Study finds RSV responsible for most infant hospitalizations in the European Union

In a recent study posted to the medRxiv* preprint server, researchers used statistical modeling to estimate hospitalizations due to respiratory syncytial virus (RSV) infections in children under five years of age in 28 nations of the European Union (EU) and Norway. 

Study: 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. Image Credit: SUKJAI PHOTO / Shutterstock

Background

Around 22% of acute lower respiratory infections (ALRI) globally, resulting in ~101,400 deaths in young children annually, are due to RSV infections. Studies have estimated the burden of RSV infections, subsequent hospitalizations, and mortality in children in a European country. However, there is a lack of studies determining RSV-related hospitalizations in the whole of the EU for young children below five years.

About the study

In the present study, researchers collated data from several sources between 2006 and 2018. For instance, they used data from the REspiratory Syncytial virus Consortium in EUrope (RESCEU) project encompassing regularly collected data on hospital admissions for six countries – Denmark, Finland, England, Norway, Scotland, and the Netherlands. In addition, they added additional data for Spain and France from the literature.

The researchers searched MEDLINE and EMBASE databases between 1 January 2019 and 30 November 2021 for original articles using the exact search string as the Li et al. systematic review. They further assessed all articles for eligibility; for instance, they checked all eligible articles by backward citation chaining. Finally, the researchers organized all the extracted data in a spreadsheet. They also assessed all the included studies for quality and calculated an overall score.

They used regression models to calculate published and unpublished national estimates of RSV-associated hospitalizations in EU countries to feed as input data for statistical analyses. They stratified data by age and country. Accordingly, it had the following age groups: zero to two, three to five, six to 11, 12 to 35, and 36 to 59 months.

They used a two-stage-modeling approach, adapted from prior work evaluating influenza-related mortality. In stage 1, the researchers identified age-stratified estimates of RSV-related hospitalizations from respiratory viruses (or other causes) for each year, calculated using regression models. This data and data extracted from the literature that met the inclusion criteria were input for Stage 2.

In two steps of Stage 2, they utilized the countrywide estimates of RSV-related hospitalizations to extrapolate the cumulative hospitalization burden for all EU countries and Norway. The first, called the data creation step, relied on two sets of 10 country-specific indicators representing population-level health conditions from a geographical and demographic perspective. The statistical modeling fetched four result sets, each related to one set of 10 country-specific indicators and one modeling approach.

They calculated the median of the results from all four models to calculate the total annual number and RSV-related hospitalization rates (per 1,000 people) for all the included countries for the zero to two, three to five, six to 11, 12 to 35, and 36 to 59 months age bands. The study search adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Study findings

The study analysis covered 1,372 unique records from MEDLINE and EMBASE databases and 33 articles identified by backward citation chaining. In addition, it covered two studies reporting RSV-related hospitalization estimates for Spain and France from 1997 to 2011 and 2010 to 2018, respectively. Intriguingly, data from eight EU countries used in the study analysis represented ~40% of the Norway and EU population.

The study analysis revealed that RSV was associated with an average of 245,244 hospital admissions per year in children below five years, with most cases in children below one year and one to two years (75% and 20.7%). However, the impact was the highest for infants below two months of age (71.6/1,000 children). Strikingly, on average, RSV infection accounted for the hospitalization of 10 of 1000 children in the EU annually.

Indeed, RSV is a leading cause of infant hospitalizations in the EU, especially when considering respiratory infections-related hospitalizations. These numbers are much lower in countries like Sweden, Denmark, Italy, and Portugal. The countries with the highest number of RSV-related hospitalizations were France, the United Kingdom (UK), and Germany, with 46,027, 39,296, and 34,719 hospitalizations per year, respectively, in children below five years.

The researchers noted that the annual RSV-related hospitalization rates varied substantially across EU countries. While the Netherlands had the lowest rates in nearly all age groups, Norway had the lowest rates in the three-to-four-year age group, and France had the highest rates. Also, they noted the highest relative difference in the age group of 12-to-35-month-old infants, with rates in France being five-fold than in the Netherlands.

Conclusions

The study results showed that in children below five years, RSV, on average, led to ~250,000 respiratory hospitalizations annually in the 28 EU nations covered in this analysis. Of these, 65.4% of hospitalizations in Denmark and 80.7% in Spain occurred, on average, in zero to 11-month-old infants and 93.9% in Portugal, and 97.7% in Norway in those aged less than 23 months.

Similar to prior studies, RSV-related hospitalization increased with decreasing age, with infants below one year bearing the highest burden, especially those aged zero to two months. Thus, RSV immunization in the first six months of birth could prove highly beneficial in containing RSV infections among younger children. Furthermore, the study estimates could help optimize public health responses, allowing more resource allocation to pediatric hospitals during the winter season and supporting decisions regarding future RSV immunization and mitigation programs.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.