Respiratory syncytial virus (RSV), is a common viral respiratory illness. It primarily affects children, with nearly all children contracting it by two years old. However, it can occur at any age, and may cause severe disease in the elderly. In infants, young children and the elderly, RSV infection may lead to lower respiratory tract infection (LRTI), such as bronchiolitis or pneumonia. In older children and otherwise healthy adults it more commonly manifests as a mild upper respiratory tract infection.
Signs and symptoms of RSV include the following:
| Non-specific features of viral illness | Features of upper respiratory tract illness | Features of lower respiratory tract illness |
| Fever (≥ 38°C); Lethargy; Irritability; and Decreased appetite. | Runny nose; and Ear infection. | Cough; and Wheeze. |
Signs of severe RSV infection include any signs of respiratory distress such as shortness of breath, increased breathing rate and any signs of increased work of breathing including nasal flaring, grunting, accessory respiratory muscle use or intercostal/subcostal recessions. While most children hospitalised due to RSV infection are otherwise healthy, with no pre-existing medical conditions, risk factors for severe RSV infection include:
| Age | Comorbidities | Environmental factors |
| < Six months; and ≥ 60 years. | Pre-term birth; Congenital heart disease; Immunocompromised state; and Reduced functional capacity or frailty. | Creche; Long-term care facility; and Tobacco smoke exposure. |
RSV is transmitted directly via contact with respiratory droplets (coughing/sneezing) and indirectly via contact with contaminated surfaces. The onset of symptoms after RSV infection typically occurs within two to eight days. Infection with RSV does not confer life-long immunity. Re-infection may occur throughout life and is common in all age groups.
RSV has a seasonal distribution, with incidence peaking in winter and early spring. Typically, the highest numbers of cases occur in December and January. Since the COVID-19 pandemic however, RSV has begun to circulate earlier, with onset in early October in the 2021/22 and 2022/23 seasons. This trend was seen in Ireland and internationally.
RSV has been a notifiable disease in Ireland since January 2012. Detailed information on the epidemiology of RSV in Ireland can be found on the HPSC Respiratory Virus Notification Data Hub (respiratoryvirus.hpsc.ie). Cases of RSV may be under-reported as it is primarily a clinical diagnosis. Confirmatory testing is conducted if indicated. In young children a rapid nasopharyngeal swab is the investigation of choice.
In 2022, almost 4,000 children in Ireland aged nought to four years tested positive for RSV. Of these, nearly 2,500 were admitted to hospital. Most of these admissions, and almost all ICU admissions, occurred in children under one year of age. In terms of the older population, just over 1,500 adults aged 65 years and older tested positive for RSV in 2022. Of these, nearly 150 were admitted to hospital. As the majority of admissions occur during the RSV season, there is increased pressure on hospitals during this time.
Complications of RSV include bronchiolitis, pneumonia, superimposed bacterial infections, respiratory distress, exacerbation of chronic conditions such as asthma or chronic obstructive pulmonary disease, and hospitalisation. In infants, RSV is the most common cause of bronchiolitis and pneumonia.
The management of RSV infection is dependent on the presentation and severity of disease. The majority of those infected with RSV can be managed with supportive treatment. Adequate fluid intake should be ensured whilst antipyretics and gentle nasal suctioning can be used if indicated. Hospitalisation is indicated when there are any signs of respiratory distress as previously outlined, or for dehydration. Supplemental oxygen may be indicated for persistent hypoxaemia, while administration of IV fluids might be required for dehydration.
Ribavirin is an antiviral agent that is licensed for the treatment of RSV infection in some member states of the EU and in the United States. It is not currently licensed in Ireland and it is not currently recommended by EU or US guidelines for the routine treatment of RSV. This is due to the inconsistent evidence for the efficacy of ribavirin for treatment of RSV, its side-effect profile, its cost profile, and the complexity of its delivery system.
Primary prevention measures for RSV infection can be stratified into general measures for prevention, active immunisation, and passive immunisation. The characterisation of the RSV fusion glycoprotein (F protein) has resulted in the development of a number of vaccines and monoclonal antibody therapies for the prevention of RSV.
General measures for the prevention of transmission of RSV at home include frequent and careful handwashing, good respiratory etiquette, and cleaning of contaminated surfaces such as door handles. Infected individuals should be excluded from childcare, school and work until they are well.
Active immunisation is achieved with vaccination against RSV. It involves inducing the body’s immune system to produce antibodies and/or cell mediated immunity to protect against infection. The first RSV vaccines were approved by the European Medicines Agency (EMA) in 2023. These include ‘RSVPreF3’ (Arexvy, GlaxoSmithKline) and ‘RSVpreF’ (Abrysvo, Pfizer). Both agents are licensed for the vaccination against RSV in adults ≥ 60 years. RSVpreF (Abrysvo) is also licensed for vaccination of pregnant women, in order to provide the passive protection of infants, which is detailed further below. Both vaccines are administered intramuscularly.
