Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Children Aged 5–11 Years — United States, October 12–January 1, 2023

On October 12, 2022, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for bivalent (mRNA encoding the spike protein from the SARS-CoV-2 ancestral strain and BA.4/BA.5 Omicron variants) formulations of Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines for use as a single booster dose ≥2 months after completion of primary series or monovalent booster vaccination for children aged 5–11 years (Pfizer-BioNTech) and 6–17 years (Moderna); on December 8, 2022, FDA amended the EUAs to include children aged ≥6 months (1,2). The Advisory Committee on Immunization Practices (ACIP) recommends that all persons aged ≥6 months receive an age-appropriate bivalent mRNA booster dose (3). The safety of bivalent mRNA booster doses among persons aged ≥12 years has previously been described (4). To characterize the safety of bivalent mRNA booster doses among children aged 5–11 years after receipt of bivalent Pfizer-BioNTech and Moderna booster doses, CDC reviewed adverse events and health impacts reported to v-safe,* a voluntary, smartphone-based U.S. safety surveillance system established by CDC to monitor adverse events after COVID-19 vaccination, and to the Vaccine Adverse Event Reporting System (VAERS), a U.S. passive vaccine safety surveillance system co-managed by CDC and FDA^† (5). During October 12–January 1, 2023, a total of 861,251 children aged 5–11 years received a bivalent Pfizer-BioNTech booster, and 92,108 children aged 6–11 years received a bivalent Moderna booster.^§ Among 3,259 children aged 5–11 years registered in v-safe who received a bivalent booster dose, local (68.7%) and systemic reactions (49.5%) were commonly reported in the week after vaccination. Approximately 99.8% of reports to VAERS for children aged 5–11 years after bivalent booster vaccination were nonserious. There were no reports of myocarditis or death after bivalent booster vaccination. Eighty-four percent of VAERS reports were related to vaccination errors, 90.5% of which did not list an adverse health event. Local and systemic reactions reported after receipt of a bivalent booster dose are consistent with those reported after a monovalent booster dose; serious adverse events are rare. Vaccine providers should provide this information when counseling parents or guardians about bivalent booster vaccination. Preliminary safety findings from the first 11 weeks of bivalent booster vaccination among children aged 5–11 years are reassuring. Compared with the low risk of serious health effects after mRNA COVID-19 vaccination, the health effects of SARS-CoV-2 infection include death and serious long-term sequalae (6). ACIP recommends that all persons aged ≥6 months receive an age-appropriate bivalent mRNA booster dose ≥2 months after completion of a COVID-19 primary series or receipt of a monovalent booster dose.^¶

A parent or guardian with a v-safe account can register a child aged <15 years and complete health surveys on behalf of the child.** Health surveys sent daily during the week after vaccination ask questions about local injection site and systemic reactions and health impacts experienced; registrants can provide additional information about these reactions or health impacts via free text responses. CDC’s v-safe call center personnel contact registrants who report receiving medical care to request further information; registrants are also encouraged to complete a VAERS report, if indicated.

VAERS accepts reports of postvaccination adverse events from health care providers, vaccine manufacturers, and members of the public.^†† Providers in the CDC COVID-19 Vaccination Program are required to file VAERS reports for observed adverse events after vaccination and for vaccination errors. Signs, symptoms, and diagnoses reported to VAERS are assigned Medical Dictionary for Regulatory Activities preferred terms (MedDRA PTs) by VAERS personnel.^§§ Death certificates and autopsy reports are requested for any reported death.

