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Nirsevimab Effectiveness Against Intensive Care Unit Admission for Respiratory Syncytial Virus in Infants — 24 States, December 2024–April 2025
Weekly / November 20, 2025 / 74(37);580–588
Laura D. Zambrano, PhD1,*; Regina M. Simeone, PhD1,*; Margaret M. Newhams, MPH2; Amanda B. Payne, PhD1; Natasha B. Halasa, MD3; Amber O. Orzel-Lockwood, MPH2; Jemima M. Calixte, MS2; Satoshi Kamidani, MD, PhD4; Hillary Crandall, MD5; Melissa A. Cameron, MD6; Jennifer E. Schuster, MD7; Aline B. Maddux, MD8; Kathleen Chiotos, MD9; Katherine Irby, MD10; Steven L. Shein, MD11; Mary Allen Staat, MD12; Lora M. Martin, MSN13; Samina S. Bhumbra, MD14; Ryan A. Nofziger, MD15; Jigar C. Chauhan, MD16,17; Danielle M. Zerr, MD18,19; Shira J. Gertz, MD20; Judith A. Guzman-Cottrill, DO21; Michele Kong, MD22; Janet R. Hume, MD23; Bria M. Coates, MD24; Kelly N. Michelson, MD24; Emily R. Levy, MD25; Tamara T. Bradford, MD26,27; Stephanie P. Schwartz, MD28; Tracie C. Walker, MD28; Melissa S. Stockwell, MD29,30; Austin Biggs, MD31; Alexander H. Hogan, MD32,33; Katherine Lindsey, MPH1,34; Angela P. Campbell, MD1,†; Adrienne G. Randolph, MD2,35,†; Overcoming RSV Investigators (View author affiliations)
View suggested citationSummary
What is already known about this topic?
Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization and intensive care unit (ICU) admission in the United States. Effectiveness of nirsevimab, a long-acting monoclonal antibody, has been established against RSV-associated lower respiratory tract infection and hospitalization among infants; nirsevimab is currently recommended by CDC to prevent severe RSV-related disease. Data are more limited regarding its effectiveness against RSV infection resulting in ICU admission and respiratory failure.
What is added by this report?
In this multicenter case-control investigation, nirsevimab was 80% effective at preventing RSV-associated ICU admission and 83% effective at preventing acute respiratory failure among infants admitted to an ICU with respiratory symptoms during their first RSV season.
What are the implications for public health practice?
These data support recommendations to use nirsevimab as a prevention strategy to protect infants from severe outcomes from RSV infection.
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Abstract
Respiratory syncytial virus (RSV) is a leading cause of intensive care unit (ICU) admission and respiratory failure among infants (children aged <1 year) in the United States. In August 2023, CDC’s Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect against RSV-associated lower respiratory tract infection among all infants aged <8 months born during or entering their first RSV season. Following licensure, nirsevimab effectiveness has been demonstrated against RSV-associated infant hospitalization, but evidence regarding effectiveness against RSV-associated critical illness is limited. In a 27-hospital case-control investigation, nirsevimab effectiveness against both RSV-associated infant ICU admission and acute respiratory failure (illness requiring continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation) after hospital admission was evaluated during December 1, 2024−April 15, 2025. Among 457 case-patients who received a positive RSV test result and 302 control patients who received a negative RSV test result admitted to an ICU with respiratory symptoms, 14% and 45%, respectively, had received nirsevimab ≥7 days before symptom onset. Nirsevimab was 80% effective (95% CI = 70%–86%) against RSV-associated ICU admission and 83% effective (95% CI = 74%–90%) against acute respiratory failure when received a median of 52 days (IQR = 32–89 days) and 50 days (IQR = 32–86 days) before onset for each respective endpoint. These estimates support the recommendation for use of nirsevimab as a prevention strategy to protect infants against severe outcomes from RSV infection.
Introduction
Respiratory syncytial virus (RSV) is a leading cause of intensive care unit (ICU) admission and acute respiratory failure in U.S. infants (1,2). Pooled, prelicensure, placebo-controlled clinical trials of nirsevimab, a long-acting anti-RSV monoclonal antibody, indicated high efficacy against RSV lower respiratory tract infection resulting in hospitalization and ICU admission (3). In August 2023, the Advisory Committee on Immunization Practices (ACIP) recommended nirsevimab for all infants aged <8 months born during or entering their first RSV season whose mothers had not received maternal RSV vaccine >14 days before delivery (3). Postlicensure, effectiveness of nirsevimab in preventing RSV-associated hospitalization among young infants has been demonstrated to be high (4), but real-world effectiveness in preventing RSV-associated ICU admission and acute respiratory failure has not been rigorously assessed using large U.S. multicenter patient networks. In this analysis of data from a large, multicenter surveillance network, the effectiveness of 1 dose of nirsevimab against both RSV-associated ICU admission and acute respiratory failure among hospitalized infants aged <1 year was estimated.
