Effectiveness of Monovalent and Bivalent mRNA Vaccines in Preventing COVID-19–Associated Emergency Department and Urgent Care Encounters Among Children Aged 6 Months–5 Years

Abbreviations: BV = bivalent; ED = emergency department; ICD-10 = International Classification of Diseases, Tenth Revision; KPNC = Kaiser Permanente Northern California; KPNW = Kaiser Permanente Northwest; MV = monovalent; NA = not applicable; UC = urgent care; VE = vaccine effectiveness.
*Children who received Pfizer-BioNTech COVID-19 vaccine were excluded from the Moderna VE analyses. Ninety-six Moderna bivalent dose recipients are included in the table but were excluded from the monovalent Moderna-specific primary series analyses.
^†Children who received Moderna COVID-19 vaccine were excluded from the Pfizer-BioNTech VE analyses. A total of 226 recipients of Pfizer-BioNTech bivalent doses are included in the table but were excluded from the monovalent Pfizer-BioNTech–specific primary series analyses.
^§Variant predominance was defined as the period during which a variant accounted for ≥50% of all sequenced specimens in the U.S. Department of Health and Human Services region where the site is located. XBB-related sublineages predominated at Columbia University beginning December 31, 2022; at Intermountain Healthcare and University of Colorado beginning January 28, 2023; at HealthPartners and Children's Minnesota and KPNC beginning February 4, 2023; and at KPNW beginning February 11, 2023.
^¶Children whose caregiver reported non-Hispanic ethnicity and any of the following for race were classified as other, non-Hispanic: American Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, or other race, or whose caregiver reported not Hispanic with no corresponding race chosen. Children whose caregiver did not report race and ethnicity were classified as unknown.
**Periods were divided based on when children were eligible for inclusion in analyses according to updates to primary series vaccination policy as follows: July 4, 2022 = 14 days after recommendation of the monovalent primary series; August 1, 2022 = first children eligible for inclusion in analyses of second dose of Pfizer-BioNTech or Moderna monovalent vaccine; September 19, 2022 = first children eligible for inclusion in analyses of third dose of Pfizer-BioNTech monovalent vaccine; December 24, 2022 = first children eligible for inclusion in analyses of bivalent vaccines; and May 4 = first children eligible for inclusion after receipt of bivalent primary series doses. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us-appendix.html
^††Asthma included children with the following ICD-10 discharge code: J45*; prematurity included children with the following ICD-10 discharge code: P07*; chronic lung disease of prematurity included children with the following ICD-10 discharge code: P27.1. Data on chronic lung disease of prematurity were not available from one site.
^§§Vaccination status categories are mutually exclusive. Percentages reflect column percentages among analytic sample and because of exclusion criteria do not reflect vaccine coverage in the population of children with ED/UC encounters. Among all control-children aged 6–23 months, 2–4 years, and 5 years (including children aged 5 years who received the Pfizer-BioNTech 10-μg dose), 10.2%, 13.1%, and 13.4% received ≥1 COVID-19 vaccine dose, respectively. Ten children who received a bivalent dose but did not complete a primary series were dropped, including two children who received 1 bivalent Moderna dose only, four children who received 1 monovalent Pfizer-BioNTech and 1 bivalent Pfizer-BioNTech dose, three children who received 1 monovalent Pfizer-BioNTech dose only, and one child who received 2 bivalent Pfizer-BioNTech doses.

Abbreviations: NA = not applicable; Ref = referent group; VE = vaccine effectiveness.
*VE was calculated as (1 – adjusted odds ratio) x 100%, estimated using a test-negative case-control design, adjusted for age, sex, race and ethnicity, geographic region, and calendar time (days since January 1, 2021).
^†Different analysis periods were used for each product and dose number because vaccinated children became eligible to be included 14 days after the dose at different times: 1 dose of Moderna and Pfizer-BioNTech on July 4, 2022; 2 doses of Pfizer-BioNTech on July 25, 2022; 2 doses of Moderna on August 1, 2022; 3 doses of Pfizer-BioNTech on September 19, 2022; and bivalent doses on December 24, 2022.
^§Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case status. This imprecision indicates that the actual VE could be substantially different from the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual could increase precision and allow more precise interpretation.
^¶Children included in this estimate were either unvaccinated (received zero COVID-19 vaccine doses) or had received ≥1 bivalent vaccine dose from either manufacturer. Among those who received a bivalent vaccine dose, any combination of monovalent and bivalent doses was included, but at a minimum children had to have received 2 Moderna doses or 3 Pfizer-BioNTech doses (i.e., a complete primary series).
**This estimate was calculated using unadjusted exact methods because of the small number of vaccinated case-patients. All three vaccinated case-patients received bivalent Pfizer-BioNTech doses; vaccinated control-patients included those who received both bivalent Moderna (96) and Pfizer-BioNTech (223) doses.

Authors and Disclosures

Ruth Link-Gelles, PhD¹, Allison Avrich Ciesla, PhD^1,2, Elizabeth A.K. Rowley DrPH³, Nicola P. Klein MD, PhD⁴, Allison L. Naleway, PhD⁵, Amanda B. Payne, PhD¹, Anupam Kharbanda, MD⁶, Karthik Natarajan, PhD^7,8, Malini B. DeSilva, MD⁹, Kristin Dascomb, MD, PhD¹⁰, Stephanie A. Irving, MHS⁵, Ousseny Zerbo, PhD⁴, Sarah E. Reese, PhD³, Ryan E. Wiegand, PhD¹, Morgan Najdowski, MPH¹, Toan C. Ong, PhD¹¹, Suchitra Rao, MBBS^11; Melissa S. Stockwell, MD^8,12,13, Ashley Stephens, MD^8,12, Kristin Goddard, MPH⁴, Yessica C. Martinez, MPH³, Zachary A. Weber, PhD³, Bruce Fireman⁴, John Hansen, MPH⁴, Julius Timbol, MS⁴, Shaun J. Grannis, MD^14,15, Michelle A. Barron, MD¹¹, Peter J. Embi, MD¹⁶, Sarah W. Ball, ScD³, Manjusha Gaglani, MBBS^17,18, Nancy Grisel, MPP¹⁰, Julie Arndorfer, MPH¹⁰, Mark W. Tenforde, MD, PhD¹⁹ and Katherine E. Fleming-Dutra, MD<sup>1

1</sup>Coronavirus and Other Respiratory Viruses Division, National Center for Immunization and Respiratory Diseases, CDC; ²Eagle Health Analytics, San Antonio, Texas; ³Westat, Rockville, Maryland; ⁴Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California Division of Research, Oakland, California; ⁵Kaiser Permanente Center for Health Research, Portland, Oregon; ⁶Children's Minnesota, Minneapolis, Minnesota; ⁷Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York; ⁸New York-Presbyterian Hospital, New York, New York; ⁹HealthPartners Institute, Minneapolis, Minnesota; ¹⁰Division of Infectious Diseases and Clinical Epidemiology, Intermountain Healthcare, Salt Lake City, Utah; ¹¹School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; ¹²Division of Child and Adolescent Health, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York; ¹³Department of Population and Family Health, Columbia University Mailman School of Public Health, New York, New York; ¹⁴Center for Biomedical Informatics, Regenstrief Institute, Indianapolis, Indiana; ¹⁵School of Medicine, Indiana University, Indianapolis, Indiana; ¹⁶Vanderbilt University Medical Center, Nashville, Tennessee; ¹⁷Section of Pediatric Infectious Diseases, Department of Pediatrics, Baylor Scott & White Health, Temple, Texas; ¹⁸Department of Medical Education, Texas A&M University College of Medicine, Temple, Texas; ¹⁹Influenza Division, National Center for Immunization and Respiratory Diseases, CDC.

Corresponding author
Ruth Link-Gelles, media@cdc.gov.

All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Nicola P. Klein reports institutional support from Pfizer, Merck, GSK, Sanofi Pasteur, and Protein Sciences (now Sanofi Pasteur). Allison L. Naleway reports institutional support from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy study and from Vir Biotechnology for an unrelated influenza study. Suchitra Rao reports grant support from GSK. No other potential conflicts of interest were disclosed.

Sidebar

Summary

What is already known about this topic?

The original monovalent COVID-19 mRNA vaccines were first recommended in the United States in June 2022 for young children; bivalent vaccines were recommended in December 2022. Postauthorization vaccine effectiveness data in this age group are limited.

What is added by this report?

Monovalent and bivalent mRNA vaccines helped provide protection against COVID-19–associated emergency department and urgent care visits among children aged 6 months–4 years (Pfizer-BioNTech) and 6 months–5 years (Moderna).

What are the implications for public health practice?

All children should stay up to date with recommended COVID-19 vaccines, including initiating COVID-19 vaccination immediately when they become eligible.