Defining the Burden of Disease of RSV in Europe: estimates of RSV-associated hospitalisations in children under 5 years of age. A systematic review and modelling study

Background Respiratory syncytial virus (RSV) infections cause an estimated 22-50 million episodes of acute lower respiratory infections (ALRI) every year in children younger than 5 years. To date, no overall estimate of RSV-associated hospitalisations in children under 5 years has been published for the European Union (EU). Through statistical modelling, we estimated the RSV hospitalisation burden in children under 5 years of age in EU countries and Norway, by age group and country. Methods We collated national RSV-associated hospitalisation estimates calculated using linear regression models in children under 5 years via the RESCEU project for Denmark, England, Finland, Norway, the Netherlands and Scotland during 2006-2018. A systematic literature review was conducted to collect additional estimates. Using the multiple imputation and nearest neighbour matching extrapolation methods, we estimated RSV-associated hospitalisation rates in all EU countries. Results Additional estimates for Spain and France were found in the literature and added to the analysis. We estimated that an average of 245,244 (95%CI 224,688-265,799) hospital admissions with a respiratory infection per year were associated with RSV in children under the age of 5, with most cases occurring among children aged less than 1 year (75%). Infants aged less than 2 months represented the most affected group (71.6 per 1,000 children; 95%CI: 66.6-76.6). The hospitalisation rates varied widely across countries: for example, estimated rates in the 0-2 months age group ranged from 47.4 (37.5-57.3) per 1,000 in the Netherlands to 98.3 (88.5-108.1) per 1,000 in France. Conclusion To our knowledge, this is the first attempt to estimate the overall RSV hospitalisation burden in children under the age of 5 years in the EU. Our findings will help support decisions regarding prevention efforts, and they will also represent an important benchmark to understand changes in the RSV burden following the introduction of RSV immunisation programs in Europe. ### Competing Interest Statement HC reports grants, personal fees, and nonfinancial support from World Health Organization. Grants and personal fees from Sanofi Pasteur. Grants from Bill and Melinda Gates Foundation. All payments were made via the University of Edinburgh. HC is a shareholder in the Journal of Global Health Ltd. JP declares that Nivel has received unrestricted research grants regarding the epidemiology of RSV from Sanofi Pasteur and IMI in the past 12 months. ### Funding Statement This work is part of RESCEU. RESCEU has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116019. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication only reflects the author's view, and the JU is not responsible for any use that may be made of the information it contains herein. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors