Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is a common virus that can infect people of all ages. It is highly contagious, and it is thought that almost all children will be infected with RSV by two years of age. While RSV can cause a range of respiratory conditions, it typically presents as a mild cold. However, it can cause severe illness in infants, young children, and older adults.

Infection with RSV can develop into pneumonia. In infants, RSV is a significant cause of morbidity and mortality and the main pathogen responsible for bronchiolitis. Studies demonstrate that RSV bronchiolitis has a more severe clinical course than non-RSV bronchiolitis in children. The duration of hospitalisation tends to be longer, and there is an increased need for supplemental oxygen, admission to paediatric intensive care units, and mechanical ventilation. There is also some evidence to suggest that a lower respiratory tract infection (LRTI) with RSV in early childhood is associated with ongoing morbidity, including asthma and impaired lung function.

The incidence of RSV varies throughout the year. In most temperate regions of Australia, outbreaks tend to occur during autumn and winter, with a peak in June and July. Seasonality is often less distinct in tropical parts of the country but may coincide with rainy seasons.

Three new preventative medicines have recently become available in Australia: two vaccines and one monoclonal antibody. As RSV is most likely to be serious in the very young and older adults, preventative therapies focus on these populations.

Vaccines

There are two RSV vaccines available: Arexvy® and Abrysvo®. These are both non-live vaccines containing protein subunits that target the pre-fusion F protein. This protein is highly conserved among different RSV strains and has a vital role in viral entry, making it an ideal vaccine target. Abrysvo® is a bivalent vaccine containing antigens from both RSV subgroup A and subgroup B. Arexvy® is a single valent vaccine but contains an adjuvant to improve immunogenicity.

Both vaccines are indicated for use in patients 60 years of age and older to prevent lower respiratory tract disease caused by RSV. There is no brand preference in this population and either product can be used. Vaccination can occur at any time of year, but preferably before the start of the RSV season.

Abrysvo® is also indicated for active immunisation of pregnant women for the prevention of RSV disease in infants from birth to six months of age. The Australian Technical Advisory Group on Immunisation (ATAGI) recommends that administration occur between 28 and 36 weeks of gestation. If the vaccine is not administered before 36 weeks gestation, it may be given as soon as possible. However, adequate protection may not develop in the newborn if given less than two weeks before delivery. Studies demonstrate that maternal immunisation reduces the risk of severe RSV disease in infants less than six months of age by around 70%. The pregnant woman may also receive protection, although studies have not evaluated this as RSV disease is typically mild in women of childbearing age. Arexvy® is not recommended for use during pregnancy.

The Australian Immunisation Handbook recommendations for RSV vaccination are summarised below:

• Adults ≥ 75 years
  • Single dose of Arexvy® or Abrysvo® recommended
• 60-64 years (no risk factors for severe RSV disease)
  • Single dose of Arexvy® or Abrysvo® may be considered
  • This age group has a lower risk of severe RSV disease than people ≥ 75 years; therefore, the benefits may be lower.
• Aboriginal and Torres Strait Islander people
  • Single dose of Arexvy® or Abrysvo® recommended for those ≥ 60 years
• People with risk factors for severe RSV disease
  • Single dose of Arexvy® or Abrysvo® recommended for those ≥ 60 years
  • Risk factors include some cardiac conditions, chronic respiratory conditions, immunocompromising conditions, chronic metabolic conditions, chronic kidney disease (stage 4 or 5), chronic neurological conditions, and obesity (BMI ≥ 30).
• Pregnancy and lactation
  • Single dose of Abrysvo® recommended at 28-36 weeks gestation
  • Not recommended during lactation as there is no evidence that vaccination would protect the infant via breastfeeding alone.

Both Arexvy® and Abrysvo® are only indicated for administration to adults. When administered during pregnancy, Abrysvo® protects infants via passive immunity. There are currently no vaccines available for infants that provide active immunity against RSV.

