The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation
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Le résumé fourni par la source
Patients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. We studied the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n = 38). Patients with herpes simplex virus encephalitis (HSVE, n = 10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n = 28) served as controls. We used proteomics, enzyme-linked immunoassays, and semiquantitative cytokine arrays to characterize inflammatory proteins. Autoantibody screening was performed with cell-based assays and native tissue staining. RNA sequencing of long-non-coding RNA and circular RNA was done to study the transcriptome. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients with, e.g., downregulation of the apolipoproteins and extracellular matrix proteins. Protein upregulation of the complement system, the serpin proteins pathways, and other proteins including glycoproteins alpha-2 and alpha-1 acid. Importantly, calculation of interleukin-6, interleukin-16, and CXCL10 CSF/serum indices suggest that these inflammatory mediators reach the CSF from the systemic circulation, rather than being produced within the CNS. Antibody screening revealed no pathological levels of known neuronal autoantibodies. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly (p < 0.01) higher in those with bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, and two circRNAs being significantly differentially expressed in COVID-19 than in non-neuroinflammatory controls and neurodegenerative patients. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms deserves further investigation.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation
- Date Crossref
- 09/02/2023
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Otto-von-Guericke-Universität Magdeburg pays non établi dans la noticeUniversité ou école supérieure
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Humboldt-Universität zu Berlin pays non établi dans la noticeUniversité ou école supérieure
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Freie Universität Berlin pays non établi dans la noticeUniversité ou école supérieure
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Charité - Universitätsmedizin Berlin pays non établi dans la noticeÉtablissement de santé
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Aarhus University Interdisciplinary Nanoscience Center pays non établi dans la noticeUniversité ou école supérieure
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Omiics (Denmark) pays non établi dans la noticeEntreprise
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Vivantes Klinikum pays non établi dans la noticeÉtablissement de santé
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German Center for Neurodegenerative Diseases pays non établi dans la noticeStructure de recherche
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University Hospital Magdeburg Department of Neurology pays non établi dans la noticeÉtablissement de santé
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German Center for Lung Research pays non établi dans la noticeStructure de recherche
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Heidelberg University pays non établi dans la noticeUniversité ou école supérieure
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Medical Faculty Infectiology and Inflammation (GC-I3) pays non établi dans la noticeUniversité ou école supérieure
Otto-von-Guericke-Universität Magdeburg, Humboldt-Universität zu Berlin et Freie Universität Berlin, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.