{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:27:51Z","timestamp":1787020071559,"version":"build-2736575974"},"reference-count":106,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: The potential long-term effects of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection on the brain structure have not yet been fully elucidated. Even though existing studies have reported structural changes in the post-COVID-19 period, the results remain highly inconsistent and controversial. As such, identifying an imaging biomarker for post-COVID brains is still under investigation. This review aims to comprehensively summarize the structural MRI (sMRI) studies that focus on volumetric brain changes at least two weeks following COVID-19 infection. Methods: A systematic literature search was conducted on PubMed, SCOPUS, Web of Science, EMBASE, and Google Scholar up to 9 September 2025. Studies that utilized sMRI to assess volumetric brain changes post-COVID at greater than two weeks following infection were included. Exclusion criteria encompassed research involving pediatric or adolescent populations and imaging modalities other than sMRI. Preprints, reviews, case reports, case series and post-mortem studies were also excluded. Results: Forty-one studies satisfied the inclusion criteria and consisted of 2895 patients and 1729 healthy controls. Despite the wide variability in image acquisition protocols, data processing methods, and comorbidities between studies, multiple studies reported statistically significant volumetric reductions in the hippocampus, amygdala, thalamus, basal ganglia, nucleus accumbens and the cerebellum months to years after infection, especially in older hospitalized patients with severe COVID-19. Conclusions: The emerging literature reports long-term volume changes across various brain regions in individuals previously infected with COVID-19; however, the evidence is inconsistent. Specific imaging biomarkers following exposure to SARS-CoV-2 infection and the underlying mechanisms of these changes are yet to be identified. Future studies with harmonized imaging protocols, longitudinal designs, and integrated biomarker and clinical data are needed to define robust biomarkers and elucidate the pathophysiology of these findings.<\/jats:p>","DOI":"10.3390\/brainsci15121255","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:02:07Z","timestamp":1763974927000},"page":"1255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Brain Volumetric Changes Post-COVID-19: A Systematic Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9666-5623","authenticated-orcid":false,"given":"Engy","family":"Elkoury","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Tanta University, Tanta 31511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Yehia","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic Arizona, 5777 E Mayo Blvd, Phoenix, AZ 85054, USA"},{"name":"Department of Neuroscience, Graduate School of Biomedical Sciences, Mayo Clinic College of Medicine, Phoenix, AZ 85259, USA"},{"name":"Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth C.","family":"Caparelli","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonas E.","family":"Geda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dakota","family":"Ortega","sequence":"additional","affiliation":[{"name":"Preclinical Imaging Core, Arizona State University, Tempe, AZ 85257, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson","family":"Yamada","sequence":"additional","affiliation":[{"name":"School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85282, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0019-6284","authenticated-orcid":false,"given":"Sasha","family":"Hakhu","sequence":"additional","affiliation":[{"name":"School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85282, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Beeman","sequence":"additional","affiliation":[{"name":"Preclinical Imaging Core, Arizona State University, Tempe, AZ 85257, USA"},{"name":"School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85282, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7745-3572","authenticated-orcid":false,"given":"Thomas J.","family":"Ross","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Yang","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic Arizona, Phoenix, AZ 85259, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4237-7776","authenticated-orcid":false,"given":"John D.","family":"Port","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55906, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0652-0862","authenticated-orcid":false,"given":"Osama A.","family":"Abulseoud","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic Arizona, 5777 E Mayo Blvd, Phoenix, AZ 85054, USA"},{"name":"Department of Neuroscience, Graduate School of Biomedical Sciences, Mayo Clinic College of Medicine, Phoenix, AZ 85259, 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