What is Respiratory Syncytial Virus (RSV)?

What is Respiratory Syncytial Virus (RSV)?

RSV is a single-stranded RNA virus belonging to the Pneumoviridae family that causes respiratory tract infections ranging from mild cold-like symptoms to severe, life-threatening pneumonia and respiratory distress, with the highest morbidity and mortality occurring in infants, older adults (especially ≥75 years), and immunocompromised individuals. 1

Viral Structure and Classification

• RSV is classified into two subtypes—RSV-A and RSV-B—based on variations in the attachment (G) protein, with alternating predominance patterns observed between seasons 1
• The virus contains 10 genes encoding 11 proteins, including the critical fusion (F) protein and attachment (G) protein that are targets for vaccines and monoclonal antibodies 1
• RSV is named for its characteristic ability to induce fusion of respiratory epithelial cells into multinucleated giant cells called syncytia 1

Clinical Manifestations and Disease Spectrum

The clinical presentation varies dramatically from asymptomatic infection to severe respiratory failure, with symptoms including fever, runny nose, cough, and in severe cases, bronchiolitis or pneumonia. 2

• In healthy adults, RSV typically causes upper respiratory tract infections that resemble the common cold but tend to be more severe than average, sometimes mimicking influenza 3
• Lower respiratory tract involvement can lead to acute pneumonia, severe respiratory distress, and exacerbations of underlying chronic conditions such as COPD, asthma, and heart failure 1, 4
• Distinguishing RSV from other viral respiratory infections based on clinical grounds alone is not possible with sufficient precision to be clinically useful 5

Immunology and Reinfection Patterns

• The immune response to RSV is short-lived, with protective antibodies and T cells waning within weeks to months after infection 1
• Reinfections occur commonly throughout life, even without antigenic variation of the virus, because immunity is neither complete nor durable 1, 3
• Severe RSV disease is associated with inappropriate or dysregulated host immune responses rather than simply viral load 1

Epidemiology and Disease Burden

RSV accounts for 4.59 million cases of lower respiratory tract infection worldwide across all ages annually, with community-based studies estimating yearly incidence at 3-7% in adults aged ≥60 years in high-income countries. 1, 5

• RSV is identified in 6-11% of outpatient respiratory tract infection consultations in older adults and accounts for 4-11% of adults hospitalized with respiratory tract infection 5
• Among hospitalized adults with RSV, 6-15% require intensive care admission, and 1-12% die 5
• Mortality rates in hospitalized elderly patients are 4.6% in those aged 60-74 years and 6.1% in those ≥75 years 6
• The disease burden of RSV is comparable to influenza in adults, though RSV patients tend to be older with more comorbidities and respiratory symptoms but less frequently present with fever 5

High-Risk Populations

Individuals at highest risk for severe outcomes include those ≥75 years, adults ≥50 years with chronic conditions (COPD, asthma, heart failure, coronary artery disease, diabetes, chronic kidney disease, chronic liver disease), immunocompromised patients, and nursing home residents. 1, 6

• Patients on systemic corticosteroids face the highest hospitalization risk compared to other underlying conditions 6
• Long-term sequelae are common and include deterioration of underlying diseases, particularly heart failure and COPD 5
• Elderly patients with dementia have significantly higher mid- to long-term mortality following RSV infection (adjusted hazard ratio = 1.86) 6

Diagnosis

• The reference standard for diagnosis is RT-PCR, as point-of-care tests perform less well with lower viral loads 6, 5
• Testing samples from a single respiratory tract site may result in underdetection 5
• Nucleic acid-based testing is particularly recommended for elderly patients at high risk for severe disease and immunocompromised individuals 6

Prevention Strategies

Three RSV vaccines are now approved for adults ≥60 years (RSVPreF3/Arexvy from GSK, RSVpreF/Abrysvo from Pfizer, and mRESVIA/mRNA-1345), with vaccination recommended for all persons ≥60 years and those ≥50 years with risk factors. 1, 6, 4

• Vaccination should preferably be administered between September and November before RSV season begins 1
• The vaccine can be co-administered with influenza vaccine at different injection sites 6
• For infants and young children not eligible for vaccines, passive immunization with monoclonal antibodies (nirsevimab or palivizumab) is recommended 7, 8

Treatment Approach

Treatment for RSV remains primarily supportive care, including adequate hydration, supplemental oxygen when SpO2 falls persistently below 90%, and management of underlying condition exacerbations. 7, 6, 4

• Ribavirin (aerosolized or oral) combined with intravenous immunoglobulin may be considered for severely immunocompromised patients, hematopoietic stem cell transplant recipients, and mechanically ventilated patients with documented severe RSV infection, though evidence is limited to observational studies 7, 6
• Antibacterial medications should only be used when specific indications of bacterial co-infection exist 7
• Palivizumab has no therapeutic benefit for treating established RSV infection and is only approved for prevention in high-risk infants 7, 9