Bronchiolitis, RSV, and the RSV Immunization: A Guide for Parents

Written By Brandon Hunter

TL;DR Summary

  • Respiratory Syncytial Virus (RSV) usually causes cold symptoms in infants and children, but can also cause infection of the airways and lungs which leads to difficulty breathing and can require hospitalization

  • Beyfortus (nirsevimab) is a new immunization that the AAP and CDC recommend giving to all infants <8 months, and infants with high risk for bad infections 8-19 months

  • The immunization is given at the start of the “RSV season” and gives children immunity against the virus for ~5 months

  • Clinical trials have shown that the risk of needing to be hospitalized from an RSV infection dropped from 4% to 0.8% in premature healthy infants, and from 1.6% to 0.6% in full term healthy infants

  • Adverse events did not occur any more with nirsevimab than with a placebo treatment (saline);

    • In the study of premature infants, 3 died in the placebo group and 2 died in the nirsevimab group, no deaths were related to the immunzizaiton

    • In the study of full term infants, 3 infants died in the nirsevimab group, but they were investigated and determined not to be related to the immunization

  • Bottom line: yes, you should have your child immunized!

    • If your child is healthy and born full term, even though their risk of requiring hospitalization from RSV is low (~1-3% in the US), the immunization drops your child’s risk of needing to be hospitalized by 62%

    • If your child is healthy but was born prematurely, their risk of being hospitalized from RSV is higher (~3-6% in the US), the immunization drops your child’s risk of needing hospitalization by 80%

    • It is not associated with increased rates of adverse events

 

Introduction

As a parent, you may have heard of RSV (Respiratory Syncytial Virus) or bronchiolitis, especially if you have young children. These terms can be worrisome, particularly when they're associated with difficulty breathing and potential hospitalizations. RSV is a common virus that infects the respiratory tract, causing cold-like symptoms in most cases. However, in some instances, especially in infants and young children, RSV can lead to a more severe infection called bronchiolitis, which affects the small airways in the lungs (bronchioles) and can result in breathing difficulties.

Recently, a groundbreaking development in the fight against RSV has emerged – the FDA approval of Beyfortus (nirsevimab), a new immunization recommended by the American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC) for infants under 8 months old and high-risk infants between 8-19 months old. This is huge news for parents, as the immunization has been shown to significantly reduce the risk of severe RSV infections and hospitalizations in clinical trials.

In this post, we'll dive deeper into what RSV is, how the new immunization works, and the evidence behind its effectiveness. We'll also discuss the importance of considering this immunization for your child and how it can help protect them during the peak RSV season. By the end of this article, you'll have a better understanding of RSV, bronchiolitis, and the potential impact of this new immunization in keeping your little one healthy.

 

What is RSV?

  • RSV stands for Respiratory Syncytial Virus and it’s one of the most common viruses that infects children (and adults, especially the elderly!)

  • Usually (70-80% of the time), when a person is infected with RSV, it just presents as an upper respiratory tract infection (URI)

    • URI is fancy way of saying a ‘cold’, or an infection that mainly affects the upper respiratory tract - the nose, sinuses, and throat

    • The lower respiratory tract, which is made up of the trachea, bronchi, bronchioles, alveoli, and lungs, is not infected (see below)

  • In young children less than 2 years old, RSV known for causing bronchiolitis (20-30% of the time), which is an infection of the small airways of the lungs (lower respiratory tract)

 
 

A diagram of the basic anatomical features of the human lungs, including alveoli and bronchioles, by Sumaiya. This work is licensed under the Creative Commons Attribution-Share Alike 4.0 International license. For more details and to view the original, visit Wikimedia Commons.

The respiratory tract, bronchioles, and bronchiolitis

The respiratory tract starts with your nose, mouth, throat, and the trachea which is the tube (“airway”) in your throat that goes to your lungs. The trachea divides into two smaller airways called bronchi that go to the left and right lung.

