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COVID -19 Vaccine Safety Surveillance:
Summary from VSD RCA
Nicola Klein, MD, PhD
Director, Kaiser Permanente Vaccine Study Center
Kaiser Permanente Northern California
Advisory Committee in Immunization Practices
September 12, 2023

2Vaccine Safety Datalink
•Active surveillance: newly licensed vaccines
̶Rapid Cycle Analysis (RCA) 
•Evaluate vaccine safety:
̶of new recommendations for existing vaccines
̶for vaccines in high -risk populations, particularly pregnant women 
(+ other groups)
•Develop new methods for vaccine safety assessment
•Test hypotheses that emerge from elsewhere (e.g.,  
VAERS, clinical trials, other platforms).

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 who are beyond their risk interval are expected to 
be  similar to current vaccinees who are within their risk interval. They serve as better comparators than 
unvaccinated individuals, historical controls or non -concurrent self controls because they permit:
‒Careful adjustment for potential biases associated with calendar time, site, and demographic 
factors 
‒Analyses that can begin sooner than alternative methods 
•Supplemental analyses conducted weekly: Unvaccinated/un -boosted comparators would also be available 
to provide context in real time 
3
Aims:
1. To monitor the safety of COVID -19 vaccines weekly using pre -
specified outcomes of interest among VSD members. 
2. To describe the uptake of COVID -19 vaccines over time 
among eligible VSD members overall and in strata by age, site, 
and race/ethnicity.
Surveillance began in December 2020 and was ready when 
the first doses of COVID -19 vaccines were given.VSD COVID -19 Vaccine RCA
4
Inclusion in prior vaccine safety studies
•Acute disseminated encephalomyelitis 
•Anaphylaxis*
•Encephalitis / myelitis
•Guillain -Barré syndrome
•Immune thrombocytopenia 
•Kawasaki disease 
•Narcolepsy and cataplexy*
•Seizures 
•Transverse myelitis Hypothetical concerns regarding an 
association with COVID -19 disease 
•Acute myocardial infarction  
•Acute respiratory distress syndrome*
•Disseminated intravascular coagulation 
•Multisystem Inflammatory Syndrome*  
•Pulmonary embolism
•Stroke, hemorrhagic
•Stroke, ischemic 
•Thrombotic thrombocytopenic purpura 
•Venous thromboembolism  
5•Cerebral venous sinus thrombosis 
•Myocarditis / pericarditis 
•Thrombosis with thrombocytopenia syndromeOutcomes added/enhanced due to emerging 
concerns
Imbalances in phase 3 COVID -19 vaccine clinical 
trials
•Appendicitis 
•Bell’s palsy
*monitored without comparators Only chart confirmed cases
COVID Vaccine Safety RCA Surveillance: Monitoring 
23 Serious Outcomes   

Vaccinee with Myocarditis in Risk Interval and a Concurrent Comparator
On each calendar day that an outcome occurred 
in a vaccinee (e.g., June 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 they were in the same age 
group and of the same sex, race, and at the same 
VSD site. 
Comparison Interval 22 -42 days post -vaccination 42 22
 June 3
Vaccinated 
May 31
Risk Interval 1 -21 days post -vaccination21
June 3
Vaccinated 
May 30
6
7September: Interim mRNA vaccines safety 
surveillance, including myocarditis/pericarditis risk 
(JAMA )September: 
Bivalent boosters 
Pfizer (≥12y) and 
Moderna (≥18y)September: Bivalent 
boosters. Monovalent 
boosters discontinuedMay: Pfizer 
monovalent 
booster 5 -
11yMarch: 2nd 
monovalent 
booster 
(≥50y)January: 
Pfizer 
monovalent 
booster
12-15ySeptember/October: 
Adult monovalent 
booster; Pfizer 
(≥16y), Moderna and 
Janssen (≥18y)
October: Myocarditis/pericarditis 
rates after primary and monovalent 
boosters <40y ( Ann Int Med )August: Risk of myocarditis/ 
pericarditis Pfizer vs Moderna 
(Vaccine )April: GBS following 
Janssen vaccine ( JAMA
Network Open )December: 
EUA Moderna 
(≥18y) and 
Pfizer (≥16y)
November/December: first 
VSD signal, ischemic stroke 
after bivalent Pfizer ≥65y
October: 
Bivalent 
boosters Pfizer 
(5-11y) and 
Moderna (6 -17y)December: 
Bivalent boosters 
Pfizer (6m -4y) and 
Moderna (6m -5y)May: EUA 
Pfizer 12 -
15y
May: 
myocarditis/
pericarditis 
after mRNA 
vaccines 
reportedAugust: FDA 
approves 
Pfizer (≥16y)
October: 
EUA Pfizer 
5-11y January: FDA 
approves 
Moderna 
(≥18y) May 2022: Janssen 
vaccine no longer 
recommendedJune: EUA Pfizer (6m –4y), 
Moderna (6m –17y)
July: EUA 
Novavax 
vaccine (≥18y)2020
Primary 
Series
Monovalent 
Boosters
Bivalent mRNA 
Boosters
VSD COVID -19 RCA 
Safety Publications2021 2022 2023
March: >200 
million doses 
given in US 
by the end 
AprilApril: 
Janssen 
and CVST 
concernsFebruary: 
Janssen 
EUA 
(≥18y)
June : mRNA 
vaccine safety 
6m-5y (Pediatrics )July: FDA 
safety 
warning re: 
GBS and 
Janssen. 
