Effect of Vaccination on Platelet Mitochondrial Bioenergy Function of Patients with Post-Acute COVID-19.

BACKGROUND: Mitochondrial dysfunction and redox cellular imbalance indicate crucial function in COVID-19 pathogenesis. Since 11 March 2020, a global pandemic, health crisis and economic disruption has been caused by SARS-CoV-2 virus. Vaccination is considered one of the most effective strategies for preventing viral infection. We tested the hypothesis that preventive vaccination affects the reduced bioenergetics of platelet mitochondria and the biosynthesis of endogenous coenzyme Q10 (CoQ10) in patients with post-acute COVID-19. MATERIAL AND METHODS: 10 vaccinated patients with post-acute COVID-19 (V + PAC19) and 10 unvaccinated patients with post-acute COVID-19 (PAC19) were included in the study. The control group (C) consisted of 16 healthy volunteers. Platelet mitochondrial bioenergy function was determined with HRR method. CoQ10, γ-tocopherol, α-tocopherol and ß-carotene were determined by HPLC, TBARS (thiobarbituric acid reactive substances) were determined spectrophotometrically. RESULTS: Vaccination protected platelet mitochondrial bioenergy function but not endogenous CoQ10 levels, in patients with post-acute COVID-19. CONCLUSIONS: Vaccination against SARS-CoV-2 virus infection prevented the reduction of platelet mitochondrial respiration and energy production. The mechanism of suppression of CoQ10 levels by SARS-CoV-2 virus is not fully known. Methods for the determination of CoQ10 and HRR can be used for monitoring of mitochondrial bioenergetics and targeted therapy of patients with post-acute COVID-19.

Paper-based colorimetric detection of COVID-19 using aptasenor based on biomimetic peroxidase like activity of ChF/ZnO/CNT nano-hybrid.

Corona Virus Disease 2019 (COVID-19) as the infectious disease caused the pandemic disease around the world through infection by SARS-CoV-2 virus. The common diagnosis approach is Quantitative RT-PCR (qRT-PCR) which is time consuming and labor intensive. In the present study a novel colorimetric aptasensor was developed based on intrinsic catalytic activity of chitosan film embedded with ZnO/CNT (ChF/ZnO/CNT) on 3,3',5,5'-tetramethylbenzidine (TMB) substrate. The main nanocomposite platform was constructed and functionalized with specific COVID-19 aptamer. The construction subjected with TMB substrate and H2O2 in the presence of different concentration of COVID-19 virus. Separation of aptamer after binding with virus particles declined the nanozyme activity. Upon addition of virus concentration, the peroxidase like activity of developed platform and colorimetric signals of oxidized TMB decreased gradually. Under optimal conditions the nanozyme could detect the virus in the linear range of 1-500 pg mL and LOD of 0.05 pg mL. Also, a paper-based platform was used for set up the strategy on applicable device. The paper-based strategy showed a linear range between 50 and 500 pg mL with LOD of 8 pg mL. The applied paper based colorimetric strategy showed reliable results for sensitive and selective detection of COVID-19 virus with the cost-effective approach.

Chemistry Related to the Catalytic Cycle of the Antioxidant Ebselen.

The antioxidant drug ebselen has been widely studied in both laboratories and in clinical trials. The catalytic mechanism by which it destroys hydrogen peroxide via reduction with glutathione or other thiols is complex and has been the subject of considerable debate. During reinvestigations of several key steps, we found that the seleninamide that comprises the first oxidation product of ebselen underwent facile reversible methanolysis to an unstable seleninate ester and two dimeric products. In its reaction with benzyl alcohol, the seleninamide produced a benzyl ester that reacted readily by selenoxide elimination, with formation of benzaldehyde. Oxidation of ebselen seleninic acid did not afford a selenonium seleninate salt as previously observed with benzene seleninic acid, but instead generated a mixture of the seleninic and selenonic acids. Thiolysis of ebselen with benzyl thiol was faster than oxidation by ca. an order of magnitude and produced a stable selenenyl sulfide. When glutathione was employed, the product rapidly disproportionated to glutathione disulfide and ebselen diselenide. Oxidation of the S-benzyl selenenyl sulfide, or thiolysis of the seleninamide with benzyl thiol, afforded a transient thiolseleninate that also readily underwent selenoxide elimination. The S-benzyl derivative disproportionated readily when catalyzed by the simultaneous presence of both the thiol and triethylamine. The phenylthio analogue disproportionated when exposed to ambient or UV (360 nm) light by a proposed radical mechanism. These observations provide additional insight into several reactions and intermediates related to ebselen.

