[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-462489-105":59,"doc-detail-462489-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","cognition-cytokines-blood-brain-barrier-and-beyond-in-covid-19-a-narrative-review","Cognition, Cytokines, Blood-Brain Barrier, and Beyond in COVID-19 - A Narrative Review","","Numerous studies report cognitive impairment in COVID-19 patients from acute to postacute phases, linked to blood inflammation that affects blood–brain barrier (BBB) permeability and enables leakage of glial and neuronal proteins. A clear time-resolved classification of cognitive deficits and molecular blood events remains insufficient. This narrative review synthesizes neuropsychological consequences and evidence for altered cytokines and BBB disruption as mediators across post-infection stages.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/cognition-cytokines-blood-brain-barrier-and-beyond-in-covid-19-a-narrative-review/462489/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/cognition-cytokines-blood-brain-barrier-and-beyond-in-covid-19-a-narrative-review/462489.png","ImageObject",300,407,{"name":92,"@type":93},"Bintang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What mechanisms are proposed to explain cognitive impairment after COVID-19?","Question",{"text":112,"@type":113},"The review links cognitive difficulties to inflammatory responses affecting blood–brain barrier permeability, leakage of neural proteins, and proposed contributors such as direct CNS effects, systemic and neuroinflammation, and prolonged hypoxia.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does cognitive dysfunction appear to progress over time after infection?",{"text":117,"@type":113},"It appears to follow a temporal course, starting with acute focal attention and working memory/executive deficits and evolving into more persistent multidomain impairments in post-COVID-19 phases.",{"name":119,"@type":110,"acceptedAnswer":120},"Which cytokines and BBB-related biomarkers are highlighted as associated with cognitive deficits?",{"text":121,"@type":113},"The review discusses elevated antiviral, inflammatory, and monocyte chemoattractant cytokines beyond the acute phase (including IL-6, IL-13, IL-8, IL-1β, TNFα, and MCP1) and neurovascular unit proteins (e.g., PPIA, MMP-9, S100β, GFAP, NFL), with TGFβ noted as a related biomarker when disruption persists.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},462489,1791158489,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":26,"preview_page_count":4},962085564381,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Review  \nCognition, Cytokines, Blood–Brain Barrier, and Beyond in COVID-19: A Narrative Review  \nAna Barajas 1,2, Gemma Riquelme-Alacid 3, América Vera-Montecinos 3,4 and Belén Ramos 3,5,6, *  \nAcademic Editor: Marcella Reale  \nReceived: 4 November 2025  \nRevised: 27 December 2025  \nAccepted: 28 December 2025  \nPublished: 5 January 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Department of Clinical and Health Psychology, Universitat Autònoma de Barcelona, Bellatera, 08193 Cerdanyola del Vallès, Spain; [ana.barajas@uab.cat](ana.barajas@uab.cat)  \n2 Serra Húnter Programme, Government of Catalonia, 08002 Barcelona, Spain  \n3 Psiquiatria Molecular, Institut de Recerca Sant Joan de Déu, Parc Sanitari Sant Joan de Déu, 08830 Sant Boi de Llobregat, Spain; [gemma.riquelme@sjd.es](gemma.riquelme@sjd.es) (G.R.-A.); [america.vera@uss.cl](america.vera@uss.cl) (A.V.-M.)  \n4 Departamento de Ciencias Biológicas y Químicas, Facultad De Ciencias, Universidad San Sebastián, Sede Tres Pascualas Lientur 1457, Concepción 4080871, Chile  \n5 Centro de Investigación Biomédica 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  \n6 Faculty of Medicine, University of Vic—Central University of Catalonia, 08500 Vic, Spain  \n* Correspondence: belen.ramos@sjd.es  \nAbstract  \nNumerous studies report cognitive impairment in COVID-19 patients from the acute to postacute phases, linked to blood inflammation affecting blood–brain 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 (IFNγ, CXCL1, CXCL10), inflammatory (IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, GM-CSF, TNFα), and monocytechemoattractants (MCP1/CCL2, MCP3/CCL7, MIP-1α/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- 1β, TNFα, 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 (S100β, 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 TGFβ 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.  \nKeywords: COVID-19 disease; SARS-CoV-2; cognition; cytokine; blood–brain barrier; mental health  \n1. Introduction  \nThe coronavirus (SARS-CoV-2) that causes coronavirus disease (COVID-19) was first identified in Wuhan City, Hubei Province, China, on 29 December 2019 [1] . It was declared a pandemic by the World Health Organization (WHO) on 11 March 2020 ","cbCaifM1Rt29c9g0","https://ap.wps.com/l/cbCaifM1Rt29c9g0","pdf",1369702,24,"English","# Abstract\n# 1. Introduction","[{\"question\":\"What mechanisms are proposed to explain cognitive impairment after COVID-19?\",\"answer\":\"The review links cognitive difficulties to inflammatory responses affecting blood–brain barrier permeability, leakage of neural proteins, and proposed contributors such as direct CNS effects, systemic and neuroinflammation, and prolonged hypoxia.\"},{\"question\":\"How does cognitive dysfunction appear to progress over time after infection?\",\"answer\":\"It appears to follow a temporal course, starting with acute focal attention and working memory/executive deficits and evolving into more persistent multidomain impairments in post-COVID-19 phases.\"},{\"question\":\"Which cytokines and BBB-related biomarkers are highlighted as associated with cognitive deficits?\",\"answer\":\"The review discusses elevated antiviral, inflammatory, and monocyte chemoattractant cytokines beyond the acute phase (including IL-6, IL-13, IL-8, IL-1β, TNFα, and MCP1) and neurovascular unit proteins (e.g., PPIA, MMP-9, S100β, GFAP, NFL), with TGFβ noted as a related biomarker when disruption persists.\"}]","Cognition, Cytokines, Blood-Brain Barrier, and Beyond in COVID-19 - A Narrative Review | PDF",1790764224]