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Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity

BACKGROUND: SARS-CoV-2 infection can lead to the abnormal induction of cytokines and a dysregulated hyperinflammatory state that is implicated in disease severity and risk of death. There are several molecules present in blood associated with immune cellular response, inflammation, and oxidative str...

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Autores principales: Rocha Santos Passos, Fabiolla, Heimfarth, Luana, Souza Monteiro, Brenda, Bani Corrêa, Cristiane, Rodrigues de Moura, Tatiana, Antunes de Souza Araújo, Adriano, Ricardo Martins-Filho, Paulo, Quintans-Júnior, Lucindo José, de Souza Siqueira Quintans, Jullyana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published by Elsevier B.V. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8730710/
https://www.ncbi.nlm.nih.gov/pubmed/35063743
http://dx.doi.org/10.1016/j.intimp.2021.108502
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author Rocha Santos Passos, Fabiolla
Heimfarth, Luana
Souza Monteiro, Brenda
Bani Corrêa, Cristiane
Rodrigues de Moura, Tatiana
Antunes de Souza Araújo, Adriano
Ricardo Martins-Filho, Paulo
Quintans-Júnior, Lucindo José
de Souza Siqueira Quintans, Jullyana
author_facet Rocha Santos Passos, Fabiolla
Heimfarth, Luana
Souza Monteiro, Brenda
Bani Corrêa, Cristiane
Rodrigues de Moura, Tatiana
Antunes de Souza Araújo, Adriano
Ricardo Martins-Filho, Paulo
Quintans-Júnior, Lucindo José
de Souza Siqueira Quintans, Jullyana
author_sort Rocha Santos Passos, Fabiolla
collection PubMed
description BACKGROUND: SARS-CoV-2 infection can lead to the abnormal induction of cytokines and a dysregulated hyperinflammatory state that is implicated in disease severity and risk of death. There are several molecules present in blood associated with immune cellular response, inflammation, and oxidative stress that could be used as severity markers in respiratory viral infections such as COVID-19. However, there is a lack of clinical studies evaluating the role of oxidative stress-related molecules including glial fibrillary acidic protein (GFAP), the receptor for advanced glycation end products (RAGE), high mobility group box-1 protein (HMGB1) and cyclo-oxygenase-2 (COX-2) in COVID-19 pathogenesis. AIM: To evaluate the role of oxidative stress-related molecules in COVID-19. METHOD: An observational study with 93 Brazilian participants from September 2020 to April 2021, comprising 23 patients with COVID-19 admitted to intensive care unit (ICU), 19 outpatients with COVID-19 with mild to moderate symptoms, 17 individuals reporting a COVID-19 history, and 34 healthy controls. Blood samples were taken from all participants and western blot assay was used to determine the RAGE, HMGB1, GFAP, and COX-2 immunocontent. RESULTS: We found that GFAP levels were higher in patients with severe or critical COVID-19 compared to outpatients (p = 0.030) and controls (p < 0.001). A significant increase in immunocontents of RAGE (p < 0.001) and HMGB1 (p < 0.001) were also found among patients admitted to the ICU compared to healthy controls, as well as an overexpression of the inducible COX-2 (p < 0.001). In addition, we found a moderate to strong correlation between RAGE, GFAP and HMGB1 proteins. CONCLUSION: SARS-CoV-2 infection induces the upregulation of GFAP, RAGE, HMGB1, and COX-2 in patients with the most severe forms of COVID-19.
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spelling pubmed-87307102022-01-06 Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity Rocha Santos Passos, Fabiolla Heimfarth, Luana Souza Monteiro, Brenda Bani Corrêa, Cristiane Rodrigues de Moura, Tatiana Antunes de Souza Araújo, Adriano Ricardo Martins-Filho, Paulo Quintans-Júnior, Lucindo José de Souza Siqueira Quintans, Jullyana Int Immunopharmacol Article BACKGROUND: SARS-CoV-2 infection can lead to the abnormal induction of cytokines and a dysregulated hyperinflammatory state that is implicated in disease severity and risk of death. There are several molecules present in blood associated with immune cellular response, inflammation, and oxidative stress that could be used as severity markers in respiratory viral infections such as COVID-19. However, there is a lack of clinical studies evaluating the role of oxidative stress-related molecules including glial fibrillary acidic protein (GFAP), the receptor for advanced glycation end products (RAGE), high mobility group box-1 protein (HMGB1) and cyclo-oxygenase-2 (COX-2) in COVID-19 pathogenesis. AIM: To evaluate the role of oxidative stress-related molecules in COVID-19. METHOD: An observational study with 93 Brazilian participants from September 2020 to April 2021, comprising 23 patients with COVID-19 admitted to intensive care unit (ICU), 19 outpatients with COVID-19 with mild to moderate symptoms, 17 individuals reporting a COVID-19 history, and 34 healthy controls. Blood samples were taken from all participants and western blot assay was used to determine the RAGE, HMGB1, GFAP, and COX-2 immunocontent. RESULTS: We found that GFAP levels were higher in patients with severe or critical COVID-19 compared to outpatients (p = 0.030) and controls (p < 0.001). A significant increase in immunocontents of RAGE (p < 0.001) and HMGB1 (p < 0.001) were also found among patients admitted to the ICU compared to healthy controls, as well as an overexpression of the inducible COX-2 (p < 0.001). In addition, we found a moderate to strong correlation between RAGE, GFAP and HMGB1 proteins. CONCLUSION: SARS-CoV-2 infection induces the upregulation of GFAP, RAGE, HMGB1, and COX-2 in patients with the most severe forms of COVID-19. Published by Elsevier B.V. 2022-03 2022-01-05 /pmc/articles/PMC8730710/ /pubmed/35063743 http://dx.doi.org/10.1016/j.intimp.2021.108502 Text en © 2021 Published by Elsevier B.V. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Rocha Santos Passos, Fabiolla
Heimfarth, Luana
Souza Monteiro, Brenda
Bani Corrêa, Cristiane
Rodrigues de Moura, Tatiana
Antunes de Souza Araújo, Adriano
Ricardo Martins-Filho, Paulo
Quintans-Júnior, Lucindo José
de Souza Siqueira Quintans, Jullyana
Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity
title Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity
title_full Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity
title_fullStr Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity
title_full_unstemmed Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity
title_short Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity
title_sort oxidative stress and inflammatory markers in patients with covid-19: potential role of rage, hmgb1, gfap and cox-2 in disease severity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8730710/
https://www.ncbi.nlm.nih.gov/pubmed/35063743
http://dx.doi.org/10.1016/j.intimp.2021.108502
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