COVID-19 Vaccine Safety in Adolescents Aged 12–17 Years

United States, December 14, 2020-July 16, 2021

Anne M. Hause, PhD; Julianne Gee, MPH; James Baggs, PhD; Winston E. Abara, MD; Paige Marquez, MSPH; Deborah Thompson, MD; John R. Su, MD, PhD; Charles Licata, PhD; Hannah G. Rosenblum, MD; Tanya R. Myers, PhD; Tom T. Shimabukuro, MD; David K. Shay, MD

Disclosures

Morbidity and Mortality Weekly Report. 2021;70(31):1053-1058.

Abstract and Introduction

Introduction

As of July 30, 2021, among the three COVID-19 vaccines authorized for use in the United States, only the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine is authorized for adolescents aged 12–17 years. The Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Pfizer-BioNTech vaccine for use in persons aged ≥16 years on December 11, 2020;^[1] the EUA was expanded to include adolescents aged 12–15 years on May 10, 2021,^[2] based on results from a Phase 3 clinical trial.^[3] Beginning in June 2021, cases of myocarditis and myopericarditis (hereafter, myocarditis) after receipt of Pfizer-BioNTech vaccine began to be reported, primarily among young males after receipt of the second dose.^[4,5] On June 23, 2021, CDC's Advisory Committee on Immunization Practices (ACIP) reviewed available data and concluded that the benefits of COVID-19 vaccination to individual persons and the population outweigh the risks for myocarditis and recommended continued use of the vaccine in persons aged ≥12 years.^[6] To further characterize safety of the vaccine, adverse events after receipt of Pfizer-BioNTech vaccine reported to the Vaccine Adverse Event Reporting System (VAERS) and adverse events and health impact assessments reported in v-safe (a smartphone-based safety surveillance system) were reviewed for U.S. adolescents aged 12–17 years during December 14, 2020–July 16, 2021. As of July 16, 2021, approximately 8.9 million U.S. adolescents aged 12–17 years had received Pfizer-BioNTech vaccine.* VAERS received 9,246 reports after Pfizer-BioNTech vaccination in this age group; 90.7% of these were for nonserious adverse events and 9.3% were for serious adverse events, including myocarditis (4.3%). Approximately 129,000 U.S. adolescents aged 12–17 years enrolled in v-safe after Pfizer-BioNTech vaccination; they reported local (63.4%) and systemic (48.9%) reactions with a frequency similar to that reported in preauthorization clinical trials. Systemic reactions were more common after dose 2. CDC and FDA continue to monitor vaccine safety and provide data to ACIP to guide COVID-19 vaccine recommendations.

VAERS is a passive vaccine safety surveillance system comanaged by CDC and FDA that monitors adverse events after vaccination.^[7] VAERS accepts reports from anyone, including health care providers, vaccine manufacturers, and members of the public. Under COVID-19 vaccine EUA requirements, health care providers must report certain adverse events after vaccination to VAERS, including death.^† Signs, symptoms, and diagnostic findings in VAERS reports are assigned Medical Dictionary for Regulatory Activities (MedDRA) preferred terms by VAERS staff members.^§ VAERS reports are classified as serious if any of the following are reported: hospitalization or prolongation of hospitalization, life-threatening illness, permanent disability, congenital anomaly or birth defect, or death.^¶ Reports of serious adverse events receive follow-up to obtain additional information, including medical records; for reports of death, death certificates and autopsy reports are obtained, if available. CDC physicians reviewed available information for each decedent to form an impression about cause of death.

CDC established v-safe, a voluntary smartphone-based active safety surveillance system, to monitor adverse events after COVID-19 vaccination. Adolescents who receive a COVID-19 vaccine are eligible to enroll in v-safe, through self-enrollment or as a dependent of a parent or guardian, and receive scheduled text reminders about online health surveys.** Health surveys sent in the first week after vaccination include questions about local injection site and systemic reactions and health impacts.^†† If a report indicated medical attention was sought, VAERS staff members contacted the reporter and encouraged completion of a VAERS report, if indicated.

VAERS and v-safe data were assessed by sex, age group, and race/ethnicity for U.S. adolescents aged 12–17 years who received Pfizer-BioNTech vaccine during December 14, 2020–July 16, 2021. VAERS reports for adolescents aged 12–15 years were excluded if vaccination occurred before EUA age expansion on May 10, 2021. FDA used empirical Bayesian data mining to monitor for disproportional reporting of adverse events by vaccine among VAERS reports for persons aged 12–17 years^§§.^[8] SAS software (version 9.4; SAS Institute) was used to conduct all analyses. These surveillance activities were reviewed by CDC and conducted consistent with applicable federal law and CDC policy.^¶¶

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*https://covid.cdc.gov/covid-data-tracker/#datatracker-home
^† https://vaers.hhs.gov/faq.html
^§Each VAERS report might be assigned more than one MedDRA preferred term. A MedDRA-coded event does not indicate a medically confirmed diagnosis. https://www.meddra.org/how-to-use/basics/hierarchy
^¶Based on the Code of Federal Regulations Title 21. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr
**Adolescents aged <15 years must be enrolled by a parent or guardian and may not self-enroll. Health check-ins are sent via text messages that link to web-based surveys on days 0–7 after vaccination; then weekly through 6 weeks after vaccination; and then 3, 6, and 12 months after vaccination.
^††Participants in v-safe self-identify the severity of their symptoms, defined as mild (noticeable, but not problematic), moderate (limit normal daily activities), or severe (make daily activities difficult or impossible). Health impacts include whether the vaccine recipient was unable to perform normal daily activities, missed school or work, or received care (i.e., telehealth, clinic or emergency department visit, or hospitalization) from a medical professional because of new symptoms or conditions.
^§§FDA used the Multi-Item Gamma Poisson Shrinker algorithm to calculate the Empirical Bayes Geometric Mean and its associated 90% confidence interval (EB05, EB95). An EB05 ≥2 (more than twice expected) was considered the threshold for defining a vaccine-event pair reported disproportionately.
^¶¶45 C.F.R. part 46, 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.

