Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study

• Published in: Journal of translational medicine 2022-05, Vol.20 (1), p.216-216, Article 216
• Main Authors: Chen, Xiong, Hong, Xiaosi, Gao, Wenjing, Luo, Shulu, Cai, Jiahao, Liu, Guochang, Huang, Yinong
• Format: Article
• Language: English
• Subjects: Accelerometers; Age; Behavior; Biobanks; Body mass index; Causal effect; Computer use; Control; Coronaviruses; COVID-19; COVID-19 - epidemiology; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Disease transmission; Epidemics; Exercise; Genome-Wide Association Study; Genomes; Health aspects; Homeostasis; Hospitalization; Humans; Insulin; Insulin resistance; Laboratories; Leisure; Leisure Activities; Leisure sedentary behavior (LSB); Mendelian randomization (MR); Mendelian Randomization Analysis; Metabolism; Mortality; Obesity; Pandemics; Phenotypes; Physical activity; Physical activity (PA); Public health; Risk factors; Sedentary Behavior; Sensitivity analysis; Severe acute respiratory syndrome coronavirus 2; Smoking; Social interactions
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-022-03407-6

The 2019 coronavirus disease pandemic (COVID-19) poses an enormous threat to public health worldwide, and the ensuing management of social isolation has greatly decreased opportunities for physical activity (PA) and increased opportunities for leisure sedentary behaviors (LSB). Given that both PA and LSB have been established as major influencing factors for obesity, diabetes and cardiometabolic syndrome, whether PA/LSB in turn affects the susceptibility to COVID-19 by disrupting metabolic homeostasis remains to be explored. In this study, we aimed to systematically evaluate the causal relationship between PA/LSB and COVID-19 susceptibility, hospitalization and severity using a Mendelian randomization study. Data were obtained from a large-scale PA dataset (N = 377,000), LSB dataset (N = 422,218) and COVID-19 Host Genetics Initiative (N = 2,586,691). The causal effects were estimated with inverse variance weighted, MR-Egger, weighted median and MR-PRESSO. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot. Risk factor analyses were further conducted to investigate the potential mediators. Genetically predicted accelerometer-assessed PA decreased the risk for COVID-19 hospitalization (OR = 0.93, 95% CI 0.88-0.97; P = 0.002), while leisure television watching significantly increased the risk of COVID-19 hospitalization (OR = 1.55, 95% CI 1.29-1.88; P = 4.68 × 10 ) and disease severity (OR = 1.85, 95% CI 1.33-2.56; P = 0.0002) after Bonferroni correction. No causal effects of self-reported moderate to vigorous physical activity (MVPA), accelerometer fraction of accelerations > 425 milligravities, computer use or driving on COVID-19 progression were observed. Risk factor analyses indicated that the above causal associations might be mediated by several metabolic risk factors, including smoking, high body mass index, elevated serum triglyceride levels, insulin resistance and the occurrence of type 2 diabetes. Our findings supported a causal effect of accelerometer-assessed PA on the reduced risk of COVID-19 hospitalization as well as television watching on the increased risk of COVID-19 hospitalization and severity, which was potentially mediated by smoking, obesity and type 2 diabetes-related phenotypes. Particular attention should be given to reducing leisure sedentary behaviors and encouraging proper exercise during isolation and quarantine for COVID-19.