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

Abstract

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.

High levels of NfL, GFAP, TAU and UCH-L1 as potential predictor biomarkers of severity and lethality in acute COVID-19

“…The early involvement of the nervous system is well documented. [1,13] The neurological manifestations include encephalopathy, Guillain-Barré syndrome, acute disseminated encephalomyelitis, ischemic stroke, epilepsy and neuropathy as part of a broad spectrum that continues to be described. [13,[22][23][24] For a better understanding of how COVID-19 can impact nervous system and to validate candidate biomarkers for a practical approach of severity assessment, we enrolled 108 subjects from a 706-patient population admitted at the HUCFF ICU during the pandemics, between July 2020 and October 2021.…”

“…Also, they can act as potential tools for severity and mortality assessment during the acute infection. [11][12][13] NfL -a cytoskeletal intermediate lament protein of neurons -consists of an important biomarker of axonal damage and degeneration, strongly related to several neurological diseases, such as Multiple Sclerosis and Acute Disseminated Encephalomyelitis. [14].…”

Accelerated brain age in young to early middle-aged adults after mild to moderate COVID-19 infection

“…Patients with COVID-19 demonstrate post-infection upregulation of inflammatory biomarkers (49, 50) with the extent of the inflammatory response depending on disease severity (49, 50). Research among middle-aged COVID-19 survivors has shown significant inflammation-related astrocytic damage and neural dysfunction regardless of disease severity (51). Inflammation after COVID-19 infection may also impair cognition via reduced serotonin levels (52).…”

Effect of Parecoxib Sodium Preemptive Analgesia on the Recovery Period of General Anesthesia in Patients Undergoing Glioma Resection

“…COX-2 is an inducible enzyme, which usually exists at low levels in tissues but can be induced and produced in large quantities in the case of infection and injury. COX-2 is mainly expressed in neurons of cerebral cortex, hippocampus, amygdala, and spinal dorsal horn [ 12 ]. COX-2 expression was significantly increased in microglia and astrocytes under continuous neuroinflammatory response [ 13 ].…”