Iron metabolism disorder irritates susceptibility to bacterial pneumonia, viral pneumonia, and sepsis

<bold>Background:</bold> Recent studies showed ferritin increasing and hemoglobin decreasing associated with the severity of COVID-19, or mortality of sepsis. However, the potential relationship between iron metabolism disorders and susceptibility to pneumonia remains inadequately unclear. <bold>Aims:</bold> To explore the association between iron metabolism disorder and susceptibility to bacterial pneumonia, viral pneumonia, and sepsis. <bold>Methods:</bold> A meta-analysis of SNPs related to iron levels was conducted and integrated into GWAS from the FinnGen biobank. A two-sample Mendelian randomization (MR) analysis was performed to ascertain the association, followed by MR meta-analysis. <bold>Results:</bold> Serum iron levels have negative association with susceptibility to bacterial pneumonia (OR, 0.85; 95% CI, 0.73-0.99; p=0.04), influenza pneumonia (OR, 0.86; 95% CI, 0.73-0.99; p=0.03), and sepsis (OR, 0.81; 95% CI, 0.72-0.91; p=0.0004) (Fig. 1). Increased transferrin saturation (TSAT) and decreased total iron-binding capacity (TIBC) were associated with increased susceptibility to bacterial pneumonia and sepsis. The indirect effect of increased TSAT on bacterial pneumonia via neutrophil was 6.5% (95% CI, 5.7% to 7.2%). <bold>Conclusion:</bold> Iron metabolism disorder irritates susceptibility to bacterial pneumonia, viral pneumonia, and sepsis, particularly evident with decreased serum iron levels, and increased TSAT and TIBC. <fig><object-id>erj;64/suppl_68/OA5459/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> Fig. 1 Summary of MR analysis results