Effectiveness of nirsevimab against hospitalization for RSV bronchiolitis according to RSV lineages
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Importance
Nirsevimab, a monoclonal antibody against RSV, was implemented in France in September 2023. Recently, rare resistance-associated substitutions were described in RSV but the effectiveness according to lineages remains unclear.
Objective
We aimed to estimate the effectiveness of nirsevimab against hospitalization for RSV bronchiolitis according to RSV lineages.
Design
We conducted a multicenter test-negative case-control study from October 15, 2023 to March 15, 2025.
Setting
This study was based on data from three national multicentric prospective studies. The 12 participating centers were secondary or tertiary hospital with a pediatric department located in France.
Participants
We included all children younger than 12 months who were hospitalized for RSV bronchiolitis in one of the participating centers in France during the two first RSV epidemic seasons following the implementation of nirsevimab (from October 15, 2023 to February 29, 2024, and from October 10, 2024 to March 15, 2025).
Main outcomes and measures
The main outcome of the study was the RSV test result of bronchiolitis cases. RSV whole-genome sequencing was performed using a tiled amplicon approach covering the complete viral genome, as previously described in the POLYRES studies. We estimated the effectiveness of nirsevimab by a multivariable logistic regression model adjusted for potential confounders. We estimated the adjusted risk of immunization failure for each lineage by calculating relative odds ratio to a reference lineage. A range of sensitivity analyses were conducted.
Results
We included 3019 infants with bronchiolitis among which 2273 had a positive RSV test (case patients) and 746 had a negative RSV test (control patients). Overall, 373/2273 (16.4%) case patients were immunized by nirsevimab versus 423/746 (56.7%) control patients. The adjusted effectiveness of nirsevimab against hospitalization for bronchiolitis was 88.4% (95% CI, 84.5–91.4) with RSV-B and 79.4% (95% CI, 73.7–83.8) with RSV-A. The risk of immunization failure was 3.2-fold (95% CI 1.8–5.7) higher for lineages derived from A.D.3 than for lineages derived from B.D.4.1.
Conclusion and relevance
In this multicentric case-control study, we observed that nirsevimab effectiveness was variable across RSV lineages, with a lower effectiveness against A.D.3 lineages compare to others. Further surveillance is needed to confirm these findings and assess their implication on RSV lineages epidemiology as nirsevimab use expands.
KEYPOINT
Question
Does the effectiveness of nirsevimab against hospitalization for RSV-bronchiolitis change based on the RSV lineages?
Findings
In this case-control test negative design study that include 3019 infants, the effectiveness of nirsevimab against hospitalization for bronchiolitis was significantly higher with RSV-B than with RSV-A. Specifically, we found a 3.2-fold risk of immunization failure with lineages derived from A.D.3 than with lineages with highest effectiveness.
Meaning
This study suggest that nirsevimab effectiveness varies substantially across RSV lineages, with lineages derived from A.D.3 less susceptible to nirsevimab. This highlight the importance of molecular and clinical surveillance over the coming years of wide nirsevimab use.
