{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:32:43Z","timestamp":1791045163207,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:p>More than six years after the emergence of COVID-19, Japan continues to experience persistently elevated excess mortality despite entering a post-pandemic phase. Excess mortality, defined as the difference between observed and expected deaths, reflects both direct and indirect effects of the pandemic, including healthcare disruption, delayed care, and broader social changes. In Japan, mortality decreased slightly in 2020 but increased markedly from 2022 onward, with annual excess deaths approaching 100,000, despite widespread vaccination and the predominance of the less virulent Omicron variant. Multiple factors may underlie this sustained increase, including population aging, changes in healthcare access, delayed diagnosis and treatment, regional disparities, and psychosocial stress. Some ecological and observational studies have reported a statistical association between repeated COVID-19 booster vaccination and excess mortality in Japan; however, these findings do not establish causality, and a causal relationship cannot currently be concluded. Against this background, this narrative review examines persistent excess mortality in Japan, uses the literature on repeated booster vaccination as an illustrative example to highlight methodological limitations, and discusses the need for nationwide, linked individual-level data infrastructure and appropriate analytical frameworks for more robust future evaluations.<\/jats:p>","DOI":"10.3389\/fpubh.2026.1878166","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T05:26:55Z","timestamp":1782192415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Persistent excess mortality in post-pandemic Japan: current evidence, methodological limitations, and future directions"],"prefix":"10.3389","volume":"14","author":[{"given":"Hiroshi","family":"Kusunoki","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Osaka Dental University","place":["Hirakata, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University","place":["Kawagoe, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Niigata University Graduate School of Medical and Dental Sciences","place":["Niigata, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Kakeya","sequence":"additional","affiliation":[{"name":"Institute of Systems and Information Engineering, University of Tsukuba","place":["Tsukuba, Japan"]},{"name":"Transdisciplinary Review Association","place":["Moriya, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref1","first-page":"7","article-title":"Persistent excess mortality in post-pandemic Japan associated with COVID-19 vaccination and respiratory infections","volume":"36","author":"Takahashi","year":"2026","journal-title":"J KIBI Int Univ Res Inst Health Welf."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"584","DOI":"10.31662\/jmaj.2024-0298","article-title":"Significant increase in excess deaths after repeated COVID-19 vaccination in Japan","volume":"8","author":"Kakeya","year":"2025","journal-title":"JMA J"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1056\/NEJMsa2514268","article-title":"Updated evidence for COVID-19, RSV, and influenza vaccines for 2025-2026","volume":"393","author":"Scott","year":"2025","journal-title":"N Engl J Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e2557415","DOI":"10.1001\/jamanetworkopen.2025.57415","article-title":"Estimated effectiveness of 2024-2025 COVID-19 vaccination against severe COVID-19","volume":"9","author":"Ma","year":"2026","journal-title":"JAMA Netw Open"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"73","DOI":"10.15585\/mmwr.mm7406a1","article-title":"Interim estimates of 2024-2025 COVID-19 vaccine effectiveness among adults aged 18 years - VISION and IVY networks, September 2024-January 2025","volume":"74","author":"Link-Gelles","year":"2025","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"128276","DOI":"10.1016\/j.vaccine.2026.128276","article-title":"Effectiveness of bivalent BA.1 mRNA booster vaccines during the autumn 2022 COVID-19 booster programme in adults aged 50+ in England: observational matched cohort study using OpenSAFELY","volume":"76","author":"Madley-Dowd","year":"2026","journal-title":"Vaccine"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e2546822","DOI":"10.1001\/jamanetworkopen.2025.46822","article-title":"COVID-19 mRNA vaccination and 4-year all-cause mortality among adults aged 18\u201359 years in France","volume":"8","author":"Semenzato","year":"2025","journal-title":"JAMA Netw Open"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"128043","DOI":"10.1016\/j.vaccine.2025.128043","article-title":"Vaccine protection against COVID-19 mortality in relation to time since last booster dose among nursing home residents in Sweden - a case-control study over 35 months","volume":"71","author":"Bj\u00f6rk","year":"2026","journal-title":"Vaccine"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2350091","DOI":"10.1080\/21645515.2024.2350091","article-title":"Association between mRNA COVID-19 vaccine boosters and mortality in Japan: the VENUS study","volume":"20","author":"Mimura","year":"2024","journal-title":"Hum Vaccin Immunother"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.3390\/healthcare13111305","article-title":"Unraveling rising mortality: statistical insights from Japan and international comparisons","volume":"13","author":"Kusunoki","year":"2025","journal-title":"Healthcare"},{"key":"ref11","article-title":"Ministry of Health, Labour and Welfare, preliminary demographic statistics: December 2025, published 2026-02-26","year":""},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e002357","DOI":"10.1136\/bmjph-2024-002357","article-title":"Excess mortality during and after the COVID-19 emergency in Japan: a two-stage interrupted time-series design","volume":"3","author":"Devanathan","year":"2025","journal-title":"BMJ Public Health"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2025070103","DOI":"10.20944\/preprints202507.0103.v4","article-title":"Association