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

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

in 631/326/596/4130 / 631/443/319 / 692/4020/2741/416 / 692/699/255/2514 / 692/699/2743/137 / Aged / Aged, 80 and over / Angiotensin-Converting Enzyme 2 - biosynthesis / Angiotensin-Converting Enzyme 2 - genetics / Antibodies / Beta cells / Biomedical and Life Sciences / Cells / Cells, Cultured / Coronaviruses / COVID-19 / COVID-19 - physiopathology / Diabetes / Diabetes Mellitus / Female / Granule cells / Humans / Hyperglycemia / Infections / Insulin secretion / Islets of Langerhans / Islets of Langerhans - cytology / Islets of Langerhans - physiopathology / Islets of Langerhans - virology / Life Sciences / Male / Nkx6.1 protein / Nucleocapsids / Pancreas / Pancreas, Exocrine - cytology / Pancreas, Exocrine - physiopathology / Pancreas, Exocrine - virology / Pancreatic Diseases - etiology / Pancreatic Diseases - virology / Peptides / Proteins / SARS-CoV-2 - growth & development / Secretory vesicles / Serine Endopeptidases - biosynthesis / Serine Endopeptidases - genetics / Severe acute respiratory syndrome coronavirus 2 / Transcriptomics / Variance analysis / Virus Internalization / Virus Replication

2021

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

2021

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2021

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Journal Article

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

Read, Clarissa,

Sparrer, Konstantin M. J.,

Wessbecher, Isabel M.,

Fois, Giorgio,

Koepke, Lennart,

Frick, Manfred,

Müller, Janis A.,

Heller, Sandra,

MacDonald, Patrick E.,

Kirchhoff, Frank,

Krüger, Jana,

Grüner, Beate,

Conzelmann, Carina,

Schuster, Michael,

Peters, Lynn,

Stenzinger, Albrecht,

Groß, Rüdiger,

Seufferlein, Thomas,

Stenger, Steffen,

Eiseler, Tim,

Merle, Uta,

Steinhart, Johannes,

Barth, Thomas F. E.,

Kleger, Alexander,

Gehrmann, Julia,

Münch, Jan,

Wagner, Martin,

van Vuuren, Joanne,

Liebau, Stefan,

Costa, Ivan G.,

Lickert, Heiko,

Weil, Tatjana,

Breunig, Markus,

Bozzo, Caterina Prelli,

Walther, Paul

2021

Overview

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. SARS-CoV-2 is shown to infect and replicate in human pancreatic tissue, including in β-cells, which is associated with morphological, transcriptomic and functional changes.

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Publisher

Nature Publishing Group UK,Nature Publishing Group

Subject

/ Aged