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

Bailey, Adam L.; Dmytrenko, Oleksandr; Greenberg, Lina; Bredemeyer, Andrea L.; Ma, Pan; Liu, Jing; Penna, Vinay; 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; Zhang, Xianwen; 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.

There is ongoing debate as to whether cardiac complications of coronavirus disease 2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology and provides a model system to study this emerging disease.