Respiratory Syncytial Virus (RSV) Infection

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Respiratory syncytial virus (RSV) is the primary etiologic pathogen of bronchiolitis and a common agent for pneumonia in infant and the elderly. Despite its global impact, treatment remains primarily supportive.

Description

  • RSV remains one of the most common causes of childhood illness and the most common cause of hospitalization in infants, with 90–95% of children infected by 24 months of age.
  • RSV-associated lower respiratory tract infections (LRTIs) are characterized as bronchiolitis or pneumonia, may end with respiratory failure, and death.
  • In adults, RSV typically causes upper respiratory tract infection (URTI), but life-threatening LRTI/acute cardiac events and worsening of asthma/chronic obstructive pulmonary disease (COPD)/congestive heart failure (CHF) can occur in high-risk populations.
  • Infections occur in seasons lasting between 3 and 5 months during autumn and winter. In tropical regions, the infection circulates all year long.

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 LRTIs worldwide, and 3.2 million hospitalizations in children aged <5 years.
  • Morbidity and mortality in the United States per year: 2.1 million outpatient visits and 80,000 hospitalizations for RSV in children aged <5 years; 160,000 hospitalizations and 10,000 deaths for RSV in adults aged ≥65 years.
  • RSV cases are particularly increasing in the wake of the COVID-19 pandemic.

Prevalence

Difficult to conclude accurately

Etiology and Pathophysiology

  • RSV is 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 is 4 to 6 days.
    • Natural RSV infections result in incomplete immunity; recurrent infections are common.
    • RSV causes neutrophil-intensive airway inflammation. It develops in the cytoplasm of infected cells and matures by budding from the membrane.

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 prematurely; low birth weight, male gender; underlying cardiopulmonary disease; HIV; Down syndrome
    • Any age group with persistent asthma; children <5 years with socioeconomic vulnerability; immunodeficiency; siblings with asymptomatic RSV infection; second-hand 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
  • For severe or life-threatening RSV infection
    • Preterm infants born ≤28 weeks, 6 days of gestation, or who are <12 months at the start of RSV season; infants with bronchopulmonary dysplasia who are <1 year or <23 months and requiring treatment; infants ≤12 months of age who are being medically treated for acyanotic heart disease or have moderate to severe pulmonary hypertension
  • Children <2 years with congenital heart disease, chronic lung disease, weakened immune systems, or who have neuromuscular disorders.
  • Adults aged ≥75 years living in nursing homes or long-term care facilities or adults with chronic lung or heart disease (asthma, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, cerebrovascular disease, chronic kidney disease, severe obesity, weakened immune systems, organ transplant recipients, receiving chemotherapy)

General Prevention

  • Good hygiene by covering coughs and sneezes, washing or sanitizing hands often, and cleaning frequently touched surfaces; avoid passive smoke exposure. Isolate patients with proven or suspected RSV.
  • Immunizations:
    • Adult: single-dose RSV vaccine for everyone aged ≥75 years, and adults aged 60 to 74 years at increased risk for severe RSV disease. Adults who have received the RSV vaccine should not receive another dose.
    • Pregnancy: maternal vaccination with the RSVpreF vaccine between 32 0/7 and 36 6/7 weeks’ gestation
    • Infants: administration of the long-acting monoclonal antibody (mAb) nirsevimab to infants aged <8 months entering their first RSV season if the mother is unimmunized, or for children between the ages of 8 and 19 months who are at increased risk for severe RSV disease before their second RSV season.
  • 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.
  • 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%)

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