www.nature.

com/pr

CORRESPONDENCE
Nirsevimab decreased the subsequent risk of respiratory
syncytial virus infection and wheezing in the 2023–2024
RSV season
© The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc 2025

Pediatric Research; https://doi.org/10.1038/s41390-024-03782-4 wheezing. Infants were tracked from the index date until the
earliest of the following censoring events: occurrence of the pre-
specified outcomes, death, loss to follow-up, or the end of the
follow-up period (up to 365 days after the index date).
A 1:1 propensity score matching (greedy nearest-neighbor
INTRODUCTION matching algorithm with a caliper of 0.1 pooled standard
Preventing respiratory syncytial virus (RSV) infection in infants and deviations [SD] of the logit of the propensity score) was
young children is a global public health priority.1 Long-term completed based on age, sex, race, socioeconomic status, prenatal
respiratory outcomes associated with RSV infection are recurrent and perinatal conditions, and congenital abnormalities to match
1234567890();,:

wheezing and childhood asthma, as respiratory viruses can cause each subject in the nirsevimab cohort to a select eligible control.
airway epithelial damage, inflammatory changes in the airways, We excluded individuals with outcomes that occurred prior to the
bronchial hyperresponsiveness, and cytokine overproduction.2 In index date from the analysis. We calculated hazard ratios (HRs)
July 2023, the U.S. Food and Drug Administration approved with 95% confidence interval (CIs) using the Cox proportional
nirsevimab, a monoclonal antibody with an extended half-life for hazards model. All statistical analyses were performed in the
preventing RSV infection in both preterm and term infants.3 TriNetX Advanced Analytics Platform and RStudio (Version
However, nirsevimab real-world impact post-approval and wide- 2024.04.2 + 764).
spread use on its effectiveness in preventing respiratory infections
and their consequences, especially wheezing, remains limited.
Hence, we used a real-time database to compare the effectiveness RESULTS
of nirsevimab in immunized infants from the 2023–2024 RSV We identified 192,677 infants, including 7052 (3.6%) infants who
season who received nirsevimab prophylaxis to those who did received nirsevimab and 185,625 (96.3%) infants in the
not. unmatched non-recipient group. After matching, there were
7042 infants in each group. In the nirsevimab group, nirsevimab
was administrated shortly after birth in 97.4% infants (mean age at
METHODS index [SD]: 0 [2.4] months; 49.6% female). In the matched non-
This population-based cohort study was conducted using the recipient group, 97.5% received their first vaccine shortly after
TriNetX Research Network, a de-identified electronic medical birth (mean age at index [SD] was 0 [2.4] months; 47.2% female).
record database from 93 health-care organizations, which are The baseline characteristics of study participants are listed in
mainly tertiary care centers in the U.S. but also include some Supplementary eTable 2 of the online supplement. The median
global centers. Given the anonymized nature of the dataset as per follow-up duration was 233 days (interquartile range [IQR], 47 days)
the deidentification standard defined in Section §164.514(a) of the for the nirsevimab group and was for 245 days (IQR, 58 days) for
HIPAA Privacy Rule, the study was exempt from institutional the non-recipient group.
review board review and informed consent. This study followed Infants who received nirsevimab had a significantly lower risk of
the Strengthening the Reporting of Observational Studies in RSV infection compared to infants who did not (HR: 0.24; 95% CI,
Epidemiology (STROBE) reporting guidelines. We used Interna- 0.17–0.33). Additionally, nirsevimab recipients also had a lower risk
tional Statistical Classification of Diseases and Related Health of wheezing (HR: 0.73; 95% CI, 0.58–0.93) over the 365-day
Problems, Tenth Revision (ICD-10) codes, Current Procedural observation (Table 1).
Terminology (CPT), and RxNorm to identify the exposure,
covariates, and outcomes (Supplementary eTable 1). We identified
infants (i.e., age <12 months) who had an encounter for routine DISCUSSION
immunizations from October 1, 2023 to March 31, 2024: infants In this real-world, post-approval study of nirsevimab, we found
who received nirsevimab and at least one routine immunization that the administration of nirsevimab to infants during the
were included in the nirsevimab group. Those who received only 2023–2024 RSV season significantly decreased the risk of RSV
routine immunization but not nirsevimab were included in the infection and wheezing for up to 365 days post-prophylaxis. Our
non-recipient group. The index date was the date of the findings align with existing evidence from clinical trials and large
nirsevimab administration or the first encounter for routine cohort studies, demonstrating the effectiveness of nirsevimab in
childhood immunization. The outcomes of interest were RSV reducing the incidence of RSV infection.3–6 In infants, RSV
infection, including codes for bronchiolitis, bronchitis, pneumonia, bronchiolitis, especially severe disease, is associated with acute
otitis media, and upper respiratory infection all due to RSV, and and recurrent wheezing. Though the mechanism is yet to be fully

