Nirsevimab Effectiveness Against Medically Attended Respiratory Syncytial Virus Illness and Hospitalization Among Alaska Native Children — Yukon-Kuskokwim Delta Region, Alaska, October 2023–June 2024

Brian Lefferts, MPH1; Sara Bressler, MSPH2; James W. Keck, MD2,3; Christine Desnoyers, MBA1; Ellen Hodges, MD1; Gerald January1; Kristina Morris, MSN1; Leslie Herrmann, MD1; Rosalyn Singleton, MD2; Sarah Aho, MPH4; Julia Rogers, PhD4,5; Katherine Newell, DPhil4,6; Elizabeth Ohlsen, MD4; Ruth Link-Gelles, PhD7; Fatimah S. Dawood, MD7; Dana Bruden, MS2; Marc Fischer, MD2; Joseph Klejka, MD1; Heather M. Scobie, PhD2 (

Summary

What is already known about this topic?

To prevent severe respiratory syncytial virus (RSV) illness, nirsevimab is recommended for all infants aged What is added by this report?

In Alaska’s Yukon-Kuskokwim Delta, nirsevimab was 89% effective in preventing RSV-associated hospitalization for infants in their first RSV season and 76% and 88% effective against medically attended illness for children in their first and second seasons, respectively.

What are the implications for public health practice?

Nirsevimab can prevent severe RSV illness among AI/AN infants and children entering their first and second RSV seasons.

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Abstract

Respiratory syncytial virus (RSV) is a leading cause of hospitalization among young children. Historically, American Indian and Alaska Native (AI/AN) children have experienced high rates of RSV-associated hospitalization. In August 2023, a preventive monoclonal antibody (nirsevimab) was recommended for all infants aged

Introduction

Respiratory syncytial virus (RSV) is a leading cause of hospitalization among young children (1). Historically, American Indian and Alaska Native (AI/AN) children have experienced high rates of RSV-associated hospitalization, with threefold to sevenfold higher rates in Alaska’s Yukon-Kuskokwim Delta region than in other U.S. areas (2,3). In August 2023, CDC’s Advisory Committee on Immunization Practices (ACIP) recommended a long-acting monoclonal antibody (nirsevimab) for all infants aged 4). In clinical trials among children in their first RSV season, nirsevimab efficacy was 79% for preventing medically attended RSV-associated lower respiratory tract infection and 81% for preventing RSV-associated hospitalization through 150 days after receipt (4). In September 2023, ACIP recommended that all infants be protected against severe RSV either through maternal RSV vaccination during pregnancy or infant receipt of nirsevimab; a majority of infants do not need protection from both products (5). This evaluation in Alaska’s Yukon-Kuskokwim Delta region provides the first real-world estimates of nirsevimab effectiveness among AI/AN children in their first and second RSV seasons.

Evaluation Site

The Yukon-Kuskokwim Delta region in southwestern Alaska includes approximately 27,000 persons (90% Alaska Native persons) living in the regional hub and 48 remote villages not connected by roads.* Yukon-Kuskokwim Health Corporation (YKHC), a tribal health organization, manages a regional hospital that performs RSV RNA testing and 46 village clinics that send swabs to the regional hospital for RNA testing. An estimated 1,591 children aged † (4). YKHC administered nirsevimab to 756 (48%) children aged §

Data Source and Inclusion Criteria

A deidentified database was developed that included demographic, clinical, laboratory testing, and immunization data from YKHC electronic health records and the state immunization information system.¶ Eligible children were aged †† Visits were excluded if the child 1) had received nirsevimab 1 dose of nirsevimab on different dates, or 1 dose of palivizumab (a different preventive monoclonal antibody to prevent severe RSV); 2) had a mother who received RSV vaccine during pregnancy; 3) had received a negative RSV test result but had an RSV discharge code; or 4) was ineligible for nirsevimab.

Data Analysis

Nirsevimab effectiveness against medically attended ARI associated with RSV infection was evaluated using a test-negative design. Case-patients were those who had received a positive RSV test result. Control patients had received a negative RSV test result. Children were stratified by their RSV season based on their age on October 1, 2023 (first season included those aged §§ Effectiveness was calculated as (1 − adjusted odds ratio) × 100%. Sensitivity analyses were conducted excluding cases and controls in which SARS-CoV-2 or influenza virus was detected. Effectiveness was also determined by time since receipt and against hospitalization. Analyses were conducted using SAS (version 9.4; SAS Institute). This activity was reviewed by CDC, determined not to be research, and conducted consistent with applicable federal law and CDC policy.¶¶ YKHC and the Alaska Native Tribal Health Consortium approved this project.

