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 upper respiratory symptoms to severe, life-threatening lower respiratory disease, particularly affecting infants, older adults, and immunocompromised individuals. 1

Viral Structure and Classification

• RSV is an enveloped, negative-sense, single-stranded RNA virus classified in the Orthopneumovirus genus of the Pneumoviridae family 2
• The viral genome contains 10 genes encoding 11 proteins, including the critical attachment protein (G) and fusion protein (F) that mediate cell entry 1
• RSV exists as two subtypes (RSV-A and RSV-B) based on variations in the G protein, with alternating predominance patterns between seasons 1
• The virus is named for its characteristic ability to induce fusion of respiratory epithelial cells into multinucleated giant cells called syncytia 1

Clinical Significance and Disease Burden

RSV represents a major global health threat with substantial morbidity and mortality:

• RSV caused 4.59 million cases of lower respiratory tract infection worldwide in 2021, with 12.5 million cases in 2019 before the COVID-19 pandemic 1
• The virus infects most children by age 2 years, with virtually all children experiencing at least one infection during their first two years of life 1
• RSV-associated mortality rates in adults aged ≥70 years now exceed those in children under 5 years, representing a paradigm shift in understanding the disease burden 3
• Among hospitalized elderly patients, mortality rates reach 4.6% in those aged 60-74 years and 6.1% in those ≥75 years 4

Pathophysiology and Immune Response

The virus employs several mechanisms that contribute to disease severity and recurrent infections:

• RSV induces short-lived immune responses, with protective antibodies and T cells waning within weeks to months, making reinfections common even without antigenic variation 1
• Severe RSV disease is associated with inappropriate or dysregulated host immune responses rather than the virus itself 1
• The virus demonstrates immunomodulatory mechanisms that interfere with effective immune clearance 1
• RSV can cause exacerbations of underlying chronic conditions including COPD, asthma, heart failure, and coronary artery disease 1

Clinical Manifestations

Clinical presentations vary dramatically from asymptomatic infection to severe respiratory failure:

• Upper respiratory tract infections with rhinorrhea, cough, and fever are common in all age groups 5
• Lower respiratory tract disease including bronchiolitis and pneumonia occurs primarily in high-risk populations 2, 6
• Severe life-threatening respiratory distress can develop, particularly in premature infants, elderly adults, and immunocompromised patients 1
• Extrapulmonary complications may occur, though respiratory manifestations predominate 2

High-Risk Populations

Certain groups face substantially elevated risk for severe RSV disease:

• Premature infants (≤35 weeks gestation, especially ≤28 weeks) have the highest pediatric risk 1, 7
• Infants with bronchopulmonary dysplasia or hemodynamically significant congenital heart disease 1, 8
• Adults aged ≥60 years, particularly those ≥75 years 1, 4
• Patients with chronic conditions including COPD, asthma, heart failure, diabetes, chronic kidney disease, chronic liver disease, and immunocompromise 1
• Immunocompromised individuals including transplant recipients, those on chronic immunosuppressive therapy, and patients with HIV 7, 4
• Residents of nursing homes or long-term care facilities 1
• Patients with frailty or dementia 1

Current Treatment Landscape

No specific antiviral therapy is approved for routine clinical use in RSV infection—treatment remains primarily supportive care 7, 2, 6:

• Adequate hydration and oxygen supplementation for hypoxemia (SpO2 <90%) 7
• Analgesics such as acetaminophen or ibuprofen for fever and pain management 7
• Ribavirin is restricted to severely immunocompromised patients, particularly hematopoietic stem cell transplant recipients with lower respiratory tract disease, though evidence is limited to observational data 7, 9
• Corticosteroids are explicitly not recommended for routine RSV management 1, 7

Prevention Strategies

Prevention through vaccination and passive immunization has become the cornerstone of RSV management:

For Adults:

• Three RSV vaccines are now approved for adults: RSVPreF3 (Arexvy), RSVpreF (Abrysvo), and mRNA-1345 (mRESVIA) 4, 3
• Vaccination is recommended for all adults aged ≥60 years and adults aged 50-59 years with risk factors 1, 4
• Vaccines should preferably be administered between September and November before RSV season 1
• RSV vaccines can be co-administered with influenza vaccine at different injection sites 1, 4

For Infants:

• Palivizumab (Synagis) provides passive immunization for high-risk infants, reducing RSV hospitalization by 45-55% 7, 8
• Dosing is 15 mg/kg intramuscularly monthly throughout RSV season, maximum 5 doses 7, 8
• Nirsevimab, a newer long-acting monoclonal antibody, is now recommended for all infants <8 months entering their first RSV season 7, 2, 6
• Active vaccination of pregnant women reduces severe LRTI in young infants with 69.4% efficacy 6

Diagnostic Considerations

• Nucleic acid-based testing (RT-PCR) is the preferred diagnostic method, particularly for high-risk populations 4
• Testing is especially important in immunocompromised patients, transplant recipients, and those with severe underlying cardiopulmonary disease 7, 4
• Palivizumab may interfere with immunological-based RSV diagnostic tests such as antigen detection assays 8
• Routine testing is not necessary for outpatient bronchiolitis cases where management will be supportive regardless 7

Key Clinical Pitfalls to Avoid

• Never use palivizumab for treatment of established RSV infection—it is only approved for prevention in high-risk infants 7, 8
• Avoid routine use of corticosteroids in RSV management, as they may delay viral clearance and provide no benefit 1, 7, 4
• Do not prescribe antibiotics without specific evidence of bacterial co-infection 7
• Recognize that patients on systemic corticosteroids (≥10-15 mg prednisone daily) face significantly elevated risk for severe RSV outcomes 4
• Hand hygiene is the single most important measure to prevent nosocomial transmission—alcohol-based rubs are preferred 7