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

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.
Competing Interests: Supported by the National Institutes of Health (R01 HL141086 to Dr. M.J. Greenberg; R01 HL138466, and R01 HL139714 to Dr. Lavine; 75N93019C00062, and R01 AI127828 to Dr. Diamond); Burroughs Welcome Fund (1014782 to Dr. Lavine); Defense Advanced Research Project Agency (HR001117S0019 to Dr. Diamond); the March of Dimes Foundation (FY18-BOC-430198 to Dr. M.J. Greenberg.); Foundation of Barnes-Jewish Hospital (8038–88 to Dr. Lavine.); and Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital (CH-II-2017–628 to Dr. Lavine; PM-LI-2019-829 to Drs. Lavine and M.J. Greenberg.). Imaging was performed in the Washington University Center for Cellular Imaging (WUCCI) which is funded, in part by the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital (CDI-CORE-2015-505, CDI-CORE-2019-813) and the Foundation for Barnes-Jewish Hospital (3770). Dr. Diamond is a consultant for Inbios, Eli Lilly, Vir Biotechnology, NGM Biopharmaceuticals; is a member of the Scientific Advisory Board of Moderna; and has received funding and unrelated sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. Dr. Lavine is a member of the Medtronic: DT-PAS/APOGEE trial advisory board; and has received funding and unrelated sponsored research agreements from Amgen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(© 2021 The Authors.)