Special Issue "ROS and COVID"

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (15 February 2021) | Viewed by 33103

Special Issue Editors

Prof. Dr. Dimitrios Kouretas
E-Mail Website
Guest Editor
Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece
Interests: antioxidant activity; plant phenolics; exercise; functional foods; toxicology; redox nutrition; antioxidant administration
Special Issues, Collections and Topics in MDPI journals
Dr. Konstantinos Poulas
E-Mail Website
Guest Editor
Department of Pharmacy, University of Patras, 26500 Patras, Greece
Interests: immunology; structural biology; molecular biology; COVID-19; SARS-CoV-2 spike function; cholinergic pathway
Special Issues, Collections and Topics in MDPI journals
Dr. Konstantinos Farsalinos
grade E-Mail Website
Guest Editor
Prof. Dr. Joanna Floros
E-Mail Website
Guest Editor
Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA

Special Issue Information

Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2. While the disease is mild in many cases, severe COVID-19 involves a hyper-inflammatory response, commonly called a cytokine storm, characterized by the release of pro-inflammatory cytokines that can lead to acute respiratory distress syndrome and death. It is known that pulmonary immunity in elderly persons is compromised, with impaired innate and adaptive cellular immune responses and reduced function of the lung itself. While overall innate immune responses may decline with age, inflammatory cytokines such as IL-6 and TNF-a, and acute phase reactants such as C-reactive protein, are elevated in older adults, maintaining a low level of chronic inflammation associated with increased levels of oxidative stress which drive the sustained levels of inflammation. Risk factors for severe COVID-19 such as obesity and diabetes are also associated with oxidative stress. Viral entry into the cytoplasm of the lung host epithelial cells results in interactions that affect cell metabolism and induce oxidative stress responses. The resulting inflammation and oxidative stress may have a negative impact on the expression and function of pulmonary surfactant, further compromising gas exchange and surfactant-protein-mediated innate host defense. For this reason, the study of reactive oxidant species (ROS) of all facets (nutrition modalities, supplements administration, redox biomarker study, antioxidant involvement, drug–protein interaction, the genetics of lung innate immune molecules such as the surfactant proteins, and the physiology and/or biochemistry of ROS in COVID-19) is of particular interest and constitutes the scope of the present Special Issue.

Prof. Dr. Dimitrios Kouretas
Dr. Konstantinos Poulas
Dr. Konstantinos Farsalinos
Prof. Dr. Joanna Floros
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (11 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review, Other

Editorial
ROS and COVID
Antioxidants 2022, 11(2), 339; https://doi.org/10.3390/antiox11020339 - 09 Feb 2022
Cited by 2 | Viewed by 539
Abstract
In recent years, the pandemic of coronavirus disease 19 (COVID-19), an infectious disease caused by variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has indisputably emerged as the predominant public health issue [...] Full article
(This article belongs to the Special Issue ROS and COVID)

Research

Jump to: Editorial, Review, Other

Article
Differential Redox State and Iron Regulation in Chronic Obstructive Pulmonary Disease, Acute Respiratory Distress Syndrome and Coronavirus Disease 2019
Antioxidants 2021, 10(9), 1460; https://doi.org/10.3390/antiox10091460 - 14 Sep 2021
Cited by 6 | Viewed by 1092
Abstract
In patients affected by Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD) and Coronavirus Disease 2019 (COVID-19), unclear mechanisms negatively interfere with the hematopoietic response to hypoxia. Although stimulated by physiological hypoxia, pulmonary hypoxic patients usually develop anemia, which may ultimately [...] Read more.
In patients affected by Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD) and Coronavirus Disease 2019 (COVID-19), unclear mechanisms negatively interfere with the hematopoietic response to hypoxia. Although stimulated by physiological hypoxia, pulmonary hypoxic patients usually develop anemia, which may ultimately complicate the outcome. To characterize this non-adaptive response, we dissected the interplay among the redox state, iron regulation, and inflammation in patients challenged by either acute (ARDS and COVID-19) or chronic (COPD) hypoxia. To this purpose, we evaluated a panel of redox state biomarkers that may integrate the routine iron metabolism assays to monitor the patients’ inflammatory and oxidative state. We measured redox and hematopoietic regulators in 20 ARDS patients, 20 ambulatory COPD patients, 9 COVID-19 ARDS-like patients, and 10 age-matched non-hypoxic healthy volunteers (controls). All the examined pathological conditions induced hypoxia, with ARDS and COVID-19 depressing the hematopoietic response without remarkable effects on erythropoietin. Free iron was higher than the controls in all patients, with higher levels of hepcidin and soluble transferrin receptor in ARDS and COVID-19. All markers of the redox state and antioxidant barrier were overexpressed in ARDS and COVID-19. However, glutathionyl hemoglobin, a candidate marker for the redox imbalance, was especially low in ARDS, despite depressed levels of glutathione being present in all patients. Although iron regulation was dysfunctional in all groups, the depressed antioxidant barrier in ARDS, and to a lesser extent in COVID-19, might induce greater inflammatory responses with consequent anemia. Full article
(This article belongs to the Special Issue ROS and COVID)
Show Figures

