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Emerging evidence points towards an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While pre-existing diabetes is associated with severe COVID-19, it is unclear if COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β-cells can be infected by SARS-CoV-2 and cause β-cell depletion. We found that the SARS-CoV-2 receptor, ACE2 and related entry factors (TMPRSS2, NRP1, TRFC) are expressed in β-cells, with selectively high expression of NRP1. We discovered 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 demonstrated 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 that observed in Type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β-cell killing.
Published in Cell Metabolism (May 18, 2021):
