Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza

• DOI: 10.3389/fimmu.2023.1220028
• Publication Date: 2023-07-18T08:50:57Z
• Authors: Tanya Novak; Jeremy Chase Craw...; Georg Hahn; Mark W. Hall; Simone A. Thair; Margaret M. Newhams; Janet Chou; Peter M. Mourani; Keiko M. Tarquinio; Barry Markovitz; Laura L. Loftis; Scott L. Weiss; Renee Higgerson; Adam J. Schwarz; Neethi P. Pinto; Neal J. Thomas; Rainer G. Gedeit; Ronald C. Sanders; Sidharth Mahapatra; Bria M. Coates; Natalie Z. Cvijan...; Kate G. Ackerman; David W. Tellez; Patrick McQuillen; Stephen C. Kurachek; Steven L. Shein; Christoph Lange; Paul G. Thomas; Adrienne G. Randolph
• Keywords: Organ dysfunction

Background Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) life-threatening and fatal complication severe influenza infection. Methods We measured RNA expression 469 biologically plausible candidate genes children admitted to North American pediatric intensive care units with infection without MODS. Whole blood samples from 191 influenza-infected (median age 6.4 years, IQR: 2.2, 11) were collected median 27 hours following admission; 45 second sample was approximately seven days later. Extracted hybridized NanoString mRNA probes, counts normalized, analyzed using linear models controlling bacterial co-infections (FDR q<0.05). Results Comparing near admission, Prolonged MODS ≥7 (n=38; 9 deaths) had significant upregulation nine transcripts associated neutrophil degranulation ( RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared those who recovered more rapidly (n=27). These present early predicted or death when patients recovered, however paired longitudinal samples, they not differentially expressed over time. Instead, five involved protein metabolism and/or adaptive immunity signaling pathways RPL3, MRPL3, HLA-DMB, EEF1G , CD8A ) recovery within week. Conclusion Thus, increased indicated worse clinical outcomes infection, consistent reports adult cohorts influenza, sepsis, acute respiratory distress syndrome.