COVID-19 mRNA Vaccine Safety Among Children Aged 6 Months–5 Years — United States, June 18, 2022–August 21, 2022

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On June 17, 2022, the Food and Drug Administration (FDA) amended the Emergency Use Authorization (EUA) for mRNA COVID-19 vaccines to include children aged 6 months–4 years for receipt of BNT162b2 (Pfizer-BioNTech) (administered as 3 doses, 3 μg [0.2 mL] each) and children aged 6 months–5 years for receipt of mRNA-1273 (Moderna) (administered as 2 doses, 25 μg [0.25 mL] each) (1,2). In preauthorization clinical trials, the Pfizer-BioNTech vaccine was administered to 3,013 children aged 6 months–4 years (3) and the Moderna vaccine was administered to 5,011 children aged 6 months–5 years (4). Most adverse events reported in these trials were mild to moderate in severity and no serious vaccine-related adverse events were reported. To characterize postauthorization safety of COVID-19 vaccine primary series among young children, CDC reviewed adverse events and health impacts after receipt of Pfizer-BioNTech and Moderna vaccines that were reported to v-safe, a voluntary smartphone-based U.S. safety surveillance system established by CDC to monitor adverse events after COVID-19 vaccination (https://vsafe.cdc.gov/en/), and the Vaccine Adverse Event Reporting System (VAERS), a U.S. passive vaccine safety surveillance system managed by CDC and FDA. During June 18–August 21, 2022, approximately 599,457children aged 6 months–4 years received the Pfizer-BioNTech vaccine and 440,773 aged 6 months–5 years received the Moderna vaccine*; approximately 23,266 children were enrolled in v-safe after mRNA COVID-19 vaccination. The most frequent systemic reactions reported to v-safe after receipt of Pfizer-BioNTech or Moderna vaccines were irritability or crying among approximately one half of children aged 6 months–2 years. Among children aged ≥3 years, systemic reactions after vaccination were less frequently reported; injection site pain was the most frequently reported reaction among these older children. VAERS received a total of 1,017 reports of adverse events after Pfizer-BioNTech or Moderna vaccination among children aged 6 months–4 years and children aged 6 months–5 years; 998 (98.1%) events were classified as nonserious and 19 (1.9%) as serious. No reports of myocarditis after vaccination were reported. These initial safety findings are similar to those from preauthorization clinical trials (3,4). Health care providers and parents of young children should be aware that local and systemic reactions are expected after vaccination with Pfizer-BioNTech or Moderna vaccine and that serious adverse events are rare.

On June 20, 2022, v-safe was modified to allow parents and guardians to enroll children aged 6 months–4 years after any mRNA COVID-19 vaccine dose. Text message reminders are sent to parents or guardians to complete online health surveys for their child.^† Health surveys sent in the first postvaccination week include questions about local injection site and systemic reactions (i.e., mild, moderate, or severe) and health impacts.^§ Specific questions were included for children aged 6 months–2 years who might not be able to describe reactions or who might experience reactions that are different from those experienced by children aged ≥3 years.^¶ CDC’s v-safe call center contacts registrants who indicate that medical care was received after vaccination and encourages completion of a VAERS report.

VAERS is a national passive vaccine safety surveillance system managed by CDC and FDA that monitors adverse events after vaccination (5). VAERS accepts reports of postvaccination adverse events from health care providers, vaccine manufacturers, and members of the public.** Signs, symptoms, and diagnostic findings in VAERS reports are assigned Medical Dictionary for Regulatory Activities preferred terms (MedDRA PTs) by VAERS staff.^†† Reports of serious events to VAERS^§§ were reviewed by CDC and FDA physicians to form a consensus clinical impression based on available data. Using selected MedDRA PTs, a search was performed to identify possible cases of myocarditis, a rare adverse event that has been associated with mRNA COVID-19 vaccines (6).

Local and systemic reactions and health impacts reported to v-safe during the week after vaccination were described for children aged 6 months–4 years who received Pfizer-BioNTech vaccine and children aged 6 months–5 years who received Moderna vaccine during June 18–August 21, 2022. VAERS reports were described by serious and nonserious status, demographic characteristics, and MedDRA PTs. Analyses were conducted using SAS software (version 9.4; SAS Institute); p-values <0.05 were considered statistically significant. These surveillance activities were reviewed by CDC and conducted consistent with applicable federal law and CDC policy.^¶¶

Acknowledgments

Allison DeSantis, Charles Licata, Isaac McCullum, and David Yankey.

