Introduction
Respiratory syncytial virus (RSV) is a seasonal respiratory virus that, while able to cause infection throughout life,1 is a leading cause of childhood lower respiratory tract infections (RTIs).2–4 In Northern hemisphere countries, prior to the COVID-19 pandemic,5–7 RSV typically occurred in epidemics each winter,8 9 causing bronchiolitis, an inflammatory condition of the small airways, as well as ‘colds’, croup and pneumonia. RSV-associated RTI is a leading cause of hospitalisation among infants within the UK10 and is responsible for up to 10% of paediatric intensive care unit (PICU) admissions.11 The median duration of stay for children hospitalised with bronchiolitis is 66 hours (IQR: 38–99), but can be prolonged in those with severe disease.12 Very young children, those with underlying conditions and premature children13 14 have higher rates of mortality and morbidity from RSV infection.
Diagnosis of bronchiolitis is typically clinical,15 relying on history and clinical examination, with clinical features including coryza, breathing difficulties, cough and crepitations on auscultation.15 16 RSV may be identified as a causative pathogen through PCR testing; within the UK, however, these tests are rarely used for children treated within the community. Even within UK hospitals, systematic screening for causative organisms for RTIs is often not routinely performed outside of peak viral seasons.17
Given RSV is an RNA virus, samples need to be processed as soon as possible or stored at −80°C to prevent degradation, again limiting community or hospital testing. Multiple sampling methodologies are available, including nasopharyngeal aspiration (NPA) and nasal swabbing (NS). Existing studies are conflicted on the sensitivity and reliability of NS-based PCR compared with NPA,18–24 but NS is associated with reduced infant distress and increased acceptability to parents/carers22 and is currently the clinical standard among many paediatric units within the UK.
Many other pathogens can also cause bronchiolitis or exist as a co-infection with RSV,25–28 with a viral co-infection rate of approximately 6%.2 RSV is also associated with a higher incidence of co-infection with Streptococcus pneumoniae (Spn),16 29 and recent studies have demonstrated RSV is able to augment bacterial growth and density in Spn co-infection.30 31 Data on co-infection in paediatric RTIs are limited within the UK, as are data on circulation of RSV outside the typical RSV season.
Similarly, data on RSV-associated RTI and associated economic costs in the UK outside a hospital setting are scarce, largely due to a lack of systematic testing with sensitive, wide-spectrum PCR assays, which are costly and difficult to implement on a large scale. To our knowledge, only three studies have been published exploring the socioeconomic burden of RSV within primary care—two outside of the UK32 33 and one within the UK that was significantly limited by the COVID-19 pandemic.34
Currently, the only approved preventative therapies for RSV-associated RTI within the UK are monoclonal antibodies (mAbs), which may be classed as a ‘passive vaccine’. Two are currently available: palivizumab and nirsevimab. Palivizumab is an mAb that binds to and inactivates the fusion glycoprotein on the surface of RSV, preventing entry into cells.35 36 A recent meta-analysis demonstrated reduced risk of hospitalisation due to RSV infection (risk ratio 0.44, 95% CI 0.30 to 0.64),37 and palivizumab has been shown to be cost-effective in certain groups.38 39 Within the UK, it is only available for children considered at high risk of severe disease, for example, children with congenital heart disease. It is administered to children at highest risk of severe disease as an injection each month of the RSV season and costs around £5000 per child per season. Nirsevimab, which was recently approved for use in the UK,40 also binds to the fusion glycoprotein, but has a longer half-life, requiring once-off administration as opposed to monthly. Recent studies have demonstrated efficacy in reducing medically attended RSV infection, with a relative risk reduction of 79.5% (95% CI 65.9 to 87.7).41–44 Further large-scale studies into use of nirsevimab are ongoing, and as of yet the UK has not released guidance on its use; however, given the reduction in dosing requirements, it is hoped that nirsevimab may prove a more attractive option for wide-scale clinical use than palivizumab.45
Development of a novel RSV vaccination has been a public health goal for many decades, and there are currently a raft of potential candidates in development with a range of mechanisms of action.46 At the time of writing, only four candidates for paediatric vaccines have reached phase II trials, with none in phase III development. Similarly a maternal vaccine, conferring immunity in early infancy through trans-placental antibody transfer, may be a potential preventative option in the future,47 provided it is cost-effective.48 An improved understanding of RSV Protein F49 has provided a potential candidate for a maternal vaccine (NCT04424316) developed by Pfizer, which is currently undergoing phase III trials. As of yet, however, no maternal, adult or paediatric RSV vaccines are commercially available.
Given the increasing speed of development of preventative treatments for RSV, accurate and granular data on the burden of RSV disease in both hospitals and primary care are needed to inform public health policies and immunisation programmes for these vaccines.
Here, we describe our observational study of incidence of laboratory-confirmed RSV-associated RTI within primary, secondary and tertiary healthcare settings in Merseyside, Cheshire and Bristol. We aim to collect data on the incidence of RSV and other pathogens (including Spn carriage) in patients presenting to healthcare settings with RTI from December 2021 to March 2023, encompassing two UK winter periods and the intervening months. We will also gather information on health economic and quality of life (QoL) burden that RSV-associated RTI has on parents/carers, families and healthcare settings. These data will be used to help inform the discussion around future prevention strategies for RSV.