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Human iPSC-Derived Cardiomyocytes are Susceptible to SARS-CoV-2 Infection

View ORCID ProfileArun Sharma, Gustavo Garcia Jr., View ORCID ProfileVaithilingaraja Arumugaswami, Clive N. Svendsen
doi: https://doi.org/10.1101/2020.04.21.051912
Arun Sharma
1Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
2Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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  • For correspondence: arun.sharma@cshs.org VArumugaswami@mednet.ucla.edu clive.svendsen@cshs.org
Gustavo Garcia Jr.
3Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
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Vaithilingaraja Arumugaswami
3Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
4Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA
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  • For correspondence: arun.sharma@cshs.org VArumugaswami@mednet.ucla.edu clive.svendsen@cshs.org
Clive N. Svendsen
1Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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  • For correspondence: arun.sharma@cshs.org VArumugaswami@mednet.ucla.edu clive.svendsen@cshs.org
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SUMMARY

Coronavirus disease 2019 (COVID-19) is a viral pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is predominantly defined by respiratory symptoms, but cardiac complications including arrhythmias, heart failure, and viral myocarditis are also prevalent. Although the systemic ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well-understood. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model system to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and immunofluorescence demonstrated that SARS-CoV-2 can enter and replicate within hiPSC-CMs, localizing at perinuclear locations within the cytoplasm. Viral cytopathic effect induced hiPSC-CM apoptosis and cessation of beating after 72 hours of infection. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating the mechanisms of infection and potentially a cardiac-specific antiviral drug screening platform.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵# Lead Contact: Clive N. Svendsen, PhD., Address: 127 S. San Vicente Blvd., Pavilion, Room 8405, Los Angeles, CA 90048, Phone: +1 310-248-8072, Email: clive.svendsen{at}cshs.org

  • Conflict of Interest Statement: The authors have declared that no conflict of interest exists.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 21, 2020.
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Human iPSC-Derived Cardiomyocytes are Susceptible to SARS-CoV-2 Infection
Arun Sharma, Gustavo Garcia Jr., Vaithilingaraja Arumugaswami, Clive N. Svendsen
bioRxiv 2020.04.21.051912; doi: https://doi.org/10.1101/2020.04.21.051912
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Human iPSC-Derived Cardiomyocytes are Susceptible to SARS-CoV-2 Infection
Arun Sharma, Gustavo Garcia Jr., Vaithilingaraja Arumugaswami, Clive N. Svendsen
bioRxiv 2020.04.21.051912; doi: https://doi.org/10.1101/2020.04.21.051912

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