Respiratory Syncytial Virus

Aka: Respiratory Syncytial Virus, Bronchiolitis, RSV, RSV Bronchiolitis, Metapneumovirus

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II. Epidemiology: RSV

  1. Incidence: 2.1 Million children under age 5 years seek medical attention for RSV annually in the U.S.
  2. Annual epidemics occur winter to early spring
    1. Range: November to April
    2. Peak: January to February
  3. Overall hospitalization rate: 1-2% (57,000 per year in United States)
    1. Youngest children are at highest risk for hospitalization (esp. age <90 days)
    2. RSV Bronchiolitis results in hospitalization of 2-3% of infants <12 months old
  4. Attack rates
    1. Daycare exposure: 100% infection rate
    2. Sibling exposure: 40% infection rate
  5. Cohorts Affected
    1. Children under age 2 years (usually 1-6 months old)
    2. Of infants at risk, 50% will be infected
      1. By age 2 years, nearly all children will have had one RSV infection (at least 90%)
      2. Prior infection is no protection against future infection
    3. Older children and adults
      1. Common Cold-like Syndrome
      2. Rhinorrhea, Sore Throat, and cough
    4. Elderly and Immunocompromised patients
      1. Severe Pneumonia may result

III. Risk Factors: More Severe Course

  1. Prematurity
  2. Passive Smoke Exposure
  3. Complex Congenital Heart Disease
  4. Chronic lung disease
  5. Immunosuppression
  6. Neuromuscular disease
  7. Metabolic disorder
  8. Staat (2002) Semin Respir Infect 17:15-20 [PubMed]

IV. Pathophysiology: RSV

  1. Enveloped, nonsegmented, negative-strand RNA virus (Paramyxoviridae Family)
    1. Subtypes A (causes more severe disease)
    2. Subtypes B
  2. Transmission
    1. Close contact
    2. Fingers or fomites
    3. Self inoculation of Conjunctiva or anterior nares
    4. Coarse aerosols from coughing or sneezing
  3. Viral load peaks at 4 to 5 days
    1. Corresponds to peak illness severity at 3-5 days
  4. Incubation: 2 to 8 days
  5. Virus shedding: 3-8 days (up to 4 weeks in infants)
  6. Duration of illness (under age 2 years)
    1. Initial symptoms start to abate at 7 days
    2. Coughing and Wheezing often persist 2-3 weeks
    3. Median: 12 days
    4. Prolonged in 10% of cases as long as 4 weeks
  7. Re-infection with different RSV forms is common
    1. Prior RSV infection confers no Immunity against new infection
  8. Infectious course
    1. Viral replication starts in the nasopharynx
    2. Spreads to the small Bronchiole epithelial lining
    3. Lower respiratory tract infection onset within 3 days with increased airway edema and mucous production, and ultimately tissue necrosis
    4. Results in small airway obstruction, air trapping and increased airway resistance

V. Causes: Bronchiolitis

  1. Respiratory Syncytial Virus (RSV)
    1. Responsible for 50-80% of cases
    2. Coninfection with other virus (e.g Rhinovirus) affects up to 30% of hospitalized RSV cases
      1. Mansbach (2012) Arch Pediatr Adolesc Med 166(8): 700-6 [PubMed]
  2. Human Metapneumovirus (MPV)
    1. Emerging paramyxovirus
    2. Similar presentation as RSV
    3. Hamelin (2004) Clin Infect Dis 38:983-90 [PubMed]
  3. Parainfluenza
  4. Rhinovirus
  5. Influenza
  6. Adenovirus
  7. Human Bocavirus

VI. Symptoms

  1. Viral prodrome (initial 2-3 days)
    1. Coryza
    2. Rhinorrhea
  2. Typical symptoms in infants and young children
    1. Cough (98%)
    2. Low grade fever (75%)
    3. Labored breathing (73%)
    4. Wheezing (65%)
    5. Rhinorrhea
    6. Mild systemic symptoms
  3. Typical symptoms in older children
    1. Cough
    2. Coryza
    3. Rhinorrhea
    4. Conjunctivitis
  4. Severe illness
    1. Grunting
    2. Nasal flaring
    3. Intercostal retractions
    4. Tachypnea or Dyspnea
    5. Hypoxia and Cyanosis
    6. Apparent Life Threatening Event or Apnea
      1. Premature Infants or very young infants are at increased risk
      2. May occur without other signs of respiratory distress

