National Center for Emerging and Zoonotic Infectious Diseases

COVID-19 mRNA bivalent booster vaccine safety

Advisory Committee on Immunization Practices (ACIP) meeting

February 24, 2023

Tom T. Shimabukuro, MD, MPH, MBA

Director, Immunization Safety Office

Division of Healthcare Quality Promotion 

Centers for Disease Control and Prevention (CDC)
Topics

 Describe CDC’s Vaccine Safety Datalink (VSD) Rapid Cycle Analysis (RCA) 

monitoring methods and assessment processes for statistical signals

 Describe VSD RCA signal detection and signal assessment for ischemic 

stroke after Pfizer-BioNTech COVID-19 mRNA bivalent booster dose 

vaccination in the age group 65 years and older

 Describe rates of myocarditis/pericarditis following COVID-19 mRNA 

vaccination

2
Background: COVID-19 mRNA bivalent booster 

vaccination in the United States

 Bivalent COVID-19 mRNA booster vaccinations first became available in the 

United States in September 2022

 As of February 8, 2023, 52.5 million COVID-19 mRNA bivalent booster doses 

administered in people ages 5 years and older in the United States*

• Includes 22.3 million doses in people ages 65 years and older*

 CDC and partners monitor the safety of licensed and authorized U.S. vaccines 

using multiple complementary systems (Vaccine Information and Safety Studies | Vaccine Safety | CDC)

 Safety data support CDC recommendations that everyone eligible for a COVID19 mRNA bivalent booster get vaccinated

* CDC COVID Data Tracker: Vaccinations in the US 3
VSD COVID-19 Rapid Cycle Analysis: 

Preliminary Analyses of Ischemic Stroke after 

Pfizer-BioNTech Bivalent Booster Dose

Prepared by:

Kaiser Permanente Northern California Vaccine Study Center

Presented by Tom Shimabukuro, MD, MPH, MBA

Centers for Disease Control and Prevention

4
Vaccine Safety Datalink (VSD)

 Established in 1990

 Collaborative project between CDC and 9 integrated healthcare organizations

 Includes electronic health record data on ~12.5 million individuals across all sites 5
Strengths of VSD Rapid Cycle Analysis (RCA)

 Population

• ~12.5 million people (equal to ~4% of the U.S. population) across VSD data sites are 

geographically and racially/ethnically diverse

 Data 

• Near real-time data, with analyses updated weekly

• Access to comprehensive medical records, including exposures (vaccination) and outcomes, 

allowing rapid chart reviews to obtain additional clinical information as needed

 Innovative Methods

• Vaccinated concurrent comparators: Recent vaccinees as comparators are expected to be more similar to current vaccinees than unvaccinated individuals with the following advantages

‒

‒

Careful adjustment for potential biases associated with calendar time, site, and demographic factors 

Analyses can begin sooner than alternative methods 

• Supplemental analyses conducted weekly: Unvaccinated/un-boosted comparators would also be available to provide context in real time 

• Using vaccinated concurrent comparators with supplemental analyses offers substantial benefits 

compared with either unvaccinated or historical comparators 

6
VSD RCA for bivalent boosters

 Pre-specified outcomes were assessed during weekly sequential 

monitoring after COVID-19 bivalent booster vaccination*

• Risk of pre-specified outcomes 1–21 days following a bivalent vaccination 

compared with bivalent vaccinated individuals who were 22–42 days 

following the bivalent dose

• All analyses adjusted for age, sex, race/ethnicity, VSD site, calendar time 

(days) and seasonality (time)

• Signal if p-value <0.01 (1-sided)

* Rapid Cycle Analysis (RCA) to monitor the safety of COVID-19 vaccines in near real-time within the Vaccine Safety Datalink. Available at: 

Rapid Cycle Analysis (RCA) to monitor the safety of COVID-19 vaccines in near real-time within the Vaccine Safety Datalink (cdc.gov) 7
Vaccinee with outcome in the risk interval and a concurrent comparator

“bivalent vaccinated individuals only”

On each calendar day that an outcome 

occurred in a vaccinee (e.g., October 3), we 

compared vaccinees in their risk interval (day 

1–21) with similar vaccinees in their 

comparison interval (day 22–42)

