Physiology of cardiomyocyte injury in COVID-19

Siddiq, Mustafa M.; Chan, Angel T.; Miorin, Lisa; Yadaw, Arjun S.; Beaumont, Kristin G.; Kehrer, Thomas; White, Kris M.; Cupic, Anastasija; Tolentino, Rosa E.; Hu, Bin; Stern, Alan D.; Tavassoly, Iman; Hansen, Jens; Martinez, Pedro; Dubois, Nicole; Schaniel, Christoph; Iyengar-Kapuganti, Rupa; Kukar, Nina; Giustino, Gennaro; Sud, Karan; Nirenberg, Sharon; Kovatch, Patricia; Goldfarb, Joseph; Croft, Lori; McLaughlin, Maryann A.; Argulian, Edgar; Lerakis, Stamatios; Narula, Jagat; García -Sastre, Adolfo; Iyengar, Ravi

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System shows that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrate cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with SARS-CoV-2 in the presence of interleukins, with clinical findings, to investigate plausible mechanisms of cardiac disease in COVID-19 patients. We infected hiPSC-derived cardiomyocytes, from healthy human subjects, with SARS-CoV-2 in the absence and presence of interleukins. We find that interleukin treatment and infection results in disorganization of myofibrils, extracellular release of troponin-I, and reduced and erratic beating. Although interleukins do not increase the extent, they increase the severity of viral infection of cardiomyocytes resulting in cessation of beating. Clinical data from hospitalized patients from the Mount Sinai Health system show that a significant portion of COVID-19 patients without prior history of heart disease, have elevated troponin and interleukin levels. A substantial subset of these patients showed reduced left ventricular function by echocardiography. Our laboratory observations, combined with the clinical data, indicate that direct effects on cardiomyocytes by interleukins and SARS-CoV-2 infection can underlie the heart disease in COVID-19 patients.