Research

18 pages, 3254 KiB

Open AccessArticle

Hydroxytyrosol Recovers SARS-CoV-2-PLpro-Dependent Impairment of Interferon Related Genes in Polarized Human Airway, Intestinal and Liver Epithelial Cells

by Annalisa Crudele, Antonella Smeriglio, Mariarosaria Ingegneri, Nadia Panera, Marzia Bianchi, Maria Rita Braghini, Anna Pastore, Valeria Tocco, Rita Carsetti, Salvatore Zaffina, Anna Alisi and Domenico Trombetta

Antioxidants 2022, 11(8), 1466; https://doi.org/10.3390/antiox11081466 - 27 Jul 2022

Cited by 4 | Viewed by 2805

Abstract

The SARS-CoV-2 pandemic has caused approximately 6.3 million deaths, mainly due to the acute respiratory distress syndrome or multi-organ failure that characterizes COVID-19 acute disease. Post-acute COVID-19 syndrome, also known as long-COVID, is a condition characterized by a complex of symptoms that affects [...] Read more.

The SARS-CoV-2 pandemic has caused approximately 6.3 million deaths, mainly due to the acute respiratory distress syndrome or multi-organ failure that characterizes COVID-19 acute disease. Post-acute COVID-19 syndrome, also known as long-COVID, is a condition characterized by a complex of symptoms that affects 10–20% of the individuals who have recovered from the infection. Scientific and clinical evidence demonstrates that long-COVID can develop in both adults and children. It has been hypothesized that multi-organ effects of long-COVID could be associated with the persistence of virus RNA/proteins in host cells, but the real mechanism remains to be elucidated. Therefore, we sought to determine the effects of the exogenous expression of the papain-like protease (PLpro) domain of the non-structural protein (NSP3) of SARS-CoV-2 in polarized human airway (Calu-3), intestinal (Caco-2), and liver (HepG2) epithelial cells, and to evaluate the ability of the natural antioxidant hydroxytyrosol (HXT) in neutralizing these effects. Our results demonstrated that PLpro was able to induce a cascade of inflammatory genes and proteins (mainly associated with the interferon pathway) and increase the apoptotic rate and expression of several oxidative stress markers in all evaluated epithelial cells. Noteably, the treatment with 10 μM HXT reverted PL-pro-dependent effects almost completely. This study provides the first evidence that SARS-CoV-2 PLpro remaining in host cells after viral clearance may contribute to the pathogenetic mechanisms of long-COVID. These effects may be counteracted by natural antioxidants. Further clinical and experimental studies are necessary to confirm this hypothesis. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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14 pages, 658 KiB

Open AccessArticle

Hyperferritinemia, Low Circulating Iron and Elevated Hepcidin May Negatively Impact Outcome in COVID-19 Patients: A Pilot Study

by Robert Szabo, Cristina Petrisor, Constantin Bodolea, Robert Simon, Ioana Maries, Sebastian Tranca and Teodora Mocan

Antioxidants 2022, 11(7), 1364; https://doi.org/10.3390/antiox11071364 - 14 Jul 2022

Cited by 7 | Viewed by 2182

Abstract

Inflammation in COVID-19 produces intracellular iron overload with low circulating iron available for metabolic processes. The accumulated intracellular iron generates reactive species of oxygen and results in ferroptosis, a non-programmed cell death. Since no organ is spared, iron dysmetabolism increases the mortality and [...] Read more.

Inflammation in COVID-19 produces intracellular iron overload with low circulating iron available for metabolic processes. The accumulated intracellular iron generates reactive species of oxygen and results in ferroptosis, a non-programmed cell death. Since no organ is spared, iron dysmetabolism increases the mortality and morbidity. Hepcidin and the mediator interleukin 6 are believed to play a role in the process. Our aim is to evaluate the predictive values of serologic iron and inflammatory parameters in COVID-19 critically ill patients. Hence, 24 patients were included. Hepcidin and interleukin 6, along with routine blood parameters, were determined and outcomes, such as death, multiple organ damage (MOD), anemia, and need for transfusions, were assessed. The results of this pilot study indicate that iron metabolism parameters individually, as well as models consisting of multiple laboratory and clinical variables, may predict the outcomes. Further larger studies are needed to validate the results of this pilot stud. However, this paper identifies a new direction for research. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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10 pages, 532 KiB

Open AccessArticle

Dramatic Decrease of Vitamin K2 Subtype Menaquinone-7 in COVID-19 Patients

by Harald Mangge, Florian Prueller, Christine Dawczynski, Pero Curcic, Zdenka Sloup, Magdalena Holter, Markus Herrmann and Andreas Meinitzer

Antioxidants 2022, 11(7), 1235; https://doi.org/10.3390/antiox11071235 - 24 Jun 2022

Cited by 6 | Viewed by 5308

Abstract

(1) Background: Vitamin K (VK) is a fat-soluble compound with a common chemical structure, a 2-methyl-1,4-naphthoquinone ring, and a variable aliphatic side-chain. VK is involved in the synthesis of blood-clotting proteins, bone stability, anti-oxidative, and immune inflammatory-modulatory functions. Vitamin K also activates [...] Read more.

