Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is an enveloped, single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae and the genus Orthopneumovirus. Two subtypes (A and B) are present in outbreaks, but type A causes more severe disease. Respiratory syncytial virus causes infections of the lungs and respiratory tract and spreads via respiratory droplets. Respiratory syncytial virus is a leading cause of lower respiratory tract infections in infants and young children. Complications include bronchiolitis, pneumonia, and otitis media. Respiratory syncytial virus is managed with supportive care.

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Classification

RNA Viruses Flowchart Classification

RNA virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA or RNA. RNA genome viruses can be further characterized by either a single- or double-stranded RNA. “Enveloped” viruses are covered by a thin coat of cell membrane (usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses. Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly employed as messenger RNA (mRNA), which is translated into proteins. “Negative-sense,” single-stranded viruses employ RNA dependent RNA polymerase, a viral enzyme, to transcribe their genome into messenger RNA.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics

Taxonomy and structure

  • Genus Pneumovirus 
  • Family Paramyxoviridae
  • Single-stranded, linear, negative-sense RNA
  • Enveloped virus
  • Large helical capsid carries RNA-dependent RNA polymerase in virion

Basic features

  • Absence of hemagglutinin
  • Consists of 2 serotypes
  • Limited to the respiratory tract
  • Two subtypes (A and B) are present in outbreaks; type A causes more severe disease.

Clinically relevant species

  • The Paramyxoviridae family consists of 3 genera:
    • Paramyxovirus, which includes the parainfluenza and mumps viruses 
    • Orthopneumovirus, which includes the respiratory syncytial virus (RSV)
    • Morbillivirus, which includes the measles virus
  • The Paramyxoviridae family causes 30%–40% of all acute respiratory infections in infants and children.
RSV Respiratory syncytial virus

Electron micrograph of respiratory syncytial virus

Image: “Electron micrograph of RSV” by CDC. License: Public Domain

Pathogenesis

Transmission and replication cycle

Transmission: 

Respiratory droplets from an infected individual come into contact with the mucosa of the eyes, mouth, or nose of another individual.

Replication cycle:

  • Once an individual is exposed, there is a fusion of the viral and host cell membranes. 
    • The viral surface glycoproteins F and G control viral attachment and the initial stages of infection.
    • The viral nucleocapsid and polymerase enter the host cell cytoplasm.
  • RNA-dependent RNA polymerase transcribes the viral genome into mRNA, which is translated by host proteins.
  • The RNA polymerase synthesizes a positive-sense antigenome, a complementary template strand used to construct negative-sense RNA.
  • The resultant RNA is packaged into nucleocapsids and transported to the plasma membrane for assembly and budding.
Schematic image of RSV Respiratory Syncytial Virus life cycle

Schematic image of respiratory syncytial virus (RSV) life cycle

Image: “Schematic image of RSV life cycle” by Bawage S et al. License: CC BY 3.0, cropped by Lecturio.

Natural reservoirs

  • Humans
  • Cattle
  • Sheep
  • Goats

Pathophysiology

  • The infection spreads within the respiratory tract, without systemic spread.
  • RSV spreads by cell-to-cell transfer along intracytoplasmic bridges (syncytia) from the upper to the lower respiratory tract (the terminal bronchioles)
  • Lytic viral replication causes epithelial cell sloughing → exposing nociceptive nerve fibers → stimulating the cough reflex
  • Influx of PMNs into the airway → replaced by lymphomononuclear infiltration of the peribronchiolar tissue and increased microvascular permeability → submucosal edema and swelling
  • Mucous secretions increase in quantity and viscosity → widespread mucous plugging

Diseases Caused by Respiratory Syncytial Virus

Although RSV is limited to the respiratory tract, it can manifest as illnesses of varying severity depending on the individual’s age and state of the immune system.

