Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications.

Autor:	Barros-Aragão FGQ; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100.; Institute of Medical Biochemistry Leopoldo De Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil, 21941-902.; Centre for Neuroscience Studies, Department of Biomedical and Molecular Sciences & Department of Psychiatry, Queen's University, Kingston, Ontario, Canada, K7L 3N6., Pinto TP; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100., Carregari VC; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil, 13083-862., Rezende NBS; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100., Pinheiro TL; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100.; Institute of Medical Biochemistry Leopoldo De Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil, 21941-902., Reis-de-Oliveira G; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil, 13083-862., Cabral-Castro MJ; Institute of Microbiology Paulo de Goés, UFRJ, Rio de Janeiro, Brazil, 21941-902.; Department of Pathology, Faculty of Medicine, Universidade Federal Fluminense, Niterói, RJ, Brazil, 24210-346., Queiroz DC; Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil, 31270-901., Fonseca PLC; Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil, 31270-901., Gonçalves AL; Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil, 31270-901., de Freitas GR; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100., Sudo FK; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100., Mattos P; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100., Bozza FA; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100., Rodrigues EC; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100., Aguiar RS; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100.; Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil, 31270-901., Rodrigues RS; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100., Brandão CO; Neurolife Laboratories, Rio de Janeiro, Brazil, 22210-903., Souza AS; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100., Martins-de-Souza D; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100.; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil, 13083-862., De Felice FG; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100.; Institute of Medical Biochemistry Leopoldo De Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil, 21941-902.; Centre for Neuroscience Studies, Department of Biomedical and Molecular Sciences & Department of Psychiatry, Queen's University, Kingston, Ontario, Canada, K7L 3N6., Tovar-Moll F; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil, 22281-100.
Jazyk:	angličtina
Zdroj:	Brain, behavior, & immunity - health [Brain Behav Immun Health] 2024 Jun 13; Vol. 39, pp. 100805. Date of Electronic Publication: 2024 Jun 13 (Print Publication: 2024).
DOI:	10.1016/j.bbih.2024.100805
Abstrakt:	COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored. To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out. We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2's spike protein in patients' CSF by multiple reaction monitoring analysis. Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations. Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62-62.23 vs. Mild 3.91 pg/mL CI 1.5-10.3 patients, p = 0.019). CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4-4.4 vs. Non-Pronounced 2.0, CI 1.4-2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89-123.31 vs Non-Pronounced 6.22, CI 2.9-13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases. Competing Interests: none. (© 2024 The Authors.)
Databáze:	MEDLINE
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