Schizophrenia as metabolic disease. What are the causes?

Schizophrenia (SZ) is a devastating neurodevelopmental disease with an accelerated ageing feature. The criteria of metabolic disease firmly fit with those of schizophrenia. Disturbances in energy and mitochondria are at the core of complex pathology. Genetic and environmental interaction creates changes in redox, inflammation, and apoptosis. All the factors behind schizophrenia interact in a cycle where it is difficult to discriminate between the cause and the effect. New technology and advances in the multi-dispensary fields could break this cycle in the future.

Omicron Spike Protein is Vulnerable to Reduction.

SARS-CoV-2 virus spike (S) protein is an envelope protein responsible for binding to the ACE2 receptor, driving subsequent entry into host cells. The existence of multiple disulfide bonds in the S protein makes it potentially susceptible to reductive cleavage. Using a tri-part split luciferase-based binding assay, we evaluated the impacts of chemical reduction on S proteins from different virus variants and found that those from the Omicron family are highly vulnerable to reduction. Through manipulation of different Omicron mutations, we found that alterations in the receptor binding module (RBM) are the major determinants of this vulnerability. Specifically we discovered that Omicron mutations facilitate the cleavage of C480-C488 and C379-C432 disulfides, which consequently impairs binding activity and protein stability. The vulnerability of Omicron S proteins suggests a mechanism that can be harnessed to treat specific SARS-CoV-2 strains.

Redox Imbalance and Its Metabolic Consequences in Tick-Borne Diseases.

One of the growing global health problems are vector-borne diseases, including tick-borne diseases. The most common tick-borne diseases include Lyme disease, tick-borne encephalitis, human granulocytic anaplasmosis, and babesiosis. Taking into account the metabolic effects in the patient's body, tick-borne diseases are a significant problem from an epidemiological and clinical point of view. Inflammation and oxidative stress are key elements in the pathogenesis of infectious diseases, including tick-borne diseases. In consequence, this leads to oxidative modifications of the structure and function of phospholipids and proteins and results in qualitative and quantitative changes at the level of lipid mediators arising in both reactive oxygen species (ROS) and ROS enzyme-dependent reactions. These types of metabolic modifications affect the functioning of the cells and the host organism. Therefore, links between the severity of the disease state and redox imbalance and the level of phospholipid metabolites are being searched, hoping to find unambiguous diagnostic biomarkers. Assessment of molecular effects of oxidative stress may also enable the monitoring of the disease process and treatment efficacy.

Pro-and Antioxidant Status in Newborn with COVID-19.

There is practically no information on the state of oxidative stress reactions in newborns with coronavirus infections. At the same time, such studies are extremely important and can contribute to better understanding of the process of reactivity in patients of different ages. The content of pro- and antioxidant status indicators was assessed in 44 newborns with confirmed COVID-19. It was found that the content of compounds with unsaturated double bonds, primary, secondary, and final LPO products were elevated in newborns with COVID-19. These changes were accompanied by higher SOD activity and retinol level and reduced activity of glutathione peroxidase. Contrary to popular opinion, newborns can be a COVID-19-susceptible age group and require more close monitoring of metabolic reactions during the period of neonatal adaptation that is an aggravating background during infection.

Effects of TND1128 (a 5-deazaflavin derivative), with self-redox ability, as a mitochondria activator on the mouse brain slice and its comparison with ß-NMN.

