Document text
COVID -19 vaccine safety surveillance
for the 2023 -2024 season
Jonathan Duffy, MD, MPH
Immunization Safety Office
June 27, 2024National Center for Emerging and Zoonotic Infectious Diseases
•Vaccine Adverse Event Reporting System (VAERS)
•V-s afe
•Vaccine Safety Datalink (VSD)CDC surveillance systems monitoring COVID -19
vaccine safety
2
•The Vaccine Safety Datalink (VSD) identified two statistical signals for mRNA COVID- 1 9 vaccines
during the 2023 -2024 season
-Guillain -B arré syndrome (GBS) following Pfizer COVID -19 vaccine among people aged ≥65 years
•An association between mRNA COVID -19 v accines and GBS had not been observed prior to this season
in VSD or other systems
•The increased rate ratio observed during the 2023- 2024 season may or may not represent a true risk
•If ther e is a true risk, it is estimated to be similar to what is considered acceptable for other adult
vaccines
-Ischemic stroke following Moderna (aged ≥65 years) and Pfizer (aged 50 -6 4 years) COVID -19 vaccines
•The VSD previously observed a statistical signal for ischemic stroke during 2022-2023 for bivalent
P
fizer COVID -19 vaccine (aged ≥65 years)
•Available data do not provide clear and consistent evidence of a safety problem for ischemic stroke wi
th mRNA COVID -19 vaccines
•No other new or unexpected safety concerns were identified for the 2023 -2024 C OVID -19 vaccines
•Any real or theoretical risks of vaccine adverse events need to be placed in the context of the
b
enefits of COVID- 19 vaccines in preventing COVID- 19 and its potentially serious complicationsKey points up front
3
Vaccine Adverse Event Reporting System
(VAERS)
5
VAERS: U.S. reports following COVID -19 vaccination1
Manufacturer Reports
NAge,
years
Median (IQR)Sex,
female
N (%)Non -serious
N (%)Serious2
N (%)Onset interval,
days
Median (IQR)
Pfizer 7,215 57 (33– 70) 4,129 (57) 6,781 (94) 434 (6) 0 (0–3)
Moderna 5,954 60 (31– 72) 3,474 (58) 5,502 (92) 457 (8) 0 (0–1)
Novavax 153 51 (35–70) 86 (56) 140 (92) 13 (8) 1 (0–2)
Unknown 176 58.5 ( 34–71) 95 (54) 152 (86) 24 (14) 0 (0–1)
Total 13,491 59 (32–71) 7,780 (58) 12,568 (93) 923 (7) 0 (0–2)
1. Reports received during September 12, 2023 – April 19, 2024; reported date of vaccination during September 12, 2023 – April 1 9, 2024 or missing
2. Based on the U. S. Code of Federal Regulations (21 CFR 600.80), classification of a serious adverse event includes a repor t of one of the following:
death, life -threatening illness, hospitalization or prolongation of hospitalization, permanent disability, congenital anomaly, o r birth defect. 6
VAERS: most frequent MedDRA Preferred Terms
following COVID -19 vaccination by manufacturer
Pfizer Moderna Novavax
MedDRA PTN=7,215
n (%)MedDRA PTN=5,954
n (%)MedDRA PTN=153
n (%)
COVID -19 1899 (26) Fever 743 (13) Headache 21 (13)
Headache 485 (7) Fatigue 729 (12) Fever 19 (12)
Fatigue 465 (6) Headache 712 (12) Pain 18 (11)
Fever 407 (6) Pain 546 (9) Pain in extremity 18 (11)
Pain 365 (5) Pain in extremity 502 (8) Fatigue 15 (9)
Reports received during September 12, 2023 – April 19, 2024; reported date of vaccination during September 12, 2023 – April 19, 2024 or missing.
MedDRA PT = Medical Dictionary for Regulatory Activities Preferred Terms ( https://www.meddra.org ). More than one MedDRA Preferred Term may be
assigned to a single report.
