{"doi":"10.1101/2020.11.04.364315","title":"SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis","abstract":"Epidemiological studies of the COVID-19 pandemic have revealed evidence of cardiac involvement and documented that myocardial injury and myocarditis are predictors of poor outcomes. Nonetheless, little is understood regarding SARS-CoV-2 tropism within the heart and whether cardiac complications result directly from myocardial infection. Here, we develop a human engineered heart tissue model and demonstrate that SARS-CoV-2 selectively infects cardiomyocytes. Viral infection is dependent on expression of angiotensin-I converting enzyme 2 (ACE2) and endosomal cysteine proteases, suggesting an endosomal mechanism of cell entry. After infection with SARS-CoV-2, engineered tissues display typical features of myocarditis, including cardiomyocyte cell death, impaired cardiac contractility, and innate immune cell activation. Consistent with these findings, autopsy tissue obtained from individuals with COVID-19 myocarditis demonstrated cardiomyocyte infection, cell death, and macrophage-predominate immune cell infiltrate. These findings establish human cardiomyocyte tropism for SARS-CoV-2 and provide an experimental platform for interrogating and mitigating cardiac complications of COVID-19.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":118942,"datarank":0.5333022092234121,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.0,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":552520,"name":"Oleksandr Dmytrenko","orcid":"0000-0003-2659-2086","position":1,"is_corresponding":false},{"id":553297,"name":"Lina Greenberg","orcid":null,"position":2,"is_corresponding":false},{"id":552521,"name":"Andrea Bredemeyer","orcid":"0000-0003-2970-5998","position":3,"is_corresponding":false},{"id":552522,"name":"Pan Ma","orcid":"0000-0002-0815-849X","position":4,"is_corresponding":false},{"id":20712,"name":"Jianjun Liu","orcid":"0000-0002-3255-3019","position":5,"is_corresponding":false},{"id":552523,"name":"Vinay Penna","orcid":"0000-0002-9082-7874","position":6,"is_corresponding":false},{"id":552524,"name":"Lulu Lai","orcid":"0000-0002-3352-9467","position":7,"is_corresponding":false},{"id":106514,"name":"Emma S. 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