Overview

Respiratory syncytial (sin-SISH-uh) virus (RSV) is a common virus that infects the lungs and airways, so common in fact that one study suggests that almost all infants will have been infected by age 2.¹ RSV is a leading cause of acute lower respiratory tract infection in infants, with a prevalence of 46% in Europe.² RSV has similar clinical manifestations in infants as other common respiratory viruses, such as influenza, and is also seasonal, with a peak in January/February. The most common presentations of RSV infection are pneumonia or bronchiolitis, the latter of which causes 2.4% of infants to be hospitalised annually.³ It is estimated that RSV accounts for between 94,600 and 149,400 infant deaths worldwide every year, and can also have lasting effects in terms of developmental delays, particularly in the respiratory system.⁴ 

RSV infection in infants has been related to an increased incidence of asthma and recurrent wheezing in later childhood.⁵ Additionally, research now shows that maternal infection during pregnancy can cause neurological and respiratory developmental delays in the infant.⁶ 

Symptoms of RSV in infants

In mild cases of RSV infection, symptoms include:

• Congestion
• Fever
• Dry cough
• Sore throat
• Sneezing

In severe cases, infants will also show some/all of the following symptoms:

• Short, shallow or rapid breathing, or appearing to struggle to breathe
• Persistent cough
• Reduced feeding
• Increased tiredness
• Irritability 
• Skin that appears bluish

Complications and high-risk groups

For most infants, RSV infection will be mild and unlikely to result in hospitalisation. However, certain risk factors increase the chance of a more severe infection requiring a hospital stay. These include:

• Premature birth
• Immunosuppressed individuals
• Malnutrition
• Inborn errors of metabolism 
• Pre-existing health conditions such as chronic lung diseases ⁷

These risk factors all increase the likelihood of a more severe RSV infection as they each contribute to an impaired immune system. All of these risk factors were found to result in increased incidence of admission to ICU, requirement for mechanical ventilation, longer hospital stays, and even death.⁸ However, these complications are not only found in the high-risk groups, in fact, as many as 75% of infant RSV hospitalisations are infants with no pre-existing health conditions that were born at term.⁹ 

RSV transmission in infants

As RSV is a respiratory virus, it spreads most commonly through droplets, released when an infected person sneezes, coughs, speaks, or exhales. This can cause infection by direct contact with these droplets, droplets in the air, or indirectly by landing on surfaces. RSV can survive on different surfaces for varying durations, which is why it is important that we cover our nose and mouth when coughing and sneezing, and clean any surfaces that may be exposed to such droplets.¹⁰ 

The ease at which RSV can spread accounts for its high incidence. The R₀, which means the average number of people one infected person will go on to infect, is estimated at 3, potentially increasing to 5 in the colder winter months.¹¹ This number may be even higher in infants, particularly in childcare settings. One study has shown that RSV spreads very quickly through children in daycare, in fact within 6 days of the first positive case 50% of the other children tested positive for RSV.¹² 

Evidence shows that the transmission of RSV also occurs between the mother and the developing foetus. RSV can infect different cell types within the placenta, allowing it to cross the placenta and infect the fetal lungs.¹³ 

How RSV might cause developmental delays

Respiratory delays

RSV infection resulting in hospitalisation has been associated with recurrent wheezing in later childhood as well as allergic asthma in adolescence.¹⁴ It is currently unknown exactly how RSV infection is related to subsequent respiratory conditions, whether RSV directly increases the risk of asthma or perhaps a third factor is responsible for both a more severe reaction to RSV and the development of asthma/recurrent wheezing. Very early bronchiolitis has been shown to disrupt early lung development, which could result in smaller lungs that are more vulnerable to disease, potentially explaining the association between RSV-related hospitalisation and late redevelopment of asthma or wheezing.¹⁵ 