VII. Signs

  1. See Clinical Severity Scoring System Tool
  2. Respiratory
    1. Common findings
      1. Diffuse Wheezing
      2. Rales
    2. Other findings
      1. Rhonchi
      2. Tachypnea
      3. Cough
      4. Accessory Muscle use (e.g. Intercostal retractions)
      5. Hypoxia (Oxygen Saturation <92%)
      6. Cyanosis
  3. Hydration
    1. Assess for Dehydration (mucous membranes, alertness, Skin Turgor, decreased Urine Output)

VIII. Differential Diagnosis

  1. See Wheezing
  2. Reactive airway disease
  3. Foreign Body Aspiration
  4. High fever suggests alternative diagnosis (e.g. Pneumonia)
    1. Especially consider in unimmunized children

IX. Evaluation: Age under 3 months

  1. Infants under age 30 days
    1. Complete full Neonatal Sepsis evaluation for febrile infants under 1 month of age (despite Bronchiolitis diagnosis)
  2. Infants under age 60 days
    1. Evaluation based on clinical evaluation
    2. Admit all infants under 60 days of age with Bronchiolitis due to apnea risk
  3. Infants ages 60-90 days of age
    1. Ill appearing, febrile infants should be evaluated for bacteremia (and coinfection)
    2. Non-toxic febrile infants at 60-90 days with Bronchiolitis do not need a bacteremia work-up
      1. Blood Cultures and Lumbar Puncture are not needed
      2. Urinalysis and Urine Culture should still be performed
      3. Ralston (2011) Arch Pediatr Adolesc Med 165(10):951-6 [PubMed]

X. Labs

  1. Blood Culture indications
    1. Not needed in routine cases
    2. Consider in toxic appearing children, fever >38.5 C (101.3 F) or ICU admission
  2. Complete Blood Count (CBC) is not routinely recommended
  3. Venous Blood Gas (VBG) Indications
    1. Children who appear to be tiring
    2. Severe respiratory distress
    3. FIO2 requirements >40%
  4. RSV swabs or washings of nasopharynx, throat, or Sputum
    1. Bronchiolitis (and RSV) is a clinical diagnosis based on symptoms and signs (see above)
      1. Does not require lab testing for confirmation
      2. RSV is only one cause of Bronchiolitis (e.g. MPV, parainfluenza, Influenza, Adenovirus, bocavirus)
      3. A negative RSV does not exclude other Bronchiolitis cause
    2. Indications
      1. RSV is a clinical diagnosis and routine testing is not recommended
      2. Other diagnosis considered (e.g. Sepsis in age under 2-3 months)
        1. RSV positive puts a child at very low risk of serious Bacterial Infection
        2. Levine (2004) Pediatrics 113(6): 1728-34 [PubMed]
      3. Inpatient room placement (shared inpatient rooms)
        1. Consider grouping patients with similar symptoms instead of basing on lab criteria
      4. Epidemiologic data to define start of outbreak
    3. Efficacy
      1. Test Sensitivity: 80-90%
      2. Test Specificity: 90-99%
  5. Urinalysis and Urine Culture
    1. Consider in patients with RSV severe enough to consider admission
    2. Urinary Tract Infections are present in 2-5% of RSV cases
      1. However this is similar to baseline UTI rate in asymptomatic children
      2. Urinalysis is controversial in febrile children with Bronchiolitis (some guidelines recommend)
  6. RSV is associated with a decreased risk of other conditions
    1. Decreased risk of Meningitis
    2. Decreased risk of bacteremia

XI. Imaging: Chest XRay

  1. Indications
    1. Not routinely recommended in Bronchiolitis (very low yield)
      1. Chest XRay risks False Positives and antibiotics overuse
    2. High fever
    3. Hypoxemia (Oxygen Saturation <90%)
    4. Severe symptoms (e.g. ICU admission)
    5. Comorbid cardiopulmonary disease
    6. Respiratory complications (e.g. Pneumonia, Pneumothorax)
  2. Findings consistent with Bronchiolitis
    1. Hyperexpansion or hyperinflation
    2. Peribronchial thickening or peribronchial markings
    3. Atelectasis
    4. Variable infiltrates or Viral Pneumonia
      1. May lead to False PositivePneumonia diagnoses (and unnecessary antibiotics)

