TY - JOUR
T1 - SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas
AU - Müller, Janis A.
AU - Groß, Rüdiger
AU - Conzelmann, Carina
AU - Krüger, Jana
AU - Merle, Uta
AU - Steinhart, Johannes
AU - Weil, Tatjana
AU - Koepke, Lennart
AU - Bozzo, Caterina Prelli
AU - Read, Clarissa
AU - Fois, Giorgio
AU - Eiseler, Tim
AU - Gehrmann, Julia
AU - van Vuuren, Joanne
AU - Wessbecher, Isabel M.
AU - Frick, Manfred
AU - Costa, Ivan G.
AU - Breunig, Markus
AU - Grüner, Beate
AU - Peters, Lynn
AU - Schuster, Michael
AU - Liebau, Stefan
AU - Seufferlein, Thomas
AU - Stenger, Steffen
AU - Stenzinger, Albrecht
AU - MacDonald, Patrick E.
AU - Kirchhoff, Frank
AU - Sparrer, Konstantin M.J.
AU - Walther, Paul
AU - Lickert, Heiko
AU - Barth, Thomas F.E.
AU - Wagner, Martin
AU - Münch, Jan
AU - Heller, Sandra
AU - Kleger, Alexander
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85100397450&partnerID=8YFLogxK
U2 - 10.1038/s42255-021-00347-1
DO - 10.1038/s42255-021-00347-1
M3 - Article
C2 - 33536639
AN - SCOPUS:85100397450
SN - 2522-5812
VL - 3
SP - 149
EP - 165
JO - Nature Metabolism
JF - Nature Metabolism
IS - 2
ER -