Neuroinvasion of SARS-CoV-2 in human and mouse brain
Top Cited Papers
Open Access
- 28 February 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 218 (3)
- https://doi.org/10.1084/jem.20202135
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 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.Funding Information
- National Institutes of Health (R01AI157488, R01NS111242, T32GM007205, F30CA239444, 2T32AI007517, K23MH118999)
- Yale University
- Emergent Ventures at the Mercatus Center
- Mathers Foundation
- Ludwig Family Foundation
- Howard Hughes Medical Institute
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