Type I IFNs Decrease SARS-CoV-2 Replication in Human Cardiomyocytes and Increase Cytokine Production in Macrophages.
Verónica Durán, Eirini Nikolouli, Shambhabi Chatterjee, Bibiana Costa, Andreas Pavlou, Annett Ziegler, Jennifer Becker, Kira Baumann, Matthias Bruhn, Kathrin Haake, Anna Rafiei Hashtchin, Ingrid Gensch, Andrea Korte, Yvonne Lisa Behrens, Shen-Ying Zhang
Abstract
Open AccessThe cellular basis of COVID-19 severity in patients with deficiencies in type I IFN immunity remains unclear. In this study, we differentiated cardiomyocytes and macrophages from IFNAR1 competent (IFNAR1comp) and deficient (IFNAR1def) induced pluripotent stem cells (iPSCs), and analyzed virus replication and cytokine production after exposure to SARS-CoV-2. Cardiomyocytes expressed the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and showed abundant SARS-CoV-2 replication, which was higher in IFNAR1def than IFNAR1comp cells. Treatment with exogenous IFNα mitigated infection in IFNAR1comp, but not in IFNAR1def cardiomyocytes. In contrast, macrophages did not express ACE2 and did not support SARS-CoV-2 replication, but produced pro-inflammatory cytokines upon virus exposure, which was impaired in IFNAR1def macrophages. In conclusion, type I IFNs decrease SARS-CoV-2 replication in human iPSC-derived cardiomyocytes, while they increase cytokine responses of macrophages.