RT Journal Article SR Electronic T1 A Human 3D neural assembloid model for SARS-CoV-2 infection JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.02.09.430349 DO 10.1101/2021.02.09.430349 A1 Lu Wang A1 David Sievert A1 Alex E. Clark A1 Hannah Federman A1 Benjamin D. Gastfriend A1 Eric Shusta A1 Sean P. Palecek A1 Aaron F. Carlin A1 Joseph Gleeson YR 2021 UL http://biorxiv.org/content/early/2021/02/09/2021.02.09.430349.abstract AB Clinical evidence suggests the central nervous system (CNS) is frequently impacted by SARS-CoV-2 infection, either directly or indirectly, although mechanisms remain unclear. Pericytes are perivascular cells within the brain that are proposed as SARS-CoV-2 infection points1. Here we show that pericyte-like cells (PLCs), when integrated into a cortical organoid, are capable of infection with authentic SARS-CoV-2. Prior to infection, PLCs elicited astrocytic maturation and production of basement membrane components, features attributed to pericyte functions in vivo. While traditional cortical organoids showed little evidence of infection, PLCs within cortical organoids served as viral ‘replication hubs’, with virus spreading to astrocytes and mediating inflammatory type I interferon transcriptional responses. Therefore, PLC-containing cortical organoids (PCCOs) represent a new ‘assembloid’ model2 that supports SARS-CoV-2 entry and replication in neural tissue, and PCCOs serve as an experimental model for neural infection.Competing Interest StatementThe authors have declared no competing interest.