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

Arun Sharma1,2, Gustavo Garcia3,4, Yizhou Wang5

  • 1Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Cell Reports. Medicine
|August 25, 2020
PubMed

Insights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human heart cells, causing damage and apoptosis. This study establishes a model for investigating cardiac complications of coronavirus disease 2019 (COVID-19).

Area of Science:

  • Cardiology
  • Virology
  • Stem Cell Biology

Background:

  • Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, presents with respiratory symptoms but also cardiac complications like viral myocarditis.
  • The direct impact of SARS-CoV-2 on human cardiomyocytes remains unclear, hindering understanding of COVID-19's cardiac effects.

Purpose of the Study:

  • To investigate the mechanisms of SARS-CoV-2 infection in human cardiomyocytes using a human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model.
  • To elucidate the cellular and molecular responses of hiPSC-CMs to SARS-CoV-2 infection.

Main Methods:

  • Utilized hiPSC-CMs as an in vitro model for SARS-CoV-2 infection.
  • Employed microscopy to visualize viral entry and cytopathic effects.
  • Conducted RNA sequencing to analyze gene expression changes in infected hiPSC-CMs.

Main Results:

  • Demonstrated that SARS-CoV-2 can infect hiPSC-CMs via the ACE2 receptor.
  • Observed viral replication, apoptosis, and cessation of beating in infected hiPSC-CMs within 72 hours.
  • Revealed SARS-CoV-2 infection activates innate immune pathways, antiviral responses, and inhibits metabolic pathways, including suppressing ACE2 expression.

Conclusions:

  • SARS-CoV-2 directly infects human cardiomyocytes in vitro, leading to cellular damage and functional impairment.
  • The hiPSC-CM model provides a platform for studying COVID-19's cardiac mechanisms.
  • This model can be utilized for screening potential cardiac-specific antiviral therapies for COVID-19.

Keywords:
COVID-19SARS-CoV-2cardiologycardiomyocytescardiovascular biologycoronavirusheartinduced pluripotent stem cellsstem cellviral myocarditis

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