8

Results using vaccinated concurrent 
comparators
9
Klein NP, Lewis N, et. al. JAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.1507210
Outcomes Monitored Without Comparators
11
12
JAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.15072
VSD COVID -19 RCA Surveillance:
Outcomes Monitored Due to Emerging Concerns
13
14September: Interim mRNA vaccines safety 
surveillance, including myocarditis/pericarditis risk 
(JAMA )September: 
Bivalent boosters 
Pfizer (≥12y) and 
Moderna (≥18y)September: Bivalent 
boosters. Monovalent 
boosters discontinuedMay: Pfizer 
monovalent 
booster 5 -
11yMarch: 2nd 
monovalent 
booster 
(≥50y)January: 
Pfizer 
monovalent 
booster
12-15ySeptember/October: 
Adult monovalent 
booster; Pfizer 
(≥16y), Moderna and 
Janssen (≥18y)
October: Myocarditis/pericarditis 
rates after primary and monovalent 
boosters <40y ( Ann Int Med )August: Risk of myocarditis/ 
pericarditis Pfizer vs Moderna 
(Vaccine )April: GBS following 
Janssen vaccine ( JAMA
Network Open )December: 
EUA Moderna 
(≥18y) and 
Pfizer (≥16y)
November/December: first 
VSD signal, ischemic stroke 
after bivalent Pfizer ≥65y
October: 
Bivalent 
boosters Pfizer 
(5-11y) and 
Moderna (6 -17y)December: 
Bivalent boosters 
Pfizer (6m -4y) and 
Moderna (6m -5y)May: EUA 
Pfizer 12 -
15y
May: 
myocarditis/
pericarditis 
after mRNA 
vaccines 
reportedAugust: FDA 
approves 
Pfizer (≥16y)
October: 
EUA Pfizer 
5-11y January: FDA 
approves 
Moderna 
(≥18y) May 2022: Janssen 
vaccine no longer 
recommendedJune: EUA Pfizer (6m –4y), 
Moderna (6m –17y)
July: EUA 
Novavax 
vaccine (≥18y)2020
Primary 
Series
Monovalent 
Boosters
Bivalent mRNA 
Boosters
VSD COVID -19 RCA 
Safety Publications2021 2022 2023
March: >200 
million doses 
given in US 
by the end 
AprilApril: 
Janssen 
and CVST 
concernsFebruary: 
Janssen 
EUA 
(≥18y)
June : mRNA 
vaccine safety 
6m-5y (Pediatrics )July: FDA 
safety 
warning re: 
GBS and 
Janssen. 
Myocarditis and Pericarditis 
Following mRNA Vaccines
15
Myocarditis / Pericarditis Among Subgroup 
<40 Years of Age
17•Chart reviews began May 2021
•All identified cases of myocarditis/pericarditis during the 98 days after 
vaccination were chart reviewed, followed by infectious disease clinician 
and/or a cardiologist adjudication to:
•Confirm case was incident following vaccination
•Met CDC case definition (myocarditis, pericarditis, or myopericarditis)
•Evaluated level of certainty for myocarditis
Clustering of Confirmed Myocarditis/pericarditis by Days Since Most 
Recent Dose of any mRNA Vaccine Among 12 -39 Year -Olds
18
JAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.15072
19
Klein NP, Lewis N, et. al. JAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.15072
•No safety signals for any outcome in the 21 days after both mRNA doses in 
the overall VSD population, including all ages ≥12 years.
•In the subgroup aged 12 –39 years, the rate ratio for myocarditis/pericarditis 
was elevated after both Pfizer and Moderna during days 0 -21 after 
vaccination, and especially during days 0 -7.
̶In subgroup analyses, both mRNA vaccines were associated with 
myocarditis/pericarditis in persons aged 12 -39 years. 
•In the VSD, rate of anaphylaxis after mRNA vaccines was ~ 5 cases / million 
doses.
•VSD surveillance was ongoing.Summary
(data through June 2021)
20
21September: Interim mRNA vaccines safety 
surveillance, including myocarditis/pericarditis risk 
(JAMA )September: 
Bivalent boosters 
Pfizer (≥12y) and 
Moderna (≥18y)September: Bivalent 
boosters. Monovalent 
boosters discontinuedMay: Pfizer 
monovalent 
booster 5 -
11yMarch: 2nd 
monovalent 
booster 
(≥50y)January: 
Pfizer 
monovalent 
booster
12-15ySeptember/October: 
Adult monovalent 
booster; Pfizer 
(≥16y), Moderna and 
Janssen (≥18y)
October: Myocarditis/pericarditis 
rates after primary and monovalent 
boosters <40y ( Ann Int Med )August: Risk of myocarditis/ 
pericarditis Pfizer vs Moderna 
(Vaccine )April: GBS following 
Janssen vaccine ( JAMA
Network Open )December: 
EUA Moderna 
(≥18y) and 
Pfizer (≥16y)
November/December: first 
VSD signal, ischemic stroke 
after bivalent Pfizer ≥65y
October: 
Bivalent 
boosters Pfizer 
(5-11y) and 
Moderna (6 -17y)December: 
Bivalent boosters 
Pfizer (6m -4y) and 
Moderna (6m -5y)May: EUA 
Pfizer 12 -
15y
May: 
myocarditis/
pericarditis 
after mRNA 
vaccines 
reportedAugust: FDA 
approves 
Pfizer (≥16y)
October: 
EUA Pfizer 
5-11y January: FDA 
approves 
Moderna 
(≥18y) May 2022: Janssen 
vaccine no longer 
recommendedJune: EUA Pfizer (6m –4y), 
Moderna (6m –17y)
July: EUA 
Novavax 
vaccine (≥18y)2020
Primary 
Series
Monovalent 
Boosters
Bivalent mRNA 
Boosters
VSD COVID -19 RCA 
Safety Publications2021 2022 2023
March: >200 
million doses 
given in US 
by the end 
AprilApril: 
Janssen 
and CVST 
concernsFebruary: 
Janssen 
EUA 
(≥18y)
June : mRNA 
vaccine safety 
6m-5y (Pediatrics )July: FDA 
safety 
warning re: 
GBS and 
Janssen. 
22Sequential Test1
Outcome Event in 
Risk 
IntervalAdjusted Rate 
Ratio (95% CI)21-sided 
P-value'Signal’ 1 -
sided p 
<0.0048?
Myocarditis / 
pericarditis 138 1.72 <0.001 YesRCA Signal* for Myocarditis/Pericarditis in the 1 -21 Day Risk 
Interval, all VSD population ≥12 years
Compared with Outcome Events in Vaccinated Comparators on the Same Calendar Days 
*signal as of August 20211Sequential test requires 1 -sided p < 0.0048 for a signal. This keeps the probability of a false positive signal (due to chance 
alone) below 0.05 in 2 years of surveillance. 
2Adjusted for VSD site, 5 -year age group, sex, race/ethnicity, and calendar date. Comparison interval is 22 –42 days after 
either dose.
23
•This study assessed whether the risk of myocarditis/pericarditis 
after Moderna differs from that after Pfizer
•We conducted both indirect and direct head -to-head 
comparisons among 18 –39-year-olds
24
Verified Myocarditis and Pericarditis in the 0 -7 Day Risk Interval, among 18 –39-
Year -Olds by Product and Dose, December 14, 2020 -January 14, 2022
Compared with Outcome Events in Vaccinated Comparators on the Same Calendar Days 
Goddard, et al. Vaccine .
