cdc.gov/coronavirus

Myocarditis and COVID-19 

Vaccine Intervals: 

International Data and Policies

Danielle Moulia, MPH

ACIP Meeting

February 4, 2021
Discussion background and framework

 Goal: Examine international data and policies on preferential 

recommendations of an mRNA vaccine product or extended primary series 

intervals as they relate to myocarditis and/or pericarditis* 

Discussion framework

 International data on risk of myocarditis by mRNA vaccine product, focusing 

on the highest risk group – young males post dose 2

 International data on extended primary series interval: risk of myocarditis 

and vaccine effectiveness 

 International policies and recommendations

* Myocarditis and/or pericarditis will be referred to generally as “myocarditis,” unless a specific study is being referenced. 
International Data on Risk of Myocarditis 

by mRNA Product
US: Summary of findings

 VAERS: National, passive surveillance

 Among males ages 18–24 years, the myocarditis* reporting rate after a 

second dose of Moderna was 40 per million

 VSD: Nine integrated healthcare organizations, active surveillance

 Among males ages 18–39 years, the myocarditis/pericarditis** rate after a 

second dose of Moderna was 1.5x (aRR‡: 1.5 [0.86–2.61]) than Pfizer

*As of January 13th, 2022; CDC case definition; 7-day risk period; **As of January 15th, 2022; CDC case definition, 7-day risk period

‡Adjusted for VSD site, age, sex, race/ethnicity, and calendar date

VAERS: Vaccine Adverse Events Reporting System VSD: Vaccine Safety Datalink

Source: Su J. Myopericarditis following mRNA COVID-19 vaccination: Updates from the Vaccine Adverse Event Reporting System (VAERS). Slides presented to ACIP WG Dec 17, 2020.

Klein, N. Myocarditis Analyses in the Vaccine Safety Datalink: Rapid Cycle Analyses and “Head-to-Head” Product Comparisons. Slides.
Canada: Summary of findings

 Abraham et al. CAEFISS, passive and enhanced surveillance data

 Among males ages 18–29 years the myocarditis/pericarditis* reporting rate 

after a second dose of Moderna (140 per million doses) was ~5x (aRR‡: 4.73 

[3.19–7.20]) higher than Pfizer (25 per million doses)

 Buchan et al. Ontario, period of enhanced passive surveillance

 Among males ages 18–24 years, the myocarditis/pericarditis** reporting rate 

after a second dose Moderna (300 per million doses) was ~5x higher than 

Pfizer (59 per million doses)

*From December 1, 2020 to October 8,2021; Myocarditis/pericarditis meeting level 1-4 of the Brighton Collaboration case definition, 7 day risk period ** From December 14, 2020 to 

September 4, 2021, myocarditis/pericarditis meeting level 1-4 of the Brighton Collaboration case definition, study length risk period; ‡Poisson model conditioned by week 

CAEFISS: Canadian Adverse Events Following Immunization Surveillance System

Source: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3988612. Accessed 1/23/2022

https://www.medrxiv.org/content/10.1101/2021.12.02.21267156v1.article-metrics. Accessed 1/23/2022
United Kingdom: Summary of findings

 Yellow Card reporting: Passive and active surveillance of adverse events

 Among persons ages 18–29 years, the myocarditis and pericarditis* reporting 

rate after a second dose of Moderna (71 per million doses) was ~2.5x higher 

than Pfizer (24 per million doses)

 Patone et al: Self-controlled case series of myocarditis** hospitalizations in the 

UK

 Among males ages <40 years, additional events of myocarditis after a second 

dose of Moderna (101 per million doses) was >8x than Pfizer (12 per million 

doses)

*As of January 19, 2022, reports of suspected myocarditis and pericarditis associated with COVID-19 vaccines ; ** As of November 15, 2021, inpatient admission or death due to 

primary and secondary ICD-10 of myocarditis, 28 day risk period

Source: https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting#yellow-card-reports. 

Accessed 1/22/2022. 

