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

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

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.