02019nas a2200337   4500000000100000000000100001008004100002260001500043653001300058653001500071653001500086653001900101653002700120653001600147653001000163653003500173653001400208653002200222100001600244700001900260700001600279700002300295700001900318700003300337700002200370245007800392300001100470490000600481520118000487022001401667       2020                            d  c2020-07-2110aCOVID-1910aSARS-CoV-210acardiology10acardiomyocytes10acardiovascular biology10acoronavirus10aHeart10ainduced pluripotent stem cells10aStem cell10aviral myocarditis1 aArun Sharma1 aGustavo Garcia1 aYizhou Wang1 aJasmine T. Plummer1 aKouki Morizono1 aVaithilingaraja Arumugaswami1 aClive N. Svendsen00aHuman iPSC-Derived Cardiomyocytes Are Susceptible to SARS-CoV-2 Infection  a1000520 v13 aCoronavirus 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.  a2666-3791