Update on the risk of myocarditis and pericarditis with COVID-19 mRNA vaccines
20/12/2021
(a) EMA Pharmacovigilance Risk Assessment Committee (PRAC)
The Pharmacovigilance Risk Assessment Committee (PRAC), of the European Medicines Agency (EMA), at a meeting on 29 November to 2 December 2021, assessed the most recent data on known risk of myocarditis and pericarditis following vaccination with two mRNA-based COVID-19 vaccines – the Pfizer-BioNTech Comirnaty vaccine and the Spikevax vaccine (known previously as the Moderna vaccine). This review included two large European epidemiological studies. One study was conducted using data from the French national health system (EPI-PHARE), while the other was based on registry data from Nordic countries.
For the Comirnaty vaccine, the results of the French study indicated that, in a period of seven days after the second dose, there were approximately 0.26 extra cases of myocarditis per 100,000 vaccinated 12- to 29-year-old males, compared to unexposed persons. In the Nordic study, in a period of 28 days after the second dose, there were 0.57 extra cases of myocarditis per 100,000 vaccinated 16- to 24-year-old males, compared to unexposed persons.
In the case of Spikevax, the French study showed that in a period of seven days after the second dose there were approximately 1.3 extra cases of myocarditis per 100,000 vaccinated 12- to 29-year-old males, compared to unexposed persons. The Nordic study showed that in a period of 28 days after the second dose of Spikevax there were approximately 1.9 extra cases of myocarditis per 100,000 vaccinated 16- to 24-year-old males, compared to unexposed persons.
Based on the data reviewed, PRAC has determined that the overall risk for both of these conditions is “very rare,” meaning that up to one in 10,000 vaccinated people may be affected. Additionally, the data show that the increased risk of myocarditis after vaccination is highest in younger males. Myocarditis and pericarditis have occurred primarily within 14 days after vaccination, and have more often been observed after the second vaccination.
The EMA confirms that the benefits of all authorized COVID-19 vaccines continue to outweigh their risks, given the risk of COVID-19 illness and related complications, and given that scientific evidence shows that they reduce deaths and hospitalizations due to COVID-19.
Source: EMA. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 29 November – 2 December 2021 Available at: https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-riskassessment-committee-prac-29-november-2-december-2021
(b) Public Health Agency of Canada
On 3 December 2021, the Public Health Agency of Canada (PHAC) released updated guidance on the use of COVID-19 vaccines licensed in Canada in people 12 years of age and older, in the context of case reports of myocarditis and pericarditis following administration of COVID-19 mRNA vaccines. These recommendations are based on current scientific evidence and the expert opinion of the National Advisory Committee on Immunization (NACI). The updated recommendations include:
- The preferential use of a complete series of an mRNA COVID-19 vaccine over the use of viral vector COVID-19 vaccines in all authorized age groups.
- In order to further minimize the rare risk of myocarditis and/or pericarditis in individuals aged 12 to 29 years, use of the Pfizer-BioNTech Comirnaty COVID-19 vaccine (30 mcg) is recommended, rather than Moderna's Spikevax vaccine (100 mcg), to initiate or complete a primary vaccination series. The second dose of a primary series should be provided eight weeks after the first dose. It was noted that emerging evidence in adults suggests that a longer interval between the first and second dose of a primary series results in a stronger immune response and higher vaccine effectiveness. New data suggest that, for mRNA vaccines, longer intervals may also be associated with a lower risk of myocarditis and/or pericarditis in adolescents and young adults.
- Based on clinical judgment, the Moderna Spikevax vaccine (100 mcg) may be considered for adolescents and adults 12 to 29 years of age who are moderately to severely immunocompromised, given new evidence that Moderna’s Spikevax vaccine (100 mcg) may have a slightly higher vaccine effectiveness and may provide longer protection against infection and severe COVID-19 outcomes, compared to the Pfizer-BioNTech Comirnaty vaccine (30 mcg).
- Booster doses: For people 18 to 29 years of age who are eligible to receive a booster dose of an mRNA vaccine, the use of the Pfizer-BioNTech booster dose (30 mcg) may be provided at least six months after the completion of a primary vaccine series.
- Everyone who is offered an mRNA COVID-19 vaccine should be informed of the rare risk of experiencing myocarditis and/or pericarditis following vaccination.
For more information on these recommendations, see: Public Health Agency of Canada. Summary of the National Advisory Committee on Immunization (NACI) Rapid Response of December 3, 2021. Available at:
(c) UK Health Security Agency
On 29 November 2021, the UK Health Security Agency (UKHSA) published clinical guidance to support the detection and management of clinical cases of myocarditis and pericarditis associated with coronavirus (COVID-19) vaccination. It is a living document and will be reviewed and updated as further data become available.
UKHSA indicates that, as of 17 November 2021, the overall reporting rate across all age groups for myocarditis following vaccination with the Pfizer vaccine is 10 cases per million doses administered; for pericarditis, it is 7 cases per million doses administered. For Moderna, the overall reporting rate for myocarditis is 36 cases per million doses; for pericarditis, it is 21 cases per million doses. In people under 18 years of age, the reported rate for myocarditis and pericarditis is 10 cases per million doses (first or unknown dose) of the Pfizer vaccine, which is the recommended vaccine for use in this age group.
The following is a summary of the clinical recommendations:
- In pediatric patients recently vaccinated against COVID-19 (within the last 10 days), features of concern that may require further investigation include: significant chest pain (new onset and unexplained), tachycardia or tachypnea, dyspnea (new onset and unexplained), palpitations (new onset and unexplained), dizziness or syncope (new onset and unexplained), and general clinical concern.
In case of suspected myocarditis or pericarditis, initial investigations should include 12-lead electrocardiogram (ECG); inflammatory blood markers (C-reactive protein [CRP], full blood count [FBC], and erythrocyte sedimentation rate [ESR]); and troponin. In case of abnormal ECG or troponin, the pediatric cardiology team should be consulted on a further management plan, including cardiac imaging (echocardiogram, cardiac magnetic resonance imaging [MRI], and rhythm monitoring [Holter 24h, stress ECG]). - In individuals under the age of 40 who have recently been vaccinated against COVID-19 (within 10 days), features of concern that may require further investigation include: significant chest pain (new onset and unexplained), tachycardia or tachypnea, dyspnea (new onset and unexplained), palpitations (new onset and unexplained), dizziness or syncope (new onset and unexplained), and general clinical concern.
In the case of suspected myocarditis or pericarditis, initial investigations should include: 12-lead ECG and inflammatory blood markers (CRP, FBC, and ESR), and troponin. In the case of abnormal ECG or troponin, the cardiology team should be consulted on a further management plan, which may include cardiac imaging (echocardiogram, cardiac MRI) and rhythm monitoring (Holter 24h, stress ECG).
- Further follow-up: Patients that did not require referral to hospital on initial presentation or who have normal initial investigations do not require further follow-up.
All patients that did not require initial hospital care should be advised to seek medical attention if symptoms persist or worsen within 5 days.
Patients requiring outpatient follow-up should be referred to cardiology and an assessment undertaken within 4 weeks.
For more information on this guidance, see: UK Health Security Agency. Guidance: Myocarditis and pericarditis after COVID-19 vaccination: clinical management guidance for healthcare professionals. 29 Nov 2021. Available at:
https://www.gov.uk/government/publications/myocarditis-and-pericarditis-after-covid-19-vaccination/myocarditis-andpericarditis-after-covid-19-vaccination-guidance-for-healthcare-professionals