Risk of Coronavirus Disease 2019 Messenger RNA Vaccination-Associated Myocarditis and Pericarditis – A Systematic Review of Population-Based Data

Figures & data

Table 1 Characteristics of Seventeen Population-Based Studies Included for the Comparison of the Sex- and Age-Specific Incidence of Myocarditis and/or Pericarditis Following mRNA COVID-19 Vaccinations

Study	Study Period	Study Population	Data Source	Number of Individuals Receiving Two Doses of mRNA Vaccination	Data Collection	Myocarditis/Pericarditis	Case Ascertainment	Criteria	Observational Period After Vaccination	Number of Cases	Stratum with the Highest Incidence (per Million Doses)
Australia^Citation17	2021/3/1-2022/11/13	Recipients aged 5 years or older received a total of 44.3 million doses of BNT vaccines and 5.4 million doses of Moderna vaccines	Safety reports from Australian Department of Health	NA	Passive surveillance	Myocarditis and pericarditis	Reports were reviewed against an internationally accepted criteria	NA	NA	BNT 706; Moderna 116	Male, 2nd dose, Moderna, age 12–17: 236
Canada, Ontario^Citation9	2020/12/14- 2021/9/4 (primary analysis on those vaccinated on or after 2021/6/1)	All individuals in Ontario, Canada (population 14.7 million) aged 12 years or older who received at least one dose of COVID-19 mRNA vaccine (total 19.74 million doses)	The Public Health Case and Contact Management Solution and Ontario’s electronic reporting system for COVID-19 Adverse Events Following Immunization to identify reports of myocarditis and pericarditis following COVID-19 vaccination submitted to local Public Health Units	BNT 5.83 million; Moderna 3.21 million	Passive surveillance 2020/12-2021/5; Enhanced surveillance 2021/6/1-	Myocarditis and. pericarditis	Case level review of all reports was completed by a group of specialized nurses and physicians on the vaccine safety team	Brighton criteria of definite, probable, and possible cases	No restriction on time to onset	BNT 159; Moderna 138	Male, 2nd dose, Moderna, age 18–24: 299.5
Canada, nationwide^Citation18	2020/12-2021/10/8	9.20 million individuals aged 18–39 years received at least one dose of mRNA COVID-19 vaccines	Reports of myocarditis and pericarditis submitted to the Canadian Adverse Events Following Immunization Surveillance System (CAEFISS) by provincial/ territorial/federal public health authorities received from their local or regional public health units	BNT 53.24 million; Moderna 28.05 million	Active and passive surveillance	Myocarditis and pericarditis	Cases were reviewed and verified by public health nurses and physicians at public health organizations, and underwent additional medical review after submission to CAEFISS	Brighton criteria of definite, probable, and possible cases	7 days for both vaccine doses	BNT 143; Moderna 229	Male, 2nd dose, Moderna, age 18–29: 139.5
Canada, British Columbia^Citation19	2020/12/15- 2022/3/10	3.99 million individuals aged 12 years or older received at least one dose of mRNA COVID-19 vaccines	Population health administrative data from the BC COVID-19 Cohort	NA	Active surveillance	Myocarditis	NA	NA	7 days and 21 days for both vaccine dose	BNT 84; Moderna 57	Male, 2nd dose, Moderna, age 18–29: 229.7 (21 days of observational period)
Denmark, Nygaard et al^Citation20	2021/5/15 – 2021/8/15	A total of 133,477 male and 127,857 female Danish inhabitants 12–17 years of age who received the first dose of BNT vaccine	A multicenter study including all 18 Danish Pediatric Departments for prospective real-time data collection of vaccine-associated disease from May 15, 2021. Cases of myopericarditis were cross checked with the Danish VAERS	NA	Active surveillance	Myocarditis and pericarditis	NA	NA	No restriction on time to onset	BNT 15	Male, 1st dose, BNT, age 12–17: 97
Denmark, Husby et al^Citation12	2020/10/1-2021/10/5	4.93 million of residents aged 12 years or older; excluding individuals with prior hospital diagnosis of myocarditis or pericarditis between 2017/1/1-2020/9/30	Danish Vaccination Register, Danish National Patient Register, Register of Laboratory Results for Research	BNT 3.42 million; Moderna 0.48 million	Active surveillance	Myocarditis	Co-occurrence of increased troponin and hospital stay more than 24 hours	NA	28 days for both vaccine doses	BNT 48; Moderna 21	Male, 2nd dose, Moderna, age 12–39: 94
Nordic countries^Citation21	2020/12/27-2021/10/5	23.1 million residents aged 12 years or older in Denmark, Finland, Norway, and Sweden	Nationwide health registers on SARS-CoV-2 vaccination, myocarditis and pericarditis diagnoses in Denmark, Finland, Norway, and Sweden	BNT 13.32 million; Moderna 1.96 million	Active surveillance	Myocarditis and pericarditis	NA	NA	28 days for both vaccine doses	BNT 220; Moderna 75	Male, 2nd dose, Moderna, age 16–24: 198.1
France^Citation22	2020/12/27-2021/09/20	44.18 million individuals aged 12 years or older received at least one dose of mRNA COVID-19 vaccines	Reports of myocarditis submitted to the regional pharmacovigilance centers (CRPV) of Bordeaux, Marseille, Toulouse, and Strasbourg	BNT 34.09 million; Moderna 4.77 million	Passive surveillance	Myocarditis	Reviewed and analyzed by the CRPVs	NA	NA	BNT 377; Moderna 106	Male, 2nd dose, Moderna, age 16–24: 138.9
