@article{253c46f8693546d5bc687e49b3356d1f,
title = "Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19",
abstract = "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.",
keywords = "ACE2, CD34, COVID-19, SARS-CoV-2, TMPRSS2, insulin, islet, pancreas, type 1 diabetes, type 2 diabetes",
author = "Irina Kusmartseva and Wenting Wu and Farooq Syed and {Van Der Heide}, Verena and Marda Jorgensen and Paul Joseph and Xiaohan Tang and Eduardo Candelario-Jalil and Changjun Yang and Harry Nick and Harbert, {Jack L.} and Posgai, {Amanda L.} and Paulsen, {John David} and Richard Lloyd and Sirlene Cechin and Alberto Pugliese and Martha Campbell-Thompson and {Vander Heide}, {Richard S.} and Carmella Evans-Molina and Dirk Homann and Atkinson, {Mark A.}",
note = "Funding Information: We thank the families of the organ donors and autopsy subjects for the gift of tissues. We also thank Jill K. Gregory, CMI (Icahn School of Medicine at Mount Sinai, New York, NY) for preparing the graphical abstract. These efforts were supported by NIH P01 AI042288 and UC4 DK108132 (M.A.A.); JDRF (M.A.A.); NIH R01 DK122160 (M.C.-T.); NIH R01 AI134971 and P30 DK020541 (D.H.); JDRF 3-PDF-2018-575-A-N (V.V.D.H.); R01 DK093954 , R21 DK119800-01A1 , UC4 DK104166 , and U01 DK127786 (C.E.-M.); VA Merit Award I01BX001733 (C.E.-M.); Imaging Core of NIH/ NIDDK P30 DK097512 (C.E.-M.); gifts from the Sigma Beta Sorority , the Ball Brothers Foundation , and the George and Frances Ball Foundation (C.E.-M.); 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 ). The authors also wish to acknowledge the Islet and Physiology Core of the Indiana Diabetes Research Center ( P30DK097512 ). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Funding Information: We thank the families of the organ donors and autopsy subjects for the gift of tissues. We also thank Jill K. Gregory, CMI (Icahn School of Medicine at Mount Sinai, New York, NY) for preparing the graphical abstract. These efforts were supported by NIH P01 AI042288 and UC4 DK108132 (M.A.A.); JDRF (M.A.A.); NIH R01 DK122160 (M.C.-T.); NIH R01 AI134971 and P30 DK020541 (D.H.); JDRF 3-PDF-2018-575-A-N (V.V.D.H.); R01 DK093954, R21 DK119800-01A1, UC4 DK104166, and U01 DK127786 (C.E.-M.); VA Merit Award I01BX001733 (C.E.-M.); Imaging Core of NIH/NIDDK P30 DK097512 (C.E.-M.); gifts from the Sigma Beta Sorority, the Ball Brothers Foundation, and the George and Frances Ball Foundation (C.E.-M.); 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). The authors also wish to acknowledge the Islet and Physiology Core of the Indiana Diabetes Research Center (P30DK097512). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. I.K. researched data, generated figures, and wrote the manuscript; W.W. F.S. V.V.D.H. M.J. P.J. X.T. E.C.-J. and C.Y. researched data and reviewed and edited the manuscript; H.N. generated Figure 2A, contributed to discussion, and reviewed and edited the manuscript; J.L.H. and J.D.P. reviewed pathology and reviewed and edited the manuscript; A.L.P. contributed to discussion and wrote the manuscript; R.L. S.C. and A.P. contributed to discussion and reviewed and edited the manuscript; R.S.V.H. procured COVID-19 autopsy tissues, reviewed pathology, and reviewed and edited the manuscript; M.C.-T. reviewed pathology and wrote the manuscript; and C.E.-M. D.H. and M.A.A. conceived of the study and wrote the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = dec,
day = "1",
doi = "10.1016/j.cmet.2020.11.005",
language = "English",
volume = "32",
pages = "1041--1051.e6",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "6",
}