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• W4308695951 abstract "In the slipstream of the extraordinary, worldwide natural experiment reducing close human contact to mitigate the spread of SARS-CoV-2, a drastically but temporarily diminished transmission of respiratory syncytial virus (RSV) in children occurred in the winter of 2020–21.1Bardsley M Morbey RA Hughes HE et al.Epidemiology of respiratory syncytial virus in children younger than 5 years in England during the COVID-19 pandemic, measured by laboratory, clinical, and syndromic surveillance: a retrospective observational study.Lancet Infect Dis. 2022; (published online Sept 2.)https://doi.org/10.1016/S1473-3099(22)00525-4Summary Full Text Full Text PDF PubMed Scopus (21) Google Scholar This glimpse of a world without RSV gained momentum for the urgent need for preventive strategies for this prototypical paediatric pathogen, which causes a spectrum of mild upper-respiratory to severe lower-respiratory tract disease in young children. With the estimation that one out of every 50 deaths in children younger than 5 years is attributable to RSV, the impact of this virus on global child health is very high.2Li Y Wang X Blau DM et al.Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis.Lancet. 2022; 399: 2047-2064Summary Full Text Full Text PDF PubMed Scopus (113) Google Scholar Although most case fatalities occur among children living in low-income and middle-income countries, substantial short-term morbidity and economic impact result in an equally high burden in high-income countries. In addition, RSV infection in early life is associated with long-term respiratory dysfunction.3Brunwasser SM Snyder BM Driscoll AJ et al.Assessing the strength of evidence for a causal effect of respiratory syncytial virus lower respiratory tract infections on subsequent wheezing illness: a systematic review and meta-analysis.Lancet Respir Med. 2020; 8: 795-806Summary Full Text Full Text PDF PubMed Scopus (36) Google Scholar Seasonal outbreaks of RSV put major pressure on health-care system performance, ranging from primary care physician to specialised paediatric critical care settings. In a survey among inpatient and outpatient clinicians, almost 50% of the respondents considered RSV to be very to extremely disruptive for hospital bed capacity and patient flow while delaying access to elective care.4EHMAThe health system burden of respiratory syncytial virus (RSV) in Europe (EHMA White Paper).https://ehmaorg/2022/04/19/the-health-system-burden-of-rsv-in-europe-ehmas-white-paper/Date: 2022Date accessed: October 20, 2022Google Scholar Moreover, infant hospitalisation for RSV is a major emotional, physical, and organisational stressor for parents, caregivers, and siblings, and its influence on household members persists well beyond discharge.5Lapillonne A Regnault A Gournay V et al.Impact on parents of bronchiolitis hospitalization of full-term, preterm and congenital heart disease infants.BMC Pediatr. 2012; 12: 171Crossref PubMed Scopus (24) Google Scholar The multifaceted impact of RSV underlines the need for an effective prevention programme. Now, almost 60 years after first unsuccessful vaccination attempts, and 25 years after approval for passive immunisation with palivizumab,6American Academy of Pediatrics Committee on Infectious DiseasesAmerican Academy of Pediatrics Bronchiolitis Guidelines CommitteeUpdated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection.Pediatrics. 2014; 134: e620-e638Crossref PubMed Scopus (478) Google Scholar which has shown moderate benefit but is licensed for specific high-risk infants only, we are at the advent of novel promising compounds, notably nirsevimab, and strategies such as maternal vaccination, to be made available for protection of all infants.7Hammitt LL Dagan R Yuan Y et al.Nirsevimab for prevention of RSV in healthy late-preterm and term infants.N Engl J Med. 2022; 386: 837-846Crossref PubMed Scopus (112) Google Scholar In preparation of the implementation and cost-effectiveness evaluation of such widescale prevention programmes, we are still very much in need of real-world data on the health-care burden of RSV in children. In this light, the study by Joanne Wildenbeest and colleagues8Wildenbeest JG Billard M-N Zuurbier RP et al.The burden of respiratory syncytial virus in healthy term-born infants in Europe: a prospective birth cohort study.Lancet Respir Med. 2022; (published online Nov 10.)https://doi.org/10.1016/S2213-2600(22)00414-3Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar in this issue of The Lancet Respiratory Medicine, is an important contribution. As most hospitalised RSV-infected children are without known risk factors,9Hall CB Weinberg GA Blumkin AK et al.Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age.Pediatrics. 