Patone M. 2021 MedRxiv preprint. https://www.medrxiv.org/content/10.1101/2021.12.23.21268276v1.full.pdf. Accessed 1/22/2022.
Nordic Countries: Nordic cohort, myocarditis results

 Presented to VaST on 1/10/2022

 All residents ages 12 years and older in Denmark, Finland, Norway, and 

Sweden (23.1M) from December 2020 – October 2022

 Inpatient care for myocarditis and pericarditis

 Within a 7-day risk period after either dose, the rate ratio of myocarditis 

for Moderna vaccine vs. an unvaccinated comparator was higher than 

Pfizer vaccine vs. an unvaccinated comparator

– The highest rate ratios observed were among those receiving a 

second dose of Moderna in a heterologous mRNA primary series 

VaST: Vaccine Technical Advisory Workgroup

Source: Hovi et al., Slides not publicly available.
Denmark: SARS-CoV-2 vaccination and myocarditis or 

myopericarditis: population-based cohort study

 Design: Retrospective cohort

 Period: October 2020 – October 2021

 Population: 5M persons living in Denmark ages ≥12 years

 Outcome: Hospital diagnosis of myocarditis or pericarditis, increased 

troponin levels, and a hospital stay lasting >24 hours, 28-day risk period

 Adjusted using: Cox proportional hazard model with covariates for age, 

sex, vaccine priority group, season, and clinical comorbidities

Source: Husby et al., SARS-CoV-2 vaccination and myocarditis or myopericarditis: population-based cohort study BMJ 2021; 375 :e068665 doi:10.1136/bmj-2021-068665
Denmark: SARS-CoV-2 vaccination and myocarditis or 

myopericarditis: population-based cohort study

Population Product Absolute Rate per 

100,000 doses

aHR, Unvaccinated 

Comparator 

12–39 years Pfizer, after any dose 1.6 (1.0 to 2.6) 1.48 (0.74 to 2.98)

Moderna, after any dose 5.7 (3.3 to 9.3) 5.24 (2.47 to 11.12)

Males, ≥12 

years

Pfizer, after any dose 1.5 (1.0 to 2.2) 0.82 (0.50 to 1.34)

Moderna, after any dose 6.3 (3.6 to 10.2) 3.22 (1.75 to 5.93)

Females, ≥12 

years

Pfizer, after any dose 1.3 (0.8 to 1.9) 3.73 (1.82 to 7.65)

Moderna, after any dose 2.0 (0.7 to 4.8) 6.33 (2.11 to 18.96)

Males, 12–39 

years

Pfizer, post dose 2 1.8 (0.8 to 3.4)* 1.54 (0.62 to 3.81)*

Moderna, post dose 2 9.4 (5.0 to 16.0)* 9.80 (4.20 to 22.84)*

*conducted as part of a post hoc analysis

aHR: Adjusted hazards ratio. Adjusted for age, sex, vaccine priority group, season, and clinical comorbidities.

Source: Husby et al., SARS-CoV-2 vaccination and myocarditis or myopericarditis: population-based cohort study. BMJ 2021; 375:e068665 doi:10.1136/bmj-2021-068665.
France and Germany: Summary of findings

 Germany: National, passive surveillance

 Among males ages 18–29 years, the myocarditis/pericarditis* 

reporting rate after any dose of Moderna (117 per million doses) 

was >2x higher than Pfizer (47 per million doses) 

 France: Regional, enhanced passive surveillance 

 Among males ages 18–24 years, the myocarditis** reporting rate 

after a second dose of Moderna (139 per million doses) was ~3x 

higher than Pfizer (43 per million doses) 

*As of September 30, 2021; all reports post mRNA vaccination; **As of September 20, 2021; all reports post mRNA vaccine

Source: https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2021/Ausgaben/46_21.pdf. Accessed 1/23/2022.

https://www.omedit-auvergne-rhone-alpes.ars.sante.fr/index.php/system/files/2021-10/ANSM_Rapport_CRPV_Moderna_22102021.pdf. Accessed 1/23/2022. 

