Cardiovascular Research

, volume 116 , issue 14 , pages 2207-2215

SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes

Denisa Bojkova ¹

Julian U.G. Wagner ^{2, 3}

Mariana Shumliakivska ²

Galip S Aslan ²

Umber Saleem ^{3, 4}

Arne Hansen ^{3, 4}

Guillermo Luxán ²

Stefan Günther ^{5, 6}

Minh Duc Pham ⁷

Jaya Krishnan ^{6, 7}

Patrick N Harter ⁸

Utz H Ermel ⁹

Achilleas S. Frangakis ⁹

Hendrik Milting ¹⁰

Andreas M. Zeiher ^{4, 6, 7}

Karin Klingel ¹¹

Jindrich Cinatl ¹

Andreas Dendorfer ^{4, 12}

Thomas Eschenhagen ^{3, 4}

Carsten Tschöpe ^{3, 13}

Sandra Ciesek ^{1, 14, 15}

Stefanie Dimmeler ^{2, 3, 6}

Hide authors affiliations Show authors affiliations: 15 affiliations

Institute of Medical Virology, University of Frankfurt, Paul-Ehrlich-Str. 40, 60590 Frankfurt, Germany |

Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt, Germany |

German Center for Cardiovascular Research (DZHK), Germany |

⁴

Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany |

⁵

Max Planck Institute Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany |

⁶

Cardiopulmonary Institute (CPI), Frankfurt, Germany |

⁷

Department of Medicine, Cardiology, Goethe University Hospital, Theodor Stern Kai 7, 60590 Frankfurt, Germany |

⁸

Neurological Institute (Edinger Institute), University of Frankfurt, Heinrich-Hoffmann Strasse 7, 60528 Frankfurt, Germany |

⁹

Institute of Biophysics and BMLS, University of Frankfurt, Campus Riedberg, Maxvon-Laue Strasse 15, 60438 Frankfurt, Germany |

¹⁰

Heart and Diabetes Center NRW, University Hospital of the Ruhr University Bochum, Clinic for Thoracic and Cardiovascular Surgery, Erich & Hanna Klessmann Institute, Georgstr. 11, 32545 Bad Oeyenhausen, Germany |

¹¹

Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tuebingen, Liebermeisterstraße 8, 72076 Tuebingen, Germany |

¹²

Walter-Brendel-Centre of Experimental Medicine, University Hospital, LMU Munich, Marchioninistr. 27, 81377 Munich, Germany |

¹³

Department of Cardiology, Campus Virchow Klinikum (CVK), Charité, and Berlin Institute of Health (BIH), Berlin Brandenburger Center for Regenerative Therapies (BCRT), University Medicine Berlin, Berlin, Germany

Charité - Universitätsmedizin Berlin

Berlin Institute of Health at Charité - Universitätsmedizin Berlin

¹⁴

Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Branch Translational Medicine and Pharmacology, Theodor Stern Kai 7, 60590 Frankfurt, Germany |

¹⁵

German Centre for Infection Research (DZIF), External partner site, Frankfurt, Germany |

Publication type: Journal Article

Publication date: 2020-09-23

Oxford University Press

Cardiovascular Research

scimago Q1

wos Q1

SJR: 3.947

CiteScore: 21.3

Impact factor: 13.3

ISSN: 00086363, 17553245

DOI: 10.1093/cvr/cvaa267

Copy DOI

PubMed ID: 32966582

Cardiology and Cardiovascular Medicine

Physiology

Physiology (medical)

Abstract

Aims

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic. SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk of mortality. It is unclear whether cardiac injury is caused by direct infection of cardiomyocytes or is mainly secondary to lung injury and inflammation. Here, we investigate whether cardiomyocytes are permissive for SARS-CoV-2 infection.

