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. 2022 Dec 12;40(52):7622-7630.
doi: 10.1016/j.vaccine.2022.10.088. Epub 2022 Nov 7.

A post-marketing safety assessment of COVID-19 mRNA vaccination for serious adverse outcomes using administrative claims data linked with vaccination registry in a city of Japan

Yoshinori Takeuchi  1 , Masao Iwagami  2 , Sachiko Ono  3 , Nobuaki Michihata  4 , Kohei Uemura  5 , Hideo Yasunaga  6
Affiliations

A post-marketing safety assessment of COVID-19 mRNA vaccination for serious adverse outcomes using administrative claims data linked with vaccination registry in a city of Japan

Yoshinori Takeuchi et al. Vaccine. .

Abstract

Introduction: The safety profiles of COVID-19 vaccines are incompletely evaluated in Japan.

Objectives: To examine the risk of serious adverse effects after COVID-19 mRNA vaccination (BNT162b2 and mRNA-1273) in cohort studies and self-controlled case series (SCCS).

Methods: Using an administrative claims database linked with the COVID-19 vaccination registry in a city in Japan between September 2020 and September 2021, we identified health insurance enrolees aged ≥ 18 years. We evaluated the risk of acute myocardial infarction, appendicitis, Bell's palsy, convulsions/seizures, disseminated intravascular coagulation, immune thrombocytopenia, pulmonary embolism, haemorrhagic or ischemic stroke, venous thromboembolism, and all-cause mortality, 21 days following any COVID-19 mRNA vaccination, compared with non-vaccination periods. For the cohort studies, we estimated incidence rate ratios (IRRs) by Poisson regression and rate differences (IRDs) by weighted least-squares regression, adjusting for sex, age, and Charlson comorbidity index. We applied a modified SCCS design to appropriately treat outcome-dependent exposures. For the modified SCCS, we estimated within-subject IRRs by weighted conditional Poisson regression. Subgroup analyses stratified by sex and age were also conducted.

Results: We identified 184,491 enrolees [male: 87,218; mean (standard deviation) age: 64.2 (19.5) years] with 136,667 first and 127,322 s dose vaccinations. The risks of any outcomes did not increase in any analyses, except for the fact that the modified SCCS indicated an increased risk of pulmonary embolism after the first dose in women (within-subject IRR [95%CI]: 3.97 [1.18-13.32]).

Conclusion: The findings suggested that the COVID-19 mRNA vaccine was generally safe, whilst a signal of pulmonary embolism following the first dose of the COVID-19 mRNA vaccine was observed.

Keywords: Cohort study; Medical information database; Observational study; Pharmacoepidemiology; Self-controlled case series.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: YT has received consultant fees from Pharmaceuticals and Medical Devices Agency and EPARK, Inc. YT has received lecture fees from SAS Institute Japan Ltd. YT has been conducting a collaborative study, which is not related to this article, with Pfizer Inc. SO is a member of the Department of Eat-loss Medicine, a cooperative program between the University of Tokyo and ITO EN Ltd and received grants from KAKENHI, and Health, Labour, and Welfare Policy Research Grants, not related to the submitted work. No other potential competing interests relevant to this study are reported.

Figures

Fig. 1
Fig. 1
Graphical representation of the study timeline; definition of the look-back and follow-up periods. The follow-up period was defined as the observation period other than the 180-day look-back period. The follow-up period for each participant was divided into the following 3 categories (at a maximum) according to the COVID-19 mRNA vaccination status: dose 1 risk period (21 days after the first dose), dose 2 risk period (21 days after the second dose), and control period (otherwise). Abbreviation: COVID-19, coronavirus disease 2019.
Fig. 2
Fig. 2
Flow diagram of participant selection for the study cohort. Abbreviation: COVID-19, coronavirus disease 2019.
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