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
2

Vaccine 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 prespecified 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 syndrome

Outcomes added/enhanced due to emerging 

concerns

Imbalances in phase 3 COVID-19 vaccine clinical 

trials

• Appendicitis 

• Bell’s palsy

Only chart confirmed cases *monitored without comparators

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), we 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 

22 June 3 42

Vaccinated 

May 3

1

Risk Interval 1-21 days post-vaccination

21 June 3

Vaccinated 

May 30

6
7

September: Interim mRNA vaccines safety 

surveillance, including myocarditis/pericarditis risk 

(JAMA)

September: 

Bivalent boosters 

Pfizer (≥12y) and 

Moderna (≥18y)

September: Bivalent 

boosters. Monovalent 

boosters discontinued

May: Pfizer 

monovalent 

booster 5-

11y

March: 2nd 

monovalent 

booster 

(≥50y)

January: 

Pfizer 

monovalent 

booster

12-15y

September/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 

reported

August: FDA 

approves 

Pfizer (≥16y)

October: 

EUA Pfizer 

5-11y 

January: FDA 

approves 

Moderna 

(≥18y) 

May 2022: Janssen 

vaccine no longer 

recommended

June: 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 Publications

2021 2022 2023

March: >200 

million doses 

given in US 

by the end 

April

April: 

Janssen 

and CVST 

concerns

February: 

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.2021.15072

10
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
14

September: Interim mRNA vaccines safety 

surveillance, including myocarditis/pericarditis risk 

(JAMA)

September: 

Bivalent boosters 

Pfizer (≥12y) and 

Moderna (≥18y)

September: Bivalent 

boosters. Monovalent 

boosters discontinued

May: Pfizer 

monovalent 

booster 5-

11y

March: 2nd 

monovalent 

booster 

(≥50y)

January: 

Pfizer 

monovalent 

booster

12-15y

September/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 

reported

August: FDA 

approves 

Pfizer (≥16y)

October: 

EUA Pfizer 

5-11y 

January: FDA 

approves 

Moderna 

(≥18y) 

May 2022: Janssen 

vaccine no longer 

recommended

June: 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 Publications

2021 2022 2023

March: >200 

million doses 

given in US 

by the end 

April

April: 

Janssen 

and CVST 

concerns

February: 

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
21

September: Interim mRNA vaccines safety 

surveillance, including myocarditis/pericarditis risk 

(JAMA)

September: 

Bivalent boosters 

Pfizer (≥12y) and 

Moderna (≥18y)

September: Bivalent 

boosters. Monovalent 

boosters discontinued

May: Pfizer 

monovalent 

booster 5-

11y

March: 2nd 

monovalent 

booster 

(≥50y)

January: 

Pfizer 

monovalent 

booster

12-15y

September/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 

reported

August: FDA 

approves 

Pfizer (≥16y)

October: 

EUA Pfizer 

5-11y 

January: FDA 

approves 

Moderna 

(≥18y) 

May 2022: Janssen 

vaccine no longer 

recommended

June: 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 Publications

2021 2022 2023

March: >200 

million doses 

given in US 

by the end 

April

April: 

Janssen 

and CVST 

concerns

February: 

Janssen 

EUA 

(≥18y)

June : mRNA 

vaccine safety 

6m-5y (Pediatrics)

July: FDA 

safety 

warning re: 

GBS and 

Janssen. 
22

Sequential Test1

Outcome Event in 

Risk 

Interval

Adjusted Rate 

Ratio (95% CI)2

1-sided 

P-value

'Signal’ 1-

sided p 

<0.0048?

Myocarditis / 

pericarditis 

138 1.72 <0.001 Yes

RCA 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 2021

1Sequential 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*
27

September: Interim mRNA vaccines safety 

surveillance, including myocarditis/pericarditis risk 

(JAMA)

September: 

Bivalent boosters 

Pfizer (≥12y) and 

Moderna (≥18y)

September: Bivalent 

boosters. Monovalent 

boosters discontinued

May: Pfizer 

monovalent 

booster 5-

11y

March: 2nd 

monovalent 

booster 

(≥50y)

January: 

Pfizer 

monovalent 

booster

12-15y

September/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 

reported

August: FDA 

approves 

Pfizer (≥16y)

October: 

EUA Pfizer 

5-11y 

January: FDA 

approves 

Moderna 

(≥18y) 

May 2022: Janssen 

vaccine no longer 

recommended

June: 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 Publications

2021 2022 2023

March: >200 

million doses 

given in US 

by the end 

April

April: 

Janssen 

and CVST 

concerns

February: 

Janssen 

EUA 

(≥18y)

June : mRNA 

vaccine safety 

6m-5y (Pediatrics

July: FDA 

safety 

warning re: 

GBS and 

Janssen. 
• Findings were consistent with an association between increased risk of GBS and

Janssen COVID-19 vaccine.

