Clinical Course, Viral Load, and (Sub)Type of Influenza in Hospitalized Children in Southern Germany

This study aimed to assess the relationship between clinical course and influenza virus characteristics by quantifying viral load and performing phylogenetic analyses in hospitalized children. Children aged 0-3 years presenting with an acute respiratory tract infection (RTI) at the Childrens' Hospital Heidelberg/Germany were included and nasopharyngeal swabs were collected. Viral load was quantified by real-time polymerase chain reaction and influenza virus (sub)type was identified by haemagglutinin gene sequencing. Among 1464 respiratory samples collected, 139 were positive for influenza virus, and 112 samples were selected for viral load analysis and sequencing. Influenza-positive children were significantly older than influenza-negative children (p < 0.001) and presented with symptoms of rhinitis (94.8%), cough (83.7%), and fever (54.3%). They presented most frequently with admission diagnoses of upper RTI (22.3%), febrile convulsion (18.7%), and pneumonia (15.8%). Children with high viral load were younger (p < 0.001), however clinical presentation was not associated with viral load levels. Comparing influenza A (n = 104/139) and B (n = 35/139) infections, no differences in demographic or clinical characteristics were identified. Children with influenza A(H1N1)pdm09 (n = 54/104) had pneumonia (p = 0.002), tachypnoea (p = 0.004), rales (p = 0.041), and retractions (p = 0.015) more frequently compared to influenza A(H3N2)-infected children (n = 50/104). Phylogenetic analyses showed that the identified influenza virus strains were consistent with nationwide and European data in the corresponding seasons. Viral load and influenza type A compared to B did not correlate with a more severe course of disease; however, viral load was higher in younger children and influenza subtype A(H1N1)pdm09 was significantly associated with lower RTI.