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

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134 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
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

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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

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title = "SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis",

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.",

keywords = "cardiomyocyte, coronavirus disease 2019, engineered heart tissue, myocarditis, severe acute respiratory syndrome coronavirus 2",

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

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = apr,

doi = "10.1016/j.jacbts.2021.01.002",

language = "English",

volume = "6",

pages = "331--345",

journal = "JACC: Basic to Translational Science",

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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, PY, 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

TY - JOUR

T1 - SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis

AU - Bailey, Adam L.

AU - Dmytrenko, Oleksandr

AU - Greenberg, Lina

AU - Bredemeyer, Andrea L.

AU - Ma, Pan

AU - Liu, Jing

AU - Penna, Vinay

AU - Winkler, Emma S.

AU - Sviben, Sanja

AU - Brooks, Erin

AU - Nair, Ajith P.

AU - Heck, Kent A.

AU - Rali, Aniket S.

AU - Simpson, Leo

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.

PY - 2021/4

Y1 - 2021/4

N2 - 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.

AB - 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.

KW - cardiomyocyte

KW - coronavirus disease 2019

KW - engineered heart tissue

KW - myocarditis

KW - severe acute respiratory syndrome coronavirus 2

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U2 - 10.1016/j.jacbts.2021.01.002

DO - 10.1016/j.jacbts.2021.01.002

M3 - Article

C2 - 33681537

AN - SCOPUS:85104326032

SN - 2452-302X

VL - 6

SP - 331

EP - 345

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

IS - 4

ER -

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

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Keywords

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