Most respiratory syncytial virus (RSV) infections are mild, but some severe cases can require hospitalization. Infants and children are very susceptible to RSV infection and the most serious cases (usually involving bronchiolitis or pneumonia) will be admitted to NICU/PICU.
BY Bill Pruitt, MBA, RRT, CPFT, AE-C, FAARC
Most respiratory syncytial virus (RSV) infections are mild, but some severe cases can require hospitalization. Infants and children are very susceptible to RSV infection and the most serious cases (usually involving bronchiolitis or pneumonia) will be admitted to NICU/PICU. RSV is spread primarily by inhaling respiratory droplets when a person carrying the virus coughs or sneezes, and through direct contact with a contaminated surface, and is highly transmissible.1,2 In children under one year of age, RSV is the most common infectious agent that causes bronchiolitis and pneumonia.
Incidence and Pathology
Annual hospitalizations for children under 5 years old average around 58,000 and is the cause of death in between 100 to 500 in this population. RSV cases occur mostly during the fall and winter in temperate climates while in the tropics RSV is active throughout the year.1,2 Across the globe RSV annually causes some 1.4 million infections in infants less than 1 year old and is the cause of death for some 120,000 children under 5 years old.3 The virus initially infects the upper airways then spreads to the lower airways where it brings about inflammation and edema in the bronchi and death of epithelial cells. Mucus production is increased along with impaired secretion clearance resulting in mucus plugs and blocked airways along with increased work of breathing, cough, hyperinflation, and altered gas exchange.4 Hospital admission is considered when an infant displays marked respiratory distress, SpO2 less than 92% on room air, significant reduction in feeding, clinical dehydration, or history of apnea.2
Symptoms, Diagnosis, and Risk Factors
RSV infection in infants and young children starts with rhinorrhea and decreased appetite followed in 24 to 72 hours later by cough, sneezing, fever, prolonged expiration, crepitation, and wheezing. For very young infants, apnea may appear with or without the other symptoms.2,5 RSV is often diagnosed clinically based on the signs, symptoms, and presentation of the illness and may be confirmed by laboratory tests.
The two most common tests are real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) and antigen testing (which is very sensitive in children by not in adults). The virus may also be cultured in the lab. rRT-PCR tests are more sensitive than culture and antigen testing.4 Point of care testing in the emergency department or primary care center is useful to improve confidence in the clinical diagnosis, support decisions to withhold antibiotics, and aid in effective, accurate communication with parents. For hospitalized infants, lab testing to confirm the viral infection supports the decision for cohorting or placing the infant on isolation and initiating infection control protocols to minimize nosocomial infections. Due to the high transmission risk of RSV, nosocomial infection is a major concern.2 The virus is able to survive from 6-12 hours on various surfaces (beds, toys, table tops, etc) and up to 25 minutes on contaminated skin (ie hands).2
Very young infants are most susceptible to severe disease, and high risk for RSV is linked to prematurity, infants <6 months of age, infants and toddlers <2 years old who have chronic lung or congenital heart disease, children with immunosuppression, and children with neuromuscular disease and associated issues with aspiration.5 Most infants present with a low-grade fever but research has found that up to about a third of the cases will exhibit a fever over 39ᵒC. Often the source of the infection involves contact with a family member or a care-giver who has recently had upper respiratory symptoms (ie a cold).2
Treatment, Prophylaxis, Vaccine Research
There are several published clinical guidelines for management of infants with bronchiolitis although none are specific for RSV.2 Research into various interventions has been published but based on large meta-analysis, management of RSV is supportive in order to allow the body’s defense system time to fight the infection.2
The possible treatment interventions mentioned in the guidelines (but not given a recommendation for routine use) include the following:
- Ribavirin is the only licensed drug available for treatment of RSV but due to the risk of serious side-effects (suppression of bone marrow, possibly a carcinogen) and minimal proof of benefit—it is not a recommended choice for treatment.
