SARS-CoV-2 infection induces beta cell transdifferentiation

Cell Metab. 2021 Aug 3;33(8):1577-1591.e7. doi: 10.1016/j.cmet.2021.05.015. Epub 2021 May 19.


Recent clinical data have suggested a correlation between coronavirus disease 2019 (COVID-19) and diabetes. Here, we describe the detection of SARS-CoV-2 viral antigen in pancreatic beta cells in autopsy samples from individuals with COVID-19. Single-cell RNA sequencing and immunostaining from ex vivo infections confirmed that multiple types of pancreatic islet cells were susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS-CoV-2 infection, beta cells showed a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin1, respectively, suggesting cellular transdifferentiation. Trajectory analysis indicated that SARS-CoV-2 induced eIF2-pathway-mediated beta cell transdifferentiation, a phenotype that could be reversed with trans-integrated stress response inhibitor (trans-ISRIB). Altogether, this study demonstrates an example of SARS-CoV-2 infection causing cell fate change, which provides further insight into the pathomechanisms of COVID-19.

Keywords: COVID-19; EgIF2; PRSS1; diabetes; human islets; insulin; trypsin 1.

Publication types

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

MeSH terms

  • Acetamides / pharmacology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • COVID-19 / mortality
  • COVID-19 / virology*
  • Cell Transdifferentiation* / drug effects
  • Chlorocebus aethiops
  • Cyclohexylamines / pharmacology
  • Cytokines / metabolism
  • Eukaryotic Initiation Factor-2 / metabolism
  • Female
  • Glucagon
  • Host-Pathogen Interactions
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / virology*
  • Male
  • Middle Aged
  • Phenotype
  • SARS-CoV-2 / pathogenicity*
  • Signal Transduction
  • Tissue Culture Techniques
  • Trypsin / metabolism
  • Vero Cells
  • Young Adult


  • 2-(4-chlorophenoxy)-N-(4-(2-(4-chlorophenoxy)acetamido)cyclohexyl)acetamide
  • Acetamides
  • Cyclohexylamines
  • Cytokines
  • Eukaryotic Initiation Factor-2
  • Insulin
  • Glucagon
  • PRSS1 protein, human
  • Trypsin