XII. Evaluation: Hospitalization Indications

  1. Place in respiratory isolation if admitted
  2. Central Apnea risk
    1. Witnessed apneic event
    2. RSV in infant under 6-8 weeks of age or birth weight <2.5 kg
      1. Prior recommendations were for hospitalizing children as old as age 2-3 months
      2. Highest risk: Full-term infant <1 month of age OR Preterm Infant at <48 weeks post-conception
      3. Walsh (2015) Pediatrics 136(5): e1228-36 +PMID:26482666 [PubMed]
      4. Willmerth (2006) Ann Emerg Med 48(4): 441-7 [PubMed]
  3. Comorbidity (one or more non-functioning systems)
    1. Comorbid cardiopulmonary disease (e.g. Cystic Fibrosis, Congenital Heart Defect)
    2. Comorbid Immunodeficiency
  4. Dehydration
    1. Inability to maintain adequate hydration
    2. Feeding difficulty (due to respiratory distress)
  5. Respiratory distress
    1. See Clinical Severity Scoring System Tool
    2. See Respiratory Distress in Children with Pneumonia
    3. See Pediatric Early Warning Score (PEWS Score)
    4. Respiratory Rate >40 breaths per minute
      1. See Tachypnea for criteria based on age
    5. Oxygen Saturation <90%
      1. Brief minor desaturations are common with sleeping and eating
      2. Do not contraindicate disposition home in children with otherwise reassuring findings
      3. Principi (2016) JAMA Pediatr 170(6):602-8 +PMID:26928704 [PubMed]
    6. Retractions (intercostal, supraclavicular, abdominal)
    7. Inability to tolerate oral intake
    8. Lethargy
    9. Hypercarbia
    10. Chest XRay changes (e.g. Atelectasis)
    11. Cyanosis

XIII. Management: Effective Measures

  1. General Measures
    1. Constantly reassess for signs of impending Respiratory Failure
      1. May be signaled by a 'normalization' of the Respiratory Rate (due to respiratory muscle Fatigue)
    2. Humidified Oxygen to keep Oxygen Saturation >90% (>88% while asleep)
      1. Low threshold to transition to Humidified High Flow Nasal Cannula as needed (see below)
      2. In practice, humidified High Flow Nasal Cannula (HHFNC) is typically used instead
    3. Suctioning of secretions
      1. Paramount intervention both during the acute evaluation and for home
        1. Especially for the obligate nose breathers age <2 years
      2. Includes gentle Nasal Saline with suctioning (avoid Trauma and secondary edema)
      3. Provide parents with a hospital-grade nasal suction bulb
        1. Acorn manual nasal aspirator
        2. NoseFrida
      4. Consider nasal Decongestant (Neo-Synephrine)
        1. Neo-Synephrine (Phenylephrine) is preferred (If a nasal Decongestant is used in children)
        2. Avoid afrin (Oxymetazoline) in children
          1. Risk of Central alpha-2 Agonist, Clonidine-like CNS depression ("One Pill Can Kill" list)
    4. Hydration
    5. Frequent feedings
      1. Parents should anticipate smaller volume feedings more frequently (every 3-4 hours) for the first 5 days of RSV
  2. Severe cases
    1. Humidified High Flow Nasal Cannula (HHFNC)
      1. Indicated in increased Work of Breathing (e.g. retractions, grunting, apnea, nasal flaring) or Hypoxia
      2. Humidified High Flow Nasal Cannula starting at 2 L/kg/min and titrate as needed
        1. See Humidified High Flow Nasal Cannula for protocol
      3. Efficacy
        1. Prevents airway collapse and Atelectasis
        2. Decreases work of breathing
        3. Effective and well tolerated
    2. Nasal continuous positive airway pressure (nasal CPAP or nCPAP) or RAM Cannula
      1. Alternative to Humidified High Flow Nasal Cannula
      2. Offers greater PEEP than HHFNC
    3. Endotracheal Intubation with Mechanical Ventilation
      1. Indicated in severe Hypoxia refractory to above measures
      2. Nasal CPAP has been effective at reducing the number of children requiring intubation for Bronchiolitis
    4. Helium-Oxygen therapy
      1. Rarely used
      2. Martinon-Torres (2002) Pediatrics 109:68-73 [PubMed]

