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

Authors :
Song E
Zhang C
Israelow B
Lu-Culligan A
Prado AV
Skriabine S
Lu P
Weizman OE
Liu F
Dai Y
Szigeti-Buck K
Yasumoto Y
Wang G
Castaldi C
Heltke J
Ng E
Wheeler J
Alfajaro MM
Levavasseur E
Fontes B
Ravindra NG
Van Dijk D
Mane S
Gunel M
Ring A
Kazmi SAJ
Zhang K
Wilen CB
Horvath TL
Plu I
Haik S
Thomas JL
Louvi A
Farhadian SF
Huttner A
Seilhean D
Renier N
Bilguvar K
Iwasaki A
Source :
BioRxiv : the preprint server for biology [bioRxiv] 2020 Sep 08. Date of Electronic Publication: 2020 Sep 08.
Publication Year :
2020

Abstract

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 whether the virus can infect the brain, or what the consequences of CNS infection are. 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 the infected and neighboring neurons. However, 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. Second, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. Finally, in brain autopsy from patients who died of COVID-19, we detect SARS-CoV-2 in the cortical neurons, and note pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

Details

Language :
English
Database :
MEDLINE
Journal :
BioRxiv : the preprint server for biology
Accession number :
32935108
Full Text :
https://doi.org/10.1101/2020.06.25.169946