Safety Monitoring of COVID-19 Vaccine Booster Doses Among Adults

United States, September 22, 2021-February 6, 2022

Anne M. Hause, PhD; James Baggs, PhD; Paige Marquez, MSPH; Tanya R. Myers, PhD; John R. Su, MD; Phillip G. Blanc, MD; Jane A. Gwira Baumblatt, MD; Emily Jane Woo, MD; Julianne Gee, MPH; Tom T. Shimabukuro, MD; David K. Shay, MD

Disclosures

Morbidity and Mortality Weekly Report. 2022;71(7):249-254.

Abstract and Introduction

Introduction

During September 22, 2021–February 6, 2022, approximately 82.6 million U.S. residents aged ≥18 years received a COVID-19 vaccine booster dose.* The Food and Drug Administration (FDA) has authorized a booster dose of either the same product administered for the primary series (homologous) or a booster dose that differs from the product administered for the primary series (heterologous). These booster authorizations apply to all three COVID-19 vaccines used in the United States^†.^[1–3] The Advisory Committee on Immunization Practices (ACIP) recommended preferential use of an mRNA COVID-19 vaccine (mRNA-1273 [Moderna] or BNT162b2 [Pfizer-BioNTech]) for a booster, even for persons who received the Ad26.COV2.S (Janssen [Johnson & Johnson]) COVID-19 vaccine for their single-dose primary series.^§ To characterize the safety of COVID-19 vaccine boosters among persons aged ≥18 years during September 22, 2021–February 6, 2022, CDC reviewed adverse events and health impact assessments following receipt of a booster that were reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination, and adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system managed by CDC and FDA. Among 721,562 v-safe registrants aged ≥18 years who reported receiving a booster, 88.8% received homologous COVID-19 mRNA vaccination. Among registrants who reported a homologous COVID-19 mRNA booster dose, systemic reactions were less frequent following the booster (58.4% [Pfizer-BioNTech] and 64.4% [Moderna], respectively) than were those following dose 2 (66.7% and 78.4%, respectively). The adjusted odds of reporting a systemic reaction were higher following a Moderna COVID-19 vaccine booster, irrespective of the vaccine received for the primary series. VAERS has received 39,286 reports of adverse events after a COVID-19 mRNA booster vaccination for adults aged ≥18 years, including 36,282 (92.4%) nonserious and 3,004 (7.6%) serious events. Vaccination providers should educate patients that local and systemic reactions are expected following a homologous COVID-19 mRNA vaccine booster; however, these reactions appear less common than those following dose 2 of an mRNA-based vaccine. CDC and FDA will continue to monitor vaccine safety and provide data to guide vaccine recommendations and protect public health.

V-safe (https://vsafe.cdc.gov/en/) is a voluntary, smartphone-based U.S. safety surveillance system established to monitor adverse events after COVID-19 vaccination. The platform allows existing registrants to report receiving a COVID-19 booster dose and new registrants to enter information about all COVID-19 vaccine doses received. Health surveys are sent daily during the first week after receipt of each dose and include questions about local injection site and systemic reactions and health impacts.^¶ CDC's v-safe call center contacts registrants who indicate that medical care was sought after vaccination and encourages completion of a VAERS report, if indicated.

VAERS is a U.S. national passive vaccine safety surveillance system managed by CDC and FDA that monitors adverse events after vaccination.^[4] VAERS accepts reports from health care providers, vaccine manufacturers, and members of the public.** VAERS reports are classified as serious if there are any reports of hospitalization, prolongation of hospitalization, life-threatening illness, permanent disability, congenital anomaly or birth defect, or death.^†† VAERS staff members assign Medical Dictionary for Regulatory Activities (MedDRA) preferred terms to the signs, symptoms, and diagnostic findings in VAERS reports.^§§ Previous reports of myocarditis and pericarditis following receipt of COVID-19 vaccine were identified by a search for selected MedDRA preferred terms;^[5] CDC staff members attempted to collect information from health care providers about clinical course and determined whether the case definition for myocarditis or pericarditis was met.^¶¶

