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JACC Basic Transl Sci
. 2021 Feb 26.
doi: 10.1016/j.jacbts.2021.01.002. Online ahead of print.
SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis
Adam L Bailey 1 , Oleksandr Dmytrenko 2 , Lina Greenberg 3 , Andrea L Bredemeyer 2 , Pan Ma 2 , Jing Liu 2 , Vinay Penna 2 , Emma S Winkler 1 , Sanja Sviben 4 , Erin Brooks 5 , Ajith P Nair 6 , Kent A Heck 7 , Aniket S Rali 8 , Leo Simpson 6 , Mehrdad Saririan 9 , Dan Hobohm 9 , W Tom Stump 3 , James A Fitzpatrick 4 10 , Xuping Xie 11 , Xianwen Zhang 11 , Pei-Yong Shi 11 , J Travis Hinson 12 13 , Weng-Tein Gi 14 , Constanze Schmidt 14 , Florian Leuschner 14 , Chieh-Yu Lin 1 , Michael S Diamond 1 2 15 , Michael J Greenberg 3 , Kory J Lavine 1 2 16
Affiliations
- PMID: 33681537
- PMCID: PMC7909907
- DOI: 10.1016/j.jacbts.2021.01.002
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: 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.