Incidence, risk factors, natural history, and hypothesised mechanisms of myocarditis and pericarditis following covid-19 vaccination: living evidence syntheses and review

Abstract

ObjectivesTo synthesise evidence on incidence rates and risk factors for myocarditis and pericarditis after use of mRNA vaccination against covid-19, clinical presentation, short term and longer term outcomes of cases, and proposed mechanisms.DesignLiving evidence syntheses and review.Data sourcesMedline, Embase, and the Cochrane Library were searched from 6 October 2020 to 10 January 2022; reference lists and grey literature (to 13 January 2021). One reviewer completed screening and another verified 50% of exclusions, using a machine learning program to prioritise records. A second reviewer verified all exclusions at full text, extracted data, and (for incidence and risk factors) risk of bias assessments using modified Joanna Briggs Institute tools. Team consensus determined certainty of evidence ratings for incidence and risk factors using GRADE (Grading of Recommendations, Assessment, Development and Evaluation).Eligibility criteria for selecting studiesLarge (>10 000 participants) or population based or multisite observational studies and surveillance data (incidence and risk factors) reporting on confirmed myocarditis or pericarditis after covid-19 mRNA vaccination; case series (n≥5, presentation, short term clinical course and longer term outcomes); opinions, letters, reviews, and primary studies focused on describing or supporting hypothesised mechanisms.Results46 studies were included (14 on incidence, seven on risk factors, 11 on characteristics and short term course, three on longer term outcomes, and 21 on mechanisms). Incidence of myocarditis after mRNA vaccines was highest in male adolescents and male young adults (age 12-17 years, range 50-139 cases per million (low certainty); 18-29 years, 28-147 per million (moderate certainty)). For girls and boys aged 5-11 years and women aged 18-29 years, incidence of myocarditis after vaccination with BNT162b2 (Pfizer/BioNTech) could be fewer than 20 cases per million (low certainty). Incidence after a third dose of an mRNA vaccine had very low certainty evidence. For individuals of 18-29 years, incidence of myocarditis is probably higher after vaccination with mRNA-1273 (Moderna) compared with Pfizer (moderate certainty). Among individuals aged 12-17, 18-29, or 18-39 years, incidence of myocarditis or pericarditis after dose two of an mRNA vaccine for covid-19 might be lower when administered ≥31 days compared with ≤30 days after dose one (low certainty). Data specific to men aged 18-29 years indicated that the dosing interval might need to increase to ≥56 days to substantially drop myocarditis or pericarditis incidence. For clinical course and short term outcomes, only one small case series (n=8) was found for 5-11 year olds. In adolescents and adults, most (>90%) myocarditis cases involved men of a median 20-30 years of age and with symptom onset two to four days after a second dose (71-100%). Most people were admitted to hospital (≥84%) for a short duration (two to four days). For pericarditis, data were limited but more variation than myocarditis has been reported in patient age, sex, onset timing, and rate of admission to hospital. Three case series with longer term (3 months; n=38) follow-up suggested persistent echocardiogram abnormalities, as well as ongoing symptoms or a need for drug treatments or restriction from activities in >50% of patients. Sixteen hypothesised mechanisms were described, with little direct supporting or refuting evidence.ConclusionsThese findings indicate that adolescent and young adult men are at the highest risk of myocarditis after mRNA vaccination. Use of a Pfizer vaccine over a Moderna vaccine and waiting for more than 30 days between doses might be preferred for this population. Incidence of myocarditis in children aged 5-11 years is very rare but certainty was low. Data for clinical risk factors were very limited. A clinical course of mRNA related myocarditis appeared to be benign, although longer term follow-up data were limited. Prospective studies with appropriate testing (eg, biopsy and tissue morphology) will enhance understanding of mechanism.

Single-cell sequencing of PBMC characterizes the altered transcriptomic landscape of classical monocytes in BNT162b2-induced myocarditis

“…Among multiple side effects of BNT162b2 vaccination, myocarditis in particular has been extensively investigated, yet its exact pathogenesis still remains unknown ( 44 ). Although several case studies have reported clinical changes in BNT162b2-MyoC patients, our understanding of BNT162b2-MyoC is still limited mainly due to scarcity of tissue sampling and lack of empirical evidence ( 45 ). Moreover, based on published literature reviews ( 46 , 47 ), among few empirical studies that were conducted with tissue samples from patients, there hasn’t been research that featured detailed transcriptomic profile of the harvested tissues.…”

Long covid and apheresis: a miracle cure sold on a hypothesis of hope

“…If you haven’t experienced myocarditis or pericarditis after vaccination, you might be reassured by data on its low incidence and its mild and self limiting nature (doi:10.1136/bmj-2021-069445). 18 Even though these risks don’t outweigh the benefits of vaccination (doi:10.1136/bmj.o1554),19 the risks loom larger if you’ve been affected by them.…”

Risk of Myocarditis after Covid-19 mRNA Vaccination: Impact of Booster Dose and Dosing Interval

“…Covid-19 mRNA vaccines have been shown to be associated with a short-term increased risk of myocarditis, with the highest risk observed after the second dose relative to the first. 1 The extent of the risk associated with more distant booster doses is less clear, with reports of a lower incidence relative to the second dose 2 or an increase with sequential doses. 3 Besides, it has been suggested that extending the timing between the first two doses could lower the risk of heart inflammation.…”

“…Extending our previous study 1 , we conducted a matched case-control study within the entire French population aged 12 or older, from the beginning of the Covid-19 vaccination campaign in December, 27, 2020 to January, 31, 2022.…”