We have no definitive treatment for dementia characterized by prolonged neuronal death due to the enormous accumulation of foreign matter, such as ß-amyloid. Since Alzheimer's type dementia develops slowly, we may be able to delay the onset and improve neuronal dysfunction by enhancing the energy metabolism of individual neurons. TND1128, a derivative of 5-deazaflavin, is a chemical known to have an efficient self-redox ability. We expected TND1128 as an activator for mitochondrial energy synthesis. We used brain slices prepared from mice 22 ± 2 h pretreated with TND1128 or ß-NMN. We measured Ca2+ concentrations in the cytoplasm ([Ca2+]cyt) and mitochondria ([Ca2+]mit) by using fluorescence Ca2+ indicators, Fura-4F, and X-Rhod-1, respectively, and examined the protective effects of drugs on [Ca2+]cyt and [Ca2+]mit overloading by repeating 80K exposure. TND1128 (0.01, 0.1, and 1 mg/kg s.c.) mitigates the dynamics of both [Ca2+]cyt and [Ca2+]mit in a dose-dependent manner. ß-NMN (10, 30, and 100 mg/kg s.c.) also showed significant dose-dependent mitigating effects on [Ca2+]cyt, but the effect on the [Ca2+]mit dynamics was insignificant. We confirmed the mitochondria-activating potential of TND1128 in the present study. We expect TND1128 as a drug that rescues deteriorating neurons with aging or disease.

Hypotheses on Atherogenesis Triggering: Does the Infectious Nature of Atherosclerosis Development Have a Substruction?

Since the end of the 20th century, it has been clear that atherosclerosis is an inflammatory disease. However, the main triggering mechanism of the inflammatory process in the vascular walls is still unclear. To date, many different hypotheses have been put forward to explain the causes of atherogenesis, and all of them are supported by strong evidence. Among the main causes of atherosclerosis, which underlies these hypotheses, the following can be mentioned: lipoprotein modification, oxidative transformation, shear stress, endothelial dysfunction, free radicals' action, homocysteinemia, diabetes mellitus, and decreased nitric oxide level. One of the latest hypotheses concerns the infectious nature of atherogenesis. The currently available data indicate that pathogen-associated molecular patterns from bacteria or viruses may be an etiological factor in atherosclerosis. This paper is devoted to the analysis of existing hypotheses for atherogenesis triggering, and special attention is paid to the contribution of bacterial and viral infections to the pathogenesis of atherosclerosis and cardiovascular disease.

Electrochemical Characterisation and Confirmation of Antioxidative Properties of Ivermectin in Biological Medium.

Ivermectin (IVM) is a drug from the group of anthelmintics used in veterinary and human medicine. Recently, interest in IVM has increased as it has been used for the treatment of some malignant diseases, as well as viral infections caused by the Zika virus, HIV-1 and SARS-CoV-2. The electrochemical behaviour of IVM was investigated using cyclic (CV), differential pulse (DPV) and square wave voltammetry (SWV) at glassy carbon electrode (GCE). IVM showed independent oxidation and reduction processes. The effect of pH and scan rate indicated the irreversibility of all processes and confirmed the diffusion character of oxidation and reduction as an adsorption-controlled process. Mechanisms for IVM oxidation at the tetrahydrofuran ring and reduction of the 1,4-diene structure in the IVM molecule are proposed. The redox behaviour of IVM in a biological matrix (human serum pool) showed a pronounced antioxidant potential similar to that of Trolox during short incubation, whereas a prolonged stay among biomolecules and in the presence of an exogenous pro-oxidant (tert-butyl hydroperoxide, TBH) resulted in a loss of its antioxidant effect. The antioxidant potential of IVM was confirmed by voltametric methodology which is proposed for the first time.

New insights into the regulatory roles of glutathione in NLRP3-inflammasome-mediated immune and inflammatory responses.

Glutathione (GSH) is the most abundant non-protein thiol (-SH) in mammalian cells. Its synthesis and metabolism serve to maintain cellular reduction-oxidation (redox) homeostasis, which is important for multiple cellular processes including proliferation, differentiation and death. An accumulating body of evidence suggests that the essential roles of GSH extended far beyond its oxidant and electrophile scavenger activities and regulatory role in the lifespan of cells. Recent findings revealed that altered GSH levels are closely associated with a wide range of pathologies including bacterial and viral infections, neurodegenerative diseases and autoimmune disorders, all of which are also characterized by aberrant activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. As a result of these findings, GSH was assigned a central role in influencing the activation of the NLRP3 inflammasome. To expand on our recent advances in understanding this process, we discuss here the emerging roles of GSH in activation of the NLRP3 inflammasome, and the therapeutic potential of GSH in its associated pathologies.