By similar, we mean that on the same calendar 

day, they were in the same age group and of 

the same sex, race/ethnicity, and at the same 

VSD site

Comparison Interval 22–42 days post-vaccination 

22 October 3 42

Vaccinated with 

Bivalent Booster 

September 3

1

Risk Interval 1–21 days post-vaccination

21 October 3

Vaccinated with 

Bivalent Booster 

September 30

8
9

VSD COVID-19 vaccine RCA prespecified surveillance outcomes

Prespecified outcomes Settings

Acute disseminated encephalomyelitis Emergency dept, Inpatient

Acute myocardial infarction Emergency dept, Inpatient

Acute respiratory distress syndrome Emergency dept, Inpatient

Anaphylaxis* Emergency dept, Inpatient

Appendicitis Emergency dept, Inpatient

Bell’s palsy Emergency dept, Inpatient, Outpatient

Cerebral venous sinus thrombosis Emergency dept, Inpatient

Disseminated intravascular coagulation Emergency dept, Inpatient

Encephalitis / myelitis / encephalomyelitis Emergency dept, Inpatient

Guillain-Barré syndrome Emergency dept, Inpatient

Immune thrombocytopenia Emergency dept, Inpatient, Outpatient

Kawasaki disease Emergency dept, Inpatient

Multisystem inflammatory syndrome in children/adults (MIS-C/MIS-A) Emergency dept, Inpatient

Myocarditis / pericarditis* Emergency dept, Inpatient

Narcolepsy / cataplexy Emergency dept, Inpatient, Outpatient

Pulmonary embolism Emergency dept, Inpatient

Seizures/Convulsions (including 0-7 days for youngest ages) Emergency dept, Inpatient

Stroke, hemorrhagic Emergency dept, Inpatient

Stroke, ischemic Emergency dept, Inpatient

Thrombosis with thrombocytopenia syndrome Emergency dept, Inpatient

Thrombotic thrombocytopenic purpura Emergency dept, Inpatient

Transverse myelitis Emergency dept, Inpatient

Venous thromboembolism Emergency dept, Inpatient, Outpatient

*All outcomes are first ever in the ICD-10 era, except anaphylaxis which is first in 7 days, and myocarditis/pericarditis which is first in 60 days

 In COVID-19 bivalent booster vaccine monitoring, VSD RCA detected a statistical signal for ischemic stroke after 

Pfizer-BioNTech bivalent booster vaccination in the age group 65 years and older

 No other VSD RCA pre-specified surveillance outcomes have signaled in any age groups for either of the mRNA 

COVID-19 bivalent booster vaccines or when data for the two mRNA vaccine types are combined/pooled
VSD investigations of an RCA signal to assess whether it 

reflects a real effect of vaccination on an outcome

 Data quality assessment for errors, anomalies, or missing/late-arriving data

 Analyses using different comparators than primary concurrent (e.g., un-boosted, 

unvaccinated or “historical” comparators) to supplement our primary analyses

 Additional investigations to provide context (e.g., background rates, etc.)

 Graphic displays of outcome incidence day by day after vaccination, using temporal scan 

statistics to assess apparent clustering

• Examine the temporal clustering of outcome events in subgroups defined by demographics, site or 

simultaneous exposure (e.g., flu vaccine)

 If the signal is driven by a strong association in one subgroup or VSD site, further 

analyses by site or subgroup as appropriate

 Chart review to confirm cases and collect additional data (e.g., date of symptom onset). 