Methods
Participants
This case-control investigation relied on the Overcoming RSV Network, an extension of the CDC-funded Overcoming COVID-19 Network to conduct RSV surveillance, to collect data from 27 pediatric hospitals in 24 states that actively enrolled patients and documented information on their demographic and clinical characteristics and RSV immunization status. Infants (children aged <1 year) who were admitted to an ICU with respiratory symptoms§ that began ≤14 days before hospital admission were prospectively enrolled. Case-patients were infants born during April 1, 2024–March 31, 2025, who were admitted to an ICU during hospitalization for laboratory-confirmed¶ RSV-associated disease during December 1, 2024–April 15, 2025. Control patients were born during the same period but received a negative RSV test result** ≤1 day before or during hospitalization. Case-patients and control patients were enrolled and matched in a targeted 1:1 ratio by site, date of hospital admission (within 30 days), and age group (<1 month, 1–2 months, 3–5 months, and 6–11 months). Control patients were admitted to an ICU during November 1, 2024–April 15, 2025, to account for matching within 30 days of hospitalization to a case-patient. Nirsevimab receipt was defined as having received 1 dose ≥7 days before hospitalization, to account for the time to peak antibody concentration.†† Infants were a priori excluded§§ from the analysis if 1) verification of RSV immunization product receipt was unsuccessful,¶¶ 2) nirsevimab was received <7 days before illness onset or before October 1, 2024, or >1 nirsevimab dose was received, 3) palivizumab (a monoclonal antibody indicated for children aged <2 years at high risk for severe RSV infection) was received,*** 4) the birth mother received maternal RSV vaccine during pregnancy, 5) illness onset occurred >14 days before hospitalization, 6) the first positive RSV test result was received >3 days after admission, or 7) the infant was aged <7 days at symptom onset.
Statistical Analysis and Product Effectiveness Estimation
The primary analysis assessed nirsevimab effectiveness against RSV-related ICU admission using all eligible ICU-admitted case-patients and control patients. A secondary analysis assessed effectiveness against acute respiratory failure, defined as illness requiring respiratory support within an ICU (above the patient’s baseline received at home preadmission)††† involving continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or invasive mechanical ventilation (IMV). The secondary analysis included case-patients with acute respiratory failure and all control patients.
Balance of matching factors and potential covariates between case-patients and control patients was assessed to identify potential confounding using the absolute value of the standardized mean differences (SMD).§§§ Unconditional multivariable logistic regression was used to estimate odds ratios for the ICU admission and respiratory failure outcomes among the entire enrolled population, using generalized estimating equations to address within-hospital site correlation, and adjusting for infant age in months, biweekly date of hospital admission, U.S. Census Bureau region, the presence of one or more specified underlying medical conditions,¶¶¶ and social vulnerability index of infant’s residential zip code.**** The primary analysis was stratified by interval from nirsevimab dose to symptom onset (7–59 days and ≥60 days) to account for the mean nirsevimab half-life from trial data of 59 days (5). Nirsevimab effectiveness was calculated as (1 − adjusted odds ratio) x 100%.
To account for potential differences in matching characteristics between case-patients and control patients in the overall sample, a post hoc analysis was performed using conditional multivariable logistic regression, incorporating only matched 1:1 case-patients and control patient pairs. SAS software (version 9.4; SAS Institute) was used to conduct all analyses. This activity was reviewed by CDC, deemed not research, and conducted consistent with applicable federal law and CDC policy.††††
Results
Characteristics of Enrolled Population
A total of 917 infants admitted to an ICU were enrolled, including 548 (60%) case-patients and 369 (40%) control patients. After the exclusion of 91 (17%) case-patients and 67 (18%) control patients,§§§§ 457 case-patients and 302 control patients remained. Distributions of sex, race and ethnicity, and hospital U.S. Census Bureau region¶¶¶¶ were similar among case-patients and control patients (Table 1). Compared with control patients, case-patients less commonly had a history of one or more underlying medical conditions (11% versus 34%, SMD = 0.59). Among the 62 (14%) case-patients and 136 (45%) control patients who received nirsevimab, the median interval from administration of the nirsevimab dose to symptom onset was 64 days among case-patients (IQR = 45–109 days) and 46 days among control patients (IQR = 29–83 days) (SMD = 0.39).
Among case-patients and control patients, 237 (52%) and 165 (55%), respectively, met criteria for acute respiratory failure. Among control patients, the highest level of respiratory support received above the patient’s preadmission baseline (11% CPAP, 17% BiPAP, and 27% IMV) was similar to or higher than that received by case-patients (14% CPAP, 25% BiPAP, and 14% IMV). Median length of hospital and ICU stay was 6 days (IQR = 4–9 days) and 4 days (IQR = 3–6 days), respectively, for case-patients and 6 days (IQR = 4–11 days) and 4 days (IQR = 2–7 days) for control patients. Two case-patients and two control patients required extracorporeal membrane oxygenation; and one case-patient and four control patients died during their hospitalization.
