Publication Date
1-1-2023
Journal
Frontiers in Immunology
DOI
10.3389/fimmu.2023.1220028
PMID
37533854
PMCID
PMC10390830
PubMedCentral® Posted Date
7-18-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Multiple Organ Failure, Influenza, Human, Transcriptome, Phenotype, Hospitalization, Bacterial Infections, sepsis, organ failure, pediatric intensive care, neutrophil degranulation, MODS, neutrophil transcripts, critical care
Abstract
BACKGROUND: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.
METHODS: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05).
RESULTS: Comparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (
CONCLUSION: Thus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.
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Community Health and Preventive Medicine Commons, Critical Care Commons, Medical Sciences Commons, Pediatrics Commons
