Co-seasonality and co-detection of respiratory viruses and bacteraemia in children: a retrospective analysis

Objectives: The aim of this study was to assess the co-seasonality and co-detection of respiratory viral infections and bacteraemia in children since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods: Children <18 years old were eligible for inclusion if they had a respiratory infection and a positive PCR-based assay for respiratory viruses as well as a positive blood culture between 2010 and 2018 at a single referral centre in the United States, regardless of their underlying medical condition or antibiotic treatment history. Monthly incidence rates of respiratory viruses and bacteraemia were analysed with a seasonal-trend decomposition procedure based on loess (STL) and cross-correlation functions using time series regression modelling. Results: We identified 7415 unique positive respiratory virus tests, including 2278 respiratory syncytial virus (RSV) (31%), 1825 influenza viruses (24%), 1036 parainfluenza viruses (14%), 1017 human metapneumovirus (hMPV) (14%), 677 seasonal coronaviruses (9%), and 582 adenoviruses (8%), together with a total of 11 827 episodes of bacteraemia. Significant co-seasonality was found between all-cause bacteraemia and RSV (OR = 1.76, 95%CI 1.50–2.06, p < 0.001), influenza viruses (OR = 1.38, 95%CI 1.13–1.68, p 0.002), and seasonal coronaviruses (OR = 1.18, 95%CI 1.09–1.28, p < 0.001), respectively. Analysis of linked viral–bacterial infections in individual children indicated that the rate ratio (RR) of bacteraemia associated with hMPV (RR = 2.73, 95%CI 1.12–6.85, p 0.019) and influenza (RR = 2.61, 95%CI 1.21–6.11, p 0.013) were more than double that of RSV. Staphylococcus aureus and Streptococcus pneumoniae were the most commonly identified pathogens causing bacteraemia. Conclusions: There is a significant association between hMPV and influenza viruses and bacteraemia of all causes in hospitalized children at a single paediatric centre in the United States. Large multicentre studies are needed to confirm these findings and to elucidate the mechanisms by which hMPV potentiates the virulence and invasive capacity of diverse bacteria.