Genes associated with Multiple Organ Dysfunction Syndrome during severe pediatric influenza

Abstract

Abstract Influenza remains a global pathogen that causes significant morbidity and mortality even in previously healthy children. Multiple Organ Dysfunction Syndrome (MODS) is a potential complication developed during severe infection. This multi-site, national study investigated which genes are associated with resolving, developing, or predicting prolonged MODS in children admitted to ICU with severe influenza. PAXgene whole blood RNA from 216 influenza positive patients (median age 6.7 years, IQR: 2.6, 11.2) was extracted and hybridized to 469 NanoString nCounter® mRNA probes including positive/negative controls. Absolute mRNA molecules were quantified, normalized to 5 reference genes, and analyzed using linear models controlling for age, bacteria co-infections and type I error via FDR. Children who developed MODS had significantly higher levels of the antimicrobial Lactotransferrin (LTF) mRNA expression than those that never had MODS (p=0.04) whilst the latter group showed significantly higher expression of Transforming Growth Factor β1 (TGFBI) (p=0.04). In children with prolonged MODS, nine neutrophil degranulation genes were upregulated including TCN1, RETN, and LCN2 (p<0.001) which have previously been implicated in sepsis-related ARDS and mortality, and as biomarkers for severe influenza in adults. This study highlighted a panel of genes that are associated with MODS during severe pediatric influenza and could potentially be used for predicting and managing this complication. Supported by grants from NIH/Department of Health and Human Services 1R21HD095228-01