Cardiometabolic traits, sepsis and severe covid-19 with respiratory failure: a Mendelian randomization investigation
Ponsford J Mark,
Venexia M Walker,
Robyn E Wootton,
Luke S P Moore,
Ben M Brumpton,
Jan Kristian Damas,
Neil M Davies,
Bjørn Olav Åsvold,
P. Simon Jones,
Posted 20 Jun 2020
medRxiv DOI: 10.1101/2020.06.18.20134676
Posted 20 Jun 2020
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.
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