Age and Sex-Specific Risks of Myocarditis and Pericarditis Following Covid-19 Messenger RNA Vaccines By Brian Simpson

A recent paper in Nature Communications, outlines research involving hospital discharge and vaccine data, of 1612 cases of myocarditis and 1613 cases of pericarditis that occurred in France in the period from May 12, 2021 to October 31, 2021. It was found that there was an increased risk of myocarditis and pericarditis during the first week following vaccination, and particularly after the second dose, particularly in people aged 18 to 24 years, not just males. “Estimates of excess cases attributable to vaccination also reveal a substantial burden of both myocarditis and pericarditis across other age groups and in both males and females.”

The mainstream medical journals have begun the snail’s pace of catching up with reality.

https://www.nature.com/articles/s41467-022-31401-5

“Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines

Nature Communications volume 13, Article number: 3633 (2022) Cite this article

Abstract

Cases of myocarditis and pericarditis have been reported following the receipt of Covid-19 mRNA vaccines. As vaccination campaigns are still to be extended, we aimed to provide a comprehensive assessment of the association, by vaccine and across sex and age groups. Using nationwide hospital discharge and vaccine data, we analysed all 1612 cases of myocarditis and 1613 cases of pericarditis that occurred in France in the period from May 12, 2021 to October 31, 2021. We perform matched case-control studies and find increased risks of myocarditis and pericarditis during the first week following vaccination, and particularly after the second dose, with adjusted odds ratios of myocarditis of 8.1 (95% confidence interval [CI], 6.7 to 9.9) for the BNT162b2 and 30 (95% CI, 21 to 43) for the mRNA-1273 vaccine. The largest associations are observed for myocarditis following mRNA-1273 vaccination in persons aged 18 to 24 years. Estimates of excess cases attributable to vaccination also reveal a substantial burden of both myocarditis and pericarditis across other age groups and in both males and females.

Discussion

In this nationwide study involving a population of 32 million people aged 12 to 50 years having received 46 million doses of mRNA vaccines, we provide detailed estimates of the risk of myocarditis and pericarditis by sex, age categories and vaccine type. We find that vaccination with both mRNA vaccines was associated with an increased risk of myocarditis and pericarditis within the first week after vaccination. The associations were particularly pronounced after the second dose, and were evident in both males and females. We found a trend of increased risks towards younger age groups but a significant risk was also found in males over 30 years to develop myocarditis and in females over 30 years to develop a pericarditis after vaccination. Reassuringly, these cases of myocarditis and pericarditis, although requiring hospitalization, did not result in more severe outcomes than those unrelated to vaccination.

Our results are generally consistent with those reported by the pharmacovigilance systems in France and other countries8^,13^,14^,15^,16. Several common factors in terms of the characteristics and prognosis of cases identified, and the temporal relationship between vaccine exposure and the event of interest, suggest a consistent underlying mechanism5^,6^,17^,18. As found in our analyses, various reports indicate that the risk is more pronounced with the mRNA-1273 vaccine7^,10^,19^,20, even though there was no difference in rates between the two vaccines in the passive surveillance reporting in the US4.

Our findings bring new elements in showing that the risk of acute cardiac inflammation after vaccination is not confined to myocarditis in young men4^,5^,6^,14. First, in line with results from a cohort study in Nordic countries11, our analyses show a significant risk and population burden of pericarditis following the second dose of the BNT162b2 and mRNA-1273 vaccine. Often comprised in a combined outcome of myopericarditis7^,19^,21, pericarditis as specific entity has been less studied for its association with mRNA vaccines, and even more rarely regarding the mRNA-12173 vaccine. For the BNT162b2 vaccine, results are inconsistent with either reports of a positive association11^,18 or an absence of association8^,9^,10. Barda et al. and Lai et al. found a non-significant risk ratio of 1.27 and odds ratio of 1.06, respectively, for the combined effect of first and second dose of the BNT162b2 vaccine8^,9. Patone et al. found a non-significant relative incidence of pericarditis in the week after both doses of the BNT162b2 vaccine of approximately 0.6, while the association with mRNA-1273 could not be quantified10. Considering that the risk of myocarditis following the BNT162b2 vaccine is also found lower in the later study than in others, we hypothesized that the probably weaker association with pericarditis might be more difficult to reveal. This discrepancy could also reflect different diagnostic practices as pericarditis is a retrospective diagnosis of exclusion.

Second, by differentiating the risk between adolescent (aged 12 to 17 years) and young men or women (18–25 years), we estimate that the number of excess cases after the second dose of BNT162b2 vaccine is lower in adolescents compared to young adults. This is consistent with findings from surveillance data in Israel22 but in contrast with those from the US4. There is some support for the role of sex hormones in the increased susceptibility for myocarditis of young men compared to women23^,24^,25. While we do find higher absolute burden of myocarditis and pericarditis in adolescent males and men, we also find that the female counterpart also faces a significant risk, notably of pericarditis for women over 30 years after the second dose of the mRNA-1273 vaccine, which has not yet been shown.

There are several factors that support the hypothesis of a causal relationship between exposure to mRNA vaccines and the risk of myocarditis and pericarditis. First, the associations remained strong, even after adjusting for a history of these conditions or recent SARS-CoV-2 infection, and in a period during which most common respiratory viruses were not widely circulating26^,27. Second, the time that elapsed between exposure to the vaccine and hospitalization was very short for both conditions, particularly after the second dose. Third, in most cases, the associations did not persist after seven days following exposure. Fourth, the stronger risk associated with the second dose and the mRNA-1273 vaccine, which contains a larger amount of mRNA, suggest a dose response relationship28.

The strengths of our study include the large sample size, population-based character and the assessment of cases and exposure to vaccines in high-quality and comprehensive databases. It allowed us to include 1612 confirmed cases of myocarditis and 1613 of pericarditis, occurring in a period during which 46 million doses of the two mRNA vaccines were administered. This study provides population estimates of vaccine associated risk and burden at a national level, which cannot be informed by passive case notification surveillance. Furthermore, results were consistent after adjusting for other risk factors, including SARS-CoV-2 infection, and different periods.

Our study has several limitations. First, the National Health Data System provides little clinical and no laboratory information concerning cases. The cases included in this study were identified solely on the basis of the diagnosis codes associated with hospital admissions. We therefore could not detect asymptomatic or mild forms of myocarditis and pericarditis that would not require hospitalization. Nevertheless, the incidence of myocarditis and pericarditis before the Covid-19 pandemic, estimated using the SNDS data, is consistent with the figures reported by other countries14. Furthermore, the observed durations of stay and post-discharge treatments were consistent with typical presentations of these conditions. Second, while our assessment of severity indicators within four weeks post-discharge indicates a favourable clinical outcome of post-vaccination carditis in their acute phase, we could not investigate potential long-term consequences. Third, we did not study the Covid-19 booster vaccination which was not yet recommended for healthy younger adults in our study period. Finally, associations across age and sex subgroups could not always be quantified for both vaccines or only with a considerable degree of uncertainty due to the limited time span of observation. The extent of the risk for certain subgroups, especially among women, for whom the incidence appears to be lower, warrants further studies and meta-analyses26^,29.

In conclusion, this study provides strong evidence of an increased risk of myocarditis and of pericarditis in the week following vaccination against Covid-19 with mRNA vaccines in both males and females, in particular after the second dose of the mRNA-1273 vaccine. Future studies based on an extended period of observation will allow to investigate the risk related to the booster dose of the vaccines and monitoring the long-term consequences of these post vaccination acute inflammations.”