ArticleStem cell reports2021
SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function.
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In one paragraph
Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Stem Cell Extracellular Vesicles as Anti-SARS-CoV-2 Immunomodulatory Therapeutics: A Systematic Review of Clinical and Preclinical Studies.Stem cell reviews and reports · 2024Pooled it
- Systems biology analysis reveals miRNA-mRNA networks associated with cardiomyocyte responses to SARS-CoV-2 infection.NPJ systems biology and applications · 2026Article
- SARS-CoV-2 Persistence and Cardiovascular Sequelae in the Post-COVID Era: A Public Health Microbiology Perspective on Sudden Cardiac Death and Pulmonary Thromboembolism.Microorganisms · 2026Review
- SARS-CoV-2-infected cardiomyocytes exhibit upregulated necroptosis, but no evidence of mitochondrial permeability transition.Journal of molecular and cellular cardiology plus · 2026Article
- Unbiased cleavage site prediction uncovers viral antagonism of host innate immunity by SARS-CoV-2 3C-like protease.JCI insight · 2026Article
- Deceiving the gatekeepers: virus modulation of gap junctions.Microbiology and molecular biology reviews : MMBR · 2025Review
- Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.Journal of molecular and cellular cardiology · 2025Review
- A Vascularized Human Organ Chip Reveals SARS-CoV-2 Susceptibility in Developmentally Guided Tissue Maturation.Cellular and molecular bioengineering · 2025Article
- Selective Inhibition of Vascular Smooth Muscle Cell Function by COVID-19 Antiviral Drugs: Impact of Heme Oxygenase-1.Antioxidants (Basel, Switzerland) · 2025Article
- The Role of SARS-CoV-2 Spike Protein in Long-term Damage of Tissues and Organs, the Underestimated Role of Retrotransposons and Stem Cells, a Working Hypothesis.Endocrine, metabolic & immune disorders drug targets · 2025Review
- Risk impact of SARS-CoV-2 coronavirus and spike protein on cardiac tissue: a comprehensive review.Physiological research · 2024Review
- The protective effect of serum antibodies in preventing SARS-CoV-2 virus entry into cardiac muscle.Physiological research · 2024Article
- Infiltrating monocytes drive cardiac dysfunction in a cardiomyocyte-restricted mouse model of SARS-CoV-2 infection.Journal of virology · 2024Article
- Lab-on-a-chip models of cardiac inflammation.Biomicrofluidics · 2024Review
- Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection.American heart journal plus : cardiology research and practice · 2024Article
- SARS-CoV-2 pathogenesis in an angiotensin II-induced heart-on-a-chip disease model and extracellular vesicle screening.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Factors Associated with Prolonged SARS-CoV-2 Viral Positivity in an Italian Cohort of Hospitalized Patients.Diseases (Basel, Switzerland) · 2024Article
- Infectious factors in myocarditis: a comprehensive review of common and rare pathogens.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Review
- The emerging role of heart-on-a-chip systems in delineating mechanisms of SARS-CoV-2-induced cardiac dysfunction.Bioengineering & translational medicine · 2024Review
- Cardiac tissue model of immune-induced dysfunction reveals the role of free mitochondrial DNA and the therapeutic effects of exosomes.Science advances · 2024Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 5 institutions in 2 countries.
Silvia MarchianoDepartment of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Tien-Ying HsiangCenter for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Akshita KhannaDepartment of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Ty HigashiDepartment of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA; Department of Mechanical Engineering, University of Washington, 3720 15th Avenue NE, Seattle, WA 98105, USA.
Leanne S WhitmoreCenter for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Johannes BargehrWellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambridge CB2 0QQ, UK.
Hongorzul DavaapilWellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambridge CB2 0QQ, UK.
Jean ChangCenter for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Elise SmithCenter for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Lay Ping OngWellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambridge CB2 0QQ, UK.
Maria ColzaniWellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambridge CB2 0QQ, UK.
Hans ReineckeDepartment of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Xiulan YangDepartment of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Lil PabonDepartment of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA; Sana Biotechnology, 188 E Blaine Street, Seattle, WA 98102, USA.
Sanjay SinhaWellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambridge CB2 0QQ, UK.