Figure 1

Article
Preliminary Findings on the Association of the Lipid Peroxidation Product 4-Hydroxynonenal with the Lethal Outcome of Aggressive COVID-19
Antioxidants 2021, 10(9), 1341; https://doi.org/10.3390/antiox10091341 - 25 Aug 2021
Cited by 13 | Viewed by 1128
Abstract
Major findings of the pilot study involving 21 critically ill patients during the week after admission to the critical care unit specialized for COVID-19 are presented. Fourteen patients have recovered, while seven passed away. There were no differences between them in respect to [...] Read more.
Major findings of the pilot study involving 21 critically ill patients during the week after admission to the critical care unit specialized for COVID-19 are presented. Fourteen patients have recovered, while seven passed away. There were no differences between them in respect to clinical or laboratory parameters monitored. However, protein adducts of the lipid peroxidation product 4-hydroxynonenal (HNE) were higher in the plasma of the deceased patients, while total antioxidant capacity was below the detection limit for the majority of sera samples in both groups. Moreover, levels of the HNE-protein adducts were constant in the plasma of the deceased patients, while in survivors, they have shown prominent and dynamic variations, suggesting that survivors had active oxidative stress response mechanisms reacting to COVID-19 aggression, which were not efficient in patients who died. Immunohistochemistry revealed the abundant presence of HNE-protein adducts in the lungs of deceased patients indicating that HNE is associated with the lethal outcome. It seems that HNE was spreading from the blood vessels more than being a consequence of pneumonia. Due to the limitations of the relatively small number of patients involved in this study, further research on HNE and antioxidants is needed. This might allow a better understanding of COVID-19 and options for utilizing antioxidants by personalized, integrative biomedicine approach to prevent the onset of HNE-mediated vitious circle of lipid peroxidation in patients with aggressive inflammatory diseases. Full article
(This article belongs to the Special Issue ROS and COVID)
Show Figures

Figure 1

Article
Electron Donor–Acceptor Capacity of Selected Pharmaceuticals against COVID-19
Antioxidants 2021, 10(6), 979; https://doi.org/10.3390/antiox10060979 - 18 Jun 2021
Cited by 4 | Viewed by 1726
Abstract
More than a year ago, the first case of infection by a new coronavirus was identified, which subsequently produced a pandemic causing human deaths throughout the world. Much research has been published on this virus, and discoveries indicate that oxidative stress contributes to [...] Read more.
More than a year ago, the first case of infection by a new coronavirus was identified, which subsequently produced a pandemic causing human deaths throughout the world. Much research has been published on this virus, and discoveries indicate that oxidative stress contributes to the possibility of getting sick from the new SARS-CoV-2. It follows that free radical scavengers may be useful for the treatment of coronavirus 19 disease (COVID-19). This report investigates the antioxidant properties of nine antivirals, two anticancer molecules, one antibiotic, one antioxidant found in orange juice (Hesperidin), one anthelmintic and one antiparasitic (Ivermectin). A molecule that is apt for scavenging free radicals can be either an electron donor or electron acceptor. The results I present here show Valrubicin as the best electron acceptor (an anticancer drug with three F atoms in its structure) and elbasvir as the best electron donor (antiviral for chronic hepatitis C). Most antiviral drugs are good electron donors, meaning that they are molecules capable of reduzing other molecules. Ivermectin and Molnupiravir are two powerful COVID-19 drugs that are not good electron acceptors, and the fact that they are not as effective oxidants as other molecules may be an advantage. Electron acceptor molecules oxidize other molecules and affect the conditions necessary for viral infection, such as the replication and spread of the virus, but they may also oxidize molecules that are essential for life. This means that the weapons used to defend us from COVID-19 may also harm us. This study posits the idea that oxide reduction balance may help explain the toxicity or efficacy of these drugs. These results represent a further advance on the road towards understanding the action mechanisms of drugs used as possible treatments for COVID-19. Looking ahead, clinical studies are needed to define the importance of antioxidants in treating COVID-19. Full article
(This article belongs to the Special Issue ROS and COVID)
Show Figures