Head -to-Head Comparison of Moderna versus Pfizer Regarding Myocarditis and 
Pericarditis During Days 0 -7 Day Post -Vaccination in 18 –39-Year -Olds
25
➢Risk estimates of myocarditis/pericarditis in 18 –39-year-olds during days 0 -7 
after 2 doses were modestly higher after Moderna than after Pfizer.
26
Goddard K, et al. .Ann Intern Med . 2022;175:1169 -1771.* Data through August 20, 2022 
VSD incidence rates of verified myocarditis or pericarditis in the 0 –7 days after mRNA 
vaccination in 5 –39-year-olds, by product, age groups, sex and dose number*
27September: Interim mRNA vaccines safety 
surveillance, including myocarditis/pericarditis risk 
(JAMA )September: 
Bivalent boosters 
Pfizer (≥12y) and 
Moderna (≥18y)September: Bivalent 
boosters. Monovalent 
boosters discontinuedMay: Pfizer 
monovalent 
booster 5 -
11yMarch: 2nd 
monovalent 
booster 
(≥50y)January: 
Pfizer 
monovalent 
booster
12-15ySeptember/October: 
Adult monovalent 
booster; Pfizer 
(≥16y), Moderna and 
Janssen (≥18y)
October: Myocarditis/pericarditis 
rates after primary and monovalent 
boosters <40y ( Ann Int Med )August: Risk of myocarditis/ 
pericarditis Pfizer vs Moderna 
(Vaccine )April: GBS following 
Janssen vaccine ( JAMA
Network Open )December: 
EUA Moderna 
(≥18y) and 
Pfizer (≥16y)
November/December: first 
VSD signal, ischemic stroke 
after bivalent Pfizer ≥65y
October: 
Bivalent 
boosters Pfizer 
(5-11y) and 
Moderna (6 -17y)December: 
Bivalent boosters 
Pfizer (6m -4y) and 
Moderna (6m -5y)May: EUA 
Pfizer 12 -
15y
May: 
myocarditis/
pericarditis 
after mRNA 
vaccines 
reportedAugust: FDA 
approves 
Pfizer (≥16y)
October: 
EUA Pfizer 
5-11y January: FDA 
approves 
Moderna 
(≥18y) May 2022: Janssen 
vaccine no longer 
recommendedJune: EUA Pfizer (6m –4y), 
Moderna (6m –17y)
July: EUA 
Novavax 
vaccine (≥18y)2020
Primary 
Series
Monovalent 
Boosters
Bivalent mRNA 
Boosters
VSD COVID -19 RCA 
Safety Publications2021 2022 2023
March: >200 
million doses 
given in US 
by the end 
AprilApril: 
Janssen 
and CVST 
concernsFebruary: 
Janssen 
EUA 
(≥18y)
June : mRNA 
vaccine safety 
6m-5y (PediatricsJuly: FDA 
safety 
warning re: 
GBS and 
Janssen. 
•Findings were consistent withanassociation between increased riskofGBS and
Janssen COVID -19vaccine.
̶When directly compared withmRNA vaccines, t heriskofGBS after Janssen vaccine was21times
higher .
•Noevidence ofassociation between GBS andmRNA -based COVID -19vaccines.
̶Incidence ofGBS inthe21days after mRNA vaccines wassimilar totheexpected background rate
̶Nostatistical signals inweekly surveillance withvaccinated concurrent comparators
•Since publication and through February 2023, VSD identified 5 additional confirmed 
cases of GBS: 4 after mRNA vaccines and 1 after Janssen.
̶2 were in 1 -21 risk interval (1 mRNA, 1 Janssen), 1 in 22 –42 day interval, and 2 in 43 –84 day interval.
̶All new cases were among males aged 55 -65 years, except one case in a 4 -year-old male.
•ACIP preferentially recommended mRNA -based COVID -19vaccines over Janssen
vaccine in December 2021. (https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7103a4 -H.pdf )
̶FDA revoked Janssen EUA as of June 2023. (https://www.fda.gov/vaccines -blood -biologics/coronavirus -covid -19-cber -regulated -biologics/janssen -
covid -19-vaccine )Summary: Guillain -Barre After COVID -19 Vaccination in the VSD
28(JAMA Netw Open. 2022;5(4):e228879. https://doi.org/10.1001/jamanetworkopen.2022.8879 )
29September: Interim mRNA vaccines safety 
surveillance, including myocarditis/pericarditis risk 
(JAMA )September: 
Bivalent boosters 
Pfizer (≥12y) and 
Moderna (≥18y)September: Bivalent 
boosters. Monovalent 
boosters discontinuedMay: Pfizer 
monovalent 
booster 5 -
11yMarch: 2nd 
monovalent 
booster 
(≥50y)January: 
Pfizer 
monovalent 
booster
12-15ySeptember/October: 
Adult monovalent 
booster; Pfizer 
(≥16y), Moderna and 
Janssen (≥18y)
October: Myocarditis/pericarditis 
rates after primary and monovalent 
boosters <40y ( Ann Int Med )August: Risk of myocarditis/ 
pericarditis Pfizer vs Moderna 
(Vaccine )April: GBS following 
Janssen vaccine ( JAMA
Network Open )December: 
EUA Moderna 
(≥18y) and 
Pfizer (≥16y)
November/December: first 
VSD signal, ischemic stroke 
after bivalent Pfizer ≥65y
October: 
Bivalent 
boosters Pfizer 
(5-11y) and 
Moderna (6 -17y)December: 
Bivalent boosters 
Pfizer (6m -4y) and 
Moderna (6m -5y)May: EUA 
Pfizer 12 -
15y
May: 
myocarditis/
pericarditis 
after mRNA 
vaccines 
reportedAugust: FDA 
approves 
Pfizer (≥16y)
October: 
EUA Pfizer 
5-11y January: FDA 
approves 
Moderna 
(≥18y) May 2022: Janssen 
vaccine no longer 
recommendedJune: EUA Pfizer (6m –4y), 
Moderna (6m –17y)
July: EUA 
Novavax 
vaccine (≥18y)2020
Primary 
Series
Monovalent 
Boosters
Bivalent mRNA 
Boosters
VSD COVID -19 RCA 
Safety Publications2021 2022 2023
March: >200 
million doses 
given in US 
by the end 
AprilApril: 
Janssen 
and CVST 
concernsFebruary: 
Janssen 
EUA 
(≥18y)
June : mRNA 
vaccine safety 
6m-5y (Pediatrics )July: FDA 
safety 
warning re: 
GBS and 
Janssen. 
