Table 1.
Summary of findings for incident rates after receipt of Pfizer or Moderna vaccine (question one)
| Sex | Age | Data source of study, date; country*† | Risk interval | Incidence rates per million doses after dose two of either mRNA vaccine, unless otherwise stated‡§¶ | Conclusions after vaccination | Certainty about conclusions using GRADE |
|---|---|---|---|---|---|---|
| Myocarditis (after dose two) | ||||||
| Male | 5-11 years | Vaccine Adverse Events Reporting System,* 19 December; US† | 7 days | 2.3 to 4.1¶ (Pfizer) | Incidence of myocarditis after Pfizer vaccine might be fewer than 20 cases per million | Low |
| Vaccine Adverse Events Reporting System,* 9 December; US† | 12 days | 2.98 (both sexes; Pfizer) | ||||
| Vaccine Safety Datalink, 30 December; US |
21 days | No events (both sexes; myocarditis or pericarditis; Pfizer) | ||||
| 12-17 years | Vaccine Adverse Events Reporting System,* June 18; US† | Any | 139.5‡ (Pfizer) | Incidence myocarditis after Pfizer vaccine might be between 50 and 139 cases per million | Low††,‡‡ | |
| COVaxON,* 4 September; Canada | 7 days | 88.1 (Pfizer) | ||||
| Vaccine Adverse Events Reporting System,* 6 October; US† | 7 days | 49.6‡ (Pfizer) | ||||
| 12-39 years | DVR/DPR, 5 October; Denmark | 14 days | 87.7§ | We are uncertain about incidence of myocarditis with an mRNA vaccine | Very low§§ | |
| 18-29 years | Singapore Military, 24 July; Singapore | Any | 71.4 | Incidence of myocarditis with an mRNA vaccine is probably between 28 to 147 cases per million | Moderate‡‡ | |
| COVaxON* September 4; Canada | 7 days | 147.2§ (18-24 years) | ||||
| Israel Defence Forces, 7 March; Israel, | 7days | 50.7 (Pfizer; 18-24 years) | ||||
| Moderna Global Safety Database,* 30 September; worldwide | 7 days | 27.9ঠ(Moderna; 18-24 years) | ||||
| Vaccine Adverse Events Reporting System,* 6 October; USA | 7 days | 27.8‡ | ||||
| Israel Ministry of Health, 31 May; Israel** | 30 days | 82.0ঠ(Pfizer) | ||||
| 18-39 years | Singapore Military, 24 July; Singapore | Any | 60.2‡ | Incidence of myocarditis with an mRNA vaccine might be between 25 and 80 cases per million | Low | |
| US Military, 30 April; US | 4 days (all cases) | 44 (median 25 years (IQR 20-51)) | ||||
| Moderna Global Safety Database,* 30 September; worldwide | 7 days | 25.4‡ (Moderna) | ||||
| COVaxON,* 4 September; Canada | 7 day | 82.2ठ| ||||
| 30-39 years | Vaccine Adverse Events Reporting System,* 6 October; US | 7 days | 5.7§¶ | We are uncertain about the incidence of myocarditis with an mRNA vaccine | Very low††,§§ | |
| Female | 5-11 years | Vaccine Adverse Events Reporting System,* 19 December; US† | 7 days | 0-1.8¶ (Pfizer) | Incidence of myocarditis with the Pfizer vaccine might be fewer than 20 cases per million | Low |
| Vaccine Adverse Events Reporting System,* 9 December; US† | 12 days | 2.98 (both sexes; Pfizer) | ||||
| Vaccine Safety Datalink, 30 December; US | 21 days | 2.3‡ (both sexes; myocarditis or pericarditis; Pfizer) | ||||
| 12-17 years | Vaccine Adverse Events Reporting System,* June 18; US† | Any | 13.1‡ (Pfizer) | We are uncertain if the incidence of myocarditis with the Pfizer vaccine is fewer than 20 cases per million | Very low†† | |
| COVaxON,* 4 September; Canada | 7 days | 9.7 (Pfizer) | ||||
| Vaccine Adverse Events Reporting System,* 6 October; US‡ | 7 days | 5.2‡ (Pfizer) | ||||
| 18-29 years | Vaccine Adverse Events Reporting System,* 6 October; US | 7 days | 3.8ঠ| Incidence of presenting with myocarditis with an mRNA vaccine might be fewer than 20 cases per million | Low | |
| Moderna Global Safety Database,* 30 September; worldwide | 7 days | 0ঠ(ages 18-24 years; Moderna) | ||||
| COVaxON,* 4 September; Canada | 7 days | 34.6§ | ||||
| Israel Ministry of Health, 31 May; Israel** | 30 days | 8.9ঠ(16-29 years; Pfizer) | ||||
