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<jats:title>Background<\/jats:title>\n                  <jats:p>This study assesses the cerebrospinal fluid (CSF) levels of the viral receptor angiotensin-converting enzyme 2 (ACE2) and of the serine protease TMPRSS2 fragments in patients with SARS-CoV-2 infection presenting encephalitis (CoV-Enceph).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The study included biobanked CSF from 18 CoV-Enceph, 4 subjects with COVID-19 without encephalitis (CoV), 21 with non-COVID-19\u2013related encephalitis (Enceph), and 21 neurologically healthy controls. Participants underwent a standardized assessment for encephalitis. A large subset of samples underwent analysis for an extended panel of CSF neuronal, glial, and inflammatory biomarkers. ACE2 and TMPRSS2 species were determined in the CSF by western blotting.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>ACE2 was present in CSF as several species, full-length forms and 2 cleaved fragments of 80 and 85\u2005kDa. CoV-Enceph patients displayed increased CSF levels of full-length species, as well as the 80\u2005kDa fragment, but not the alternative 85\u2005kDa fragment, compared with controls and Enceph patients, characterized by increases of both fragments. Furthermore, TMPRSS2 was increased in the CSF of Enceph patients compared with controls, but not in CoV-Enceph patients. The CoV patients without encephalitis displayed unaltered CSF levels of ACE2 and TMPRSS2 species.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Patients with encephalitis displayed an overall increase in CSF ACE2, probably as a consequence of brain inflammation. The increase of the shortest ACE2 fragment only in CoV-Enceph patients may reflect the enhanced cleavage of the receptor triggered by SARS-CoV-2, thus serving to monitor brain penetrance of the virus associated with the rare encephalitis complication. TMPRSS2 changes in the CSF appeared related to inflammation, but not with SARS-CoV-2 infection.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf093","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T20:51:06Z","timestamp":1741121466000},"page":"e929-e940","source":"Crossref","is-referenced-by-count":8,"title":["Increased Cerebrospinal Fluid Angiotensin-Converting Enzyme 2 Fragments as a Read-Out of Brain Infection in Patients With COVID-19 Encephalopathy"],"prefix":"10.1093","volume":"231","author":[{"given":"Matthew P","family":"Lennol","sequence":"first","affiliation":[{"name":"Instituto de Neurociencias de Alicante, Universidad Miguel Hern\u00e1ndez-Consejo Superior de Investigaciones Cient\u00edficas (CSIC) , San Juan de Alicante ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas , San Juan de Alicante ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5140-9752","authenticated-orcid":false,"given":"Mar\u00eda-Salud","family":"Garc\u00eda-Ayll\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Alicante, Universidad Miguel Hern\u00e1ndez-Consejo Superior de Investigaciones Cient\u00edficas (CSIC) , San Juan de Alicante ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas , San Juan de Alicante ,","place":["Spain"]},{"name":"Unidad de Investigaci\u00f3n, Hospital General Universitario de Elche, Fundaci\u00f3n para el Fomento de la Investigaci\u00f3n Sanitaria y Biom\u00e9dica de la Comunitat Valenciana (FISABIO) , Elche ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5966-6737","authenticated-orcid":false,"given":"Carlos","family":"Avil\u00e9s-Granados","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Alicante, Universidad Miguel Hern\u00e1ndez-Consejo Superior de Investigaciones Cient\u00edficas (CSIC) , San Juan de Alicante ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas , San Juan de Alicante ,","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL) , Alicante ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Trasciatti","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia , Brescia ,","place":["Italy"]},{"name":"Department of Continuity of Care and Frailty, Neurology Unit, Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili Hospital , Brescia ,","place":["Italy"]},{"name":"Neurobiorepository and Laboratory of Advanced Biological Markers, University of Brescia and ASST Spedali Civili Hospital , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Tolassi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia , Brescia ,","place":["Italy"]},{"name":"Department of Continuity of Care and Frailty, Neurology Unit, Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili Hospital , Brescia ,","place":["Italy"]},{"name":"Neurobiorepository and Laboratory of Advanced Biological Markers, University of Brescia and ASST Spedali Civili Hospital , Brescia 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,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg , Gothenburg ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal ,","place":["Sweden"]},{"name":"Department of Neurodegenerative Disease, Institute of Neurology, University College London , London ,","place":["United Kingdom"]},{"name":"UK Dementia Research Institute, University College London , London ,","place":["United Kingdom"]},{"name":"Hong Kong Center for Neurodegenerative Diseases , Hong Kong ,","place":["China"]},{"name":"Department of Medicine, School of Medicine and Public Health, University of Wisconsin , Madison, Wisconsin ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg , Gothenburg ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal ,","place":["Sweden"]},{"name":"Paris Brain Institute (ICM), Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Sorbonne University , Paris ,","place":["France"]},{"name":"Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of University of Science and Technology of China (USTC) , Hefei 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