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; Katrin Sippel; Martin Heni; Andreas Fritsche; Robert Wagner; Carolin E M Jakob; Hubert Preißl; Alexander von Werder; Yascha Khodamoradi; Stefan Borgmann; Maria Madeleine Rüthrich; Frank Hanses; Martina Haselberger; Christiane Piepel; Martin Hower; Jürgen Vom Dahl; Kai Wille; Christoph Römmele; Janne Vehreschild; Melanie Stecher; Michele Solimena; Michael Roden; Annette Schürmann; Baptist Gallwitz; Martin Hrabe de Angelis; David S Ludwig; Matthias B Schulze; Bjoern Erik Ole Jensen; Andreas L Birkenfeld

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

Front Med (Lausanne). 2022 May 11:9:875430. doi: 10.3389/fmed.2022.875430. eCollection 2022.

Authors

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 Khodamoradi⁷, Stefan Borgmann⁸, Maria Madeleine Rüthrich⁹, Frank Hanses¹⁰, Martina Haselberger¹¹, Christiane Piepel¹², Martin Hower¹³, Jürgen Vom Dahl¹⁴, Kai Wille¹⁵, Christoph Römmele¹⁶, Janne Vehreschild^{3

4

17}, Melanie Stecher^{4

5}, Michele Solimena^{3

18}, Michael Roden^{3

19

20}, Annette Schürmann^{3

21}, Baptist Gallwitz², Martin Hrabe de Angelis^{3

22

23}, David S Ludwig^{24

25

26}, Matthias B Schulze^{3

27}, Bjoern Erik Ole Jensen²⁸, Andreas L Birkenfeld^{1

2

3}

Affiliations

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.

Abstract

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 diagnosis in the Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort were studied. LEOSS is a European non-interventional multi-center cohort study established in March 2020 to investigate the epidemiology and clinical course of SARS-CoV-2 infection. Data from hospitalized patients and those who received ambulatory care, with a positive SARS-CoV-2 test, were included in the study. An additive effect of obesity, diabetes and hypertension on the risk of mortality was observed, which was particularly strong in young and middle-aged patients. Compared to young and middle-aged (18-55 years) patients without obesity, diabetes and hypertension (non-obese and metabolically healthy; n = 593), young and middle-aged adult patients with all three risk parameters (obese and metabolically unhealthy; n = 31) had a similar adjusted increased risk of mortality [OR 7.42 (95% CI 1.55-27.3)] as older (56-75 years) non-obese and metabolically healthy patients [n = 339; OR 8.21 (95% CI 4.10-18.3)]. Furthermore, increased CRP levels explained part of the elevated risk of COVID-19-related mortality with age, specifically in the absence of obesity and impaired metabolic health. In conclusion, the modifiable risk factors obesity, diabetes and hypertension increase the risk of COVID-19-related mortality in young and middle-aged patients to the level of risk observed in advanced age.

Keywords: COVID-19; diabetes; hypertension; impaired metabolic health; mortality; obesity.

Copyright © 2022 Stefan, Sippel, Heni, Fritsche, Wagner, Jakob, Preißl, von Werder, Khodamoradi, Borgmann, Rüthrich, Hanses, Haselberger, Piepel, Hower, vom Dahl, Wille, Römmele, Vehreschild, Stecher, Solimena, Roden, Schürmann, Gallwitz, Hrabe de Angelis, Ludwig, Schulze, Jensen and Birkenfeld.