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

Adam L. Bailey, Oleksandr Dmytrenko, Lina Greenberg, Andrea L. Bredemeyer, Pan Ma, Jing Liu, Vinay Penna, Emma S. Winkler, Sanja Sviben, Erin Brooks, Ajith P. Nair, Kent A. Heck, Aniket S. Rali, Leo Simpson, Mehrdad Saririan, Dan Hobohm, W. Tom Stump, James A. Fitzpatrick, Xuping Xie, Xianwen ZhangPei Yong Shi, J. Travis Hinson, Weng Tein Gi, Constanze Schmidt, Florian Leuschner, Chieh Yu Lin, Michael S. Diamond, Michael J. Greenberg, Kory J. Lavine

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish
Pages (from-to)331-345
Number of pages15
JournalJACC: Basic to Translational Science
Volume6
Issue number4
DOIs
StatePublished - Apr 2021

Keywords

  • cardiomyocyte
  • coronavirus disease 2019
  • engineered heart tissue
  • myocarditis
  • severe acute respiratory syndrome coronavirus 2

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