Unravel the distinct effects of adiposity at different life stages on COVID-19 susceptibility and severity: A life-course Mendelian randomization study.

Childhood obesity is widely recognized as a risk factor for numerous health conditions, particularly cardiovascular disease. However, it remains unclear whether childhood adiposity directly affects the risk of COVID-19 in later life. We aimed to investigate the causal effects of early life adiposity on COVID-19 susceptibility and severity. We used genetic instruments from large-scale genome-wide association studies to examine the relationships between birth weight, childhood and adulthood adiposity indicators (including body mass index [BMI], obesity, and body size), and COVID-19 outcomes. Univariable and multivariable Mendelian randomization (MR) analyses were used to obtain the causal estimates. Univariable MR analyses found that childhood BMI and obesity were positively associated with COVID-19 risk and severity in adulthood, however, the significant associations were attenuated to null after further adjusting for adulthood adiposity indicators in multivariable MR analyses. In contrast, our analysis revealed strong evidence of a genetically predicted effect of childhood obesity on COVID-19 hospitalization (OR 1.08, 95% CI: 1.01-1.15, p = 2.12E-2), which remained robust even after adjusting for adulthood obesity and potential lifestyle confounders. Our results highlight the importance of promoting healthy weight management throughout life to reduce the risk of COVID-19.