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Here, we used multidimensional spatial immune phenotyping and machine learning methods on brains from initial COVID-19 survivors to identify the biological correlate associated with previous SARS-CoV-2 challenge. Compared to healthy controls, individuals with post-COVID-19 revealed a high percentage of TMEM119<jats:sup>+<\/jats:sup>P2RY12<jats:sup>+<\/jats:sup>CD68<jats:sup>+<\/jats:sup>Iba1<jats:sup>+<\/jats:sup>HLA-DR<jats:sup>+<\/jats:sup>CD11c<jats:sup>+<\/jats:sup>SCAMP2<jats:sup>+<\/jats:sup> microglia assembled in prototypical cellular nodules. In contrast to acute SARS-CoV-2 cases, the frequency of CD8<jats:sup>+<\/jats:sup> parenchymal T cells was reduced, suggesting an immune shift toward innate immune activation that may contribute to neurological alterations in post-COVID-19 patients.<\/jats:p>","DOI":"10.1007\/s00401-024-02770-6","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T16:01:38Z","timestamp":1722009698000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["High throughput spatial immune mapping reveals an innate immune scar in post-COVID-19 brains"],"prefix":"10.1007","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2205-5427","authenticated-orcid":false,"given":"Marius","family":"Schwabenland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilara","family":"Hasavci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle","family":"Frase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6036-3327","authenticated-orcid":false,"given":"Nikolaus","family":"Deigendesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg M.","family":"Buescher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten D.","family":"Mertz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Ondruschka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Altmeppen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Matschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Glatzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Thimme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas A.","family":"Hosp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Blank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Bengsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0349-1955","authenticated-orcid":false,"given":"Marco","family":"Prinz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"2770_CR1","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.jhep.2022.03.040","volume":"77","author":"T Boettler","year":"2022","unstructured":"Boettler T, Csernalabics B, Salie H, Luxenburger H, Wischer L, Salimi Alizei E et al (2022) SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis. 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