Hospitalised Myocarditis and Pericarditis Cases in Germany Indicate a Higher Post-Vaccination Risk for Young People Mainly after COVID-19 Vaccination

It was recently described that the overall risk of myopericarditis after receiving a COVID-19 vaccine is low, except for younger males receiving mRNA vaccines [...].


Introduction
It was recently described that the overall risk of myopericarditis after receiving a COVID-19 vaccine is low, except for younger males receiving mRNA vaccines [1]. The meta-analysis was based on observational studies on people in the general population who had myopericarditis in temporal relation to receiving vaccines [1]. In order to determine if these findings were supported by the case numbers in Germany, we evaluated the number of hospitalised cases, including those receiving intensive-care treatment, with myocarditis or pericarditis before the pandemic (2019), during the pandemic but without COVID-19 vaccines (2020), and during the pandemic with COVID-19 vaccines (2021).

Materials and Methods
Hospital renumeration data from Germany based on the International Classification of Diseases (ICD-10) were analysed [2]. Myocarditis was assumed when the principal diagnosis was coded as I40.8 (other acute myocarditis), I40.9 (acute myocarditis, unspecified), or I51.4 (myocarditis, unspecified); pericarditis was assumed when the principal diagnosis was coded as I30.9 (acute pericarditis, unspecified). An adverse reaction to COVID-19 vaccines was assumed when the secondary diagnosis was coded as U12.9 (COVID-19 vaccines causing adverse effects in therapeutic use, unspecified). An adverse reaction to any vaccine including a COVID-19 vaccine was assumed when the secondary diagnosis was coded as Y59.9 (complications due to vaccines or biological substances) or T88.1 (other complications following immunisation, not classified elsewhere).

2020 2021
Total Thereof U12.9, Y59.9, or T88. * Number of cases with the additional secondary diagnosis U12.9 were subtracted; the value of the sum of individual age groups and value of the total of all age groups can differ due to unspecified values < 4 in individual age groups. ** Number of cases with the additional secondary diagnosis U12.9 or Y59.9 were subtracted; the value of the sum of individual age groups and value of the total of all age groups can differ due to unspecified values < 4 in individual age groups. *** Values "< 4" are not included in the total.

Discussion
In 2019 and 2020, only very few cases of myocarditis or pericarditis were associated with vaccines, suggesting that only a few other vaccines contributed to the case number in 2021. The large increase in hospitalised myocarditis or pericarditis cases in 2021 compared to 2019 and 2020 is only partly explained by vaccine-related adverse events or COVID-19. A general underreporting of adverse events has been described previously and may be an explanation for this finding [3]. In addition, the vaccine's efficacy for symptomatic COVID-19 decreased in Germany among juveniles aged 12 to 17 from approximately 90% in early December 2021 to approximately 10% in late April 2022. At the time, the protective effect for hospitalisation was mostly between 30% and 65%, with peaks up to 90% and 100%, based on overall low case numbers [4].
A recent study on the incidence of myocarditis in a cohort of 65,785 patients aged 18 to 39 years found an incidence of 9.1 cases per 100,000 booster doses up to 21 days after a booster vaccination. This rate was substantially higher than the 0.2 cases reported by the Vaccine Adverse Event Reporting System, which is a passive system relying on patients or providers to report events [5].

Conclusions
We support the call for a comprehensive and careful benefit-risk evaluation of COVID-19 vaccines.
Author Contributions: Both authors conceived the idea. K.M. analysed and interpreted the data, K.M. and G.K. wrote the manuscript, G.K. searched the literature, and both authors revised and edited the manuscript. Both authors contributed equally. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.

Data Availability Statement:
The data supporting this article are available in InEK DatenBrowser at https://datenbrowser.inek.org/ (accessed 25 February 2022). Use of the data is restricted to non-commercial purposes.