Figure 1

Article
Effects of Ozone Treatment on Personal Protective Equipment Contaminated with SARS-CoV-2
Antioxidants 2020, 9(12), 1222; https://doi.org/10.3390/antiox9121222 - 03 Dec 2020
Cited by 17 | Viewed by 2172
Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing profound health, economic, and social problems worldwide. Management of personal protective equipment (PPE) and its potential limited availability have created concerns about the increased risks for healthcare professionals at hospitals and nursing homes. [...] Read more.
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing profound health, economic, and social problems worldwide. Management of personal protective equipment (PPE) and its potential limited availability have created concerns about the increased risks for healthcare professionals at hospitals and nursing homes. Ozone is a powerful oxidant agent. The objectives of this study were to examine the effects of ozone treatment on PPE contaminated with SARS-CoV-2, and to explore whether relative humidity could modify those effects. Methods: PPE contaminated by heat-inactivated SARS-CoV-2 were treated with different ozone concentrations, exposure times, and relative humidity conditions. SARS-CoV-2 gene amplification was assessed by real-time polymerase chain reaction. Results: There was no amplification of SARS-CoV-2 in PPE after the following ozone exposures: 30 s at 10,000 ppm (20 g/m3), 5 min at 4000 ppm, and 10 min at 2000 ppm. At lower ozone concentrations, 4–12 ppm (0.008–0.024 g/m3), the effects were highly dependent on the relative humidity conditions. Conclusions: Oxidative stress induced by ozone exposure eliminated heat-inactivated SARS-CoV-2 in different PPE components under appropriate exposure times, ozone concentrations, and relative humidity conditions. These findings could have implications in decreasing the risk of contamination associated with personal protective equipment management and in increasing its availability. Further research in the original SARS-CoV-2 strain is guaranteed. Full article
(This article belongs to the Special Issue ROS and COVID)
Show Figures

Graphical abstract

Article
Sex and SP-A2 Dependent NAD(H) Redox Alterations in Mouse Alveolar Macrophages in Response to Ozone Exposure: Potential Implications for COVID-19
Antioxidants 2020, 9(10), 915; https://doi.org/10.3390/antiox9100915 - 25 Sep 2020
Cited by 9 | Viewed by 2704
Abstract
Co-enzyme nicotinamide adenine dinucleotide (NAD(H)) redox plays a key role in macrophage function. Surfactant protein (SP-) A modulates the functions of alveolar macrophages (AM) and ozone (O3) exposure in the presence or absence of SP-A and reduces mouse survival in a [...] Read more.
Co-enzyme nicotinamide adenine dinucleotide (NAD(H)) redox plays a key role in macrophage function. Surfactant protein (SP-) A modulates the functions of alveolar macrophages (AM) and ozone (O3) exposure in the presence or absence of SP-A and reduces mouse survival in a sex-dependent manner. It is unclear whether and how NAD(H) redox status plays a role in the innate immune response in a sex-dependent manner. We investigated the NAD(H) redox status of AM from SP-A2 and SP-A knockout (KO) mice in response to O3 or filtered air (control) exposure using optical redox imaging technique. We found: (i) In SP-A2 mice, the redox alteration of AM in response to O3 showed sex-dependence with AM from males being significantly more oxidized and having a higher level of mitochondrial reactive oxygen species than females; (ii) AM from KO mice were more oxidized after O3 exposure and showed no sex differences; (iii) AM from female KO mice were more oxidized than female SP-A2 mice; and (iv) Two distinct subpopulations characterized by size and redox status were observed in a mouse AM sample. In conclusions, the NAD(H) redox balance in AM responds to O3 in a sex-dependent manner and the innate immune molecule, SP-A2, contributes to this observed sex-specific redox response. Full article
(This article belongs to the Special Issue ROS and COVID)
Show Figures