https://ansm.sante.fr/uploads/2021/10/22/20211021-covid-19-vaccins-pfizer-focus-1-2.pdf. Accessed 1/23/2022.
Myocarditis rate ratios (Moderna vs. Pfizer) country, 

subgroup, and dose

Klein, USA, M 18–39y, post dose 2₽

Buchan, Canada-Ontario, M 18–24y, post dose 2*

France, M 18–24y, post dose 2*

Abraham, Canada, M 18–29y, post dose 2‡

Husby, Denmark, M 12–39y, post dose 2*

Rate Ratio

0 5 10 15 20

*Unadjusted rate ratio; ‡Adjusted with a Poisson model conditioned by calendar week of vaccine administration; ₽ Adjusted for VSD site, age, sex, race/ethnicity, and calendar date

Source. Husby et al., SARS-CoV-2 vaccination and myocarditis or myopericarditis: population-based cohort study. BMJ 2021; 375:e068665 doi:10.1136/bmj-2021-068665

https://ansm.sante.fr/uploads/2021/10/22/20211021-covid-19-vaccins-pfizer-focus-1-2.pdf. Accessed 1/23/2022.

Klein, N. Myocarditis Analyses in the Vaccine Safety Datalink: Rapid Cycle Analyses and “Head-to-Head” Product Comparisons. Slides.

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3988612. Accessed 1/23/2022

https://www.medrxiv.org/content/10.1101/2021.12.02.21267156v1.article-metrics. Accessed 1/23/2022
Summary of findings: Myocarditis risk by mRNA product

 Risk of myocarditis may be higher for Moderna than Pfizer vaccine

 Limitations: observational data; rates not readily comparable due to 

differences in:

– Case definition and risk interval length

– Subpopulations

– Case ascertainment

– Calendar time and vaccine implementation factors, including extended primary series intervals

 A limited number of geographic locations are administering both 

Moderna and Pfizer and had data available.
International Data on Risk of Myocarditis 

with an Extended Primary Series Interval 
Ontario, Canada: Myocarditis/pericarditis by interval

 Design: Retrospective, population-based cohort, using provincial vaccine registry 

and passive vaccine safety surveillance

 Period: December 14, 2020 to September 4, 2021

 Population: Adults ages ≥18 years receiving dose 2 on or after June 1, 2021 in 

Ontario; 19,740,741 doses of mRNA vaccines

 Outcome: Myocarditis/pericarditis meeting level 1–3 of the Brighton Collaboration 

case definition

 Analysis: Crude reporting rates; overall rate following dose 2 by product estimated 

using Poisson regression, adjusted for dose 1 product and interval

– Dosing intervals: ≤30 days (≤4 weeks), 31–55 days (5–7 weeks), ≥56 days (≥8 

weeks)

Source: Buchan S et al. Dec 2021, MedRxiv preprint.
Ontario, Canada: Reporting rate of myocarditis/pericarditis per million 

doses among males ages 18–24 years by vaccine product* and interval

Source: Buchan S et al. Dec 2021, MedRxiv preprint.

*Moderna-Pfizer not shown here because there were no reported events in males ages 18–24 years; a smaller number of males in this age group received this schedule (n=8,853).

0

200

400

600

800

1000

1200

1400

1600

1800

≤4 weeks 5-7 weeks ≥8 weeks ≤4 weeks 5-7 weeks ≥8 weeks ≤4 weeks 5-7 weeks ≥8 weeks

Pfizer—Pfizer Moderna—Moderna Pfizer—Moderna

Rate (95% CI) per million doses

Males ages 18-24 y n=235,819 n=93,616 n=85,893
Summary of data: Myocarditis risk with extended 

primary series interval

 Rates of myocarditis may be lower with extended primary 

series interval

 Reduced rates of myocarditis with extended interval were 

observed with Moderna and Pfizer vaccines 

Source: Buchan S. Dec 2021, MedRxiv preprint.
International Data on Vaccine Effectiveness 

with an Extended Primary Series Interval
British Columbia and Quebec, Canada: Vaccine 

effectiveness by primary series interval

 Design: Test-negative case-control design to estimate vaccine effectiveness

 Period: May 30 to October 2, 2021

 Population: Community-dwelling adults ages ≥18 years in British Columbia (BC) and 

Quebec, Canada; 1,235,447 specimens, including 44,673 test-positive cases and 

2,460 hospitalizations

 Outcome: Infections and hospitalizations due to SARS-CoV-2, confirmed by RT-PCR

 Analysis: Multivariable logistic regression to estimate odds ratios: 