| 18-39 years | COVaxON,* 4 September; Canada | 7 days | 22.8‡§ | We are uncertain about the incidence of myocarditis with an mRNA vaccine | Very low§§ | |
| Moderna Global Safety Database,* 30 September; worldwide | 7 days | 2.7‡ (Moderna) | ||||
| 30-39 years | Vaccine Adverse Events Reporting System,* 6 October; US | 7 days | 0.6§¶ | We are uncertain about the incidence of myocarditis with an mRNA vaccine | Very low††,§§ | |
| Myocarditis (after dose three) | ||||||
| Male | 13-39 years | NIMS/NHS, 15 November; UK | 28 days | 13¶ (Pfizer) 0 events/8856 (Moderna) |
We are uncertain about the incidence of myocarditis with mRNA vaccines | Very low§§,¶¶,*** |
| 7 days | 0§¶ | |||||
| ≥40 years | NIMS/NHS, 15 November; UK | 28 days | 3¶ (Pfizer) 0 events/143 066 (Moderna) |
Incidence of myocarditis with mRNA vaccines might be fewer than 20 cases per million | Low††† | |
| 7 days | 0§¶ | |||||
| Female | 13-39 years | NIMS/NHS, 15 November; UK | 28 days | 0§¶ | We are uncertain about the incidence of myocarditis with mRNA vaccines | Very low§§,¶¶ |
| 7 days | 0§¶ | |||||
| ≥40 years | NIMS/NHS, 15 November; UK | 28 days | 0§¶ | We are uncertain about the incidence of myocarditis with mRNA vaccines | Very low§§,¶¶ | |
| 7 days | 0§¶ | |||||
| Mayo Clinic, 17 October; US | 14d | 41.5§ | ||||
| Pericarditis | ||||||
| Male | 5-11 years | Vaccine Safety Datalink, 30 December; US | 21 days | 2.3 (both sexes; Pfizer) | We are uncertain about the incidence of pericarditis after vaccination with Pfizer | Very low§§,*** |
| Female | 5-11 years | Vaccine Safety Datalink, 30 December; US | 21 days | 2.3 (both sexes; Pfizer) | We are uncertain about the incidence of pericarditis after vaccination with Pfizer | Very low§§,*** |
Explanations for Grading of Recommendations, Assessment, Development and Evaluation (GRADE): in the plain language conclusions, we have used “probably,” “might be,” and “uncertain” to reflect level of certainty in the evidence based on GRADE of moderate, low, or very low, respectively. DPR=Danish National Patient Register; DVR=Danish Vaccination Register; IQR=interquartile range; NHS=National Health Services; NIMS=NHS Immunisation Management Service.
Passive surveillance.
Some overlap in cases with another source for this age group.
Weighted average across age groups.
Weighted average across vaccine products.
Excess incidence.
Crude incident rates were converted to excess incidence rates using the estimated adjusted incidence rate ratios (aIRRs) from the study (excess=crude incidence – (crude incidence÷aIRR); for men: 16-19 years, aIRR 8.96 (95% confidence interval 4.50 to 17.83); 20-24 years, 6.13 (3.16 to 11.88); 25-29 years, 3.58 (1.82 to 7.01); for women: 16-19 years, 2.95 (0.42 to 20.91), 20-24 years, 7.56 (1.47 to 38.96), 25-29 years, 0 (only one event).
Rated down for potential risk of bias because all data from passive reporting systems. Incidence rates might be underestimated.
Rated up for estimated incidence likely to be more than twice our clinically important threshold of 20 cases per million, highly unlikely to be seen by chance and credible to be higher than for other age categories.24
Rated down for inconsistency for only one study or for a large incidence range within one category for age or sex.
Rated down for all contributing studies as being at high risk of bias.
Rated down for indirectness of findings to entire population, based on large differences in estimates in analyses for male individuals across age groups indicating one estimate (or even a range of estimates) for all ages (for both sexes or male patients) is not credible.
All contributing studies rated at high risk of bias, however potential biases unlikely to change conclusion so did not rate down.