Features of Inflammatory Heart Reactions Following mRNA COVID-19 Vaccination at a Global Level

Abstract

Myocarditis and pericarditis may constitute adverse reactions of mRNA coronavirus disease 2019 (COVID-19) vaccines. This study aimed to document these reactions and to assess the association with patient sex and age. This is as an observational retrospective study using a case-non-case design (also called disproportionality study) on inflammatory heart reactions reported with mRNA COVID-19 vaccines within the World Health Organization (WHO) global safety database (VigiBase), up to June 30, 2021. Results are expressed using reporting odds ratios (RORs) and their 95% confidence interval (95% CI). Of 716,576 reports related to mRNA COVID-19 vaccines, 2,277 were cases of inflammatory heart reactions, including 1241 (55%) myocarditis and 851 (37%) pericarditis. The main age group was 18-29 years (704, 31%), and mostly male patients (1,555, 68%). Pericarditis onset was delayed compared with myocarditis with a median time to onset of 8 (3-21) vs. 3 (2-6) days, respectively (P = 0.001). Regarding myocarditis, an important disproportionate reporting was observed in adolescents (ROR, 22.3, 95% CI 19.2-25.9) and in 18-29 years old (ROR, 6.6, 95% CI 5.9-7.5) compared with older patients, as well as in male patients (ROR, 9.4, 95% CI 8.3-10.6). Reporting rate of myocarditis was increased in young adults and adolescents. Inflammatory heart reactions may rarely occur shortly following mRNA COVID-19 vaccination. Although an important disproportionate reporting of myocarditis was observed among adolescents and young adults, particularly in male patients, reporting rates support a very rare risk, that does not seem to compromise the largely positive benefit-risk balance of these vaccines. Furthermore, this study confirmed the value of disproportionality analyses for estimation of relative risks among subgroups of patients.

Figure 1

Demographic features of inflammatory heart reactions after mRNA coronavirus disease 2019 (COVID‐19) vaccines reported in the World Health Organization (WHO) global safety database. (a) Sex distribution according to reaction type (myocarditis or pericarditis). (b) Reaction type (myocarditis or pericarditis) distribution according to age. (c) Sex distribution according to reaction type (myocarditis or pericarditis) and age. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 2

Time to onset according to the type of inflammatory heart reaction. The y‐axis represents the percentage of cases reported when “time to onset” was reported, corresponding to a total of 1,039 myocarditis and 740 pericarditis. Time to onset was earlier for myocarditis. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 3

Features of myocarditis reporting in the United States. (a) Myocarditis reporting rate as of June 2021 according to age. Vaccine recipients are defined as the total count of vaccinated people in the United States that had a complete vaccination scheme (i.e., received a second dose of a two‐dose vaccine scheme or one dose of a single‐dose vaccine scheme; see Table  S2 for detailed rates according to time). (b) Number of myocarditis cases per month according to reporting date and to reaction onset date. (c) Reported myocarditis cases and total number of people fully vaccinated according to the age group (12–17 years old, 18–29 years old, and over 30 years old). [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 4

Reporting odds ratios for myocarditis and pericarditis in mRNA coronavirus disease 2019 (COVID‐19) vaccine recipients according to sex and age within the World Health Organization (WHO) global safety database. (a) Myocarditis. (b) Pericarditis. Case–non‐case approach is similar to case–control method but for the purposes of pharmacovigilance studies. Disproportionality in adverse drug reaction reporting between groups is expressed using RORs and their 95% CI. ROR is a ratio similar in concept to the odds ratio in case‐control studies and corresponds to the exposure odds among reported cases of inflammatory heart disorders over the exposure odds among reported non‐cases. A lower bound of the 95% CI of the ROR over 1.0 suggests that inflammatory heart disorders are more frequently reported in COVID‐19 mRNA vaccine recipients specific group compared with control group. We performed the main analysis and a secondary analysis stratified according to age groups and sex. *Inflammatory heart disorder cases were individual case safety reports were retrieved using the high level terms “noninfectious myocarditis” and “noninfectious pericarditis” according to the Medical Dictionary for Regulatory Activities (MedDRA, https://www.meddra.org/), coded as reactions. Cases of myopericarditis have been considered as myocarditis. **Non‐cases were reports containing any other reaction. ROR, reporting odds‐ratio; 95% CI, 95% confidence interval. [Colour figure can be viewed at wileyonlinelibrary.com]