Methods and results

Two strains of SARS-CoV-2 infected human induced pluripotent stem cell-derived cardiomyocytes as demonstrated by detection of intracellular double-stranded viral RNA and viral spike glycoprotein expression. Increasing concentrations of viral RNA are detected in supernatants of infected cardiomyocytes, which induced infections in Caco-2 cell lines, documenting productive infections. SARS-CoV-2 infection and induced cytotoxic and proapoptotic effects associated with it abolished cardiomyocyte beating. RNA sequencing confirmed a transcriptional response to viral infection as demonstrated by the up-regulation of genes associated with pathways related to viral response and interferon signalling, apoptosis, and reactive oxygen stress. SARS-CoV-2 infection and cardiotoxicity was confirmed in a 3D cardiosphere tissue model. Importantly, viral spike protein and viral particles were detected in living human heart slices after infection with SARS-CoV-2. Coronavirus particles were further observed in cardiomyocytes of a patient with coronavirus disease 2019. Infection of induced pluripotent stem cell-derived cardiomyocytes was dependent on cathepsins and angiotensin-converting enzyme 2, and was blocked by remdesivir.

Conclusion

This study demonstrates that SARS-CoV-2 infects cardiomyocytes in vitro in an angiotensin-converting enzyme 2- and cathepsin-dependent manner. SARS-CoV-2 infection of cardiomyocytes is inhibited by the antiviral drug remdesivir.

Found

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200

Cite this

GOST |

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GOST Copy

Bojkova D. et al. SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes // Cardiovascular Research. 2020. Vol. 116. No. 14. pp. 2207-2215.

GOST all authors (up to 50) Copy

Bojkova D., Wagner J. U., Shumliakivska M., Aslan G. S., Saleem U., Hansen A., Luxán G., Günther S., Pham M. D., Krishnan J., Harter P. N., Ermel U. H., Frangakis A., Milting H., Zeiher A. M., Klingel K., Cinatl J., Dendorfer A., Eschenhagen T., Tschöpe C., Ciesek S., Dimmeler S. SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes // Cardiovascular Research. 2020. Vol. 116. No. 14. pp. 2207-2215.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1093/cvr/cvaa267

UR - https://doi.org/10.1093/cvr/cvaa267

TI - SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes

T2 - Cardiovascular Research

AU - Bojkova, Denisa

AU - Wagner, Julian U.G.

AU - Shumliakivska, Mariana

AU - Aslan, Galip S

AU - Saleem, Umber

AU - Hansen, Arne

AU - Luxán, Guillermo

AU - Günther, Stefan

AU - Pham, Minh Duc

AU - Krishnan, Jaya

AU - Harter, Patrick N

AU - Ermel, Utz H

AU - Frangakis, Achilleas S.

AU - Milting, Hendrik

AU - Zeiher, Andreas M.

AU - Klingel, Karin

AU - Cinatl, Jindrich

AU - Dendorfer, Andreas

AU - Eschenhagen, Thomas

AU - Tschöpe, Carsten

AU - Ciesek, Sandra

AU - Dimmeler, Stefanie

PY - 2020

DA - 2020/09/23

PB - Oxford University Press

SP - 2207-2215

IS - 14

VL - 116

PMID - 32966582

SN - 0008-6363

SN - 1755-3245

ER -

BibTex |

Cite this

BibTex (up to 50 authors) Copy

@article{2020_Bojkova,

author = {Denisa Bojkova and Julian U.G. Wagner and Mariana Shumliakivska and Galip S Aslan and Umber Saleem and Arne Hansen and Guillermo Luxán and Stefan Günther and Minh Duc Pham and Jaya Krishnan and Patrick N Harter and Utz H Ermel and Achilleas S. Frangakis and Hendrik Milting and Andreas M. Zeiher and Karin Klingel and Jindrich Cinatl and Andreas Dendorfer and Thomas Eschenhagen and Carsten Tschöpe and Sandra Ciesek and Stefanie Dimmeler},

title = {SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes},

journal = {Cardiovascular Research},

year = {2020},

volume = {116},

publisher = {Oxford University Press},

month = {sep},

url = {https://doi.org/10.1093/cvr/cvaa267},

number = {14},

pages = {2207--2215},

doi = {10.1093/cvr/cvaa267}

}

MLA

Cite this

MLA Copy

Bojkova, Denisa, et al. “SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes.” Cardiovascular Research, vol. 116, no. 14, Sep. 2020, pp. 2207-2215. https://doi.org/10.1093/cvr/cvaa267.

Publisher

Oxford University Press

Journal

Cardiovascular Research

scimago Q1

wos Q1

SJR

3.947

CiteScore

21.3

Impact factor

13.3

ISSN

00086363 (Print)

17553245 (Electronic)