Nirsevimab Effectiveness
Overall, 62 (14%) of 457 case-patients and 136 (45%) of 302 control patients had received nirsevimab ≥7 days before illness onset (Table 2). Nirsevimab effectiveness against RSV-associated ICU admission among infants in their first RSV season was 80% (95% CI % = 70%–86%); the median interval from nirsevimab receipt to symptom onset was 52 days (IQR = 32–89 days). Effectiveness against acute respiratory failure among all enrolled ICU-admitted patients was 83% (95% CI = 74%–90%); the median interval from nirsevimab receipt to symptom onset was 50 days (IQR = 32–86 days). When stratified by interval from receipt of nirsevimab to symptom onset, nirsevimab effectiveness against RSV-associated ICU admission was 86% (95% CI = 77%–92%) at 7–59 days after the dose and 66% (95% CI = 47%–79%) at 60–183 days. Including only 226 matched pairs, overall effectiveness against ICU admission was 76% (95% CI = 59%–86%).
Discussion
In this multisite analysis of 759 U.S. infants admitted to an ICU for acute respiratory infection during their first RSV season, nirsevimab was 80% effective against RSV-associated ICU admission a median of 52 days from receipt to symptom onset and 83% effective against RSV-associated acute respiratory failure. CDC recommends nirsevimab to prevent severe illness among infants and young children (3) and recently added clesrovimab as a second infant monoclonal antibody option in June 2025 (6). This investigation demonstrated effectiveness of nirsevimab against severe RSV-related outcomes in a population of infants who received it up to 6 months before onset of respiratory symptoms.
Strengths of this analysis include a large and geographically heterogeneous sample and systematic methods for verifying nirsevimab receipt through electronic health records or state immunization information systems. Few studies have been adequately powered to assess nirsevimab effectiveness against RSV-associated illness resulting in ICU admission or acute respiratory failure in infants during their first RSV season. Previously, the only postlicensure U.S. analysis demonstrated 85% effectiveness against ICU admission; however, these results were from a single regional health system lacking nationwide generalizability (7). That U.S. analysis was included in a meta-analysis that included studies from France and Spain, indicating a pooled estimate of nirsevimab effectiveness against RSV-related ICU admission of 81% (8). In this investigation, most (89%) infants admitted to an ICU for RSV-associated illness were otherwise healthy, and 71% were born at term, aligning with previous descriptions of infants with severe RSV (9,10).
Limitations
The findings in this report are subject to at least five limitations. First, clinical RSV testing was used to identify case-patients and control patients, but expanded clinical respiratory viral testing was not conducted consistently across sites; therefore, the possible contribution of other respiratory viruses, particularly among case-patients, could not be assessed. Second, a matched control patient was not identified for each case-patient; however, a post hoc analysis limited to matched case-patients and control patient pairs, conducted to assess the impact of matching imbalance on results, yielded similar results compared with the primary analysis. Third, although nirsevimab receipt was verified through examination of infant immunization records, ascertainment of maternal RSV vaccine receipt might have been incomplete. This could have resulted in misclassification of infants who were protected against RSV as unprotected, and biased the results toward the null, thereby diluting the observed effectiveness of the intervention relative to the true value (if differential misclassification did not occur). Fourth, although timing from dose receipt to symptom onset might impact effectiveness, this investigation was not sufficiently powered to precisely assess duration of protection from nirsevimab. Finally, as an observational investigation, this study is likely subject to residual confounding by unmeasured factors and variables, although the study’s effectiveness estimates align with those of previous studies and meta-analyses.
Implications for Public Health Practice
In this large case-control investigation, nirsevimab was protective against RSV-associated ICU admission and acute respiratory failure during the 2024–25 U.S. RSV season. Most children admitted to an ICU for RSV were previously healthy. ACIP recommends that infants be protected against severe RSV through either infant receipt of a long-acting RSV monoclonal antibody (nirsevimab or clesrovimab) or maternal RSV vaccination during pregnancy. These findings add to growing evidence supporting the effectiveness of monoclonal antibody immunization against severe outcomes from RSV infection in infants during their first RSV season and can be used by clinicians and parents to guide use of this prevention product.
Acknowledgments
Abby L. Martin, Ralph D. Whitehead, Jr., Ryan E. Wiegand, CDC.