From there, the airways keep dividing again and again! The smallest airways are called bronchioles - when these get infected or inflamed, we call it bronchiolitis.

The image on the right is a close up of bronchioles, the small airways that eventually terminate in alveoli, which are tiny air sacs. Alveoli are the fundamental unit of the lungs and they are the place that gas exchange happens - this is where the body takes oxygen into the blood and gets rid of carbon dioxide to be exhaled.

 

“-itis” just means “inflammation” generally, so in this case, you have inflammation of the small airways = “bronchiole-itis”, or bronchiolitis (appendicitis = inflamed appendix, tonsilitis = inflamed tonsils, meningitis = etc.)

Inflammation refers to the response of your body’s immune system to something that it doesn’t recognize and it means that white blood cells are active in that area leading to swelling

 

What are the symptoms of an RSV infection?

  • Most commonly (70-80% of the time) RSV will show up as a child having symptoms of a cold (URI symptoms) - cough, congestion, runny nose, coughing, sneezing, and sometimes fever

  • Sometimes (20-30% of the time) though, RSV will cause infection of the lower respiratory tract, usually bronchiolitis -

    • With bronchiolitis, in addition to the URI symptoms above, since the LOWER airways are affected, so the child will also have difficulty breathing because those small airways are usually clear and move air in and out easily, but now they’re inflamed plugged up with mucus and swelling

    • Increased work of breathing - children use all of the muscles around their ribs, belly, and neck, to breathe - air doesn’t move as easily through the inflamed bronchioles so the child has to use his/her extra muscles to force air in and out

    • Fast breathing (tachypnea) - children can’t take as big of a breath as normal, so instead they take smaller breaths and breathe faster to compensate

    • A whistling sound in the lungs (wheezing) is heard when you listen with the stethoscope, and if it’s really bad, can sometimes be heard without a stethoscope - the air is moving through even smaller tubes now so makes the wheezing sound

  • One quick note here - the focus of this article isn’t on diagnosis and treatment of RSV, but doctors have different preferences about whether testing is needed to confirm if a patient has RSV or not when they come in with respiratory symptoms.

    • For most viruses that cause URIs or bronchiolitis, you don’t treat the virus directly with medicine to kill the virus, instead just supporting the child’s breathing with oxygen, suctioning, breathing treatments, and things like that

    • Some of the other examples of viruses that cause URIs or bronchiolitis are rhinovirus, parainfluenza, coronavirus (not COVID, but COVID can cause it too!)

    • So, since identifying the exact virus would not change how you treat the patient, many providers will skip testing, or limit testing to viruses that would receive treatment (COVID, influenza)

 

Recognizing Increased Work of Breathing

The diaphragm is the main muscle used for breathing and sits below the lungs and above the belly. When a child is sick, the diaphragm alone can’t generate enough force to get enough air in and out, so “accessory muscles” (muscles of the neck, chest, and abdomen) help out. Use of these muscles shows up in a few ways:

  • Suprasternal retractions (above the collar bones) - infants use the muscles attached to their collar bones to generate extra force, so you often see indentation around the neck as these muscles contract

  • Intercostal retractions (between the ribs) - infants use the muscles that connect their ribs as well, so you see indentation between the ribs (ribs look more obvious) when they are taking a breath in (see the pic to the right)

  • Subcostal retractions, belly breathing (underneath the lowest ribs) - you often see a big shadow between the lowest ribs and the belly and see the belly pop out more than normal as the infant engages these muscles

  • Other signs of difficulty breathing

    • Nasal flaring - the nostrils move in and out showing that there is rapid movement of air

    • Grunting - a sound made during exhalation that the infant makes to keep his/her lungs inflated, often mistaken for a crying / whining sound

 
 

A photograph attributed to Bobjgalindo. This image is distributed under the Creative Commons Attribution-Share Alike 4.0 International license. For further details and to view the original image, visit Wikipedia.

 

How Big of a Problem is RSV and when do cases occur?

