Abstract Background The host response pathways associated with progression to severe influenza disease and mechanisms of vaccination on mitigating illness severity in children are not well understood. Methods We conducted a prospective observational case-control study of children aged 2 to 18 years hospitalized with polymerase chain reaction-confirmed influenza infection from 2020 to 2022. We compared the host transcriptome and cytokine profiles in blood of children within 5 days of influenza infection (cases) with healthy asymptomatic controls undergoing elective surgery. We analyzed transcription profiles as a function of (1) infected cases versus uninfected controls, (2) severe versus nonsevere, and (3) vaccinated versus unvaccinated. Pathway analysis on differentially expressed genes was performed. Results Among 11 infected cases and 12 uninfected controls, there were no significant differences with respect to age, sex, or any high-risk medical condition, but a higher proportion of cases were Hispanic (45.5% vs 8.3%, P = .0007) and unvaccinated (72.7% vs 33.3%, P = .036). Compared with controls, 5277 genes were differentially expressed in influenza infection. Pathway analysis revealed major themes of gene enrichment related to interferon responses and innate inflammatory responses, confirmed with plasma cytokine analyses. We identified 102 differentially expressed genes between vaccinated and unvaccinated cases. Strong upregulation of B-cell and neutrophil responses and to a lesser extent, innate inflammatory and interferon responses, were observed in vaccinated compared with unvaccinated children. Vaccinated cases shared similar biosignatures with uninfected controls. Conclusions Our study demonstrated differences in gene expression profiles of children with influenza infection that support disease mitigation through vaccination.
Rao et al. (Thu,) studied this question.