Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment.

Autor: Greene C; Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland., Connolly R; Department of Neurology, Health Care Centre, St James's Hospital, Dublin, Ireland., Brennan D; Department of Neurology, Health Care Centre, St James's Hospital, Dublin, Ireland., Laffan A; Department of Neurology, Health Care Centre, St James's Hospital, Dublin, Ireland., O'Keeffe E; Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland., Zaporojan L; Department of Neurology, Health Care Centre, St James's Hospital, Dublin, Ireland., O'Callaghan J; Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland., Thomson B; Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland., Connolly E; The Irish Longitudinal Study on Ageing, School of Medicine, Trinity College Dublin, Dublin, Ireland., Argue R; Clinical Research Facility, St James's Hospital, Dublin, Ireland., Meaney JFM; Thomas Mitchell Centre for Advanced Medical Imaging (CAMI), St. James's Hospital & Trinity College Dublin, Dublin, Ireland., Martin-Loeches I; Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization, Trinity Centre for Health Sciences, St James's University Hospital, Dublin, Ireland., Long A; Trinity Translational Medicine Institute, Trinity College Dublin, St James's Hospital, Dublin, Ireland., Cheallaigh CN; Trinity Translational Medicine Institute, Trinity College Dublin, St James's Hospital, Dublin, Ireland.; Department of Immunology, St James's Hospital, Dublin, Ireland., Conlon N; Department of Immunology, St James's Hospital, Dublin, Ireland.; St James's Hospital, Tallaght University Hospital, Trinity College Dublin Allied Researchers (STTAR) Bioresource, Trinity College Dublin, Dublin, Ireland., Doherty CP; Department of Neurology, Health Care Centre, St James's Hospital, Dublin, Ireland. cdohert@tcd.ie.; Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. cdohert@tcd.ie.; FutureNeuro, Science Foundation Ireland Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland. cdohert@tcd.ie., Campbell M; Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland. matthew.campbell@tcd.ie.; FutureNeuro, Science Foundation Ireland Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland. matthew.campbell@tcd.ie.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2024 Mar; Vol. 27 (3), pp. 421-432. Date of Electronic Publication: 2024 Feb 22.
DOI: 10.1038/s41593-024-01576-9
Abstrakt: Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood-brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.
(© 2024. The Author(s).)
Databáze: MEDLINE
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