cdc.gov/coronavirus

COVID-19 Vaccine Safety Updates

Advisory Committee on Immunization Practices (ACIP)

Oct 21, 2021

Tom Shimabukuro, MD, MPH, MBA

Vaccine Safety Team

CDC COVID-19 Vaccine Task Force
Topics

 Overview of myocarditis following COVID-19 vaccination

 Update on the safety of Janssen COVID-19 Vaccine

 Safety of a Janssen COVID-19 primary vaccination followed by an 

additional mRNA COVID-19 vaccination

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Myocarditis and Myocarditis with Pericarditis 

(Myopericarditis) Following COVID-19 Vaccination
Myocarditis and myopericarditis following mRNA 

COVID-19 vaccination

 Evidence from multiple safety monitoring systems in multiple 

countries supports the finding of an increased risk of myocarditis 

and myopericarditis following mRNA COVID-19 vaccination*

• Risk:

‒ Highest in adolescents and young adults

‒ Males > females

‒ Following dose 2 > dose 1

• Onset clusters within a few days of vaccination, mostly within a week

• Cases have tended to be clinically mild

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* Gargano et al. Use of mRNA COVID-19 Vaccine After Reports of Myocarditis Among Vaccine Recipients: Update from the Advisory Committee on Immunization Practices — United States, June 2021. MMWR Morb Mortal Wkly Rep 

2021;70:977–982. 

Mallapaty S. Heart-inflammation risk from Pfizer COVID vaccine is very low. Nature. 2021 Oct 8. doi: 10.1038/d41586-021-02740-y. 

Myocarditis and pericarditis following vaccination with COVID-19 mRNA vaccines in Ontario. Available at: Myocarditis and Pericarditis Following Vaccination with COVID-19 mRNA Vaccines in Ontario: December 13, 2020 to August 7, 

2021 (publichealthontario.ca).

Comirnaty and Spikevax: possible link to very rare cases of myocarditis and pericarditis. Available at Comirnaty and Spikevax: possible link to very rare cases of myocarditis and pericarditis | European Medicines Agency (europa.eu).

Paterlini M. Covid-19: Sweden, Norway, and Finland suspend use of Moderna vaccine in young people "as a precaution". BMJ. 2021 Oct 11;375:n2477.
Myocarditis and myopericarditis following mRNA 

COVID-19 vaccination – presentation topics

 Highlights from:

• U.S. Food and Drug Administration (FDA) monitoring

• U.S. Department of Defense (DoD) monitoring

• Department of Veterans Affairs (VA)

• International surveillance

• CDC investigation of long-term effects of myocarditis

 Vaccine Adverse Event Reporting System (VAERS) and Vaccine Safety 

Datalink (VSD) updates on myocarditis and myopericarditis following mRNA 

COVID-19 vaccination will be provided separately during this safety session
https://www.fda.gov/media/153090/download 6
7 https://www.fda.gov/media/153090/download

Center for Biologics Evaluation 

and Research (CBER) 

Biologics Effectiveness and 

Safety (BEST) Initiative 
https://www.fda.gov/media/153090/download 8
• Military Health System continues to identify and follow patients with myocarditis 

following COVID-19 vaccination

• Overall rate of myocarditis within 7 days of vaccination is 10 cases per million doses, 

but risk is strongly dependent on patient age and sex, and vaccine dose and type; 

rate of myocarditis in younger (under age 20) males after 2nd dose mRNA vaccine is 

>100 cases per million doses

• Approximately two-thirds of patients report feeling fully recovered within 6 weeks of 

diagnosis; standard American College of Cardiology recommendations limit strenuous 

activity for 3-6 months; follow-up within Military Health System is ongoing

Slide courtesy Margaret Ryan MD, MPH, Defense Health Agency (DHA) 
Department of Veterans Affairs active surveillance

Rapid Cycle Analysis (RCA) for COVID-19 vaccines

• Weekly analysis comparing observed to expected number of prespecified 

outcomes from historical rates adjusting for sequential tests 

• Near-real time chart reviews for assessment of specific incident events

 Initial chart review to assess presumptive events

 Detailed chart review:

‒ Subject matter experts confirm outcomes through defined criteria

‒ Evaluates the timeframe of onset (i.e., within risk period)

Collaborators/Federal Partners – CDC, FDA, DOD

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Slides courtesy Fran Cunningham, Pharm D, Department of Veterans Affairs
Summary of VA RCA for myocarditis/pericarditis

• Vaccinated population 

 3.5 million Moderna doses administered (1.84 million dose 1, 1.70 million dose 2)

 3.1 million Pfizer-BioNTech doses administered (1.64 million dose 1, 1.46 million dose 2)

 Limited use of the Janssen vaccine in VA population (~270 thousand doses)

 89% male; 60% aged 65+ years old, with Janssen vaccinated cohort younger

• No statistical signals for myocarditis/pericarditis with any COVID-19 vaccine, although limited 

data available for Janssen vaccine 

• 7 chart confirmed myocarditis/myopericarditis cases

 6 in males and 1 in a female

 Median age 37 years (range 24-66 years)