- Bronchodilators (Beta-2 agonist and anticholinergic medications) have often been prescribed due to wheezing, prolonged expiration) but have not reduced hospital admission, length of stay, or length of the course of the illness. Additionally, side effects including tachycardia, tremor and increased desaturation are common. (However, a trail of bronchodilator therapy may help rule out asthma as a cause of the wheezing).
- Nebulized adrenaline may reduce hospitalization but after 7 days, this effect is no longer significant. The latest recommendations (NICE from 2015) state that there is insufficient evidence to support routine use of adrenalin (with or without corticosteroids) in the treatment plan.6
- Corticosteroids are commonly ordered in the treatment of RSV but the meta-analysis has bound no benefit of either systemic or inhaled corticosteroids (including no reduction of admission or length of stay). In addition, routine use should be avoided due to the potential side effects of reduced growth and bone mineral density).
- Nebulized hypertonic saline (a mucolytic agent) is thought to reduce airway secretions. However, based on randomized, controlled trails, the evidence suggests that hypertonic saline should not be routinely used or only considered in infants with a prolonged length of stay (ie more than 72 hrs). It was noted that the vast majority of infants are hospitalized for less than 48 hrs.
- Antibiotics should not be used as a prophylactic treatment. Based on a large study from the USA only 1.2% of infants having a severe RSV bronchiolitis developed a secondary bacterial infection. If the diagnosis is clearly a viral bronchiolitis (whether or not laboratory testing has proven RSV) prophylactic antibiotics are not warranted.
- Heliox has not been proven to reduce admissions, length of stay, or the need for mechanical ventilation, although it may reduce clinical scores in the early hours of starting treatment. It has been suggested that more research is needed in the use of heliox; at present it has not been recommended for routine use.
Supplemental oxygen, nutritional support, and adequate hydration is the foundation of this supportive approach. Increasing respiratory support may be warranted depending on the severity of the infection, starting with high-flow nasal cannula therapy, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), noninvasive ventilation (NIV), intubation and mechanical ventilation, and rarely extracorporeal membrane oxygenation (ECMO) may be used.2,7 Chest physiotherapy should be considered for infants who have difficulty clearing secretions (ie for those with cystic fibrosis or a neuromuscular disease that decreases spontaneous secretion clearance activity). Either a naso- or orogastric feeding tube should be placed in infants who cannot take sufficient fluids orally (ie less than 50% of the normal intake).2
For prophylactic measures in RSV, palivizumab is the only licensed agent available. Palivizumab (PVM) is a humanized monoclonal antibody against the RSV F protein and is indicated in prevention of serious lower respiratory tract infections from RSV in premature babies and those with underlying conditions that puts them at high risk.8 PVM has been shown to reduce the risk of hospitalization for infants predisposed to developing RSV from 39-78% and is given in monthly injections. PVM is expensive but is about to come off patent, but at this time cost-benefit analysis has limited its use to a small population of those at most risk (less than 3% of the birth cohort).2,8
Research is underway to develop a vaccine for RSV but so far, none has made it through the process to become approved. Maternal vaccination is considered to be the best approach should a vaccine become available and several have shown promise in the studies published thus far.2-3 (Maternal antibodies are known to pass to the infant in the womb through the placenta and also passed on during breastfeeding.3)
COVID-19 Impact on RSV
The incidence of RSV (as well as influenza and other viral infections) that usually occurs through the fall and winter dropped significantly during 2020-2021 season. The hypothesis for this decrease is that the efforts to reduce the incidence of COVID-19 infection also affected the rates of infection for other viruses. Physical distancing, reducing exposure to crowds, wide-spread use of masks, careful handwashing, limitations on international travel, isolation of those who exhibited symptoms, strict infection control practices, and changes in procedures that produce aerosols are mentioned as possible actions that reduced the transmission of viruses including RSV.1,9 In June 2021, the CDC released a health advisory stating that in the Health and Human Services (HHS) Regions 4 and 6 there have been increases in the detection of RSV. These two regions include several states across the southern portion of the US (including Ala, Fla, Ga, Ky, Miss, NC, SC, and Tenn, Ark, La, NM, Ok, and Tex).