Overcoming RSV Investigators
Michele Kong, Children’s of Alabama, Birmingham, Alabama; Meghan Murdock, Children’s of Alabama, Birmingham, Alabama; Heather Kelley, Children’s of Alabama, Birmingham, Alabama; Candice Colston, Children’s of Alabama, Birmingham, Alabama; Katherine Irby, Arkansas Children’s Hospital, Little Rock, Arkansas; Ronald C. Sanders, Arkansas Children’s Hospital, Little Rock, Arkansas; Masson Yates, Arkansas Children’s Hospital, Little Rock, Arkansas; Ashlyn Madding, Arkansas Children’s Hospital, Little Rock, Arkansas; Melissa A. Cameron, Rady Children’s Hospital, San Diego, California; Michael Henne, Rady Children’s Hospital, San Diego, California; Aline B. Maddux, Children’s Hospital Colorado, Aurora, Colorado; Ariana Valenzuela, Children’s Hospital Colorado, Aurora, Colorado; Natasha Baig, Children’s Hospital Colorado, Aurora, Colorado; Lexi Petruccelli, Children’s Hospital Colorado, Aurora, Colorado; Rachel Greer, Children’s Hospital Colorado, Aurora, Colorado; Heidi Sauceda, Children’s Hospital Colorado, Aurora, Colorado; Frances Zorensky, Children’s Hospital Colorado, Aurora, Colorado; Alexander H. Hogan, Connecticut Children’s Medical Center, Hartford, Connecticut; Katherine Herbst, Connecticut Children’s Medical Center, Hartford, Connecticut; Carlie Defelice, Connecticut Children’s Medical Center, Hartford, Connecticut; Gretchen Blume, Connecticut Children’s Medical Center, Hartford, Connecticut; Jigar C. Chauhan, Nemours Children’s Hospital, Wilmington, Delaware; Scott L. Weiss, Nemours Children’s Hospital, Wilmington, Delaware; Rebecca Clifford, Nemours Children’s Hospital, Wilmington, Delaware; Jenna Lapira, Nemours Children’s Hospital, Wilmington, Delaware; Satoshi Kamidani, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia; Mark D. Gonzalez, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia; Caroline R. Ciric, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia; Jong-Ha C. Choi, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia; Gabriella Ess, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia; Anna K. Mitchell, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia; Luis W. Salazar, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia; Janelle J. Spencer-Ramirez, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia; Kelly N. Michelson, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois; Bria M. Coates, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois; Sarah Jae Wershil, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois; Samina S. Bhumbra, Riley Hospital for Children, Indianapolis. Indiana; Mary Stumpf, Riley Hospital for Children, Indianapolis. Indiana; Tamara T. Bradford, Children’s Hospital of New Orleans, New Orleans, Louisiana; Adrienne G. Randolph, Boston Children’s Hospital, Boston, Massachusetts; Margaret M. Newhams, Boston Children’s Hospital, Boston, Massachusetts; Amber O. Orzel-Lockwood, Boston Children’s Hospital, Boston, Massachusetts; Jemima M. Calixte, Boston Children’s Hospital, Boston, Massachusetts; Amira Toivonen, Boston Children’s Hospital, Boston, Massachusetts; Callum Ackerman, Boston Children’s Hospital, Boston, Massachusetts; Janet R. Hume, University of Minnesota Masonic Children’s Hospital, Minneapolis, Minnesota; Emily R. Levy, Mayo Clinic, Rochester, Minnesota; Chloe A Schluttner, Mayo Clinic, Rochester, Minnesota; Carly R Crowley, Mayo Clinic, Rochester, Minnesota; Lora M.; Martin, Children’s Hospital of Mississippi, Jackson, Mississippi; Joseph M. Majure, Children’s Hospital of Mississippi, Jackson, Mississippi; Lacy Malloch, Children’s Hospital of Mississippi, Jackson, Mississippi; Maygan Martin, Children’s Hospital of Mississippi, Jackson, Mississippi; Jennifer E. Schuster, Children’s Mercy Kansas City Kansas City, Missouri; Berenice Marrufo, Children’s Mercy Kansas City, Kansas City, Missouri; Allison Scott, Children’s Mercy Kansas City Kansas City, Missouri; Shira J. Gertz, Cooperman Barnabas Medical Center, Livingston, New Jersey; Elizabeth Ricciardi, Cooperman Barnabas Medical Center, Livingston, New Jersey; Melissa S. Stockwell, Columbia University Irving Medical Center, New York, New York; Celibell Y. Vargas, Columbia University Irving Medical Center, New York, New York; Raul A. Silverio Francisco, Columbia University Irving Medical Center, New York, New York; Tom Connors, Columbia University Irving Medical Center, New York, New York; Stephanie P. Schwartz, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Tracie C. Walker, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Alison Mathers, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Ryan A. Nofziger, Akron Children’s Hospital, Akron, Ohio; Nicole Twinem, Akron Children’s Hospital, Akron, Ohio; Heather Anthony, Akron Children’s Hospital, Akron, Ohio; Olivia Kennedy, Akron Children’s Hospital, Akron, Ohio; Mary Allen Staat, Cincinnati Children’s Hospital, Cincinnati, Ohio; Chelsea C. Rohlfs, Cincinnati Children’s Hospital, Cincinnati, Ohio; Steven L. Shein, UH Rainbow Babies and Children’s Hospital, Cleveland, Ohio; Rajashri Rasal, UH Rainbow Babies and Children’s Hospital, Cleveland, Ohio; Judith A. Guzman-Cottrill, Oregon Health and Science University, Portland, Oregon; Chelsea Heisler, Oregon Health and Science University, Portland, Oregon; Kathleen Chiotos, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Jenny Bush, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Alanah Mckelvey, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Rebecca Douglas, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Myooran Sivarupan, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Glory Edioma, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Taylor A. Slocumb, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Austin Biggs, MUSC Children’s Health, Charleston, South Carolina; Zach Rusler, MUSC Children’s Health, Charleston, South Carolina; Natasha B. Halasa, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee; Laura S. Stewart, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee; Kristina A. Betters, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee; Annika Conlee, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee; Madeline Spradley, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee; Adriana Blanco Vasquez, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee; Eliana Rebolledo, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee; Hillary Crandall, University of Utah and Primary Children’s Hospital, Salt Lake City, Utah; Danielle M. Zerr, Seattle Children’s Hospital, Seattle, Washington; Amanda Adler, Seattle Children’s Hospital, Seattle, Washington.