 Median onset 3 days (range 1-18 days)

 Most after dose 2: Pfizer-BioNTech dose 2 (n=4) and dose 1 (n=1), Moderna dose 2 (n=2)

 Highest rate in 18-39-year-olds

 All cases clinically resolved

• Absence of myocarditis signal in VA data likely due to age differences in VA population

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Slides courtesy Fran Cunningham, Pharm D, Department of Veterans Affairs
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https://www.publichealthontario.ca/-/media/documents/ncov/epi/covid-19-

myocarditis-pericarditis-vaccines-epi.pdf?sc_lang=en

Mevorach et al. Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 

in Israel. N Engl J Med. 2021 Oct 6. doi: 10.1056/NEJMoa2109730.

Witberg et al. Myocarditis after Covid-19 Vaccination in a Large Health Care 

Organization. N Engl J Med. 2021 Oct 6. doi: 10.1056/NEJMoa2110737

Paterlini M. Covid-19: Sweden, Norway, and Finland suspend use of Moderna vaccine in young people "as 

a precaution". BMJ. 2021 Oct 11;375:n2477. 

https://www.ema.europa.eu/en/news/comirnaty-spikevax-possible-link-very-rare-cases-myocarditis-pericarditis
CDC enhanced surveillance for myocarditis outcomes after 

mRNA COVID-19 vaccination in VAERS case reports* 

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 Purpose: Assess functional status and clinical outcomes among 

individuals reported to have developed myocarditis after mRNA 

COVID-19 vaccination

 Methods: A two-component survey conducted at least 90 days after 

the onset of myocarditis symptoms

• Patient survey: Ascertains functional status, clinical symptoms, quality of 

life, and need for medication or other medical treatment 

• Healthcare provider (e.g., cardiologist): Gather data on cardiac health and 

functional status

 Timeline: data collection August 2021–November 2021 (anticipated)

* https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/myo-outcomes.html
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CDC enhanced surveillance for myocarditis outcomes after 

mRNA COVID-19 vaccination in VAERS case reports* (cont.) 

 As of August 2021, VAERS had received 826 reports of myocarditis or 

myopericarditis after COVID-19 vaccination that met case definition

 To date, around 680 patients have reached 90 days post-myocarditis diagnosis

• Of these, 282 (41%) have received at least one phone call

‒ Of the 282 patients who have received a call, 168 (60%) completed the 

survey and 67 (24%) were unreachable or declined to participate

 Of the 168 patients surveyed, 132 (79%) provided cardiologist or 

healthcare provider contact information

o Of the 132 cardiologist or healthcare providers, 26 have completed the survey 

o Remaining 106 in the process of being contacted

* https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/myo-outcomes.html
Update on the Safety of Janssen COVID-19 Vaccine
https://www.fda.gov/media/153132/download 16
https://www.fda.gov/media/153132/download 17
https://www.fda.gov/media/153132/download 18
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Existing safety 

concerns

Emerging 

potential 

safety 

concerns

https://www.fda.gov/mediaCDC/153132/download

https://www.bestinitiat

ive.org/wpcontent/uploads/2021/

01/C19-Vaccine-SafetyAESI-Background-RateProtocol-2020.pdf
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Vaccine Safety Datalink (VSD) Rapid Cycle Analysis 

(RCA) findings for Janssen COVID-19 vaccine

 VSD conducts RCA, which is near real-time sequential monitoring for 

prespecified surveillance outcomes of interest

 A relatively small number of Janssen COVID-19 vaccinations (~440 thousand) 

administered compared to mRNA COVID-19 vaccinations (~14 million)

 No statistical signals detected for any VSD RCA prespecified surveillance 

outcomes following Janssen COVID-19 vaccination in the 1–21-day risk interval

 Descriptive analysis indicates an imbalance of Guillain-Barré syndrome (GBS) 

cases following Janssen COVID-19 vaccination compared to mRNA COVID-19 

vaccination with proportionally more GBS cases being observed after Janssen 

COVID-19 vaccination 
21 https://emergency.cdc.gov/han/2021/han00442.asp

Thrombosis with thrombocytopenia syndrome (TTS)
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Reporting rates of confirmed TTS cases (N=47) in VAERS after Janssen 

COVID-19 vaccination (15.3 million doses administered as of Oct 13, 2021†)

Females (n=34) Males (n=13)

Age group

TTS

cases 

Doses

admin.

Reporting rate‡

(per million)

TTS

cases 

Dose 

admin.

