Cardiomyocytes Infected by SARS-CoV-2 Recruit Cardiotoxic Macrophages [scRNA-seq dataset]
Heart injury has been reported in up to 20% of COVID-19 patients, yet the cause of myocardial histopathology is unknown. We examined heart tissue from autopsies of healthy and COVID-19 patients using RNA-seq and identified a strikingly increased CCL2 expression and macrophage population in COVID-19 heart sample. Transwell assays using hESC-derived cardiomyocytes (CMs) and macrophages revealed that SARS-CoV-2 infected CMs secrete CCL2, which recruits macrophages, and this was validated using adult human CMs. Macrophages recruited by CCL2 from infected CMs secrete IL-6 and TNF-a, which causes increased ROS and cell apoptosis of CMs. Finally, a high content chemical screen using FDA-approved drugs identified ranolozine and tofacitinib, which rescue SARS-CoV-2 infected CMs from macrophages-induced cardiotoxicity. Overall design: scRNA-seq of three conditions: hESC-derived cardiomyocytes hESC-derived cardiomyocytes+SARS-CoV-2 Pseudo-entry virus hESC-derived cardiomyocytes+macrophages+SARS-CoV-2 Pseudo-entry virus