Highlight
– Multicentre TriNetX analysis (Kitano et al., 2025) examined association between timing of last nirsevimab dose and RSV test-positivity among children <24 months tested for RSV (Jul 2023–Jun 2025).
– Receiving nirsevimab within 6 months of testing halved the odds of a positive RSV test (OR 0.49; 95% CI 0.42–0.57); protection persisted, though attenuated, when dose was 6–11 months prior (OR 0.67; 95% CI 0.48–0.94).
– No significant protective association was seen when last dose was >12 months before testing (OR 1.21; 95% CI 0.89–1.65). Findings are hypothesis generating and limited by confounding and database constraints.
Background and disease burden
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection in infants and young children worldwide and a major driver of pediatric hospitalizations during seasonal epidemics. Estimations from global burden studies highlight the large morbidity and mortality attributable to RSV in children under 5 years, particularly in infants under 1 year (Shi et al., Lancet 2017). Historically, immunoprophylaxis with palivizumab (monthly injections during RSV season) reduced hospitalization risk in selected high-risk infants but was impractical and costly for universal use (IMpact-RSV Study Group, Pediatrics 1998; AAP guidance).
Long-acting monoclonal antibodies, notably nirsevimab (marketed as Beyfortus), were developed to provide season-long protection with a single intramuscular dose and have been adopted into some national immunization or prophylaxis programs for infants. Understanding the duration of protection conferred in real-world settings is critical for policy, dosing schedules, and evaluating potential impact on RSV epidemiology.
Study design and methods
Kitano and colleagues performed a multicentre retrospective cohort study using the TriNetX global clinical research network, which aggregates electronic health records from participating institutions. The study population comprised children <24 months who underwent microbiologic testing for RSV (PCR or antigen) between July 2023 and June 2025.
Exposure groups were defined by timing of most recent nirsevimab dose before RSV testing: within 6 months, 6–11 months, and beyond 12 months. The reference comparator was children with no record of nirsevimab. The authors used propensity score matching (PSM) by epidemic season to balance measured covariates between groups and then estimated odds ratios (ORs) for a positive RSV test result in the most recent epidemic season.
Key findings
Study population (last epidemic season, unmatched counts reported):
- Received nirsevimab within 6 months before testing: 4,627 children
- Received nirsevimab 6–11 months before testing: 861 children
- Received nirsevimab >12 months before testing: 532 children
- No nirsevimab recorded: 210,626 children
Primary results (propensity-score matched, last epidemic season):
- Nirsevimab within 6 months vs no nirsevimab: OR for a positive RSV test = 0.49 (95% CI 0.42–0.57), p < 0.001 — ~51% lower odds of test-positivity.
- Nirsevimab 6–11 months vs no nirsevimab: OR = 0.67 (95% CI 0.48–0.94), p = 0.020 — ~33% lower odds, attenuated effect.
- Nirsevimab >12 months vs no nirsevimab: OR = 1.21 (95% CI 0.89–1.65), p = 0.234 — no statistically significant reduction, point estimate toward no protection.
These data suggest a graded association between recency of nirsevimab administration and reduced odds of RSV detection, with the strongest effect in the first 6 months and an apparent window of benefit up to about 11 months. The authors conclude that preventive effects were maintained up to 12 months but not beyond, and they caution interpretation because of study limitations.
Interpretation and biological plausibility
Nirsevimab is a monoclonal antibody engineered for extended half-life compared with earlier antibodies such as palivizumab; this pharmacologic design supports a single-dose strategy intended to cover a typical RSV season. Pharmacokinetic and immunobiologic studies have demonstrated prolonged serum persistence relative to non–half-life–extended antibodies, but the expected clinical window of robust neutralizing activity is generally considered to span months, not years. The observed protection up to 11 months in this real-world cohort is plausible for an extended half-life mAb, though direct antibody measurements correlating concentration with protection were not available in this study and cannot be inferred from test-positivity alone.
Strengths
- Large, multinational electronic health record (EHR) dataset allowing contemporary, real-world assessment over multiple epidemic seasons.
- Objective microbiologic endpoints (PCR/antigen testing) rather than diagnostic codes alone.
- Use of propensity score matching by epidemic season to reduce confounding on measured variables.
