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However, the dynamic brain structure\u2013symptom relationships and their potential for predicting long-term outcomes remain unclear. We conducted a longitudinal study of 144 individuals with long COVID (mean age: 37.8 \u00b1 10.1 years, 48.6% male). All participants experienced mild COVID-19 and were not hospitalized. Structural MRI and comprehensive psychiatric and cognitive assessments were performed at 1, 2 and 12 months post-infection. A cohort of 68 healthy controls (mean age: 36.0 \u00b1 10.3 years; 41.2% male) completed the same assessment protocol at baseline. Regularized canonical correlation analysis was employed to identify multivariate associations between 13 psychiatric and cognitive measures and both grey matter volume and cortical thickness, and to assess whether early structural features predicted symptom outcomes at 1 year. Neuropsychiatric symptoms were linked to coordinated structural covariance patterns across distributed brain regions in long COVID; these associations strengthened from 1 to 3 months post-infection and were absent in controls. A stable cognitive-affective symptom dimension showed the strongest brain\u2013behaviour coupling. Notably, the neural substrates of this coupling diverged over time: grey matter volume associations remained localized to prefrontal-limbic circuits, whereas cortical thickness associations expanded to frontoparietal regions. Critically, reduced grey matter volume in the right cuneus and superior frontal gyri, along with decreased cortical thickness in the left supramarginal gyrus at 3 months post-infection, were significantly linked to poorer executive function and greater fatigue 1 year later. Our findings delineate evolving neuroanatomical signature of long COVID, where distinct patterns of grey matter volume and cortical thickness underpin a core symptom profile and predict long-term neuropsychiatric symptoms. These results provide insight into the neural mechanisms of long COVID and identify specific targets for monitoring and early intervention.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag232","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:19:49Z","timestamp":1781695189000},"source":"Crossref","is-referenced-by-count":0,"title":["Dynamic multivariate patterns of brain structure\u2013neuropsychiatric symptom associations in long COVID"],"prefix":"10.1093","volume":"8","author":[{"given":"Wenrui","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Medical Imaging, the First Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi Province 710061 ,","place":["China"]},{"name":"School of Future Technology, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi Province 710049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gengchen","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, the First Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi Province 710061 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi Province 710004 ,","place":["China"]},{"name":"Laboratory Center of Stomatology, College of Stomatology, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi Province 710004 ,","place":["China"]},{"name":"Department of Medical Imaging, College of Stomatology, Xi\u2019an Jiaotong University , Xi'an, Shaanxi Province 710004 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingpu","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, the First Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi Province 710061 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiange","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, the First Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi Province 710061 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0979-6979","authenticated-orcid":false,"given":"Liming","family":"Fan","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, Xi\u2019an Jiaotong University School of Life Science and Technology , Xi\u2019an, Shaanxi Province 710049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haining","family":"Li","sequence":"additional","affiliation":[{"name":"PET\/CT Center, the First Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi Province 710061 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, the First Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi Province 710061 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, the First Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi Province 710061 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