SARS-CoV-2 infects human pancreatic β-cells and elicits β-cell impairment. Wu et al.

Emerging evidence points towards an intricate relationship between the pandemic coronavirus disease 2019 (COVID-19) and diabetes. While pre-existing diabetes is associated with severe COVID-19, recent evidence suggests COVID-19 induces new-onset type 1 diabetes (T1D), convoluting diabetes as cause or consequence. To mechanistically link COVID-19 to T1D, we tested whether insulin-producing pancreatic β-cells can be infected by SARS-CoV-2 and cause β-cell depletion. We find the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, TRFC) are expressed in β-cells, with NRP1 selectively high. We discover that SARS-CoV-2 infects human pancreatic β-cells in patients who succumbed to COVID-19 and selectively infects human islet β-cells in vitro. We demonstrate SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces β-cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β-cell signaling, similar to T1D. Our study shows SARS-CoV-2 can directly induce β-cell killing, explaining T1D in COVID-19 patients.