30
Monovalent Booster Uptake Among Persons Aged≥12 Years in the VSD, Over Time* 
* Data through September 10, 2022 when monovalent booster were discontinued in favor of bivalent boosters.  

Summary of RCA Findings in the 1 -21 Day Risk Interval After Monovalent Boosters ≥12 Years
Compared with Outcome Events 22 -42 Days After in Vaccinated Comparators*
➢Following mRNA primary series and monovalent booster , only myocarditis/pericarditis met the 
signaling criteria in the 21 days among ages ≥12 years in the VSD population.Signal?** Signal?**
*Final analyses through September 2022
**Signaling threshold P<0.01 (one -sided)
Signal?** Signal?** Signal?** Signal?** Signal?** Signal?**
1Comparison interval is 22 –42 days after booster dose.
2Adjusted for VSD site, 5 -year age group, sex, race/ethnicity, calendar date, and time since primary series.
3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y->booster doses.
4One additional case was in the risk interval but not included because there were no appropriate comparators. This case is inc luded in the events/million dose calculation.
5Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.Analysis
Ages VaccineEvents 
inRisk
IntervalEvents in 
Comparison 
Interval1Adjusted 
Rate Ratio295%
Confidence
Interval2-Sided
P-valueEvents/Million 
Doses
Monovalent 
Booster312 -17 Pfizer415 4 7.21 2.04 –29.66 0.002 59.9 (34.3 –97.3)
18–39 Either 22 10 4.46 2.02 –10.37 <0.001 15.8 (9.9 –23.9)
18–39 Pfizer 11 5 4.81 1.55 –16.81 0.006 14.3 (7.1 –25.5)
18–39 Moderna56 4 3.27 0.82 –14.23 0.093 16.8 (7.3 –33.1)
32Verified Myocarditis and Pericarditis in0–7 Days Following 
Monovalent Booster in 12 –39-Year -Olds
Compared with Events on the Same Calendar Days among Boosted Comparators
33September: Interim mRNA vaccines safety 
surveillance, including myocarditis/pericarditis risk 
(JAMA )September: 
Bivalent boosters 
Pfizer (≥12y) and 
Moderna (≥18y)September: Bivalent 
boosters. Monovalent 
boosters discontinuedMay: Pfizer 
monovalent 
booster 5 -
11yMarch: 2nd 
monovalent 
booster 
(≥50y)January: 
Pfizer 
monovalent 
booster
12-15ySeptember/October: 
Adult monovalent 
booster; Pfizer 
(≥16y), Moderna and 
Janssen (≥18y)
October: Myocarditis/pericarditis 
rates after primary and monovalent 
boosters <40y ( Ann Int Med )August: Risk of myocarditis/ 
pericarditis Pfizer vs Moderna 
(Vaccine )April: GBS following 
Janssen vaccine ( JAMA
Network Open )December: 
EUA Moderna 
(≥18y) and 
Pfizer (≥16y)
November/December: first 
VSD signal, ischemic stroke 
after bivalent Pfizer ≥65y
October: 
Bivalent 
boosters Pfizer 
(5-11y) and 
Moderna (6 -17y)December: 
Bivalent boosters 
Pfizer (6m -4y) and 
Moderna (6m -5y)May: EUA 
Pfizer 12 -
15y
May: 
myocarditis/
pericarditis 
after mRNA 
vaccines 
reportedAugust: FDA 
approves 
Pfizer (≥16y)
October: 
EUA Pfizer 
5-11y January: FDA 
approves 
Moderna 
(≥18y) May 2022: Janssen 
vaccine no longer 
recommendedJune: EUA Pfizer (6m –4y), 
Moderna (6m –17y)
July: EUA 
Novavax 
vaccine (≥18y)2020
Primary 
Series
Monovalent 
Boosters
Bivalent mRNA 
Boosters
VSD COVID -19 RCA 
Safety Publications2021 2022 2023
March: >200 
million doses 
given in US 
by the end 
AprilApril: 
Janssen 
and CVST 
concernsFebruary: 
Janssen 
EUA 
(≥18y)
June : mRNA 
vaccine safety 
6m-5y (Pediatrics )July: FDA 
safety 
warning re: 
GBS and 
Janssen. 
34Primary Series uptake among persons aged 5 -11 years in the VSD, over time* 
* Data through 
February 4, 
2023426,177
3,122450,217
2,256
Summary of RCA Findings in the 1 -21 Day Risk Interval, 5 –11-year-olds
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators*
Outcome Both
Event Doses
1 -21 Appendicitis No No No
Bell's palsy No No No
Encephalitis / myelitis / encephalomyelitis No No No
Stroke, hemorrhagic No No No
Stroke, ischemic No - No
Immune thrombocytopenia No No No
Kawasaki disease No No No
Myocarditis / pericarditis No No No
Seizures No No No
Thrombotic thrombocytopenic purpura No - NoPfizer
Risk 
Interval 
DaysDose 1 Dose 2
➢Among children aged 5 -11 years in the VSD, no outcome met the signaling criteria in the 
21 days after primary series vaccination.Signal?** Signal?**
*Final analyses through January 2023
**Signaling threshold P<0.061 (one -sided)
36

37September: Interim mRNA vaccines safety 
surveillance, including myocarditis/pericarditis risk 
(JAMA )September: 
Bivalent boosters 
Pfizer (≥12y) and 
Moderna (≥18y)September: Bivalent 
boosters. Monovalent 
boosters discontinuedMay: Pfizer 
monovalent 
booster 5 -
11yMarch: 2nd 
monovalent 
booster 
(≥50y)January: 
Pfizer 
monovalent 
booster
12-15ySeptember/October: 
Adult monovalent 
booster; Pfizer 
(≥16y), Moderna and 
Janssen (≥18y)
October: Myocarditis/pericarditis 
rates after primary and monovalent 
boosters <40y ( Ann Int Med )August: Risk of myocarditis/ 
pericarditis Pfizer vs Moderna 
(Vaccine )April: GBS following 
Janssen vaccine ( JAMA
Network Open )December: 
EUA Moderna 
(≥18y) and 
Pfizer (≥16y)
November/December: first 
VSD signal, ischemic stroke 
after bivalent Pfizer ≥65y
October: 
Bivalent 
boosters Pfizer 
(5-11y) and 
Moderna (6 -17y)December: 
Bivalent boosters 
Pfizer (6m -4y) and 
Moderna (6m -5y)May: EUA 
Pfizer 12 -
15y
May: 
myocarditis/
pericarditis 
after mRNA 
vaccines 
reportedAugust: FDA 
approves 
Pfizer (≥16y)
October: 
EUA Pfizer 
5-11y January: FDA 
approves 
Moderna 
(≥18y) May 2022: Janssen 
vaccine no longer 
recommendedJune: EUA Pfizer (6m –4y), 
Moderna (6m –17y)
July: EUA 
Novavax 
vaccine (≥18y)2020
Primary 
Series
Monovalent 
Boosters
Bivalent mRNA 
Boosters
VSD COVID -19 RCA 
Safety Publications2021 2022 2023
March: >200 
million doses 
given in US 
by the end 
AprilApril: 
Janssen 
and CVST 
concernsFebruary: 
Janssen 
EUA 
(≥18y)
June : mRNA 
vaccine safety 
6m-5y (Pediatrics )July: FDA 
safety 
warning re: 
GBS and 
Janssen. 
