207.1 🎓 醫孞生版

207.1.0.1 📌 䞀頁重點

  • Virus: ssRNA, Pneumoviridae family, related to HMPV
  • Universal childhood infection (95%+ infected by 2 yr)
  • Re-infection lifelong (immunity wanes)
  • High-risk groups:
    • < 6 months (especially < 3 months) — most severe pediatric
    • Preterm infants
    • Bronchopulmonary dysplasia / chronic lung disease of prematurity
    • Congenital heart disease (hemodynamically significant)
    • Immunocompromise
    • ≥ 65 yr (similar mortality to flu in this age group)
    • Chronic cardiopulmonary disease
    • Nursing home residents
  • Clinical (infants):
    • Bronchiolitis (#1 form): wheezing + tachypnea + retractions + fever 1-3 days after URI prodrome
    • Apnea (especially preterm < 3 mo)
    • Hypoxia + respiratory failure (severe)
    • Pneumonia
  • Clinical (older child / adult):
    • URI / common cold (mild)
    • Bronchitis
    • Pneumonia (elderly, immunocompromise)
    • COPD / asthma exacerbation
  • Diagnosis:
    • Multiplex respiratory PCR
    • Rapid antigen test (sens ~ 70%)
    • Not routinely needed in classic bronchiolitis
  • Treatment:
    • Supportive: oxygen, hydration, suction, mechanical ventilation
    • NO routine antiviral (ribavirin limited efficacy, rare use)
    • Bronchodilators / steroid generally NOT helpful in bronchiolitis (AAP 2014)
    • High-flow nasal cannula + CPAP for moderate-severe
    • Mechanical ventilation for severe
  • Prevention (2023-2024 game changer):
    • Nirsevimab (Beyfortus, FDA 2023) — long-acting mAb against F protein; single dose covers RSV season
      • Universal infants entering 1st RSV season (ACIP 2024)
      • High-risk children entering 2nd season
    • Maternal RSVpreF vaccine (Abrysvo) — Pfizer; 32-36 wk gestation
      • Maternal Ab transfer protects newborn ≀ 6 mo
    • Adult vaccines (2023 FDA approvals):
      • Arexvy (GSK) — RSVpreF subunit
      • Abrysvo (Pfizer) — RSVpreF subunit
      • mRESVIA (Moderna, FDA 2024) — mRNA
      • For ≥ 60 yr (some 50+) routine; or chronic disease 18+
    • Palivizumab (Synagis) — older mAb, monthly during RSV season, high-risk infants only — being replaced

207.1.0.2 1⃣ Virology

  • ssRNA, Pneumoviridae family
  • Subgroups A + B (slightly antigenically distinct)
  • Surface proteins F (fusion) + G (attachment) primary antigens
  • F protein has prefusion + postfusion conformations
  • Prefusion F (RSVpreF) is the optimal vaccine + mAb target (Crank, McLellan 2013-)
207.1.0.2.1 Cell Entry
  • F protein mediates fusion
  • G protein attachment via CX3CR1 (ciliated airway epithelium)
  • Cell-to-cell spread via syncytium formation (multinucleated giant cells) — hence “syncytial”
207.1.0.2.2 Pathogenesis
  • Airway epithelium destruction + sloughing
  • Edema, mucus plugging
  • Bronchiolar narrowing → wheezing
  • Co-infection / secondary bacterial possible

207.1.0.3 2⃣ Epidemiology

207.1.0.3.1 Seasonality
  • N hemisphere: late autumn-early spring (Oct-April peak Dec-Feb)
  • S hemisphere: opposite
  • Tropical: less seasonal
  • 2023-2024 post-COVID resurgence (immunity gap)
207.1.0.3.2 Burden
  • #1 cause of pediatric LRTI globally
  • ~ 60,000 pediatric deaths < 5 yr globally (mostly LMIC)
  • ~ 60,000 hospitalizations + 14,000 deaths/yr ≥ 65 USA
  • Annual epidemics highly predictable
207.1.0.3.3 Re-infection
  • Universal childhood acquisition
  • Lifelong re-infection (immunity wanes)
  • Older adults + immunocompromise: severe re-infection
  • ~ 5-10% of CAP in elderly

207.1.0.4 3⃣ Clinical — Pediatric

207.1.0.4.1 Bronchiolitis (Infant)
  • #1 viral LRTI in infants globally
  • Peak age 2-6 months
  • Onset: 2-3 day URI prodrome → respiratory distress
  • Wheezing, tachypnea, retractions, nasal flaring
  • Hypoxia + respiratory failure in severe
  • Fever low-grade
  • Auscultation: wheezes + crackles
  • Self-limited 7-10 days
207.1.0.4.2 Apnea (Preterm + < 3 mo)
  • Especially preterm infants + < 3 months
  • Can be presenting feature
  • Monitoring critical (preterm)
207.1.0.4.3 Pneumonia
  • LRTI in young children
  • Bilateral interstitial infiltrates
207.1.0.4.4 Severe Disease Criteria
  • Respiratory rate > 70
  • SaO2 < 92% on room air
  • Severe retractions / accessory muscle use
  • Cyanosis
  • Apnea
  • Dehydration
  • Toxic appearance
207.1.0.4.5 Hospitalization Criteria
  • Hypoxia
  • Respiratory failure (impending or established)
  • Dehydration / unable to feed
  • Apnea
  • Severe respiratory distress
207.1.0.4.6 Bronchiolitis Long-term
  • Increased risk of asthma / wheezing in childhood (mechanism debated)
  • Recurrent wheezing post-RSV common

