International sharing of coronavirus disease 2019 (COVID-19) vaccine safety information is important for better decision making in each country. We previously published the Japanese systems for COVID-19 vaccines safety monitoring and the statistics for the 1st and 2nd doses until 14 November, 2021,1 followed by our updated report of the 3rd dose (initiated December 2021) and vaccinations for children aged 5–11 years (initiated February 2022) until 15 May, 2022.2 Afterwards, in September 2022, Japan introduced bivalent vaccines covering Omicron BA.1 variants, and in October 2022, those covering Omicron BA.4/BA.5 variants, either for the 3rd, 4th, or 5th dose (not accepted as the 1st or 2nd dose). Moreover, vaccinations for infants and young children, aged 6 months to 4 years, were started in October 2022. The current report is an update on COVID-19 vaccine safety information in Japan until 12 March, 2023, including booster doses for Omicron variants for people aged ≥12 years and vaccinations for infants and young children. The booster doses for the Omicron variants for children aged 5–11 years were started in March 2023; therefore, they are not included in this report.
As of 12 March 2023, the cumulative number of booster doses for people aged ≥12 years by manufacturer (Pfizer or Moderna), number of dose (3rd, 4th, or 5th dose), age and sex, overall (including both monovalent and bivalent vaccines) and bivalent vaccines for Omicron BA.1 and BA.4/BA.5 variants, are shown in Appendix pp 1−3. Among the 8,186,613 and 43,397,362 doses administered of Pfizer vaccines for Omicron BA.1 and BA.4/BA.5, respectively, there were 97 and 527 individual case safety reports from healthcare professionals and 171 and 603 from the marketing authorisation holder (MAH), respectively. Among the 3,161,510 and 1,034,573 doses administered of Moderna vaccines for Omicron BA.1 and BA.4/BA.5, respectively, there were 55 and 23 reports from healthcare professionals and 45 and 18 from MAH, respectively. The age distributions by number of doses, as well as those of all vaccines (including monovalent and bivalent vaccines), are presented in Appendix pp 4–9. The Fig. 1 presents the reporting proportions by manufacture, number of dose, and age.
Fig. 1.
The proportion of individual case safety reports from healthcare professionals and the marketing authorisation holder by manufacturer, number of dose, and age, for bivalent vaccines for Omicron BA.1 and BA.4/BA.5 variants, as of 12 March 2023. MAH, marketing authorization holder. ∗The reporting proportion for mRNA-1273 bivalent vaccines for Omicron BA.4/BA.5 in the population aged 70–79 years old was 0.11%.
According to the Brighton classifications 1–3, the number of confirmed cases of myocarditis and pericarditis was 1 (woman aged >80 years) and 0, respectively, for Pfizer vaccines for Omicron BA.1, and 4 (2 men aged 35–39 and >80 years; 2 women aged 30–34 and 55–59 years) and 1 (man aged >80 years), respectively, for Pfizer vaccines for Omicron BA.4/BA.5. There were 39 and 18 confirmed cases of myocarditis and pericarditis for any Pfizer booster doses (including monovalent and bivalent vaccines), respectively. There were no confirmed cases of myocarditis and pericarditis for the Moderna bivalent vaccines, whereas there were 24 and 13 confirmed cases for any Moderna booster doses, respectively. The reporting rates of myocarditis according to age and sex are presented in Appendix pp 10−12. The reporting rates of anaphylaxis by age and sex are presented in Appendix pp 13−15. Regarding death, the number of deduplicated reports from healthcare professionals and MAH was 6 and 82 for Pfizer vaccines for Omicron BA.1 and BA.4/BA.5, respectively, whereas there were 305 reports for any Pfizer booster doses. There were 5 and 1 reports for Moderna bivalent vaccines for Omicron BA.1 and BA.4/BA.5, respectively, whereas there were 137 reports for any Moderna booster doses. The reporting rates of death by number of doses are presented in Appendix p 16. None of the cases were confirmed by experts as having a suggested causal relationship between vaccination and death, except for 1 case (woman aged 42 years) with the Pfizer vaccine for BA.4/BA.5.
For infants and young children, as of 12 March 2023, among the 369,270 doses administered (163,978 as the 1st, 144,268 as the 2nd, and 61,024 as the 3rd dose) of Pfizer monovalent vaccines, there were 6 (5 [0.0030%], 0, and 1 [0.0016%], respectively) reports from healthcare professionals and 16 (12 [0.0073%], 4 [0.0028%], and 0, respectively) from MAH. The details are presented in Appendix pp 17−18; no cases of strongly suspected myocarditis/pericarditis were reported.
In summary, the reporting rates of serious adverse events (including myocarditis/pericarditis, anaphylaxis, and death) associated with bivalent vaccines for Omicron variants were generally not higher than those for any booster doses (including monovalent and bivalent vaccines). In addition, the reporting rate of serious adverse events was low in children aged 6 months to 4 years, which is in line with reports in the US.3,4
As we previously discussed,1 potential limitations of the report may include underestimation of the numbers and incidence rates of adverse events by using the spontaneous reporting data.
No additional safety-related regulatory actions were issued by the Japanese government since the introduction of these vaccines until April 2023. The Japanese government is making ongoing efforts to collect and present updated safety information.
Contributors
TY, MIwagami, and CI drafted the manuscript. TY, SK, MT, MIzumi, SY, HK, YB, NK, and TI had full access to and verified all data in the study and were responsible for data acquisition, analysis, interpretation, and drafting the manuscript. AO, TM, KN, SH, and RT contributed substantially to data interpretation and drafting the manuscript. All authors have final responsibility for the decision to submit the manuscript for publication.
Data sharing statement
The data for this report are available to the public (Japanese language only) in the webpage of the Ministry of Health, Labour and Welfare of Japan (https://www.mhlw.go.jp/stf/shingi/shingi-kousei_284075.html).
Declaration of interests
AO received grants from Eisai Co., Ltd.; SHIONOGI & Co., Ltd.; Takeda Pharmaceutical Co.; Eli Lilly Japan K.K.; Chugai Pharmaceutical Co., Ltd.; and Pfizer Japan Inc. All other authors declare no competing interests.
Acknowledgements
The authors thank the members of the Health Sciences Council and the Pharmaceutical Affairs and Food Sanitation Council for their contributions to the council. This study was supported by the National Center for Global Health and Medicine Intramural Research Fund (Grant Number: 21A2010) for investigating the legal and regulatory framework for post-approval vaccine safety monitoring. The funders had no role in the design, data collection, data analysis, interpretation, or writing of the manuscript.
Footnotes
Supplementary data related to this article can be found at https://doi.org/10.1016/j.lanwpc.2023.100885.
Contributor Information
Chieko Ishiguro, Email: chishiguro@hosp.ncgm.go.jp.
Ryo Takagi, Email: takagiryo@mod.go.jp.
Appendix A. Supplementary data
References
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