What are the risks and management strategies for coinfection with Respiratory Syncytial Virus (RSV)?

Risk of Coinfection with RSV

Coinfection with RSV and other respiratory viruses is common (occurring in 18-44% of cases), but the clinical impact on disease severity remains controversial, with most evidence suggesting no significant worsening of outcomes except for specific RSV-hMPV coinfections. 1

Epidemiology of RSV Coinfections

• Coinfection rates are substantial, with approximately 18% of infants with acute respiratory illness showing coinfection with two or more viruses, and up to 40-44% of hospitalized viral respiratory tract infections involving bacterial or viral coinfections 1

• Rhinovirus (RV) is the most common coinfecting virus with RSV, though adenovirus (ADV), human metapneumovirus (hMPV), and parainfluenza viruses (PIVs) are also frequently codetected 1

• Among coronavirus infections specifically, 43.8% were found to have coinfection with an additional virus 1

Impact on Clinical Outcomes: The Evidence is Mixed

Evidence Against Increased Severity

• In immunocompetent children with lower respiratory tract infection, RSV coinfection with any other respiratory virus was NOT associated with more severe disease than RSV infection alone 1

• Some studies in highly immunocompromised patient populations show no difference in patient outcomes when comparing coinfections to single virus infections 1

• A 2023 prospective study found that patients with single RSV infection actually had HIGHER disease severity compared to those with RSV coinfections, including higher PICU admission rates (OR = 5.9), longer hospitalization duration, and higher severity scores 2

Evidence Supporting Increased Severity

• RSV-hMPV coinfection specifically shows increased risk: Meta-analysis demonstrates higher ICU admission rates (OR = 7.2,95% CI = 2.1-25.1) compared to RSV mono-infection, with a trend toward longer hospital stays 3

• RSV-ADV coinfections were associated with increased risk of life-threatening disease (ICU admission, mechanical ventilation, or death) compared to RSV single-virus infections 1

• RSV-influenza coinfections showed increased length of hospital stay compared to RSV alone 1

• Infants with RSV and a second virus in lower respiratory tract infections demonstrated increased length of stay in some studies 1

High-Risk Populations for Severe Coinfection

Immunocompromised Children

• RSV infection in immunocompromised children can progress to respiratory failure and death, with mortality rates of 5-8.6% in various retrospective studies 1

• **Profound lymphopenia (<100 cells/mm³) is the critical risk factor** for progression from upper to lower respiratory tract disease, while lymphocyte counts >1000 cells/mm³ appear protective 1

• Specific high-risk groups include:

  • Allogeneic HSCT recipients (4 of 5 deaths in one series) 1
  • Children with severe combined immunodeficiency 1
  • Solid organ transplant recipients (though no deaths in some series) 1
  • Children receiving chemotherapy for malignancy (37% progression to lower respiratory tract disease, 5% mortality) 1

• Fungal coinfection (Aspergillus species) and bacterial coinfection (bacteremia/fungemia) significantly increase mortality risk in immunocompromised patients 1

• Viral-bacterial coinfection in community-acquired pneumonia is associated with more complicated courses (hospital death or mechanical ventilation ≥7 days) than bacteria alone, viruses alone, or no identified etiology 1

Other High-Risk Groups

• Children with Down syndrome have increased RSV hospitalization rates (42-67/1000 child-years vs 12/1000 in controls), though 41-51% have concurrent cardiac or pulmonary risk factors 1

• Children with neuromuscular disease who are hospitalized with RSV tend to be older and may have progressive susceptibility to respiratory disease with age 1

• Congenital heart disease patients show 45% reduction in hospitalization with prophylaxis, indicating baseline high risk 4

Management Implications

Diagnostic Considerations

• Palivizumab can interfere with RSV diagnostic assays, including rapid chromatographic/enzyme immunoassays, immunofluorescence assays, and direct immunofluorescence assays using monoclonal antibodies targeting RSV F protein 4

• RT-PCR assays are not inhibited by palivizumab and should be used for laboratory confirmation when clinical suspicion is high despite negative immunological assays 4

• Multiplex molecular panels may have decreased sensitivity for certain targets (RSVA, influenza A, adenovirus) compared to singleplex assays 1

Prophylaxis Strategy

• Palivizumab provides 55% reduction in RSV hospitalization in premature infants and those with chronic lung disease, and 45% reduction in children with hemodynamically significant congenital heart disease 4

• Palivizumab does NOT reduce mortality from RSV infection and does not significantly decrease recurrent wheezing rates 5

• Dosing is 15 mg/kg monthly throughout RSV season (typically November through April), with additional dose needed after cardiopulmonary bypass 4

• Consider prophylaxis for children <24 months who are profoundly immunocompromised, though population-based data on efficacy in this group are limited 1, 5

Clinical Pitfalls to Avoid

• Do not assume all coinfections worsen outcomes: The majority of evidence suggests RSV coinfections (except RSV-hMPV) do not significantly increase severity in immunocompetent children 1, 2

• Do not rely solely on antibody levels in immunocompromised patients: Preexisting anti-RSV antibody concentration does NOT correlate with progression from upper to lower respiratory tract disease in HSCT recipients 1

• Monitor absolute lymphocyte count closely: Lymphopenia <100 cells/mm³ is the strongest predictor of progression to severe disease in immunocompromised patients, not the degree of immunosuppression itself 1

• Recognize that viral shedding occurs before symptom onset: Individuals are infectious even before symptomatic presentation begins, complicating infection control efforts 6