 Consider epidemiologic studies to further investigate surveillance findings

10

Rapid Cycle Analysis (RCA) to monitor the safety of COVID-19 vaccines in near real-time within the Vaccine Safety Datalink. Available at: Rapid 

Cycle Analysis (RCA) to monitor the safety of COVID-19 vaccines in near real-time within the Vaccine Safety Datalink (cdc.gov)
VSD COVID-19 RCA preliminary analyses: 

Ischemic stroke after Pfizer-BioNTech bivalent 

booster among people ≥65 years of age

11
Number of COVID-19 bivalent booster doses and influenza vaccine doses 

administered over time among persons aged ≥65 years, by vaccine type in VSD

12
VSD RCA Ischemic Stroke Definition

ICD-10 CODES TO FIND INCIDENT 

CASES 

ICD-10 CODES FOR LOOKBACK TO ADJUST 

ONSET DATE (in all settings)

ICD-10 CODES - TO DETECT PREVALENCE 

(history of, in all settings) ICD-10 CODES - OTHER CAUSE EXCLUSIONS (in all settings) 

Stroke, ischemic 

(settings = Emergency, Inpatient)

Codes to adjust Stroke, ischemic onset 

(if seen within 1 day before case) Stroke, ischemic - Review for Prevalence - 1ST EVER Other possible causes of Stroke, ischemic

G45.8 Other transient cerebral 

ischemic attacks and 

related syndromes Adjust onset date if occurs in the 1 day prior to 

incident case: Exclude if occurs EVER prior to incident case:

Exclude if COVID-19 in the last 30 days prior to incident case (not 

including same day): 

G45.9 Transient cerebral 

ischemic attack, 

unspecified

COVID-19 DIAGNOSIS 

I63.* Cerebral infarction Z92.82 Status post administration of tPA

(rtPA) in a different facility within 

the last 24 hours prior to admission 

to current facility

Z86.73 Personal history of transient ischemic 

attack (TIA), and cerebral infarction 

without residual deficits

OR

COVID-19 POSITIVE LAB TEST

R51.* Headache I69.* Sequelae of cerebrovascular disease Exclude if occurs in the time period noted prior to incident case 

(not including same day):

R47.* Speech disturbances, not 

elsewhere classified I48.*

Atrial fibrillation and flutter (if seen EVER prior to 

incident case)

R29.810 Facial weakness I21.* Acute myocardial infarction (if seen within 28 days prior 

to incident case)

R53.1 Weakness

S15.*

Injury of blood vessels at neck level (if seen within 1 day 

prior to incident case)

R42.* Dizziness and giddiness

I74.*

Arterial embolism and thrombosis (if seen within 1 day 

prior to incident case)

R41.82 Altered mental status, unspecified D57.* Sickle-cell disorders (if seen EVER prior to incident case)

R40.4 Transient alternation of awareness

D68.5*

Primary thrombophilia (if seen EVER prior to incident 

case)

G81.9* Hemiplegia, unspecified

H53.9 Unspecified visual disturbance

H53.13* Sudden visual loss

13
Bivalent RCA concurrent comparator analyses of

ischemic strokes during a 1–21-day Risk Interval versus 

a 22–42-day Comparison Interval*

Nominal analysis Sequential analysis

Age group 

(years) Vaccine Risk events (N)

Comp 

events (N)

Adjusted 

Rate Ratio

95% 

Confidence 

Interval

1-sided

p-value

Signal? 

1-sided 

p <0.01

18–64

Pfizer 39 38 1.09 0.68 – 1.75 0.398 No

Moderna 14 26 0.49 0.24 – 0.95 0.990 No

65+ Pfizer 143 117 1.36 1.05 – 1.76 0.011 No

Moderna 68 63 1.17 0.82 – 1.67 0.224 No

* Data through Feb 4, 2023

14
Ischemic stroke after Pfizer-BioNTech bivalent booster, age ≥65 

years, counts and adjusted rate ratios (Oct 16, 2022 – Feb 4, 2023)

15

0

3.95

4.38

1.51

1.25

1.49

1.92 1.85 1.89

1.57 1.53 1.54 1.47 1.46 1.36 1.39

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

0

20

40

60

80

100

120

140

160

Rate Ratio

Number of Cases in Risk or Comp Window

1-21 Day Risk Interval 22-42 Day Comp Interval Rate Ratio

RR = 1.36 (95% CI 1.05-1.76)

Red dot represents sequential signal: p-value <0.01 (1-sided)
Ischemic stroke by day after Pfizer-BioNTech bivalent 

boosters, people ages ≥65 Years*

* Data cutoff 3 weeks prior

Significant cluster days 13–22, 

p-value = 0.0150

16
Ischemic stroke preliminary chart review: Cases ≥65 years old during 

days 11–21 post-Pfizer-BioNTech bivalent booster vaccination

 Review of a subset of cases at one site (N=24); 22 of 24 were incident stroke/TIA (pos. pred. value 92%)

