Abstract
BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a significant impact on global health. While the virus primarily affects the respiratory system, the intricate interplay between immune cells and the virus remains poorly understood. This study investigates the causal relationship between 731 immune cell phenotypes and COVID-19 using Mendelian randomization (MR) analysis. METHODS: A bidirectional two-sample MR analysis was conducted using genetic variants strongly associated with immune cell phenotypes as instrumental variables. Data for 731 immune cell phenotypes were sourced from the Genome-Wide Association Study (GWAS) catalog, while data for COVID-19 susceptibility were obtained from the OPEN GWAS database. Five MR methods (inverse variance weighted [IVW], MR-Egger, weighted median, simple mode, and weighted mode) were used to estimate causal effects, with IVW as the primary analysis method. RESULTS: The study identified 57 immune cell phenotypes causally associated with COVID-19 risk across two independent GWAS datasets. Five immune cell phenotypes were consistently associated with COVID-19 risk across both datasets: CD3- lymphocyte %lymphocyte (protective), CD27 on CD20- (protective), CD20 on IgD+ CD38- unsw mem (increased risk), CD27 on IgD- CD38- (increased risk), and CD19 on B cell (increased risk). Sensitivity analyses confirmed the robustness of the findings. CONCLUSION: This study provides compelling evidence for a causal relationship between specific immune cell phenotypes and COVID-19 risk. These findings highlight the potential for targeting these immune cell phenotypes as novel therapeutic targets for COVID-19 treatment and prevention.