Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic beta cells can be infected by SARS-CoV-2 and cause beta cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in beta cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic beta cells in patients who succumbed to COVID-19 and selectively infects human islet beta cells invitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces beta cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic beta cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce beta cell killing.
View details for DOI 10.1016/j.cmet.2021.05.013
View details for PubMedID 34081912