Viral respiratory tract infections in children

Abstract: The most common infection in humans is viral respiratory tract infections which predominantly present as the ‘common cold’. In some circumstances however, respiratory viruses cause acute lower respiratory tract infections (RTIs) and due to the high absolute number of infection the contribution of these cases to total morbidity and mortality are substantial. For several reasons relating to physiology and immunology, children account for a great amount of morbidity caused by viral respiratory infections, namely influenza virus (IFV) and respiratory syncytial virus (RSV). The aims of this thesis are to define burden and risk-factors associated with severe IFV and RSV infections among children. In papers I, III, IV and study V (in manuscript), we retrospectively investigated risk-factors, complications and epidemiological drivers associated with RSV and IFV based on hospitalized children 0-17 years old residing in the Northern Stockholm region. In total, these studies span over 21 years from 1st July 1998 until 30th June 2019. A total of 1,050 IFV and 5,253 RSV cases were included over that period. Our results indicate that a steep rise in birth rates combined with viral interference caused by the pandemic H1N1 Influenza A virus (IFV-A pdm09) in 2009-10 were likely contributors to the disruption of the delayed biennial cyclicity of RSV epidemics. We derived that the cold winters coinciding with the altered epidemic pattern had a lesser role. Our data reveals a triennial pattern of IFV epidemics 2008 – 2019 and a rise in influenza type B (IFV-B) in the same period. It is not clear whether this is related to improved IFV-B diagnostics or a true change in IFV ecology. Furthermore, we identified children with neuromuscular conditions to be at substantial risk of severe IFV infection, warranting improved vaccine coverage. Regarding RSV, our findings illustrate the importance of older siblings as a ‘vector’ for disease transmission to newborns, who are the most susceptible to severe disease during their first three months of life. In paper II, the potential for the urinary PGE2 metabolite (u-tPGEM) to identify children with severe viral infections, was investigated. We established baseline values for u-tPGEM in infancy and found higher levels among hospitalized children with lower RTIs and gastroenteritis, but not in infants with upper RTIs. Further studies are required to understand more about the immunological pathways involved in viral RTIs to predict disease progression in an individual and hopefully identify targets for future treatments. Taken together, our findings improve the understanding of dynamics involved in seasonal epidemics which can help us to prepare what is to come in the wake of the Covid-19 pandemic. These results also indicate which group would benefit the most from prevention efforts. In the long-term, describing immunological pathways involved in severe viral respiratory infections can help us to finally advance from the current therapeutic plateau.