Corresponding author: Laura D. Zambrano, lzambrano@cdc.gov.
1Coronavirus and Other Respiratory Viruses Division, National Center for Immunization and Respiratory Diseases, CDC; 2Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts; 3Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee; 4The Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta and the Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; 5Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, Utah; 6Division of Pediatric Hospital Medicine, UC San Diego–Rady Children’s Hospital, San Diego, California; 7Division of Pediatric Infectious Diseases, Department of Pediatrics, Children’s Mercy Kansas City, Kansas City, Missouri; 8Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado; 9Division of Critical Care Medicine, Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; 10Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children’s Hospital, Little Rock, Arkansas; 11Department of Pediatrics, UH Rainbow Babies and Children’s Hospital, Cleveland, Ohio; 12Department of Pediatrics, Cincinnati Children’s Hospital, Cincinnati, Ohio; 13Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi; 14Ryan White Center for Pediatric Infectious Disease and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; 15Division of Critical Care Medicine, Department of Pediatrics, Akron Children’s Hospital, Akron, Ohio; 16Division of Pediatric Critical Care, Nemours Children’s Hospital, Wilmington, Delaware; 17Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania; 18Division of Infectious Diseases, Department of Pediatrics, University of Washington, Seattle, Washington; 19Seattle Children’s Research Institute, Seattle, Washington; 20Division of Pediatric Critical Care, Department of Pediatrics, Cooperman Barnabas Medical Center, Livingston, New Jersey; 21Department of Pediatrics, Oregon Health and Science University, Portland, Oregon; 22Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama; 23Division of Pediatric Critical Care, University of Minnesota Masonic Children’s Hospital, Minneapolis, Minnesota; 24Division of Pediatric Critical Care Medicine, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois; 25Divisions of Pediatric Infectious Diseases and Pediatric Critical Care Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota; 26Division of Cardiology, Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana; 27Children’s Hospital of New Orleans, New Orleans, Louisiana; 28Department of Pediatrics, University of North Carolina at Chapel Hill Children’s Hospital, Chapel Hill, North Carolina; 29Division of Child and Adolescent Health, Department of Pediatrics, Vagelos College of Physicians and Surgeons and Department of Population and Family Health, Columbia University, New York, New York; 30New York-Presbyterian Hospital, New York, New York; 31Department of Pediatric Critical Care, Medical University of South Carolina and Shawn Jenkins Children’s Hospital, Charleston, South Carolina; 32Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut; 33Division of Hospital Medicine, Connecticut Children’s, Hartford, Connecticut; 344ES Corporation, San Antonio, Texas; 35Departments of Anesthesia and Pediatrics, Harvard Medical School, Boston, Massachusetts.
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Katherine Irby reports institutional support from the National Institutes of Health (NIH). Satoshi Kamidani reports institutional support from NIH, Pfizer, Moderna, Meissa, Bavarian Nordic, and Sanofi, and receipt of payment or honoraria from the American Academy of Pediatrics. Kelly N. Michelson reports institutional support from the Patient-Centered Outcomes Research Institute, NIH, the Greenwall Foundation, and Friends of Prentice; payment or honoraria from the University of Chicago; membership on the Normal Moments board; and is a cofounder of Missing Pieces, a program of the HAP foundation, and serves in an advisory position to that organization, from which she might receive future financial benefits related to her engagement with the program. Jennifer E. Schuster reports institutional support from NIH, the Food and Drug Administration, and the state of Missouri; receipt of consulting fees from the Association of professionals in Infection Control and Epidemiology; speaking honoraria from the Missouri American Academy of Pediatrics (AAP); and paid membership on the Association of American Medical Colleges Advisory Board for a grant awarded for vaccine confidence. Regina M. Simeone reports stock in Pfizer owned by her spouse, which was sold in April 2022. Mary Allen Staat reports institutional support from NIH, Merck, and Cepheid; receipt of royalties from UpToDate Inc.; and consulting fees from Merck. Melissa S. Stockwell reports receipt of support from subcontracts from Boston Children’s Hospital, Vanderbilt University (for RSV surveillance), and Westat (for vaccine effectiveness surveillance), and a service agreement from AAP, paid to trustees of Columbia University. Natasha B. Halasa reports receipt of grant support from Merck and receipt of consulting fees as a member of an advisory board for CSL-Seqirus. Hillary Crandall reports institutional support from the National Institute of General Medical Sciences, NIH and from Mortensen and Milne for expert testimony. Danielle M. Zerr reports institutional support from Merck and participation on endpoint adjudication committees for two Allovir trials. Michele Kong reports institutional support from NIH and uncompensated membership of the Jefferson County Health Department University of Alabama Callahan Board, KultureCity. Janet R. Hume reports institutional support from the National Institute for Allergy and Infectious Diseases (NIAID) and the National Institute of Child Health and Human Development, NIH, and unpaid service on a data safety monitoring board for an institutional study of magnesium sulfate as adjuvant analgesia and its effect on opiate use by postoperative transplant patients in the pediatric intensive care unit at the University of Minnesota. Bria M. Coates reports institutional support from NIAID and the National Heart, Lung, and Blood Institute, NIH. Adrienne G. Randolph reports institutional support from NIH and receipt for royalties from UpToDate, Inc. for section editor duties; consulting fees from Inotrem, Inc. and ThermoFisher, Inc.; honoraria from St. Jude Children’s Research Center and Volition, Inc.; travel or meeting support from the International Sepsis Forum; participation on a data safety monitoring board for NIH and Randomised, Embedded, Multi-factorial; Adaptive Platform Trial for Community-Acquired Pneumonia; service as chair of the International Sepsis Forum; and institutional receipt of equipment, materials, or other services from Illumina, Inc. No other potential conflicts of interest were disclosed.
