Causal Associations Between Basal Metabolic Rate and COVID-19

Many coronavirus disease 2019 (COVID-19) risk factors, including obesity and diabetes, are associated with an abnormal basal metabolic rate (BMR). We aimed to evaluate whether BMR could impact the susceptibility to or severity of COVID-19. We performed genetic correlation and Mendelian randomization (MR) analyses to assess genetic correlations and potential causal associations between BMR (n = 448,348) and three COVID-19 outcomes: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, and critical COVID-19 (n = 1,086,211-2,597,856). A multivariable MR (MVMR) analysis was used to estimate the direct effect of BMR on COVID-19 independent of BMI and type 2 diabetes. BMR has positive genetic correlations with the COVID-19 outcomes (genetic correlations 0.213-0.266). The MR analyses indicated that genetic liability to BMR confers causal effects on SARS-CoV-2 infection (odds ratio 1.14, 95% CI 1.09-1.20, P = 1.65E-07), hospitalized COVID-19 (1.31, 1.18-1.46, P = 8.69E-07), and critical COVID-19 (1.04, 1.19-1.64, P = 4.89E-05). Sensitivity analysis of MR showed no evidence of directional pleiotropy or heterogeneity, indicating the robustness of its results. The MVMR analysis showed that the causal effects of BMR on hospitalized COVID-19 and critical COVID- 19 were dependent on BMI and type 2 diabetes but that BMR may affect the SARS-CoV- 2 infection risk independently of BMI and type 2 diabetes (odds ratio 1.09, 95% CI 1.03-1.15, P = 4.82E-03). Our study indicates that a higher BMR contributes to amplifying the susceptibility to and severity of COVID-19. The causal effect of BMR on the severity of COVID-19 may be mediated by BMI and type 2 diabetes.