– Adjusted for age group (18–49, 50–69, 70–79, ≥80 years); sex; epi week of the 

analysis period (weeks 22–39, categorical); and region of the province

– Dosing intervals: 3–4 weeks, 5–6 weeks, 7–8 weeks, 9–11 weeks, 12–15 weeks, 

16+ weeks

Source: Skowronski DM. 2021, MedRxiv preprint. 
85 85

91 91

88

91 91

93

97

99 98

95 94

98

50

55

60

65

70

75

80

85

90

95

100

0 2 4 6 8

British Columbia

VE against infection VE against hospitalization

British Columbia and Quebec, Canada: Vaccine 

effectiveness of any two doses of mRNA vaccines by 

primary series interval

Source: Skowronski DM. 2021, MedRxiv preprint. 

3–4w 5–6w 7–8w 9–11w 12–15w ≥16w ≥7w

Time between dose 1 and dose 2 (weeks)

Adjusted two dose VE (%: 95% CI)

VE against infection VE against Hospitalization

79

85

89 89 89 90 89

87

97 98 97 96 95

97

50

55

60

65

70

75

80

85

90

95

100

0 1 2 3 4 5 6 7 8

Quebec

3–4w 5–6w 7–8w 9–11w 12–15w ≥16w ≥7w

Time between dose 1 and dose 2 (weeks)
England: Serological responses and vaccine 

effectiveness by primary series interval

 Design: Test-negative case-control design to estimate vaccine effectiveness

 Period: October 2020 to June 2021

 Population: Symptomatic adults ages ≥50 years attending community testing (n=308,764 

unvaccinated persons; n=16,237 persons received Pfizer primary series vaccine); serological 

responses of 421 immunocompetent adults ages 50–89 years given two doses of Pfizer at 

different intervals

 Outcome: Testing SARS-CoV-2 positive by PCR through NHS, following COVID-19 compatible 

symptoms; serological responses 14–34 days post-dose 2

 Analysis: Logistic regression to estimate odds ratios by vaccination status

– Adjusted for a week of onset, age group, gender, region, index of multiple deprivation, ethnicity, 

health/social care worker, care home resident, flagged as clinically at extremely increased risk for COVID19 illness, and flagged as extended risk groups among adults ages <65 years 

– Dosing intervals: 3–4, 5–6, 7–8, 9–12 and >12 weeks

Source: Amirthalingam G. 2021, Nat Commun.
 Pfizer vaccine 

effectiveness against 

symptomatic SARSCoV-2 infection was 

higher with an 

extended interval (>6 

weeks) compared to a 

standard interval (3–4 

weeks) for all age 

groups.

Source: Amirthalingam G. 2021, Nat Commun.

Age: ≥80 ≤Jan4 | ≥80 >Jan 4 | 65–79 | 50–64

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

Post Dose 2 Vaccine Effectiveness (95% CI)

3-4 9-12 | 3-4 9-12 >12 | 3-4 7-8 9-12 >12 | 3-4 5-6 7-8 9-12 >12 

Interval between Dose 1 and 2 (weeks)

England: 

Pfizer vaccine 

effectiveness by 

primary series 

interval
Summary: Immunogenicity with extended primary 

series interval

 Payne et al. (UK ): Among SARS-CoV-2 infection naïve persons in an observational 

cohort, serological responses were higher after an extended dosing interval (6–14 

week) compared to a standard interval (3–4 week).

– Among persons with an extended interval, there were higher antibody and B 

cell responses, as well as sustained B and T cell responses, compared to a 

standard interval. 

– An extended interval may promote efficient T cell expansion and long-term 

memory cell persistence.

 Amirthalingam et al. (England), Parry et al. (England), & Grunau et al (Canada): 

Neutralizing antibody titers were higher following an extended dosing interval with 

mRNA vaccine, compared to a standard interval.

Source: Payne R. 2021, Cell.; Amirthalingam G. 2021, Nat Commun.; Parry H. 2022, Npj Vaccines.; Grunau B. 2022, Clin Inf Dis.
Summary of data: Vaccine effectiveness with extended 

primary series interval

 Extended primary series interval may improve immunogenicity and 

vaccine effectiveness.

