Obesity has an impact on COVID-19 susceptibility and severity: a two-sample Mendelian randomization study

Freuer, D.; Linseisen, J.; Meisinger, C.

Background Recent observational studies suggested obesity to be a possible risk factor for COVID-19 disease in the wake of the coronavirus (SARS-CoV-2) infection. However, the causality as well as the role of body fat distribution in this context still unclear. Thus, using a two-sample Mendelian randomization (MR) approach, we investigated the causal impact of obesity on the susceptibility and severity of COVID-19. Methods Obesity was quantified by body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). Summary statistics of genome-wide association studies (GWASs) for these anthropometric measures were drawn from the GIANT consortium (Locke et al. (n=322154); Shungin et al. (n=232101)) and for the COVID-19 susceptibility (n=1079768) as well as hospitalization (n = 900687) from the COVID-19 Host Genetics Initiative. Causal estimates were calculated using Single Nucleotide Polymorphisms (SNPs) and sensitivity analyses were done applying several robust MR techniques. Results Genetically predicted BMI was significantly associated (per one SD) with both, COVID-19 susceptibility (OR=1.41; 95% CI: 1.15 - 1.72; P-value=0.001) and hospitalization (OR=1.60; 95% CI: 1.19 - 2.14; P-value=0.006). WC was associated with the susceptibility (OR=1.38; 95% CI: 1.07 - 1.78; P-value=0.015) but not with hospitalization. WHR was not associated with any of the COVID-19 outcomes. Conclusions This study provides evidence for a causal impact of overall obesity on the susceptibility and severity of COVID-19. Therefore, obese people should be regarded as a risk group. Future research is necessary to investigate the underlying mechanisms linking obesity with COVID-19.