Inflammatory cytokines as biomarkers for disease severity in pediatric viral pneumonia: a systematic review and meta-analysis.
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BACKGROUND: Severe progression of viral pneumonia in children is associated with adverse clinical outcomes. Inflammatory cytokines have been proposed as potential biomarkers for both disease presence and severity; however, existing evidence remains inconsistent. This systematic review and meta-analysis aimed to evaluate the association between inflammatory cytokines and pediatric viral pneumonia by comparing healthy controls with affected children, as well as children with mild disease versus those with moderate-to-severe disease, and to further assess the diagnostic performance of interleukin-6 (IL-6). METHODS: A systematic literature search was conducted in seven databases up to January 25, 2026. Studies involving children (<18 years) with viral pneumonia that reported inflammatory cytokine levels in healthy controls and patients, or stratified patients by disease severity, were included. A total of 19 studies were ultimately included in the meta-analysis. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were pooled using random-effects models. Subgroup, sensitivity, and publication bias analyses were performed. A diagnostic test accuracy meta-analysis was conducted to evaluate the ability of IL-6 to identify moderate-to-severe disease. RESULTS: Nineteen studies were included. Compared with healthy controls, children with viral pneumonia had significantly higher levels of IL-6, C-reactive protein (CRP), procalcitonin (PCT), and tumor necrosis factor-α (TNF-α). Further severity-stratified analysis showed that children in the moderate-to-severe group had significantly higher levels of IL-6 (WMD =-13.07, 95% CI: -16.88 to -9.26), CRP (WMD =-10.16, 95% CI: -17.20 to -3.12), PCT (WMD =-0.37, 95% CI: -0.59 to -0.15), and TNF-α (WMD =-1.08, 95% CI: -1.65 to -0.51) compared with those in the mild group. Subgroup analyses demonstrated that IL-6 consistently discriminated disease severity across pathogen types, age groups, and sample sizes. The pooled sensitivity and specificity of IL-6 for identifying moderate-to-severe disease were 0.80 (95% CI: 0.68-0.89) and 0.78 (95% CI: 0.64-0.87), respectively, with an area under the summary receiver operating characteristic curve of 0.86. CONCLUSIONS: Inflammatory cytokines are significantly elevated in children with viral pneumonia compared with healthy controls and are further increased in those with moderate-to-severe disease. Among these biomarkers, IL-6 demonstrates stable severity discrimination and moderate diagnostic accuracy, suggesting its potential value for early identification of children at risk of severe disease progression.