LAUSR

Significance Neurological and neuropsychiatric symptoms occur in as many as one-third of patients with or recovering from COVID-19. To address severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neural tropism, we evaluated the vulnerability of primary developing and adult cortical tissue and stem-cell-derived cortical organoids to SARS-CoV-2 infection. We observe robust infection and viral replication in human cortical astrocytes; they become reactive, have increased growth factor signaling, and activate cellular stress. Despite infection in astroglial cells, there is minimal infection of other neural cell types, including neurons. Surprisingly, we discover that astrocyte infection is unlikely to be mediated by the predominant coronavirus receptor, ACE2, and instead observe alternative glycoproteins, CD147 and DPP4, expressed on astrocytes; they are necessary and sufficient for SARS-CoV-2 infection.