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Publication : Does SARS-Cov-2 invade the brain? Translational lessons from animal models.

First Author  Natoli S Year  2020
Journal  Eur J Neurol PubMed ID  32333487
Mgi Jnum  J:287925 Mgi Id  MGI:6423513
Doi  10.1111/ENE.14277 Citation  Natoli S, et al. (2020) Does SARS-Cov-2 invade the brain? Translational lessons from animal models. Eur J Neurol
abstractText  The current coronavirus disease (COVID-19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS-CoV-2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus from a translational perspective. Animal models of SARS and Middle East respiratory syndrome (MERS), caused by structurally similar coronaviruses during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by coronaviruses and the potential for CNS spread of SARS-CoV-2. One key finding that may unify these pathogens is that all require angiotensin-converting enzyme 2 (ACE2) as a cell entry receptor. The CoV spike glycoprotein, by which SARS_CoV-2 binds to cell membranes, binds ACE2 with a higher affinity compared to SARS-CoV. The expression of this receptor in neurons and endothelial cells hints that SARS-CoV-2 may have higher neuroinvasive potential compared to previous coronaviruses. Yet, how such invasiveness might contribute to respiratory failure or cause direct neurological damage remains to be determined. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune-mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune-mediated pathogenicity in the short- and medium- term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous coronavirus infections and discuss their potential relevance to COVID-19.
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