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.
Highlights
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome–cornavirus-2 (SARS-CoV-2), affects multiple tissues, including the pancreas [1]
angiotensin-converting enzyme 2 (ACE2) expression was dramatically decreased in small ducts of male and female SARS-CoV-2–infected nonhuman primates (NHPs) compared with noninfected controls (Figure 1, I and J)
We observed colocalization for SARS-CoV-2-NP with CD31+ endothelial cells in all 5 male and female subjects who had died from COVID-19, including one normoglycemic individual (COVID19-4), which we did not observe in pancreata from noninfected controls (Figure 5, D and E)
Summary
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome–cornavirus-2 (SARS-CoV-2), affects multiple tissues, including the pancreas [1]. Evidence suggests that COVID-19 is associated with new onset of ketosis-prone forms of diabetes or the insulinopenic decompensation of preexisting diabetes [2,3,4]. These observations raise the prospect of a diabetogenic effect of SARS-CoV-2, beyond the known stress response associated with acute illness. Multiple studies report the expression of ACE2 and TMPRSS2 in pancreatic exocrine ductal cells [8, 9, 12, 13]. We used publicly available single-cell RNA sequencing (scRNA-seq) data sets, pancreatic sections from male and female controls, SARS-CoV-2–infected nonhuman primates (NHPs), and patients who had died from COVID-19, to assess the expression of ACE2 and TMPRSS2 and localize SARS-CoV-2 infection across pancreatic cells and examine the effect of SARS-CoV-2 infection on pancreatic histopathology
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