Early T-Lymphocyte Depletion Predicts Mortality in Critically Ill Children With Severe Infections: An Exploratory Analysis of Cytokine Pathways.

Abstract

Severe infections can lead to substantial reductions in T cell counts, yet its prognostic relevance and potential cytokine-mediated mechanisms remain poorly defined in pediatric populations. This study aimed to investigate whether T cell counts are associated with mortality, and to what extent this association is mediated by circulating cytokines. Prospective cohort study. A 55-bed PICU. Children 28 days to 18 years old admitted to the PICU due to infections, excluding those with preexisting conditions known to potentially impact T cell counts. None. A total of 252 patients were enrolled, with a median age of 4.16 years (interquartile range: 1.18-7.73), and 56.35% were male. CD3 + T cell count was nonlinearly associated with mortality ( p overall = 0.027; p nonlinear = 0.013), with a risk plateau beyond the inflection point at 705.14 cells/μL in restricted cubic spline models. The lower T cell group had markedly increased 30-, 60-, and 90-day mortality ( p < 0.05). Kaplan-Meier analysis showed that patients in the lower T cell group had significantly higher mortality ( p = 0.011). Multivariable Cox models confirmed an independent association between low T cell group and increased mortality risk, with a hazard ratio of 2.62 (95% CI, 1.12-6.14) for 90-day mortality. Mediation analysis showed that platelet-derived growth factor (PDGF)-AA mediates a substantial portion of this effect, accounting for 71.19% of the total pathway. Early T cell depletion independently predicts mortality in critically ill children with severe infections. These findings support the prognostic value of early immune profiling and suggest a potential immunoregulatory role for PDGF-AA.