ACE2 and SARS-CoV-2 Expression in the Normal and COVID-19 Pancreas (preprint)

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 the key molecule for SARS-CoV-2 infection of cells, angiotensin-converting enzyme-2 (ACE2). Specifically, we analyzed five public scRNAseq 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) patients. These in silico and ex vivo analyses demonstrated pancreatic expression of ACE2 is prominent in pancreatic ductal epithelium and the microvasculature, with rare endocrine cell expression of this molecule. Pancreata from COVID-19 patients demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression primarily limited to ducts. SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, appears an unlikely central pathogenic feature of COVID-19 as it relates to diabetes.Funding: These efforts were supported by NIH P01 AI42288 and UC4 DK108132 (MAA), JDRF (MAA), NIH R01 DK122160 (MCT), NIH R01 AI134971 (DH), NIH P30 DK020541 (D.H.), JDRF 3-PDF-2018-575-A-N (VvdH), R01 DK093954 (CEM); VA Merit Award I01BX001733 (CEM), Imaging Core of NIH/NIDDK P30 DK097512 (CEM), gifts from the Sigma Beta Sorority, the Ball Brothers Foundation, and the George and Frances Ball Foundation (CEM), the Network for Pancreatic Organ donors with Diabetes (nPOD; RRID:SCR_014641) (5-SRA-2018-557-Q-R) and The Leona M. & Harry B. Helmsley Charitable Trust (2018PG-T1D053).Conflict of Interest: The authors declare no relevant conflicts of interest exist.Ethical Approval: Transplant-quality pancreas, duodenum, and kidney were recovered by JDRF nPOD (www.jdrfnpod.com) from 36 COVID-19 negative organ donors without diabetes (Table S2) according to established protocols and procedures (Campbell-Thompson et al., 2012), as approved by the University of Florida Institutional Review Board (201400486), the United Network for Organ Sharing (UNOS), and according to federal guidelines with informed consent obtained from each donor’s legal representative.

ACE2 and SARS-CoV-2 Expression in the Normal and COVID-19 Pancreas (preprint)

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 the key molecule for SARS-CoV-2 infection of cells, angiotensin-converting enzyme-2 (ACE2). Specifically, we analyzed five public scRNAseq 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) patients. These in silico and ex vivo analyses demonstrated pancreatic expression of ACE2 is prominent in pancreatic ductal epithelium and the microvasculature, with rare endocrine cell expression of this molecule. Pancreata from COVID-19 patients demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression primarily limited to ducts. SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, appears an unlikely central pathogenic feature of COVID-19 as it relates to diabetes.