Reporting rate‡

(per million)

18–29 yrs 4 1,130,467 3.5 3 1,640,147 1.8

30–39 yrs 11 1,079,231 10.2 2 1,517,490 1.3

40–49 yrs 9 1,145,500 7.9 4 1,450,634 2.8

50–64 yrs 8 2,053,566 3.9 4 2,405,659 1.7

65+ yrs 2 1,115,936 1.8 0 1,023,268 0

* Source of doses administered: https://covid.cdc.gov/covid-data-tracker/#vaccinations

† Reporting rate = TTS cases per 1 million Janssen COVID-19 vaccine doses administered

 Cases include 5 deaths related to complications from TTS following Janssen COVID-19 vaccination

• Median age 37 years (range 29–52 years); 4 of 5 female; all 5 had cerebral venous sinus thrombosis

• None received heparin; median platelet count nadir 15,000/μL (range 9,000-31,000/μL)

• Anti-PF4 antibody ELISA testing performed for 4 decedents, all positive with optical density values >2.0
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Summary of Janssen COVID-19 safety monitoring

 Existing safety concerns for Janssen COVID-19 vaccine

• Current evidence suggests a causal association for TTS, though the condition is rare 

(47 confirmed cases after 15.3 million Janssen COVID-19 vaccinations administered) 

‒ Most cases are in women, with most aged 18-49 years old

• Monitoring in VAERS and VSD suggest a possible association between Guillain-Barré 

syndrome and Janssen COVID-19 vaccination

 CDC, FDA, and federal partners will continue to assess emerging potential 

safety concerns (myocarditis/pericarditis, immune thrombocytopenia, 

thromboembolic events)
Safety of Janssen COVID-19 Primary Vaccination 

Followed by an Additional mRNA COVID-19 

Vaccine Dose: Vaccine Safety Datalink (VSD)
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VSD Rapid Cycle Analysis (RCA)

 VSD is monitoring the safety of COVID-19 vaccines weekly for prespecified 

outcomes of interest 

 As of October 16, 2021, approximately 14.3 million doses have been 

administered and around 7.2 million members are fully vaccinated

COVID-19 vaccine

combination

# of people 

fully vaccinated

Moderna + Moderna 2,711,487

Pfizer-BioNTech + Pfizer-BioNTech 4,026,967

Janssen one dose only 442,299

Janssen + mRNA dose 5,463

Janssen + mRNA dose 

(with a minimum of 60 days between doses) 3,662
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VSD demographics in persons with Janssen primary + additional 

mRNA vaccine dose with a minimum of 60 days between doses

n = 3,662

0

100

200

300

400

500

600

# Vaccinated

Age Group

 -

 500

 1,000

 1,500

 2,000

 2,500

Female Male

# Vaccinated

Sex
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VSD COVID-19 vaccine prespecified 

surveillance outcomes Settings Risk window

(days)

Exclude if 

COVID-19 in the 

prior X days

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

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

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

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

Appendicitis E, I 1-21, 1-42

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

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

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

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

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

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

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

Multisystem inflammatory syndrome in children/adults E, I 0-84

Myocarditis / pericarditis – First in 60 Days E, I 1-21, 1-42 30 days

Narcolepsy / cataplexy E, I, O 0-84

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

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

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

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

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

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

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

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

Abbreviations: E=ED, I=Inpatient, O=Outpatient
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VSD Rapid Cycle Analysis (RCA)

Prespecified

outcome (n=2)

Patient 

sex

Patient age 

in years

Interval b/w Janssen 

primary dose & subsequent

mRNA vaccination

Acute myocardial

infarction Male 50–64 125 days

Seizure Female 25–29 142 days

* Both were following a Pfizer-BioNTech vaccine dose

 Among the 3,662 persons who received a Janssen primary vaccination and 

a subsequent mRNA vaccination at a minimum interval of 60 days after the 

Janssen primary dose, 2 prespecified surveillance outcomes*were 

detected in the 1–42-day risk interval
VSD summary of heterologous dose safety

 Limited data are available on a Janssen primary vaccination 

followed by an additional mRNA COVID-19 vaccination at a 

minimum interval of 60 days after the Janssen primary vaccination

• There is a lack of evidence to date of a safety problem with 

respect to any of the prespecified VSD surveillance outcomes 

for this vaccination practice

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 Report adverse events following 

vaccination to VAERS even if you 

aren’t sure if the vaccination 

caused the adverse event

 Enroll yourself in v-safe

 Healthcare providers, encourage 

your patients to enroll in v-safe

 Parents and guardians, you can 

enroll your children in v-safe

What can you do for vaccine safety?

Please get involved, your participation matters

http://vaers.hhs.gov

vsafe.cdc.gov/en/
Acknowledgments

 VAERS Team

• VAERS TTS abstraction team

• VAERS Myopericarditis abstraction team

• VAERS data team

 Clinical Immunization Safety Assessment Project

 CDC team investigating long-term effects of myocarditis

 VSD Team, VSD participating sites, and investigators from Kaiser Permanente 

Northern California and the Marshfield Clinic Research Institute

 CDC COVID-19 Data Monitoring and Reporting Group

 FDA/Center for Biologics Evaluation and Research

 U.S. Department of Defense

 U.S. Department of Veterans Affairs

Thanks to the many people who made analysis of these data possible:

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Disclaimer

 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 (CDC)

 Mention of a product or company name is for identification 

purposes only and does not constitute endorsement by CDC

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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.

Thank you!

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