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 Zhang; Pei-Yong Shi; J. Travis Hinson; Weng Tein Gi; Constanze Schmidt; Florian Leuschner; Chieh Yu Lin; Michael S. Diamond; Michael J. Greenberg; Kory J. Lavine

doi:10.1016/j.jacbts.2021.01.002

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

129 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 language	English (US)
Pages (from-to)	331-345
Number of pages	15
Journal	JACC: Basic to Translational Science
Volume	6
Issue number	4
DOIs	https://doi.org/10.1016/j.jacbts.2021.01.002
State	Published - Apr 2021

Keywords

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

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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Bailey, A. L., Dmytrenko, O., Greenberg, L., Bredemeyer, A. L., Ma, P., Liu, J., Penna, V., Winkler, E. S., Sviben, S., Brooks, E., Nair, A. P., Heck, K. A., Rali, A. S., Simpson, L., Saririan, M., Hobohm, D., Stump, W. T., Fitzpatrick, J. A., Xie, X., ... Lavine, K. J. (2021). SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis. JACC: Basic to Translational Science, 6(4), 331-345. https://doi.org/10.1016/j.jacbts.2021.01.002

Bailey, AL, Dmytrenko, O, Greenberg, L, Bredemeyer, AL, Ma, P, Liu, J, Penna, V, Winkler, ES, Sviben, S, Brooks, E, Nair, AP, Heck, KA, Rali, AS, Simpson, L, Saririan, M, Hobohm, D, Stump, WT, Fitzpatrick, JA, Xie, X, Zhang, X, Shi, P-Y, Hinson, JT, Gi, WT, Schmidt, C, Leuschner, F, Lin, CY, Diamond, MS, Greenberg, MJ & Lavine, KJ 2021, 'SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis', JACC: Basic to Translational Science, vol. 6, no. 4, pp. 331-345. https://doi.org/10.1016/j.jacbts.2021.01.002

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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.",

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AU - Saririan, Mehrdad

AU - Hobohm, Dan

AU - Stump, W. Tom

AU - Fitzpatrick, James A.

AU - Xie, Xuping

AU - Zhang, Xianwen

AU - Shi, Pei-Yong

AU - Hinson, J. Travis

AU - Gi, Weng Tein

AU - Schmidt, Constanze

AU - Leuschner, Florian

AU - Lin, Chieh Yu

AU - Diamond, Michael S.

AU - Greenberg, Michael J.

AU - Lavine, Kory J.

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

Abstract

Keywords

ASJC Scopus subject areas

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