SARS-CoV-2 infects multiple organs. Severe presentations of COVID-19 not only affect the respiratory tract, the digestive tract and the cardiovascular and nervous system, but also glucose metabolism. Researchers at Ulm University Medical Center have now discovered that SARS-CoV-2 infects the insulin-producing beta cells of the pancreas. This may explain the occurrence of diabetes-like symptoms in COVID-19 patients and the impairment of glucose metabolism in diabetic patients with COVID-19. The findings were published in the journal Nature Metabolism.
In severe courses of COVID-19, symptoms typically found in type 1 diabetes mellitus are more frequently observed. The symptoms range from hyperglycaemia – high blood glucose levels – to increased acidity of the blood, called ketoacidosis. A recently published study by Ulm University investigates how these typical diabetes symptoms could occur in COVID-19 patients. The scientists exposed pancreatic tissue to SARS-CoV-2 and discovered that the islets of Langerhans can be infected with the coronavirus. These small, spherically arranged structures are home to insulin-producing beta cells. “These beta cells express certain protein molecules, viral entry proteins, without which SARS-CoV-2 cannot infect the cells. The human proteins TMPRSS2 and ACE2 are, so to speak, the lock that coronaviruses open with their key spike protein to enter the cells. The viral components are then replicated, releasing numerous new infectious viral particles,” explains Professor Jan Münch, head of the study at the Institute of Molecular Virology. With their experiments, the scientists were also able to show that infected insulin-producing tissue undergoes decisive changes in form and function.
Another revealing finding in autopsies performed on deceased COVID-19 patients revealed SARS-CoV-2 infections of the pancreas. Even after viral proteins were no longer observed in the lungs, they could still be detected in the pancreas. The relevance of this finding for the clinical progression of the disease is still unclear. “What is known so far is that inflammation of the pancreas occurs in active COVID-19 cases,” explains Heisenberg Professor Alexander Kleger, one of the heads of the study. Another unresolved question is whether the acute impairment of insulin production in COVID-19 patients can lead to diabetes in the long term.
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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 Peters, Michael 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 and Alexander Kleger , in: Nature Metabolism (https://www.nature.com/articles/s42255-021-00347-1) doi 10.1038/s42255-021-00347-1
Cover Photo by Elvira Eberhardt/Ulm University: The team in Ulm includes researchers from the Department of Internal Medicine 1 and the Institute of Molecular Virology at Ulm University Medical Center. Pictured (from left): Rüdiger Groß, Carina Conzelmann, Professor Martin Wagner, Jana Krüger, Professor Alexander Kleger, Dr Sandra Heller, Professor Jan Münch and Dr Janis Müller.