38Monovalent Booster Uptake Among Persons Aged5-11 Years in the VSD, Over Time* 
* Data through September 10, 2022 

Summary of RCA Findings in the 1 -21 Day Risk Interval after Monovalent Booster, 5 –11-year-olds
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators*
➢Among children aged 5 -11 years in the VSD, no outcome met the signaling criteria in the 
21 days after monovalent booster vaccination. However, vaccine uptake was low.
Signal?**
*Final analyses through January 2023
**Signaling threshold P<0.011 (one -sided)
40September: Interim mRNA vaccines safety 
surveillance, including myocarditis/pericarditis risk 
(JAMA )September: 
Bivalent boosters 
Pfizer (≥12y) and 
Moderna (≥18y)September: Bivalent 
boosters. Monovalent 
boosters discontinuedMay: Pfizer 
monovalent 
booster 5 -
11yMarch: 2nd 
monovalent 
booster 
(≥50y)January: 
Pfizer 
monovalent 
booster
12-15ySeptember/October: 
Adult monovalent 
booster; Pfizer 
(≥16y), Moderna and 
Janssen (≥18y)
October: Myocarditis/pericarditis 
rates after primary and monovalent 
boosters <40y ( Ann Int Med )August: Risk of myocarditis/ 
pericarditis Pfizer vs Moderna 
(Vaccine )April: GBS following 
Janssen vaccine ( JAMA
Network Open )December: 
EUA Moderna 
(≥18y) and 
Pfizer (≥16y)
November/December: first 
VSD signal, ischemic stroke 
after bivalent Pfizer ≥65y
October: 
Bivalent 
boosters Pfizer 
(5-11y) and 
Moderna (6 -17y)December: 
Bivalent boosters 
Pfizer (6m -4y) and 
Moderna (6m -5y)May: EUA 
Pfizer 12 -
15y
May: 
myocarditis/
pericarditis 
after mRNA 
vaccines 
reportedAugust: FDA 
approves 
Pfizer (≥16y)
October: 
EUA Pfizer 
5-11y January: FDA 
approves 
Moderna 
(≥18y) May 2022: Janssen 
vaccine no longer 
recommendedJune: EUA Pfizer (6m –4y), 
Moderna (6m –17y)
July: EUA 
Novavax 
vaccine (≥18y)2020
Primary 
Series
Monovalent 
Boosters
Bivalent mRNA 
Boosters
VSD COVID -19 RCA 
Safety Publications2021 2022 2023
March: >200 
million doses 
given in US 
by the end 
AprilApril: 
Janssen 
and CVST 
concernsFebruary: 
Janssen 
EUA 
(≥18y)
June : mRNA 
vaccine safety 
6m-5y (PediatricsJuly: FDA 
safety 
warning re: 
GBS and 
Janssen. 
41Primary Series Uptake Among Persons Aged≥12 Years in the VSD, Over Time* 
* Data through May 21, 2022Dose 1 Dose 2 Total
Pfizer 4,669,621 4,558,067 9,227,688
Moderna 3,014,353 2,951,499 5,965,852
Janssen 511,944 NA 511,944
Total 8,195,918 7,509,566 15,705,484
Final RCA Findings in the 1 -21 Day Risk Interval After Primary Series ≥12 Years
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators*
*Final analyses through May 2022
**Signaling threshold P<0.01 (one -sided)Signal?** Signal?** Signal?** Signal?** Signal?** Signal?** Signal?**
43September: Interim mRNA vaccines safety 
surveillance, including myocarditis/pericarditis risk 
(JAMA )September: 
Bivalent boosters 
Pfizer (≥12y) and 
Moderna (≥18y)September: Bivalent 
boosters. Monovalent 
boosters discontinuedMay: Pfizer 
monovalent 
booster 5 -
11yMarch: 2nd 
monovalent 
booster 
(≥50y)January: 
Pfizer 
monovalent 
booster
12-15ySeptember/October: 
Adult monovalent 
booster; Pfizer 
(≥16y), Moderna and 
Janssen (≥18y)
October: Myocarditis/pericarditis 
rates after primary and monovalent 
boosters <40y ( Ann Int Med )August: Risk of myocarditis/ 
pericarditis Pfizer vs Moderna 
(Vaccine )April: GBS following 
Janssen vaccine ( JAMA
Network Open )December: 
EUA Moderna 
(≥18y) and 
Pfizer (≥16y)
November/December: first 
VSD signal, ischemic stroke 
after bivalent Pfizer ≥65y
October: 
Bivalent 
boosters Pfizer 
(5-11y) and 
Moderna (6 -17y)December: 
Bivalent boosters 
Pfizer (6m -4y) and 
Moderna (6m -5y)May: EUA 
Pfizer 12 -
15y
May: 
myocarditis/
pericarditis 
after mRNA 
vaccines 
reportedAugust: FDA 
approves 
Pfizer (≥16y)
October: 
EUA Pfizer 
5-11y January: FDA 
approves 
Moderna 
(≥18y) May 2022: Janssen 
vaccine no longer 
recommendedJune: EUA Pfizer (6m –4y), 
Moderna (6m –17y)
July: EUA 
Novavax 
vaccine (≥18y)2020
Primary 
Series
Monovalent 
Boosters
Bivalent mRNA 
Boosters
VSD COVID -19 RCA 
Safety Publications2021 2022 2023
March: >200 
million doses 
given in US 
by the end 
AprilApril: 
Janssen 
and CVST 
concernsFebruary: 
Janssen 
EUA 
(≥18y)
June : mRNA 
vaccine safety 
6m-5y (Pediatrics )July: FDA 
safety 
warning re: 
GBS and 
Janssen. 
