Corpus overview


MeSH Disease

Human Phenotype


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    Cardiometabolic Risk Factors for COVID-19 Susceptibility and Severity: A Mendelian Randomization Analysis

    Authors: Aaron Leong; Joanne Cole; Laura N. Brenner; James B. Meigs; Jose C. Florez; Josep M. Mercader; Fernando Bozza; Carlo Palmieri; Daniel Munblit; Jan Cato Holter; Anders Benjamin Kildal; Clark D Russell; Antonia Ho; Lance Turtle; Thomas M Drake; Anna Beltrame; Katrina Hann; Ibrahim Richard Bangura; Rob Fowler; Sulaiman Lakoh; Colin Berry; David J Lowe; Joanne McPeake; Madiha Hashmi; Anne Margarita Dyrhol-Riise; Chloe Donohue; Daniel R Plotkin; Hayley Hardwick; Natalie Elkheir; Nazir Lone; Annemarie B Docherty; Ewen M Harrison; Kenneth J Baille; Gail Carson; Malcolm G Semple; Janet T Scott

    doi:10.1101/2020.08.26.20182709 Date: 2020-09-01 Source: medRxiv

    Importance: Early epidemiological studies report associations of diverse cardiometabolic conditions especially body mass index (BMI), with COVID-19 susceptibility and severity, but causality has not been established. Identifying causal risk factors is critical to inform preventive strategies aimed at modifying disease risk. Objective: We sought to evaluate the causal associations of cardiometabolic conditions with COVID-19 susceptibility and severity. Design: Two-sample Mendelian Randomization (MR) Study. Setting: Population-based cohorts that contributed to the genome-wide association study (GWAS) meta-analysis by the COVID-19 Host Genetics Initiative. Participants: Patients hospitalized with COVID-19 diagnosed by RNA PCR, serologic testing SERO, or clinician diagnosis. Population controls defined as anyone who was not a case in the cohorts. Exposures: Selected genetic variants associated with 17 cardiometabolic diseases MESHD, including diabetes MESHD, coronary artery disease MESHD, stroke HP stroke MESHD, chronic kidney disease HP chronic kidney disease MESHD, and BMI, at p<5 x 10-8 from published largescale GWAS. Main outcomes: We performed an inverse-variance weighted averages of variant-specific causal estimates for susceptibility, defined as people who tested positive for COVID-19 vs. population controls, and severity, defined as patients hospitalized with COVID-19 vs. population controls, and repeated the analysis for BMI using effect estimates from UKBB. To estimate direct and indirect causal effects of BMI through obesity HP obesity MESHD-related cardiometabolic diseases, we performed pairwise multivariable MR. We used p<0.05/17 exposure/2 outcomes=0.0015 to declare statistical significance. Results: Genetically increased BMI was causally associated with testing positive for COVID-19 [6,696 cases / 1,073,072 controls; p=6.7 x 10-4, odds ratio and 95% confidence interval 1.08 (1.03, 1.13) per kg/m2] and a higher risk of COVID-19 hospitalization [3,199 cases/897,488 controls; p=8.7 x 10-4, 1.12 (1.04, 1.21) per kg/m2]. In the multivariable MR, the direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes MESHD but persisted when conditioning on the effects on coronary artery disease MESHD, stroke HP stroke MESHD, chronic kidney disease HP chronic kidney disease MESHD, and c-reactive protein. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes. Conclusions and Relevance: Genetic evidence supports BMI as a causal risk factor for COVID-19 susceptibility and severity. This relationship may be mediated via type 2 diabetes MESHD. Obesity HP may have amplified the disease burden of the COVID-19 pandemic either single-handedly or through its metabolic consequences.

    A phenome-wide association study (PheWAS) of COVID-19 outcomes by race using the electronic health records data in Michigan Medicine

    Authors: Maxwell Salvatore; Tian Gu; Jasmine A. Mack; Swaraaj Prabhu Sankar; Snehal Patil; Thomas S. Valley; Karandeep Singh; Brahmajee K. Nallamothu; Sachin Kheterpal; Lynda Lisabeth; Lars G. Fritsche; Bhramar Mukherjee

    doi:10.1101/2020.06.29.20141564 Date: 2020-07-01 Source: medRxiv

    Blacks/African Americans are overrepresented in the number of hospitalizations and deaths from COVID-19 in the United States, which could be explained through differences in the prevalence SERO of existing comorbidities. We performed a disease-disease MESHD phenome-wide association study (PheWAS) using data representing 5,698 COVID-19 patients from a large academic medical center, stratified by race. We explore the association of 1,043 pre-occurring conditions with several COVID-19 outcomes: testing positive, hospitalization, ICU admission, and mortality. Obesity HP Obesity MESHD, iron deficiency anemia HP iron deficiency anemia MESHD and type II diabetes were associated with susceptibility in the full cohort, while ill-defined descriptions/complications of heart disease MESHD and stage III chronic kidney disease HP kidney disease MESHD were associated among non-Hispanic White (NHW) and non-Hispanic Black/African American (NHAA) patients, respectively. The top phenotype hits in the full, NHW, and NHAA cohorts for hospitalization were acute renal failure MESHD, hypertension HP hypertension MESHD, and insufficiency/arrest respiratory failure MESHD arrest respiratory HP failure, respectively. Suggestive relationships between respiratory issues and COVID-19-related ICU admission and mortality were observed, while circulatory system diseases showed stronger association in NHAA patients. We were able to replicate some known comorbidities related to COVID-19 outcomes while discovering potentially unknown associations, such as endocrine/metabolic conditions related to hospitalization and mental disorders MESHD related to mortality, for future validation. We provide interactive PheWAS visualization for broader exploration.

