{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:56:38Z","timestamp":1790913398843,"version":"4.1.0"},"reference-count":198,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Infection with severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) has caused millions of deaths worldwide. Although the incidence of severe acute cases has declined, the prevalence of long COVID, also known as post\u2010acute sequelae of COVID\u201019 (PASC), is rising. The pathological mechanisms underlying severe COVID\u201019, along with the relationship to neurological disorders and potential risk for neurodegeneration, remain poorly understood. The aim of this narrative review is to summarize neuropathological features described in postmortem human COVID\u201019 brains (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009352). Furthermore, analysis of biofluids and neuroimaging from PASC patients underline long\u2010term changes in the proteome and CNS response following the infection. Postmortem brain studies from severe COVID\u201019 patients highlight disruption of the fluid\u2010brain barriers and vascular dysregulation defined by endothelial inflammation and disruption, hemorrhages, and hypoxic\u2013ischemic damage. Neuroinflammation, including astrogliosis, microglia nodules and infiltration of adaptive immune cells, has been reported in the olfactory bulb, medulla oblongata, midbrain and cerebellum. Neuronal damage was demonstrated in the hippocampus, midbrain and cerebellum in severe COVID\u201019 and protein aggregation was observed in the midbrain and entorhinal cortex. Neuropathological burden and elevated blood and\/or cerebrospinal fluid (CSF) levels of proinflammatory cytokines (e.g. IL\u20106) and neuro\u2010axonal proteins (e.g. NfL) correlated with severity of anosmia, memory deficits, and cerebellar ataxia. Elderly patients and\/or patients with underlying neurological diseases were more susceptible and had worsened symptoms. Potential disease mechanisms underlying neurological symptoms observed in severe COVID\u201019 are vascular and fluid\u2010brain barrier abnormalities, chronic neuroinflammation, persistent axonal damage and protein aggregation. In PASC patients, an altered biofluid proteome with increased neuronal proteins and pro\u2010inflammatory cytokines was observed. The pathological burden in affected brain regions may contribute to manifestations such as anosmia, memory deficits, and cerebellar ataxia.\n                  <\/jats:p>","DOI":"10.1111\/bpa.70101","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T23:09:43Z","timestamp":1776899383000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human brain matters: Navigating the neuropathology of\n                    <scp>COVID<\/scp>\n                    \u201019"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1974-3619","authenticated-orcid":false,"given":"Juliana M.","family":"Nieuwland","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Aging Biomedical Primate Research Centre  Rijswijk The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1599-2650","authenticated-orcid":false,"given":"Angelica","family":"Scaramuzza","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam UMC Vrije University Amsterdam  Amsterdam The Netherlands"},{"name":"Section Clinical Neuroanatomy and Biobanking and Life Sciences, Department of Anatomy and Neurosciences, Amsterdam UMC Vrije University Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7689-3042","authenticated-orcid":false,"given":"Marianna","family":"Bugiani","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam UMC Vrije University Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma D. 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