{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:18:45Z","timestamp":1779916725695,"version":"3.53.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T00:00:00Z","timestamp":1689206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>This study aimed to investigate microglial and macrophage activation in 17 patients who died in the context of a COVID-19 infection in 2020 and 2021.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Through immunohistochemical analysis, the lysosomal marker CD68 was used to detect diffuse parenchymal microglial activity, pronounced perivascular macrophage activation and macrophage clusters. COVID-19 patients were compared to control patients and grouped regarding clinical aspects. Detection of viral proteins was attempted in different regions through multiple commercially available antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Microglial and macrophage activation was most pronounced in the white matter with emphasis in brain stem and cerebellar areas. Analysis of lesion patterns yielded no correlation between disease severity and neuropathological changes. Occurrence of macrophage clusters could not be associated with a severe course of disease or preconditions but represent a more advanced stage of microglial and macrophage activation. Severe neuropathological changes in COVID-19 were comparable to severe Influenza. Hypoxic damage was not a confounder to the described neuropathology. The macrophage\/microglia reaction was less pronounced in post COVID-19 patients, but detectable i.e. in the brain stem. Commercially available antibodies for detection of SARS-CoV-2 virus material in immunohistochemistry yielded no specific signal over controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The presented microglial and macrophage activation might be an explanation for the long COVID syndrome.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1229641","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T02:12:30Z","timestamp":1689300750000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas"],"prefix":"10.3389","volume":"14","author":[{"given":"Julian A.","family":"Stein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Kaes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrun","family":"Smola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Schulz-Schaeffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1007\/s00405-020-05965-1","article-title":"Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study","volume":"277","author":"Lechien","year":"2020","journal-title":"Arch Otorhinolaryngol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/s41593-020-00758-5","article-title":"Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19","volume":"24","author":"Meinhardt","year":"2021","journal-title":"Nat Neurosci"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1007\/s10072-020-04486-3","article-title":"The neurological manifestations of COVID-19: a review article","volume":"41","author":"Niazkar","year":"2020","journal-title":"Neurol Sci"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"117118","DOI":"10.1016\/j.jns.2020.117118","article-title":"Neurology of COVID-19 in Singapore","volume":"418","author":"Koh","year":"2020","journal-title":"J Neurol Sci"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3238\/PersNeuro.2021.07.12.02","article-title":"COVID-19 in der Neurologie: Das klinische Bild wird pr\u00e4ziser","volume":"118","author":"Berlitt","year":"2021","journal-title":"Dtsch Arztebl Int"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/S1474-4422(20)30308-2","article-title":"Neuropathology of patients with COVID-19 in Germany: a post-mortem case series","volume":"19","author":"Matschke","year":"2020","journal-title":"Lancet Neurol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/s41586-021-03710-0","article-title":"Dysregulation of brain and choroid plexus cell types in severe COVID-19","volume":"595","author":"Yang","year":"2021","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1007\/s00292-021-00924-x","article-title":"COVID-19 and the central and peripheral nervous system","volume":"42","author":"Ritschel","year":"2021","journal-title":"Pathologie"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"3856","DOI":"10.1111\/ene.15045","article-title":"Neuropathological findings from COVID-19 patients with neurological symptoms argue against a direct brain invasion of SARS-CoV-2: a critical systematic review","volume":"28","author":"Cosentino","year":"2021","journal-title":"Eur J Neurol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1056\/NEJMc2019373","article-title":"Neuropathological features of COVID-19","volume":"383","author":"Solomon","year":"2020","journal-title":"N Engl J Med"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol (Berl)"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1212\/WNL.41.4.479","article-title":"The consortium to establish a registry for Alzheimer\u2019s disease (CERAD). 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