, co-expressionof ACE2 and other putative viral receptor targets, and central nervous system pathology relatedto cerebrovascular disease, other pathophysiological manifestations of COVID19, and pre-existent co-morbidities. A better understanding of COVID19 pathophysiology in the brainthrough this and other studies will inform clinicians of more effective and personalized treatmentprotocols for patients infected with SARS-Cov-2 who may be predisposed to having neurologicalcomplications.