* These authors contributed equally to this report.
† These senior authors contributed equally to this report.
§ Respiratory symptoms sufficient for inclusion included one or more of the following: cough, shortness of breath, wheezing, apnea, use of new or elevated oxygen support for the acute illness, or new pulmonary findings on chest imaging. Symptom onset date was determined by caregiver report if caregiver interview was conducted and onset date was known; if not known, symptom onset date was estimated by subtracting date of hospital admission from the median days between symptom onset and admission date in records with complete data.
¶ Clinically obtained test from a respiratory sample that is positive for RSV by polymerase chain reaction (PCR) or other nucleic acid amplification test (NAAT), or antigen testing during hospitalization or in a health care setting before hospitalization.
** Clinically obtained test from a respiratory sample that is negative by PCR or other NAAT for RSV performed during hospitalization or in a health care setting within 1 calendar day before admission to the site hospital.
†† In clinical trials, peak neutralizing antibody concentration levels were reached in adults by day 6 after intramuscular administration.
§§ In addition to listed exclusion criteria, infants were not eligible for inclusion in the primary analysis if 1) they were never discharged from their birth hospitalization, 2) they had previously been enrolled in the RSV nirsevimab effectiveness investigation since December 1, 2024, and 3) the infant’s home state immunization information system could not be accessed.
¶¶ Immunization product receipt was considered verified if the infant’s immunization status was identified through either their state’s immunization information system or in their electronic medical record. Plausible self-report from caregiver interview data was considered a source for verification if the caregiver provided both a date and location where immunization was received.
*** Palivizumab was considered to have been potentially received if documentation review during product verification indicated that an anti-RSV monoclonal antibody was received, but type was not specified. The American Academy of Pediatrics publishes recommendations for palivizumab (Respiratory Syncytial Virus | Red Book: 2024–2027 Report of the Committee on Infectious Diseases | Red Book Online | American Academy of Pediatrics). Effective December 31, 2025, palivizumab will no longer be available in the United States in the context of current recommendations for nirsevimab and clesrovimab.
††† Receipt of respiratory support that was higher than that required at baseline was evaluated. Analyses of highest level of respiratory support received excluded one case-patient and one control patient who were receiving invasive mechanical ventilation at baseline and one control patient who was receiving CPAP at baseline with no increased level of respiratory support during the hospitalization.
§§§ SMDs measure the magnitude of difference between group means and proportions. An SMD with an absolute value of the difference ≥0.2 indicated nonnegligible differences in variable distribution.
¶¶¶ Specified underlying medical conditions in the case report form included respiratory disorders (chronic lung disease, bronchopulmonary dysplasia, cystic fibrosis, assistance required for secretion clearance, reactive airway disease, obstructive sleep apnea, tracheomalacia/laryngomalacia, and congenital airway disorders), cardiac disorders (congenital heart disease, history of cardiac repair [surgery or interventional catheterization], pulmonary hypertension, and congestive heart failure), immune or oncologic disorders (primary immunodeficiency, HIV, and acquired immune deficiency, and includes receipt of high-dose corticosteroid therapy for any rheumatologic, oncologic, or autoinflammatory disorder), neurologic or neuromuscular disorders (muscular dystrophy, static encephalopathy, spastic quadriplegia, seizure disorder, neuromuscular weakness, and hydrocephalus), endocrine disorders (including diabetes), and metabolic or confirmed genetic disorders (trisomy 21 or any other chromosomal disorder, mitochondrial disorder, or fatty acid deficit).