Characteristics of Children Included in the Evaluation

Overall, 472 children had medically attended ARI visits (14% hospitalization, 70% emergency department, and 16% outpatient clinic) meeting inclusion and exclusion criteria, including 68 (14%) patients with positive RSV test results and 404 (86%) patients with negative RSV test results (

Receipt of Nirsevimab

Overall, 48% of all children had received nirsevimab ≥7 days before the ARI medical visit; this percentage was lower among children in their second RSV season (37%) and among those living in the regional hub (35%) than among children in their first season (55%) and those living in other villages (53%). Overall, among patients with positive RSV test results, 10 (15%) had received nirsevimab; 217 (54%) patients with negative RSV test results had received nirsevimab.

Nirsevimab Effectiveness

Overall, nirsevimab effectiveness against medically attended RSV illness was 82% (

Among children who received nirsevimab overall, the median interval from receipt to ARI medical visit was 91 days (range = 7–255 days) (Table 2) (Supplementary Figure, https://stacks.cdc.gov/view/cdc/168889). Effectiveness against medically attended RSV illness was 90% at 7–89 days after nirsevimab receipt and 77% at 90–179 days after receipt.

Overall, 64 children were hospitalized for ARI, including 23 patients with positive RSV test results, three of whom received nirsevimab. Nirsevimab effectiveness against RSV-associated hospitalization was 93% among children overall and 89% among children in their first RSV season, who accounted for 49 (77%) hospitalizations. Because of small numbers, effectiveness against hospitalization was not estimated for the 15 children who were in their second RSV season.

Discussion

In this evaluation of 472 children with medically attended ARI in Alaska’s Yukon-Kuskokwim Delta region, nirsevimab was 89% effective against RSV hospitalization among children in their first season and 76% and 88% effective against medically attended RSV illness among children in their first and second RSV seasons, respectively. Consistent with previous studies among infants in their first RSV season (6–8), this evaluation documents nirsevimab effectiveness in an AI/AN population known to be at increased risk for severe RSV illness (2,3) and at a longer median interval from nirsevimab receipt (91 days) (8). Some evidence of waning overall effectiveness was observed (90% at 7–89 days and 77% at 90–179 days after receipt), but 95% CIs were wide and overlapped. These real-world estimates support current recommendations for nirsevimab to prevent severe RSV among infants in their first and second RSV seasons (4,5).

Compared with other U.S. data (6), a relatively high proportion of children aged ††† Compared with an average of 56 RSV-associated hospitalizations among children aged §§§ 28 RSV-associated hospitalizations occurred during the 2023–24 season (including five RSV hospitalizations that were excluded in the evaluation¶¶¶), and three occurred in children who received nirsevimab ≥7 days earlier. An adequate, timely nirsevimab supply and increased coverage might further reduce RSV hospitalizations during the 2024–25 season (9).

Limitations

The findings in this report are subject to at least five limitations. First, all RSV testing was clinician-directed, with inpatient and emergency visits accounting for the majority (84%) of included visits; possible exclusion of some children with milder illness could have affected estimated nirsevimab effectiveness. Second, low RSV incidence during the spring might have biased effectiveness estimates. Third, small numbers prevented estimation of effectiveness by time since receipt stratified by the child’s RSV season and against hospitalization among children in their second RSV season. Fourth, nirsevimab dosage**** was not ascertained, preventing effectiveness estimation by dosage. Finally, this evaluation was conducted predominantly among AI/AN children in one region of Alaska, and findings might not be generalizable.

Implications for Public Health Practice

Nirsevimab was highly effective in preventing medically attended RSV illness and hospitalization among AI/AN children in Alaska’s Yukon-Kuskokwim Delta region during their first and second RSV seasons. These findings support current CDC recommendations for all infants in their first RSV season to either receive nirsevimab or be protected through maternal vaccination and for children entering their second season with increased risk for severe RSV illness, including all AI/AN children, to receive nirsevimab (4,5).

Acknowledgments

Community members of the Yukon-Kuskokwim Delta region and service providers of Yukon-Kuskokwim Health Corporation; Victoria Balta, Ian Blake, CDC.

Corresponding author: Heather M. Scobie, hscobie@cdc.gov.

