RT Journal Article SR Electronic T1 SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.04.364315 DO 10.1101/2020.11.04.364315 A1 Adam L. Bailey A1 Oleksandr Dmytrenko A1 Lina Greenberg A1 Andrea L. Bredemeyer A1 Pan Ma A1 Jing Liu A1 Vinay Penna A1 Lulu Lai A1 Emma S. Winkler A1 Sanja Sviben A1 Erin Brooks A1 Ajith P. Nair A1 Kent A. Heck A1 Aniket S. Rali A1 Leo Simpson A1 Mehrdad Saririan A1 Dan Hobohm A1 W. Tom Stump A1 James A. Fitzpatrick A1 Xuping Xie A1 Pei-Yong Shi A1 J. Travis Hinson A1 Weng-Tein Gi A1 Constanze Schmidt A1 Florian Leuschner A1 Chieh-Yu Lin A1 Michael S. Diamond A1 Michael J. Greenberg A1 Kory J. Lavine YR 2020 UL http://biorxiv.org/content/early/2020/11/05/2020.11.04.364315.abstract AB Epidemiological studies of the COVID-19 pandemic have revealed evidence of cardiac involvement and documented that myocardial injury and myocarditis are predictors of poor outcomes. Nonetheless, little is understood regarding SARS-CoV-2 tropism within the heart and whether cardiac complications result directly from myocardial infection. Here, we develop a human engineered heart tissue model and demonstrate that SARS-CoV-2 selectively infects cardiomyocytes. Viral infection is dependent on expression of angiotensin-I converting enzyme 2 (ACE2) and endosomal cysteine proteases, suggesting an endosomal mechanism of cell entry. After infection with SARS-CoV-2, engineered tissues display typical features of myocarditis, including cardiomyocyte cell death, impaired cardiac contractility, and innate immune cell activation. Consistent with these findings, autopsy tissue obtained from individuals with COVID-19 myocarditis demonstrated cardiomyocyte infection, cell death, and macrophage-predominate immune cell infiltrate. These findings establish human cardiomyocyte tropism for SARS-CoV-2 and provide an experimental platform for interrogating and mitigating cardiac complications of COVID-19.Competing Interest StatementKory Lavine - Medtronic: DT-PAS/APOGEE trial advisory board. M.S.D. is a consultant for Inbios, Eli Lilly, Vir Biotechnology, NGM Biopharmaceuticals, and on the Scientific Advisory Board of Moderna. The Lavine laboratory has received funding and unrelated sponsored research agreements from Amgen. The Diamond laboratory has received funding and unrelated sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. Lina Greenberg, W. Tom Stump, Michael Greenberg, Adam Bailey, Oleksandr Dmytrenko, Andrea Bredemeyer - None.