**** 2022 Social Vulnerability Index (SVI) scores (SVI | Place and Health – Geospatial Research, Analysis, and Services Program (GRASP) | ATSDR) were linked to patients by the first four digits of their zip code, extrapolated to U.S. Census Bureau tract using the U.S. Postal Service tract-to-zip code crosswalk file from the U.S. Department of Housing and Urban Development (HUD USPS ZIP Code Crosswalk Files | HUD USER). Where a zip code matched to multiple U.S. Census Bureau tracts, a weighted average for SVI was computed using tract-based population estimates derived from the American Community Survey (2018–2022) estimates, embedded within the SVI data set.
†††† 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.
§§§§ A total of 917 (548 case-patients and 369 control patients) were initially enrolled. Infants excluded from the analysis included 91 (17%) case-patients and 67 (18%) control patients who 1) received palivizumab or an unknown monoclonal antibody (one case-patient and 1 control patient); 2) were born to mothers who received maternal RSV vaccine during pregnancy (54 case-patients and 46 control patients); 3) received >1 dose of nirsevimab (one control patient); 4) had onset of symptoms <7 days after nirsevimab receipt (eight case-patients and nine control patients); 5) received nirsevimab outside of the nirsevimab season, April 1–September 30, 2024 (three case-patients and five control patients); 7) had illness onset >14 days before hospitalization (four case-patients and three control patients); 8) received a first positive RSV test result (by PCR, NAAT, or antigen testing) ≥3 days after hospital admission (11 case-patients); or 9) were aged <7 days on the date of hospitalization (10 case-patients and two control patients).
¶¶¶¶ U.S. Census Bureau Regions and Divisions of the United States
References
- McLaughlin JM, Khan F, Schmitt HJ, et al. Respiratory syncytial virus-associated hospitalization rates among US infants: a systematic review and meta-analysis. J Infect Dis 2022;225:1100–11. https://doi.org/10.1093/infdis/jiaa752 PMID:33346360
- Shanklin A, Olson T, Patel AK, Trujillo Rivera EA, Pollack MM. Respiratory syncytial virus and U.S. pediatric intensive care utilization. JAMA Netw Open 2024;7:e2440997. https://doi.org/10.1001/jamanetworkopen.2024.40997 PMID:39453655
- Jones JM, Fleming-Dutra KE, Prill MM, et al. Use of nirsevimab for the prevention of respiratory syncytial virus disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices—United States, 2023. MMWR Morb Mortal Wkly Rep 2023;72:920–5. https://doi.org/10.15585/mmwr.mm7234a4 PMID:37616235
- Moline HL, Toepfer AP, Tannis A, et al.; New Vaccine Surveillance Network Collaborators. Respiratory syncytial virus disease burden and nirsevimab effectiveness in young children from 2023–2024. JAMA Pediatr 2025;179:179–87. https://doi.org/10.1001/jamapediatrics.2024.5572 PMID:39652359
- Griffin MP, Yuan Y, Takas T, et al.; Nirsevimab Study Group. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med 2020;383:415–25. https://doi.org/10.1056/nejmoa1913556 PMID:32726528
- Moulia DL, Link-Gelles R, Chu HY, et al. Use of clesrovimab for prevention of severe respiratory syncytial virus–associated lower respiratory tract infections in infants: recommendations of the Advisory Committee on Immunization Practices—United States, 2025. MMWR Morb Mortal Wkly Rep 2025;74:508–14. https://doi.org/10.15585/mmwr.mm7432a3 PMID:40880502
- <jrn[REMOVED IF= FIELD]Xu H, Aparicio C, Wats A, et al. Estimated effectiveness of nirsevimab against respiratory syncytial virus. JAMA Netw Open 2025;8:e250380. https://doi.org/10.1001/jamanetworkopen.2025.0380 PMID:40063022
- Sumsuzzman DM, Wang Z, Langley JM, Moghadas SM. Real-world effectiveness of nirsevimab against respiratory syncytial virus disease in infants: a systematic review and meta-analysis. Lancet Child Adolesc Health 2025;9:393–403. https://doi.org/10.1016/s2352-4642(25)00093-8 PMID:40319903
- Halasa N, Zambrano LD, Amarin JZ, et al.; RSV-PIC Investigators. Infants admitted to US intensive care units for RSV infection during the 2022 seasonal peak. JAMA Netw Open 2023;6:e2328950. https://doi.org/10.1001/jamanetworkopen.2023.28950 PMID:37581884
- Jabagi MJ, Cohen J, Bertrand M, et al. Nirsevimab effectiveness at preventing RSV-related hospitalization in infants. NEJM Evid 2025;4:EVIDoa2400275. https://doi.org/10.1056/EVIDoa2400275 PMID:39998305
Abbreviations: BiPAP = bilevel positive airway pressure; CPAP = continuous positive airway pressure; ECMO = extracorporeal membrane oxygenation; ICU = intensive care unit; IMV = invasive mechanical ventilation; NAAT = nucleic acid amplification test; PCR = polymerase chain reaction; RSV = respiratory syncytial virus; SMD = standardized mean difference.
