SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis

• Published in: bioRxiv
• Main Authors: Bailey, Adam L, Dmytrenko, Oleksandr, Greenberg, Lina, Bredemeyer, Andrea L, Ma, Pan, Liu, Jing, Penna, Vinay, Lai, Lulu, Winkler, Emma S, Sviben, Sanja, Brooks, Erin, Nair, Ajith P, Heck, Kent A, Rali, Aniket S, Simpson, Leo, Saririan, Mehrdad, Hobohm, Dan, Stump, W Tom, Fitzpatrick, James A, Xie, Xuping, Shi, Pei-Yong, Hinson, J Travis, Gi, Weng-Tein, Schmidt, Constanze, Leuschner, Florian, Lin, Chieh-Yu, Diamond, Michael S, Greenberg, Michael J, Lavine, Kory J
• Format: Journal Article Paper
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 05.11.2020; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: ACE2; Angiotensin; Angiotensin-converting enzyme 2; Apoptosis; Autopsy; Biotechnology; Cardiomyocytes; Cell activation; Cell death; Coronaviruses; COVID-19; Epidemiology; Heart diseases; Immunology; Infections; Laboratories; Macrophages; Muscle contraction; Myocarditis; Pandemics; Severe acute respiratory syndrome coronavirus 2; Tropism; COVID-19; Myocarditis; SARS-CoV-2; Engineered Heart Tissue; Cardiomyocyte; Macrophage
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2020.11.04.364315

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.