– Neutralizing antibody titers were higher following an extended dosing interval 

(6–14 week) with mRNA vaccine, compared to a standard interval (3–4 week). 1-4

– mRNA vaccine effectiveness against infection and hospitalization was 5–10% 

higher with an extended interval (7–8 weeks vs. 3–4 weeks). 5

 Limitation: Data collected prior to Omicron surge 

1 Payne R. 2021, Cell.

2 Grunau B. 2022, Clin Infect Dis.

3 Amirthalingam G. 2021, Nat Commun

4 Parry H. 2022, Npj Vaccines

5 Skowronski DM. 2021, MedRxiv preprint. 
International Policies and 

Recommendations
Canada

 NACI strongly recommends a complete mRNA COVID-19 

vaccine series for persons ages ≥12 years. 

– Ages 12–29 years: Pfizer is preferred for the primary series.

– Ages 18–20 years: Pfizer may be preferred for a booster.

mRNA vaccine product Immunization 

schedule

Minimum 

interval

Authorized 

interval Optimal interval

Pfizer-BioNTech 

Comirnaty 2-dose schedule 19 days 21 days 8 weeks

Moderna Spikevax 2-dose schedule 21 days 28 days 8 weeks

Source: National Advisory Committee on Immunization: Updated Guidance on the use of COVID-19 Vaccines. (slides)

https://www.canada.ca/en/public-health/services/diseases/coronavirus-disease-covid-19/vaccines/safety-side-effects.html#myocarditis-and-pericarditis. Accessed 1/23/2022

https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-26-covid-19-vaccine.html#a5.4. Accessed 2/1/2022.
United Kingdom

 Preferential recommendation for Pfizer in persons ages 12–17 

years

 Interval: at least 8 weeks 

– Ages 16–17 years, at higher risk*: at least 8 weeks

– Ages 16–17 years, not at high risk: 12 week

– Ages 12–15 years, higher risk of severe COVID-19: at least 8 weeks

– Ages 12–15 years, contact of immunosuppressed person: 8 weeks

– Ages 12–15 years, not high risk, no contacts: 12 weeks

*In a recognized clinical risk group (see table 3) and those who work in health and social care should receive two doses of vaccine at an interval of at least eight weeks. This includes those 

aged 16 to 17 years who expect to share living accommodation on most days (and therefore for whom continuing close contact is unavoidable) with individuals of any age who are 

immunosuppressed

Source: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1045852/Greenbook-chapter-14a-11Jan22.pdf. Accessed 1/22/2022 
Nordic countries

 Sweden: Pfizer is recommended for persons ages 12–30 years over Moderna.

 Interval: 3–4 weeks

 Norway: Pfizer should be offered to persons ages 12–30 years. Children and 

adolescents ages 5–15 years may receive 1 or 2 doses based on parents' decision; 

persons ages ≥ 16 years should receive 2 doses

 Interval: 3–12 weeks

– Persons ages 16–18 years: 8–12 weeks

– Children ages 5–15 years with severe underlying conditions: 8–12 weeks, but 

can be adapted down to 3 weeks based on medical assessment

Source: https://www.fhi.no/en/id/vaccines/coronavirus-immunisation-programme/coronavirus-vaccine/#vaccination-of-children-and-adolescents. Accessed 1/22/2022 

https://www.lakemedelsverket.se/en/coronavirus/covid-19-vaccine. Accessed 1/23/2022

https://thl.fi/en/web/infectious-diseases-and-vaccinations/what-s-new/coronavirus-covid-19-latest-updates/vaccines-and-coronavirus/getting-vaccinated-against-covid-19-how-why-and-whenhttps://www.sst.dk/en/English/Corona-eng/Vaccination-against-covid-19/COVID-19-vaccines-in-Denmark
Nordic Countries

 Finland: Boys and men ages 12–30 years only offered Pfizer. Girls and 

women ages >12 years are offered Pfizer or Moderna. 