RSV infection of the foetus via the mother can disrupt neurotrophic pathways during development. These neurotrophic pathways are responsible for ensuring that developing neurons target and connect to the appropriate tissues/cells correctly. It is suggested that in utero RSV infection interferes with this, particularly in the developing lungs, resulting in atypical innervation of the airways.¹⁶ When this is combined with reinfection with RSV postnatally, the immune response is hyperactive, leading to more severe symptoms and hospitalisation.¹⁷

Neurological delays

As mentioned previously, RSV can infect various types of cells, not just those in the respiratory system. The genetic material of RSV has been found in the cerebral-spinal fluid (CSF), which is the liquid surrounding and protecting the brain and spinal cord.¹⁸ RSV was also found in several different parts of the brain, including the hippocampus, the region associated with learning and memory.¹⁹ The developmental impacts of this may include learning impairments, such as reduced school readiness by age 5.²⁰ Language acquisition, as measured by responsiveness to native and nonnative sounds at ages 6 and 12 months, was found to be diminished in infants that had been infected with RSV. This is an important developmental event, and this impairment suggests potential long-term problems with learning and memory following RSV infection.²¹ The exact mechanism behind this is unclear and requires further research. 

There is a barrier between the brain and the blood to protect the brain by stopping harmful toxins from entering, as well as delivering nutrients. This blood-brain barrier increases in permeability in response to RSV infection, allowing immune cells and cytokines (proteins released by immune cells) to enter the brain, resulting in encephalitis. This inflammatory environment in the developing brain is a likely mechanism by which RSV causes neurodevelopmental delays.^22,23

Preventing and treating RSV

Treatment for RSV

For most infants, RSV infection will not require a hospital stay and can be managed at home by making sure the infant is hydrated and comfortable. Keeping the infant upright when awake and using saline drops may help reduce nasal congestion. Additionally, children's paracetamol may be given to infants over 2 months and children’s ibuprofen to those over 3 months, to ease any pain or discomfort.²⁴  However, should the infection progress to more severe bronchiolitis, an infant may require hospital care in the form of oxygen, IV fluids, mechanical ventilation, and tube feeding. This is most common in infants younger than 6 months.²⁵

Preventing RSV

As with all respiratory viruses, maintaining good hygiene is vital in reducing the spread of RSV infection. This includes covering the mouth and nose when sneezing or coughing, frequent hand washing, immediately discarding used tissues, regularly cleaning potentially contaminated surfaces, and staying away from other people when you are unwell. People experiencing cold or flu-like symptoms must stay away from newborn babies.^24,25

Vaccines for RSV

There are 2 preventative medicines approved by the CDC; a vaccine for pregnant women who are between 32 and 36 weeks in the RSV season, and the second is a preventative antibody for all babies less than 8 months old before entering their first RSV season. If the maternal vaccine is given, the baby will also be protected from RSV and will not require subsequent RSV immunisation, in the majority of cases. The second option provides the baby with antibodies against RSV. Antibodies are proteins made by our immune system to target specific proteins on the surface of viruses and bacteria. Providing babies with RSV antibodies will prime their immune systems, and reduce the chance of severe infection from RSV. In some cases, the antibody vaccine may be given to infants older than 6 months, for example, those that have chronic health conditions, are immunosuppressed, or were born premature.²⁶ These vaccines have been approved in the UK but no vaccination schedule is in place yet.

Conclusion

RSV is a common respiratory virus that almost all infants will become infected with by age 2. For the majority of infants, this presents as typical cold or flu symptoms. However, for some infants, RSV will result in a more severe infection, resulting in hospitalisation, the potential need for a ventilator, and, in extreme cases, death. More research is needed to ascertain whether RSV infection can cause developmental delays in the respiratory system and whether this is the cause of the increased incidence of wheezing and asthma following RSV infection, or if another factor predisposes an infant to both. However, there is evidence to support a role for RSV in neurological developmental delays including impairments in learning and language acquisition. Whilst these neurological delays are uncommon, together with the high prevalence of this virus and the fact that it is a leading cause of infant hospitalisation, it is clear that more research is needed into the long-term effects of RSV infections on development.