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Institute at UCL","award":["860197"],"award-info":[{"award-number":["860197"]}]},{"name":"UK Dementia Research Institute at UCL","award":["JPND2021-00694"],"award-info":[{"award-number":["JPND2021-00694"]}]},{"name":"UK Dementia Research Institute at UCL","award":["UKDRI-1003"],"award-info":[{"award-number":["UKDRI-1003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The levels of several glial and neuronal plasma biomarkers have been found to increase during the acute phase in COVID-19 patients with neurological symptoms. However, replications in patients with minor or non-neurological symptoms are needed to understand their potential as indicators of CNS injury or vulnerability. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), and total Tau (T-tau) were determined by Single molecule array (Simoa) immunoassays in 45 samples from COVID-19 patients in the acute phase of infection [moderate (n = 35), or severe (n = 10)] with minor or non-neurological symptoms; in 26 samples from fully recovered patients after ~2 months of clinical follow-up [moderate (n = 23), or severe (n = 3)]; and in 14 non-infected controls. Plasma levels of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), were also determined by Western blot. Patients with COVID-19 without substantial neurological symptoms had significantly higher plasma concentrations of GFAP, a marker of astrocytic activation\/injury, and of NfL and T-tau, markers of axonal damage and neuronal degeneration, compared with controls. All these biomarkers were correlated in COVID-19 patients at the acute phase. Plasma GFAP, NfL and T-tau levels were all normalized after recovery. Recovery was also observed in the return to normal values of the quotient between the ACE2 fragment and circulating full-length species, following the change noticed in the acute phase of infection. None of these biomarkers displayed differences in plasma samples at the acute phase or recovery when the COVID-19 subjects were sub-grouped according to occurrence of minor symptoms at re-evaluation 3 months after the acute episode (so called post-COVID or \u201clong COVID\u201d), such as asthenia, myalgia\/arthralgia, anosmia\/ageusia, vision impairment, headache or memory loss. Our study demonstrated altered plasma GFAP, NfL and T-tau levels in COVID-19 patients without substantial neurological manifestation at the acute phase of the disease, providing a suitable indication of CNS vulnerability; but these biomarkers fail to predict the occurrence of delayed minor neurological symptoms.<\/jats:p>","DOI":"10.3390\/ijms24032715","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:52:02Z","timestamp":1675219922000},"page":"2715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Transient Changes in the Plasma of Astrocytic and Neuronal Injury Biomarkers in COVID-19 Patients without Neurological Syndromes"],"prefix":"10.3390","volume":"24","author":[{"given":"Matthew P.","family":"Lennol","sequence":"first","affiliation":[{"name":"Instituto de Neurociencias de Alicante, Universidad Miguel Hern\u00e1ndez-CSIC, 03550 San Juan de Alicante, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 03550 San Juan de Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80 M\u00f6lndal, Sweden"},{"name":"Centre for Age-Related Medicine, Stavanger University Hospital, 4005 Stavanger, Norway"},{"name":"Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London SE5 8AF, UK"},{"name":"Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, NIHR Biomedical Research Centre for Mental Health, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Moreno-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departmento de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), General University Hospital of Alicantet, 03010 Alicante, Spain"},{"name":"Departmento de Medicina Cl\u00ednica, Universidad Miguel Hern\u00e1ndez de Elche, 03550 Alicante, 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-CSIC, 03550 San Juan de Alicante, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 03550 San Juan de Alicante, Spain"},{"name":"Unidad de Investigaci\u00f3n, Hospital General Universitario de Elche, FISABIO, 03203 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-9867","authenticated-orcid":false,"given":"Jose-Manuel","family":"Ramos-Rincon","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), General University Hospital of Alicantet, 03010 Alicante, Spain"},{"name":"Departmento de Medicina Cl\u00ednica, Universidad Miguel Hern\u00e1ndez de Elche, 03550 Alicante, Spain"},{"name":"Departmento de Medicina Interna, Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0219-9055","authenticated-orcid":false,"given":"Mariano","family":"Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), General University Hospital of Alicantet, 03010 Alicante, Spain"},{"name":"Departmento de Medicina Cl\u00ednica, Universidad Miguel Hern\u00e1ndez de Elche, 03550 Alicante, Spain"},{"name":"Departamento Reumatolog\u00eda, Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7922-5664","authenticated-orcid":false,"given":"Jos\u00e9-Manuel","family":"Le\u00f3n-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), General University Hospital of Alicantet, 03010 Alicante, Spain"},{"name":"Departmento Neumolog\u00eda, Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Boix","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), General University Hospital of Alicantet, 03010 Alicante, Spain"},{"name":"Departmento de Medicina Cl\u00ednica, Universidad Miguel Hern\u00e1ndez de Elche, 03550 Alicante, Spain"},{"name":"Unidad de Enfermedades Infecciosas, Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Gil","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), General University Hospital of Alicantet, 03010 Alicante, Spain"},{"name":"Departmento Neumolog\u00eda, Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain"}],"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 at the University of Gothenburg, 431 80 M\u00f6lndal, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 413 45 M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3854-4874","authenticated-orcid":false,"given":"Esperanza","family":"Merino","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), General University Hospital of Alicantet, 03010 Alicante, Spain"},{"name":"Unidad de Enfermedades Infecciosas, Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80 M\u00f6lndal, Sweden"},{"name":"Biomedical Research Unit for 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