The cysS gene (ncgl0127) of Corynebacterium glutamicum is required for sulfur assimilation and affects oxidative stress-responsive cysteine import.

The OsnR protein functions as a transcriptional repressor of genes involved in redox-dependent stress responses. Here, we studied Corynebacterium glutamicum ORF ncgl0127 (referred to as cysS in this study), one of the target genes of OsnR, to reveal its role in osnR-mediated stress responses. The ΔcysS strain was found to be a cysteine auxotroph, and the transcription levels of the sulfur assimilatory genes and cysR, the master regulatory gene for sulfur assimilation, were low in this strain. Complementation of the strain with cysR transformed the strain into a cysteine prototroph. Cells challenged with oxidants or cysteine showed transcriptional stimulation of the cysS gene and decreased transcription of the ncgl2463 gene, which encodes a cysteine/cystine importer. The transcription of the ncgl2463 gene was increased in the ΔcysS strain and further stimulated by cysteine. Unlike the wild-type strain, ΔcysS cells grown with an excess amount of cysteine showed an oxidant- and alkylating agent-resistant phenotype, suggesting deregulated cysteine import. Collectively, our data suggest that the cysS gene plays a positive role in sulfur assimilation and a negative role in cysteine import, in particular in cells under oxidative stress.

Cardiologic evaluation of Turkish mitochondrial fatty acid oxidation disorders.

BACKGROUND: Mitochondrial fatty acid oxidation disorders (FAODs) cause impairment in energy metabolism and can lead to a spectrum of cardiac pathologies including cardiomyopathy and arrhythmias. The frequency of underlying cardiac pathologies and the response to recommended treatment in FAODs was investigated. METHODS: Sixty-eight children (35 males, 33 females) with the diagnosis of a FAOD were included in the study. Cardiac function was evaluated with 12-lead standard electrocardiography, echocardiography, and 24 h Holter monitoring. RESULTS: Forty-five patients (66%) were diagnosed after disease symptoms developed and 23 patients (34%) were diagnosed in the pre-symptomatic period. Among symptomatic patients (n: 45), cardiovascular findings were detected in 18 (40%) patients, including cardiomyopathy in 14 (31.1%) and conduction abnormalities in 4 (8.8%) patients. Cardiac symptoms were more frequently detected in primary systemic carnitine deficiency (57.1%). Patients with multiple acyl-CoA dehydrogenase, long-chain 3-hydroxyacyl-CoA dehydrogenase, and mitochondrial trifunctional protein deficiencies also had an increased frequency of cardiac symptoms. Patients with medium-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and carnitine palmitoyltransferase I deficiencies had a lower prevalence of cardiac symptoms both during admission and during clinical follow up. Cardiomyopathy resolved completely in 8/14 (57%) patients and partially in 2/14 (14.3%) patients with treatment. Two patients with cardiomyopathy died in the newborn period; cardiomyopathy persisted in 1 (7.1%) patient with very long-chain acyl-CoA dehydrogenase deficiency. CONCLUSION: Early diagnosis, treatment and follow up made a significant contribution to the improvement of cardiac symptoms of patients with FAODs.

Systemic redox imbalance in severe COVID-19 patients.

The aim of this study was to evaluate the systemic redox state and inflammatory markers in intensive care unit (ICU) or non-ICU severe COVID-19 patients during the hospitalization period. Blood samples were collected at hospital admission (T1) (Controls and COVID-19 patients), 5-7 days after admission (T2: 5-7 days after hospital admission), and at the discharge time from the hospital (T3: 0-72 h before leaving hospital or death) to analyze systemic oxidative stress markers and inflammatory variables. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were analyzed in peripheral granulocytes and monocytes. THP-1 human monocytic cell line was incubated with plasma from non-ICU and ICU COVID-19 patients and cell viability and apoptosis rate were analyzed. Higher total antioxidant capacity, protein oxidation, lipid peroxidation, and IL-6 at hospital admission were identified in both non-ICU and ICU COVID-19 patients. ICU COVID-19 patients presented increased C-reactive protein, ROS levels, and protein oxidation over hospitalization period compared to non-ICU patients, despite increased antioxidant status. Granulocytes and monocytes of non-ICU and ICU COVID-19 patients presented lower MMP and higher ROS production compared to the healthy controls, with the highest values found in ICU COVID-19 group. Finally, the incubation of THP-1 cells with plasma acquired from ICU COVID-19 patients at T3 hospitalization period decreased cell viability and apoptosis rate. In conclusion, disturbance in redox state is a hallmark of severe COVID-19 and is associated with cell damage and death.