Graphical abstract

Article
Adelmidrol: A New Promising Antioxidant and Anti-Inflammatory Therapeutic Tool in Pulmonary Fibrosis
Antioxidants 2020, 9(7), 601; https://doi.org/10.3390/antiox9070601 - 09 Jul 2020
Cited by 31 | Viewed by 2376
Abstract
Background: Chronic pulmonary diseases are characterized by airway remodeling due to complex multicellular responses and the production of free oxygen radicals. They lead to a progressive decline of pulmonary functions. Adelmidrol is an analogue of palmitoylethanolamide (PEA), which is a well-known anti-inflammatory and [...] Read more.
Background: Chronic pulmonary diseases are characterized by airway remodeling due to complex multicellular responses and the production of free oxygen radicals. They lead to a progressive decline of pulmonary functions. Adelmidrol is an analogue of palmitoylethanolamide (PEA), which is a well-known anti-inflammatory and anti-oxidant compound. In this study, we investigated the efficacy of adelmidrol (10 mg/Kg) for bleomycin-induced pulmonary fibrosis in mice. Methods: Bleomycin intratracheal administration was performed on the first day and for the following twenty-one days, mice were treated with adelmidrol (10 mg/Kg). Results: The survival rate and body weight gain were recorded daily. At the end of the experiment, adelmidrol-administered animals showed reduced airway infiltration by inflammatory cells, Myeloperoxidase (MPO) activity, and pro-inflammatory cytokine overexpression (IL,6 IL-1β, TNF-α, and TGF-1β). Moreover, adelmidrol treatment was able to manage the significant incapacity of antioxidants and elevation of the oxidant burden, as shown by the MDA, SOD, and GSH levels and decreased nitric oxide production. It was also able to significantly modulate the JAK2/STAT3 and IκBα/NF-kB pathway. Histologic examination of the lung tissues showed reduced sample injury, mast cell degranulation, chymase activity, and collagen deposition. Conclusions: In sum, our results propose adelmidrol as a therapeutic approach in the treatment of pulmonary fibrosis. Full article
(This article belongs to the Special Issue ROS and COVID)
Show Figures

Graphical abstract

Review

Jump to: Editorial, Research, Other

Review
Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19
Antioxidants 2020, 9(9), 894; https://doi.org/10.3390/antiox9090894 - 21 Sep 2020
Cited by 9 | Viewed by 2250
Abstract
Chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as treatments for COVID-19. These drugs have been studied for many decades, primarily in the context of their use as antimalarials, where they induce oxidative stress-killing of the malarial parasite. Less appreciated, however, is evidence [...] Read more.
Chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as treatments for COVID-19. These drugs have been studied for many decades, primarily in the context of their use as antimalarials, where they induce oxidative stress-killing of the malarial parasite. Less appreciated, however, is evidence showing that CQ/HCQ causes systemic oxidative stress. In vitro and observational data suggest that CQ/HCQ can be repurposed as potential antiviral medications. This review focuses on the potential health concerns of CQ/HCQ induced by oxidative stress, particularly in the hyperinflammatory stage of COVID-19 disease. The pathophysiological role of oxidative stress in acute respiratory distress syndrome (ARDS) has been well-documented. Additional oxidative stress caused by CQ/HCQ during ARDS could be problematic. In vitro data showing that CQ forms a complex with free-heme that promotes lipid peroxidation of phospholipid bilayers are also relevant to COVID-19. Free-heme induced oxidative stress is implicated as a systemic activator of coagulation, which is increasingly recognized as a contributor to COVID-19 morbidity. This review will also provide a brief overview of CQ/HCQ pharmacology with an emphasis on how these drugs alter proton fluxes in subcellular organelles. CQ/HCQ-induced alterations in proton fluxes influence the type and chemical reactivity of reactive oxygen species (ROS). Full article
(This article belongs to the Special Issue ROS and COVID)
Show Figures