Passive immunisation is the provision of rapid, temporary protection against infection with administration of exogenously produced antibodies. For RSV, monoclonal antibodies targeting the RSV fusion (F) protein may be used for passive immunisation. Two such monoclonal antibodies are available: ‘Palivizumab’ (Synagis), Astra Zeneca) and ‘nirsevimab’ (Beyfortus), Sanofi). Palivizumab (Synagis) was approved by the EMA in 1999, while nirsevimab (Beyfortus) was approved by the EMA in 2022. Passive immunisation of infants can also be achieved by maternal vaccination with RSVpreF (Abrysvo), as a result of transplacental antibody transfer.
Palivizumab is a humanised monoclonal antibody licensed for passive immunisation against RSV in high-risk children, including ex-premature infants, children with chronic lung disease of prematurity, and children with haemodynamically-significant congenital heart disease. It is administered once monthly, as an intramuscular injection, during the RSV season. The first dose is given prior to the start of the RSV season, while subsequent monthly doses are administered throughout the season at 28-32 day intervals.
Nirsevimab is a long-acting recombinant human monoclonal antibody licensed for the passive immunisation of neonates and infants in their first RSV season, for the prevention of RSV-associated LRTI. It is administered as a single intramuscular injection prior to the start of the RSV season, or from birth if the infant is born during the RSV season. The duration of protection given by nirsevimab is a minimum of five months, based on clinical and pharmacokinetic data. The EMA is currently reviewing an extension of the indication to include a second RSV season.
Maternal vaccination with RSVpreF (Abrysvo) protects infants, from birth to six months of age, against RSV-associated LRTI. It confers passive immunisation to the infant by transplacental antibody transfer. When administered in pregnancy, RSVpreF should be given as a single dose between week 24 to 36 of gestation.
The Minister for Health, on 18 June 2024, announced the implementation of an infant RSV Immunisation Pathfinder Programme. Under this programme, all newborn infants from 1 September 2024 to February 2025 will be eligible for administration of nirsevimab (Beyfortus). This is a temporary, publicly funded pilot programme. The aim of such a pathfinder initiative is to explore approaches to improve health outcomes in a community or population.
Since 1 September 2024, administration of nirsevimab has been recommended for all newborn babies before discharge home from the maternity hospital to protect them from RSV infection in the first days and weeks of life, when the risk of serious outcomes is at its greatest. One dose of nirsevimab will provide protection to the infant for 150 days. It is administered as an intramuscular injection and can be given from birth. As part of the RSV Pathfinder Programme, pregnant women are provided with written and verbal information on the RSV immunisation programme at their antenatal clinics and soon after birth of their baby. It is estimated that 28,000 infants will receive immunisation against RSV in the 2024-25 RSV season.
This administration of nirsevimab to newborn infants will not interfere with the infants’ immune response to vaccines in the current immunisation schedule, as nirsevimab is a form of passive antibody immunisation. Therefore, it can be co-administered with any primary childhood immunisation. Newborn babies who receive nirsevimab from hospitals soon after birth can commence the normal course of vaccinations that start at two months of age.
The use of nirsevimab has been recommended for this interim immunisation programme over maternal vaccination with RSVpreF (Abrysvo), due to the increased availability of real-world safety, efficacy and acceptability data for nirsevimab, compared to RSVpreF (Abrysvo). Further trial data on both of these agents is provided below. The National Immunisation Advisory Committee (NIAC) stated that direct comparisons could not be drawn in terms of the efficacy of both agents due to differences in trial designs and outcomes. Palivizumab is not considered a suitable agent due to the requirement for multiple administrations and its associated cost.
In addition to the pathfinder programme, from 1 September 2024 nirsevimab will be administered to high-risk babies who were previously eligible for Palivizumab (Synagis). This switch over has been recommended by NIAC.
In the longer term, it remains to be seen what immunisation strategy will be adopted in Ireland for the prevention of RSV in both infants and older adults.
The Health Information and Quality Authority (HIQA) published a ‘rapid Health Technology Assessment (HTA) of immunisation against RSV in Ireland’ on 13 August 2024. This assessment focused in particular on the one-year costs of various immunisation strategies for infants <one year and adults ≥65 years for the 2025 – 2026 RSV season. It looked at three nirsevimab-based strategies for the general infant population and four strategies for the seasonal vaccination of older adults. It was found that the estimated one-year cost for immunisation of infants in their first RSV season ranged from €9.3 to €19 million, depending on the strategy used. The estimated one-year cost for immunisation of adults ≥65 years was €146 million, while for immunisation of adults ≥75 years was €76.2 million. Estimated hospital cost offsets were considerably higher for infants compared to older adults. In addition to the above costs, it was estimated the cost of implementing a new RSV immunisation programme for the HSE’s National Immunisation Office would be €2.3 million.