    A survival analysis of COVID-19 in the Mexican population

    Authors: Guillermo Salinas-Escudero; María Fernanda Carrillo-Vega; Víctor Granados-García; Silvia Martínez-Valverde; Filiberto Toledano-Toledano; Juan Garduño-Espinosa

    doi:10.21203/ Date: 2020-06-29 Source: ResearchSquare

    Background. At present, the Americas region contributes to the largest number of cases of COVID-19 worldwide. In this area, Mexico is in third place respecting deaths (20,781 total deaths), rate that may be explained by the high proportion of the population over 50 years and the rate of chronic diseases MESHD. The aim of the present work was estimate the risk factors associated with the death rate, considering the time between symptoms onset TRANS and the death occurrence, in the Mexican population. Methods. Information of all the confirmed cases TRANS for COVID-19 reported on the public dataset released by the Epidemiological Surveillance System for Viral Respiratory Diseases MESHD of the Mexican Ministry of Health was analyzed. Kapplan-Meier curves were plotted, and a Cox proportional hazard model was constructed. Results. The analysis included 16,752 registries of confirmed cases TRANS of COVID-19 with mean age TRANS 46.55±15.55 years; 58.02% (n=9719) men and 9.37% (n=1,569) died. Men (H.R. 1.21, p<0.01, 95% C.I. 1.09-1.35), older age TRANS (H.R. 8.24, p<0.01, 95% C.I. 4.22-16.10), CKD (H.R. 1.85, p<0.01, 95% C.I. 1.51-2.25), pneumonia HP pneumonia MESHD (H.R. 2.07, p<0.01, 95% C.I. 1.81-2.38), hospitalization and ICU admissions (H.R. 5.86, p<0.01, 95% C.I. 4.81-7.14, and H.R. 1.32, p<0.01, 95% C.I. 1.12-1.55, respectively), intubation (H.R. 2.93, p<0.01, 95% C.I. 2.50-3.45) and health care in public health services (more than twice the risk, p<0.01), were independent factors increasing the risk of death MESHD due to COVID-19. Conclusions. The risk of dying at any time during follow-up was especially higher in men, individuals at the older age groups TRANS, with chronic kidney disease HP chronic kidney disease MESHD and people hospitalized in the public health services.

    How many are at increased risk of severe COVID-19 disease? Rapid global, regional and national estimates for 2020

    Authors: Andrew Clark; Mark Jit; Charlotte Warren-Gash; Bruce Guthrie; Harry HX Wang; Stewart W Mercer; Colin Sanderson; Martin McKee; Christopher Troeger; Kanyin I Ong; Francesco Checchi; Pablo Perel; Sarah Joseph; Hamish P Gibbs; Amitava Banerjee; LSHTM CMMID COVID-19 working group; Rosalind M Eggo

    doi:10.1101/2020.04.18.20064774 Date: 2020-04-22 Source: medRxiv

    Background The risk of severe COVID-19 disease is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 illness, and how this varies between countries may inform the design of possible strategies to shield those at highest risk. Methods We estimated the number of individuals at increased risk of severe COVID-19 disease by age TRANS (5-year age groups TRANS), sex and country (n=188) based on prevalence SERO data from the Global Burden of Disease MESHD ( GBD MESHD) study for 2017 and United Nations population estimates for 2020. We also calculated the number of individuals without an underlying condition that could be considered at-risk because of their age TRANS, using thresholds from 50-70 years. The list of underlying conditions relevant to COVID-19 disease was determined by mapping conditions listed in GBD to the guidelines published by WHO and public health agencies in the UK and US. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. Results We estimate that 1.7 (1.0 - 2.4) billion individuals (22% [15-28%] of the global population) are at increased risk of severe COVID-19 disease. The share of the population at increased risk ranges from 16% in Africa to 31% in Europe. Chronic kidney disease HP Chronic kidney disease MESHD ( CKD MESHD), cardiovascular disease MESHD ( CVD MESHD), diabetes MESHD and chronic respiratory disease MESHD ( CRD MESHD) were the most prevalent conditions in males TRANS and females TRANS aged TRANS 50+ years. African countries with a high prevalence SERO of HIV MESHD/ AIDS MESHD and Island countries with a high prevalence SERO of diabetes MESHD, also had a high share of the population at increased risk. The prevalence SERO of multimorbidity (>1 underlying conditions) was three times higher in Europe than in Africa (10% vs 3%). Conclusion Based on current guidelines and prevalence SERO data from GBD, we estimate that one in five individuals worldwide has a condition that is on the list of those at increased risk of severe COVID-19 disease. However, for many of these individuals the underlying condition will be undiagnosed or not severe enough to be captured in health systems, and in some cases the increase in risk may be quite modest. There is an urgent need for robust analyses of the risks associated with different underlying conditions so that countries can identify the highest risk groups and develop targeted shielding policies to mitigate the effects of the COVID-19 pandemic.

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MeSH Disease
Human Phenotype

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