Graphical abstract

Review
The Importance of Redox Status in the Frame of Lifestyle Approaches and the Genetics of the Lung Innate Immune Molecules, SP-A1 and SP-A2, on Differential Outcomes of COVID-19 Infection
Antioxidants 2020, 9(9), 784; https://doi.org/10.3390/antiox9090784 - 25 Aug 2020
Cited by 13 | Viewed by 3055
Abstract
The pandemic of COVID-19 is of great concern to the scientific community. This mainly affects the elderly and people with underlying diseases. People with obesity are more likely to experience unpleasant disease symptoms and increased mortality. The severe oxidative environment that occurs in [...] Read more.
The pandemic of COVID-19 is of great concern to the scientific community. This mainly affects the elderly and people with underlying diseases. People with obesity are more likely to experience unpleasant disease symptoms and increased mortality. The severe oxidative environment that occurs in obesity due to chronic inflammation permits viral activation of further inflammation leading to severe lung disease. Lifestyle affects the levels of inflammation and oxidative stress. It has been shown that a careful diet rich in antioxidants, regular exercise, and fasting regimens, each and/or together, can reduce the levels of inflammation and oxidative stress and strengthen the immune system as they lead to weight loss and activate cellular antioxidant mechanisms and reduce oxidative damage. Thus, a lifestyle change based on the three pillars: antioxidants, exercise, and fasting could act as a proactive preventative measure against the adverse effects of COVID-19 by maintaining redox balance and well-functioning immunity. Moreover, because of the observed diversity in the expression of COVID-19 inflammation, the role of genetics of innate immune molecules, surfactant protein A (SP-A)1 and SP-A2, and their differential impact on the local lung microenvironment and host defense is reviewed as genetics may play a major role in the diverse expression of the disease. Full article
(This article belongs to the Special Issue ROS and COVID)
Show Figures

Graphical abstract

Review
The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19
Antioxidants 2020, 9(7), 624; https://doi.org/10.3390/antiox9070624 - 16 Jul 2020
Cited by 73 | Viewed by 12495
Abstract
The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease [...] Read more.
The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease has a mild or even asymptomatic progression. A common denominator in all conditions associated with COVID-19 appears to be the impaired redox homeostasis responsible for reactive oxygen species (ROS) accumulation; therefore, levels of glutathione (GSH), the key anti-oxidant guardian in all tissues, could be critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19. The present review provides a biochemical investigation of the mechanisms leading to deadly inflammation in severe COVID-19, counterbalanced by GSH. The pathways competing for GSH are described to illustrate the events concurring to cause a depletion of endogenous GSH stocks. Drawing on evidence from literature that demonstrates the reduced levels of GSH in the main conditions clinically associated with severe disease, we highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19. Finally, we discuss the current data about the feasibility of increasing GSH levels, which could be used to prevent and subdue the disease. Full article
(This article belongs to the Special Issue ROS and COVID)
Show Figures

Figure 1

Other

Opinion
Can Prophylactic High Flow of Humidified and Warmed Filtered Air Improve Survival from Bacterial Pneumonia and SARS-CoV-2 in Elderly Individuals? The Role of Surfactant Protein A
Antioxidants 2021, 10(5), 640; https://doi.org/10.3390/antiox10050640 - 22 Apr 2021
Cited by 3 | Viewed by 995
Abstract
In this opinion article, we discuss a serendipitous observation we made in a study investigating survival in aged mice after bacterial infection. This observation involved a non-invasive ventilation approach that led to variable and higher survival in male and female mice with different [...] Read more.
In this opinion article, we discuss a serendipitous observation we made in a study investigating survival in aged mice after bacterial infection. This observation involved a non-invasive ventilation approach that led to variable and higher survival in male and female mice with different genetic backgrounds for the innate immune molecule, surfactant protein A (SP-A). We suggest that employing the best ventilatory modality, whether that be HFNC or another method, may augment the role of other factors such as SP-A genetics and sex in a personalized approach, and may ultimately improve the outcome. Full article
(This article belongs to the Special Issue ROS and COVID)
Back to TopTop