Myocarditis Analyses in the Vaccine Safety Datalink: 

Rapid Cycle Analyses and “Head-to-Head” Product 

Comparisons

Nicola Klein, MD, PhD

Kaiser Permanente Vaccine Study Center

Kaiser Permanente Northern California
• Established in 1990

• Collaborative project between CDC and 9 integrated healthcare organizations 

The Vaccine Safety Datalink (VSD)

2
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.

VSD Rapid Cycle Analysis (RCA)

3
# Outcomes Settings Risk Window 

(days) Chart Review Monitoring Only

Exclude if COVID19 in the Prior X 

Days

1 Acute disseminated encephalomyelitis E, I 1-21, 1-42 Yes

2 Acute myocardial infarction – First Ever E, I 1-21, 1-42 30 days

3 Acute respiratory distress syndrome E, I 0-84 Yes 42 days

4 Anaphylaxis – First in 7 days E, I 0-1 Yes Yes

5 Appendicitis E, I 1-21, 1-42

6 Bell’s palsy – First Ever E, I, O 1-21, 1-42 30 days

7 Cerebral venous sinus thrombosis E, I 1-21, 1-42 Yes 30 days

8 Disseminated intravascular coagulation E, I 1-21, 1-42 42 days

9 Encephalitis / myelitis / encephalomyelitis E, I 1-21, 1-42 30 days

10 Guillain-Barré syndrome E, I 1-21, 1-42 Yes

11 Immune thrombocytopenia E, I, O 1-21, 1-42 30 days

12 Kawasaki disease E, I 1-21, 1-42

13 Multisystem inflammatory syndrome in children/adults (MIS-C/MIS-A) E, I 0-84 Yes

14 Myocarditis / pericarditis – First in 60 Days E, I 1-21, 1-42 Yes (subgroup) 30 days

15 Narcolepsy / cataplexy E, I, O 0-84 Yes

16 Pulmonary embolism – First Ever E, I 1-21, 1-42 30 days

17 Seizures E, I 1-21, 1-42 30 days

18 Stroke, hemorrhagic E, I 1-21, 1-42 30 days

19 Stroke, ischemic E, I 1-21, 1-42 30 days

20 Thrombosis with thrombocytopenia syndrome – First Ever E, I 1-21, 1-42 Yes 30 days

21 Thrombotic thrombocytopenic purpura E, I 1-21, 1-42 30 days

22 Transverse myelitis E, I 1-21, 1-42 Yes

23 Venous thromboembolism – First Ever E, I, O 1-21, 1-42 30 days

VSD COVID-19 Vaccine RCA Outcomes

Abbreviations: E=ED, I=Inpatient, O=Outpatient

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COVID-19 Vaccine Uptake 

& Primary Analyses

(Data Through 10/09/2021)

5
VSD COVID-19 Vaccine Totals

6
VSD COVID-19 Vaccine Totals

7
First Dose Totals by Week for the 18-39 Year-Old Age Group

8
Days Between Dose 1 & Dose 2 for mRNA Vaccines 

Administered in the VSD among 18-39 Year-Olds

# of People Vaccinated

836,855

546,961

0

100,000

200,000

300,000

400,000

500,000

600,000

700,000

800,000

900,000

15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43

Dose Interval: Days from Dose 1 to Dose 2

Pfizer Doses

Moderna Doses

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• For the primary analysis, the number of outcomes observed in the risk interval 

(1-21 days) after COVID-19 vaccination were compared to the number 

expected.

• The expected was derived from “vaccinated concurrent comparators” who 

were in a comparison interval (days 22-42) after COVID-19 vaccination.

• On each day that an outcome occurred, vaccinees who were in their risk 

interval were compared with similar vaccinees who were concurrently in their 

comparison interval. 

─Comparisons were adjusted for age group, sex, race/ethnicity, VSD site, as well 

as calendar date.

Analytic Strategy

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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

11
Myocarditis/Pericarditis in 21-Day Risk Interval after 

Either Dose of any mRNA Vaccine

Compared with Outcome Events in Vaccinated Comparators on the Same Calendar Days 

1Sequential test requires 1-sided p < 0.0048 (Fisher) 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.