44Primary Series Uptake Among Persons Aged6 Months -5 Years in the VSD, 
Over Time* 
* Data through March 18, 2023Dose 1 Dose 2 Dose 3 Total
Pfizer 70,580 62,452 30,641 163,673
Moderna 59,872 52,134 NA 112,006
Total 130,452 114,586 30,641 275,679
45RCA in the 1 -21 Day Risk Interval, 6 months -4/5-year-olds 
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators on the Same Calendar Days, June 18, 2022 –March 18, 2023
Goddard K, Donahue JG, Lewis N, Hanson KE, Weintraub ES, Fireman B, Klein NP. Safety of COVID -19 mRNA Vaccination Among Young Ch ildren in the Vaccine Safety Datalink. Pediatrics. 2023 Jul 1;152(1):e2023061894. doi: 10.1542/peds.2023 -061894.
46RCA in the 1 -21 Day Risk Interval, 6 months -4/5-year-olds 
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators on the Same Calendar Days, June 18, 2022 –March, 2023
Goddard K, Donahue JG, Lewis N, Hanson KE, Weintraub ES, Fireman B, Klein NP. Safety of COVID -19 mRNA Vaccination Among Young Ch ildren in the Vaccine Safety Datalink. Pediatrics. 2023 Jul 1;152(1):e2023061894. doi: 10.1542/peds.2023 -061894.•Among children 6 month -4/5 years, no outcome met the signaling 
criteria in the 21 days after primary series. 
•No cases of myocarditis or pericarditis within the risk interval 
•However, vaccine uptake has been low 
47September: Interim mRNA vaccines safety 
surveillance, including myocarditis/pericarditis risk 
(JAMA )September: 
Bivalent boosters 
Pfizer (≥12y) and 
Moderna (≥18y)September: Bivalent 
boosters. Monovalent 
boosters discontinuedMay: Pfizer 
monovalent 
booster 5 -
11yMarch: 2nd 
monovalent 
booster 
(≥50y)January: 
Pfizer 
monovalent 
booster
12-15ySeptember/October: 
Adult monovalent 
booster; Pfizer 
(≥16y), Moderna and 
Janssen (≥18y)
October: Myocarditis/pericarditis 
rates after primary and monovalent 
boosters <40y ( Ann Int Med )August: Risk of myocarditis/ 
pericarditis Pfizer vs Moderna 
(Vaccine )April: GBS following 
Janssen vaccine ( JAMA
Network Open )December: 
EUA Moderna 
(≥18y) and 
Pfizer (≥16y)
November/December: first 
VSD signal, ischemic stroke 
after bivalent Pfizer ≥65y
October: 
Bivalent 
boosters Pfizer 
(5-11y) and 
Moderna (6 -17y)December: 
Bivalent boosters 
Pfizer (6m -4y) and 
Moderna (6m -5y)May: EUA 
Pfizer 12 -
15y
May: 
myocarditis/
pericarditis 
after mRNA 
vaccines 
reportedAugust: FDA 
approves 
Pfizer (≥16y)
October: 
EUA Pfizer 
5-11y January: FDA 
approves 
Moderna 
(≥18y) May 2022: Janssen 
vaccine no longer 
recommendedJune: EUA Pfizer (6m –4y), 
Moderna (6m –17y)
July: EUA 
Novavax 
vaccine (≥18y)2020
Primary 
Series
Monovalent 
Boosters
Bivalent mRNA 
Boosters
VSD COVID -19 RCA 
Safety Publications2021 2022 2023
March: >200 
million doses 
given in US 
by the end 
AprilApril: 
Janssen 
and CVST 
concernsFebruary: 
Janssen 
EUA 
(≥18y)
June : mRNA 
vaccine safety 
6m-5y (PediatricsJuly: FDA 
safety 
warning re: 
GBS and 
Janssen. 
48Bivalent Booster Uptake Among Persons Aged ≥12 Years, Over Time* 
* Data through March 18, 2023
Pfizer -BioNTech
Moderna1,855,946
851,807
Summary RCA Findings in the 1 -21 Day Risk Interval after Bivalent Booster 6 months -64 years
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators*
*Analyses through March 2023
**Signaling threshold P<0.01 (one -sided)Signal?** Signal?**Risk Interval 
DaysAge GroupOutcomeEither mRNA Pfizer ModernaEvent
1 -21 0-4y Kawasaki disease No No -
5-11y Appendicitis No No -
Bell's palsy No No -
Stroke, hemorrhagic No No -
Immune thrombocytopenia No No -
Seizures No No -
12-17y Appendicitis No No No
Bell's palsy No No -
Encephalitis / myelitis / encephalomyelitis No No -
Immune thrombocytopenia No No -
Seizures No No -
Venous thromboembolism No No -
18-64y Acute disseminated encephalomyelitis No No -
Acute myocardial infarction No No No
Appendicitis No No No
Bell's palsy No No No
Cerebral venous sinus thrombosis No No No
Disseminated intravascular coagulation No - No
Encephalitis / myelitis / encephalomyelitis No No No
Guillain -Barre syndrome No No -
Stroke, hemorrhagic No No No
Stroke, ischemic No No No
Immune thrombocytopenia No No No
Myocarditis / pericarditis No No No
Seizures No No No
Transverse myelitis No No -
Thrombotic thrombocytopenic purpura No No No
Thrombosis with thrombocytopenia syndrome No No No
Venous thromboembolism No No No
Pulmonary embolism (subset of VTE) No No No➢Among ages 5 -64 years in 
the VSD, no outcomes have 
met the signaling criteria in 
the 21 days after bivalent 
booster vaccine. 
