The association of obesity-related traits on COVID-19 severity and hospitalization is affected by socio-economic status: a multivariable Mendelian randomization study

BACKGROUND: Due to its large impact on human health, socio-economic status (SES) could at least partially influence the established association between obesity and coronavirus disease 2019 (COVID-19) severity. To estimate the independent effect of body size and SES on the clinical manifestations of COVID-19, we conducted a Mendelian randomization (MR) study. METHODS: Applying two-sample MR approaches, we evaluated the effects of body mass index (BMI, n = 322 154), waist circumference (WC, n = 234 069), hip circumference (n = 213 019) and waist–hip ratio (n = 210 088) with respect to three COVID-19 outcomes: severe respiratory COVID-19 (cases = 8779, controls = 1 000 875), hospitalized COVID-19 (cases = 17 992, controls = 1 810 493) and COVID-19 infection (cases = 87 870, controls = 2 210 804). Applying a multivariable MR (MVMR) approach, we estimated the effect of these anthropometric traits on COVID-19 outcomes accounting for the effect of SES assessed as household income (n = 286 301). RESULTS: BMI and WC were associated with severe respiratory COVID-19 [BMI: odds ratio (OR) = 1.51, CI = 1.24–1.84, P = 3.01e-05; WC: OR = 1.48, 95% CI = 1.15–1.91, P = 0.0019] and hospitalized COVID-19 (BMI: OR = 1.50, 95% CI = 1.32–1.72, P = 8.83e-10; WC: OR = 1.41, 95% CI = 1.20–1.67, P = 3.72e-05). Conversely, income was associated with lower odds of severe respiratory (OR = 0.70, 95% CI = 0.53–0.93, P = 0.015) and hospitalized COVID-19 (OR = 0.78, 95% CI = 0.66–0.92, P = 0.003). MVMR analyses showed that the effect of these obesity-related traits on increasing the odds of COVID-19 negative outcomes becomes null when accounting for income. Conversely, the association of income with lower odds of COVID-19 negative outcomes is not affected when including the anthropometric traits in the multivariable model. CONCLUSION: Our findings indicate that SES contributes to the effect of obesity-related traits on COVID-19 severity and hospitalization.