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

[Display omitted] •SARS-CoV-2 directly infects cardiomyocytes in patients with COVID-19 myocarditis and does not infect cardiac macrophages, fibroblasts, or endothelial cells.•COVID-19 myocarditis is characterized by a myeloid-rich inflammatory infiltrate.•SARS-CoV-2 infects cardiomyocytes through a...

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Vydáno v:	JACC. Basic to translational science Ročník 6; číslo 4; s. 331 - 345
Hlavní autoři:	Bailey, Adam L., Dmytrenko, Oleksandr, Greenberg, Lina, Bredemeyer, Andrea L., Ma, Pan, Liu, Jing, Penna, Vinay, Winkler, Emma S., Sviben, Sanja, Brooks, Erin, Nair, Ajith P., Heck, Kent A., Rali, Aniket S., Simpson, Leo, Saririan, Mehrdad, Hobohm, Dan, Stump, W. Tom, Fitzpatrick, James A., Xie, Xuping, Zhang, Xianwen, Shi, Pei-Yong, Hinson, J. Travis, Gi, Weng-Tein, Schmidt, Constanze, Leuschner, Florian, Lin, Chieh-Yu, Diamond, Michael S., Greenberg, Michael J., Lavine, Kory J.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Elsevier Inc 01.04.2021 Elsevier
Témata:	cardiomyocyte Cardiovascular Clinical Research coronavirus disease 2019 engineered heart tissue myocarditis severe acute respiratory syndrome coronavirus 2 COVID-19 EHT ACE2 SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 coronavirus disease 2019 myocarditis cardiomyocyte hPSC engineered heart tissue LV coronavirus disease-2019 human pluripotent stem cell(s) left ventricle engineered heart tissues angiotensin converting enzyme 2 severe acute respiratory syndrome-coronavirus-2 ACE2, angiotensin converting enzyme 2 LV, left ventricle COVID-19, coronavirus disease-2019 SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2 hPSC, human pluripotent stem cell(s) EHT, engineered heart tissues
ISSN:	2452-302X, 2452-302X
On-line přístup:	Získat plný text
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Shrnutí:	[Display omitted] •SARS-CoV-2 directly infects cardiomyocytes in patients with COVID-19 myocarditis and does not infect cardiac macrophages, fibroblasts, or endothelial cells.•COVID-19 myocarditis is characterized by a myeloid-rich inflammatory infiltrate.•SARS-CoV-2 infects cardiomyocytes through an ACE2 and endosomal cysteine protease dependent pathway.•Infection of hPSC-derived cardiomyocytes and engineered heart tissues show that cytokine production, sarcomere disassembly, and cell death were a direct consequence of cardiomyocyte infection.•SARS-CoV-2 reduces cardiomyocyte contractility through sarcomere breakdown and cardiomyocyte cell death. 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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Drs. Lin, Diamond, M. J. Greenberg, and Lavine contributed equally to this work and are joint senior authors. Drs. Bailey and L. Greenberg, and Mr. Dmytrenko contributed equally to this work and are joint first authors.
ISSN:	2452-302X 2452-302X
DOI:	10.1016/j.jacbts.2021.01.002