50VSD Incidence Rates of Verified Myocarditis or Pericarditis in the 0 –7 
Days After Bivalent Booster in Ages 12 –39 years*
Dose 2 primary series 
Pfizer -BioNTechMonovalent booster dose 
Pfizer -BioNTechBivalent Booster Doses 
(Pfizer and Moderna)
Age Group 
(yrs)Cases Total
Dose 2 (N)Incidence rate/
million doses
(95% CI)Cases Total 
Doses 
(N)Incidence rate/
million doses
(95% CI)Cases Total Doses 
(N)Incidence rate/
million doses
(95% CI)
Pfizer
12–17
Males
Females45
6308,046
311,247146.1 (106.6 –195.5)
19.3 (7.1 –42.0)14
2129,487
139,118108.1 (59.1 –181.4)
14.4 (1.7 –51.9)0
055,649
57,7760.0 (0.0 –53.8)
0.0 (0.0 –51.9)
18–29
Males
Females27
2331,889
400,32181.4 (53.6 –118.4)
5.0 (0.6 –18.0)7
1166,973
240,22641.9 (16.9 –86.4)
4.2 (0.1 –23.2)1
060,338
95,16216.6 (0.4 –92.3)
0.0 (0.0 –31.5)
30–39
Males
Females5
3341,527
410,71314.6 (4.8 –34.2)
7.3 (1.5 –21.3)3
1197,554
268,41215.2 (3.1 –44.4)
3.7 (0.1 –20.8)0
097,171
133,3050.0 (0.0 –30.8)
0.0 (0.0 –22.5)
Moderna
18–29
Males
Females19
0195,809
243,56097.0 (58.4 –151.5)
0.0 (0.0 –12.3)7
1109,337
156,70764.0 (25.7 –131.9)
6.4 (0.2 –35.6)0
022,247
35,3930.0 (0.0 –134.7)
0.0 (0.0 –84.6)
30–39
Males
Females8
1216,583
259,78036.9 (15.9 –72.8)
3.9 (0.1 –21.4)1
2149,468
191,7656.7 (0.2 –37.3)
10.4 (1.3 –37.7)1
041,820
55,81623.9 (0.6 –133.2)
0.0 (0.0 –53.7)
* Primary series and monovalent booster data through August 20, 2022; ; 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 .Bivalent booster data through March 11, 2023
51September: Interim mRNA vaccines safety 
surveillance, including myocarditis/pericarditis risk 
(JAMA )September: 
Bivalent boosters 
Pfizer (≥12y) and 
Moderna (≥18y)September: Bivalent 
boosters. Monovalent 
boosters discontinuedMay: Pfizer 
monovalent 
booster 5 -
11yMarch: 2nd 
monovalent 
booster 
(≥50y)January: 
Pfizer 
monovalent 
booster
12-15ySeptember/October: 
Adult monovalent 
booster; Pfizer 
(≥16y), Moderna and 
Janssen (≥18y)
October: Myocarditis/pericarditis 
rates after primary and monovalent 
boosters <40y ( Ann Int Med )August: Risk of myocarditis/ 
pericarditis Pfizer vs Moderna 
(Vaccine )April: GBS following 
Janssen vaccine ( JAMA
Network Open )December: 
EUA Moderna 
(≥18y) and 
Pfizer (≥16y)
November/December: first 
VSD signal, ischemic stroke 
after bivalent Pfizer ≥65y
October: 
Bivalent 
boosters Pfizer 
(5-11y) and 
Moderna (6 -17y)December: 
Bivalent boosters 
Pfizer (6m -4y) and 
Moderna (6m -5y)May: EUA 
Pfizer 12 -
15y
May: 
myocarditis/
pericarditis 
after mRNA 
vaccines 
reportedAugust: FDA 
approves 
Pfizer (≥16y)
October: 
EUA Pfizer 
5-11y January: FDA 
approves 
Moderna 
(≥18y) May 2022: Janssen 
vaccine no longer 
recommendedJune: EUA Pfizer (6m –4y), 
Moderna (6m –17y)
July: EUA 
Novavax 
vaccine (≥18y)2020
Primary 
Series
Monovalent 
Boosters
Bivalent mRNA 
Boosters
VSD COVID -19 RCA 
Safety Publications2021 2022 2023
March: >200 
million doses 
given in US 
by the end 
AprilApril: 
Janssen 
and CVST 
concernsFebruary: 
Janssen 
EUA 
(≥18y)
June : mRNA 
vaccine safety 
6m-5y (PediatricsJuly: FDA 
safety 
warning re: 
GBS and 
Janssen. 
Ischemic Stroke Following Pfizer Bivalent 
Booster Vaccination in 65+ Years of Age
52
53Number of COVID -19 Bivalent Booster Doses and Influenza Vaccine Doses 
Administered Over Time Among Persons Aged ≥65 years, by Vaccine Type

Risk Interval Days Age GroupOutcomeEither mRNA Pfizer ModernaEvent
1 -21 65+ Acute myocardial infarction No No No
Appendicitis No No No
Bell's palsy No No No
Cerebral venous sinus thrombosis No No -
Disseminated intravascular coagulation No No No
Guillain -Barre syndrome No No No
Stroke, hemorrhagic No No No
Stroke, ischemic Yes Yes No
Immune thrombocytopenia No No No
Myocarditis / pericarditis No No No
Seizures No No No
Thrombotic thrombocytopenic purpura No No No
Thrombosis with thrombocytopenia syndrome No No No
Venous thromboembolism No No No
Pulmonary embolism (subset of VTE) No No NoSummary RCA Findings in the 1 -21 Day Risk Interval After Bivalent Booster ≥65 years
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators*
*Analyses through March 2023
**Signaling threshold P<0.01 (one -sided)Signal?** Signal?**
➢Ischemic stroke signaled in the 21 days after bivalent booster vaccine among ≥65 years in the VSD.Signal?**
55Ischemic Stroke AfterPfizer -BioNTech Bivalent Booster , Age ≥65 years, 
Counts and Adjusted Rate Ratios (Oct 15, 2022 –March 18 , 2023)
Red dot represents sequential signal: p -value <0.01 (1 -sided)RR= 1.25 (95% CI 0.98 –1.59)
56Ischemic Stroke by Day after Pfizer -BioNTech Bivalent 
Booster, People Aged ≥65 Years*
Cluster days 13 –22, p -value = 0.0637
*Data cutoff 2/28/2023
57Post -Signal analyses*:
Ischemic Stroke Incidence During Days 1 –21 Compared with Days 22 –42, 
Among ≥65 Years With and Without Simultaneous Influenza Vaccination
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 27 1.59 (0.99 –2.61) 0.06
Bivalent Pfizer + same day
standard dose flu vaccine8 11 0.73 (0.28 -1.83) 0.50
Bivalent Pfizer without any
same day flu vaccine107 99 1.08 (0.82 –1.42) 0.58
* Analyses only include vaccination data through January 14, 2023, and stroke outcome data through February 25, 2023
** Adjusted by 5 -year age groups
58

59Additional Considerations for Stroke Outcome
▪Small numbers of strokes and imprecise rate ratios limit some analyses 
•Uptake of Moderna booster was delayed and reduced due to distribution delays
•Follow -up of individuals concurrently given bivalent booster + hi -dose flu was limited by small numbers
▪Difficult to interpret temporal clustering which attenuated as rate ratio attenuated
▪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
Anaphylaxis
•The rate of anaphylaxis was ~ 5 cases/million doses for the mRNA primary series.