Hong Kong^Citation11	2021/6/14-2021/9/4	178,163 individuals aged 12–27 years (51.8% of the population) received at least one dose of the BNT vaccine (total 305,406 doses)	Reports of myocarditis/pericarditis cases admitted to one of the public funded hospitals through the Advanced Incident Reporting System to the Drug Office of the Department of Health Hong Kong	NA	Active surveillance	Myocarditis and pericarditis	Suspected cases were investigated according to the Hong Kong Pediatric Investigation Protocol, which was implemented in all HA hospitals. The study team followed the myocarditis and pericarditis case definitions	Brighton criteria of definite, probable, and possible cases	14 and 28 days for both vaccine doses	BNT 33	Male, 2nd dose, Moderna, age 12–17: 388.8 (28 days of observational period)
Israel^Citation7	2020/12/20-2021/5/31	9.29 million of residents aged 16 years or older	Data received by the Ministry of Health about all hospitalizations on subjects aged ≥16 years where myocarditis was the primary reason for admission.	BNT 5.13 million	Passive surveillance 2020/12-2021/1; Active surveillance 2021/2-	Myocarditis	Hospital records were reviewed by cardiologist/rheumatologist	Brighton criteria of definite and probable cases	21 days for both vaccine doses	BNT 136	Male, 2nd dose, BNT, age 16–19: 150.7
Israel, adolescent^Citation24	2021/6/2-2021/10/20	Adolescents aged 12–15 years	Data received by the Ministry of Health about all hospitalizations on subjects aged 12–15 years where myocarditis was the primary reason for admission	BNT 0.33 million	Active surveillance	Myocarditis	Medical records were reviewed by cardiologist/rheumatologist	Brighton criteria of definite and probable cases	21 days for both vaccine doses	BNT 13	Male, 2nd dose, BNT, age 12–15: 80.9
Japan, MHLW^Citation25	2021/2/17-2022/7/10	100.88 million residents aged 10 years or older received at least one dose of mRNA COVID-19 vaccines	Reports of suspected adverse reactions from vaccine marketing authorisation holders to the Pharmaceuticals and Medical Devices Agency under the Ministry of Health, Labour and Welfare (MHLW)	BNT 83.61 million; Moderna 16.10 million	Passive surveillance	Myocarditis and pericarditis	Additional investigations and causality assessments, and reports evaluation were conducted by the Pharmaceuticals and Medical Devices Agency.	NA	No restriction on time to onset	BNT 486; Moderna 332	Male, 2nd dose, Moderna, age 10–14: 154.8
Japan, Yamaguchi et al^Citation26	2021/2/17-2022/5/15	102.21 million residents aged 12 years or older received at least one dose of mRNA COVID-19 vaccines	Reports of suspected adverse reactions from vaccine marketing authorisation holders to the Pharmaceuticals and Medical Devices Agency under the Ministry of Health, Labour and Welfare	BNT 85.81 million; Moderna 16.40 million	Passive surveillance	Myocarditis	Additional investigations and causality assessments, and reports evaluation were conducted by the Pharmaceuticals and Medical Devices Agency	NA	28 days for both vaccine doses	BNT 394; Moderna 251	Male, 2nd dose, Moderna, age 15–19: 129.6
Taiwan^Citation27	2021/3/22-2022/2/9	19.8 million of individuals aged 12 years or above who received at least one dose of COVID-19 mRNA vaccines	Reports of myocarditis to the Vaccine Adverse Event Reporting System in Taiwan	BNT 5.50 million; Moderna 3.57 million	Passive surveillance	Myocarditis and. pericarditis	Hospital records were reviewed by clinical pharmacists	Brighton criteria of definite, probable, and possible cases	No restriction on time to onset	BNT 160; Moderna 44	Male, 2nd dose, BNT, age 12–17: 122.9
United States, VAERS^Citation8	2020/12/14-2021/8/31	192.41 million individuals aged 12 years or older received at least one dose of mRNA COVID-19 vaccines	Reports of myocarditis to the US Vaccine Adverse Event Reporting System (VAERS)	BNT 95.53 million; Moderna 66.16 million	Passive surveillance	Myocarditis	Reviewed by CDC physicians and public health professionals	US CDC criteria of confirmed and probable cases	No restriction on time to onset	BNT 1136; Moderna 490	Male, 2nd dose, BNT, age 16–17: 105.9 (7 days of observational period)
United States, claims databases^Citation28	2020/12/18-2021/12/25	15.1 million individuals aged 18–64 years who received at least one dose of a COVID-19 mRNA vaccine in four claims databases in the US	Four administrative claims databases in the US (Optum, HealthCore, Blue Health Intelligence, and CVS Health)	NA	Active surveillance	Myocarditis and pericarditis	NA	NA	No restriction on time to onset	BNT/ Moderna 411	Male, 2nd dose, Moderna, age 18–25: 142.0 (1–7 days after an mRNA vaccination.)
United States, VSD^Citation29	2020/12/14-2022/1/15	Members aged 18–39 years of eight integrated healthcare organizations within the Vaccine Safety Datalink (VSD) and vaccinated with either mRNA vaccine.	The electronic health records and medical or pharmacy claims data from eight VSD data-contributing sites for capture of vaccination records along with comprehensive data on demographics, comorbidities, and healthcare utilization	BNT 1.41 million; Moderna 0.88 million	Active surveillance	Myocarditis and pericarditis	All identified potential cases underwent medical record review	US CDC criteria of confirmed and probable cases	7 days for both vaccine doses	BNT 41; Moderna 38	NA

