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

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.
Graphical Abstract
Highlights • ACE2 mRNA and protein are expressed in human pancreatic ducts and microvasculature • ACE2 mRNA was rarely detected and at low levels in human pancreatic endocrine cells • Pancreatic ACE2 protein expression changes across the lifespan and correlates with BMI • SARS-CoV-2 NP was detected in ducts, but not endocrine cells, of COVID-19 pancreata
Kusmartseva et al. demonstrate preferential ACE2 expression in pancreatic microvascular and ductal structures, suggesting these constitute a more likely target than islet endocrine cells in SARS-CoV-2 infection. This notion was supported by detection of SARS-CoV-2 nucleocapsid protein in ductal epithelium, but not endocrine cells, of pancreata from individuals with COVID-19.