Metal-induced oxidative stress and human plasma protein oxidation after SARS-CoV-2 infection.

Pathogenesis of COVID-19 by SARS-CoV-2 resulted in a global pandemic and public health emergency in 2020. Viral infection can induce oxidative stress through reactive oxygen species (ROS). Inflammation and environmental stress are major sources of oxidative stress after infection. Micronutrients such as iron, copper, zinc, and manganese play various roles in human tissues and their imbalance in blood can impact immune responses against pathogens including SARS CoV-2. We hypothesized that alteration of free metal ions during infection and metal-catalyzed oxidation plays a critical role towards pathogenesis after infection. We analyzed convalescent and hospitalized COVID-19 patient plasma using orthogonal analytical techniques to determine redox active metal concentrations, overall protein oxidation, oxidative modifications, and protein levels via proteomics to understand the consequences of metal-induced oxidative stress in COVID-19 plasma proteins. Metal analysis using ICP-MS showed significantly greater concentrations of copper in COVID-19 plasma compared to healthy controls. We demonstrate significantly greater total protein carbonylation, other oxidative modifications, and deamidation of plasma proteins in COVID-19 plasma compared to healthy controls. Proteomics analysis showed that levels of redox active proteins including hemoglobulin were elevated in COVID-19 plasma. Molecular modeling concurred with potential interactions between iron binding proteins and SARS CoV-2 surface proteins. Overall, increased levels of redox active metals and protein oxidation indicate that oxidative stress-induced protein oxidation in COVID-19 may be a consequence of the interactions of SARS-CoV-2 proteins with host cell metal binding proteins resulting in altered cellular homeostasis.

Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis.

BACKGROUND: The COVID-19 pandemic has become a huge threat to human health, infecting millions of people worldwide and causing enormous economic losses. Many novel small molecule drugs have been developed to treat patients with COVID-19, including Paxlovid, which block the synthesis of virus-related proteins and replication of viral RNA, respectively. Despite satisfactory clinical trial results, attention is now being paid to the long-term side effects of these antiviral drugs on the musculoskeletal system. To date, no study has reported the possible side effects, such as osteoarthritis, of Paxlovid. This study explored the effects of antiviral drug, Paxlovid, on chondrocyte proliferation and differentiation. METHODS: In this study, both in vitro and in vivo studies were performed to determine the effect of Paxlovid on chondrocyte degeneration and senescence. Furthermore, we explored the possible mechanism behind Paxlovid-induced acceleration of cartilage degeneration using transcriptome sequencing and related inhibitors were adopted to verify the downstream pathways behind such phenomenon. RESULTS: Paxlovid significantly inhibited chondrocyte extracellular matrix protein secretion. Additionally, Paxlovid significantly induced endoplasmic reticulum stress, oxidative stress, and downstream ferroptosis, thus accelerating the senescence and degeneration of chondrocytes. In vivo experiments showed that intraperitoneal injection of Paxlovid for 1 week exacerbated cartilage abrasion and accelerated the development of osteoarthritis in a mouse model. CONCLUSIONS: Paxlovid accelerated cartilage degeneration and osteoarthritis development, potentially by inducing endoplasmic reticulum stress and oxidative stress. Long-term follow-up is needed with special attention to the occurrence and development of osteoarthritis in patients treated with Paxlovid.

Alteration in Redox Status and Lipoprotein Profile in COVID-19 Patients with Mild, Moderate, and Severe Pneumonia.