̶ When directly compared with mRNA vaccines, the risk of GBS after Janssen vaccine was 21 times

higher.

• No evidence of association between GBS and mRNA-based COVID-19 vaccines.

̶ Incidence of GBS in the 21 days after mRNA vaccines was similar to the expected background rate

̶ No statistical signals in weekly surveillance with vaccinated 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-19 vaccines 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/janssencovid-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)
29

September: Interim mRNA vaccines safety 

surveillance, including myocarditis/pericarditis risk 

(JAMA)

September: 

Bivalent boosters 

Pfizer (≥12y) and 

Moderna (≥18y)

September: Bivalent 

boosters. Monovalent 

boosters discontinued

May: Pfizer 

monovalent 

booster 5-

11y

March: 2nd 

monovalent 

booster 

(≥50y)

January: 

Pfizer 

monovalent 

booster

12-15y

September/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 

reported

August: FDA 

approves 

Pfizer (≥16y)

October: 

EUA Pfizer 

5-11y 

January: FDA 

approves 

Moderna 

(≥18y) 

May 2022: Janssen 

vaccine no longer 

recommended

June: 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 Publications

2021 2022 2023

March: >200 

million doses 

given in US 

by the end 

April

April: 

Janssen 

and CVST 

concerns

February: 

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 primary->booster doses.

4One additional case was in the risk interval but not included because there were no appropriate comparators. This case is included 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 cases are included in the events/million dose calculation.

Analysis

Ages Vaccine

Events 

in Risk

Interval

Events in 

Comparison 

Interval1

Adjusted 

Rate Ratio2

95%

Confidence

Interval

2-Sided

P-value

Events/Million 

Doses

Monovalent 

Booster3

12 - 17 Pfizer4

15 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 Moderna5

6 4 3.27 0.82 – 14.23 0.093 16.8 (7.3 – 33.1)

32

Verified Myocarditis and Pericarditis in 0–7 Days Following 

Monovalent Booster in 12–39-Year-Olds

Compared with Events on the Same Calendar Days among Boosted Comparators
33

September: Interim mRNA vaccines safety 

surveillance, including myocarditis/pericarditis risk 

(JAMA)

September: 

Bivalent boosters 

Pfizer (≥12y) and 

Moderna (≥18y)

September: Bivalent 

boosters. Monovalent 

boosters discontinued

May: Pfizer 

monovalent 

booster 5-

11y

March: 2nd 

monovalent 

booster 

(≥50y)

January: 

Pfizer 

monovalent 

booster

12-15y

September/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 

reported

August: FDA 

approves 

Pfizer (≥16y)

October: 

EUA Pfizer 

5-11y 

January: FDA 

approves 

Moderna 

(≥18y) 

May 2022: Janssen 

vaccine no longer 

recommended

June: 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 Publications

2021 2022 2023

March: >200 

million doses 

given in US 

by the end 

April

April: 

Janssen 

and CVST 

concerns

February: 

Janssen 

EUA 

(≥18y)

June : mRNA 

vaccine safety 

6m-5y (Pediatrics)

July: FDA 

safety 

warning re: 

GBS and 

Janssen. 
34

Primary Series uptake among persons aged 5-11 years in the VSD, over time* 

* Data through 

February 4, 

2023

426,177

3,122

450,217

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 - No

Pfizer

Risk 

Interval 

Days

Dose 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
37

September: Interim mRNA vaccines safety 

surveillance, including myocarditis/pericarditis risk 

(JAMA)

September: 

Bivalent boosters 

Pfizer (≥12y) and 

Moderna (≥18y)