Table 1. Adverse event reports for adolescents aged 12–17 years who received the Pfizer-BioNTech COVID-19 vaccine, by demographic characteristics and reported symptoms (N = 9,246) — Vaccine Adverse Event Reporting System, United States, December 14, 2020–July 16, 2021
Characteristic	Total, % (N = 9,246)	Severity, %*
Characteristic	Total, % (N = 9,246)	Nonserious (n = 8,383)	Serious, excluding death (n = 849)	Death (n = 14)
Sex
Female	52.9	55.3	29.1	35.7
Male	45.8	43.2	70.7	64.3
Unknown	1.4	1.5	0.2	0
Age group, yrs
12–15	58.1	58.7	53.4	28.6
16–17	41.9	41.3	46.6	71.4
Ethnicity
Hispanic or Latino	10.4	9.6	18.4	7.1
Non-Hispanic or Latino	44.1	43.4	51.2	50.0
Unknown ethnicity	45.5	47.1	30.4	42.9
Race
American Indian or Alaska Native	0.8	0.8	0.5	0
Asian	5.2	5.0	7.3	7.1
Black	3.2	3.0	5.3	7.1
Native Hawaiian or Pacific Islander	0.3	0.2	0.7	0
White	45.1	44.2	53.8	71.4
Multiracial	2.1	2.2	2.0	0
Other	13.1	13.9	5.4	0
Unknown race	30.2	30.8	25.0	14.3

Abbreviation: VAERS = Vaccine Adverse Event Reporting System.
*VAERS reports are classified as serious if any of the following are reported: hospitalization or prolongation of hospitalization, life-threatening illness, permanent disability, congenital anomaly or birth defect, or death.

Table 2. Most frequent symptoms, signs, diagnostic results, and conditions* reported to the Vaccine Adverse Event Reporting System for adolescents aged 12–17 years after receipt of the Pfizer-BioNTech COVID-19 vaccine (N = 9,246) — United States, December 14, 2020–July 16, 2021
Symptom, sign, diagnostic result, or condition	% Reporting
Nonserious reports (n = 8,383)
Dizziness	21.2
Syncope	14.4
Nausea	10.4
Headache	10.0
Fever	8.3
Loss of consciousness	7.5
Excessive sweating	7.4
Fatigue	7.2
Pallor	7.1
Product administered to patient outside of indicated age range	7.0
Product storage error	6.4
Vomiting	6.4
Difficulty breathing	5.3
Chest pain	4.9
Pain	4.6
Serious reports, including reports of death ^† (n = 863)
Chest pain	56.4
Increased troponin	41.7
Myocarditis	40.3
Increased c-reactive protein	30.6
Negative SARS-CoV-2 test result	29.4
Fever	28.3
Normal echocardiogram	26.9
Abnormal electrocardiogram	25.6
Headache	22.2
Difficulty breathing	21.4
Elevated electrocardiogram ST segment	20.5
Normal chest radiograph	19.7
Intensive care	18.1
Vomiting	17.0
Nausea	16.6

Abbreviations: MedDRA = Medical Dictionary for Regulatory Activities; VAERS = Vaccine Adverse Event Reporting System.
*Signs and symptoms in VAERS reports are assigned MedDRA preferred terms by VAERS staff members. Each VAERS report might be assigned more than one MedDRA preferred term, which can include normal diagnostic findings. A MedDRA-coded event does not indicate a medically confirmed diagnosis. https://www.meddra.org/how-to-use/basics/hierarchy
^†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.

Table 3. Reactions reported by adolescents aged 12–17 years (N = 129,059) who completed at least one v-safe health check-in survey on days 0–7 after receiving Pfizer BioNTech COVID-19 vaccine — United States, December 14, 2020–July 16, 2021
Event	% of v-safe enrollees reporting reaction or health impact*
	Age 16–17 yrs, dose (no.)		Age 12–15 yrs, dose (no.)
	Dose 1 (66,350)	Dose 2 (41,040)	Dose 1 (62,709)	Dose 2 (38,817)
Any injection site reaction	62.7	64.4	63.9	62.4
Itching	5.7	6.3	5.8	5.5
Pain	60.2	62.0	61.2	59.9
Redness	3.4	4.9	4.1	5.3
Swelling	7.7	9.9	7.5	8.9
Any systemic reaction	55.7	69.9	48.9	63.4
Abdominal pain	4.7	8.5	4.1	7.0
Myalgia	25.4	40.7	21.4	31.4
Chills	8.3	26.2	6.8	21.1
Diarrhea	4.2	4.9	3.1	3.3
Fatigue	34.1	52.3	27.4	44.6
Fever	9.9	31.0	9.3	29.9
Headache	29.8	50.6	25.2	43.7
Joint pain	7.9	18.2	6.3	12.4
Nausea	10.2	19.8	7.5	14.8
Rash	1.2	1.1	1.2	1.2
Vomiting	1.1	2.3	1.0	2.6
Any health impact	11.0	28.6	10.6	25.4
Unable to perform normal daily activities	9.0	24.7	9.3	23.1
Unable to work or attend school	3.7	11.6	2.4	6.1
Needed medical care	0.5	0.6	0.5	0.8
Telehealth	0.1	0.2	0.1	0.2
Clinic	0.2	0.2	0.2	0.3
Emergency department visit	0.1	0.2	0.1	0.2
Hospitalization	0.02	0.03	0.02	0.04