{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:12:24Z","timestamp":1788883944001,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To describe the neuropathological findings in two cases of fatal Coronavirus Disease 2019 (COVID\u201019) with neurological decline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Severe acute respiratory syndrome coronavirus\u20102 (SARS\u2010CoV\u20102) infection was confirmed in both patients by reverse transcription polymerase chain reaction (RT\u2010PCR) from nasopharyngeal swabs antemortem. Coronial autopsies were performed on both patients and histological sampling of the brain was undertaken with a variety of histochemical and immunohistochemical stains. RNAscope\u00ae in situ hybridization (ISH) using the V\u2010nCoV2019\u2010S probe and RT\u2010PCR SARS\u2010CoV\u20102 ribonucleic acid (RNA) was performed in paraffin\u2010embedded brain tissue sampled from areas of pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Case 1 demonstrated severe multifocal cortical infarction with extensive perivascular calcification and numerous megakaryocytes, consistent with a severe multi\u2010territorial cerebral vascular injury. There was associated cerebral thrombotic microangiopathy. Case 2 demonstrated a brainstem encephalitis centred on the dorsal medulla and a subacute regional infarct involving the cerebellar cortex. In both cases, ISH and RT\u2010PCR for SARS\u2010CoV\u20102 RNA were negative in tissue sampled from the area of pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our case series adds calcifying cerebral cortical infarction with associated megakaryocytes and brainstem encephalitis to the spectrum of neuropathological findings that may contribute to the neurological decompensation seen in some COVID\u201019 patients. Viral RNA was not detected in post\u2010mortem brain tissue, suggesting that these pathologies may not be a direct consequence of viral neuroinvasion and may represent para\u2010infectious phenomena, relating to the systemic hyperinflammatory and hypercoagulable syndromes that both patients suffered.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12662","type":"journal-article","created":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T07:37:08Z","timestamp":1600241828000},"page":"17-25","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Neuropathological findings in two patients with fatal COVID\u201019"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-5023","authenticated-orcid":false,"given":"M. P.","family":"Jensen","sequence":"first","affiliation":[{"name":"Barts Health NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Le Quesne","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit University of Cambridge Cambridge UK"},{"name":"Institute of Cancer Sciences University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3690-2386","authenticated-orcid":false,"given":"L.","family":"Officer\u2010Jones","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Teod\u00f2sio","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Thaventhiran","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ficken","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Goddard","sequence":"additional","affiliation":[{"name":"Department of Pathology Royal Papworth Hospital Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Virology Addenbrooke\u2019s Hospital and University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Menon","sequence":"additional","affiliation":[{"name":"University Division of Anaesthesia University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. S. J.","family":"Allinson","sequence":"additional","affiliation":[{"name":"Department of Pathology Addenbrooke\u2019s Hospital Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"WHO Director\u2010General's opening remarks at the media briefing on COVID\u201019. [2020]; Available from:https:\/\/www.who.int\/dg\/speeches\/detail\/who\u2010director\u2010general\u2010s\u2010opening\u2010remarks\u2010at\u2010the\u2010media\u2010briefing\u2010on\u2010covid\u201019\u2013\u201011\u2010march\u20102020."},{"key":"e_1_2_10_3_1","first-page":"683","volume-title":"Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan","author":"Mao L","year":"2021"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2019373"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14134"},{"key":"e_1_2_10_6_1","article-title":"Histopathology and Ultrastructural Findings of Fatal COVID\u201019 Infections","author":"Bradley BT","year":"2020","journal-title":"medRxiv"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31282-4"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02166-2"},{"key":"e_1_2_10_9_1","article-title":"Pathophysiology of SARS\u2010CoV\u20102: targeting of endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID\u201019 autopsy experience","author":"Bryce C","year":"2020","journal-title":"medRxiv"},{"key":"e_1_2_10_10_1","first-page":"1","article-title":"Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID\u201019","author":"Jaunmuktane Z","year":"2020","journal-title":"Acta Neuropathol"},{"key":"e_1_2_10_11_1","first-page":"jnnp\u20102020\u201032358","article-title":"Characteristics of ischaemic stroke associated with COVID\u201019","author":"Beyrouti R","year":"2020","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glaa131"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06301-2"},{"issue":"7","key":"e_1_2_10_14_1","first-page":"681","article-title":"Pulmonary and cardiac pathology in Covid\u201019: the first autopsy series from new orleans","volume":"8","author":"Fox SE","year":"2020","journal-title":"medRxiv"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2015432"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30937-5"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.004"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25915"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-020-03062-7"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3988\/jcn.2017.13.3.227"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1509458"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.11.044"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(20)30287-X"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2020.03.062"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2020.116884"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050828"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.04.041"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14888"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181eaa9c8"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnan.12662","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12662","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.12662","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12662","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T18:55:07Z","timestamp":1693767307000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,24]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1111\/nan.12662"],"URL":"https:\/\/doi.org\/10.1111\/nan.12662","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,24]]},"assertion":[{"value":"2020-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}