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.
Keywords: ACE2, angiotensin converting enzyme 2; COVID-19, coronavirus disease-2019; EHT, engineered heart tissues; LV, left ventricle; SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2; cardiomyocyte; coronavirus disease 2019; engineered heart tissue; hPSC, human pluripotent stem cell(s); myocarditis; severe acute respiratory syndrome coronavirus 2.
© 2021 The Authors.