 Interval: 6–12 weeks for persons ages ≥5 years

 Denmark: Both Pfizer and Moderna vaccines are approved for persons 

ages ≥12 years. 

 Interval: 3–6 weeks (median interval: 5 weeks)
Singapore and Taiwan

 Singapore: Children under age 18 years should receive Pfizer vaccine.

 Interval: At least 21 days; guidance notes myocarditis risk may decrease with 

a longer interval, but encourages a second dose at 21 days due to Omicron

 Taiwan: Both Pfizer and Moderna vaccines are approved for persons ages 

≥12 years. 

 Interval: At least 12 weeks 

Source: https://www.cdc.gov.tw/En/Bulletin/Detail/YPIDZwC4HjqBMtGi4jynHQ?typeid=158. Accessed 1/31/22

https://www.moh.gov.sg/covid-19/vaccination/faqs---children-related-vaccination-matters. Accessed 1/31/22
Australia

 Both Pfizer and Moderna vaccines are approved for persons ages 12 

years and older. 

 Interval: At least 3 weeks (Pfizer) or 4 weeks (Moderna)

– Children ages 5–11 years (Pfizer): 8 weeks 

• Can be shortened in special circumstances to a minimum of 3 

weeks, such as in an outbreak response, prior to the initiation 

of significant immunosuppression, or international travel

Source: https://www.health.gov.au/initiatives-and-programs/covid-19-vaccines/advice-for-providers/clinical-guidance/doses-and-administration. Accessed 1/30/2022.

https://www.health.gov.au/sites/default/files/documents/2021/12/atagi-recommendations-on-pfizer-covid-19-vaccine-use-in-children-aged-5-to-11-years_0.pdf. Accessed 1/30/2022.
France and Germany

 France: HAS recommends persons under the age of 30 years be 

given Pfizer over Moderna when available. 

 Interval: 6 weeks

 Germany: STIKO recommends persons under the age of 30 

years be given Pfizer over Moderna. 

 Interval: 3–6 weeks

HAS: Haute Autorité de Santé; STIKO: Standing Committee on Vaccination

Source: https://www.nitag-resource.org/sites/default/files/2021-12/48_21.pdf. Accessed 1/23/2022.

https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2021/46/Art_03.html. Accessed 1/23/2022.

https://www.reuters.com/business/healthcare-pharmaceuticals/french-health-authority-advises-against-moderna-covid-19-vaccine-under-30s-2021-11-09/. Accessed 1/23/2022.
Limitations

 Not a systematic review; data are biased toward findings that influenced 

national vaccine policy

 Limited number of countries are administering both Moderna and Pfizer

 Caution should be used when comparing myocarditis/pericarditis rates 

across studies as surveillance systems, case definitions and risk intervals, 

subpopulation age ranges, and vaccine implementation differ substantially

 National vaccine policies have evolved; some policies extending the primary 

series interval evolved from implementation strategies to reach the most 

people with a first dose
Conclusion

 Observational data suggest myocarditis/pericarditis may be associated with 

– Moderna vs. Pfizer in persons ages 18–29 years, especially males

– Shorter primary series interval

 Several countries have implemented policies or recommendations to 

lengthen the interval between doses (range: 6-12 weeks) in the primary 

series and/or preferentially recommend use of Pfizer among males and/or 

persons aged <30 years, which may mitigate the risk of 

myocarditis/pericarditis and improve vaccine effectiveness
Acknowledgements

 Katie Curran

 Sara Oliver

 Megan Wallace

 Monica Godfrey

 Amy Blain

 Amimah Asif

 Sarah Mbaeyi

 Evelyn Twentyman

 Tara Jatloui

 Susan Goldstein

 Jack Gersten

 Jefferson Jones

 Eddie Shanley

 Anthony Fiore

 Stephen Hadler 

 Valerie Morelli

 JoEllen Wolicki

 Elisha Hall

 Erin Ricketts

 Faisal Minhaj

 Heather Scobie

 VTF ACIP WG Team

 ACIP COVID-19 Vaccines Work Group

 Vaccine Task Force

 Epi Task Force

 Data Analytics and Visualization Task Force

 Respiratory Viruses Branch
For more information, contact CDC

1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.