Action of SARS CoV2 in Human Brain Cultures

PROJECT Summary: There is emerging evidence that SARS-CoV2 or COVID19 gains entry into human brain cells leading to asequela of neurologic symptoms. There is concern that SARS-CoV2 may lead to neurotoxicity and thatneuronal death in the regions of the brain that control respiration and cardiac function may be a contributingfactor to the acute loss of cardio respiratory function and death. SARS-CoV2 could gain access to the brain byseveral routes including through the nose, or neurons innervating infected lung tissue or through the cells liningblood capillaries in the brain. COVID-19 patients lose their sense of smell or taste often before the onset ofrespiratory symptoms and a patient presented with Guillain-Barré syndrome before testing positive for SARS-CoV2. It appears that at least 36% of COVID19 patients had neurologic manifestations including headache,nausea, loss of consciousness, strokes, confusion, encephalitis, meningitis and seizures. These clinicalobservations strongly indicate a role for SARS-CoV2 in the death of neurons and importantly the brain may beone of the first tissues infected and affected. The actions of SARS-CoV2 on the different cells in the brain, aswell as the infectivity, tropism, and replication in brain cells is not yet known. In this application we propose toevaluate: (1) The tropism and replication of SARS-CoV2 in human microglia, astrocytes, neurons, anddetermine relative susceptibility? (2) The mechanisms of cellular injury and evaluate potential protectiveapproaches. (3) Determine the transcriptional responses to SARS CoV2 infection in human neurons,astrocytes, and microglia at the single cell level to gain new insight into the differential response of brain cellsto SARS CoV2 to better understand the neural deficits the virus causes.