Cebey López, MiriamHerberg, JethroPardo Seco, Jacobo JoséGómez Carballa, AlbertoMartinón Torres, NazarethSalas Ellacuriaga, AntonioMartinón Sánchez, José MaríaJusticia Grande, AntonioRivero Calle, IreneSumner, EdwardFink, ColinMartinón Torres, FedericoGENDRES network2017-10-202017-10-202016-04-20Cebey-López M, Herberg J, Pardo-Seco J, Gómez-Carballa A, Martinón-Torres N, Salas A, et al. (2016) Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children? PLoS ONE 11(4): e0152481. doi:10.1371/journal. pone.0152481http://hdl.handle.net/10347/15917Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective roleeng© 2016 Cebey-López et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedjournal article10.1371/journal.pone.01524811932-6203open access