ORIGINAL RESEARCH published: 11 May 2022 doi: 10.3389/fmed.2022.875430 Frontiers in Medicine | www.frontiersin.org 1 May 2022 | Volume 9 | Article 875430 Edited by: Roger Nlandu Ngatu, Kagawa University, Japan Reviewed by: Olivier Mukuku, Institut Supérieur des Techniques Médicales de Lubumbashi, Democratic Republic of Congo Jens Jordan, German Aerospace Center (DLR), Germany Quanman Li, Zhengzhou University, China *Correspondence: Norbert Stefan norbert.stefan@med.uni-tuebingen.de † These authors have contributed equally to this work Specialty section: This article was submitted to Infectious Diseases - Surveillance, Prevention and Treatment, a section of the journal Frontiers in Medicine Received: 14 February 2022 Accepted: 08 April 2022 Published: 11 May 2022 Citation: Stefan N, Sippel K, Heni M, Fritsche A, Wagner R, Jakob CEM, Preißl H, von Werder A, Khodamoradi Y, Borgmann S, Rüthrich MM, Hanses F, Haselberger M, Piepel C, Hower M, vom Dahl J, Wille K, Römmele C, Vehreschild J, Stecher M, Solimena M, Roden M, Schürmann A, Gallwitz B, Hrabe de Angelis M, Ludwig DS, Schulze MB, Jensen BEO and Birkenfeld AL (2022) Obesity and Impaired Metabolic Health Increase Risk of COVID-19-Related Mortality in Young and Middle-Aged Adults to the Level Observed in Older People: The LEOSS Registry. Front. Med. 9:875430. doi: 10.3389/fmed.2022.875430 Obesity and Impaired Metabolic Health Increase Risk of COVID-19-Related Mortality in Young and Middle-Aged Adults to the Level Observed in Older People: The LEOSS Registry Norbert Stefan 1,2,3 * † , Katrin Sippel 1,2,3† , Martin Heni 1,2,3 , Andreas Fritsche 1,2,3 , Robert Wagner 1,2,3 , Carolin E. M. Jakob 4,5 , Hubert Preißl 1,3 , Alexander von Werder 5,6 , Yascha Khodamoradi 7 , Stefan Borgmann 8 , Maria Madeleine Rüthrich 9 , Frank Hanses 10 , Martina Haselberger 11 , Christiane Piepel 12 , Martin Hower 13 , Jürgen vom Dahl 14 , Kai Wille 15 , Christoph Römmele 16 , Janne Vehreschild 3,4,17 , Melanie Stecher 4,5 , Michele Solimena 3,18 , Michael Roden 3,19,20 , Annette Schürmann 3,21 , Baptist Gallwitz 2 , Martin Hrabe de Angelis 3,22,23 , David S. Ludwig 24,25,26 , Matthias B. Schulze 3,27 , Bjoern Erik Ole Jensen 28† and Andreas L. Birkenfeld 1,2,3† on behalf of the LEOSS Study Group 1 Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich, Tübingen, Germany, 2 Department of Internal Medicine IV, University Hospital of Tübingen, Tübingen, Germany, 3 German Center for Diabetes Research (DZD), Munich, Germany, 4 Department of Internal Medicine I, Faculty of Medicine, University Hospital Cologne, Cologne, University of Cologne, Cologne, Germany, 5 German Center for Infection Research (DZIF), Partner-Site Bonn-Cologne, Cologne, Germany, 6 Department of Internal Medicine II, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich, Munich, Germany, 7 Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany, 8 Department of Infectious Diseases and Infection Control, Ingolstadt Hospital, Ingolstadt, Germany, 9 Department of Internal Medicine II, University Hospital Jena, Jena, Germany, 10 Emergency Department, University Hospital Regensburg, Regensburg, Germany, 11 Department of Internal Medicine I, Passau Hospital, Passau, Germany, 12 Department of Internal Medicine I, Hospital Bremen-Center, Bremen, Germany, 13 Department for Pneumology, Infectiology, Internal Medicine and Intensive Care, gGmbH, Dortmund, Germany, 14 Division of Cardiology, Hospital Maria Hilf Mönchengladbach, Mönchengladbach, Germany, 15 University Clinic for Hematology, Oncology, Hemostaseology and Palliative Care, University of Bochum, Minden, Germany, 16 Internal Medicine III - Gastroenterology and Infectious Diseases, University Hospital of Augsburg, Augsburg, Germany, 17 Department of Internal Medicine, Hematology and Oncology, University Hospital Cologne, Goethe University Frankfurt, Frankfurt am Main, Germany, 18 Helmholtz Center Munich, Faculty of Medicine, Paul Langerhans Institute Dresden, University Hospital, Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, 19 Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich-Heine University, Düsseldorf, Germany, 20 Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich- Heine University, Düsseldorf, Germany, 21 Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany, 22 Institute of Experimental Genetics, Helmholtz Zentrum München, Oberschleißheim, Germany, 23 TUM School of Life Sciences (SoLS), Chair of Experimental Genetics, Technische Universität München, Freising, Germany, 24 New Balance Foundation Obesity Prevention Center, Boston Children’s Hospital, Boston, MA, United States, 25 Department of Pediatrics, Harvard Medical School, Boston, MA, United States, 26 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States, 27 Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany, 28 Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany Advanced age, followed by male sex, by far poses the greatest risk for severe COVID- 19. An unresolved question is the extent to which modifiable comorbidities increase the risk of COVID-19-related mortality among younger patients, in whom COVID-19-related hospitalization strongly increased in 2021. A total of 3,163 patients with SARS-COV-2