Viral infiltration of pancreatic islets in patients with COVID-19.

Thomas Dienemann, Stefan R Bornstein, Barbara Ludwig, Michele Solimena, Dirk Lindemann, Gustavo Baretton, Raul R Gainetdinov, Vsevolod A Zinserling, Natalia Y Semenova, Roman N Rodionov, Katja Evert, Charlotte Steenblock, Jessica Pablik, Annette Schürmann, Andreas Linkermann, Anne von Mässenhausen, Natalia Jarzebska, Undine Schubert, Janine Schmid, Marko Barovic, Ilona Berger, Stefanie Richter

Journal: Nature communications 2021;12(1):3534

PMID: 34112801

Free Full Text on Nature Publishing Group View on PubMed

Abstract

Metabolic diseases are associated with an increased risk of severe COVID-19 and conversely, new-onset hyperglycemia and complications of preexisting diabetes have been observed in COVID-19 patients. Here, we performed a comprehensive analysis of pancreatic autopsy tissue from COVID-19 patients using immunofluorescence, immunohistochemistry, RNA scope and electron microscopy and detected SARS-CoV-2 viral infiltration of beta-cells in all patients. Using SARS-CoV-2 pseudoviruses, we confirmed that isolated human islet cells are permissive to infection. In eleven COVID-19 patients, we examined the expression of ACE2, TMPRSS and other receptors and factors, such as DPP4, HMBG1 and NRP1, that might facilitate virus entry. Whereas 70% of the COVID-19 patients expressed ACE2 in the vasculature, only 30% displayed ACE2-expression in beta-cells. Even in the absence of manifest new-onset diabetes, necroptotic cell death, immune cell infiltration and SARS-CoV-2 viral infection of pancreatic beta-cells may contribute to varying degrees of metabolic dysregulation in patients with COVID-19.

Address: Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Institute of Virology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; CRTD/DFG-Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany.; Paul Langerhans Institute Dresden (PLID) of the Helmholtz Center Munich at the University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; German Center for Diabetes Research (DZD e. V.), Neuherberg, Germany.; University Centre for Vascular Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Biotechnology Center, Technische Universität Dresden, Dresden, Germany.; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Potsdam, Germany.; Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.; Department of Pathology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Department of Surgery, University of Regensburg, Regensburg, Germany.; Institute of Pathology, University of Regensburg, Regensburg, Germany.; S. P. Botkin Clinical Infectious Diseases Hospital, St. Petersburg, Russia.; V. A. Almasov Scientific Research Center, St. Petersburg, Russia.; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.; St. Petersburg State University Hospital, St. Petersburg State University, St. Petersburg, Russia.; Department of Endocrinology and Diabetology, University Hospital Zurich, Zurich, Switzerland.; Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. [email protected].; Department of Diabetes, School of Life Course Science and Medicine, King's College London, London, UK. [email protected].

DOI: 10.1038/s41467-021-23886-3

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MeSH Terms: Adult, Aged, Angiotensin-Converting Enzyme 2, Autopsy, COVID-19, Diabetes Complications, Diabetes Mellitus, Dipeptidyl Peptidase 4, Female, HMGN Proteins, Humans, Insulin-Secreting Cells, Male, Middle Aged, Neuropilin-1, Organ Specificity, Receptors, Coronavirus, SARS-CoV-2, Serine Endopeptidases