September: Bivalent 

boosters. Monovalent 

boosters discontinued

May: Pfizer 

monovalent 

booster 5-

11y

March: 2nd 

monovalent 

booster 

(≥50y)

January: 

Pfizer 

monovalent 

booster

12-15y

September/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 

reported

August: FDA 

approves 

Pfizer (≥16y)

October: 

EUA Pfizer 

5-11y 

January: FDA 

approves 

Moderna 

(≥18y) 

May 2022: Janssen 

vaccine no longer 

recommended

June: 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 Publications

2021 2022 2023

March: >200 

million doses 

given in US 

by the end 

April

April: 

Janssen 

and CVST 

concerns

February: 

Janssen 

EUA 

(≥18y)

June : mRNA 

vaccine safety 

6m-5y (Pediatrics)

July: FDA 

safety 

warning re: 

GBS and 

Janssen. 
38

Monovalent Booster Uptake Among Persons Aged 5-11 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)
40

September: Interim mRNA vaccines safety 

surveillance, including myocarditis/pericarditis risk 

(JAMA)

September: 

Bivalent boosters 

Pfizer (≥12y) and 

Moderna (≥18y)

September: Bivalent 

boosters. Monovalent 

boosters discontinued

May: Pfizer 

monovalent 

booster 5-

11y

March: 2nd 

monovalent 

booster 

(≥50y)

January: 

Pfizer 

monovalent 

booster

12-15y

September/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 

reported

August: FDA 

approves 

Pfizer (≥16y)

October: 

EUA Pfizer 

5-11y 

January: FDA 

approves 

Moderna 

(≥18y) 

May 2022: Janssen 

vaccine no longer 

recommended

June: 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 Publications

2021 2022 2023

March: >200 

million doses 

given in US 

by the end 

April

April: 

Janssen 

and CVST 

concerns

February: 

Janssen 

EUA 

(≥18y)

June : mRNA 

vaccine safety 

6m-5y (Pediatrics

July: FDA 

safety 

warning re: 

GBS and 

Janssen. 
41

Primary Series Uptake Among Persons Aged ≥12 Years in the VSD, Over Time* 

* Data through May 21, 2022

Dose 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?**
43

September: Interim mRNA vaccines safety 

surveillance, including myocarditis/pericarditis risk 

(JAMA)

September: 

Bivalent boosters 

Pfizer (≥12y) and 

Moderna (≥18y)

September: Bivalent 

boosters. Monovalent 

boosters discontinued

May: Pfizer 

monovalent 

booster 5-

11y

March: 2nd 

monovalent 

booster 

(≥50y)

January: 

Pfizer 

monovalent 

booster

12-15y

September/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 

reported

August: FDA 

approves 

Pfizer (≥16y)

October: 

EUA Pfizer 

5-11y 

January: FDA 

approves 

Moderna 

(≥18y) 

May 2022: Janssen 

vaccine no longer 

recommended

June: 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 Publications

2021 2022 2023

March: >200 

million doses 

given in US 

by the end 

April

April: 

Janssen 

and CVST 

concerns

February: 

Janssen 

EUA 

(≥18y)

June : mRNA 

vaccine safety 

6m-5y (Pediatrics)

July: FDA 

safety 

warning re: 

GBS and 

Janssen. 
44

Primary Series Uptake Among Persons Aged 6 Months- 5 Years in the VSD, 

Over Time* 

* Data through March 18, 2023

Dose 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
45

RCA 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 Children in the Vaccine Safety Datalink. Pediatrics. 2023 Jul 1;152(1):e2023061894. doi: 10.1542/peds.2023-061894.
46

RCA 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 Children 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 
47

September: Interim mRNA vaccines safety 

surveillance, including myocarditis/pericarditis risk 

(JAMA)

September: 

Bivalent boosters 

Pfizer (≥12y) and 

Moderna (≥18y)

September: Bivalent 

boosters. Monovalent 

boosters discontinued

May: Pfizer 

monovalent 

booster 5-

11y

March: 2nd 

monovalent 

booster 

(≥50y)

January: 

Pfizer 

monovalent 

booster

12-15y

September/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 

reported

August: FDA 

approves 

Pfizer (≥16y)

October: 

EUA Pfizer 

5-11y 

January: FDA 

approves 

Moderna 

(≥18y) 

