Extracellular Oxidative Stress Markers in COVID-19 Patients with Diabetes as Co-Morbidity

Abstract

COVID-19 patients have a higher risk of developing inflammatory responses associated with serious and even fatal respiratory diseases. The role of oxidative stress in exacerbating manifestations in COVID-19 pathogenesis is under-reported.This study aimed touseserum levels of superoxide dismutase (SOD3) and glutathione-S-transferase (GSTp1) by ELISA, zinc (ErbaChem5), ferritin and free iron (VitrosChemistry, Ortho Clinical Diagnosis, Raritan, NJ, USA) at the first encounter of randomly selected RT-PCR-positive COVID-19 patients, for assessing disease severity. The parameters which helped in identifying the severity, leading to poor prognosis, were neutrophil:lymphocyte higher than 4, high CRP, low SOD3 values and high GSTp1 values, and diabetes mellitus as a co-morbidity. Higher zinc levels correlated with high GSTp1 and low SOD3, indicating the protective effect of zinc on ROS. The increased high GSTp1 shows an anticipated protective biochemical response, to mitigate the low SOD3 values due to ROS consumption. Decreased SOD3 levels indicate a state of high oxidative stress at cellular levels, and an anticipated increase in GSTp1 levels points to the pathophysiological bases of increasing severity with age, sex, and co-morbidities, such asdiabetes. High levels of initial GSTp1 and zinc levels possibly offer protection to redox reactions at the cellular level in severe COVID-19 infection, preventing deterioration.

Long-COVID post-viral chronic fatigue syndrome and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study

“…There are some data that acute COVID-19 infection is accompanied by signs of oxidative stress, including increased expression of ROS-response genes and glycolysis in peripheral blood mononuclear cells 62 , increased MDA (TBARS assay), F-isoprostane, 8-hydroxy-2’-deoxyguanosine, AOPP and nitrotyrosine levels, and lowered glutathione (GSH), −SH groups, selenium, zinc, TAC and vitamin D 39, 63–69 . Lage et al reported that activation of the NLRP3 inflammasome, including increased mitochondrial superoxide production and lipid peroxidation, may persist after short-term patient recovery 70 .…”

Glutathione deficiency in the pathogenesis of SARS-CoV-2 infection and its effects upon the host immune response in severe COVID-19 disease

“…GSH is essential for immunomodulation of both innate and adaptive immune system functions, including T-lymphocyte proliferation, polymorphonuclear neutrophil phagocytosis, and dendritic cell functions, and is also important for fine-tuning the innate immune response to infection and for the first step of adaptive immunity involving antigen-presenting cell (macrophages, dendritic cells)related antigen presentation (Morris et al, 2013;Diotallevi et al, 2017). GSH works to modulate the behavior of many immune cells, augmenting both, innate immunity (and trained innate immunity or innate immune memory; Netea et al, 2020;Chumakov et al, 2021;Ferreira et al, 2021;Gong et al, 2021;Brueggeman et al, 2022), severely affected by SARS-CoV-2 viral infection (Polonikov, 2020;Rodrigues et al, 2020;Forcados et al, 2021;Kozlov et al, 2021;Bellanti et al, 2022;Paludan and Mogensen, 2022), and adaptive immunity (Dröge et al, 1991;Dröge and Breitkreutz, 2000;Dröge, 2002c;Ghezzi, 2011;Morris et al, 2013;Fraternale et al, 2017), as well as conferring protection against oxidative stress caused by microbial, parasitic and viral infections such as SARS-CoV-2 that causes COVID-19 disease (Morris et al, 2013;Diotallevi et al, 2017;Derouiche, 2020;Polonikov, 2020;Silvagno et al, 2020;Suhail et al, 2020;Forcados et al, 2021;Pérez de la Lastra et al, 2021;Bellanti et al, 2022;Kumar P. et al, 2022). Persistent and uncontrolled oxidative stress and exacerbating NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome activation during severe COVID-19 disease (Lage et al, 2022), induce production of pro-inflammatory cyto...…”

“…2022.979719 Frontiers in Microbiology 09 frontiersin.org Polonikov, 2020;Sestili and Fimognari, 2020;Silvagno et al, 2020;Bartolini et al, 2021). SARS-CoV-2 markedly decreases the levels of cellular thiols, essentially lowering the reduced form of GSH; and the use of antivirals that enhance activation of the Nrf2 transcription factor together with N-acetylcysteine administration restore GSH levels correcting the SARS-CoV-2mediated impaired GSH metabolism (Aquilano et al, 2014;Khanfar and Al Qaroot, 2020;Sestili and Fimognari, 2020;Silvagno et al, 2020;Bartolini et al, 2021;Bourgonje et al, 2021;Fraternale et al, 2021;Kumar P. et al, 2022; Figure 4). Alterations in the intracellular redox status are often associated with GSH depletion (Polonikov, 2020) and endogenous GSH deficiency, due either to decreased biosynthesis and/or increased consumption, is a marked contributor to the pathogenesis of numerous diseases via mechanisms including oxidative stress and inflammation.…”

“…GSH was shown to be the main inhibitor in the active site of the main protease (M pro ), the essential protein for virus invasion, and cysteine (Cys300) glutathionylation inhibits M pro activity by blocking its dimerization supporting the use of GSH in COVID-19 patients (Davis et al, 2021;Linani et al, 2022). GSH deficiency has been associated with increased ROS and more severe clinical COVID-19 (Guillin et al, 2019;Derouiche, 2020;Grigoletto Fernandes et al, 2020;Guloyan et al, 2020;Polonikov, 2020;Sestili and Fimognari, 2020;Silvagno et al, 2020;Suhail et al, 2020;Bourgonje et al, 2021;Forcados et al, 2021;Kozlov et al, 2021;Pérez de la Lastra et al, 2021;Kumar P. et al, 2022). SARS-CoV-2 affects intracellular GSH levels by decreasing intracellular NRF2 function, that plays a key role in protecting cells from oxidative damage by upregulating GSH production (Rahman and MacNee, 2000;Guloyan et al, 2020;Polonikov, 2020;Sharifi-Rad et al, 2020;Silvagno et al, 2020;Bartolini et al, 2021).…”

Anti-Coronavirus Efficiency and Redox-Modulating Capacity of Polyphenol-Rich Extracts from Traditional Bulgarian Medicinal Plants

“…Both COVID-19 and all viral infections have been reported to cause oxidative stress in infected tissues, following a possible cytokine storm, blood clotting, and exacerbation of hypoxia—a life-threatening systemic inflammatory syndrome involving elevated levels of circulating cytokines—as well as iron overload [ 107 ]. Therefore, antioxidant therapy and the removal of excess iron from the body with special drugs can be useful in the prevention of oxidative stress symptoms.…”