Percents represent the number of reports divided by the total number of reports for each vaccine. 7
V-safe
•Participants self -e nroll at https://vsafe.cdc.gov
•Post -v accination surveys
-Daily during the first week
-Weekly through w eek 6
•Daily surveys solicit adverse events and health impacts after v accination
-Local r eactions (e.g., pain, redness, swelling)
-Systemic reactions (e.g., fatigue, headache, muscle pain)
-Health impacts (e.g., unable to perform normal daily activities, missed school or
w
ork, or received medical care)V-safe methods
9
V-safe: characteristics of participants with reported
COVID -19 vaccination1
CharacteristicVaccine manufacturer, %
Moderna
N=4,828Pfizer
N=4,481Novavax
N=258Do not know
N=576Total
N=10,143
Female sex assigned at birth 61.5 61.2 69.4 63.7 61.7
Age group, years
3-17 0.2 0.6 0.8 - 0.4
18-59 26.5 30.8 41.9 34.6 29.3
≥60 73.3 68.6 57.4 65.5 70.4
Immunocompromised 7.7 7.0 8.5 5.0 7.2
Vaccine(s) co -administered 18.3 21.0 14.0 33.0 20.2
Influenza 8.1 9.9 7.8 17.0 9.4
RSV 3.5 3.5 2.3 4.9 3.5
Other 6.7 7.6 3.9 11.1 7.3
1. For 10,143 V -safe participants aged ≥3 years enrolled in the COVID -19 protocol with ≥1 completed daily survey during Septembe r 11, 2023- May 27, 2024.
10
V-safe: percent of people aged ≥3 years who reported reactions and health
impacts at least once in days 0 -7 following COVID -19 vaccination,
by manufacturer
0.7 0.6 0.4 0.7
0102030405060708090100
Any symptoms Injection site
reactionSystemic reaction Unable to
complete daily
activitiesUnable to work or
attend schoolGot medical carePercent
Moderna Pfizer Novavax Don't know
11
Vaccine Safety Datalink
(VSD)
Vaccine Safety Datalink (VSD)
Collaborative
pr
oject between
CDC and 13 integrated healthcare organizations
Population of ~1
3.5 million
people annually
13
•Sequential monitoring as data become available
•Monitors a limited set of prespecified outcomes of special interest
•Designed to detect statistical signals (values above specified statistical
thresholds)
•Statistical signals are potential associations and f urther investigation is
required before concluding that a safety concern existsVSD Rapid Cycle Analysis (RCA) surveillance
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•Time period: September 10, 2023 – April 27, 2024
•Evaluated the first COVID -19 vaccine dose received during this period
•Design: analysis using COVID -19 vaccinated concurrent comparators
-Compares the outcome incidence among vaccinees in a risk interval with
outcome incidence on the same day among vaccinees in a comparison interval
-Adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site
•Statistical signal criteria:
-The signal threshold is determined from an alpha- spending plan that keeps the
overall chance of a Type 1 error <0.05 during the surveillance period
-Supplemental rate ratios with exact 95% confidence intervals VSD RCA methods for the
2023 -2024 COVID -19 vaccine
15
VSD pre -specified outcomes
Acute disseminated encephalomyelitis (ADEM)
Acute myocardial infarction
Encephalitis / myelitis / encephalomyelitis
(not ADEM or TM)
Guillain -Barré syndrome (GBS)
Hemorrhagic stroke
Ischemic stroke
Immune thrombocytopenia
Myocarditis / pericarditis
Pulmonary embolism
Seizure
Transverse myelitis (TM)
16
RCA COVID -19 Primary and Supplemental Analyses
Parameters Primary Analyses Supplemental Analyses
Vaccine TypesModerna
NovavaxPfizerPfizer & Moderna combinedPfizer with fluPfizer with flu high dose/adjuvant Moderna with fluModerna with flu high dose/adjuvant Pfizer without same day vaccinesModerna without same day vaccines
Risk vs. Comparison Intervals1-21 days vs 43- 63 days
1-42 days vs 43- 84 daysFor myocarditis/pericarditis: 1-21 days vs 22- 42 days
Age Groups0-4 y
5-11 y
12-17 y
18-64 y
≥65 yAllages (≥ 6 months )
