COVID-19 vaccine associated myocarditis in Norway - a nationwide validation study

Abstract

Abstract Background The SARS-CoV-2 pandemic led to worldwide initiation of vaccination campaigns. The new mRNA vaccines were unexpectedly associated with vaccine-associated myocarditis (VAM). The incidence and severity of VAM has not been validated in a nation-wide and well-defined population. From December 2020 onwards the mRNA vaccines Comirnaty and Spikevax have been in widespread use in Norway. The National Patient Register (NPR) includes all hospital contacts with corresponding diagnostic codes (ICD-10), and all vaccinations are registered in the Norwegian Immunization Register (SYSVAK). Purpose We aimed to identify and validate all cases of suspected COVID-19 VAM in Norway during the national vaccination campaign between 2020-22. Methods We identified all cases of myocarditis acquired within 90 days of a COVID-19 vaccination through linkage of diagnostic codes for myocarditis in NPR and vaccination data in SYSVAK. Cases were included from December 2020 through April 2022. We assessed medical records, cardiac imaging, and biochemistry to retrospectively validate all myocarditis cases. The Brighton Criteria (international criteria for myocarditis diagnosis following immunization with defining levels of diagnostic certainty) were used to confirm the VAM diagnosis. Results From December 2020 to April 2022, 4 114 750 unique subjects (2 036 792 men and 2 077 958 women, median age first dose 47 years) above 16 years of age, received 10 915 098 unique doses of COVID-19 vaccines (8 651 703[79%] Comirnaty and 2 263 395[21%] Spikevax). Of 277 cases of myocarditis identified in NPR<90 days after receiving a COVID-19 vaccine, 176(64%) were validated as VAM (78 definite, 90 probable, and 8 possible VAM). Among the patients with VAM, 137(78%) were men with median age 30(IQR 24-47) years, and 39(22%) were women with median age 54(IQR 32-65) years. There were 4 cases of VAM per 100 000 vaccinated subjects: 7 per 100 000 men and 2 per 100 000 women. Sixty-three percent of VAM occurred after the second mRNA vaccine dose. There were 3.3 cases of VAM per 100 000 unique doses of Spikevax compared to 1.1 per 100 000 unique doses of Comirnaty. The most common time interval from vaccination to VAM was 3 days and occurred in 30 patients (17.3% of VAM, 93% men), and 34% of VAM (90% men) occurred during the first 5 days from vaccination(Figure). Median duration of hospital stay was 4(IQR 3-5) days, with only 7(4%) patients needing intensive care and 1 myocarditis related patient death during hospitalization. Conclusions In this unique nationwide study including all COVID-19 vaccinated subjects in Norway from 2020-22 we found 4 cases of VAM per 100 000 vaccinated subjects. The majority of VAM occurred in young men. Interestingly, women presented later than men with VAM and most frequently at middle to older age. The occurrence of this unexpected serious adverse event underscores the importance of large studies in broad populations in future vaccine programs.