1Yukon-Kuskokwim Health Corporation, Bethel, Alaska; 2Arctic Investigations Program, CDC; 3Alaska Native Tribal Heath Consortium, Anchorage, Alaska; 4Section of Epidemiology, State of Alaska Department of Health; 5Epidemic Intelligence Service, CDC; 6Career Epidemiology Field Officer Program, CDC; 7Coronavirus and Other Respiratory Viruses Division, National Center for Immunization and Respiratory Diseases, CDC.

All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. James W. Keck reports grant support from the National Institutes of Health (NIH) for the Alaska Native Center for Health Research Project and for the Wastewater Assessment for Coronavirus in Kentucky: Implementing Enhanced Surveillance Technology; from the National Science Foundation for the Pandemic Environmental Surveillance Center for Assessing Pathogen Emergency Project; from NIH for the COVID-19 infection and diabetes incidence in Native American People project; from NIH for the Neqkiuryaraq – The Art of Preparing Food Project; from Greenwall Foundation for the developing stakeholder-engaged ethical guidance for public health wastewater surveillance project service; and as safety officer and chair of the Data Safety Monitoring Board for National Institute of Diabetes and Digestive and Kidney Diseases-funded study: Enhancing the Diabetes Prevention Program. No other potential conflicts of interest were disclosed.

• https://data.census.gov/

† The first RSV case of the 2023–24 season in YKHC was identified on October 9, 2023.

§ Nirsevimab was first available in YKHC on October 16, 2023, and the period of administration was extended through April 30, 2024, in Alaska (https://health.alaska.gov/dph/Epi/Documents/phan/AKPHAN_20240319_RSVNextSteps.pdf). YKHC also provided RSV vaccine to 100 pregnant persons for the 2023–24 season.

¶ Current-season receipt of nirsevimab documented by state immunization information system or provider electronic health record.

** https://knowledgerepository.syndromicsurveillance.org/cdc-broad-acute-respiratory-dd-v1

†† In scenarios in which multiple tests or ARI medical visits had discordant RSV test results (e.g., negative result followed by a positive result or positive result followed by a negative result), the visits were counted as RSV test–positive visits.

§§ High-risk underlying medical conditions were ascertained from the electronic health records, including chronic lung disease of prematurity, reactive airway disease, congenital heart disease, immunocompromise, cystic fibrosis, neuromuscular disease, congenital airway abnormalities that impair the ability to clear secretions, and prematurity.

¶¶ 45 C.F.R. part 46.102(l), 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.

*** Among children in their first season, 97% were AI/AN, 78% lived outside the regional hub, and 19% had underlying medical conditions. Among the children in their second season, 100% were AI/AN, 63% lived outside the regional hub, and 12% had underlying medical conditions. These differences in characteristics by the child’s RSV season were all statistically significant (p††† https://health.alaska.gov/dph/Epi/Documents/phan/AKPHAN_20231025_NirsevimabSupplyTable.pdf

§§§ From regional surveillance data, this statistic is the 9-year average of RSV hospitalizations among children aged ¶¶¶ Another three RSV hospitalizations in the YKHC service area that occurred in children were excluded from the analysis: one child received nirsevimab 30 days earlier. None of these children received nirsevimab ≥7 days before the ARI visit.

**** Nirsevimab dosage is determined by the child’s age and weight. https://www.cdc.gov/vaccines/vpd/rsv/hcp/child.html

References

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• Overall, 32 of 504 infants with ARI medical visits including receipt of RSV tests during the analysis period were excluded. Reasons for exclusion included being born to a mother who received RSV vaccination during pregnancy (14), receipt of nirsevimab † Receipt of nirsevimab documented by state immunization information system or provider electronic health record.
  § A subset of underlying medical conditions conferring higher risk for severe RSV illness was defined as chronic lung disease of prematurity (two); congenital heart disease (eight); immunocompromise (one); cystic fibrosis (zero); Down syndrome (two); neurologic, musculoskeletal conditions, or both (51); congenital airway abnormalities (one); reactive airway disease (17); or prematurity (nine); 10 children had one or more underlying conditions.

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Abbreviations: ARI = acute respiratory illness; RSV = respiratory syncytial virus.

• Receipt of nirsevimab was calculated among eligible children with medically attended ARI medical visits and RSV-positive and RSV-negative test results. Receipt of nirsevimab was documented by state immunization information system or provider electronic health record.

• Effectiveness was calculated as (1 − adjusted odds ratio) × 100%. Odds ratios were calculated using multivariable logistic regression, adjusted by age in months at medical visit (continuous), sex, calendar month of medical visit, residence community type, and presence of a high-risk underlying condition.
  † Effectiveness against hospitalization was not estimated for children in their second season because of small numbers (15).

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