Sequential Test1

Outcome

Event

Events

in Risk 

Interval

Adjusted 

Rate Ratio2

1-sided

P-value 

(Fisher)

'Signal’ 1-sided

p < 0.0048

Myocarditis / pericarditis 138 1.72 <.001 yes

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Subgroup Analysis of Confirmed 

Myocarditis/Pericarditis after mRNA Vaccines 

among 12-39 Year-Olds 

(Data Through 10/09/2021)

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• Chart review completed for cases through October 09, 2021 for 132/135 cases (3 

pending) 

12–39-year-olds

Cases identified any time post-vaccination

• Initial chart review followed with adjudication by an infectious disease clinician 

and/or a cardiologist

Confirm incident following vaccination

Meet CDC case definition (myocarditis, pericarditis, or myopericarditis) 

Evaluate level of certainty for myocarditis

Adjudication confirmed 103/132 (78%) myocarditis/pericarditis cases

 74 confirmed cases among 12-39-year-olds, with onset 0-21 days after dose 1 (15) or 2 (59)

 44 confirmed cases among 18-39-year-olds, with onset 0-21 days after dose 1 (13) or 2 (31)

 39 confirmed cases among 18-39-year-olds, with onset 0-7 days after dose 1 (10) or 2 (29)

Myocarditis/Pericarditis Following an mRNA 

Vaccine: Chart Review Summary

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Day of Onset of Confirmed Myocarditis/Pericarditis among 

12-39 Year-Olds after Either Dose of an mRNA Vaccine

15

Three overlapping clustering identified

Days 0-4 (P <0.0001)

Days 0-3 (P <0.0001)

Days 0-5 (P <0.0001)
1Comparison interval is 22–42 days after either dose.

2Adjusted for VSD site, 5-year age group, sex, race/ethnicity, and calendar date.

3The focus should be on the lower bound of the confidence interval.

Vaccine Dose Events

in Risk

Interval

Events in 

Comparison 

Interval1

Adjusted 

Rate Ratio2

95%

Confidence

Interval

2-Sided

P-value

Excess Cases in 

Risk Period per 1 

Million Doses

Both mRNA Both Doses 66 6 21.73 9.53 - 57.34 <0.001 11.8

Dose 1 10 6 10.18 3.01 - 36.36 <0.001 3.3

Dose 2 52 5 31.28 12.83 - 91.40 <0.001 21.1

Pfizer 

Ages 12-39 

Both Doses 44 5 19.31 7.66 - 57.79 <0.001 11.5

Dose 1 5 5 8.65 2.01 - 36.99 0.005 2.3

Dose 2 35 4 30.27 11.01 - 104.40 <0.001 21.5

Moderna 

Ages 18-39

Both Doses 22 1 37.51 6.69 - 803.00 <0.001 12.8

Dose 1 5 1 10.47 1.38 - 258.35 0.020 5.2

Dose 2 17 0 very high3 11.75 -∞ <0.001 21.0

Confirmed Myocarditis/Pericarditis in the 0-7 Day Risk Interval, among 

12–39-year-olds by Product and Dose

Compared with Outcome Events in Vaccinated Comparators on the Same Calendar Days 

16

Results in this slide cannot be directly compared between Pfizer and Moderna because of the different age groups who are authorized to receive each vaccine
1Comparison interval is 22–42 days after either dose.

2Adjusted for VSD site, 5-year age group, sex, race/ethnicity, and calendar date.

3The focus should be on the lower bound of the confidence interval.

Analysis

Vaccine Dose Events

in Risk

Interval

Events in 

Comparison 

Interval1

Adjusted 

Rate Ratio2

95%

Confidence

Interval

2-Sided

P-value

Excess Cases in 

Risk Period per 1 

Million Doses

Both mRNA Both Doses 39 6 12.61 5.27 - 34.47 <0.001 8.4

Dose 1 10 6 9.69 2.90 - 34.22 <0.001 4.1

Dose 2 29 5 14.33 5.50 - 43.88 <0.001 13.1

Pfizer Both Doses 17 5 7.98 2.72 - 26.50 <0.001 5.7

Dose 1 5 5 8.05 1.89 - 33.89 0.006 3.3

Dose 2 12 4 8.77 2.56 - 35.34 <0.001 8.5

Moderna Both Doses 22 1 37.42 6.68 - 801.33 <0.001 12.8

Dose 1 5 1 10.47 1.38 - 258.35 0.020 5.2

Dose 2 17 0 very high3 11.70 - ∞ <0.001 21.0

Confirmed Myocarditis/Pericarditis in the 0-7 Day Risk Interval, among 

18–39-year-olds by Product and Dose

Compared with Outcome Events in Vaccinated Comparators on the Same Calendar Days 

17
Analysis

Risk

Interval

Dose Events

in Risk

Interval

Events in 

Comparison 

Interval1

Adjusted 

Rate Ratio2,3

95%

Confidence

Interval

2-Sided

P-value

Excess Cases in 

Risk Period per 1 

Million Doses

Days 0-21 Both Doses 30 0 very high 5.68 - ∞ <0.001 29.6

Dose 1 2 0 very high 0.31 - ∞ 0.198 3.8

Dose 2 24 0 very high 9.09 - ∞ <0.001 56.7

Days 0-7 Both Doses 27 0 very high 16.88 - ∞ <0.001 25.9

Dose 1 0 0 NE NE NE NE

Dose 2 23 0 very high 28.83 - ∞ <0.001 54.0

NE= not estimable; indicates that vaccine effect cannot be estimated.