18-49 y
50-64 y
60-74 y
≥75 yFor myocarditis/pericarditis: 12-39 y
17
VSD Results
COVID -19 vaccine doses administered in VSD
by manufacturer
19
COVID -19 vaccine doses administered in VSD
by age group
20
COVID -19 vaccine doses administered in VSD
with other vaccines on the same day1
1 Some people received more than two vaccines on the same day. Not all categories are mutually exclusive.
Flu=Influenza vaccine; Tdap=Tetanus, Diphtheria, Pertussis vaccine; RSV=Respiratory syncytial virus vaccine; Zoster=Zoster recom binant vaccine; Pneumo =Pneumococcal vaccine 21
VSD RCA statistical signals
Outcome Moderna Pfizer
Acute disseminated encephalomyelitis (ADEM) No No
Acute myocardial infarction No No
Encephalitis / myelitis / encephalomyelitis
(not ADEM or TM)No No
Guillain -Barré syndrome (GBS) No Yes
Hemorrhagic stroke No No
Ischemic stroke Yes Yes
Immune thrombocytopenia No No
Myocarditis / pericarditis No No
Pulmonary embolism No No
Seizure No No
Transverse myelitis (TM) No No
22
Guillain -Barré syndrome (GBS)
Guillain- Barré syndrome (GBS)
VSD statistical signals
Vaccine Moderna Pfizer
Risk Interval (days) 1 - 21 1 - 42 1 - 21 1 - 42
Age Group (years)
0 –4 No No No No
5 –11 No No No No
12 –17 No No No No
18 –64 No No No No
≥65 No No Yes Yes
24
Characteristics of chart -confirmed GBS cases after
Pfizer COVID -19 vaccine among people aged ≥65 years
CharacteristicRisk Interval cases
Days 1 -42
(n = 7)Comparison Interval cases
Days 43 -84
(n = 3)
Brighton Level1
1 2 0
2 5 3
3 0 0
Age Group (years)
65 – 74 4 1
75 – 84 3 2
≥85 0 0
Same day vaccines
None 5 2
Any 2 1
Influenza 1 1
Influenza + PCV 1 0
1 Sejvar et al. Guillain -Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29(3):599 -612 25
Chart -confirmed GBS concurrent comparator analysis for
Pfizer COVID -19 vaccine among people aged ≥65 y ears
AnalysisCases in
Risk Interval
(Days 1 -42)Cases in
Comparison Interval
(Days 43 -84)Adjusted Rate
Ratio1
(95% Confidence
Interval)
Pfizer, all doses 7 3 4.45 (1.07– 22.62)
Pfizer without same
day vaccines5 2 4.86 (0.88 – 38.52)
1 Adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD siteEstimated excess GBS cases: 4.1 per million doses
26
•VSD identified a statistical signal for GBS after Pfizer COVID -19 vaccine in adults aged ≥65 years
during the 2023- 2024 season
-The VSD had not identified any signals for GBS with previous mRNA COVID -19 vaccine formulations (i.e.,
original primary series, original booster, or 2022 -2023 bivalent)
-The analysis did not suggest that other vaccines administered on the same day accounted for the
increased rate
•The increased rate ratio observed for Pfizer COVID -19 vaccine during the 2023- 2024 season
may or may not represent a true risk, because a large number of analyses may find some
associations by chance alone, and surveillance analyses may have residual confounding
•There were insufficient doses of Moderna or Novavax vaccines administered in the VSD to
assess the rate of GBS with those vaccines
-There is not n ecessarily a difference in GBS rate following Pfizer COVID -19 vaccine and the other COVID -
19 vaccinesVSD summary and interpretation for GBS
27
Ischemic stroke
Ischemic stroke
VSD statistical signals
Vaccine Moderna Pfizer
Risk Interval (days) 1 - 21 1 - 42 1 - 21 1 - 42
Age Group (years)
0 –4 No No No No
5 –11 No No No No
12 –17 No No No No
18 –64 No No Yes No
≥65 No Yes No No
29
Ischemic stroke concurrent comparator analysis for
Pfizer COVID -19 vaccine among people aged 18- 64 years