The rapid HTA has been submitted to the Minister for Health and the HSE to advise on an interim policy decision on RSV immunisation for the 2025 – 2026 RSV season. The Department of Health has requested that HIQA conduct a full HTA to inform on longer-term policy decisions concerning RSV immunisation in Ireland.
The authorisation for nirsevimab was granted by the EMA based on data from three clinical trials: the MEDLEY trial, D5290C00003, and the MELODY trial.
Both D5290C00003 (phase 2b) and MELODY (phase 3) trials, two randomised, double-blind, placebo-controlled multicentre trials, evaluated the safety and efficacy of nirsevimab for the prevention of RSV-associated LRTI in term and pre-term infants. The primary end point of both trials was the incidence of medically attended RSV-associated LRTI, while the secondary endpoint for both was the hospitalisation for RSV-associated LRTI through 150 days post-administration of the dose.
D5290C00003 was conducted in healthy preterm infants between 29-35 weeks gestation. These infants were randomised in a 2:1 ratio to receive nirsevimab (n=969) or placebo (n=484). The incidence of medically attended RSV-associated LRTI was 70 per cent lower with nirsevimab compared to the placebo, while the incidence of hospitalisation was 78 per cent lower with nirsevimab.
The MELODY trial was conducted in term and late preterm infants, born after 35 weeks’ gestation. The infants were randomised in a 2:1 ratio to receive nirsevimab (n=994) or placebo (n=496). The incidence of medically attended RSV-associated LRTI was 75 per cent lower with nirsevimab compared to the placebo, while the incidence of hospitalisation was 62 per cent lower with nirsevimab.
The MEDLEY trial, a phase 2/3 randomised, double-blind, pavlivizumab-controlled multicentre trial, assessed the safety and pharmacokinetics of niresevimab in infants at risk of severe RSV-associated LRTI, who were eligible to receive palivizumab. The infants were randomised to receive nirsevimab (n=616) or palivizumab (n=309). The safety and side effect profiles between both groups were shown to be similar in terms of frequency, severity and type of adverse event.
The HARMONIE trial, a phase 3b clinical trial was reported in December 2023. This trial was conducted in infants under one year, born after 29 weeks gestation, who were entering their first RSV season. The primary endpoint was hospitalisation for RSV-associated LRTI while the secondary endpoint was very severe RSV-associated LRTI, defined as hospitalisation for RSV-associated LRTI with O2 saturation of <90 per cent and the need for supplemental oxygen. The infants were randomised to receive nirsevimab (n=4037) or standard care (n=4021). The incidence of hospitalisation for RSV-associated LRTI was 83 per cent lower for nirsevimab compared to standard care, while very severe RSV-associated LRTI was 76 per cent lower in the nirsevimab arm compared to standard care.
The NIRSE-GAL study, a three-year longitudinal population-based study, reported preliminary data in April 2024, based on three months of nirsevimab use. This study is based in the Galicia region in Spain, one of the first regions to include universal nirsevimab administration into its immunisation programme. The interim analysis, based on administration from September to December 2023, showed a 92 per cent uptake, with 9,408 of 10,259 eligible infants receiving nirsevimab. The efficacy of nirsevimab against RSV-associated LRTI hospitalisation was 82 per cent, while the efficacy against severe RSV-associated LRTI requiring supplemental oxygen was 87 per cent.
The authorisation for passive immunisation of infants with maternal vaccination with RSVpreF was granted by the EMA in August 2023 on the back of the results of the MATISSE study, a phase three clinical trial. This double-blind trial was conducted on 7,358 pregnant women in 18 countries over four RSV seasons. These women were randomly assigned, in a 1:1 ratio, to receive a single intramuscular injection of RSVpreF or a placebo, from 24-36 weeks gestation. The primary efficacy endpoints in the study were medically attended RSV-associated LRTI and medically attended severe RSV-associated LRTI. Efficacy was shown to be greater against increasingly severe disease and was shown to decrease from time of birth. For medically attended RSV-associated LRTI, the efficacy of RSVpreF was 57 per cent at 90 days after birth, which declined to 51 per cent by 180 days. For medically attended severe RSV-associated LRTI, the efficacy of RSVpreF was 82 per cent at 90 days after birth, declining to 69 per cent at 180 days.
You can find more information on RSV in Chapter 18a: Respiratory Syncytial Virus of the Immunisation Guidelines for Ireland (available at rcpi.ie > Healthcare Leadership > NIAC > Immunisation Guidelines for Ireland).
Further information on the infant RSV Pathfinder Programme is available on the HSE website and the website of the Health Protection Surveillance Centre (available at hpsc.ie > a-z > respiratory > respiratorysyncytialvirus > immunisation).
References available on request.
Highlighted Articles
