Respiratory syncytial virus (RSV)

Introduction

Respiratory syncytial virus (RSV) is a highly contagious viral pathogen that predominantly affects the respiratory tract. It is a major cause of acute lower respiratory tract infections in infants and young children worldwide, but it can also lead to significant morbidity and mortality among older adults, immunocompromised individuals, and those with chronic cardiopulmonary conditions. RSV infection ranges from mild upper respiratory symptoms to severe bronchiolitis and pneumonia, and it remains a leading cause of hospitalization in infants under one year of age.

Virology and Structure
RSV is an enveloped, single-stranded, negative-sense RNA virus belonging to the family Paramyxoviridae and genus Orthopneumovirus. It contains a helical nucleocapsid surrounded by a lipid envelope derived from the host cell membrane. The viral genome encodes several structural and non-structural proteins, with the most critical being:

• Fusion (F) protein: Mediates viral entry into host cells and facilitates cell-to-cell fusion, leading to the formation of multinucleated giant cells (syncytia).

• Attachment (G) protein: Facilitates viral attachment to host respiratory epithelial cells.

• Small hydrophobic (SH) protein: Involved in viral assembly and possibly modulates host immune responses.

The F protein is a major target for antiviral agents and preventive measures, such as monoclonal antibodies and vaccines, because of its role in viral entry and its relatively conserved structure.

Epidemiology
RSV is endemic worldwide, with annual outbreaks typically occurring during late fall, winter, and early spring in temperate climates. In tropical regions, RSV can circulate year-round, often peaking during the rainy season. Virtually all children are infected with RSV by the age of two years, and reinfections occur throughout life due to incomplete immunity.

Populations at highest risk for severe RSV disease include:

• Infants, particularly those under 6 months of age.

• Premature infants (<35 weeks gestation).

• Children with chronic lung disease or congenital heart disease.

• Immunocompromised patients.

• Older adults, especially those over 65 years.

Pathogenesis
The pathogenesis of RSV involves viral replication in the epithelial cells lining the respiratory tract. Upon entry via the nose or mouth, RSV targets the ciliated epithelial cells of the nasopharynx and, in severe cases, spreads to the lower respiratory tract. Viral replication and the host immune response contribute to inflammation, mucus hypersecretion, edema, and sloughing of epithelial cells. This leads to obstruction of small airways (bronchioles), particularly in infants, resulting in the characteristic clinical presentation of bronchiolitis.

Cell-mediated immunity plays a central role in viral clearance, but immune-mediated damage can also exacerbate airway obstruction. Reinfections are common because RSV-specific immunity is incomplete and declines over time.

Clinical Manifestations
RSV infection has a broad clinical spectrum that depends on the age and underlying health status of the patient.

1. In Infants and Young Children

   • Mild disease may present as an upper respiratory tract infection (URI) with symptoms such as rhinorrhea, nasal congestion, mild cough, and low-grade fever.

   • Moderate to severe disease can manifest as bronchiolitis, characterized by cough, tachypnea, wheezing, nasal flaring, chest retractions, and hypoxia.

   • In severe cases, apnea (particularly in young infants), dehydration, and respiratory failure can occur.

2. In Older Children and Adults

   • Usually manifests as mild cold-like symptoms with nasal congestion, cough, and sore throat.

   • In adults with chronic pulmonary or cardiac diseases, RSV may precipitate exacerbations or cause pneumonia.

3. In Immunocompromised Individuals

   • Can lead to prolonged viral shedding, severe pneumonia, and high mortality rates.

Complications

• Severe bronchiolitis requiring hospitalization.

• Pneumonia (viral or secondary bacterial).

• Apnea in young infants.

• Respiratory failure requiring mechanical ventilation.

• Long-term sequelae such as recurrent wheezing and increased risk of asthma development.

Diagnosis
Diagnosis of RSV infection can be based on clinical presentation during known outbreak seasons, but laboratory confirmation is often used in hospitalized patients or high-risk cases. Diagnostic methods include:

• Rapid antigen detection tests: Provide quick results, commonly used in pediatric settings.

• Reverse transcription polymerase chain reaction (RT-PCR): High sensitivity and specificity, now widely used.

• Viral culture: Less commonly used due to slower turnaround times.

• Serology: Mainly for epidemiological purposes.

Treatment
There is no specific curative antiviral therapy for most RSV infections; management is largely supportive, aimed at alleviating symptoms and preventing complications. However, targeted antiviral agents and immunotherapies are available for select high-risk populations.

