학술논문
The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation
Document Type
article
Author
Dirk Reinhold; Vadim Farztdinov; Yan Yan; Christian Meisel; Henrik Sadlowski; Joachim Kühn; Frank H. Perschel; Matthias Endres; Emrah Düzel; Stefan Vielhaber; Karina Guttek; Alexander Goihl; Morten Venø; Bianca Teegen; Winfried Stöcker; Paula Stubbemann; Florian Kurth; Leif E. Sander; Markus Ralser; Carolin Otto; Simon Streit; Sven Jarius; Klemens Ruprecht; Helena Radbruch; Jørgen Kjems; Michael Mülleder; Frank Heppner; Peter Körtvelyessy
Source
Journal of Neuroinflammation, Vol 20, Iss 1, Pp 1-16 (2023)
Subject
Language
English
ISSN
1742-2094
Abstract
Abstract 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