An international consortium of researchers conducted the retrospective pharmacovigilance study with a comprehensive analysis of potential safety signals associated with myocarditis/pericarditis after the primary and up to three booster doses of mRNA anti-SARS-CoV-2 vaccines in different age groups, taking into account potential gender differences. Researchers examined reporting rates of myocarditis/pericarditis after mRNA anti-SARS-CoV-2 vaccination (BNT162b2, Pfizer-BioNTech and mRNA-1273, Moderna) in the Vaccine Adverse Events Reporting System (VAERS), the United States national passive surveillance system.
The etiology of myocarditis/pericarditis, the adverse event associated with mRNA anti-SARS-CoV-2 vaccine, remains unknown. Several pathological mechanisms have been suggested, such as the dysregulated hyperactivated immune response or the cross-reactivity between the spike protein and myocardial proteins. A previous study detected elevated circulating levels of free full-length SARS-CoV-2 spike protein in adolescents and young adults with myocarditis after mRNA vaccination. https://discovermednews.com/elevated-circulating-levels-of-free-full-length-spike-protein-not-bound-by-antibodies-in-adolescents-and-young-adults-with-myocarditis-after-sars-cov-2-mrna-vaccination/
Pharmacovigilance involves monitoring the safety of therapeutic products under real-world conditions after market authorization. In the case of immunization, it includes the detection, evaluation, understanding, prevention, and communication of adverse events following immunization (AEFIs). Established surveillance systems and vigilance by healthcare professionals enabled identification of safety signals for myocarditis/pericarditis associated with mRNA COVID-19 immunization.
About the study
Researchers conducted a retrospective pharmacovigilance study, analyzing reports of myocarditis/pericarditis in the VAERS, the United States national passive surveillance system. VAERS is jointly administered by the US Centers for Disease Control and the US Food and Drug Administration. It receives reports from various stakeholders, including vaccine manufacturers, vaccine recipients, healthcare providers, and military personnel.
Scientists examined data from the VAERS website from December 2020 to July 2022. This study expanded previous analyses and included data from younger individuals, children 5 to 11 years old, approved for vaccination in November 2021, and children between 6 months and 4 years old, approved for vaccination in June 2022 in the US.
During the study period, the analysis of VAERS data revealed 5154 reports of myocarditis/pericarditis after mRNA anti SARS-CoV-2 vaccination. The highest number of reports was for Pfizer/BioNTech vaccines, 3124 (60.6%), followed by Moderna with 1738 reports (33.7%) and Janssen with 204 reports (4%). In 24 reports (0.5%), the manufacturer name was missing.
Other vaccines had fewer reports of myocarditis/pericarditis, such as influenza vaccines (20 reports, 0.39%), varicella zoster vaccines (11 reports, 0.2%), smallpox vaccines (8 reports, 0.2%), meningococcal vaccines (7 reports, 0.1%), and pneumococcal vaccines (5 reports, 0.1%). The rest of the vaccines, such as human papillomavirus, anthrax, measles, mumps, rubella, varicella, rabies, hepatitis, Japanese encephalitis, typhoid, and yellow fever vaccines, had a total of 13 reports (0.3%).
The majority of myocarditis/pericarditis AEFIs reports following mRNA COVID-19 vaccines occurred after the primary series, with 3485 (87%) cases reported following the first or second doses. Notably, the second dose of the mRNA COVID-19 vaccines showed the strongest signals. In contrast, the number of reported myocarditis/pericarditis cases for the booster doses was lower, with only 495 (12%) cases reported after the third dose, and 23 (0.6%) cases following the fourth dose.
The most frequently reported outcomes were hospitalization (2966, 34.6%), emergency room or clinic visits (2523, 29.4%), and doctor’s office visits (1991, 23.2%).
Researchers also analyzed the other cardiac AEFIs of interest: chest pain, dyspnea, palpitations, and tachycardia. For myocarditis/pericarditis, the mean time to onset (TTO) was 5.9 days, palpitations had a mean TTO of 5.6 days, chest pain and tachycardia had similar patterns, with a mean TTO of approximately 6.9 and 7.2 days, respectively, and dyspnea had a mean TTO of 9.3 days. The authors emphasized that a short TTO observed for all symptoms supports a plausible link between the occurrence of these adverse events and the COVID-19 vaccination.
Further insight was obtained through the analysis of age differences in the reporting rates of myocarditis/pericarditis cases. Approximately 37.6% of the total cases of myocarditis/pericarditis cases after vaccination were for individuals under the age of 25. The highest percentages of reported cases were in the 18–24 years old (20.6%) and 12–17 years old (16.8%) groups. The youngest age group of children between 6 months and 4 years old had 2 reported cases, whereas the group of children between 5 and 11 years old, had 21 cases.
This analysis also revealed notable gender differences in the reporting rates of myocarditis/pericarditis: males comprised the majority of reported cases (66.1%), and females accounted for 31.6% of the reports, with missing data on gender in the remaining (2.29%) reports. The highest numbers of reported cases of myocarditis/pericarditis were in the groups of males aged 12–17 years (14.7%) and 18–24 years (17.1%). Females had a relatively low percentage of reported myocarditis/pericarditis AEFIs across all age groups, with the highest percentage of cases (5.6%) in the 31–40 and 41–50-year-old age groups combined.
This difference was even more pronounced when the reporting rates of myocarditis/pericarditis cases were stratified by both age and gender. Specifically, in the 12–17-year-old age group, there were 408 reported cases, of which 363 (88.7%) were males and 45 (11.0%) were females. Similarly, in the 18–24-year-old age group, there were 433 cases, of which 367 (84.8%) were males and 66 (15.3%) were females.
Cardiovascular symptoms, including chest pain, dyspnea, palpitations, and tachycardia were evident in both genders. For chest pain and dyspnea, safety signals were detected in adolescents and young adults after the second dose of the mRNA vaccine, with no significant differences observed between genders. Safety signals were detected for palpitations after the first dose among young adult males. In contrast, for tachycardia, safety signals were observed following the first dose in young girls under the age of five.
In conclusion, this analysis revealed that males showed significant signals after the second dose of mRNA anti-SARS-CoV-2 vaccine in middle childhood, young teens, and young adults. There was a higher reporting rate of myocarditis/pericarditis after the primary vaccine series, mainly after the second dose, and particularly among males. Females showed a similar pattern, with the strongest signal seen in young female teens after the second dose of the mRNA vaccine. A booster doses resulted in a lower number of reported cases, with no significant signals detected after the fourth or fifth dose.
These results highlight the importance of continuous vaccine surveillance. The authors concluded that statistical signal detection provides an efficient way to explore potential risks within specific age groups, genders, time frames, and product types, thereby providing early warnings of potential safety concerns. In addition, further studies are needed to determine the clinical implications of these findings for public health decision-making, particularly in younger populations.
This article was published in the Journal of Clinical Medicine.
Alami, A et al. Myocarditis and Pericarditis Post-mRNA COVID-19 Vaccination: Insights from a Pharmacovigilance Perspective. J. Clin. Med. 2023, 12, 4971. Published: July, 28 2023. https://doi.org/10.3390/jcm12154971