SARS‐CoV‐2 targets neurons of 3D human brain organoids

Ramani, Anand; Müller, Lisa; Ostermann, Philipp N; Gabriel, Elke; Abida‐Islam, Pranty; Müller‐Schiffmann, Andreas; Mariappan, Aruljothi; Goureau, Olivier; Gruell, Henning; Walker, Andreas; Andrée, Marcel; Hauka, Sandra; Houwaart, Torsten; Dilthey, Alexander; Wohlgemuth, Kai; Omran, Heymut; Klein, Florian; Wieczorek, Dagmar; Adams, Ortwin; Timm, Jörg; Korth, Carsten; Schaal, Heiner; Gopalakrishnan, Jay

COVID‐19 pandemic caused by SARS‐CoV‐2 infection is a public health emergency. COVID‐19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS‐CoV‐2 on the central nervous system (CNS). Here, we show that a Düsseldorf isolate of SARS‐CoV‐2 enters 3D human brain organoids within 2 days of exposure. We identified that SARS‐CoV‐2 preferably targets neurons of brain organoids. Imaging neurons of organoids reveal that SARS‐CoV‐2 exposure is associated with altered distribution of Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Our studies, therefore, provide initial insights into the potential neurotoxic effect of SARS‐CoV‐2 and emphasize that brain organoids could model CNS pathologies of COVID‐19.