{"doi":"10.1016/j.stemcr.2021.02.008","title":"SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function","abstract":"COVID-19 patients often develop severe cardiovascular complications, but it remains unclear if these are caused directly by viral infection or are secondary to a systemic response. Here, we examine the cardiac tropism of SARS-CoV-2 in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and smooth muscle cells (hPSC-SMCs). We find that that SARS-CoV-2 selectively infects hPSC-CMs through the viral receptor ACE2, whereas in hPSC-SMCs there is minimal viral entry or replication. After entry into cardiomyocytes, SARS-CoV-2 is assembled in lysosome-like vesicles and egresses via bulk exocytosis. The viral transcripts become a large fraction of cellular mRNA while host gene expression shifts from oxidative to glycolytic metabolism and upregulates chromatin modification and RNA splicing pathways. Most importantly, viral infection of hPSC-CMs progressively impairs both their electrophysiological and contractile function, and causes widespread cell death. These data support the hypothesis that COVID-19-related cardiac symptoms can result from a direct cardiotoxic effect of SARS-CoV-2.","journal":"Stem Cell Reports","year":2021,"id":148849,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":117,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9633,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":245056,"name":"Tien-Ying Hsiang","orcid":"0000-0002-4316-4561","position":1,"is_corresponding":false},{"id":555209,"name":"Akshita Khanna","orcid":null,"position":2,"is_corresponding":false},{"id":555208,"name":"Ty Higashi","orcid":null,"position":3,"is_corresponding":false},{"id":633034,"name":"Leanne S. Whitmore","orcid":"0000-0002-8721-8701","position":4,"is_corresponding":false},{"id":548413,"name":"Johannes Bargehr","orcid":"0000-0002-9304-3573","position":5,"is_corresponding":false},{"id":633035,"name":"Hongorzul Davaapil","orcid":"0000-0001-5947-9317","position":6,"is_corresponding":false},{"id":374525,"name":"Jean Chang","orcid":"0000-0002-1268-2251","position":7,"is_corresponding":false},{"id":4997,"name":"Elise Smith","orcid":"0000-0002-4615-8204","position":8,"is_corresponding":false},{"id":633036,"name":"Lay Ping Ong","orcid":"0000-0001-7421-5117","position":9,"is_corresponding":false},{"id":633037,"name":"Maria Colzani","orcid":"0000-0002-3659-5902","position":10,"is_corresponding":false},{"id":534822,"name":"Hans Reinecke","orcid":"0000-0003-0438-2651","position":11,"is_corresponding":false},{"id":555210,"name":"Xiulan Yang","orcid":null,"position":12,"is_corresponding":false},{"id":554449,"name":"Lil Pabon","orcid":"0000-0003-3095-5011","position":13,"is_corresponding":false},{"id":344679,"name":"Sanjay Sinha","orcid":"0000-0001-5900-1209","position":14,"is_corresponding":false},{"id":633038,"name":"Behzad Najafian","orcid":"0000-0002-0904-6721","position":15,"is_corresponding":false},{"id":366670,"name":"Nathan J. Sniadecki","orcid":"0000-0001-6960-4492","position":16,"is_corresponding":false},{"id":548421,"name":"Alessandro Bertero","orcid":"0000-0002-4919-9087","position":17,"is_corresponding":false},{"id":108916,"name":"Michael Gale","orcid":"0000-0002-6332-7436","position":18,"is_corresponding":false},{"id":366668,"name":"Charles E. Murry","orcid":"0000-0003-3862-6773","position":19,"is_corresponding":false},{"id":554448,"name":"Silvia Marchianò","orcid":"0000-0001-6198-518X","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-18T23:42:46.224799Z","pmid":"33657418","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}