1Comparison interval is 22–42 days after either dose.

2Adjusted for VSD site, 5-year age group, sex, race/ethnicity, and calendar date.

3The focus should be on the lower bound of the confidence interval.

Confirmed Myocarditis/Pericarditis, among 12–17-year-olds (Pfizer only) 

in the 0-7 and 0-21 Day Risk Interval by Dose

Compared with Outcome Events in Vaccinated Comparators on the Same Calendar Days 

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Myocarditis/Pericarditis: Moderna vs Pfizer

• Analyses with vaccinated concurrent comparators indicate that both Pfizer 

and Moderna are associated with increased risk of myocarditis/pericarditis 

in 12–39-year-olds.

̶ Pfizer results include 12–39-year-olds while Moderna only includes 18–39-year-olds.

• Analyses with vaccinated concurrent comparators indirectly suggest that 

Moderna is associated with more risk of myocarditis/pericarditis than 

Pfizer.

• To directly test whether the risk of myocarditis/pericarditis after Moderna 

differs from that after Pfizer, we conducted head-to-head comparisons 

among 18–39-year-olds.

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Confirmed Myocarditis/Pericarditis: 

Moderna vs Pfizer

(Data Through 10/09/2021)

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Days between Dose 1 & Dose 2 for the Confirmed

Myocarditis/Pericarditis Cases in the 0-21 Day Risk Interval for 18-39 Year Olds

21

0

2

4

6

8

10

12

14

1 4 7 10 13 16 19 22 25 28 31 34 37 40

Count

Days between Dose 1 and Dose 2

Pfizer

Moderna
Incidence of Confirmed Myocarditis/Pericarditis in 18-39 Year-Olds: Moderna vs Pfizer

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Pfizer

Moderna
Moderna vs Pfizer “Head-to-Head” Comparison

• Moderna and Pfizer vaccinees were directly compared during the risk interval within 

groups.

• The groups are comprised of:

 Individuals inside the risk interval (days 0-7 or 0-21 post-vaccination)

 Individuals of the same age group, sex, and race/ethnicity

 From the same VSD site

 On a calendar day when an mRNA vaccinee had myocarditis / pericarditis

• We estimated rate ratios with 95% confidence intervals (rate post-Moderna / rate postPfizer).

• We tested the null hypothesis that the rate of myocarditis / pericarditis after vaccination 

does not differ between Moderna and Pfizer.

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Moderna vs Pfizer “Head-to-Head” Comparison

• Moderna and Pfizer vaccinees were directly compared during the risk interval within 

groups.

• The groups are comprised of:

 Individuals inside the risk interval (days 0-7 or 0-21 post-vaccination)

 Individuals of the same age group, sex, and race/ethnicity

 From the same VSD site

 On a calendar day when an mRNA vaccinee had myocarditis / pericarditis

• We estimated rate ratios with 95% confidence intervals (rate post-Moderna / rate postPfizer).

• We tested the null hypothesis that the rate of myocarditis / pericarditis after vaccination 

does not differ between Moderna and Pfizer.

June 21 June 28

• A 28-year-old male had myocarditis on 6/28.

• He was vaccinated 6/23 and therefore in the 0-7 day in 

risk interval.

• Comparators include everyone who, on 6/28, was in the 

0–7 day post vaccination risk interval after either mRNA 

vaccine (i.e., they were vaccinated 6/21 – 6/28). 

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1Adjusted for VSD site, age, sex, race/ethnicity, and calendar date. Adjusted rate ratio is an estimate of the Moderna rate 

divided by Pfizer rate.

2Excess cases is an estimate of the Moderna rate minus the Pfizer rate. 

