The burden of respiratory syncytial virus in healthy term-born infants in Europe: a prospective birth cohort study

Abstract

Background: Respiratory syncytial virus (RSV) is a major cause of hospitalisation in infants. The burden of RSV infection in healthy term infants has not yet been established. Accurate health-care burden data in healthy infants are necessary to determine RSV immunisation policy when RSV immunisation becomes available.

Methods: We performed a multicentre, prospective, observational birth cohort study in healthy term-born infants (≥37 weeks of gestation) in five sites located in different European countries to determine the health-care burden of RSV. The incidence of RSV-associated hospitalisations in the first year of life was determined by parental questionnaires and hospital chart reviews. We performed active RSV surveillance in a nested cohort to determine the incidence of medically attended RSV infections. The study is registered with ClinicalTrials.gov, NCT03627572.

Findings: In total, 9154 infants born between July 1, 2017, and April 1, 2020, were followed up during the first year of life and 993 participated in the nested active surveillance cohort. The incidence of RSV-associated hospitalisations in the total cohort was 1·8% (95% CI 1·6-2·1). There were eight paediatric intensive care unit admissions, corresponding to 5·5% of 145 RSV-associated hospitalisations and 0·09% of the total cohort. Incidence of RSV infection in the active surveillance cohort confirmed by any diagnostic assay was 26·2% (24·0-28·6) and that of medically attended RSV infection was 14·1% (12·3-16·0).

Interpretation: RSV-associated acute respiratory infection causes substantial morbidity, leading to the hospitalisation of one in every 56 healthy term-born infants in high-income settings. Immunisation of pregnant women or healthy term-born infants during their first winter season could have a major effect on the health-care burden caused by RSV infections.

Funding: Innovative Medicines Initiative 2 Joint Undertaking, with support from the EU's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations.

Conflict of interest statement

Declaration of interests LJB has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. UMCU has received major funding (>€100 000 per industrial partner) for investigator initiated studies from AbbVie, MedImmune, AstraZeneca, Sanofi, Janssen, Pfizer, MSD, and MeMed Diagnostics. UMCU has received major funding for the RSV GOLD study from the Bill & Melinda Gates Foundation. UMCU has received major funding as part of the public private partnership IMI-funded RESCEU and PROMISE projects with partners GSK, Novavax, Janssen, AstraZeneca, Pfizer, and Sanofi. UMCU has received major funding by Julius Clinical for participating in clinical studies sponsored by MedImmune and Pfizer. UMCU received minor funding (€1000–25 000 per industrial partner) for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, GSK, Novavax, Pfizer, Moderna, Astrazeneca, MSD, Sanofi, Genzyme, and Janssen. LJB is the founding chairman of the ReSViNET Foundation. SC has provided consultancy or investigator roles in relation to product development for Ablynx, Janssen, MedImmune, AstraZeneca, Pfizer, GSK, Vertex, AbbVie, Valneva, Fibrogen, and Boehringer Ingelheim, with fees paid to the University of Edinburgh. FM-T reports honoraria from GSK group, Pfizer, Sanofi Pasteur, MSD, Seqirus, Biofabri, and Janssen for taking part in advisory boards and expert meetings and for acting as a speaker in congresses, outside the submitted work; and principal investigator-role in randomised controlled trials for GSK, Pfizer, Sanofi Pasteur, MSD, Seqirus, Biofabri, Janssen, Ablynx, Gilead, Regeneron, Roche, Abbott, Novavax, and MedImmune, with honoraria paid to his institution. MDS acts as an investigator on behalf of the University of Oxford on research studies funded by vaccine manufacturers including GSK, Janssen, MCM vaccines, Novavax, AtraZeneca, and Pfizer. MDS was an National Institute for Heath and Care Research (NIHR) Senior Investigator and received salary support from the NIHR Oxford Biomedical Research Centre during the course of this work. MDS is currently an employee of Moderna. SBD had received honoraria from MSD and Sanofi Pasteur for taking part in advisory boards and has provided consultancy or investigator roles in relation to product development for Janssen, AstraZeneca, Pfizer, Valneva, MSD, and Sanofi Pasteur with fees paid to St George's University of London. TH has received honoraria for lectures or participation in advisory boards or data monitoring committees from Janssen, Sanofi Pasteur, Enanta, and MSD. BR is a full-time employee of the GSK group and holds shares and restricted shares in the GSK group as part of their employee remuneration. AJP is currently Chair of the Department of Health Social Cares Joint Committee on Vaccination and Immunisation and was previously a member of WHO Scientific Advisory Group for Emergencies and chair of the European Medicine's Agency Scientific Advisory Group on Vaccines. All other authors declare no competing interests.

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Figures

Figure 1

Flow chart of participants in RESCEU birth cohort study for total cohort and active surveillance cohort ARI=acute respiratory infection. RSV=respiratory syncytial virus. *Did not continue with active surveillance. †Including 16 RSV admissions (also counted in RSV admissions). ‡Including seven ARI admissions (also counted in RSV-negative admission). §Number of children with wheezing of total number of children with known wheezing status.

Figure 2

Number of all-cause and RSV-associated ARI by month for ARI (A), medically attended ARI (B), and hospitalised ARI (C) ARI and medically attended ARI are derived from the active surveillance cohort; hospitalised ARI is derived from the passive surveillance cohort. ARI=acute respiratory infection. RSV=respiratory syncytial virus.