{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:03:33Z","timestamp":1790186613231,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Infections are recognized triggers for several neuroinflammatory disorders. The coronavirus disease 2019 (COVID-19) pandemic\u2019s non-pharmaceutical interventions sharply curtailed pathogen exposure, creating a natural experiment to test infection\u2013disease links.<\/jats:p>\n                  <jats:p>Using Japan\u2019s National Claims Database, we first validated the nationwide decline with two strictly infection-dependent conditions\u2014epidemic keratoconjunctivitis and influenza-associated encephalopathy\u2014whose monthly incidences fell by &amp;gt;60% after April 2020. Next, we applied an interrupted time series design, a causal-inference method for longitudinal data, to nine immune-mediated inflammatory diseases.<\/jats:p>\n                  <jats:p>Unsupervised clustering of model-derived level and slope changes identified three data-driven clusters. The first cluster, comprising Guillain\u2013Barr\u00e9 syndrome and acute disseminated encephalomyelitis, showed large, statistically significant level reductions (P &amp;lt; 0.001), particularly in women, consistent with infection-susceptible pathophysiology. The second cluster, including myasthenia gravis and optic neuritis, exhibited transient declines followed by significant positive post-intervention slopes (P &amp;lt; 0.001), suggesting deferred diagnosis, treatment interruption or immune rebound. The third cluster, consisting of sarcoidosis, neuromyelitis optica, multiple sclerosis, Vogt\u2013Koyanagi\u2013Harada disease and Beh\u00e7et\u2019s disease, remained stable, suggesting limited or complex infectious links.<\/jats:p>\n                  <jats:p>These data-driven trajectories mirror clinical pathophysiology and demonstrate that reduced pathogen exposure affects neuroinflammatory disease onset to varying degrees. This framework supports infection-related risk stratification, preventive strategies and continuity planning in neuroimmunology practice.<\/jats:p>","DOI":"10.1093\/brain\/awaf458","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T12:55:20Z","timestamp":1765025720000},"page":"771-777","source":"Crossref","is-referenced-by-count":3,"title":["Natural experiment on neuroinflammatory disease incidence and infection links pre- and post-COVID-19"],"prefix":"10.1093","volume":"149","author":[{"given":"Masahiro","family":"Akada","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5248-5762","authenticated-orcid":false,"given":"Masayuki","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Muraoka","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Morooka","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine , Kyoto 606-8507 ,","place":["Japan"]},{"name":"Center for Innovative Research and Education in Data Science, Institute for Liberal Arts and Sciences, Kyoto University , Kyoto 606-8315 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitaka","family":"Tsujikawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"2026030512075310100_awaf458-B1","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/S0140-6736(21)00517-1","article-title":"Guillain-Barr\u00e9 syndrome","volume":"397","author":"Shahrizaila","year":"2021","journal-title":"Lancet"},{"key":"2026030512075310100_awaf458-B2","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1212\/01.wnl.0000259404.51352.7f","article-title":"Acute disseminated encephalomyelitis","volume":"68","author":"Tenembaum","year":"2007","journal-title":"Neurology"},{"key":"2026030512075310100_awaf458-B3","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis","volume":"375","author":"Bjornevik","year":"2022","journal-title":"Science"},{"key":"2026030512075310100_awaf458-B4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jns.2010.10.013","article-title":"A serological analysis of viral and bacterial infections associated with neuromyelitis optica","volume":"300","author":"Koga","year":"2011","journal-title":"J Neurol Sci"},{"key":"2026030512075310100_awaf458-B5","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.jcv.2014.09.010","article-title":"Optic neuritis associated with influenza B virus meningoencephalitis","volume":"61","author":"Vianello","year":"2014","journal-title":"J Clin Virol"},{"key":"2026030512075310100_awaf458-B6","doi-asserted-by":"crossref","first-page":"13211","DOI":"10.1038\/s41598-024-63957-1","article-title":"Effect of the COVID-19 pandemic on Vogt-Koyanagi-Harada disease","volume":"14","author":"Muto","year":"2024","journal-title":"Sci Rep"},{"key":"2026030512075310100_awaf458-B7","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s10654-020-00611-w","article-title":"Are infectious diseases risk factors for sarcoidosis or a result of reverse causation? 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