A bivalent booster dose in v-safe was defined as administration of an age-appropriate mRNA COVID-19 vaccine dose on or after October 12, 2022, to a registrant who had completed at least a primary vaccination series (2 doses of Pfizer-BioNTech or Moderna vaccine). In this report, local and systemic reactions and health impacts reported during the week after vaccination were described for v-safe registrants aged 5–11 years who received a bivalent booster dose during October 12–January 1, 2023. VAERS adverse event reports were described by serious and nonserious classification, demographic characteristics, and MedDRA PTs. Reports of serious events to VAERS were reviewed by CDC physicians to form a consensus on clinical impression based on available data.^¶¶ Possible cases of myocarditis, a rare adverse event that has been associated with mRNA COVID-19 vaccines, were identified using selected MedDRA PTs (6). All analyses were conducted using SAS software (version 9.4; SAS Institute). These surveillance activities were reviewed by CDC and conducted consistent with applicable federal law and CDC policy.***

Acknowledgments

Charles Licata, Isaac McCullum.

Corresponding author: Anne M. Hause, voe5@cdc.gov.

¹CDC COVID-19 Emergency Response Team; ²Food and Drug Administration, Silver Spring, Maryland.

References

1. Food and Drug Administration. Pfizer-BioNTech COVID-19 vaccine letter of authorization (reissued). Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2022. https://www.fda.gov/media/150386/download
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* On October 12, 2022, the Food and Drug Administration authorized bivalent (mRNA encoding the spike protein from the SARS-CoV-2 ancestral strain and BA.4/BA.5 Omicron variants formulations of Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines for use as a single booster dose ≥2 months after completion of primary series or monovalent booster vaccination for children aged 5–11 years and 6–17 years, respectively. A bivalent booster dose in v-safe was defined as an age-appropriate mRNA vaccine dose administered on or after October 12, 2022, for registrants who had completed at least a primary series (2 doses of Pfizer-BioNTech or Moderna vaccine).
^† Includes registrants who completed at least one survey during postvaccination days 0–7.
^§ Other vaccines administered during the same visit.

* On October 12, 2022, the Food and Drug Administration authorized bivalent (mRNA encoding the spike protein from the SARS-CoV-2 ancestral strain and BA.4/BA.5 Omicron variants) formulations of Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines for use as a single booster dose ≥2 months after completion of primary series or monovalent booster vaccination for children aged 5–11 years and 6–17 years, respectively. A bivalent booster dose in v-safe was defined as an age-appropriate mRNA vaccine dose administered on or after October 12, 2022, for registrants who had completed at least a primary series (2 doses of Pfizer-BioNTech or Moderna vaccine).
^† Events reported are not mutually exclusive.
^§ Percentage of registrants reported a reaction or health impact at least once during postvaccination days 0–7.

Abbreviations: MedDRA PT = Medical Dictionary for Regulatory Activities preferred term; VAERS = Vaccine Adverse Event Reporting System.
* Signs and symptoms in VAERS reports are assigned MedDRA PTs by VAERS staff members. Each VAERS report might be assigned more than one MedDRA PT, which can include normal diagnostic findings. A MedDRA PT does not indicate a medically confirmed diagnosis.
^† On October 12, 2022, the Food and Drug Administration authorized bivalent (mRNA encoding the spike protein from the SARS-CoV-2 ancestral strain and BA.4/BA.5 Omicron variants) formulations of Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines for use as a single booster dose ≥2 months after completion of primary series or monovalent booster vaccination for children aged 5–11 years and 6–17 years.
^§ The most common MedDRA PTs among reports of vaccination error included incorrect dose administered (303; 39.1%), incorrect product formulation administered (207; 26.7%), product preparation issue (177; 22.8%), and product administered to patient of inappropriate age (126; 16.3%).
^¶ The most common adverse health events MedDRA PTs for reports with nonserious vaccination errors included fever (24; 32.4%), pain in extremity (20; 27.0%), fatigue (14; 18.9%), headache (11; 14.9%), and pain (eight; 10.8%).
** Excluding reports of vaccination error. Includes the top 10 most frequently coded MedDRA PTs among nonserious reports.
^†† VAERS reports are classified as serious if any of the following are reported: hospitalization, prolongation of hospitalization, life-threatening illness, permanent disability, congenital anomaly or birth defect, or death. Serious reports to VAERS were reviewed by CDC physicians to form a clinical impression. https://www.meddra.org/how-to-use/basics/hierarchy