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

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

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.