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      COVID-19 and metabolic disease: mechanisms and clinical management

      review-article
      , PhD a , , Prof, MD a , c , d , , Prof, MD a , b , c , d , e , , Prof, MD a , , Prof, MD f , , PhD g , h , , Prof, DSc g , h , , Prof, DSc i , , Prof, MD j , , Prof, MD d , k , l , , MD a , , PhD a , , Prof, MD m , , FRCP n , , Prof, MD a , n , o , p , q , , Prof, MD r , s , , Prof, FRCP t , , Prof, MD u , , Prof, MD v , w , , Prof, MD x , y , , Prof, MD z , , Prof, FRCP aa , , Prof, MD ab , , Prof, MD ac , ad , , Prof, MD ae , , FWACP af , , MD ag , , Prof, FRCP ah , , Prof, FRCP ai , , PhD n , , Prof, MD e , , Prof, MD e , , Prof, MD aj , , Prof, MD n , ak , , Prof, MD n , al , am , , Prof, MD a , c , d , e , n , *
      The Lancet. Diabetes & Endocrinology
      Elsevier Ltd.

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          Abstract

          Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders. In this Review, we provide an update on the mechanisms of how metabolic and endocrine disorders might predispose patients to develop severe COVID-19. Additionally, we update the practical recommendations and management of patients with COVID-19 and post-pandemic. Furthermore, we summarise new treatment options for patients with both COVID-19 and diabetes, and highlight current challenges in clinical management.

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          Most cited references157

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          SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

          Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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            Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

            Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)
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              Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

              Summary The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.
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                Author and article information

                Journal
                Lancet Diabetes Endocrinol
                Lancet Diabetes Endocrinol
                The Lancet. Diabetes & Endocrinology
                Elsevier Ltd.
                2213-8587
                2213-8595
                4 October 2021
                4 October 2021
                Affiliations
                [a ]Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
                [b ]DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany
                [c ]Paul Langerhans Institute Dresden, Helmholtz Center Munich, University Hospital Carl Gustav Carus, Dresden, Germany
                [d ]German Center for Diabetes Research, Neuherberg, Germany
                [e ]Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich, Zurich, Switzerland
                [f ]Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia
                [g ]Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russia
                [h ]Institute for Regenerative Medicine, Medical Research and Education Centre, Lomonosov Moscow State University, Moscow, Russia
                [i ]Department of General Physiology, St Petersburg State University, St Petersburg, Russia
                [j ]Paris Lodron University Salzburg, Salzburg, Austria
                [k ]Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, Germany
                [l ]School of Life Sciences, Technische Universität München, Freising, Germany
                [m ]Diabetes Research Centre, University of Leicester, Leicester, UK
                [n ]Department of Diabetes, School of Life Course Science and Medicine, Kings College London, London, UK
                [o ]Department of Diabetology, Endocrinology and Nephrology, University Hospital Tübingen, Tübingen, Germany
                [p ]Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany
                [q ]Deutsches Zentrum für Diabetesforschung, Neuherberg, Germany
                [r ]Department of Endocrinology, Tan Tock Seng Hospital, Singapore
                [s ]Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
                [t ]Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
                [u ]Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA
                [v ]Amsterdam UMC, Internal Medicine, University of Amsterdam, Amsterdam, Netherlands
                [w ]Profil Institute for Metabolic Research, Neuss, Germany
                [x ]Department of Endocrinology, Diabetes, Nutrition, Montpellier University Hospital, Montpellier, France
                [y ]Institute of Functional Genomics, University of Montpellier, INSERM, CNRS, Montpellier, France
                [z ]Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
                [aa ]Imperial College London, London, UK
                [ab ]Obesity and Comorbidities Research Center, Universidade de Campinas, Campinas, Brazil
                [ac ]Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity, Hong Kong Special Administrative Region, China
                [ad ]Li Ka Shing Institute of Health Science, Chinese University of Hong Kong and Prince of Wales Hospital, Hong Kong Special Administrative Region, China
                [ae ]Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé, Yaounde, Cameroon
                [af ]Endocrine, Diabetes and Metabolic Unit, Department of Internal Medicine, Nile University of Nigeria–Asokoro Hospital, Abuja, Nigeria
                [ag ]India Diabetes Research Foundation, Dr A Ramachandran's Diabetes Hospitals, Chennai, India
                [ah ]Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi, Pakistan
                [ai ]Dubai Hospital, Dubai Health Authority and Gulf Medical University, Dubai, United Arab Emirates
                [aj ]German Diabetes Foundation, Düsseldorf, Germany
                [ak ]Bariatric and Metabolic Surgery, King's College Hospital, London, UK
                [al ]Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
                [am ]Università Cattolica del Sacro Cuore, Rome, Italy
                Author notes
                [* ]Correspondence to: Prof Stefan R Bornstein, Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany
                Article
                S2213-8587(21)00244-8
                10.1016/S2213-8587(21)00244-8
                8489878
                34619105
                180f7708-07fa-45b8-b736-7b8641214801
                © 2021 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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