• None had any history of stroke or transient ischemic attack (TIA)

• Median age of verified cases was 77.5 years

• Symptom onset date rarely shifted from electronic date

• 5 (23%) with known history of SARS-CoV-2 infection, only 1 within last 6 months 

• 0 with mention of recent exposure to SARS-CoV-2 in chart notes

• 14 (64%) had simultaneous flu vaccination on the same day (13 high-dose flu vaccines and 1 adjuvanted flu vaccine)

 Outcomes

• 13 of 22 (59%) discharged home

• 4 of 22 (18%) discharged home with home health 

• 2 of 22 (9%) discharged to a skilled nursing facility

• 3 of 22 (14%) died 

‒ One death in a 75–79-year-old male ~1 month after stroke; death was likely related to the stroke

‒ One stroke in a 65–69-year-old female noted after craniotomy, though relationship with surgery unclear; death due 

to cardiac arrest ~2.5 months later

‒ One stroke in a 70–74-year-old male during hospitalization for metastatic cancer, with subsequent death due to 

cancer-related complications during hospitalization

 Currently reviewing a random sample of risk and comparison interval cases across VSD sites 17
Age group 

(years)

Interval 

(days) Comparators Vaccine Riskevents (N)

Comp

events (N)

Adjusted 

Rate Ratio

95% 

Confidence 

Interval

P-value

(2-sided)

65+ 1–21 Not bivalent

boosted Pfizer 134 1510 1.07 0.89–1.28 0.483

* Analyses only included outcomes through December 10, 2022. 

18

Supplemental analyses:

Ischemic strokes during the 1–21-day interval comparing bivalent boosted 

vs. un-boosted concurrent comparators (but eligible for bivalent booster)*
Age group

(years)

Interval

(days) Comparators Vaccine Risk events (N)

Comp 

events (N)

Adjusted 

Rate Ratio

95%

Confidence

Interval

P-value

(2-sided)

65+

1–21 Not bivalent

boosted Pfizer 134 1510 1.07 0.89–1.28 0.483

22–42 Not bivalent

boosted Pfizer 83 1081 0.76 0.60–0.95 0.018

* Analyses only included outcomes through December 10, 2022. 

19

 Findings suggest reduced rate of stroke in comparison interval

Supplemental analyses:

Ischemic strokes during the 1–21 and 22–42-day interval comparing bivalent 

boosted vs. un-boosted concurrent comparators (but eligible for bivalent booster)*
Post-signal analyses:

Simultaneous high-dose or adjuvanted influenza vaccines

20
Analytic population

Cases in 1–21-day

Risk Interval

(N=139)

Cases in 22–42-day

Comparison Interval

(N=108)

Adjusted

Rate Ratio**

(95% CI)

P-value 

Bivalent Pfizer + same-day

high-dose or adjuvanted flu 

vaccine

43 26 1.65 (1.02 – 2.72) 0.04

Bivalent Pfizer + same day

standard dose flu vaccine 8 8 1.00 (0.36 – 2.76) 1.00

Bivalent Pfizer without any

same day flu vaccine 88 74 1.19 (0.87 – 1.62) 0.27

21

* Analyses only include vaccination data through December 3, 2022, and stroke outcome data through January 14, 2023

** Adjusted by 5-year age groups

Post-signal analyses*:

Ischemic stroke incidence during days 1–21 compared with days 22–42, 

among ≥65 years with and without simultaneous influenza vaccination
Post-signal analyses*

: 

Expected cases after bivalent booster + high-dose or adjuvanted flu vaccine, 

based on ischemic stroke incidence in un-boosted people eligible for a booster

Age at

vaccination

Expected cases in a 

3-week interval 

(Risk or Comparison)

Observed cases

in a 1–21-day

Risk Interval (N)

Observed cases 

in 22–42-day 

Comparison Interval (N)