Nirsevimab

Nirsevimab is a new long-acting monoclonal antibody that is specific for the RSV F protein. This medication is also a form of passive immunity, providing antibodies that neutralise the virus and block cell-to-cell function. Nirsevimab is indicated for the prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.

The Australian Immunisation Handbook recommends its administration in the following cases:

• Infants born to women who did not receive the RSV vaccine during pregnancy or where the vaccine was administered within two weeks of delivery;
• Infants with a condition that increases the risk of severe RSV disease (regardless of maternal vaccination). Risk factors include;
  • Preterm birth <32 weeks gestational age
  • Haemodynamically significant congenital heart disease
  • Significant immunosuppression
  • Chronic lung disease requiring ongoing oxygen or respiratory support
  • Neurological conditions that impair respiratory function
  • Cystic fibrosis with severe lung disease or weight for length <10^th percentile
  • Genetic condition that increases the risk of severe RSV disease (e.g. Trisomy 21)
• Infants born to mothers with a severe immunocompromising condition that may have impaired the maternal response to the RSV vaccine; and
• Infants born to mothers who received the RSV vaccine but subsequently underwent a treatment causing loss of maternal antibodies (e.g. cardiopulmonary bypass or extracorporeal membrane oxygenation).

A pooled analysis of randomised controlled trials demonstrates consistent efficacy across disease severity over the 150 days following a dose. A single nirsevimab dose was associated with a relative risk reduction of 79.5% for medically attended RSV LRTI and 86.0% for very severe RSV LRTI. The efficacy of nirsevimab is likely to be greatest when administered soon after birth for infants born just before or during the RSV season. For infants born outside of the RSV season, it is recommended to administer nirsevimab once before the start of the RSV season.

Nirsevimab is administered as an intramuscular injection. For neonates and infants born during or entering the RSV season, the usual recommended dose is a single injection (50mg for patients weighing less than 5kg and 100mg for patients weighing 5kg or more). There is no clinical data for infants with a body weight of less than 1kg or a postmenstrual age of less than 32 weeks. For children up to 24 months of age who remain at increased risk of severe RSV disease in their second RSV season, a single 200mg dose is recommended.

Nirsevimab is currently only available through state-managed programs in New South Wales, Queensland, and Western Australia. The National Centre for Immunisation Research and Surveillance Australia regularly updates its website with details of current availability.

Palivizumab

Palivizumab is another monoclonal antibody that neutralises RSV. This is an older medication that was first approved in Australia in 2015.

Like nirsevimab, palvizumab also provides passive immunity. It is indicated for the prevention of serious lower respiratory tract disease caused by RSV in children at high risk. However, unlike nirsevimab, palvizumab is a short-acting agent and must be administered monthly to maintain protection. It is given as an intramuscular injection with a recommended dose of 15mg/kg. Patients may receive up to five monthly doses during the RSV season.

Compared to placebo, palivizumab is associated with a relative risk reduction of 49% for RSV hospitalisation. Nirsevimab is generally preferred over palivizumab due to its longer duration of action. However, palivizumab is recommended where nirsevimab is not available.

A summary of RSV preventative therapies is shown in Table 1.

Table 1. Summary of RSV preventative therapies

Additional considerations:

While infants receive specific anti-RSV antibodies prior to birth via transplacental transfer, breastfeeding provides continuing transfer after birth. One study demonstrates that breastfeeding halves the risk of hospitalisation for RSV bronchiolitis during the first 12 months of life in moderately preterm infants. This finding is supported by many other studies that demonstrate the importance of breastfeeding in the prevention of RSV.

Hygiene is also an important consideration to reduce exposure to RSV. As RSV can be transmitted via direct and indirect contact with infectious droplets, hand hygiene and avoiding crowded places may be useful strategies. Interestingly, considerable data shows that the public health measures introduced during the COVID-19 pandemic may have significantly reduced the incidence of RSV disease.

Multiple studies demonstrate the negative impact of passive smoking on the frequency and severity of LRTI. Avoiding exposure to cigarette smoke should also form part of RSV prevention strategies.