2013; 132: e341-e348Crossref PubMed Scopus (366) Google Scholar this prospective birth cohort study involving almost 10 000 participants in five sites in five different European countries, focused on determining the first year-of-life incidence of RSV-associated hospitalisations in healthy, term-born infants. In addition, the incidence of medically attended RSV infection was analysed in a nested cohort with active surveillance for RSV infection, to include the burden for primary care physician and outpatient settings. From the study it was calculated that one in 56 (incidence 1·8% [95% CI 1·6–2·1]) healthy babies is currently hospitalised for RSV, a finding that comes astonishingly close to observations made already in 1978 in north-east England.10Martin AJ Gardner PS McQuillin J Epidemiology of respiratory viral infection among paediatric inpatients over a six-year period in north-east England.Lancet. 1978; 2: 1035-1038Summary PubMed Scopus (108) Google Scholar The current, well designed and well performed study has major strengths being a large, multicentre, international, prospective observation with high follow-up rate and combining medical record review with parental questionnaires. In addition, RSV-positive cases were defined using PCR laboratory confirmation, and multiple imputation was used to estimate RSV status in cases with missed sampling (12·9% of the overall cohort). As such, the study provides further confidence to findings from previous, smaller epidemiological studies. In view of the promising finding from the MELODY trial that nirsevimab has a 74·5% efficacy in reducing medically attended RSV infection in healthy term-born infants,7Hammitt LL Dagan R Yuan Y et al.Nirsevimab for prevention of RSV in healthy late-preterm and term infants.N Engl J Med. 2022; 386: 837-846Crossref PubMed Scopus (112) Google Scholar an interesting observation from the study by Wildenbeest and colleagues is the 14·1% (95% CI 12·3–16·0) incidence of medically attended RSV infection in the active surveillance cohort, which is probably subject to modest underestimation based on selection bias of this convenience sample.8Wildenbeest JG Billard M-N Zuurbier RP et al.The burden of respiratory syncytial virus in healthy term-born infants in Europe: a prospective birth cohort study.Lancet Respir Med. 2022; (published online Nov 10.)https://doi.org/10.1016/S2213-2600(22)00414-3Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar This incidence is much higher than the 5·0% reported in the placebo arm of the MELODY study on this primary endpoint.7Hammitt LL Dagan R Yuan Y et al.Nirsevimab for prevention of RSV in healthy late-preterm and term infants.N Engl J Med. 2022; 386: 837-846Crossref PubMed Scopus (112) Google Scholar Evidently, both study cohorts cannot directly be compared as the study by Wildenbeest and colleagues included medically attended upper-respiratory in addition to lower-respiratory tract disease, and differences in geographical distribution exist. However, it is unclear whether the efficacy of nirsevimab might translate to even higher effectiveness in real-world settings with higher exposure to RSV and when addressing outcomes that also include the outpatient health-care burden associated with mild (upper airway) disease. By contrast, the study by Wildenbeest and colleagues8Wildenbeest JG Billard M-N Zuurbier RP et al.The burden of respiratory syncytial virus in healthy term-born infants in Europe: a prospective birth cohort study.Lancet Respir Med. 2022; (published online Nov 10.)https://doi.org/10.1016/S2213-2600(22)00414-3Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar confirms once more that the risk of RSV-induced hospitalisation peaks early, around age 1 month, which raises the question whether infant passive immunisation would be successful in reducing the inpatient health-care burden. In addition, important gaps in knowledge still exist regarding the attitude of parents towards both infant and maternal vaccination, which seems of particular relevance in the post-COVID era. Of note here, the MELODY trial evaluating nirsevimab was not powered to detect a difference in hospitalisation rate. As hospitalisation is the primary driver for RSV-associated infant and parental distress and medical costs, it remains to be seen whether the coming prevention programmes will indeed be able to offload the major health-care burden associated with RSV as identified by the study of Wildenbeest and colleagues. I declare no competing interests. The burden of respiratory syncytial virus in healthy term-born infants in Europe: a prospective birth cohort studyRSV-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. Full-Text PDF" @default.
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• W4308695951 title "Respiratory syncytial virus-induced disease in healthy infants: we need to offload this burden" @default.
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