{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:15:48Z","timestamp":1791591348474,"version":"4.3.4"},"reference-count":85,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI21\/00059"],"award-info":[{"award-number":["PI21\/00059"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Numerous studies report cognitive impairment in COVID-19 patients from the acute to post-acute phases, linked to blood inflammation affecting blood\u2013brain barrier (BBB) permeability and causing leakage of glial and neuronal proteins. However, a clear classification of these cognitive deficits and molecular blood events over time is still lacking. This narrative review summarizes the neuropsychological consequences of COVID-19 and evidence of altered cytokines and BBB disruption as potential mediators of cognitive impairment across post-infection phases. Post-COVID-19 cognitive dysfunction appears to follow a temporal course, evolving from acute focal deficits in attention, working memory, and executive function to more persistent multidomain impairments. We reviewed key cytokines released into the blood during COVID-19 infection, including antiviral (IFN\u03b3, CXCL1, CXCL10), inflammatory (IL-1\u03b2, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, GM-CSF, TNF\u03b1), and monocyte chemoattractants (MCP1\/CCL2, MCP3\/CCL7, MIP-1\u03b1\/CCL3, GM-CSF, G-CSF). This analysis shows that several inflammatory and viral cytokines remain elevated beyond the acute phase and are associated with cognitive deficits, including IL-6, IL-13, IL-8, IL-1\u03b2, TNF\u03b1, and MCP1 in long-term post-COVID-19 patients. In addition, we examined studies analyzing changes over time in neurovascular unit proteins as biomarkers of BBB disruption, including extracellular matrix proteins (PPIA, MMP-9), astrocytes (S100\u03b2, GFAP), and neurons (NFL). These proteins are elevated in acute COVID-19 but generally return to control levels within six months, suggesting BBB restoration. However, in patients followed for over a year, BBB disruption persists only in those with cognitive impairment and is associated with systemic inflammation, with TGF\u03b2 as a related biomarker. Although cognitive sequelae can persist for over 12 months after SARS-CoV-2 infection, further studies are needed to investigate long-term neurocognitive outcomes and their link to sustained proinflammatory cytokine elevation and brain impact.<\/jats:p>","DOI":"10.3390\/ijms27010546","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:28:57Z","timestamp":1767626937000},"page":"546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cognition, Cytokines, Blood\u2013Brain Barrier, and Beyond in COVID-19: A Narrative Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1103-9499","authenticated-orcid":false,"given":"Ana","family":"Barajas","sequence":"first","affiliation":[{"name":"Department of Clinical and Health Psychology, Universitat Aut\u00f2noma de Barcelona, Bellatera, 08193 Cerdanyola del Vall\u00e8s, Spain"},{"name":"Serra H\u00fanter Programme, Government of Catalonia, 08002 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Riquelme-Alacid","sequence":"additional","affiliation":[{"name":"Psiquiatria Molecular, Institut de Recerca Sant Joan de D\u00e9u, Parc Sanitari Sant Joan de D\u00e9u, 08830 Sant Boi de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3468-0556","authenticated-orcid":false,"given":"Am\u00e9rica","family":"Vera-Montecinos","sequence":"additional","affiliation":[{"name":"Psiquiatria Molecular, Institut de Recerca Sant Joan de D\u00e9u, Parc Sanitari Sant Joan de D\u00e9u, 08830 Sant Boi de Llobregat, Spain"},{"name":"Departamento de Ciencias Biol\u00f3gicas y Qu\u00edmicas, Facultad De Ciencias, Universidad San Sebasti\u00e1n, Sede Tres Pascualas Lientur 1457, Concepci\u00f3n 4080871, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"Ramos","sequence":"additional","affiliation":[{"name":"Psiquiatria Molecular, Institut de Recerca Sant Joan de D\u00e9u, Parc Sanitari Sant Joan de D\u00e9u, 08830 Sant Boi de Llobregat, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Ministry of Economy, Industry and Competitiveness Institute of Health Carlos III, 28029 Madrid, Spain"},{"name":"Faculty of Medicine, University of Vic\u2014Central University of Catalonia, 08500 Vic, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and Clinical Characteristics of 99 Cases of 2019 Novel Coronavirus Pneumonia in Wuhan, China: A Descriptive Study","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1080\/13854046.2020.1803408","article-title":"Neuropsychological Functioning in Severe Acute Respiratory Disorders Caused by the Coronavirus: Implications for the Current COVID-19 Pandemic","volume":"34","author":"Rabinovitz","year":"2020","journal-title":"Clin. 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