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Journal Articles Journal of Experimental Medicine Year : 2021

Neuroinvasion of SARS-CoV-2 in human and mouse brain

Eric Song
Ce Zhang
Benjamin Israelow
Alice Lu-Culligan
Peiwen Lu
Orr-El Weizman
Feimei Liu
Yile Dai
Klara Szigeti-Buck
Yuki Yasumoto
Guilin Wang
Christopher Castaldi
Jaime Heltke
Evelyn Ng
John Wheeler
Mia Madel Alfajaro
Benjamin Fontes
Neal G Ravindra
David van Dijk
Shrikant Mane
Murat Gunel
Aaron Ring
Syed a Jaffar Kazmi
Kai Zhang
Craig B Wilen
Tamas L Horvath
Isabelle Plu
Stephane Haik
Angeliki Louvi
Shelli F Farhadian
Anita Huttner
Nicolas Renier
Kaya Bilguvar
Akiko Iwasaki
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Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.
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Licence : CC BY NC - Attribution - NonCommercial

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hal-04520425 , version 1 (25-03-2024)


Attribution - NonCommercial



Eric Song, Ce Zhang, Benjamin Israelow, Alice Lu-Culligan, Alba Vieites Prado, et al.. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal of Experimental Medicine, 2021, 218 (3), pp.e20202135. ⟨10.1084/jem.20202135⟩. ⟨hal-04520425⟩
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