Description

• In adults, RSV typically causes upper respiratory tract infection (URTI) but can progress to pneumonia or worsening of asthma and/or chronic obstructive pulmonary disease (COPD).
• In infants and children, RSV commonly presents as lower respiratory tract infection (LRTI) that manifests as bronchiolitis and rarely pneumonia, respiratory failure, and death.

Pediatric Considerations
90–95% of children are infected by 24 months; leading cause of pediatric bronchiolitis (50–90%); premature infants and infants aged <6 months are at increased risk.

Epidemiology

• Seasonality: Outbreaks of RSV disease occur each winter (October to late January).
• Morbidity and mortality: RSV infection leads to >100,000 annual hospitalizations. In the United States, 2.1 million outpatient visits for RSV in children aged <5 years.

Incidence

• Worldwide, RSV is responsible for approximately 33 million LRTI per year and up to 199,000 childhood deaths.
• Annually, RSV causes an estimated 33.1 million acute LRTI worldwide and 3.2 million hospitalizations in children aged <5 years.
• RSV cases are particularly increasing in the wake of the COVID-19 pandemic.

Prevalence
Difficult to conclude accurately

Etiology and Pathophysiology

• RSV is a single-stranded, negative-sense RNA virus belonging to the Paramyxoviridae family.
• Two subtypes, A and B, are simultaneously present in most outbreaks with A subtypes causing more severe disease.
• RSV is spread via direct contact or droplet aerosols. Incubation period ranges from 2 to 8 days, mean 4 to 6.
• Natural RSV infections result in incomplete immunity; recurrent infections are common.
  • RSV causes a neutrophil-intensive inflammation of the airway. RSV develops in the cytoplasm of infected cells and matures by budding from the plasma membrane. RSV is a major cause of asthma exacerbation and COPD.

Genetics

• Severe RSV infections may be associated with polymorphisms in cytokine-related genes, including CCR5, IL4, IL8, IL10, and IL13.
• RSV replicates in apical ciliated bronchial epithelial cells. The airway epithelium produces chemokines, which recruit neutrophils.

Risk Factors

Significant association with RSV-associated acute LRTI

• Infants born before the 35 weeks’ gestation; low birth weight, male gender; underlying cardiopulmonary disease; HIV; Down syndrome
• Any age group with persistent asthma; children aged <5 years with socioeconomic vulnerability; immunodeficiency; siblings with asymptomatic RSV infection; secondhand smoke; history of atopy, no breastfeeding; adult patients with COPD or functional disability
• Other risk factors: daycare center attendance; exposure to indoor and environmental air pollutants; multiple births, malnutrition, higher altitude

General Prevention

• Hand hygiene is the most important step to prevent the spread of RSV (1)[B].
  • Use alcohol-based rubs for hand decontamination when caring for children with bronchiolitis. When alcohol-based rubs are not available, wash the hands with soap and water (1)[B].
• Avoid passive smoke exposure (1)[B].
• Isolate patients with proven or suspected RSV.
• Palivizumab is a humanized monoclonal antibody for the prevention of severe RSV in high-risk children (2)[A]: preterm infants born ≤28 weeks, 6 days of gestation, or who are <12 months at start of RSV season; infants with bronchopulmonary dysplasia who are <1 year or <23 months of age and requiring treatment; infants ≤12 months of age who are being medically treated for acyanotic heart disease or have moderate to severe pulmonary hypertension
• Nirsevimab is a long acting monoclonal antibody recently approved by FDA. A single injection of nirsevimab administered before the RSV season protected healthy late-preterm and term infants from medically attended RSV-associated LRTI. Target populations for immunization include older infants and young children (e.g., those born prematurely or with cardiopulmonary disease or immunodeficiency).
• Nirsevimab offers a large advantage over current therapy with palivizumab, which has an involved treatment regimen of 5 monthly doses.
• Probiotics protect against RSV infection in neonatal mice through a microbiota-AM axis, suggesting that the probiotics may be a promising candidate to prevent and treat RSV infection, and deserve more research and development in the future.
• Prophylactic use is indicated for infants and children <24 months of age with:
  • Chronic lung disease (CLD) of prematurity
  • Hemodynamically significant congenital heart disease
    • Congenital abnormalities of the airway or neuromuscular disease
• AAP guidelines (2)[A]: preterm infants born <29 weeks’ gestational age (WGA) and <1 year of age at the RSV season start date; infants in the 1st year of life with CLD of prematurity; infants with HS-CHD <1 year of age at the season start date
• Dosage: maximum of 5 monthly doses beginning in November or December at 15 mg/kg per dose IM
• Breastfeeding can significantly reduce hospitalizations due to respiratory infections.

Commonly Associated Conditions

In hospitalized infants:

• Pulmonary infiltrates/atelectasis (42.8%); otitis media (25.3%); hyperinflation (20.8%); respiratory failure (14%)
• Hyperkalemia (10.1%, defined as K+ >6); apnea (8.8%); bacterial pneumonia (7.6%)