Respiratory syncytial virus (RSV) in children: a new era

The World Health Organisation estimates that respiratory syncytial virus (RSV) accounts for more than 60% of acute respiratory infections in infants and young children worldwide.¹

Globally in 2019, there were approximately 33 million cases of acute lower respiratory infections leading to more than three million hospitalisations, and it was estimated that there were 26,300 in-hospital deaths of children younger than five years.²

Yet, there is no specific treatment suitable for general use, and treatment is aimed at supporting the patient and relieving symptoms, such as fluids and oxygen if needed. The most severe cases may need artificial ventilation (mechanical breathing support) in intensive care.

In the UK, RSV occurs regularly each year with epidemics generally starting in October lasting for over four months, peaking in December. The sharp winter peak varies little in timing or magnitude resulting in pressures on various parts of the healthcare system each year.³

During this period, there are around 467,000 visits to GPs and 34,000 hospitalisations each year in the UK due to children under five being ill with RSV.⁴

Recently, there has been a raft of promising new preventative measures introduced to the market. Amongst them is nirsevimab, which was recently granted marketing authorisation in the UK for the prevention of RSV lower respiratory tract disease in newborns and infants from birth through their first RSV season.

British Journal of Family Medicine talks to Dr Natalie Vassilouthis, Global Medical Lead RSV, Sanofi, about what the introduction of nirsevimab will mean for clinical practice.

What are the signs and symptoms of RSV?

“RSV is a very contagious virus that infects around 80% of children before their second birthday,” says Dr Natalie Vassilouthis. “Symptoms can be mild, such as a runny nose and cough, all the way up to severe respiratory tract disease requiring mechanical ventilation. In some unfortunate cases, RSV can lead to death. It crosses the entire spectrum of disease.

“It is a seasonal virus in temperate regions like the UK so tends to cause epidemic spikes in the winter months, but it is impossible to understand why some years are more severe than others. During the Covid-19 pandemic, the epidemiology altered because of non-pharmaceutical interventions such as the use of masks and social distancing, but last year we did see the predictable pattern of an annual epidemic.”

RSV is also very unpredictable. One in five children will need outpatient care by age two due to RSV and one in 50 infants will be hospitalised within the first year of life, but it is impossible to tell which child is at risk. In fact, 85% of infants admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection.⁵

“Having a young child with an illness, no matter how severe, is going to have an impact on the family. Not just in terms of work lost to look after the child, but also the psychological impact of having a child who is unwell. That is without taking into consideration the traumatic experience of having a baby that is hospitalised with a respiratory illness,” says Vassilouthis.

There is also the financial burden on families. A Sanofi sponsored survey in the UK found that almost two-thirds (63%) of parents are forced to miss an average of 11 days of work due to respiratory illnesses during an infant’s first year of life. This equates to an average loss of close to £1,800 per family.

Other research places the economic burden for parents and carers at about £14 million in lost productivity and £1.5 million in out-of-pocket costs.⁶

Respiratory syncytial virus and disease burden on the NHS?

RSV is a disease that has such a wide spectrum of presentation that there are several places where it puts a burden on the NHS. The total economic impact of RSV in children under five years in the UK is estimated to be around £80 million each year. The NHS in England spends around £54 million annually because of RSV-related lower respiratory tract infections in children under five. Of infants hospitalised with acute bronchiolitis, 60-80% will be caused by RSV, costing between £37-46 million, respectively.⁴

Most of the healthcare utilisation related to RSV in children less than five years is thought to occur in GP consultations in England. There are 21.42 GP consultations per 100 children less than six months. In terms of the hospitalisation, this figure is somewhere closer to 30,000 hospitalisations a year.⁷ Once hospitalised, infants may require supportive care such as supplemental oxygen, IV fluids, and upper airway suctioning.

“Healthcare professionals do all that they can to manage the annual crises. There is a lot of planning for the annual epidemics such as RSV and influenza,” says Vassilouthis. “One of the difficulties around RSV is that it is unpredictable and there is not a specific patient group who will be more affected. Public health strategies, therefore, must be population-wide to be able to prevent that burden on the healthcare system. It is impossible to be able to implement an individual strategy.

“One of the other challenges with RSV is that there is not any specific management. It is supportive measures only, such as oxygen supplementation or mechanical ventilation. Unfortunately, there is not much beyond this that we can offer for RSV at this stage.”

There are new preventative tools in the pipeline and a couple of options that have recently been approved or are close to approval. This includes nirsevimab, which is a long-acting antibody designed for all infants for protection against RSV disease from birth through their first RSV season with a single dose.

