Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19

Kusmartseva, Irina; Wu, Wenting; Syed, Farooq; Van Der Heide, Verena; Jorgensen, Marda; Joseph, Paul; Tang, Xiaohan; Candelario-Jalil, Eduardo; Yang, Changjun; Nick, Harry; Harbert, Jack L.; Posgai, Amanda L.; Paulsen, John David; Lloyd, Richard; Cechin, Sirlene; Pugliese, Alberto; Campbell-Thompson, Martha; Vander Heide, Richard S.; Evans-Molina, Carmella; Homann, Dirk; Atkinson, Mark A.

Diabetes is associated with increased mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases. These in silico and ex vivo analyses demonstrated prominent expression of ACE2 in pancreatic ductal epithelium and microvasculature, but we found rare endocrine cell expression at the mRNA level. Pancreata from individuals with COVID-19 demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression that was primarily limited to ducts. These results suggest SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, is an unlikely central pathogenic feature of COVID-19-related diabetes.