Risk 

Interval 

days

Moderna

(N)

Pfizer 

(N)

Adjusted 

Rate 

Ratio1

95% 

Confidence 

Interval

2-sided 

p-value

Excess cases in 

risk period per 1M 

doses of Moderna

vs Pfizer2

Both 

Doses

0-7 22 16 2.56 1.32 - 5.03 0.005 8.0

0-21 23 20 2.05 1.11 - 3.83 0.023 7.1

Dose 1 0-7 5 4 2.63 0.62 - 11.83 0.186 3.6

0-21 6 6 1.76 0.51 - 6.07 0.365 3.0

Dose 2 0-7 17 12 2.72 1.25 - 6.05 0.012 13.3

0-21 17 14 2.19 1.05 - 4.65 0.037 11.5

Myocarditis/Pericarditis in 18-39 Year Olds: 

Moderna vs Pfizer

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1Adjusted for VSD site, age, sex, race/ethnicity, and calendar date. Adjusted rate ratio is an estimate of the Moderna rate 

divided by Pfizer rate.

2Excess cases is an estimate of the Moderna rate minus the Pfizer rate. 

Risk 

Interval 

days

Moderna

(N)

Pfizer 

(N)

Adjusted 

Rate 

Ratio1

95% 

Confidence 

Interval

2-sided 

p-value

Excess cases in 

risk period per 1M 

doses of Moderna

vs Pfizer2

Both 

Doses

0-7 17 15 2.24 1.09 - 4.63 0.028 5.6

0-21 18 17 1.96 0.99 - 3.91 0.054 5.3

Dose 1 0-7 3 3 2.69 0.43 - 16.94 0.276 2.2

0-21 4 5 1.45 0.32 - 6.15 0.605 1.4

Dose 2 0-7 14 12 2.28 1.00 - 5.22 0.049 9.7

0-21 14 12 2.19 0.98 - 4.97 0.057 9.4

Myocarditis/Myopericarditis (Pericarditis Excluded) in 18-39 

Year Olds: Moderna vs Pfizer

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Summary of Myocarditis/Pericarditis Analyses Days 0-7 after 

Dose 2 among 18-39 Year Olds: Moderna vs Pfizer

Includes 

Pericarditis

Sex Adjusted 

Rate 

Ratio1

95% 

Confidence 

Interval

2-sided

Pvalue

Excess Cases in Risk 

Period per 1M Doses 

of Moderna vs Pfizer 2

Yes Both Sex 2.72 1.25 - 6.05 0.012 13.3

Male 2.26 1.00 - 5.19 0.051 21.5

No Both Sex 2.28 1.00 - 5.22 0.049 9.7

Male 2.14 0.93 - 4.98 0.074 19.1

1Adjusted for VSD site, age, sex, race/ethnicity, and calendar date. Adjusted rate ratio is an estimate of the Moderna rate 

divided by Pfizer rate.

2Excess cases is an estimate of the Moderna rate minus the Pfizer rate. 

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• The VSD formally signaled for myocarditis/pericarditis 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.

̶ Pfizer results include 12–39-year-olds while Moderna only includes 18–39-year-olds.

• In subgroup analyses, both mRNA vaccines were associated with 

myocarditis/pericarditis in persons aged 12-39 years. 

Summary of Vaccinated Concurrent 

Comparators RCA Analyses 

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• Among 18–39-year-olds, rates of myocarditis/pericarditis after Moderna were significantly 

higher than after Pfizer during both the 0-21 and 0-7 day risk intervals. 

̶ Results were consistent when analyses excluded pericarditis. 

• Comparing Moderna vs Pfizer during the 0-7 days after dose 2, we estimated 13.3 excess 

cases of myocarditis/pericarditis per million doses.

• Among 18–39-year-olds, there were no clear clinical differences among 

myocarditis/pericarditis cases between Moderna and Pfizer recipients.

̶ Most had hospital length of stay 0-1 day.

̶ None were admitted to the ICU.

• Both mRNA vaccines were associated with increased risk of myocarditis/pericarditis for ages 

18-39 years, as was Pfizer for ages 12-17 years. Head-to-head comparisons provide evidence 

that the risk of myocarditis/pericarditis was higher after Moderna than after Pfizer. 

Summary of Head-to-Head Comparison of 

Moderna vs Pfizer

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• Kaiser Permanente Northern California:

• Laurie Aukes, Berwick Chan, Bruce Fireman, Kristin Goddard, Ned Lewis, Karen Nunley, Pat Ross, Arnold Yee, 

Ousseny Zerbo, Nandini Bahkshi

• Marshfield Clinic Research Institute:

• Jim Donahue, Ed Belongia, Tom Boyce, Kayla Hanson, Burney Kieke, Dave McClure, Erica Scotty

• CDC Immunization Safety Office:

• Eric Weintraub, Tat’Yana Kenigsberg, Mike McNeil, Jonathan Duffy, Frank Destefano, Tanya Myers, Tom 

Shimabukuro, Matt Oster

• 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

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