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

BioRxiv : the Preprint Server for Biology
E. SongAkiko Iwasaki

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 ...Continue Reading

Citations

Jul 12, 2020·Nature Reviews. Immunology·Clara Eléonore Pavillet, Tharini Ashtalakshmi Selvakumar
Sep 29, 2020·Frontiers in Immunology·Inmaculada Sanclemente-AlamanUlises Gómez-Pinedo
Sep 17, 2020·Nature·Michael Marshall
Oct 25, 2020·BMJ : British Medical Journal·Muge CevikMalik Peiris
Nov 29, 2020·Biology Direct·Alexei VerkhratskyYufang Shi
Feb 9, 2021·Reviews in the Neurosciences·Dian Eurike Septyaningtrias, Rina Susilowati
Oct 30, 2020·Viruses·Peter Jianrui LiuMirjam Schilling
Dec 12, 2020·Frontiers in Cellular Neuroscience·Marie-Eve TremblayAlexei Verkhratsky
Jan 6, 2021·Nature Reviews. Immunology·Oliver Harschnitz, Lorenz Studer
Jan 8, 2021·Molecular Neurobiology·Kartikay PrasadVijay Kumar
Feb 4, 2021·International Journal of Molecular Sciences·Lu Qian, Julia Tcw
Feb 16, 2021·Frontiers in Immunology·Edwin Estefan Reza-ZaldívarAlejandro Arturo Canales-Aguirre
Dec 18, 2020·Molecular Psychiatry·Deidiane Elisa RibeiroHenning Ulrich
Jan 1, 2021·Alzheimer's Research & Therapy·Scott MinersSeth Love
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Mar 2, 2021·Der Pathologe·N Ritschel„DEFEAT PANDEMIcs – Neuropathologische Referenzdiagnostik bei COVID-19“
Mar 7, 2021·Brain Sciences·Roberta FerrucciAlberto Priori
Apr 1, 2021·Clinical Microbiology Reviews·Nicola ClementiNicasio Mancini
Apr 5, 2021·Current Opinion in Toxicology·Ayse Basak EnginAtilla Engin
Apr 30, 2021·Frontiers in Neurology·Mar Pacheco-HerreroJosé Luna-Muñoz
Apr 27, 2021·Frontiers in Cellular Neuroscience·Petra TavčarJernej Jorgačevski
May 7, 2021·Annual Review of Biophysics·Francisco J Barrantes
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Methods Mentioned

BETA
Electron microscopy
single cell sequencing
RNA-seq
ELISA
light sheet microscopy

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