  • RSV causes 58-80,000 infants and children <5 years old to be hospitalized every year in the US! (CDC)

  • ~2% of all infants <1 year old will require hospitalization from RSV infection in the US (McLaughlin et al, 2022)

  • Children born prematurely and those with chronic medical problems are at risk of more severe disease needing hospitalization

  • Bronchiolitis and RSV infections tend to spike in the winter months (typically peaking in December or January), but interestingly, COVID threw off this normal cycle

    • RSV peaks in the winter because children are inside, in close contact, and spread germs more frequently

    • During COVID, everyone was isolated! So children weren’t spreading germs as much, and inpatient hospitalizations were down. It wasn’t until isolation mandates got lifted that we saw the usual uptick in admissions

This graph has a lot of lines but basically the blue lines are the rates of RSV before the pandemic (2017-2020, peaking Dec-Jan) and the black lines are after the height of the pandemic (2020-2023, variable peaks). You can see that 2020-2021 saw historically low numbers of RSV infections overall - kids weren’t interacting and exchanging germs! In 2022, the RSV peak then strangely came in July-August (as isolation was lifted). By 2022-2023 the peak has started to move back toward the usual seasonality, seeing a peak in October-November. It’s not clear where future peaks will occur but it seems like it’s getting back toward usual winter peaks.

 

How does RSV Immunization (Beyfortus/nirsevimab) work?

  • Beyfortus is the brand name for nirsevimab, which is a monoclonal antibody that protects against RSV infections that was approved by the FDA in 2023 to prevent RSV infections

    • The immune system normally makes antibodies that recognize anything that is “not self” or not a part of the body

    • When something foreign enters the body - for example, you get a cut and bacteria get into the blood stream - antibodies bind to the invader and alert the immune system that whatever they are attached to should be destroyed

  • Nirsevimab is a monoclonal antibody - this means that the medicine is made up of copies of a single antibody that has a specific target to a certain part of RSV so that if any of the virus enters the body, it will be immediately labeled and identified for destruction before it can cause serious infection

  • Most traditional vaccines act by injecting something into the body that looks like the bug (virus, bacteria) that you’re trying to protect against but can’t cause a dangerous infection - this allows the immune system to generate antibodies and be ready in case it ever faces the actual bug in the future

    • With the polio vaccine, for example, you introduce an inactivated version of the polio virus into the body so that the body will see it and make antibodies against polio in case it ever comes into contact with a real ‘live’ polio virus!

    • With nirsevimab, instead of having your body make the antibodies, the nirsevimab itself is the antibody offering protection! This is called passive immunity, because the body is protected against infection but it hasn’t made the antibodies to protect itself

Image shared under the Creative Commons Attribution-Share Alike 4.0 International license, original work by Maher33. For more information, visit Wikipedia.

1) Antibodies (in our case from a dose of nirsevimab) are shown in green (A), and pathogens (in our case, RSV), are shown in red

2) When RSV enters the body, antibodies are already around so they immediately bind it to alert immune cells

3) The immune cells go to the virus and bind the antibodies

4) The immune cells destroy the virus so it doesn’t have a chance to reproduce and cause a bad infection

 

How often is nirsevimab given, and how long are children protected?

  • A single dose of Nirsevimab is given as an injection into the muscle (similar to most other traditional vaccines) and provides protection for at least five months

  • Only one dose is needed at the beginning of RSV season (which could be a challenge to identify given the graph above!) each year

 

Which children should receive immunization?

This is the official guidance from the AAP on who should receive immunization based on the available data. It is generally recommended for all infants <8 months unless mom received a vaccine <2 weeks before birth, and infants 8-19 months with high risk of severe disease: chronic lung disease from prematurity, immunocompromise, cystic fibrosis, American Indian or Alaska Native; other patients may be included based on physician judgment.

 

What’s the evidence for using the RSV immunization (nirsevimab)?