The advisory states, “Due to reduced circulation of RSV during the winter months of 2020–2021, older infants and toddlers might now be at increased risk of severe RSV-associated illness since they have likely not had typical levels of exposure to RSV during the past 15 months.”1 There is concern that this could be a precursor to a surge in RSV in many areas. The National Health Service in the United Kingdom has released warnings that the coming RSV season could show a sharp rise in cases among infants and children due to the same reasons given in the CDC advisory.10
RSV is a serious disease, especially infants and children, and especially to those who are at high risk for severe illness. Supportive care to manage the symptoms is the recommended approach for care and possible vaccination against the virus is showing promise. For the NICU/PICU patients with RSV, supportive care may include the highest and most intense/invasive levels of respiratory and nutritional support to allow the body’s defenses to fight off the disease.
Reduction in possible nosocomial transmission is very important and infection control measures must be in place to control the spread in the hospital. Viral testing helps to clarify the diagnosis and improve other aspects of care, while careful monitoring of the cardiopulmonary system is important to alert the healthcare team to possible acute respiratory failure and prevent RSV-related deaths. Providers should be especially aware of the potential surge in RSV cases this upcoming season. This is possibly due to the dampening effect on all respiratory infections over the past 12-15 months resulting from COVID-19 precautions. The reduced exposure to the common viruses encountered by infants and children may result in increased infections since the natural antibodies to the viruses have not been produced.
Bill Pruitt, MBA, RRT, CPFT, AE-C, FAARC, is a writer, lecturer, and consultant and recently retired from over 20 years teaching at the University of South Alabama in Cardiorespiratory Care. He also volunteers at the Pulmonary Clinic at Victory Health Partners in Mobile, AL.
For more information, contact [email protected]
- From the Centers for Disease Control and Prevention (CDC) Health Alert Network: Increased Interseasonal Respiratory Syncytial Virus (RSV) Activity in Parts of the Southern United States. https://emergency.cdc.gov/han/2021/han00443.asp. Accessed 7/2/2021.
- Drysdale SB. Best practice in the prevention and management of paediatric respiratory syncytial virus infection. Therapeutic advances in infectious disease. 2016 Apr;3(2):63-71.
- Maertens K, Orije MR, Van Damme P, Leuridan E. Vaccination during pregnancy: current and possible future recommendations. European journal of pediatrics. 2020 Feb;179(2):235-42.
- Stobbelaar K, Kool M, de Kruijf D, Van Hoorenbeeck K, Jorens P, De Dooy J, Verhulst S. Nebulised hypertonic saline in children with bronchiolitis admitted to the paediatric intensive care unit: A retrospective study. Journal of paediatrics and child health. 2019 Sep;55(9):1125-32.
- From the CDC website Respiratory Syncytial Virus Infection (RSV) For Healthcare Providers. https://www.cdc.gov/rsv/clinical/index.html. Accessed 7/2/2021
- National Institute for Health and Care Excellence (NICE). (2015) Bronchiolitis: diagnosis and management of bronchiolitis in children. Clinical Guideline 9, NICE: London.
- Pichler K, Assadian O, Berger A. Viral respiratory infections in the neonatal intensive care unit—a review. Frontiers in microbiology. 2018 Oct 19;9:2484.
- DeVincenzo J, Tait D, Efthimiou J, Mori J, Kim YI, et. al. A randomized, placebo-controlled, respiratory syncytial virus human challenge study of the antiviral efficacy, safety, and pharmacokinetics of RV521, an inhibitor of the RSV-F protein. Antimicrobial agents and chemotherapy. 2020 Jan 27;64(2):e01884-19.
- Trenholme A, Webb R, Lawrence S, Arrol S, Taylor S, Ameratunga S, Byrnes CA. COVID-19 and infant hospitalizations for seasonal respiratory virus infections, New Zealand, 2020. Emerging Infectious Diseases. 2021 Feb;27(2):641.
- From the Health Service Journal: https://www.hsj.co.uk/public-health/exclusive-government-alert-over-surge-in-respiratory-virus-affecting-babies-and-toddlers/7030061.article. Accessed 7/4/2021.