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

Arun Sharma; Gustavo Garcia Jr; Yizhou Wang; Jasmine T Plummer; Kouki Morizono; Vaithilingaraja Arumugaswami; Clive N Svendsen

doi:10.1016/j.xcrm.2020.100052

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

Cell Rep Med. 2020 Jul 21;1(4):100052. doi: 10.1016/j.xcrm.2020.100052. Epub 2020 Jun 29.

Authors

Arun Sharma^{1

2}, Gustavo Garcia Jr^{3

4}, Yizhou Wang⁵, Jasmine T Plummer⁵, Kouki Morizono^{6

7}, Vaithilingaraja Arumugaswami^{3

4}, Clive N Svendsen¹

Affiliations

¹ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
² Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
³ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Genomics Core, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁶ Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁷ UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract

Coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is defined by respiratory symptoms, but cardiac complications including viral myocarditis are also prevalent. Although 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. Here, we utilize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and RNA sequencing demonstrate that SARS-CoV-2 can enter hiPSC-CMs via ACE2. Viral replication and cytopathic effect induce hiPSC-CM apoptosis and cessation of beating after 72 h of infection. SARS-CoV-2 infection activates innate immune response and antiviral clearance gene pathways, while inhibiting metabolic pathways and suppressing ACE2 expression. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating infection mechanisms and potentially a cardiac-specific antiviral drug screening platform.

Keywords: COVID-19; SARS-CoV-2; cardiology; cardiomyocytes; cardiovascular biology; coronavirus; heart; induced pluripotent stem cells; stem cell; viral myocarditis.

Abstract

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