hPSC-derived cells to model Macrophage-mediated inflammation in COVID19 HeartsÂ

We systematically compared autopsy samples from non-COVID-19 donors and COVID-19 patients using RNA-seq and immunohistochemistry. We observed strikingly increased expression levels of CCL2 as well as macrophage infiltration in heart tissues of COVID-19 patients. We generated an immuno-cardiac co-culture platform containing human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) and macrophages. We found that macrophages induce increased reactive oxygen species (ROS) and apoptosis in CMs by secreting IL-6 and TNF-α after SARS-CoV-2 exposure. Using this immuno-cardiac co-culture platform, we performed a high content screen and identified ranolazine and tofacitinib as compounds that protect CMs from macrophage-induced cardiotoxicity. We established an immuno-host co-culture system to study macrophage-induced host cell damage following SARS-CoV-2 infection, and identified FDA-approved drug candidates that alleviate the macrophage-mediated hyper-inflammation and cellular injury.