Document text
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)
m
onitoring methods and assessment processes for statistical signals
Describe VSD RCA signal detection and signal assessment for ischemic s
troke 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 v
accination
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 m RNA 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
us
ing multiple complementary systems (Vaccine Information and Safety Studies | Vaccine Safety | CDC )
Safety data support CDC recommendations that everyone eligible for a COVID -
19 mR
NA bivalent booster get vaccinated
3 *CDC COVID Data Tracker: Vaccinations in the US
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
ge
ographically and racially/ethnically diverse
Data
•Near real -time data, with analyses updated weekly
•A
ccess to comprehensive medical records, including exposures (vaccination) and outcomes,
allo
wing rapid chart reviews to obtain additional clinical information as needed
Innovative Methods
•Vaccinated concurrent comparators : Re cent 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 A
nalyses can begin sooner than alternative methods
•Supplemental analyses conducted weekly: Un vaccinated/un- boosted comparators would also be
available to provide context in real time
•Using vaccinated concurrent comparators with supplemental analyses offers substantial benefits
co
mpared with either unvaccinated or historical comparators
6
VSD RCA for bivalent boosters
Pre-specified outcomes were assessed during weekly sequential
mon
itoring after COVID-19 bivalent booster vaccination*
•Risk of pre-specified outcomes 1– 21 day s 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
(day
s) 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. Av ailable 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), w e
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 42 22 October 3
Vaccinated with
Bivalent Booster
September 31
Risk Interval 1 –21 days post -vaccination21October 3
Vaccinated with
Bivalent Booster
September 30
8
9VSD 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 daysIn COVID- 1 9 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- s pecified 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,
unv
accinated 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 s
tatistics to assess apparent clustering
•Examine the temporal clustering of outcome events in subgroups defined by demographics, site or
si
multaneous exposure (e.g., flu vaccine)
If the signal is driven by a strong association in one subgroup or VSD site, further
anal
yses 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
10R
apid Cycle Analysis (RCA) to monitor the safety of COVID -19 vaccines in near real -time within the Vaccine Safety Datalink. Avai lable 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, unspecifiedCOVID -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 facilityZ86.73 Personal history of transient ischemic attack (TIA), and cerebral infarction without residual deficitsOR
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)VaccineRisk
events (N)Comp
events (N)Adjusted
Rate Ratio95%
Confidence
Interval1-sided
p-valueSignal?
1-sided
p <0.01
18–64Pfizer 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 )
1503.954.38
1.51
1.251.491.92 1.85 1.89
1.571.531.54 1.471.461.36 1.39
00.511.522.533.544.55
020406080100120140160
Rate RatioNumber of Cases in Risk or Comp Window
1-21 Day Risk Interval 22-42 Day Comp Interval Rate RatioRR = 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 priorSignificant cluster days 13– 22,
p-value = 0.0150
16
Ischemic stroke preliminary chart review: Cases ≥65years 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 VaccineRisk
events (N)Comp
events (N)Adjusted
Rate Ratio95%
Confidence
IntervalP-value
(2-sided)
65+ 1–21Not bivalent
boostedPfizer 134 1510 1.07 0.89– 1.28 0.483
* Analyses only included outcomes through December 10, 2022.
18Supplemental 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 VaccineRisk
events (N)Comp
events (N)Adjusted
Rate Ratio95%
Confidence
IntervalP-value
(2-sided)
65+1–21Not bivalent
boostedPfizer 134 1510 1.07 0.89– 1.28 0.483
22–42Not bivalent
boostedPfizer 83 1081 0.76 0.60– 0.95 0.018
* Analyses only included outcomes through December 10, 2022.
19Findings suggest reduced rate of stroke in comparison intervalSupplemental 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 populationCases 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
vaccine43 26 1.65 (1.02 –2.72) 0.04
Bivalent Pfizer + same day
standard dose flu vaccine8 8 1.00 (0.36 –2.76) 1.00
Bivalent Pfizer without anysame day flu vaccine88 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 groupsPost -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
vaccinationExpected 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
22Findings 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
c
riteria
Additional signal investigation analyses
•Temporal clustering evaluation found a significant cluster 13–22 days after vaccination
•Supplemental analyses using un- boost ed 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-doseor
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 lowert
han 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 exposure24
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*
29Dose 2 primary series
Pfizer -BioNTech1stmonovalent booster dose
Pfizer -BioNTechBivalent booster dose
Pfizer -BioNTech
Age/sex CasesDose 2
totalIncidence rate/
million doses
(95% CI)Cases1stbooster
totalIncidence rate/
million doses
(95% CI)CasesBivalent
booster
totalIncidence rate/
million doses
(95% CI)
12–17 years
Males
Females45
6308,046
311,247146.1 (106.6– 195.5)
19.3 (7.1– 42.0)14
2129,487139,118108.1 (59.1– 181.4)
14.4 (1.7– 51.9)0048,066
49,7250.0 (0.0– 62.3)
0.0 (0.0– 60.2)
18–29 years
Males
Females27
2331,889
400,32181.4 (53.6– 118.4)
5.0 (0.6– 18.0)71166,973240,22641.9 (16.9– 86.4)
4.2 (0.1– 23.2)1
050,687
80,21119.7 (0.5– 53.1)
0.0 (0.0– 37.3)
30–39 years
Males
Females5
3341,527410,71314.6 (4.8– 34.2)
7.3 (1.5– 21.3)31197,554268,41215.2 (3.1– 44.4)
3.7 (0.1– 20.8)0
082,191
115,0140.0 (0.0– 36.4)
0.0 (0.0– 26.0)
* Primary series and 1stmonovalent 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*P
rimary 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
Moderna1stmonovalent booster dose
ModernaBivalent booster dose
Moderna
Age/sex CasesDose 2
totalIncidence rate/
million doses
(95% CI)Cases1st
booster
totalIncidence rate/
million doses
(95% CI)CasesBivalent
booster
totalIncidence rate/
million doses
(95% CI)
18–29 years
Males
Females19
0195,809
243,56097.0 (58.4 – 151.5)
0.0 (0.0 –12.3)71109,337156,70764.0 (25.7 – 131.9)
6.4 (0.2 –35.6)0
018,49929,5610.0 (0.0– 161.9)
0.0 (0.0– 101.3)
30–39 years
Males
Females8
1216,583259,78036.9 (15.9 – 72.8)
3.9 (0.1 –21.4)12149,468191,7656.7 (0.2 –37.3)
10.4 (1.3 –37.7)0
035,31847,6200.0 (0.0– 84.8)
0.0 (0.0– 62.9)
Acknowledgements
31CDC 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 GroupKaiser 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://wwwn.cdc.gov/phil/
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)ManufacturerMedian
Age (IQR),
yearsMale†
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 bivalentPreliminary 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 –e20940Chart- verified reportsChart- verified reports
+ reports under review
Manufacturer ReportsDoses
administered*Reporting rate
(per million doses
administered)ReportsDoses
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
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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
0102030405060708090100
Any injection site reaction Any systemic reaction Any health impactPercentage5-11 y
12-17
≥18Age 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 do se.
Data for participants aged 12 -17 years as of February 20, 2022. Includes 3,418 participants who completed at least 1 survey in t he 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 fi rst 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. 0102030405060708090100
Any injection site reaction Any systemic reaction Any health impactPercentage5-11 y
12-17
18-49
50-64
≥65Age group (yrs )
43