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

JCI Insight. 2021 Aug 23;6(16):e151551. doi: 10.1172/jci.insight.151551.

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.

Keywords: COVID-19; Diabetes; Endothelial cells; Thrombosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / analysis
  • Animals
  • COVID-19 / complications*
  • Chlorocebus aethiops
  • Diabetes Mellitus / etiology*
  • Female
  • Fibrosis
  • Humans
  • Macaca mulatta
  • Male
  • Pancreas / virology*
  • SARS-CoV-2 / isolation & purification*
  • Serine Endopeptidases / analysis
  • Thrombosis / etiology*

Substances

  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human