Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

Abstract

Background: 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 role.

Fig 1. Influence of bacterial superinfection, pneumococcal vaccine and the presence of viral co-infection on disease severity of children with ARI, according to oxygen and respiratory support requirement, clinical scales, hospital stay length and PICU admission.

Data are shown as OR (95% CI) for both main cohort and replication cohort. A binary logistic model was used for the binary variables (co-infection status, oxygen requirements, respiratory support needed and PICU admission), linear model for continuous variables (Wood-Downes Score and the GENVIP score) and negative binomial regression model for counted data (number of days since admission).