between hospital bed supply and health outcomes: an ecological analysis and narrative review with insights from Japan","author":"Kusunoki","year":"2025","journal-title":"Preprints"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.3390\/vaccines12121413","article-title":"Current status and significance of additional vaccination with COVID-19 vaccine in Japan: considerations from antibody levels from hybrid immunity and public perceptions","volume":"12","author":"Kusunoki","year":"2024","journal-title":"Vaccines"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2026020466","DOI":"10.20944\/preprints202602.0466.v1","article-title":"Persistent all-cause excess mortality observed in Japan after the COVID-19 pandemic","author":"Kojima","year":"2026","journal-title":"Preprints"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1795437","DOI":"10.3389\/fpubh.2026.1795437","article-title":"Age-specific patterns of all-cause mortality across COVID-19 booster dose groups in two Japanese municipalities: an exploratory analysis","volume":"14","author":"Iwamoto","year":"2026","journal-title":"Front Public Health"},{"key":"ref17","year":""},{"key":"ref18","first-page":"1","article-title":"Factors contributing to the sharp increase in excess mortality in Japan since 2021","volume":"26","author":"Takahashi","year":"2025","journal-title":"J KIBI Int Univ Res Inst Health Welf."},{"key":"ref19","first-page":"1","article-title":"Factors contributing to the spread and convergence of SARS-CoV-2 infection in Japan","volume":"23","author":"Takahashi","year":"2022","journal-title":"J KIBI Int Univ Res Inst Health Welf"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1007\/s40264-022-01186-z","article-title":"Signaling COVID-19 vaccine adverse events","volume":"45","author":"Harpaz","year":"2022","journal-title":"Drug Saf"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2200","DOI":"10.1016\/j.vaccine.2024.01.100","article-title":"COVID-19 vaccines and adverse events of special interest: a multinational global vaccine data network (GVDN) cohort study of 99 million vaccinated individuals","volume":"42","author":"Faksova","year":"2024","journal-title":"Vaccine"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e1004924","DOI":"10.1371\/journal.pmed.1004924","article-title":"Association between COVID-19 vaccination and sudden death in apparently healthy younger individuals: a population-based case-control study","volume":"23","author":"Abdel-Qadir","year":"2026","journal-title":"PLoS Med"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"7622","DOI":"10.1016\/j.vaccine.2022.10.088","article-title":"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","volume":"40","author":"Takeuchi","year":"2022","journal-title":"Vaccine"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"100600","DOI":"10.1016\/j.lanwpc.2022.100600","article-title":"Updated report of COVID-19 vaccine safety monitoring in Japan: booster shots and paediatric vaccinations","volume":"27","author":"Yamaguchi","year":"2022","journal-title":"Lancet Reg Health West Pac"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"275","DOI":"10.18632\/oncotarget.28582","article-title":"Transfected SARS-CoV-2 spike DNA for mammalian cell expression inhibits p53 activation of p21(WAF1), TRAIL death receptor DR5 and MDM2 proteins in cancer cells and increases cancer cell viability after chemotherapy exposure","volume":"15","author":"Zhang","year":"2024","journal-title":"Oncotarget"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.3390\/cancers17122006","article-title":"Repeated COVID-19 vaccination as a poor prognostic factor in pancreatic cancer: a retrospective, single-center cohort study","volume":"17","author":"Abue","year":"2025","journal-title":"Cancer"},{"key":"ref27","first-page":"2019","article-title":"Regulatory and safety assessment of COVID-19 mRNA-LNP genetic vaccines in Japan: evidence for revocation of approval and market withdrawal","volume":"8","author":"Ueda","year":"2025","journal-title":"Science, Public Health Policy and the Law"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"126830","DOI":"10.1016\/j.vaccine.2025.126830","article-title":"Comparative analysis of fourteen COVID-19 vaccine injury compensation systems and claim approval rates","volume":"52","author":"Chu","year":"2025","journal-title":"Vaccine"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"967","DOI":"10.2147\/CLEP.S553894","article-title":"Taiwan\u2019s national health insurance research database (NHIRD): in the era of artificial intelligence, causal inference, and data security","volume":"17","author":"Hsieh","year":"2025","journal-title":"Clin Epidemiol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"449","DOI":"10.2147\/CLEP.S91125","article-title":"The Danish national patient registry: a review of content, data quality, and research potential","volume":"7","author":"Schmidt","year":"2015","journal-title":"Clin Epidemiol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1093\/ije\/dyv098","article-title":"Data resource profile: clinical practice research datalink (CPRD)","volume":"44","author":"Herrett","year":"2015","journal-title":"Int J Epidemiol"},{"key":"ref32","year":""},{"key":"ref33","year":"2024"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-026-01306-1","article-title":"Freedom of scientific inquiry: reclaiming space for controversy","author":"Iwasaki","year":"2026","journal-title":"Nat Rev Immunol"}],"updated-by":[{"DOI":"10.3389\/fpubh.2026.1930686","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000}}],"container-title":["Frontiers in Public Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2026.1878166\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:44:12Z","timestamp":1784799852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2026.1878166\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":34,"alternative-id":["10.3389\/fpubh.2026.1878166"],"URL":"https:\/\/doi.org\/10.3389\/fpubh.2026.1878166","relation":{},"ISSN":["2296-2565"],"issn-type":[{"value":"2296-2565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]},"article-number":"1878166"}}