1. Supportive Care

• Maintenance of adequate oxygenation through supplemental oxygen in hypoxic patients.

• Nasal suctioning to clear secretions in infants.

• Adequate hydration, either orally or intravenously, depending on the patient’s condition.

• Mechanical ventilation or non-invasive ventilation in severe respiratory failure.

2. Pharmacologic Treatment

a. Antiviral Therapy

• Ribavirin (generic name: ribavirin): A broad-spectrum antiviral that inhibits viral RNA synthesis.

  • Formulations: Aerosolized solution (most common for RSV), oral, and intravenous forms.

  • Indications: Reserved for severe RSV infection in high-risk infants and immunocompromised patients due to cost, potential toxicity, and uncertain benefit in routine cases.

  • Dose (aerosolized): 20 mg/mL solution administered via continuous inhalation for 12–18 hours/day over 3–7 days.

b. Monoclonal Antibodies (for Prevention and High-Risk Situations)
While not used as acute treatment in established disease, monoclonal antibodies play a preventive role and may reduce disease severity if given early.

• Palivizumab (generic name: palivizumab): A humanized monoclonal antibody targeting the RSV F protein, preventing viral entry into cells.

  • Indications: Prophylaxis in high-risk infants (premature, chronic lung disease, congenital heart disease).

  • Dose: 15 mg/kg intramuscularly once monthly during RSV season.

• Nirsevimab (generic name: nirsevimab): A newer extended half-life monoclonal antibody designed for broad infant prophylaxis.

  • Dose: Single intramuscular injection per RSV season, dose varies by weight.

3. Adjunctive Therapies (Generally Not Recommended for Routine Use)

• Bronchodilators (e.g., salbutamol/albuterol) are not routinely recommended but may be trialed in cases with significant wheezing, especially if the patient has underlying reactive airway disease.

• Corticosteroids have not shown consistent benefit and are generally not recommended in otherwise healthy infants.

• Antibiotics are not indicated unless there is strong suspicion or evidence of secondary bacterial infection.

Prevention
Prevention strategies for RSV involve both non-pharmacologic and pharmacologic measures.

1. Non-Pharmacologic Measures

• Hand hygiene with soap and water or alcohol-based hand rubs.

• Avoiding close contact with infected individuals during RSV season.

• Disinfection of surfaces and objects, as RSV can survive for hours on hard surfaces.

• Use of masks and respiratory hygiene in high-risk settings.

2. Pharmacologic Prophylaxis

• Palivizumab for high-risk infants as outlined above.

• Nirsevimab for broader infant protection, potentially replacing or supplementing palivizumab in many regions.

3. Vaccines
Recent advances have led to the development of RSV vaccines for older adults and pregnant women (to confer passive immunity to infants). These vaccines target the prefusion conformation of the F protein to elicit a potent neutralizing antibody response. Although still being introduced in various countries, maternal vaccination during pregnancy can reduce the risk of severe RSV disease in newborns.

RSV in Special Populations

1. Premature Infants
Premature infants have immature lungs, limited respiratory reserve, and reduced maternal antibody transfer, making them more vulnerable to severe RSV disease. Prophylaxis with monoclonal antibodies is strongly recommended in eligible cases.

2. Immunocompromised Patients
These patients may develop prolonged, severe disease. In certain cases, ribavirin in combination with intravenous immunoglobulin (IVIG) has been used, although evidence is limited and practices vary by institution.

3. Older Adults
RSV is increasingly recognized as a cause of significant morbidity in adults over 65 years, contributing to pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD), and congestive heart failure. Vaccination strategies targeting this group are being adopted in several countries.

Public Health Impact
RSV remains one of the leading causes of pediatric hospitalization worldwide, placing a substantial economic burden on healthcare systems. Hospitalization costs, lost parental workdays, and long-term respiratory sequelae all contribute to its public health significance. In developing countries, RSV is a major contributor to child mortality, particularly where access to supportive care is limited.

Research and Future Directions
Research into RSV pathogenesis, immunity, and vaccine development has accelerated in recent years. Advances include:

• Novel antivirals targeting viral fusion and replication.

• Long-acting monoclonal antibodies for single-dose seasonal prophylaxis.

• Effective vaccines for pregnant women and older adults.

• Improved diagnostics for rapid identification and isolation of cases.

The future management of RSV is expected to shift from primarily supportive care toward a preventive model that incorporates maternal immunization, widespread infant prophylaxis, and targeted treatment for severe disease.