A major challenge in management of children with RSV infection is distinguishing viral infection from viral-bacterial coinfections. Despite the low rates of viralbacterial coinfection, RSV patients are often prescribed antibiotics . Here, we examined whether a host-immune signature combining the viral-induced proteins TRAIL and IP-10 with CRP (ImmunoXpert; Oved et al. 2015) can distinguish viral from viral-bacterial coinfection in RSV patients. 402 febrile children enrolled as part of ‘Curiosity’ . Infection etiology viral or viralbacterial coinfection was determined by a panel of experts following a review of patients’ clinical, laboratory, radiological, microbiological and follow-up data. RSV strains were detected using a respiratory multiplexPCR applied to nasal swabs . Out of 402 children with acute infection 29 had a positive RSV detection , of them, 27 had a unanimous expert panel etiology determination: 24 viral and 3 viral-bacterial coinfections. Out of 24 patients assigned viral by the expert panel, 13 were given antibiotics, indicating a 54% antibiotic overuse rate. The host-immune signature correctly identified all 3 viral-bacterial coinfection cases, as well as 22 out of the 24 (92%) simple viral patients. This supports that the signature has the potential to reduce antibiotic overuse by 6.5-fold. Our results demonstrate high antibiotic overuse rates for RSV patients, consistent with previous reports. The host-immune signature correctly distinguished simple viral from viral-bacterial coinfection and therefore has the potential to aid physicians in the correct management of children with RSV infection. studies are required to evaluate its utility in decreasing unnecessary antibiotic use for RSV patients.