Key limitations and sources of bias
Important methodological caveats substantially limit causal inference and generalizability:
- Residual confounding: PSM balances measured covariates, but unmeasured confounders (socioeconomic factors, exposure risks, care-seeking behavior, precise indications for nirsevimab) may bias results. Indication bias is possible: infants at higher baseline risk may have been preferentially targeted for prophylaxis (which would bias toward the null) or conversely, clinicians might selectively test unprotected infants more frequently.
- Misclassification of exposure and timing: EHR records may incompletely capture nirsevimab administration (administration outside participating centers, coding gaps), and timing relative to testing could be imprecise.
- Outcome ascertainment bias: Testing practices differ by center and over time; clinicians may be more or less likely to test certain infants, potentially producing detection bias. The study used test-positivity rather than clinical severity or hospitalization outcomes, which are arguably more clinically consequential.
- Immortal time and selection biases: Retrospective timing windows can introduce biases if follow-up and exposure windows are misaligned.
- Representativeness: TriNetX partners may overrepresent high-resource centers and specific healthcare systems, limiting generalizability to low-resource settings.
- Sample size for longer intervals: The number of children with doses >12 months before testing was small (n=532), reducing precision for estimates in that group.
Implications for clinicians and policymakers
These real-world data provide supportive evidence that nirsevimab is associated with lower odds of RSV detection when administered within a year prior to testing, particularly in the first 6 months. However, the observational nature and limitations preclude definitive conclusions about causal effectiveness or duration of protection.
Practical implications include:
- Support for current single-dose, season-focused use in eligible infants, consistent with pharmacologic rationale and regulatory approvals in several jurisdictions.
- Need for caution before extending assumed protective windows beyond manufacturer- or regulator-defined durations; decisions about timing (e.g., birth doses vs. seasonal targeting) should be informed by local RSV seasonality and supply considerations.
- Policy-makers should prioritize prospective surveillance linking administration records, antibody kinetics, clinical outcomes (hospitalization, ICU admission), and viral sequencing to evaluate durability and potential viral escape.
Research gaps and next steps
To move from association to actionable evidence, several research priorities are clear:
- Prospective cohort studies and pragmatic randomized trials measuring clinical endpoints (hospitalization, severity) and correlating serum antibody levels with protection over time.
- Active pharmacokinetic/pharmacodynamic studies in diverse infant subgroups (preterm, comorbidities) to define protective thresholds and optimal timing.
- Real-world effectiveness studies designed to minimize bias (target trial emulation, new-user designs) and inclusive of low- and middle-income settings.
- Monitoring for viral evolution and potential resistance to monoclonal antibodies through sequencing surveillance.
Conclusion
Kitano et al.’s TriNetX analysis suggests that receipt of nirsevimab within 6 months of RSV testing is associated with markedly lower odds of a positive RSV test, with attenuated benefit seen at 6–11 months and no clear benefit beyond 12 months. These observations align with the expected time-limited protective window of a long-acting monoclonal antibody but must be interpreted cautiously because of the limitations inherent in retrospective EHR-based analyses. Definitive assessment of duration of protection and impact on clinically meaningful outcomes requires prospectively collected data, antibody correlate studies, and randomized or rigorously designed observational effectiveness studies.
Funding and clinicaltrials.gov
Funding and declarations were provided in the original publication (Kitano et al., 2025). The present analysis is a secondary interpretation of that peer-reviewed report. Because the study was a retrospective database analysis, clinicaltrials.gov registration was not applicable.
References
1. Kitano T, Tsuzuki S, Fukuda H, Yoshida S. Long-term impact of nirsevimab on prevention of respiratory syncytial virus infection using a real-world global database. J Infect. 2025 Nov 7:106652. doi: 10.1016/j.jinf.2025.106652. Epub ahead of print. PMID: 41207638.
2. Shi T, McAllister DA, O’Brien KL, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. 2017;390(10098):946-958.
3. The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from RSV infection in high-risk infants. Pediatrics. 1998;102(3 Pt 1):531-537.
4. Centers for Disease Control and Prevention. Respiratory Syncytial Virus (RSV). Available at: https://www.cdc.gov/rsv/ (accessed 2025).
