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

• Published in: Cell reports. Medicine Vol. 1; no. 4; p. 100052
• Main Authors: Sharma, Arun, Garcia, Gustavo, Wang, Yizhou, Plummer, Jasmine T., Morizono, Kouki, Arumugaswami, Vaithilingaraja, Svendsen, Clive N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.07.2020; Elsevier
• Subjects: Advanced Basic Science; cardiology; cardiomyocytes; cardiovascular biology; coronavirus; COVID-19; heart; induced pluripotent stem cells; SARS-CoV-2; stem cell; viral myocarditis; COVID-19; cardiomyocytes; SARS-CoV-2; cardiovascular biology; stem cell; coronavirus; induced pluripotent stem cells; viral myocarditis; heart; cardiology
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2020.100052

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. [Display omitted] Human iPSC-derived cardiomyocytes are susceptible to SARS-CoV-2 infectionACE2 antibody blunts SARS-CoV-2 infection in cardiomyocytesInfected human iPSC-derived cardiomyocytes activate viral clearance pathways Sharma et al. demonstrate that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are susceptible to SARS-CoV-2 infection. This establishes a platform for understanding the mechanisms of cardiac-specific infection by SARS-CoV-2 in vitro and could potentially be employed to develop antiviral compounds.