* Case-patients received a positive RSV test result by PCR, NAAT, or antigen testing during hospitalization or in a health care setting before hospitalization. Control patients received a negative RSV test result by PCR or NAAT during hospitalization or in a health care setting within 1 calendar day of admission to the site hospital. For inclusion, all patients were required to have one or more of the following respiratory symptoms or examination findings present at hospital admission and onset within 14 days of hospital admission: cough, shortness of breath, wheezing, retractions, apnea, use of new or elevated oxygen support for the acute illness, or new pulmonary findings on chest imaging consistent with pneumonia.
† SMD ≥0.20 indicates a nonnegligible difference in variable distributions between case-patients and control patients. When calculating SMDs for differences in characteristics across multiple strata, the SMD was calculated as the weighted average of the absolute value of the SMD for each pairwise comparison between case-patients and control patients.
§ Specified underlying conditions included any of the specified respiratory conditions; cardiac conditions; immune or oncologic disorders; neurologic conditions; metabolic, genetic, or endocrine disorders; or sickle cell disease.
¶ Includes chronic lung disease, bronchopulmonary dysplasia, cystic fibrosis, assistance required for secretion clearance, reactive airway disease, obstructive sleep apnea, tracheomalacia/laryngomalacia, and congenital airway disorders.
** Includes congenital heart disease, history of cardiac repair (surgery or interventional catheterization), pulmonary hypertension, and congestive heart failure.
†† Data collected on immunosuppressive disorders included primary immunodeficiency (e.g., X-linked agammaglobulinemia, common variable immune deficiency, Wiskott-Aldrich syndrome, hyper immunoglobulin E/Job syndrome, DiGeorge syndrome (22q11 deletion), HIV infection, acquired immune deficiency (e.g., inflammatory bowel disease, juvenile idiopathic arthritis, systemic lupus erythematosus, dermatomyositis, and aplastic anemia or other disorders of bone marrow failure), including receipt of high-dose corticosteroid therapy for any rheumatologic, oncologic, or autoinflammatory disorder.
§§ Includes muscular dystrophy, static encephalopathy, spastic quadriplegia, seizure disorder, neuromuscular weakness, and hydrocephalus.
¶¶ Includes trisomy 21 or any other chromosomal disorder, mitochondrial disorder, or fatty acid deficit.
*** Date of symptom onset was determined by the onset date reported by the caregiver in the caregiver interview; if caregiver-reported symptom onset date was missing, the median number of days from the date of symptom onset to hospitalization for nonmissing records was subtracted from the date of hospitalization.
††† Analyses of highest level of respiratory support included 756 infants after excluding one case-patient and one control patient who were receiving IMV at baseline and one control patient who was receiving CPAP at baseline with no increased level of respiratory support during their hospitalization.
§§§ A total of 405 patients who required CPAP, BiPAP, or IMV during hospitalization were included in this analysis, including 238 case-patients and 167 control patients. Patients who had received preadmission respiratory support at home who required elevated levels of support after admission included 24 case-patients (five CPAP, three BiPAP, and 16 IMV during hospitalization) and 22 control patients (two CPAP, four BiPAP, and 16 IMV during hospitalization).
¶¶¶ Hospital length of stay was calculable for 755 infants.
**** ICU length of stay was calculable for 758 infants.
Abbreviations: ICU = intensive care unit; RSV = respiratory syncytial virus.
* The primary analysis included case-patients and control patients who were admitted to an ICU and assessed the relative odds of previous receipt of nirsevimab in RSV-positive case-patients compared with control patients.
† Respiratory failure was defined as requiring treatment with continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation, when level of respiratory support received during hospitalization exceeded respiratory support received at baseline. This analysis included case-patients with respiratory failure and all ICU-admitted control patients to reflect the source population of ICU-admitted patients from which acute respiratory failure may arise.
§ This analysis included only case-patients and control patients who were matched on hospital site, age group, date of hospital admission (within 30 days) and excluded any unmatched patients.
¶ This reflects an unconditional multivariable logistic regression model adjusted for age (continuous, in months), biweekly date of hospital admission, the presence of one or more underlying medical condition, social vulnerability index, and U.S. Census Bureau regions. Hospital site was included as a repeated measure.
** Because of the high correlation (ρ = 0.68; p<0.001) between age (in months) and time (in days) between receipt of nirsevimab dose to symptom onset, age (in months) was removed from these stratified adjusted models.
†† Using conditional multivariable logistic regression, matched analyses were performed on 226 matched pairs to compare results to the primary analysis, to account for potential imbalance on matching variables when including all eligible enrolled infants.
Suggested citation for this article: Zambrano LD, Simeone RM, Newhams MM, et al. Nirsevimab Effectiveness Against Intensive Care Unit Admission for Respiratory Syncytial Virus in Infants — 24 States, December 2024–April 2025. MMWR Morb Mortal Wkly Rep 2025;74:580–588. DOI: http://dx.doi.org/10.15585/mmwr.mm7437a1.
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