tetano
Editor, Senior Moderator
Nat Metab
. 2021 Feb 3.
doi: 10.1038/s42255-021-00347-1. Online ahead of print.
SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas
Janis A M?ller[SUP] #[/SUP][SUP] 1 [/SUP], R?diger Gro?[SUP] #[/SUP][SUP] 1 [/SUP], Carina Conzelmann[SUP] #[/SUP][SUP] 1 [/SUP], Jana Kr?ger[SUP] #[/SUP][SUP] 2 [/SUP], Uta Merle[SUP] 3 [/SUP], Johannes Steinhart[SUP] 4 [/SUP], Tatjana Weil[SUP] 1 [/SUP], Lennart Koepke[SUP] 1 [/SUP], Caterina Prelli Bozzo[SUP] 1 [/SUP], Clarissa Read[SUP] 5 6 [/SUP], Giorgio Fois[SUP] 7 [/SUP], Tim Eiseler[SUP] 2 [/SUP], Julia Gehrmann[SUP] 8 [/SUP], Joanne van Vuuren[SUP] 9 10 11 12 [/SUP], Isabel M Wessbecher[SUP] 13 [/SUP], Manfred Frick[SUP] 7 [/SUP], Ivan G Costa[SUP] 8 [/SUP], Markus Breunig[SUP] 2 [/SUP], Beate Gr?ner[SUP] 14 [/SUP], Lynn Peters[SUP] 14 [/SUP], Michael Schuster[SUP] 15 [/SUP], Stefan Liebau[SUP] 16 [/SUP], Thomas Seufferlein[SUP] 2 [/SUP], Steffen Stenger[SUP] 17 [/SUP], Albrecht Stenzinger[SUP] 18 [/SUP], Patrick E MacDonald[SUP] 19 [/SUP], Frank Kirchhoff[SUP] 1 [/SUP], Konstantin M J Sparrer[SUP] 1 [/SUP], Paul Walther[SUP] 5 [/SUP], Heiko Lickert[SUP] 9 10 11 12 [/SUP], Thomas F E Barth[SUP] 4 [/SUP], Martin Wagner[SUP] 20 [/SUP], Jan M?nch[SUP] 21 [/SUP], Sandra Heller[SUP] 22 [/SUP], Alexander Kleger[SUP] 23 [/SUP]
Affiliations
Abstract
Infection-related diabetes can arise as a result of virus-associated β-cell destruction. Clinical data suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), impairs glucose homoeostasis, but experimental evidence that SARS-CoV-2 can infect pancreatic tissue has been lacking. In the present study, we show that SARS-CoV-2 infects cells of the human exocrine and endocrine pancreas ex vivo and in vivo. We demonstrate that human β-cells express viral entry proteins, and SARS-CoV-2 infects and replicates in cultured human islets. Infection is associated with morphological, transcriptional and functional changes, including reduced numbers of insulin-secretory granules in β-cells and impaired glucose-stimulated insulin secretion. In COVID-19 full-body postmortem examinations, we detected SARS-CoV-2 nucleocapsid protein in pancreatic exocrine cells, and in cells that stain positive for the β-cell marker NKX6.1 and are in close proximity to the islets of Langerhans in all four patients investigated. Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that β-cell infection could contribute to the metabolic dysregulation observed in patients with COVID-19.
. 2021 Feb 3.
doi: 10.1038/s42255-021-00347-1. Online ahead of print.
SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas
Janis A M?ller[SUP] #[/SUP][SUP] 1 [/SUP], R?diger Gro?[SUP] #[/SUP][SUP] 1 [/SUP], Carina Conzelmann[SUP] #[/SUP][SUP] 1 [/SUP], Jana Kr?ger[SUP] #[/SUP][SUP] 2 [/SUP], Uta Merle[SUP] 3 [/SUP], Johannes Steinhart[SUP] 4 [/SUP], Tatjana Weil[SUP] 1 [/SUP], Lennart Koepke[SUP] 1 [/SUP], Caterina Prelli Bozzo[SUP] 1 [/SUP], Clarissa Read[SUP] 5 6 [/SUP], Giorgio Fois[SUP] 7 [/SUP], Tim Eiseler[SUP] 2 [/SUP], Julia Gehrmann[SUP] 8 [/SUP], Joanne van Vuuren[SUP] 9 10 11 12 [/SUP], Isabel M Wessbecher[SUP] 13 [/SUP], Manfred Frick[SUP] 7 [/SUP], Ivan G Costa[SUP] 8 [/SUP], Markus Breunig[SUP] 2 [/SUP], Beate Gr?ner[SUP] 14 [/SUP], Lynn Peters[SUP] 14 [/SUP], Michael Schuster[SUP] 15 [/SUP], Stefan Liebau[SUP] 16 [/SUP], Thomas Seufferlein[SUP] 2 [/SUP], Steffen Stenger[SUP] 17 [/SUP], Albrecht Stenzinger[SUP] 18 [/SUP], Patrick E MacDonald[SUP] 19 [/SUP], Frank Kirchhoff[SUP] 1 [/SUP], Konstantin M J Sparrer[SUP] 1 [/SUP], Paul Walther[SUP] 5 [/SUP], Heiko Lickert[SUP] 9 10 11 12 [/SUP], Thomas F E Barth[SUP] 4 [/SUP], Martin Wagner[SUP] 20 [/SUP], Jan M?nch[SUP] 21 [/SUP], Sandra Heller[SUP] 22 [/SUP], Alexander Kleger[SUP] 23 [/SUP]
Affiliations
- PMID: 33536639
- DOI: 10.1038/s42255-021-00347-1
Abstract
Infection-related diabetes can arise as a result of virus-associated β-cell destruction. Clinical data suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), impairs glucose homoeostasis, but experimental evidence that SARS-CoV-2 can infect pancreatic tissue has been lacking. In the present study, we show that SARS-CoV-2 infects cells of the human exocrine and endocrine pancreas ex vivo and in vivo. We demonstrate that human β-cells express viral entry proteins, and SARS-CoV-2 infects and replicates in cultured human islets. Infection is associated with morphological, transcriptional and functional changes, including reduced numbers of insulin-secretory granules in β-cells and impaired glucose-stimulated insulin secretion. In COVID-19 full-body postmortem examinations, we detected SARS-CoV-2 nucleocapsid protein in pancreatic exocrine cells, and in cells that stain positive for the β-cell marker NKX6.1 and are in close proximity to the islets of Langerhans in all four patients investigated. Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that β-cell infection could contribute to the metabolic dysregulation observed in patients with COVID-19.