Behzad NajafianDepartment of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA.
Nathan J SniadeckiDepartment of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA; Department of Mechanical Engineering, University of Washington, 3720 15th Avenue NE, Seattle, WA 98105, USA; Department of Bioengineering, University of Washington, 3720 15th Avenue NE, Seattle, WA 98105, USA.
Alessandro BerteroDepartment of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Michael GaleCenter for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA. Electronic address: mgale@uw.edu.
Charles E MurryDepartment of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA; Sana Biotechnology, 188 E Blaine Street, Seattle, WA 98102, USA; Department of Bioengineering, University of Washington, 3720 15th Avenue NE, Seattle, WA 98105, USA; Department of Medicine/Cardiology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA. Electronic address: murry@uw.edu.
University of Washington · USUniversity of Cambridge · GBAddenbrooke's Hospital · GBSana Biotechnology (United States) · USWellcome/MRC Cambridge Stem Cell Institute · GB
Funding
Washington National Primate Research CenterP51OD010425 · OD · UNIVERSITY OF WASHINGTON · PI Mari Ostendorf · 2012 to 2026
$201.8MLeadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG) - Momi-Vax DMID #21-0004 {Supplement #6}UM1AI148684 · NIAID · EMORY UNIVERSITY · PI DAVID S STEPHENS · 2020 to 2026
$77.2MUnlocking Zika Virus Immune Control and Pathogenesis with the Collaborative CrossU19AI100625 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GALE, MICHAEL · 2012 to 2021
$36.6MUniversity of Washington Arboviral Research Network (UWARN)U01AI151698 · NIAID · UNIVERSITY OF WASHINGTON · PI Michael Gale, PETER MACGARR RABINOWITZ · 2020 to 2026
$13.3MInnate Immune Regulation of Zika Virus InfectionR01AI145296 · NIAID · UNIVERSITY OF WASHINGTON · PI COYNE, CAROLYN B, DIAMOND, MICHAEL S · 2019 to 2023
$4.1MPrimate Heart RegenerationR01HL128362 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E · 2016 to 2019
$3.5MMechanisms of Cell-Based Heart RegenerationR01HL146868 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E, SNIADECKI, NATHAN JOHN · 2019 to 2022
$3.5MMechanisms of hepatic innate immune activation by HCVR01AI127463 · NIAID · UNIVERSITY OF WASHINGTON · PI GALE, MICHAEL, ROSEN, HUGO RAMON · 2017 to 2021
$2.8MThe Host Response to Hepatitis C VirusR01AI118916 · NIAID · UNIVERSITY OF WASHINGTON · PI GALE, MICHAEL · 2016 to 2020
$2.5MMechanotransduction by Melusin in Cardiac HypertrophyR01HL149734 · NHLBI · UNIVERSITY OF WASHINGTON · PI SNIADECKI, NATHAN JOHN · 2020 to 2023
$2.1MUsing the Collaborative Cross to discover immunoregulatory mechanisms that control WNV infectionR21AI145359 · NIAID · UNIVERSITY OF WASHINGTON · PI GALE, MICHAEL · 2019 to 2020
$485kBritish Heart Foundation FS/13/65/30441Medical Research Council MC_PC_17230NHLBI NIH HHS R01 HL128362NHLBI NIH HHS R01 HL146868NHLBI NIH HHS R01 HL149734NIAID NIH HHS R01 AI118916NIAID NIH HHS R01 AI127463NIAID NIH HHS R01 AI145296NIAID NIH HHS R21 AI145359NIAID NIH HHS U01 AI151698NIAID NIH HHS U19 AI100625NIAID NIH HHS UM1 AI148684NIH HHS P51 OD010425Wellcome Trust 203568/Z/16/Z
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.
Indexed as
Cells, CulturedCOVID-19HumansInduced Pluripotent Stem CellsMyocytes, CardiacRNA, MessengerRNA SplicingSARS-CoV-2Virus InternalizationRNA, Messengerarrhythmias and heart failurecardiac infectioncardiovascular diseaseCOVID-19hESC-CMshPSC-CMshuman pluripotent stem cell-derived cardiomyocytesSARS-CoV-2viral myocarditis
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.