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Background Diagnosing viral pneumonia in children is challenging. Chest radiographic imaging and clinical findings cannot reliably distinguish viral from bacterial pneumonia. Furthermore, pathogen-based diagnosis is limited by inaccessible site of infection and high asymptomatic detection rates. The objectives of this analysis were twofold: first, to establish pneumonia etiology by applying a rigorous expert panel process, and second, to evaluate whether a novel host-immune signature that integrates viral induced proteins TRAIL and IP-10 together with bacterial CRP, can accurately differentiate viral from bacterial pneumonia. Methods This analysis included 1025 febrile children enrolled in two multi-center clinical studies that evaluated the host-immune signature performance: ‘Curiosity’ study (Oved et al., PLoS One 2015) and ‘Pathfinder’ study (Srugo et al., Pediatrics 2017). Pneumonia etiology – viral or bacterial – was determined by a panel of 3 independent experts, after reviewing patients’ clinical, laboratory, microbiological, and radiological data. Only cases with majority panel assignment were included. The host-signature generated one of the three results: viral, equivocal or bacterial, based on predetermined cut-offs. Results A total of 709 children were eligible for analysis and had an expert panel etiology determination. Of them, 114 were diagnosed with pneumonia: 51 assigned viral and 63 assigned bacterial (Figure 1). The signature separated viral from bacterial pneumonia with a sensitivity of 94% (95% CI: 85%–99%) and specificity of 95% (85%–99%) with 14% equivocal test results. Out of the 51 children diagnosed with viral pneumonia by the expert panel, 40 (78%) were given antibiotics, and 43 (83%) underwent chest x-ray evaluation. The signature correctly classified 42 of these 51 viral children, indicating its potential to reduce antibiotic overuse rates by 4.4-fold (from 78% to 18%; P &lt; 0.001) and chest x-ray examination by 4.8-fold (from 83% to 18%; P &lt; 0.001). Conclusion The TRAIL/IP-10/CRP signature exhibits high accuracy for diagnosing viral pneumonia in children. The signature’s potential to safely decrease unnecessary antibiotics and chest radiographic imaging should be examined in future utility studies. Disclosures All authors: No reported disclosures.

2624. Viral Pneumonia in Children: Facing the Challenge Using the Host Response