This preprint explores the ability of SARS-CoV-2 to infect and replicate in neural tissues of mouse and human origin. Induced pluripotent stem cell lines derived from healthy donors were used to generate human brain organoids for modelling SARS-CoV-2 infection. Extensive cell death and metabolic changes occurred in both infected and neighbouring neurons, inducing locally hypoxic regions with no evidence of a type I interferon response. Organoids incubated with antibodies to ACE2 or to viral spike protein from the cerebrospinal fluid of patients with COVID-19 had decreased SARS-CoV-2 infection. Transgenic mice overexpressing human ACE2 (hACE2) in the brain had decreased survival after SARS-CoV-2 infection compared with those expressing hACE2 in lungs. This study provides insight into the neuroinvasive potential of SARS-CoV-2, which could explain neurological symptoms experienced by some patients.
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Song, E. et al. Neuroinvasive potential of SARS-CoV-2 revealed in a human brain organoid model. Preprint at bioRxiv https://doi.org/10.1101/2020.06.25.169946 (2020)
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Pavillet, C.E., Selvakumar, T.A. SARS-CoV-2 on the neural battleground. Nat Rev Immunol 20, 518 (2020). https://doi.org/10.1038/s41577-020-0399-x
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DOI: https://doi.org/10.1038/s41577-020-0399-x
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