65–69 years 7.3 8 6

70–74 years 8.5 8 7

75–79 years 9.8 11 6

80–84 years 6.3 8 3

85–89 years 4.2 5 4

90+ years 2.5 3 0

Total 38.7 43 26

* Analyses only include vaccination data through December 3, 2022, and stroke outcome data through January 14, 2023 

22

 Findings also suggest reduced rate of stroke in comparison interval
Ischemic stroke following bivalent Pfizer-BioNTech COVID-19 

mRNA booster vaccination in people ages 65+ years

 Statistical signal persistent for 8 weeks 

• Rate ratio has slowly attenuated from 1.92 to 1.36 and intermittently met signaling 

criteria

 Additional signal investigation analyses

• Temporal clustering evaluation found a significant cluster 13–22 days after vaccination

• Supplemental analyses using un-boosted concurrent comparators showed a rate ratio 

RR=1.07 (95% CI 0.89–1.28)

• Of small subset of charts reviewed, most confirmed cases had simultaneous high-dose 

or adjuvanted flu vaccine 

• Analyses evaluating simultaneous high-dose or adjuvanted flu vaccine showed a rate 

ratio RR=1.65 (95% CI 1.02–2.72; p-value 0.04)

‒ Separate analyses did not detect an elevated RR for stroke after flu vaccine alone (data not shown)

• Supplemental analyses suggest comparison interval (22–42 days) rates were lower 

than expected

23
Additional considerations

 Small numbers of strokes and imprecise rate ratios limit some analyses 

• Reduced follow-up time after Moderna booster due to distribution delays

• Simultaneous flu vaccine analyses limited by small numbers

 Difficult to interpret temporal clustering during risk and comparison intervals

 Possible unmeasured confounding 

• Results may be influenced by confounders that vary over time

• Do early adopters of bivalent booster vaccine have greater risk of near-term cardiovascular events? 

‒ Same trend has not been observed for acute myocardial infarctions 

‒ Potential impact of differential vaccine availability after EUA (Pfizer-BioNTech > Moderna)

 Possible role of SARS-CoV-2 infection before booster?

• Background incidence of SARS-CoV-2 infection was rapidly changing during bivalent booster uptake

‒ Analysis excluded cases with COVID-19 diagnosis or positive test in prior 30 days, although asymptomatic 

infections and home antigen tests are not consistently documented in EHR; however, KPNC chart reviews did not 

find recent SARS-CoV-2 infection or exposure 24
Further evaluation and key next steps

Further evaluation

 Continue to monitor weekly and explore potential data-related explanations for the 

statistical signal in VSD

 In the process of chart reviewing a random sample of 100 cases across VSD sites

 Consult with other surveillance systems to better understand: 

• Possible role of simultaneous high-dose or adjuvanted flu vaccination with COVID-19 vaccination

• Possible decreased rate of stroke in the 3–6 weeks following vaccination

Key next steps

 CDC continues to recommend that everyone eligible for a COVID-19 mRNA bivalent 

booster or a flu vaccine get vaccinated

 CDC and FDA are engaged in epidemiologic analyses regarding simultaneous of 

COVID-19 mRNA bivalent booster and flu vaccines

25
COVID-19 mRNA bivalent booster vaccination safety – data 

from other monitoring systems and programs*

 No unusual or unexpected reporting patterns observed, and no evidence of a safety 

concern detected for ischemic stroke with either COVID-19 mRNA bivalent boosters in 

Vaccine Adverse Event Reporting System (VAERS) monitoring (see supplemental slides)

 FDA monitoring in the CMS data and Department of Veterans Affairs monitoring in the VA 

system have not detected any safety signals for ischemic stroke following COVID-19 

mRNA bivalent boosters using historical comparator designs 

 Surveillance conducted by international regulatory and public health partners has not 

detected a safety concern for ischemic stroke following bivalent COVID-19 mRNA booster 

vaccination 

 No evidence of a safety signal for ischemic stroke in Pfizer’s global monitoring of bivalent 

COVID-19 mRNA booster vaccination

 No safety signals were detected for ischemic stroke for primary series or monovalent 

boosters for Pfizer-BioNTech or Moderna COVID-19 vaccines in U.S. and global monitoring