207.1.0.5 4⃣ Clinical — Adults

207.1.0.5.1 Healthy Adults
  • Common cold / URI
  • 1-2 wk self-limited
207.1.0.5.2 Elderly + High-Risk
  • Pneumonia in elderly
  • COPD + asthma exacerbation
  • Heart failure exacerbation
  • Severe systemic illness
207.1.0.5.3 Immunocompromise
  • HSCT + lung transplant — severe pneumonia + high mortality
  • Bronchiolitis obliterans in transplant
  • Treatment: aggressive supportive + ribavirin off-label
207.1.0.5.4 Nursing Home
  • Outbreaks common
  • Pneumonia
  • Mortality 10-20% in nursing home outbreaks elderly

207.1.0.6 5⃣ Diagnosis

207.1.0.6.1 Multiplex Respiratory PCR
  • Most sensitive
  • 1-2 hr turnaround
  • Useful for severe / immunocompromise / outbreak
207.1.0.6.2 Rapid Antigen Test
  • POC, 15-30 min
  • Sensitivity ~ 70% (lower than flu rapid)
  • Useful for outpatient triage
207.1.0.6.3 Clinical Diagnosis
  • Classic bronchiolitis in infant with seasonal exposure → diagnosis often clinical
  • PCR for severe / hospitalized / unclear
207.1.0.6.4 CXR
  • Hyperinflation, peribronchial thickening
  • Not routinely needed (clinical Dx)

207.1.0.7 6⃣ Treatment

207.1.0.7.1 Supportive Care Core
  • Oxygen to maintain SaO2 > 92%
  • IV fluids / NG feeds if poor oral intake
  • Suction nasopharynx (especially infants)
  • High-flow nasal cannula for moderate-severe
  • CPAP for severe
  • Mechanical ventilation for respiratory failure
  • ECMO for refractory ARDS (rare)
207.1.0.7.2 Bronchodilators (Limited Efficacy)
  • AAP 2014 guidelines: don’t routinely use bronchodilators in bronchiolitis (no clear benefit)
  • Trial dose may be considered; continue if obvious response
207.1.0.7.3 Steroids
  • Don’t routinely use in bronchiolitis (no benefit, AAP)
  • COPD / asthma exacerbation: steroid per usual algorithms
207.1.0.7.4 Antibiotics
  • Don’t routinely use unless secondary bacterial infection suspected
  • Common URI / pneumonia bacterial agents if super-infection
207.1.0.7.5 Antiviral
  • Ribavirin: limited efficacy, rare use
    • Inhaled
    • HSCT + severe immunocompromise pneumonia
    • Cost + teratogenicity (pregnancy precautions)
  • No FDA-approved adult antiviral as of 2024
207.1.0.7.6 IVIG / Hyperimmune Globulin
  • RespiGam historical (RSV-specific) — discontinued
  • Standard IVIG sometimes adjunct in severe immunocompromise
207.1.0.7.7 High-Flow Nasal Cannula
  • Standard for moderate respiratory distress
  • Improves work of breathing + oxygenation
  • Bridges to BiPAP / mechanical ventilation

207.1.0.8 7⃣ Prevention — 2023-2024 Game Changer

207.1.0.8.1 Nirsevimab (Beyfortus, FDA 2023)
  • Long-acting mAb against prefusion F protein
  • Half-life ~ 70 days → single dose covers entire RSV season
  • Indication: universal infants entering 1st RSV season; high-risk children entering 2nd season (≥ 24 mo with high-risk conditions)
  • Dose:
    • 50 mg IM if < 5 kg
    • 100 mg IM if ≥ 5 kg
  • 2024 ACIP universal recommendation
  • 5-fold reduction in RSV hospitalization (MELODY trial)
  • Replacing palivizumab in most situations
207.1.0.8.2 Maternal RSVpreF (Abrysvo)
  • Pfizer, FDA 2023
  • Given at 32-36 wk gestation
  • Maternal Ab transferred transplacental → newborn protected ≀ 6 mo
  • Alternative to nirsevimab (don’t typically give both — one or the other)
  • MATISSE trial: 70% efficacy reducing infant RSV LRTI
207.1.0.8.3 Palivizumab (Synagis)
  • Older mAb, monthly during RSV season (5 doses)
  • For high-risk infants only:
    • Preterm < 29 wk gestation
    • Chronic lung disease of prematurity
    • Hemodynamically significant congenital heart disease
  • Being replaced by nirsevimab in most institutions
207.1.0.8.4 Adult Vaccines (2023+ FDA Approvals)
207.1.0.8.4.1 Arexvy (GSK)
  • Recombinant prefusion F protein + AS01E adjuvant
  • ≥ 60 yr (initially)
  • Single dose
  • 80% efficacy preventing severe disease

207.1.0.8.4.2 Abrysvo (Pfizer)
  • Bivalent recombinant prefusion F (both A + B subgroups)
  • ≥ 60 yr + pregnant (32-36 wk)
  • Single dose
  • 86% efficacy preventing severe LRTI in elderly
207.1.0.8.4.3 mRESVIA (Moderna, FDA 2024)
  • mRNA-1345 — encoding prefusion F
  • ≥ 60 yr
  • Single dose
  • 84% efficacy preventing RSV-LRTI in trial
207.1.0.8.5 Recommendations (ACIP 2024)
  • Routine ≥ 75 yr
  • Routine 60-74 with chronic disease (cardiopulmonary, DM, CKD, immunocompromise, nursing home resident)
  • Pregnant 32-36 wk (Abrysvo)
  • Universal infants (nirsevimab)
  • Co-administration with other vaccines OK