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Role of Metabolic Syndrome Traits on Infectious Diseases: A Mendelian Randomization Study

Si Cao¹, Youjie Zeng¹, Xiaoyi Zhang²

¹Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, China.

International Journal of Public Health

|December 19, 2025

Abstract

Objectives:

To explore the causal association of metabolic syndrome (MetS) and its components [systolic blood pressure (SBP), fasting blood glucose (FG), waist circumference (WC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)] with seven infectious diseases (COVID-19 infection, hospitalized COVID-19, very severe COVID-19, bacterial pneumonia, influenza, intestinal infection, and sepsis) using Mendelian randomization (MR) analysis.

Methods:

Causal estimates were primarily obtained using the inverse-variance weighted method, with multiple sensitivity analyses conducted to assess heterogeneity and horizontal pleiotropy.

Results:

MetS was causally associated with higher risks of COVID-19 infection (OR = 1.09), hospitalized COVID-19 (OR = 1.27), very severe COVID-19 (OR = 1.40), and sepsis (OR = 1.50). Among MetS components, WC increased risks of COVID-19 infection (OR = 1.10), hospitalized COVID-19 (OR = 1.39), very severe COVID-19 (OR = 1.56), bacterial pneumonia (OR = 1.11), and sepsis (OR = 1.42), while HDL-C reduced risks of intestinal infection (OR = 0.96) and sepsis (OR = 0.92).

Conclusion:

This MR study supports a causal link between MetS traits and several infectious diseases, emphasizing the importance of metabolic management in reducing infection susceptibility.

Keywords:

COVID bacterial pneumonia causal inference intestinal infection metabolic syndrome

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