26

* These surveillance activities did not include analyses to evaluate the effect of simultaneous flu vaccination; different 

formulations of COVID-19 mRNA bivalent booster vaccinations were used globally
Myocarditis/pericarditis following 

COVID-19 mRNA vaccination in VSD
Number of COVID-19 bivalent booster doses administered over time among 

persons aged 12-39 years, by vaccine type in VSD

28 * Bivalent booster data through January 29, 2023
VSD incidence rates of verified myocarditis or pericarditis in the 0–7 days 

after Pfizer-BioNTech vaccination in people ages 12–39 years*

29

Dose 2 primary series 

Pfizer-BioNTech

1st monovalent booster dose 

Pfizer-BioNTech

Bivalent booster dose

Pfizer-BioNTech

Age/sex Cases Dose 2

total

Incidence rate/

million doses

(95% CI)

Cases 1st booster

total

Incidence rate/

million doses

(95% CI)

Cases

Bivalent

booster

total

Incidence rate/

million doses

(95% CI)

12–17 years

Males

Females

45

6

308,046

311,247

146.1 (106.6–195.5)

19.3 (7.1–42.0)

14

2

129,487

139,118

108.1 (59.1–181.4)

14.4 (1.7–51.9)

0

0

48,066

49,725

0.0 (0.0–62.3)

0.0 (0.0–60.2)

18–29 years

Males

Females

27

2

331,889

400,321

81.4 (53.6–118.4)

5.0 (0.6–18.0)

7

1

166,973

240,226

41.9 (16.9–86.4)

4.2 (0.1–23.2)

1

0

50,687

80,211

19.7 (0.5–53.1)

0.0 (0.0–37.3)

30–39 years

Males

Females

5

3

341,527

410,713

14.6 (4.8–34.2)

7.3 (1.5–21.3)

3

1

197,554

268,412

15.2 (3.1–44.4)

3.7 (0.1–20.8)

0

0

82,191

115,014

0.0 (0.0–36.4)

0.0 (0.0–26.0)

* Primary series and 1st monovalent booster data through August 20, 2022, bivalent booster data through January 29, 2023; Source: Goddard K, et 

al. Incidence of Myocarditis/Pericarditis Following mRNA COVID-19 Vaccination Among Children and Younger Adults in the United States. Ann Intern Med. 

2022;175:1169-1771.
VSD incidence rates of verified myocarditis or pericarditis in the 0–7 days 

after Moderna vaccination in people ages 18–39 years*

30

* Primary series and 1st monovalent booster data through August 20, 2022, bivalent booster data through January 29, 2023; source: Goddard K, et al. Incidence of 

Myocarditis/Pericarditis Following mRNA COVID-19 Vaccination Among Children and Younger Adults in the United States. Ann Intern Med. 2022;175:1169-1771.

Dose 2 primary series 

Moderna

1st monovalent booster dose 

Moderna

Bivalent booster dose

Moderna

Age/sex Cases Dose 2

total

Incidence rate/

million doses

(95% CI)

Cases

1st

booster

total

Incidence rate/

million doses

(95% CI)

Cases

Bivalent

booster

total

Incidence rate/

million doses

(95% CI)

18–29 years

Males

Females

19

0

195,809

243,560

97.0 (58.4 – 151.5)

0.0 (0.0 – 12.3)

7

1

109,337

156,707

64.0 (25.7 – 131.9)

6.4 (0.2 – 35.6)

0

0

18,499

29,561

0.0 (0.0–161.9)

0.0 (0.0–101.3)

30–39 years

Males

Females

8

1

216,583

259,780

36.9 (15.9 – 72.8)

3.9 (0.1 – 21.4)

1

2

149,468

191,765

6.7 (0.2 – 37.3)

10.4 (1.3 – 37.7)

0

0

35,318

47,620

0.0 (0.0–84.8)

0.0 (0.0–62.9)
Acknowledgements

31

 CDC Immunization Safety Office

• VAERS Team

• V-safe Team

• Clinical Immunization Safety Assessment 

(CISA) Project

• Vaccine Safety Datalink (VSD) Team

 COVID-19 Vaccine Task Force Data Monitoring 

and Reporting Group

 Kaiser Permanente Northern California (VSD)

