Abstract
BackgroundCross-sectional observational studies have reported obesity and cardiometabolic co-morbidities as important predictors of coronavirus disease 2019 (COVID-19) hospitalization. The causal impact of these risk factors is unknown at present.MethodsWe conducted multivariable logistic regression to evaluate the observational associations between obesity traits (body mass index [BMI], waist circumference [WC]), quantitative cardiometabolic parameters (systolic blood pressure [SBP], serum glucose, serum glycated hemoglobin [HbA1c], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and SARS-CoV-2 positivity in the UK Biobank cohort. One-sample MR was performed by using the genetic risk scores of obesity and cardiometabolic traits constructed from independent datasets and the genotype and phenotype data from the UK Biobank. Two-sample MR was performed using the summary statistics from COVID-19 host genetics initiative. Cox proportional hazard models were fitted to assess the risk conferred by different genetic quintiles of causative exposure traits.ResultsThe study comprised 1,211 European participants who were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 387,079 participants who were either untested or tested negative between 16 March 2020 to 31 May 2020. Observationally, higher BMI, WC, HbA1c and lower HDL-cholesterol were associated with higher odds of COVID-19 infection. One-sample MR analyses found causal associations between higher genetically determined BMI and LDL cholesterol and increased risk of COVID-19 (odds ratio [OR]: 1.15, confidence interval [CI]: 1.05–1.26 and OR: 1.58, CI: 1.21–2.06, per 1 standard deviation increment in BMI and LDL cholesterol respectively). Two-sample MR produced concordant results. Cox models indicated that individuals in the higher genetic risk score quintiles of BMI and LDL were more predisposed to COVID-19 (hazard ratio [HR]: 1.24, CI: 1.03–1.49 and HR: 1.37, CI: 1.14–1.65, for the top vs the bottom quintile for BMI and LDL cholesterol, respectively).ConclusionWe identified causal associations between BMI, LDL cholesterol and susceptibility to COVID-19. In particular, individuals in higher genetic risk categories were predisposed to SARS-CoV-2 infection. These findings support the integration of BMI into the risk assessment of COVID-19 and allude to a potential role of lipid modification in the prevention and treatment.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the pathogen of coronavirus disease 2019 (COVID-19), has inflicted a once-in-a-century pandemic
Multiple observational studies have reported that certain patient characteristics and comorbid conditions are associated with COVID19 susceptibility and worse outcomes (Collaborative et al, 2020; Docherty et al, 2020; Li et al, 2020)
We examined the causal relationship between obesity traits, quantitative cardiometabolic biomarkers and COVID-19 susceptibility using Mendelian randomization
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the pathogen of coronavirus disease 2019 (COVID-19), has inflicted a once-in-a-century pandemic. Elevated body mass index (BMI), a widely used surrogate of obesity, has emerged as an important risk factor for COVID-19 hospital admission, disease severity and in-hospital mortality (Kalligeros et al, 2020; Lighter et al, 2020; Palaiodimos et al, 2020; Simonnet et al, 2020). Other important constituents of metabolic syndrome namely diabetes and hypertension have been reported to be associated with at least twofold higher risk of severe or fatal COVID-19 (Kumar et al, 2020; Lippi et al, 2020). Given the observational nature of previous COVID-19 studies, the causal impact of obesity and cardiometabolic indices on COVID-19 susceptibility has not been ascertained. Cross-sectional observational studies have reported obesity and cardiometabolic co-morbidities as important predictors of coronavirus disease 2019 (COVID-19) hospitalization. The causal impact of these risk factors is unknown at present
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