Myocarditis and Pericarditis following COVID-19 Vaccination: Rapid Systematic Review of Incidence, Risk Factors, and Clinical Course

ObjectivesMyocarditis and pericarditis are adverse events of special interest after vaccination with mRNA vaccines. This rapid systematic review examined incidence rates of myocarditis and pericarditis after COVID-19 vaccination, and the presentation and clinical course of cases. DesignRapid systematic review Data sourcesMedline, Embase and the Cochrane Library were searched from October 2020 to October 6, 2021; reference lists and grey literature (to Oct 21, 2021). Review methodsRandomized controlled trials (RCTs) and large population-based/multisite observational studies and surveillance data reporting on myocarditis or pericarditis in people of any age after receiving any COVID-19 vaccine; systematic reviews of case series. A single reviewer completed screening and another verified 50% of exclusions, using a machine-learning program to prioritize records. A second reviewer verified all exclusions at full text, data extractions, and (for incidence) risk of bias assessments using Cochrane Risk of Bias 2.0 and Joanna Briggs Institute tools. Certainty of evidence ratings for incidence were based on team consensus using GRADE. Patient partners provided key messages from their interpretations of the findings. Results3457 titles/abstracts and 159 full texts were screened. For incidence rates we included 7 RCTs (n=3732 to 44,325) and 22 large observational studies/data sources using passive (n=10) and active (n=12) surveillance; for case presentation, we included 11 case series published as articles and three based on publicly available websites (n=12,636 cases). Mainly due to imprecision, the RCTs provided very low certainty evidence for incidence of myocarditis or pericarditis. From observational data, the incidence of myocarditis following mRNA vaccines is low but probably highest in males 12-17 years (55 [7-day risk] to 134 [30-day risk] cases per million; specific to Pfizer) and 18-29 years (40 [7-day risk] to 99 [21-30 day risk]) cases per million) (Moderate certainty evidence). Incidence is lower ( 90%) in their 20s, with a short symptom onset of 2 to 4 days after a second dose (71-100%). The majority of cases presented with chest pain/pressure and troponin elevation; a minority (<30%) had left ventricular dysfunction. Most were hospitalized ([≥]84%), without stays in intensive care units, for a short duration (2-4 d) and treated with anti-inflammatory and/or other supportive therapies. Almost all reports of death are from unverified cases and of unclear cause. Most cases of pericarditis were unconfirmed; for this outcome there appears to be more variation in age, sex, onset timing and rate of hospitalization. ConclusionsIncidence of myocarditis following mRNA vaccines is low but probably highest in males 12-29 years old. Existing evidence does not strongly support preference of one mRNA vaccine, even in young males. Continued active surveillance of myocarditis incidence out to 30 days from dosing is recommended with respect to i) new populations (i.e., children <12y), ii) third and subsequent doses, and iii) affected individuals receiving subsequent mRNA vaccine doses. Future research is needed to examine other risk factors and long-term effects. Funding and Registration noThis project was funded in part by the Canadian Institutes of Health Research (CIHR) through the COVID-19 Evidence Network to support Decision-making (COVID-END) at McMaster University. Not registered. O_TEXTBOXSummary boxO_ST_ABSWhat is already known about this topic?C_ST_ABSCase reports and surveillance signals of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the two-layered sac surrounding the heart) after COVID-19 vaccination appeared as early as April 2021. These have prompted ongoing surveillance and research of these complications to investigate their incidence, possible attribution to the vaccines, and clinical course. What this study addsThis review critically appraises and synthesizes the available evidence to-date on the incidence of myocarditis and pericarditis after COVID-19 vaccination in multiple countries. It summarizes the presentation and clinical course of over 12,000 reported cases. Though low, the incidence in young males 12-29 years of age is probably the highest and appears to be similar across mRNA vaccines. Most cases present with chest pain and are mild and self-limiting. Continued active surveillance is warranted especially with vaccine rollout to young children and use of third doses, and to learn of any long-term consequences. C_TEXTBOX