AnalysisCases in
Risk Interval
(Days 1 -21)Cases in
Comparison Interval
(Days 43 -63)Adjusted Rate
Ratio1
(95% Confidence
Interval)
Ages 18 -49 13 13 1.12 (0.46 – 2.67)
Ages 50 -64 69 57 1.57 (1.06 – 2.31)
1 Adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site 30
1.57
1.001.98
1.48
1.06
0.181.070.872.314.97
3.70
2.50
0.001.002.003.004.005.006.00
Pfizer Moderna3
Vaccine without any
same day vaccinesPfizer Moderna
Vaccine with or without
same day vaccines Pfizer Moderna3
Vaccine with same day
influenza vaccineAdjusted Rate Ratio &
95% Confidence IntervalIschemic stroke supplemental analyses to evaluate statistical signal for
Pfizer COVID -19 vaccine among people aged 50-64 years
a
Exact Analysis 1 -21 days vs 43- 63 days
Adjusted Rate Ratios and 95% Confidence Intervals1,2
1 Dose totals for age group: Pfizer = 572,885; Moderna = 57,012
2 Rate ratios adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site
3 This analysis not done for Moderna due to small sample size 31
Ischemic stroke concurrent comparator analysis for
Moderna COVID -19 vaccine among people aged ≥65 years
VaccineCases in
Risk Interval
(Days 1 -42)Cases in
Comparison Interval
(Days 43 -84)Adjusted Rate
Ratio1
(95% Confidence
Interval)
Moderna 53 51 1.53 (0.96 – 2.42)
1 Adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site 32
Ischemic stroke concurrent comparator analysis for
mRNA COVID -19 vaccines among people aged ≥65 years
VaccineCases in
Risk Interval
(Days 1 -42)Cases in
Comparison Interval
(Days 43 -84)Adjusted Rate
Ratio1
(95% Confidence
Interval)
Moderna 53 51 1.53 (0.96 – 2.42)
Pfizer 574 714 1.00 (0.88 – 1.14)
1 Adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site 33
Adjusted Rate Ratio &
95% Confidence Interval
Pfizer Moderna
Vaccine with or without
same day vaccines Pfizer Moderna
Vaccine with same day
influenza vaccinePfizer Moderna
Vaccine without any
same day vaccines1.001.53
1.042.53
0.951.26
0.880.96
0.831.10
0.800.701.142.42
1.295.91
1.132.24
0.001.002.003.004.005.006.007.00Ischemic stroke supplemental analyses to evaluate statistical signal for
Moderna COVID -19 vaccine among people aged ≥65 years
a
Exact Analysis 1 -42 days vs 43- 84 days
Adjusted Rate Ratios and 95% Confidence Intervals1,2
1 Dose totals for age group: Pfizer = 953,559; Moderna = 81,553
2 Rate ratios adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site 34
•VSD detected statistical signals for ischemic stroke for Pfizer and Moderna COVID -19 vaccines
during the 2023- 2024 season
-There was a lack of consistent findings across age groups or risk interv als
-There was not a significantly different risk associated with receipt of simultaneous influenza vaccine
•The VSD previously identified a statistical signal for ischemic stroke for the 2022 -2023 bivalent
formulation of Pfizer vaccine in the ≥65 years age group using the 1-21 day risk interval
•This season’s findings are consistent with CDC Immunization Safety Office’s prior
interpretation based on data review in October 2023 that stated: “Available data do not provide clear and consistent evidence of a safety problem for ischemic stroke with
bivalent mRNA COVID -19 vaccines when given alone or given simultaneously with influenza
vaccines”
1
•The statistical signals during the 2022 -20232 and the 2023- 2024 seasons require further
evaluation
-The VSD has a follow -up retrospective study in progress to further assess the risk of ischemic strokeVSD summary and interpretation for ischemic stroke