Local and systemic reactions and health impacts reported during the week following booster vaccination were described for v-safe registrants aged ≥18 years who received a COVID-19 booster (≥2 months after a single dose of Janssen COVID-19 vaccine or ≥5 months after the second dose of a COVID-19 mRNA vaccine) during September 22, 2021–February 6, 2022, and completed at least one v-safe health check-in survey in the week after each vaccination. Registrants who reported receiving a COVID-19 mRNA primary vaccination series followed by a Janssen booster (476) were excluded from the analysis because of small numbers. VAERS reports for persons aged ≥18 years who received a COVID-19 mRNA vaccine booster during September 22, 2021–February 6, 2022, were described by severity (serious versus nonserious), demographic characteristics (i.e., age, sex, race, and ethnicity), and MedDRA preferred terms. Reporting rates for myocarditis reports meeting the case definition after a booster were stratified by sex and age group. Multivariable analyses were conducted to estimate the adjusted odds of reporting an adverse event or health impact by comparing 1) dose 2 and booster for registrants who received homologous COVID-19 mRNA vaccination, and 2) homologous and heterologous booster vaccination. 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/#vaccination-demographic
^†The FDA has authorized a booster dose of either the same product administered for the primary series (homologous) or a booster dose that differs from the product administered for the primary series (heterologous). These booster authorizations apply to all three COVID-19 vaccines used in the United States: 1) Pfizer-BioNTech COVID-19 vaccine ≥5 months after dose 2 for persons aged ≥12 years, 2) Moderna COVID-19 vaccine ≥5 months after dose 2 for persons aged ≥18 years, and 3) Janssen COVID-19 vaccine ≥2 months after a single dose for persons aged ≥18 years.
^§ https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html
^¶Health surveys are sent for the most recent dose entered via text messages that link to web-based surveys on days 0–7 after receipt of vaccine dose; then weekly through 6 weeks after vaccination; and then at 3, 6, and 12 months after vaccination. Local injection site reactions include itching, pain, redness, and swelling. Systemic reactions include abdominal pain, myalgia, chills, diarrhea, fatigue, fever, headache, joint pain, nausea, rash, and vomiting. Health impacts include inability to perform normal daily activities, inability to work or attend school, and receipt of medical care.
**CDC and FDA encourage all health care providers to report adverse events to VAERS and are required by COVID-19 vaccine Emergency Use Authorizations to report certain adverse events after vaccination to VAERS, including death. https://vaers.hhs.gov/faq.html
^††VAERS reports are classified as serious based on the Code of Federal Regulations Title 21 (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr). Reports of serious adverse events receive follow-up by VAERS staff members to obtain additional information, including medical records and, for reports of death, death certificates and autopsy reports, if available.
^§§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
^¶¶Acute myocarditis was defined as presence of signs and symptoms new onset or worsening of one or more of the following signs or symptoms: chest pain, pressure, discomfort, dyspnea, shortness of breath, pain with breathing, palpitations, or syncope; or two or more of the following signs or symptoms in children aged ≤11 years: irritability, vomiting, poor feeding, tachypnea, or lethargy); and one or more new finding of elevated troponin, electrocardiogram findings consistent with myocarditis, abnormal cardiac function or wall motion on echocardiogram, cardiac magnetic resonance imaging findings consistent with myocarditis, or histopathologic findings consistent with myocarditis; and no other identifiable cause for these findings.
***The odds of reporting an adverse event or health impact following dose 2 and booster were compared for registrants who received homologous COVID-19 mRNA vaccination using a multivariable generalized estimating equations model that accounted for the correlation between registrants and adjusted for demographic variables (i.e., age, sex, race, and ethnicity). The odds of reporting an event following homologous and heterologous booster vaccination were compared using a logistic regression model that adjusted for demographic variables of registrants; p<0.01 was considered significant. Odds ratios were not adjusted for persons who reported a primary Janssen series because of small numbers. The model did not converge for the 476 registrants who reported COVID-19 mRNA vaccination primary dose followed by a Janssen booster, and these registrants were excluded from the analysis.
^†††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. Adjusted odds ratios* and 95% CI for reactions and health impacts following homologous or heterologous COVID-19 vaccine booster dose among adults aged ≥18 years, by primary vaccination series and booster vaccine product received (N = 721,562) — United States, September 22, 2021–February 6, 2022
Primary series/Booster vaccine (no.)	No. of booster doses (%)	Reaction^† (%)
Primary series/Booster vaccine (no.)	No. of booster doses (%)	Any injection site reaction	Any systemic reaction	Any health impact
Moderna^§ (n = 327,464)
Moderna	307,998 (94.1)	71.8	64.4	23.6
Pfizer-BioNTech	19,222 (5.9)	70.7	66.7	23.4
aOR (95% CI)	—	0.70 (0.68–0.73)^¶	0.85 (0.82–0.88)^¶	0.81 (0.78–0.84)^¶
Pfizer-BioNTech^§ (n = 349,545)
Pfizer-BioNTech	332,588 (95.1)	64.3	58.4	19.1
Moderna	16,725 (4.8)	87.7	82.9	39.5
aOR (95% CI)	—	2.41 (2.30–2.53)^¶	2.24 (2.14–2.33)^¶	2.06 (1.99–2.13)^¶
Janssen (n = 44,553)**
Janssen	7,656 (17.2)	52.3	56.2	16.6
Moderna	23,310 (52.3)	65.9	58.2	19.0
OR (95% CI)	—	1.76 (1.67–1.86)^¶	1.08 (1.03–1.14)^¶	1.18 (1.10–1.26)^¶
Pfizer-BioNTech	13,587 (30.5)	62.0	56.6	16.8
OR (95% CI)	—	1.49 (1.41–1.57)^¶	1.01 (0.96–1.07)	1.01 (0.94–1.09)