XIV. Management: Ineffective or inconsistently effective measures

  1. Nebulizer (not recommended as of 2014, per AAP)
    1. Precautions: AAP 2014 Guidelines
      1. AAP recommends no nebulizer treatments (including Albuterol, Epinephrine and Hypertonic Saline)
      2. AAP recommends no Corticosteroids
      3. Supplemental Oxygen is optional when Oxygen Saturations are >90%
      4. http://pediatrics.aappublications.org/content/134/5/e1474
    2. Nebulized Albuterol
      1. Background
        1. Albuterol does not improve oxygenation in RSV
        2. Albuterol does not shorten hospital stay in RSV
        3. Albuterol may offer minor symptomatic relief in RSV
        4. Albuterol has adverse effects (e.g. Tachycardia)
      2. Older approach (prior to 2014 guidelines)
        1. May be effective in up to 50% of RSV patients (especially for children with history of Asthma or atopy)
        2. May still give a trial if atopic/RAD history or Warm Respiratory Scoring Tool >4
        3. If improvement with trial then continue every 6 hours (if not, then supportive care only)
      3. References
        1. Turner (2003) Ann Emerg Med 42:709-11 [PubMed]
    3. Nebulized Atrovent
      1. See Reactive Airway Disease
      2. Some evidence as of 2011 suggesting Atrovent is effective (but not recommended by AAP 2014 Guidelines)
    4. Nebulized racemic epinephrine
      1. Not recommended by AAP 2014 Guidelines
      2. Variable efficacy and use has declined since 2007
      3. Requires 2-4 hours of observation after administration due to transient effect with risk of rebound
      4. Wainright (2003) N Engl J Med 349:27-35 [PubMed]
    5. Hypertonic Saline Nebulization (not recommended)
      1. Not recommended by AAP 2014 Guidelines for acute use (ED and short 1-2 day hospitalizations)
      2. Nebulizer dose: 4 ml of 3% Hypertonic Saline
      3. May shorten hospital stay (from >3 days)
      4. Increases cough
      5. Not effective in preventing hospitalization (may not be as useful for emergency care)
      6. Angoulvant (2017) JAMA Pediatr 171(8):e171333 PMID:28586918 [PubMed]
      7. Zhang (2008) Cochrane Database Syst Rev :CD006458 [PubMed]
  2. Systemic Corticosteroids (not recommended)
    1. Do not decrease severity of illness or shorten the disease course
    2. Not recommended by American Academy of Pediatrics
    3. Atopic Patients and older patient's with Asthma may benefit
    4. Data is mixed and some studies have shown benefit (e.g. Systemic Dexamethasone with Nebulized Epinephrine)
      1. Csonka (2003) J Pediatr 143:725-30 [PubMed]
      2. Plint (2009) N Engl J Med 360(20): 2079-89 [PubMed]
    5. Some studies have shown benefit with decreased length of hospital stay (especially children under age 1 year old)
      1. Garrison (2000) Pediatrics 105(4): E44 [PubMed]
      2. Alansari (2013) Pediatrics 132(4): e810-6 [PubMed]

XV. Management: Emergency Department Approach

  1. Attempt to determine disposition (hospitalization versus home) in the first hour
  2. Step 1: Nasal Suctioning
    1. Assess patient (consider using a scoring system)
    2. Nasal Saline and suction
    3. Consider nasal Decongestant (Neo-Synephrine) as described above (avoid afrin)
    4. Assess patient (consider using a scoring system)
  3. Step 2: Nebulized Albuterol or Albuterol MDI with Aerochamber and mask
    1. Not recommended by AAP as of 2014 but often trialed in Emergency Department
    2. May give a trial if atopic/RAD history or Warm Respiratory Scoring Tool >4
    3. Supply family with Albuterol for home if effective
    4. Consider Dexamethasone (or other Corticosteroid) in those who respond to Albuterol (or have atopic/RAD risks)
      1. Also not recommended by AAP as of 2014
  4. Step 3: High Flow Nasal Cannula (HHFNC)
    1. Indicated in increased Work of Breathing (e.g. retractions, grunting, apnea, nasal flaring)
  5. References
    1. Sloas and Orman in Herbert (2014) EM:Rap 14(7): 1-3