Table 2 Number of Cases, Proportion of Myocarditis with or without Pericarditis, Definite or Probable Cases, Cases Occurring 0–7 Days After Vaccination Over Total Cases Among Seventeen Population-Based Studies

Study	Proportion of Myocarditis with or without Pericarditis Over Total Cases	Proportion of Definite or Probable Cases Over Total Cases	Proportion of Cases 0–7 Days After Vaccination Over Total Cases
Australia, aged ≥12 years^Citation17	40.6%	78.8%	NA
Canada, Ontario, aged ≥12 years^Citation9	71.4%	96.7%	73.9%
Canada, nationwide, aged 18–39 years^Citation18	NA	93.2%	60.6%
Canada, British Columbia, aged ≥12 years^Citation19	45.8%	NA	70.2%
Denmark, Nygaard et al, aged 12–17 years^Citation20	80.0%	NA	73.3%
Denmark, Husby et al, aged ≥12 years^Citation12	NA	NA	NA%
Nordic countries, aged ≥12 years^Citation21	60.9%	NA	NA
France, aged ≥12 years^Citation22	NA	NA	NA
Hong Kong, aged 12–27 years^Citation11	93.9%	97.0%	87.9%
Israel, aged ≥16 years^Citation7	NA	90.1%	74.3%
Israel, adolescent, aged 12–15 years^Citation24	NA	NA	NA
Japan, MHLW, aged ≥10 years^Citation25	81.3%	NA	89.7%
Japan, Yamaguchi et al, aged ≥12 years^Citation26	75.1%	NA	NA
Taiwan, aged ≥12 years^Citation27	80.4%	NA	69.1%
United States, VAERS, aged ≥12 years^Citation8	74.4%	81.7%	87.3%
United States, claims databases, aged 18–64 years^Citation28	NA	NA	NA
United States, VSD, aged 18–39 years^Citation29	87.3%	83.2%	NA

Figure 1 Reported rates of myocarditis (per million persons) at 0–7 days after the first and second doses of BNT162b2 (BNT) and mRNA-1273 (Moderna) vaccine according to sex and age group.

Notes: Studies from Hong Kong, Nordics, Taiwan, the US, and Japan reported absolute risks of myocarditis (including myopericarditis but excluding pericarditis alone) at 0–7 days after the first and second doses of BNT162b2 (BNT) and mRNA-1273 (Moderna) vaccine. Each risk stratum was marked with a corresponding color.

Figure 2 Reported rates of myocarditis (per million persons) at 0–21 or 28 days after the first and second doses of BNT162b2 (BNT) and mRNA-1273 (Moderna) vaccine according to sex and age group.

Notes: Studies from Israel, Taiwan, and Japan reported absolute risks of myocarditis (including myopericarditis but excluding pericarditis alone) at 0–21 days after the first and second doses of BNT162b2 (BNT) and mRNA-1273 (Moderna) vaccine. Studies form Hong Kong and Nordics reported the risk at 0–28 days. Each risk stratum was marked with a corresponding color. **The observation period after vaccination was 28 days.

Figure 3 Reported rates of myocarditis (per million persons) without restriction on time after the first and second doses of BNT162b2 (BNT) and mRNA-1273 (Moderna) vaccine according to sex and age group.

Notes: Studies from Ontario Canada, Australia, Taiwan, Japan, and France reported absolute risks of myocarditis (including myopericarditis but excluding pericarditis alone) without restriction on time after the first and second doses of BNT162b2 (BNT) and mRNA-1273 (Moderna) vaccine. Each risk stratum was marked with a corresponding color.

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