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      Obesity & genetic predisposition with COVID-19

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          Abstract

          Objective

          We aimed to examine the associations of obesity-related traits (body mass index [BMI], central obesity) and their genetic predisposition with the risk of developing severe COVID-19 in a population-based data.

          Research Design and Methods.

          We analyzed data from 489,769 adults enrolled in the UK Biobank—a population-based cohort study. The exposures of interest are BMI categories and central obesity (e.g., larger waist circumference). Using genome-wide genotyping data, we also computed polygenic risk scores (PRSs) that represent an individual's overall genetic risk for each obesity trait. The outcome was severe COVID-19, defined by hospitalization for laboratory-confirmed COVID-19.

          Results

          Of 489,769 individuals, 33% were normal weight (BMI, 18.5–24.9 kg/m 2), 43% overweight (25.0–29.9 kg/m 2), and 24% obese (≥30.0 kg/m 2). The UK Biobank identified 641 patients with severe COVID-19. Compared to adults with normal weight, those with a higher BMI had a dose-response increases in the risk of severe COVID-19, with the following adjusted ORs: for 25.0–29.9 kg/m 2, 1.40 (95%CI 1.14–1.73; P = 0.002); for 30.0–34.9 kg/m 2, 1.73 (95%CI 1.36–2.20; P < 0.001); for 35.0–39.9 kg/m 2, 2.82 (95%CI 2.08–3.83; P < 0.001); and for ≥40.0 kg/m 2, 3.30 (95%CI 2.17–5.03; P < 0.001). Likewise, central obesity was associated with significantly higher risk of severe COVID-19 (P < 0.001). Furthermore, larger PRS for BMI was associated with higher risk of outcome (adjusted OR per BMI PRS Z-score 1.14, 95%CI 1.05–1.24; P = 0.004).

          Conclusions

          In this large population-based cohort, individuals with more-severe obesity, central obesity, or genetic predisposition for obesity are at higher risk of developing severe-COVID-19.

          Highlights

          • Individuals with more-severe obesity, central obesity are at higher risk of developing severe-COVID-19.

          • The genetic predisposition for obesity as measured by polygenic risk score is at higher risk of developing severe-COVID-19.

          • The stratified analysis by sex showed the BMI-severe COVID-19 associations were consistent across the strata, except women with class I obesity had a non-significant increase in the risk of severe COVID-19.

          • The stratified analysis by coexistent diabetes showed consistent results across the strata, while adults with both class III obesity and diabetes or adults with both a larger waist circumference and diabetes appeared to have a larger magnitude of association compared to those without diabetes.

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          Most cited references24

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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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            Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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              Is Open Access

              Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study

              Abstract Objective To describe outcomes of people admitted to hospital with coronavirus disease 2019 (covid-19) in the United States, and the clinical and laboratory characteristics associated with severity of illness. Design Prospective cohort study. Setting Single academic medical center in New York City and Long Island. Participants 5279 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection between 1 March 2020 and 8 April 2020. The final date of follow up was 5 May 2020. Main outcome measures Outcomes were admission to hospital, critical illness (intensive care, mechanical ventilation, discharge to hospice care, or death), and discharge to hospice care or death. Predictors included patient characteristics, medical history, vital signs, and laboratory results. Multivariable logistic regression was conducted to identify risk factors for adverse outcomes, and competing risk survival analysis for mortality. Results Of 11 544 people tested for SARS-Cov-2, 5566 (48.2%) were positive. After exclusions, 5279 were included. 2741 of these 5279 (51.9%) were admitted to hospital, of whom 1904 (69.5%) were discharged alive without hospice care and 665 (24.3%) were discharged to hospice care or died. Of 647 (23.6%) patients requiring mechanical ventilation, 391 (60.4%) died and 170 (26.2%) were extubated or discharged. The strongest risk for hospital admission was associated with age, with an odds ratio of >2 for all age groups older than 44 years and 37.9 (95% confidence interval 26.1 to 56.0) for ages 75 years and older. Other risks were heart failure (4.4, 2.6 to 8.0), male sex (2.8, 2.4 to 3.2), chronic kidney disease (2.6, 1.9 to 3.6), and any increase in body mass index (BMI) (eg, for BMI >40: 2.5, 1.8 to 3.4). The strongest risks for critical illness besides age were associated with heart failure (1.9, 1.4 to 2.5), BMI >40 (1.5, 1.0 to 2.2), and male sex (1.5, 1.3 to 1.8). Admission oxygen saturation of 1 (4.8, 2.1 to 10.9), C reactive protein level >200 (5.1, 2.8 to 9.2), and D-dimer level >2500 (3.9, 2.6 to 6.0) were, however, more strongly associated with critical illness than age or comorbidities. Risk of critical illness decreased significantly over the study period. Similar associations were found for mortality alone. Conclusions Age and comorbidities were found to be strong predictors of hospital admission and to a lesser extent of critical illness and mortality in people with covid-19; however, impairment of oxygen on admission and markers of inflammation were most strongly associated with critical illness and mortality. Outcomes seem to be improving over time, potentially suggesting improvements in care.
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                Author and article information

                Contributors
                Journal
                Metabolism
                Metab. Clin. Exp
                Metabolism
                Elsevier Inc.
                0026-0495
                1532-8600
                22 August 2020
                22 August 2020
                : 154345
                Affiliations
                [a ]Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
                [b ]Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
                [c ]Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
                [d ]College of Information Science and Technology, Dalian Maritime University, Dalian, Liaoning, China
                [e ]Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
                Author notes
                [* ]Corresponding author at: Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health. 655 Huntington Avenue, Building 2, Room 207, Boston, MA, USA, 02115. lliang@ 123456hsph.harvard.edu
                [1]

                These authors contributed equally to this work.

                Article
                S0026-0495(20)30209-2 154345
                10.1016/j.metabol.2020.154345
                7442576
                32835759
                91c65885-7d4a-4667-b6b3-3dd4fb073d4a
                © 2020 Elsevier Inc. 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.

                History
                : 30 July 2020
                : 13 August 2020
                : 14 August 2020
                Categories
                Article

                Molecular biology
                ards, acute respiratory distress syndrome,bmi, body mass index,covid-19, coronavirus disease 2019,prs, polygenic risk score,sars-cov-2, severe acute respiratory syndrome coronavirus 2,obesity,central obesity,body mass index,diabetes,gwas,polygenic risk score,sars-cov-2,covid-19,hospitalization,uk biobank

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