It has been developed to offer newborns and infants direct RSV protection via an antibody to help prevent medically attended lower respiratory tract infections caused by RSV. Monoclonal antibodies do not require the activation of the immune system to help offer timely, rapid and direct protection against the disease.⁸

“We are in dialogue with healthcare authorities across the world sharing data from our recent HARMONIE trial to help support the decision-making process for the 2023-24 RSV season,” Vassilouthis says.

What is the HARMONIE trial

The HARMONIE trial⁹ showed that nirsevimab reduced the incidence of hospitalisations due to very severe RSV-related lower respiratory tract disease by 75.4% compared to infants who received no RSV intervention.

Additionally, nirsevimab demonstrated a reduction of 58.04% in the incidence of all-cause lower respiratory tract disease hospitalisation compared to infants who received no RSV intervention.

She says she hopes this will have a potential public health benefit and reduce the strain on hospitals caused each year by RSV. “The trial was designed to replicate a real-life environment. So, we recruited any infant under the age of 12 months coming into their first RSV season that was not eligible for palivizumab (which is a preventative antibody for very high-risk babies).

“We recruited all infants that fell into that category if they were born after 29 weeks of gestational age. Recruitment took place across primary and secondary care depending on where they presented to the healthcare system.”

What is the most important thing healthcare professionals should know?

She adds that it is important for healthcare professionals to know that RSV is the leading cause of lower respiratory tract infection in all infants, and it causes an annual predictable burden on the healthcare system, both in primary care and secondary care.

“But we are now moving into a phase where there are several preventative measures on the horizon. By mitigating the impact that RSV has every year on the NHS, the freed-up capacity could be used to manage other conditions in healthcare,” she says.

“We are lucky that the mortality rate of RSV disease remains low in the UK due to excellent supportive care. But there are unfortunate cases each year where babies end up dying from RSV disease. Now as we move into the 2023 season, we hope that at a public health level, RSV disease becomes preventable.”

Key statistics about RSV

The World Health Organization estimates that RSV accounts for more than 60% of acute respiratory infections in infants and young children worldwide.
Of infants and young children hospitalised with acute bronchiolitis, 60% – 80% will be caused by RSV.
The economic burden for parents and carers is estimated at about £14 million in lost productivity and £1.5 million in out-of-pocket costs.
The total economic impact of RSV in children under 5 in the UK is estimated to be around £80 million each year.
The NHS in England spends around £54 million annually as a result of RSV-related lower respiratory tract infections (LRTI) in children under five.
Of infants hospitalised with acute bronchiolitis, 60% – 80% will be caused by RSV, costing between £37-£46 m respectively.

Disclaimer: Sanofi responded to the interview request and checked the article for factual accuracy only. Sanofi had no editorial control over the content.

References

Piedimonte G, Perez MK. Respiratory syncytial virus infection and bronchiolitis. Pediatr Rev. 2014 Dec;35(12):519-30. doi: 10.1542/pir.35-12-519.
Li Y, 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;399:92047–64.
https://www.gov.uk/government/publications/respiratory-syncytial-virus-rsv-symptoms-transmission-prevention-treatment/respiratory-syncytial-virus-rsv-symptoms-transmission-prevention-treatment
Fusco F, Hocking L, Stockwell S, Bonsu M, Marjanovic S, Morris S, Sussex J. The Burden of Respiratory Syncytial Virus: Understanding Impacts on the NHS, Society and Economy. Rand Health Q. 2022 Nov 14;10(1):2. PMID: 36484078; PMCID: PMC9718057
Murray J, Bottle A, Sharland M, Modi N, Aylin P, Majeed A, Saxena S; Medicines for Neonates Investigator Group. Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study. PLoS One. 2014 Feb 26;9(2):e89186. doi: 10.1371/journal.pone.0089186. PMID: 24586581; PMCID: PMC3935842.
https://www.rand.org/randeurope/research/projects/impact-of-respiratory-syncytial-virus.html
Wilkinson T, Beaver S, Macartney M, McArthur E, Yadav V, Lied-Lied A. Burden of respiratory syncytial virus in adults in the United Kingdom: A systematic literature review and gap analysis. Influenza Other Respir Viruses. 2023 Sep 21;17(9):e13188. doi: 10.1111/irv.13188. PMID: 37744994; PMCID: PMC10511839.
Centers for Disease Control and Prevention. Vaccines & Immunizations. August 18, 2017. https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm. Accessed May 2023.
Drysdale S, et al. Efficacy of nirsevimab against RSV lower respiratory tract infection hospitalization in infants: preliminary data from the HARMONIE phase 3b trial. Presented at 41st Annual Meeting of the European Society for Paediatric Infectious Diseases in Lisbon, 2023.