 Marshfield Clinic Research Institute (VSD)

 VSD sites

• HealthPartners Institute, Minneapolis, MN

• Kaiser Permanente Colorado, Denver, CO

• Kaiser Permanente Northwest, Portland, OR

• Kaiser Permanente Southern California, Los Angeles, CA

• Kaiser Permanente Washington, Seattle, WA

• Denver Health, Denver, CO
Disclaimer/disclosures

 The findings and conclusions in this presentation are those of the presenters and 

do not necessarily represent the official position of the CDC

 Mention of a product or company name is for identification purposes only and 

does not constitute endorsement by CDC

 Dr. Nicola Klein reports research support from Pfizer for COVID-19 vaccine clinical 

trials and from Pfizer, GlaxoSmithKline, Merck and Sanofi Pasteur for unrelated 

studies

32
For more information, contact CDC

1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.

Photo credit: James Gathany

(https://phil.cdc.gov/Details.

aspx?pid=8876) 
VAERS and v-safe supplemental slides
VAERS is the nation’s early warning system for vaccine safety

+

Vaccine Adverse Event 

Reporting System

http://vaers.hhs.gov

35
U.S. reports to VAERS following bivalent booster COVID-19 mRNA 

vaccination among ages ≥5 years* (as of February 6, 2023) (N=23,395)

 Distribution by age, sex, and serious status similar regardless of manufacturer

• Most reports (94%) were non-serious

• Race, ethnicity distribution comparable to monovalent COVID-19 mRNA vaccines 

(49% race and/or ethnicity unknown; 39% non-Hispanic white)

Manufacturer

Median 

Age (IQR), 

years

Male†

N (%)

Female†

N (%)

Non-serious

N (%)

Serious 

N (%)

Doses

admin‡ 

Pfizer-BioNTech 54 (33–69) 5,450 (38) 8,750 (61) 13,496 (93) 944 (7) 33,676,379

Moderna 61 (44–71) 3,378 (38) 5,457 (61) 8,460 (94) 495 (6) 19,076,635

Total 58 (37–70) 8,828 (38) 14,207 (61) 21,956 (94) 1,439 (6) 52,753,014

* Includes reports after Moderna bivalent booster among ages ≥6 years; † Excludes 360 (2%) reports where sex was not reported

‡ Doses administered among children ages 5–11 years vaccinated during October 18, 2022–February 8, 2023 36
Most frequent MedDRA Preferred Terms* to VAERS following Pfizer-BioNTech bivalent 

booster vaccination among people ages ≥5 years (as of February 6, 2023)

Rank MedDRA PT (not mutually exclusive) n (%)

1 COVID-19 1,785 (13)

2 Fatigue 1,091 (8)

3 Headache 1,067 (8)

4 Pyrexia/fever 1,016 (8)

5 SARS-CoV-2 test positive 974 (7)

6 Pain 969 (7)

7 Cough 779 (6)

8 Chills 677 (5)

9 Dizziness 571 (4)

10 Pain in extremity 554 (4)

Non-serious reports (N=13,496)† Serious reports (N=944)

Rank MedDRA PT (not mutually exclusive) n (%)

1 COVID-19 274 (29)

2 SARS-CoV-2 test positive 238 (25)

3 Dyspoena 138 (15)

4 Asthenia 109 (12)

5 Condition aggravated 93 (10)

6 Pyrexia/fever 87 (9)

7 Death‡ 83 (9)

8 Cerebrovascular accident 72 (8)

9 Cough 71 (8)

10 Fatigue 69 (7)

* Medical Dictionary for Regulatory Activities Preferred Terms (https://www.meddra.org/how-to-use/basics/hierarchy) † Clinical outcomes only, as determined by subject matter expert consensus

‡ Median age 80 years (IQR: 72–88) 37
Most frequent MedDRA Preferred Terms* to VAERS following Moderna bivalent booster 

vaccination among people ages ≥6 years (as of February 6, 2023)

Rank MedDRA PT (not mutually exclusive) n (%)

