SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment

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-CoV2 infects human pancreatic beta cells in patients who succumbed to COVID-19 and selectively infects human islet beta cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces b 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.

Automated summary

There is evidence suggesting a complex relationship between COVID-19 and diabetes, with SARS-CoV-2 being able to directly induce beta cell killing and this effect being rescued by NRP1 inhibition.