XVI. Management: Therapies with variable or limited evidence

  1. Montelukast
    1. Improved post-RSV clinical symptoms (age 3-36 months)
    2. Bisgaard (2003) Am J Respir Crit Care Med 167:379-83 [PubMed]
  2. Surfactant
    1. Tibby (2000) Am J Respir Crit Care 162:1251-6 [PubMed]
  3. Aerosolized Ribavirin (Virazole)
    1. Use limited to immunosuppressed children with severe disease
    2. May be useful early at maximal viral load
    3. Variable efficacy
    4. Cost exceeds $1000 per day
    5. Randolph (1996) Arch Pediatr Adolesc Med 150:942-7 [PubMed]

XVII. Management: Therapies not found to be useful

  1. Theophylline does not change the clinical course
  2. Antibiotics without Bacterial Infection identified
  3. Inhaled Interferon alfa-2a
  4. RSV Immune globulin for acute treatment
    1. Indicated for prophylaxis in high risk infants
    2. No evidence for benefit in acute disease
  5. Palivizumab for acute treatment
    1. Indicated for prophylaxis in high risk infants
    2. No evidence for benefit in acute disease
  6. Racemic Epinephrine mixed with Hypertonic Saline
    1. See above for AAP recommendations 2014 to not use Epinephrine nebs
    2. Observe for at least 2-3 hours after dose

XVIII. Prevention

  1. General measures
    1. Avoid contagious exposures
    2. Avoid Passive Smoke Exposure
    3. Hand Washing
    4. Exclusive Breast Feeding for first 6 months of life
  2. Medications
    1. RSV Immune Globulin (RSV-IG, Respigam)
    2. Palivizumab (Synagis)
      1. Given monthly for up to 5 months of RSV season (November 1 to March 1)
      2. See Palivizumab for indications
        1. Premature Infants born before 29 weeks gestation (<32 weeks if on oxygen >28 days)
        2. Cyanotic Congenital Heart Disease
        3. Chronic lung disease (Bronchopulmonary Dysplasia)
        4. Neuromuscular disorders

XIX. Prognosis

  1. Severe episodes: 10-20% of cases
    1. Present with Dehydration, Hypoxemia, nasal flaring, grunting, apnea, Respiratory Failure
    2. Admission rates: 19-45% of cases
    3. ICU Admission: 3% of cases
  2. Overall RSV case fatality rate: 1%
    1. Deaths: 372 per year in United States (90% are under age 1 year)
  3. More severe illness if comorbid underlying disease
    1. Congenital Heart Disease (RSV Mortality 37%)
    2. Bronchopulmonary Dysplasia (and Pulmonary Hypertension)
    3. Immunodeficiency
    4. Age <3 months
    5. Weight <11 pounds (5 kg)
    6. Premature birth (<35 weeks gestation, esp. <29 weeks gestation)

XX. Complications

  1. Persistent reactive airway disease
    1. Higher risk with more severe RSV infection or Rhinovirus
    2. Wheezing episodes persist up to 5 years in 40% of children with RSV infection
    3. Wheezing episodes persist beyond 5 years in 10% of children with RSV infection

XXI. References

  1. Serrano (2014) Crit Dec Emerg Med 28(6): 2-10
  2. Sloas and Orman in Herbert (2014) EM:Rap 14(8): 1-2
  3. Warrington (2016) Crit Dec Emerg Med 30(7): 15-20
  4. Dawson-Caswell (2011) Am Fam Physician 83(2): 141-6 [PubMed]
  5. Panitch (2003) Pediatr Infect Dis J 22:S83-8 [PubMed]
  6. Jafri (2003) Pediatr Infect Dis J 22:S89-93 [PubMed]
  7. Joseph (2011) Pediatr Emerg Med Prac 8(3) [PubMed]
  8. Smith (2017) Am Fam Physician 95(2): 94-99 [PubMed]
  9. Steiner (2004) Am Fam Physician 69:325-30 [PubMed]

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