TY - JOUR T1 - Neuroinvasive potential of SARS-CoV-2 revealed in a human brain organoid model JF - bioRxiv DO - 10.1101/2020.06.25.169946 SP - 2020.06.25.169946 AU - Eric Song AU - Ce Zhang AU - Benjamin Israelow AU - Peiwen Lu AU - Orr-El Weizman AU - Feimei Liu AU - Yile Dai AU - Klara Szigeti-Buck AU - Yuki Yasumoto AU - Guilin Wang AU - Christopher Castaldi AU - Jaime Heltke AU - Evelyn Ng AU - John Wheeler AU - Mia Madel Alfajaro AU - Benjamin Fontes AU - Neal G. Ravindra AU - David Van Dijk AU - Shrikant Mane AU - Murat Gunel AU - Aaron Ring AU - Craig B Wilen AU - Tamas L. Horvath AU - Angeliki Louvi AU - Shelli F. Farhadian AU - Kaya Bilguvar AU - Akiko Iwasaki Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/06/26/2020.06.25.169946.abstract N2 - Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Reports indicate that 30-60% of patients with COVID-19 suffer from CNS symptoms. Yet, there is no consensus whether the virus can infect the brain, or what the consequences of infection are. Following SARS-CoV-2 infection of human brain organoids, clear evidence of infection was observed, with accompanying metabolic changes in the infected and neighboring neurons. Further, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Finally, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV2.Competing Interest StatementThe authors have declared no competing interest. ER -