Human cardiac organoids to model COVID‐19 cytokine storm induced cardiac injuries
Dimitrios C. Arhontoulis, Charles M. Kerr, Dylan Richards, Kelsey Tjen, Nathaniel Hyams, Jefferey A. Jones, Kristine Y. DeLeon‐Pennell, Donald R. Menick, Hanna Bräuninger, Diana Lindner, Dirk Westermann, Ying Mei
Abstract
Acute cardiac injuries occur in 20%-25% of hospitalized COVID-19 patients. Herein, we demonstrate that human cardiac organoids (hCOs) are a viable platform to model the cardiac injuries caused by COVID-19 hyperinflammation. As IL-1β is an upstream cytokine and a core COVID-19 signature cytokine, it was used to stimulate hCOs to induce the release of a milieu of proinflammatory cytokines that mirror the profile of COVID-19 cytokine storm. The IL-1β treated hCOs recapitulated transcriptomic, structural, and functional signatures of COVID-19 hearts. The comparison of IL-1β treated hCOs with cardiac tissue from COVID-19 autopsies illustrated the critical roles of hyper-inflammation in COVID-19 cardiac insults and indicated the cardioprotective effects of endothelium. The IL-1β treated hCOs thus provide a defined and robust model to assess the efficacy and potential side effects of immunomodulatory drugs, as well as the reversibility of COVID-19 cardiac injuries at baseline and simulated exercise conditions.