Abstract P2195: SARS-CoV-2 Variants Divergently Infect And Damage Cardiomyocytes

Abstract

SARS-CoV-2 variants are known to exhibit different tropism and pathogenicity in respiratory cells, but their effect on cardiomyocytes (CMs) is unclear. Cardiac infection and damage induced by SARS-CoV-2 variants were examined using Golden Syrian hamsters and human induced pluripotent stem cell-derived (hiPSC-) CMs. Omicron BA.2 efficiently infected CMs in vitr o and in vivo , induced the most severe phenotype, and exhibited transcriptomic changes indicative of a more pro-inflammatory phenotype and increased cardiac dysfunction, compared to other variants. Increased infectivity of Omicron BA.2 is attributed to its ability to infect independently of TMPRSS2, which is absent in CMs. Our pilot study of patients infected with Omicron BA.2 in Hong Kong revealed significantly higher plasma troponin levels, consistent with severe myocardial injury. Here we reveal previously unknown differences in how different SARS-CoV-2 variants damage CMs, and that Omicron BA.2, which is generally considered mild, can induce severe CM damage in vitro , in vivo and in a subset of patients.