1 Shimabukuro TS, presentation to ACIP, October 25, 2023. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/sl ides-2023 -10-25-26/01 -VaxSafety -Shimabukuro -508.pdf
2 Klein NK, presentation to ACIP, September 12, 2023. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -09-12/07 -COVID -Klein -508.pdf 35
Conclusions
•Rates of local and/or systemic reactions reported by V -safe participants
during the first week after receiving a dose of the 2023- 2024 COVID- 19
vaccine were similar to last season
•VSD identified statistical signals for GBS and ischemic stroke
•No other new or unexpected safety concerns were identified for the 2023-
2024 COVID- 19 vaccines by VAERS, V- safe, or VSDConclusions
37
•The increased rate ratio of GBS following Pfizer COVID- 19 vaccine among people aged ≥65 years
observed during the 2023 -2024 season may or may not represent a true risk
-If there is a true risk, then t he estimated excess GBS cases of 4.1 per million doses is similar to
previous estimates for other vaccines for adults
•Influenza: 1 - 2 cases per million doses1
•Recombinant Zoster Vaccine: 3 - 6 cases per million doses2
•The VSD statistical signals for ischemic stroke after mRNA COVID- 19 vaccines during the 2023 -2024
season do not provide sufficient evidence to conclude that there is a safety concern. A follow -up VSD
study is in progress to further examine the risk of ischemic stroke after mRNA COVID- 19 vaccines
•FDA’s 2023- 2024 COVID -19 vaccine safety surveillance using commercial health plans and Medicare
claims databases results are expected later this year, which will provide additional information about
GBS, stroke, and other outcomesConclusions
381 Perez -Vilar S, et al. Guillain -Barré Syndrome After High -Dose Influenza Vaccine Administration in the United States, 2018 -2019 Season . J Infect Dis. 2021 Feb 13;223(3):416 -425.
2 Janusz CB, et al. Projected risks and health benefits of vaccination against herpes zoster and related complications in US adults . Human Vaccines & Immunotherapeutics , 18(5), 2022.
•Any real or theoretical risks of vaccine adverse events need to be placed in
the context of the benefits of COVID -19 vaccines in preventing COVID- 19
and its potentially serious complications
•CDC and FDA will continue to monitor the safety of COVID- 19 vaccinesConclusions
39
Acknowledgments
•CDC Immunization Safety Office:
-Karen Broder, Hannah Brown, Carol Ennulat , Anne Hause,
Tat’Yana Kenigsberg, Paige Marquez, Mike McNeil, Pedro
Moro, Tanya Myers, Brittney Romanson, David Shay, John Su, Lily Wang, Kimp Walton, Eric Weintraub, Bicheng (Tony)
Zhang
•Kaiser Permanente Northern California:
-Ned Lewis, Nicky Klein, Joan Bartlett, Kristin Goddard, Bruce
Fireman, Ousseny Zerbo
•Marshfield Clinic Research Institute:
-Jim Donahue, Kayla Hanson, Ed Belongia, Burney Kieke, Dave McClure, Erica Scotty•VSD Sites
• Denver Health, Denver, Colorado
• HealthPartners Institute, Minneapolis, Minnesota
• Kaiser Permanente Colorado, Denver, Colorado
• Kaiser Permanente Mid Atlantic, Rockville Maryland
• Kaiser Permanente Northern California, Oakland, California
• Kaiser Permanente Northwest, Portland, Oregon
• Kaiser Permanente Southern California, Los Angeles, California
• Kaiser Permanente Washington, Seattle, Washington
• Marshfield Clinic Research Institute, Marshfield, Wisconsin
•FDA Center for Biologics Evaluation and Research,
Office of Biostatistics and Pharmacovigilance
40
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.