• Sarah R Leist, Kenneth H Dinnon, Alexandra Schäfer, Longping V Tse, Kenichi Okuda, Yixuan J Hou, Ande West, Caitlin E Edwards, Wes Sanders, Ethan J Fritch, Kendra L Gully, Trevor Scobey, Ariane J Brown, Timothy P Sheahan, Nathaniel J Moorman, Richard C Boucher, Lisa E Gralinski, Stephanie A Montgomery, and Ralph S Baric.
• Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
• Cell. 2020 Nov 12; 183 (4): 1070-1085.e12.

AbstractThe SARS-CoV-2 pandemic has caused extreme human suffering and economic harm. We generated and characterized a new mouse-adapted SARS-CoV-2 virus that captures multiple aspects of severe COVID-19 disease in standard laboratory mice. This SARS-CoV-2 model exhibits the spectrum of morbidity and mortality of COVID-19 disease as well as aspects of host genetics, age, cellular tropisms, elevated Th1 cytokines, and loss of surfactant expression and pulmonary function linked to pathological features of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This model can rapidly access existing mouse resources to elucidate the role of host genetics, underlying molecular mechanisms governing SARS-CoV-2 pathogenesis, and the protective or pathogenic immune responses related to disease severity. The model promises to provide a robust platform for studies of ALI and ARDS to evaluate vaccine and antiviral drug performance, including in the most vulnerable populations (i.e., the aged) using standard laboratory mice.Copyright © 2020 Elsevier Inc. All rights reserved.

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