1 COVID-19 877 (10)

2 Headache 863 (10)

3 Pyrexia/fever 858 (10)

4 Fatigue 837 (10)

5 SARS-CoV-2 test positive 792 (9)

6 Pain 751 (9)

7 Cough 604 (7)

8 Chills 536 (6)

9 Pain in extremity 440 (5)

10 Oropharyngeal pain 404 (5)

Non-serious reports (N=8,460)† Serious reports (N=495)

Rank MedDRA PT (not mutually exclusive) n (%)

1 COVID-19 146 (30)

2 SARS-CoV-2 test positive 134 (27)

3 Dyspnoea 86 (17)

4 Condition aggravated 50 (10)

5 Death‡ 47 (9)

6 Asthenia 46 (9)

7 Pyrexia/fever 45 (9)

8 Cough 44 (9)

9 Anticoagulant therapy 42 (8)

10 Dizziness 38 (8)

38

* Medical Dictionary for Regulatory Activities Preferred Terms (https://www.meddra.org/how-to-use/basics/hierarchy) † Clinical outcomes only, as determined by subject matter expert consensus

‡ Median age 75 years (IQR: 66–84)
Reports to VAERS of ischemic stroke/transient ischemic attack (TIA) after 

bivalent COVID-19 mRNA vaccination (as of February 6, 2023)

 67 verified reports of ischemic stroke/TIA

• Median age: 73 years (IQR: 67–79 years)

• Median time to onset: 8 days (IQR: 3–24 days)

• 28 males, 39 females

• 47 after Pfizer-BioNTech bivalent

• 20 after Moderna bivalent

Preliminary reports of ischemic 

stroke/TIA (N=224)

Under review*

(n=130)

Excluded based 

upon chart 

review (n=27)

Verified by chart review (n=67)

* Awaiting medical records and/or healthcare provider interview; some still processing 

39
Reporting rate to VAERS of ischemic stroke/transient ischemic attack 

after bivalent COVID-19 mRNA vaccine in people ages ≥65 years 

(as of February 6, 2023)

 Incidence of ischemic stroke among people ages ≥65 years = 670–970 per 

100,000 person years†

* Doses administered as of Feb 9, 2023; † Roger et al. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation 2011;123:e18–e209 40

Chart-verified reports Chart-verified reports 

+ reports under review

Manufacturer Reports Doses 

administered*

Reporting rate 

(per million doses 

administered)

Reports Doses 

administered*

Reporting rate 

(per million doses 

administered)

Pfizer-BioNTech 47 13,217,119 2.9 139 13,217,119 8.4

Moderna 20 9,268,318 1.9 58 9,268,318 4.8
V-safe: Smartphone-based active safety monitoring

Enroll yourself or 

your dependent 

after any dose!

https://vsafe.cdc.gov

41
Reactions and health impacts reported by v-safe participants aged ≥5 years 

at least once 0-7 days after first monovalent booster dose, by age group

0

10

20

30

40

50

60

70

80

90

100

Any injection site reaction Any systemic reaction Any health impact

Percentage

5-11 y

12-17

≥18

Age group (yrs)

Data for participants aged ≥18 years as of October 23, 2022. Includes 677,009 participants who completed at least 1 survey in the first week after mRNA booster dose.

Data for participants aged 12-17 years as of February 20, 2022. Includes 3,418 participants who completed at least 1 survey in the first week after homologous booster dose. 

Data for participants aged 5-11 years as of July 31, 2022. Includes 3,249 participants who completed at least 1 survey in the first week after homologous booster dose. 42
Reactions and health impacts reported by v-safe participants aged ≥5 years 

at least once 0-7 days after bivalent booster dose, by age group

Data for participants aged ≥12 years as of October 23, 2022. Includes 311,205 participants who completed at least 1 survey in the first week after booster dose.

Data for participants aged 5-11 years as of February 5, 2023. Includes 3,588 participants who completed at least 1 survey in the first week after booster dose. 

0

10

20

30

40

50

60

70

80

90

100

Any injection site reaction Any systemic reaction Any health impact

Percentage

5-11 y

12-17

18-49

50-64

≥65

Age group (yrs)

43