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SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes
Mirza Muhammad Fahd Qadir, Manika Bhondeley, Wandy Beatty, Dina D. Gaupp, Lara A. Doyle-Meyers, Tracy Fischer, Ishitri Bandyopadhyay, Robert V. Blair, Rudolf Bohm, Jay Rappaport, Eric Lazartigues, Richard S. Vander Heide, Jay K. Kolls, Xuebin Qin, Franck Mauvais-Jarvis
Mirza Muhammad Fahd Qadir, Manika Bhondeley, Wandy Beatty, Dina D. Gaupp, Lara A. Doyle-Meyers, Tracy Fischer, Ishitri Bandyopadhyay, Robert V. Blair, Rudolf Bohm, Jay Rappaport, Eric Lazartigues, Richard S. Vander Heide, Jay K. Kolls, Xuebin Qin, Franck Mauvais-Jarvis
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Research Article COVID-19

SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes

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Abstract

Evidence suggests an association between severe acute respiratory syndrome–cornavirus-2 (SARS-CoV-2) infection and the occurrence of new-onset diabetes. We examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), the cell entry factors for SARS-CoV-2, using publicly available single-cell RNA sequencing data sets, and pancreatic tissue from control male and female nonhuman primates (NHPs) and humans. We also examined SARS-CoV-2 immunolocalization in pancreatic cells of SARS-CoV-2–infected NHPs and patients who had died from coronavirus disease 2019 (COVID-19). We report expression of ACE2 in pancreatic islet, ductal, and endothelial cells in NHPs and humans. In pancreata from SARS-CoV-2–infected NHPs and COVID-19 patients, SARS-CoV-2 infected ductal, endothelial, and islet cells. These pancreata also exhibited generalized fibrosis associated with multiple vascular thrombi. Two out of 8 NHPs developed new-onset diabetes following SARS-CoV-2 infection. Two out of 5 COVID-19 patients exhibited new-onset diabetes at admission. These results suggest that SARS-CoV-2 infection of the pancreas may promote acute and especially chronic pancreatic dysfunction that could potentially lead to new-onset diabetes.

Authors

Mirza Muhammad Fahd Qadir, Manika Bhondeley, Wandy Beatty, Dina D. Gaupp, Lara A. Doyle-Meyers, Tracy Fischer, Ishitri Bandyopadhyay, Robert V. Blair, Rudolf Bohm, Jay Rappaport, Eric Lazartigues, Richard S. Vander Heide, Jay K. Kolls, Xuebin Qin, Franck Mauvais-Jarvis

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Figure 2

ACE2 protein expression in human pancreata.

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ACE2 protein expression in human pancreata.
(A) Representative immunoflu...
(A) Representative immunofluorescence (IF) images of pancreatic islets from 2 human female and (B) male donors, showing ACE2 expression in α and β cells. Insets show colocalization of insulin (INS) with ACE2 (green arrows) and glucagon (GCG) with ACE2 (yellow arrows). (C) Quantification of β cells and (D) α cells expressing ACE2. (E) Representative IF images of pancreatic ducts from 2 human female and (F) male donors showing ACE2 expression in ductal cells (CK19). Insets show colocalization of CK19 with ACE2 (yellow arrows). (G) Quantification of pancreatic ductal cells expressing ACE2. Experiments represent n = 3 biological replicates. Bar graphs show the mean ± SD. Scale bars: 25 μm. Differences were assessed using an unpaired t test (C, D, and G).

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