Understanding real-world effectiveness of nirsevimab and the characteristics of breakthrough RSV infections: a study protocol of individual-participant-level data meta-analysis (the GEMINI study)

The recent rollout of nirsevimab across multiple countries represents an important advancement in respiratory syncytial virus (RSV) prevention. However, real-world evidence on how its effectiveness varies with infant age and time since administration, and on the characteristics of breakthrough infections, remains limited.

In this study, we aimed to conduct an international collaborative study to assess the real-world effectiveness of nirsevimab by monthly interval of chronological age and time since administration and to understand the characteristics of breakthrough infections. Both individual-participant-level data (IPD) and aggregated data will be collected from international collaborators identified by systematic review, existing collaborative network and academic conferences. The effectiveness of nirsevimab will be assessed by a test-negative study design, and a two-stage IPD meta-analysis will be conducted for data synthesis; a one-stage IPD meta-analysis will also be conducted among a subset of IPD data with sufficient sample size as an exploratory analysis. We will also describe the epidemiological, clinical and molecular features of breakthrough infections and compare them with infants and young children who were either unvaccinated and infected or vaccinated but not infected. The study will provide detailed insights into the dynamic effectiveness of nirsevimab and the characteristics of breakthrough cases.

The study protocol has been approved by the Ethics Committee of Nanjing Medical University (2025-179). Ethical approval for the contributing studies is expected to be obtained independently by local investigators from their respective ethics committees. Findings will be presented at international conferences and submitted to peer-reviewed journals for publication.