Year: 2020
Type: article
Study design: Observational Study
Abstract: Objectives To investigate whether there is a causal effect of cardiometabolic traits on risk of sepsis and severe covid-19. Design Mendelian randomisation analysis. Setting UK Biobank and HUNT study population-based cohorts for risk of sepsis, and genome-wide association study summary data for risk of severe covid-19 with respiratory failure. Participants 12,455 sepsis cases (519,885 controls) and 1,610 severe covid-19 with respiratory failure cases (2,205 controls). Exposure Genetic variants that proxy body mass index (BMI), lipid traits, systolic blood pressure, lifetime smoking score, and type 2 diabetes liability - derived from studies considering between 188,577 to 898,130 participants. Main outcome measures Risk of sepsis and severe covid-19 with respiratory failure. Results Higher genetically proxied BMI and lifetime smoking score were associated with increased risk of sepsis in both UK Biobank (BMI: odds ratio 1.38 per standard deviation increase, 95% confidence interval [CI] 1.27 to 1.51; smoking: odds ratio 2.81 per standard deviation increase, 95% CI 2.09-3.79) and HUNT (BMI: 1.41, 95% CI 1.18 to 1.69; smoking: 1.93, 95% CI 1.02-3.64). Higher genetically proxied BMI and lifetime smoking score were also associated with increased risk of severe covid-19, although with wider confidence intervals (BMI: 1.75, 95% CI 1.20 to 2.57; smoking: 3.94, 95% CI 1.13 to 13.75). There was limited evidence to support associations of genetically proxied lipid traits, systolic blood pressure or type 2 diabetes liability with risk of sepsis or severe covid-19. Similar findings were generally obtained when using Mendelian randomization methods that are more robust to the inclusion of pleiotropic variants, although the precision of estimates was reduced. Conclusions Our findings support a causal effect of elevated BMI and smoking on risk of sepsis and severe covid-19. Clinical and public health interventions targeting obesity and smoking are likely to reduce sepsis and covid-19 related morbidity, along with the plethora of other health-related outcomes that these traits adversely affect. Summary boxes What is already known on this topic Sepsis and severe covid-19 are major contributors to global morbidity and mortality. Cardiometabolic risk factors have been associated with risk of sepsis and severe covid-19, but it is unclear if they are having causal effects. What this study adds Using Mendelian randomization analyses, this study provides evidence to support that higher body mass index and lifetime smoking score both increase risk of sepsis and severe covid-19 with respiratory failure. Clinical and public health interventions targeting obesity and smoking are likely to reduce sepsis and covid-19 related morbidity, along with the plethora of other health-related outcomes that these traits adversely affect.
Source: Circulation
Authors: Mark J Ponsford, Apostolos Gkatzionis, Venexia M Walker, Andrew J Grant, Robyn E Wootton, Luke S P Moore, Segun Fatumo, Amy M Mason, Verena Zuber, Cristen Willer, Humaira Rasheed, Ben Brumpton, Kristian Hveem, Jan Kristian Damås, Neil Davies, Bjørn Olav Åsvold, Erik Solligård, Simon Jones, Stephen Burgess, Tormod Rogne, Dipender Gill
Institutions: University Hospital of Wales, Tenovus Cancer Care, Cardiff University, University of Cambridge, MRC Biostatistics Unit, Medical Research Council, University of Bristol, MRC Integrative Epidemiology Unit, University of Pennsylvania, National Health Service, Imperial College Healthcare NHS Trust, Chelsea and Westminster Hospital NHS Foundation Trust, National Institute for Health and Care Research, Imperial College London, London School of Hygiene & Tropical Medicine, NIHR Cambridge Biomedical Research Centre, University of Michigan, Michigan Medicine, Norwegian University of Science and Technology, St Olav's University Hospital, University of London, St George's, University of London, St George’s University Hospitals NHS Foundation Trust, St Mary's Hospital
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Norges Teknisk-Naturvitenskapelige Universitet, Wellcome Trust, National Institute for Health Research Health Protection Research Unit, National Institute for Health and Care Research, British Heart Foundation, Department of Health and Social Care, Royal Society, Kidney Research UK, University of Cambridge, Imperial College London, University of Bristol, Public Health England, Cambridge University Hospitals, Novo Nordisk, Helse Midt-Norge, Norges Forskningsråd, Versus Arthritis, LEO Pharma, National Institutes of Health, Fakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige Universitet, Medical Research Council, NIHR Imperial Biomedical Research Centre, NIHR Cambridge Biomedical Research Centre, Faculty of Medicine and Health, University of Sydney, Norwegian Institute of Public Health
Awards: Genetics and causality: towards more accessible and more reliable Mendelian randomization investigations, Research Excellence (round 3), G149876332, G1502031688, G1643655829, G1653514516, G2291477964, G235045266, G2538597952, G2673957436, G301055538, G3240403866, The Imperial Immunity, Inflammation, Infection and Informatics (4i) Clinician Scientist Programme, G3385530689, Neurodevelopmental disorders: what happens when children grow up and why?, The Imperial Immunity, Inflammation, Infection and Informatics (4i) Clinician Scientist Programme, G3814879049, G5001017760, G571894948, G6228397153, Mendelian randomization to hypothesis-free causal inference, G6911925389, G7227888905, G7369268829, Genetics and causality: towards more accessible and more reliable Mendelian randomization investigations, G780909024, G7964453685, G7990456425, G8201869620, G8502142660, G8518790725
OpenAlex ID: W3085879234