Received: 1 November 2024 Accepted: 13 November 2024

 Correspondence
2

(0.17, 0.33)
(0.58, 0.93)
elucidated, the general theory proposes that the shedding of
95% CI infected cells and syncytia bodies from RSV invasion might
contribute to airway hyperresponsiveness, particularly when
infection occurs during the airway development window in early
childhood.7 Previous studies have demonstrated that RSV
0.24 immunoprophylaxis effectively reduces the risk of subsequent
0.73 recurrent wheezing in the first year of life for preterm infants.8,9 In
HR

the present study, nirsevimab displayed similar effectiveness in

mitigating the risk of wheezing during infancy for those receiving
the antibody after birth. Further prospective studies are required
Cases per 1000 person-

to confirm these findings across different risk-strata populations

and to explore the long-term benefits of nirsevimab on RSV-
related morbidity in infancy and early childhood, such as asthma.
The strengths of this study include its large sample size,
longitudinal tracking, and propensity-score matching for multiple
months

covariates to minimize confounding. However, there are several

10.90

limitations. The retrospective nature of the study limits our

6.25

conclusions, and the use of ICD-10 codes may result in

misclassification bias. Last, although we employed a rigorous
matching process, unmeasured confounding may still exist and
Total person-months at

thus, may potentially affect our results.

Non-recipient group (n = 7042)

CONCLUSION
In this real-world, post-approval analysis, nirsevimab was asso-
ciated with a reduced risk of RSV infection and wheezing in
80,380
73,402

infancy. These results reaffirm the effectiveness of nirsevimab to

risk

prevent RSV infection and support the present Advisory Commit-

tee on Immunization Practices (ACIP) recommendations to
No. of events

administer nirsevimab to all eligible infants.

Comparisons of outcomes in infants receiving nirsevimab versus matched non-recipient infants.

Kevin Sheng-Kai Ma1,6 ✉, Serena Y. Tsai2,6, Chadi M. El Saleeby3,

Includes acute bronchiolitis, bronchitis, pneumonia, otitis media, and upper respiratory infection due to RSV.

Camille N. Kotton4,7 and Jonathan M. Mansbach5,7 ✉

502
800

1
Center for Global Health, Perelman School of Medicine, University of
Pennsylvania, Philadelphia, PA, USA. 2Department of Dermatology,
Massachusetts General Hospital, Boston, MA, USA. 3Divisions of
Cases per 1000 person-

Hospital Medicine and Infectious Disease, Department of Pediatrics,

Mass General for Children, Harvard Medical School, Boston, MA, USA.
4
Transplant and Immunocompromised Host Infectious Diseases Unit,
Infectious, Diseases Division, Massachusetts General Hospital,
Harvard Medical School, Boston, MA, USA. 5Department of Pediatrics,
Boston Children’s Hospital, Boston, MA, USA. 6These authors
months

contributed equally: Kevin Sheng-Kai Ma, Serena Y. Tsai. 7These

1.75
9.94

authors jointly supervised this work: Camille N. Kotton, Jonathan M.

Mansbach. ✉email: [email protected];
CI confidence interval, HR hazard ratio; RSV, Respiratory syncytial virus.

[email protected]
Total person-months at

DATA AVAILABILITY
The datasets generated during and/or analyzed during the current study are available
from the corresponding author on reasonable request.
Nirsevimab group (n = 7042)

81,302
70,796

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Correspondence and requests for materials should be addressed to
Kevin Sheng-Kai Ma or Jonathan M. Mansbach.

AUTHOR CONTRIBUTIONS Reprints and permission information is available at http://www.nature.com/

Substantial contributions to conception and design: K.S.M., S.Y.T., J.M.M. Acquisition, reprints
analysis, and interpretation of data: K.S.M., S.Y.T. Drafting the article and revising it
critically for important intellectual content: all authors. Final approval of the version Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims
to be published: all authors. in published maps and institutional affiliations.

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