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

• Published in: International immunopharmacology Vol. 104; p. 108502
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2022; Elsevier BV; Published by Elsevier B.V
• Subjects: Acidic oxides; Adolescent; Adult; Advanced glycosylation end products; Aged; Aged, 80 and over; Biomarkers - blood; Blood; Case-Control Studies; Child; Coronaviruses; COVID-19; COVID-19 - blood; COVID-19 - diagnosis; COVID-19 - immunology; COVID-19 - virology; COX-2; Cyclooxygenase 2 - blood; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytokines; Female; GFAP; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - blood; Glial Fibrillary Acidic Protein - metabolism; Glycosylation; Health risks; Healthy Volunteers; High mobility group proteins; HMGB1; HMGB1 protein; HMGB1 Protein - blood; HMGB1 Protein - metabolism; Humans; Infections; Inflammation; Inflammation - blood; Inflammation - diagnosis; Inflammation - immunology; Inflammation - virology; Male; Markers; Middle Aged; Neurological dysfunction; Oxidative stress; Oxidative Stress - immunology; Oxygenase; Pathogenesis; Patients; Prostaglandin endoperoxide synthase; Proteins; RAGE; Receptor for Advanced Glycation End Products - blood; Receptor for Advanced Glycation End Products - metabolism; SARS-CoV-2 - immunology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Signs and symptoms; Up-Regulation - immunology; Viral diseases; Young Adult; COVID-19; RAGE; HMGB1; COX-2; Neurological dysfunction; GFAP
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.108502

•Several oxidative stress-related molecules can be used as COVID-19 severity markers.•Higher GFAP, HMGB1, RAGE and COX-2 plasma levels were found in severe COVID-19 cases.•Moderate to strong correlation was found between RAGE, GFAP and HMGB1 proteins.
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.
To evaluate the role of oxidative stress-related molecules in COVID-19.
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.
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.
SARS-CoV-2 infection induces the upregulation of GFAP, RAGE, HMGB1, and COX-2 in patients with the most severe forms of COVID-19.