SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis
Adam L. Bailey, Oleksandr Dmytrenko, Lina Greenberg, Andrea Bredemeyer, Pan Ma, Jing Liu, Vinay Penna, Emma S. Winkler, Sanja Sviben, Erin G. Brooks, Ajith Nair, Kent A. Heck, Aniket S. Rali, Leo Simpson, Mehrdad Saririan, Dan Hobohm, W. Tom Stump, James A. J. Fitzpatrick, Xuping Xie, Xianwen Zhang, Pei‐Yong Shi, J. Travis Hinson, Weng‐Tein Gi, Constanze Schmidt, Florian Leuschner, Chieh‐Yu Lin, Michael Diamond, Michael J. Greenberg, Kory J. Lavine
Abstract
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.