̶The rate of anaphylaxis was <5 cases/million doses for mRNA booster doses. 
Myocarditis/Pericarditis after mRNA vaccines
•During days 0 -7 post vaccination , both mRNA vaccines were associated with increased risk of 
myocarditis/pericarditis in 12 –39-year-olds.
•Risk estimates of myocarditis/pericarditis in 18 –39-year-olds during days 0 -7 after 2 doses were 
modestly higher after Moderna than after Pfizer.
•For persons ages 12 –39 years, rates of myocarditis/pericarditis 0 –7 days after primary and 
monovalent boosters were highest among male 12 -15 and 16 –17-year-olds.
̶Evidence suggests there was an increased risk for myocarditis/pericarditis following monovalent booster dose for 
some age groups.
̶No current evidence for an increased rate of myocarditis/pericarditis following bivalent boosters. Uptake was low in 
age groups expected to be at highest risk. Summary of Safety Findings after COVID -19 Vaccines in the VSD
60
Ischemic stroke after Pfizer bivalent booster
•Rate ratio met signaling criteria consistently for 8 weeks but slowly attenuated and now 
does not meet signaling criteria
•Temporal clustering 13 –22 days after vaccination (significant at time of initial signal but 
attenuated as the rate ratio estimate attenuated) 
•Supplemental analyses using un -boosted concurrent comparators showed a rate ratio 
RR=1.07 (95% CI 0.89 –1.28) (data not shown)
•Analyses evaluating simultaneous high -dose or adjuvanted flu vaccine showed a rate ratio 
RR=1.59 ( 95% CI 0.99 –2.61)
̶Separate analyses did not detect an elevated RR for stroke after flu vaccine alone (data not shown)
GBS after Janssen vaccine
•Findings were consistent withanassociation between increased riskofGBS andJanssen
COVID -19vaccine.
61Summary of Safety Findings After COVID -19 Vaccines in the VSD
Summary of VSD COVID RCA chart review 
62Vaccine Outcome
Acute 
disseminated 
encephalo -
myelitis 
(ADEM) 
N=9Anaphylaxis
N=342Cerebral 
venous sinus 
thrombosis  
(CVST) 
N=98Guillain -
Barré 
syndrome 
(GBS)  
N=130Ischemic 
Stroke 
N=100Multisystem 
Inflammatory 
Syndrome –
Child/Adult 
(MIS -C/A) 
N=33Myocarditis/
Pericarditis 
N=935Thrombosis 
with 
thrombo -
cytopenia 
syndrome 
(TTS)    
N=32Transverse 
myelitis  
(TM)     
N=43Venous 
thrombo -
embolism 
(VTE)    
N=186TOTAL 
N=1908
Primary 
series 
(mRNA and 
Janssen)9 300 98 130 NR 33 342 
(6 months -
39 yrs)32 43 186 1173
Monovalent 
Booster 
(mRNA) NR 30 NR NR NR NR 362 
(all ages)NR NR NR 392
Bivalent 
Booster 
(mRNA)NR 12 NR NR 100 
(65+ yrs)NR 231 
(all ages)NR NR NR 343
*Counts are included per individual; however, most outcomes underwent multiple reviews (i.e., quick review, full review, clin ical 
adjudication) 
NR= not reviewed
1.Vaccine uptake was early & unpredictable. 
̶One rationale for using vaccinated concurrent comparators.
̶Most RCA findings came early and have been mostly unchanged since fall 2021. 
2.The VSD COVID -19 RCA analytic methods have been hard to understand. 
̶We believe that vaccinated concurrent comparators are less vulnerable to bias, but it is an unfamiliar approach that 
is difficult to explain how the follow up in the comparison interval is concurrent (i.e., on the same calendar day) with 
the follow up in the risk interval. 
̶However, intense public attention on COVID vaccine safety meant we frequently communicated preliminary results 
on short notice, and methods that are hard to concisely explain and understand posed substantial challenges.
3.Our vaccine safety questions have frequently changed and expanded, requiring us to rapidly 
adapt our surveillance to include new outcomes and age groups. 
̶Flexibility in routinely accommodating (sometime substantial) changes has been critical.
4.Challenging to digest and interpret the large amounts of potentially relevant data and results 
that we put “on the shelf” weekly (e.g., comparisons with unvaccinated people).
̶Supplementary analyses were available should a safety concern arise from VSD or elsewhere. 63Challenges in Rapidly Generating Vaccine Safety Evidence 
During the Pandemic
•2020 -2023 VSD COVID -19 RCA surveillance is complete.
•Future Studies -VSD may consider further investigating:
•mRNA vaccine primary series signals of VTE and AMI
•Bell’s palsy after Janssen primary and mRNA monovalent booster (limited 
data since neither vaccine is currently available or used)
•Ischemic stroke after concomitant bivalent boosters and flu vaccines in ≥65 -
year-olds in future season 
64Future Considerations 
It takes a village…
65
•Kaiser Permanente Northern California:
•Ned Lewis, Kristin Goddard, Bruce Fireman, Ousseny Zerbo, Karen Nunley, Pat Ross, Nandini Bahkshi , Laurie 
Aukes, Berwick Chan, Arnold Yee, Varun Shah
•Marshfield Clinic Research Institute:
•Jim Donahue, Kayla Hanson, Ed Belongia, Tom Boyce, Burney Kieke, Dave McClure, Erica Scotty
•CDC Immunization Safety Office:
•Eric Weintraub, Tom Shimabukuro, Matt Oster, Tat’Yana Kenigsberg, Jonathan Duffy, Frank Destefano, Tanya 
Myers 
•VSD Sites
•HealthPartners Institute, Minneapolis, Minnesota
•Kaiser Permanente Colorado, Denver, Colorado
•Kaiser Permanente Northwest, Portland, Oregon
•Kaiser Permanente Southern California, Los Angeles, California
•Kaiser Permanente Washington, Seattle, Washington
•Denver Health, Denver, ColoradoAcknowledgements
66