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 EUA letter of authorization reissued July 8, 2022. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2022. https://www.fda.gov/media/150386/download
2. Food and Drug Administration. Pfizer-BioNTech COVID-19 vaccine EUA letter of authorization reissued June 17, 2022. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2022. https://www.fda.gov/media/144636/download
3. Food and Drug Administration, Vaccines and Related Biological Products Advisory Committee. FDA briefing document: EUA amendment request for Pfizer-BioNTech COVID-19 vaccine for use in children 6 months through 4 years of age. Vaccines and Related Biological Products Advisory Committee meeting; June 15, 2022; Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2022. https://www.fda.gov/media/159195/download
4. Food and Drug Administration, Vaccines and Related Biological Products Advisory Committee. FDA briefing document: EUA amendment request for use of the Moderna COVID-19 vaccine in children 6 months through 17 years of age. Vaccines and Related Biological Products Advisory Committee meeting; June 14–15, 2022; Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2022. https://www.fda.gov/media/159189/download
5. Shimabukuro TT, Nguyen M, Martin D, DeStefano F. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS). Vaccine 2015;33:4398–405. https://doi.org/10.1016/j.vaccine.2015.07.035 PMID:26209838
6. Oster ME, Shay DK, Su JR, et al. Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021. JAMA 2022;327:331–40 . https://doi.org/10.1001/jama.2021.24110 PMID:35076665
7. CDC. COVID-19 vaccine side effects in children and teens. Atlanta, GA: US Department of Health and Human Services, CDC; 2022. Accessed July 20, 2022. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/side-effects-children-teens.html
8. Fleming-Dutra KE, Wallace M, Moulia DL, et al. Interim recommendations of the Advisory Committee on Immunization Practices for use of Moderna and Pfizer-BioNTech COVID-19 vaccines in children aged 6 months–5 years—United States, June 2022. MMWR Morb Mortal Wkly Rep 2022;71:859–68. https://doi.org/10.15585/mmwr.mm7126e2 PMID:35771731

Abbreviation: NA = not applicable.
* On June 17, 2022, the Food and Drug Administration amended the Emergency Use Authorizations for BNT162b2 (Pfizer-BioNTech) vaccine to include children aged 6 months–4 years and mRNA-1273 (Moderna) vaccine to include children aged 6 months–5 years. Safety findings for children aged ≥60 months (5 years) who received Pfizer-BioNTech vaccine have been previously described and were not included in this study.
^† Percentage of children whose parents reported a reaction or health impact at least once during days 0–7 post-vaccination. Health check-in surveys were unique for each age group (6 months–2 years and ≥3 years).

Abbreviation: NA = not applicable.
* On June 17, 2022, the Food and Drug Administration amended the Emergency Use Authorizations for BNT162b2 (Pfizer-BioNTech) vaccine to include children aged 6 months–4 years and mRNA-1273 (Moderna) vaccine to include children aged 6 months–5 years. Safety findings for children aged ≥60 months (5 years) who received Pfizer-BioNTech vaccine have been previously described and were not included in this study.
^† Percentage of registrants for whom a parent or guardian reported a reaction or health impact at least once during days 0–7 after vaccination. Includes the most severe event reported during the 0–7-day window. Parents and guardians who participate in v-safe use the following definitions to describe the severity of a child’s symptoms: mild (noticeable, but not problematic), moderate (limit normal daily activities), or severe (make daily activities difficult or impossible).
^§ Fever is self-reported and registrants are not required to record a temperature. Among children who had a reported temperature and met the definition for fever (≥100.4°F [≥38°C]) during days 0–3, fever was classified as mild (100.4°F–101.1°F [38°C–38.4°C]), moderate (101.2°F–102.0°F [38.4⁰C–38.9°C]), severe (102.1°F–104.0°F [38.9°C–40.0°C]), or very severe (>104.0°F [>40°C]).

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 was coded for one or more MedDRA PTs. A MedDRA PT does not represent a medically confirmed diagnosis and might represent a normal finding or a diagnostic test result. Vaccine administration errors that are MedDRA coded are listed separately in this table.
^† On June 17, 2022, the Food and Drug Administration amended the Emergency Use Authorizations for BNT162b2 (Pfizer-BioNTech) vaccine to include children aged 6 months–4 years and mRNA-1273 (Moderna) vaccine to include children aged 6 months–5 years. Safety findings for children aged ≥60 months (5 years) who received Pfizer-BioNTech vaccine have been previously described and were not included in this study.
^§ The most common MedDRA PTs among reports of vaccination error included incorrect dose administered, product administered to patient of inappropriate age, product preparation issue, wrong product administered, expired product administered, product storage error, and underdose.
^¶ Adverse health events coded for reports with nonserious vaccination errors included decreased appetite, diarrhea, fatigue, fever, rash, scratch, and vomiting.
** Includes the top 13 most frequently coded MedDRA PTs among nonserious reports.
^†† Because of the small number of serious reports, percentages are not provided for serious report events. VAERS reports are classified as “serious” only if one of the following events are reported: hospitalization, prolongation of hospitalization, life-threatening illness, permanent disability, congenital anomaly or birth defect, or death. All other reports are classified as “nonserious” (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr). Serious reports to VAERS were reviewed by CDC physicians to form a clinical impression, based on available information. In the table, the clinical impression for each report is listed. https://www.meddra.org/how-to-use/basics/hierarchy
^§§ Six of the seven seizure reports were for afebrile children; temperature was not reported for the other child. Two of the seven reports represented children with preexisting structural brain abnormalities. Three reports of seizures occurring within 24 hours of vaccination were made; one was of an afebrile child with a history of febrile seizures. Two additional reports of seizures were made, occurring 9 days and 18 days after vaccination.
^¶¶ The acute flaccid myelitis report represented a child recently diagnosed with hand, foot, and mouth disease and human rhinovirus B infection.
*** The anaphylaxis report was for a child who received two vaccinations after a part of the first dose was not injected. Approximately 8 hours after vaccination, the child developed signs and symptoms consistent with anaphylaxis and was treated in an emergency department and discharged.