SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas

Janis A. Müller, Rüdiger Groß, Carina Conzelmann, Jana Krüger, Uta Merle, Johannes Steinhart, Tatjana Weil, Lennart Koepke, Caterina Prelli Bozzo, Clarissa Read, Giorgio Fois, Tim Eiseler, Julia Gehrmann, Joanne van Vuuren, Isabel M. Wessbecher, Manfred Frick, Ivan G. Costa, Markus Breunig, Beate Grüner, Lynn PetersMichael Schuster, Stefan Liebau, Thomas Seufferlein, Steffen Stenger, Albrecht Stenzinger, Patrick E. MacDonald, Frank Kirchhoff, Konstantin M.J. Sparrer, Paul Walther, Heiko Lickert, Thomas F.E. Barth, Martin Wagner, Jan Münch, Sandra Heller, Alexander Kleger

Research output: Contribution to journalArticlepeer-review

395 Scopus citations

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.

Original languageEnglish
Pages (from-to)149-165
Number of pages17
JournalNature Metabolism
Volume3
Issue number2
DOIs
StatePublished - Feb 2021

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