Abbreviations: aOR = adjusted odds ratio; OR = odds ratio.
*Includes persons who completed at least one v-safe health check-in survey on days 0–7 after receipt of each vaccine dose. The odds of reporting an event following homologous (referent group) and heterologous booster vaccination were compared using a logistic regression model that adjusted for demographic variables (i.e., age, sex, race, and ethnicity) of registrants. Odds ratios were not adjusted for persons who reported a primary Janssen series because of small numbers.
^†Local injection site reactions include itching, pain, redness, and swelling. Systemic reactions include abdominal pain, myalgia, chills, diarrhea, fatigue, fever, headache, joint pain, nausea, rash, and vomiting. Health impacts include inability to perform normal daily activities, inability to work or attend school, and receipt of medical care.
^§The model did not converge for the 476 registrants who reported COVID-19 mRNA vaccination primary dose followed by a Janssen booster, and they were excluded from the analysis.
^¶P<0.01 was considered statistically significant.
**Includes persons who received a primary Janssen single-dose and one additional dose of vaccine from the listed manufacturers.

Table 2. Cases and rates* of myocarditis reported to the Vaccine Adverse Event Reporting System ^† following receipt of an mRNA COVID-19 booster dose among adults aged ≥18 years (N = 37), by age, sex, and vaccine product received — United States, September 22, 2021–February 6, 2022
Age group, yrs	No. of cases (rates)*^,§
	Pfizer-BioNTech (n = 18)		Moderna (n = 18)
	Men (n = 16)	Women (n<5)	Men (n = 10)	Women (n = 8)
18–24	5 (4.1)	<5 (<1.0)	6 (8.7)	<5 (1.1)
25–29	<5 (1.1)	0 (—)	<5 (3.2)	<5 (1.2)
30–39	<5 (1.7)	<5 (<1.0)	<5 (<1.0)	<5 (1.5)
40–49	0 (—)	0 (—)	0 (—)	<5 (<1.0)
50–64	<5 (<1.0)	0 (—)	0 (—)	<5 (<1.0)
≥65^¶	5 (<1.0)	0 (—)	<5 (<1.0)	0 (—)

Abbreviations: MedDRA = Medical Dictionary for Regulatory Activities; VAERS = Vaccine Adverse Event Reporting System.
*Cases per 1 million doses administered.
^†VAERS reports of myocarditis were identified using a combination of MedDRA preferred terms, with symptom onset during day of vaccination through day 6 after vaccination and verified to meet case definition by clinician interview with a health care provider, or clinician review of the medical record. The analysis includes persons receiving both homologous and heterologous booster doses.
^§Cells with fewer than two persons were suppressed and indicated as "<5" for confidentiality.
^¶Includes one report with sex of patient not reported.