SARS-CoV-2 Infection Induces Beta Cell Transdifferentiation

Recent clinical data has suggested a correlation between Coronavirus disease 19 (COVID-19) and diabetes. Here, we describe the detection of SARS-CoV-2 viral antigen in pancreatic beta cells in autopsy samples from COVID-19 patients. Single cell RNA-seq (scRNA-seq) and immunostaining from ex vivo infections confirmed that multiple types of pancreatic islet cells are susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS-CoV-2 infection, beta cells show a decreased expression of insulin and the increased expression of alpha and acinar cell markers, including glucagon and PRSS1/trypsin1, respectively, suggesting cellular transdifferentiation. Trajectory analysis indicated that SARS-CoV-2 induced eIF2 pathway-mediated beta cell transdifferentiation, a phenotype that could be reversed with trans-integrated stress response inhibitor (trans-ISRIB). Altogether, this study demonstrates the first example of SARS-CoV-2 infection causing cell fate change, which provides a new contributing mechanism towards the pathogenesis of COVID-19 patients.