Background: Metabolic alterations, particularly disorders of lipoprotein metabolism in COVID-19, may affect the course and outcome of the disease. This study aims at evaluating the lipoprotein profile and redox status in SARS-CoV-2 infected patients with different pneumonia severity and their association with lethal outcomes. Methods: The prospective cohort study was performed on 98 COVID-19 patients with mild, moderate, and severe pneumonia. Lipid and inflammatory parameters, lipoprotein subclasses, and redox status biomarkers were determined at the study entry and after one week. Results: Compared to patients with mild and moderate pneumonia, severely ill patients had higher oxidised low-density lipoprotein (oxLDL) and malondialdehyde levels and lower high-density lipoprotein cholesterol (HDL-C) concentrations and paraoxonase 1 activity. Reduction in the proportion of large HDL 2a subclasses with a concomitant increase in the proportion of smallest HDL 3c and small dense LDL (sdLDL) particles was observed in patients with severe disease during the time. However, these changes were reversed in the mild and moderate groups. The results showed a positive association between changes in oxLDL and total antioxidative status. However, prooxidants and antioxidants in plasma were lower in patients with lethal outcomes. Conclusions: Increased levels of oxLDL and sdLDL particles may contribute to the severity of COVID-19. The role of oxidative stress should be clarified in further studies, mainly its association with lethal outcomes.

New insights into extracellular and intracellular redox status in COVID-19 patients.

BACKGROUND: The imbalance of redox homeostasis induces hyper-inflammation in viral infections. In this study, we explored the redox system signature in response to SARS-COV-2 infection and examined the status of these extracellular and intracellular signatures in COVID-19 patients. METHOD: The multi-level network was constructed using multi-level data of oxidative stress-related biological processes, protein-protein interactions, transcription factors, and co-expression coefficients obtained from GSE164805, which included gene expression profiles of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and healthy controls. Top genes were designated based on the degree and closeness centralities. The expression of high-ranked genes was evaluated in PBMCs and nasopharyngeal (NP) samples of 30 COVID-19 patients and 30 healthy controls. The intracellular levels of GSH and ROS/O2• - and extracellular oxidative stress markers were assayed in PBMCs and plasma samples by flow cytometry and ELISA. ELISA results were applied to construct a classification model using logistic regression to differentiate COVID-19 patients from healthy controls. RESULTS: CAT, NFE2L2, SOD1, SOD2 and CYBB were 5 top genes in the network analysis. The expression of these genes and intracellular levels of ROS/O2• - were increased in PBMCs of COVID-19 patients while the GSH level decreased. The expression of high-ranked genes was lower in NP samples of COVID-19 patients compared to control group. The activity of extracellular enzymes CAT and SOD, and the total oxidant status (TOS) level were increased in plasma samples of COVID-19 patients. Also, the 2-marker panel of CAT and TOS and 3-marker panel showed the best performance. CONCLUSION: SARS-COV-2 disrupts the redox equilibrium in immune cells and the upper respiratory tract, leading to exacerbated inflammation and increased replication and entrance of SARS-COV-2 into host cells. Furthermore, utilizing markers of oxidative stress as a complementary validation to discriminate COVID-19 from healthy controls, seems promising.

Redox imbalance in COVID-19 pathophysiology.

BACKGROUND: The pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is required. METHODS: COVID-19 subjects (n = 64) and control subjects (n = 19) were enrolled, and blood was drawn within 72 h of diagnosis. Serum multiplex assays and peripheral blood mRNA sequencing was performed. Oxidant/free radical (electron paramagnetic resonance (EPR) spectroscopy, nitrite-nitrate assay) and antioxidant (ferrous reducing ability of serum assay and high-performance liquid chromatography) were performed. Multivariate analyses were performed to evaluate potential of indicated parameters to predict clinical outcome. RESULTS: Significantly greater levels of multiple inflammatory and vascular markers were quantified in the subjects admitted to the ICU compared to non-ICU subjects. Gene set enrichment analyses indicated significant enhancement of oxidant related pathways and biochemical assays confirmed a significant increase in free radical production and uric acid reduction in COVID-19 subjects. Multivariate analyses confirmed a positive association between serum levels of VCAM-1, ICAM-1 and a negative association between the abundance of one electron oxidants (detected by ascorbate radical formation) and mortality in COVID subjects while IL-17c and TSLP levels predicted need for intensive care in COVID-19 subjects. CONCLUSION: Herein we demonstrate a significant redox imbalance during COVID-19 infection affirming the potential for manipulation of oxidative stress pathways as a new therapeutic strategy COVID-19. However, further work is requisite for detailed identification of oxidants (O2•-, H2O2 and/or circulating transition metals such as Fe or Cu) contributing to this imbalance to avoid the repetition of failures using non-specific antioxidant supplementation.