May 2022: Janssen 

vaccine no longer 

recommended

June: 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 Publications

2021 2022 2023

March: >200 

million doses 

given in US 

by the end 

April

April: 

Janssen 

and CVST 

concerns

February: 

Janssen 

EUA 

(≥18y)

June : mRNA 

vaccine safety 

6m-5y (Pediatrics

July: FDA 

safety 

warning re: 

GBS and 

Janssen. 
48

Bivalent Booster Uptake Among Persons Aged ≥12 Years, Over Time* 

* Data through March 18, 2023

Pfizer-BioNTech

Moderna

1,855,946

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 

Days Age Group

Outcome

Either mRNA Pfizer Moderna

Event

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. 
50

VSD 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-BioNTech

Monovalent booster dose 

Pfizer-BioNTech

Bivalent 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

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

55,649

57,776

0.0 (0.0–53.8)

0.0 (0.0–51.9)

18–29

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

60,338

95,162

16.6 (0.4 – 92.3)

0.0 (0.0–31.5)

30–39

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

97,171

133,305

0.0 (0.0–30.8)

0.0 (0.0–22.5)

Moderna

18–29

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

22,247

35,393

0.0 (0.0–134.7)

0.0 (0.0–84.6)

30–39

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) 1

0

41,820

55,816

23.9 (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
51

September: Interim mRNA vaccines safety 

surveillance, including myocarditis/pericarditis risk 

(JAMA)

September: 

Bivalent boosters 

Pfizer (≥12y) and 

Moderna (≥18y)

September: Bivalent 

boosters. Monovalent 

boosters discontinued

May: Pfizer 

monovalent 

booster 5-

11y

March: 2nd 

monovalent 

booster 

(≥50y)

January: 

Pfizer 

monovalent 

booster

12-15y

September/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 

reported

August: FDA 

approves 

Pfizer (≥16y)

October: 

EUA Pfizer 

5-11y 

January: FDA 

approves 

Moderna 

(≥18y) 

May 2022: Janssen 

vaccine no longer 

recommended

June: 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 Publications

2021 2022 2023

March: >200 

million doses 

given in US 

by the end 

April

April: 

Janssen 

and CVST 

concerns

February: 

Janssen 

EUA 

(≥18y)

June : mRNA 

vaccine safety 

6m-5y (Pediatrics

July: FDA 

safety 

warning re: 

GBS and 

Janssen. 
Ischemic Stroke Following Pfizer Bivalent 

Booster Vaccination in 65+ Years of Age

52
53

Number 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 Group

Outcome

Either mRNA Pfizer Moderna

Event

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 No

Summary 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?**
55

Ischemic Stroke After Pfizer-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)
56

Ischemic 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
57

Post-Signal analyses*:

Ischemic Stroke Incidence During Days 1–21 Compared with Days 22–42, 

Among ≥65 Years With and Without Simultaneous Influenza Vaccination

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 27 1.59 (0.99 – 2.61) 0.06

Bivalent Pfizer + same day

standard dose flu vaccine 8 11 0.73 (0.28 - 1.83) 0.50

Bivalent Pfizer without any

same day flu vaccine 107 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
59

Additional 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 with an association between increased risk of GBS and Janssen

COVID-19 vaccine.

61

Summary of Safety Findings After COVID-19 Vaccines in the VSD
Summary of VSD COVID RCA chart review 

62

Vaccine Outcome

Acute 

disseminated 

encephalomyelitis 

(ADEM) 

N=9

Anaphylaxis

N=342

Cerebral 

venous sinus 

thrombosis 

(CVST) 

N=98

GuillainBarré 

syndrome 

(GBS) 

N=130

Ischemic 

Stroke 

N=100

Multisystem 

Inflammatory 

Syndrome –

Child/Adult 

(MIS-C/A) 

N=33

Myocarditis/

Pericarditis 

N=935

Thrombosis 

with 

thrombocytopenia 

syndrome 

(TTS) 

N=32

Transverse 

myelitis 

(TM) 

N=43

Venous 

thromboembolism 

(VTE) 

N=186

TOTAL 

N=1908

Primary 

series 

(mRNA and 

Janssen)

9 300 98 130 NR 33 342 

(6 months39 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, clinical 

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. 63

Challenges 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 

64

Future 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, Colorado

Acknowledgements

66