Low levels of the protein TRAIL are associated with illness severity in children with suspected infection.
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INTRODUCTION: Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) has a potential role in the immune response to infections. This study investigated the association between serum TRAIL levels and illness severity in children with suspected infection. METHODS: A retrospective post hoc analysis was conducted in children aged 4 months to 18 years who underwent MeMed BV testing during emergency department evaluation for suspected acute infection. Patients were categorized by serum TRAIL levels using a prespecified cutoff of ≤40 pg/mL vs. >40 pg/mL. Clinical and demographic data were compared between groups, with illness severity at presentation as the primary outcome. RESULTS: The analysis included 104 children, with 52 children in each TRAIL group. Children with TRAIL levels ≤40 pg/mL had longer hospitalization duration (4.06 ± 3.5 days vs. 2.50 ± 3.5 days, p = 0.026), higher pulse rates (147.9 ± 24.2 bpm vs. 135.5 ± 25.1 bpm, p = 0.012), and more abnormal white blood cell counts (67.3% vs. 36.5%, p = 0.003). They also had higher maximal C-reactive protein levels [128.6 [55.7-180.7] mg/L vs. 22.5 [4.4-56.2] mg/L, p < 0.001] and were more likely to receive antibiotics (85% vs. 42%, p < 0.001) and to require changes in antibiotic therapy (58% vs. 13.5%, p < 0.001). Illness severity differed significantly between groups, with severe illness observed in 44.2% of children with TRAIL ≤40 pg/mL compared with 9.6% in those with TRAIL >40 pg/mL (p < 0.001).A TRAIL cutoff of ≤40 pg/mL showed moderate discriminatory performance for severe illness (AUROC 0.73), with 82.1% sensitivity, 61.8% specificity, PPV 44.2%, and NPV 90.4%. DISCUSSION: Lower serum TRAIL levels in children were associated with more severe illness, as evidenced by extended hospital stays, increased antibiotic use, and more severe clinical presentations. These findings suggest an association between low TRAIL levels and illness severity, although differences in infection etiology between groups should be considered.