Diseases caused

  • Infants:
    • Acute bronchiolitis
    • Pneumonia
    • Acute otitis media
    • Respiratory failure
  • Immunocompromised or elderly adults: 
    • Pneumonia
    • Acute exacerbation of underlying chronic illness (e.g., chronic obstructive pulmonary disease (COPD), asthma, congestive heart failure)

Epidemiology

  • Incidence: affects 4 million–5 million children < 4 years of age per year 
    • Primarily a disease of young infants and children
    • Peak incidence at 2–8 months of age
  • > 125,000 patients with RSV infection are hospitalized annually in the United States.
  • In mild presentations of RSV, there is an equal incidence among boys and girls.
  • However, boys are 2 times more likely to require hospitalization because of RSV infections.

Risk factors

  • Premature infants
  • Infants with chronic lung disease
  • Children with congenital heart disease
  • Low birth weight
  • Maternal smoking during pregnancy
  • No breastfeeding

Clinical presentation

  • Incubation time: 4–5 days
  • Upper respiratory tract infection
    • Cough
    • Rhinorrhea
  • Lower respiratory tract infection
    • Tachypnea
    • Intercostal and subcostal retractions
    • Cyanosis
    • Wheezing and rales
    • Fever
  • Associated with otitis media, dehydration, and apneic episodes

Diagnosis

  • Laboratory studies are not typically indicated in well-appearing patients who are breathing room air, are well hydrated, and are feeding adequately. 
  • RSV-specific diagnostic tests
    • Antigen detection (point-of-care testing)
    • Molecular probes (PCR assays)
    • Culture
  • Antigen detection (point-of-care testing)
  • Molecular probes (PCR assays)
  • Culture
  • Chest X-ray for suspicion of pneumonia
Chest X-ray respiratory syncytial virus bronchiolitis

Chest X-ray of an infant with respiratory syncytial virus bronchiolitis

Image: “Chest X-ray on admission to the emergency room” by Di Nardo M et al. License: CC BY 2.0

Management

Supportive care is the mainstay of therapy for RSV infection, including oxygenation and hydration. 

Pharmacologic therapy:

  • Generally not recommended by the American Academy of Pediatrics but may be used in select cases.
  • In select cases, beta-agonists (albuterol), alpha-agonists (epinephrine), or corticosteroids may be used
  • In patients with significant underlying risk factors (e.g., transplant patients), ribavirin is used.

Prophylaxis: palivizumab, FDA-approved for children at high risk for severe RSV disease

  • Premature infants born at < 29 weeks, < 1 year of age
  • Premature infants born at < 32 weeks, < 1 year of age with chronic lung disease
  • In the 2nd year of life for children who need supplemental oxygen or long-term corticosteroid or diuretic therapy
  • Children < 24 months who have significant congenital heart disease or pulmonary hypertension

Differential Diagnosis

Acute bronchiolitis: respiratory condition caused by inflammation of the bronchioles. The majority of cases of acute bronchiolitis are caused by RSV. Patients usually present with upper respiratory symptoms, such as cough and congestion, and later develop lower respiratory signs, including dyspnea, wheezing, crackles, and hypoxia. Diagnosis is clinical, and treatment is directed at improving oxygenation and hydration. The disease is self-limiting and has a good prognosis with appropriate management.

References:

  1. Krilov L. (2019). Respiratory syncytial virus infection treatment & management. Emedicine. Retrieved February 6, 2021, from https://emedicine.medscape.com/article/971488-treatment#d8
  2. Welliver RC. (2009). Bronchiolitis and infectious asthma. Feigin RD, Cherry JD, Demmler-Harrison GJ, Kaplan SL, Eds. Textbook of Pediatric Infectious Diseases, 6th ed. Philadelphia: Saunders Elsevier, pp. 277–288.
  3. Centers for Disease Control and Prevention. (2018). Respiratory syncytial virus infection (RSV): trends and surveillance. https://www.cdc.gov/rsv/research/us-surveillance.html
  4. Graham B, Barr F. (2020). Respiratory syncytial virus infection: Treatment. UpToDate. Retrieved Feb 6, 2021, from https://www.uptodate.com/contents/respiratory-syncytial-virus-infection-treatment
  5. Ralson S, et al. (2014). Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics 134:e1474–e1502.

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