There were two major RCTs that evaluated the efficacy of nirsevimab; one in premature healthy infants, and one in fullterm healthy infants

Griffin et al, 2023 - efficacy in premature infants

  • Who was in the study - 1453 healthy premature infants (infants born between 29-35 weeks) in the >20 countries who were <1 year old (mainly <8 months)

  • What did they do - infants were randomized to receive one dose of nirsevimab or a placebo (injection of saline/salt water)

  • Major results - for infants who got nirsevimab, their rate of a bad lung infection with RSV dropped from 9.5% to 2.6% (70% reduction) and their rate of being admitted to the hospital because of RSV dropped from 4.1% to 0.8% (78% reduction)

  • Adverse events - overall rate of adverse events was low (0.5%), and were generally mild in severity, mainly rash and irritation.

    • Of note, there were 5 deaths in total reported (2 who received nirsevimab, 3 who received placebo), all were investigated and no deaths were thought related to nirsevimab or the placebo

Major results from the Griffin et al, 2020. The top red box shows the number of infants that presented to their doctor with a lower respiratory tract RSV infection in the two groups. The lower red box refers to the number of infants who were admitted to the hospital with an RSV infection in the two groups.

 

Hammit et al, 2022 - efficacy in late preterm and full term infants

  • Who was in the study - 1490 healthy late preterm and full term infants (infants born after 35 weeks) who were less than 1 year old in >20 countries

  • What did they do - infants were randomized to receive one dose of nirsevimab or a placebo (injection of saline/salt water)

  • Major results - for infants who got nirsevimab, the rate of a bad lung infection with RSV dropped from 5.0% to 1.2% (75% reduction) and the rate of being admitted to the hospital with RSV dropped from 1.6% to 0.6% (62% reduction)

  • Adverse events -

    • 3 infants did die in the nirsevimab group compared to 0 in the placebo group; each death was investigated and thought to be unrelated to the nirsevimab; all deaths occurred more than 3 months after receiving the immunization

    • 1 infant in the nirsevimab group did have a severe rash a week after receiving the immunization and it went away after 3 weeks

    • There was no difference in the rate of reported adverse events between the infants receiving nirsevimab and placebo

 

What are the side effects?

  • There were adverse side effects reported in the studies in both groups that occurred at similar frequency, implying that since they occurred at similar rates in the placebo and the nirsevimab groups, that it didn’t cause any more issues than an injection of salt water (which shouldn’t really cause any major issues at all)

    • There were 3 deaths in the nirsevimab group and 0 in the placebo group - although at face value this is concerning, the study investigators found that two deaths were related to gastroenteritis (stomach bug) in patients that did not receive medical attention, and a third was thought to be due to chronic undiagnosed illness

  • It’s possible that when more patients receive the immunization that very rare events will be associated, but overall the side effect profile is very good

 

Should You Get the RSV Immunization for Your Child?

  • Remember, getting the vaccine doesn’t prevent against all cases of infection, but even when an infection does occur, it will be more mild than it would have been otherwise

  • With the caveat that most enrollment in the studies happened in Europe, things to consider -

    • If your infant was born early (before 35 weeks), getting the immunization should drop their risk of getting an RSV infection so bad that they need to see a doctor from 10% down to 4%, and should can drop the chance that it will be so bad they need to go to the hospital from 4% down to <1%.

    • If your infant was born full term (after 35 weeks), they can drop their risk of getting an RSV infection so bad that they need to see a doctor from 5% down to 1.2%, and they can drop the chance that it will be so bad they need to go to the hospital from 1.6% down to 0.8%.

  • On balance, even though healthy full term infants have low rates of hospitalization at baseline (1.6% in the European study) I think it’s certainly worth it to get the RSV vaccine because it cuts their risk of a severe infection by more than 50% and the studies showed reported adverse events similar to placebo; the three deaths reported occured in premature infants and did not appear related to nirsevimab

 

Helpful Links

Brandon Hunter
Previous

Respiratory Anatomy 101 for Parents: Understanding Your Child's Breathing