(1) Background: Vitamin K (VK) is a fat-soluble compound with a common chemical structure, a 2-methyl-1,4-naphthoquinone ring, and a variable aliphatic side-chain. VK is involved in the synthesis of blood-clotting proteins, bone stability, anti-oxidative, and immune inflammatory-modulatory functions. Vitamin K also activates protein S, which acts as an antioxidant and anti-inflammatory. The fact that cytokine overproduction, oxidative stress, and disturbed microcirculation by thrombogenicity play a central role in severe COVID-19 prompted us to analyze this vitamin. (2) Methods: We analyzed by a validated liquid-chromatography tandem mass-spectrometry method serum vitamin K1, MK4, MK7, and VK epoxide levels in 104 healthy controls, 77 patients with non-COVID-19 pneumonia, and 135 hospitalized COVID-19 patients with potentially fatal outcomes admitted to our University Hospital between April and November 2020. We included the quotient between VK and triglyceride (TG, nmol/mmol/L) values in the analyses with respect to the TG transporter function for all VK subtypes. Additionally, we assessed anthropometric, routine laboratory, and clinical data from the laboratory and hospital information systems. (3) Results: The COVID-19 patients had significantly lower MK7 levels than non-COVID-19 pneumonia patients and healthy controls. COVID-19 and non-COVID-19 pneumonia patients had significantly lower vitamin K1 and significantly higher MK4 compared to healthy controls, but did not differ significantly from each other. Between COVID-19 non-survivors (n = 30) and survivors (n = 105) no significant differences were seen in all vitamin K subtypes, despite the fact that non-survivors had higher peak concentrations of IL-6, CRP, d-dimer, and higher oxygen needs, respectively. (4) Conclusions: The present data identified significantly decreased vitamin K1, K2 (MK7), and increased MK4 levels in patients with COVID-19 compared to healthy controls. Vitamin K2 (MK7) was lowest in COVID-19 patients irrespective of potentially fatal courses, indicating consumption of this VK subtype by COVID-19 immanent effects, most probably inflammatory and oxidative stress factors. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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17 pages, 1192 KiB

Open AccessArticle

Oxidative Stress and Inflammatory Status in COVID-19 Outpatients: A Health Center-Based Analytical Cross-Sectional Study

by Sahar Golabi, Sheyda Ghasemi, Maryam Adelipour, Reza Bagheri, Katsuhiko Suzuki, Alexei Wong, Maryam Seyedtabib and Mahshid Naghashpour

Antioxidants 2022, 11(4), 606; https://doi.org/10.3390/antiox11040606 - 22 Mar 2022

Cited by 12 | Viewed by 2721

Abstract

The antioxidant system can be critical in reducing exacerbated inflammation in COVID-19. This study compared the antioxidant and inflammatory responses between COVID-19 outpatients and seemingly healthy individuals. This descriptive-analytical cross-sectional study was conducted on 53 COVID-19 outpatients and 53 healthy individuals as controls. [...] Read more.

The antioxidant system can be critical in reducing exacerbated inflammation in COVID-19. This study compared the antioxidant and inflammatory responses between COVID-19 outpatients and seemingly healthy individuals. This descriptive-analytical cross-sectional study was conducted on 53 COVID-19 outpatients and 53 healthy individuals as controls. The serum concentrations of amyloid A (SAA), total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured and compared between COVID-19 patients and controls using the independent sample t-test before and after controlling for dietary supplement use. A generalized estimating equation (GEE) regression model, limited to COVID-19 patients, was used to evaluate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of disease symptoms on days 1, 7, 14, 21, and 28 after the disease onset. Serum concentrations of SOD (p ≤ 0.001) and GPx (p = 0.001) were significantly higher in COVID-19 patients than in controls before adjustment for dietary supplement use. GPx remained significantly higher among COVID-19 patients than in controls after adjustment for all dietary supplements (p = 0.005). Moreover, serum concentrations of GPx (p = 0.003), SOD (p = 0.022), and TAC (p = 0.028) remained significantly higher among COVID-19 patients than in controls after adjustment for vitamin D supplementation. This study showed higher GPx in COVID-19 outpatients than in controls after adjustment for dietary supplement use. Moreover, elevated SOD, GPx, and TAC concentrations were shown in COVID-19 outpatients compared to controls after adjusting for vitamin D supplementation. These results may provide a useful therapeutic target for treating oxidative stress in COVID-19 disease, which may help ameliorate the pandemic. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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23 pages, 80152 KiB

Open AccessArticle

Assessment of Antioxidant, Immunomodulatory Activity of Oxidised Epigallocatechin-3-Gallate (Green Tea Polyphenol) and Its Action on the Main Protease of SARS-CoV-2—An In Vitro and In Silico Approach

by Ramakrishna Ungarala, Manne Munikumar, Sukesh Narayan Sinha, Dileshwar Kumar, R. Shyam Sunder and Suresh Challa

Antioxidants 2022, 11(2), 294; https://doi.org/10.3390/antiox11020294 - 31 Jan 2022

Cited by 17 | Viewed by 2992

Abstract

Owing to the instability of Epigallocatechin Gallate (EGCG), it may undergo auto-oxidation and form oxidised products or dimers. In the present study, we aimed to evaluate the therapeutic effects, including antioxidation and immunomodulatory action, of the Oxidised Epigallocatechin Gallate (O-EGCG) as compared to [...] Read more.

Owing to the instability of Epigallocatechin Gallate (EGCG), it may undergo auto-oxidation and form oxidised products or dimers. In the present study, we aimed to evaluate the therapeutic effects, including antioxidation and immunomodulatory action, of the Oxidised Epigallocatechin Gallate (O-EGCG) as compared to native EGCG and the action of these compounds on main protease (M^pro) docking against SARS-CoV-2. HCT-116 (Human Colon Cancer) cell lines were used to estimate the total antioxidant capacity and lipid peroxidation levels and pro-inflammatory markers (human IL-6, IL-1β, TNF-α). Further, molecular docking analysis was performed by AutoDock and visualised in Discovery studio. Improved antioxidant capacity of O-EGCG was observed, and there was a significant decrease in the inflammatory markers (IL-1β, IL-6, and TNF-α) when O-EGCG was applied as compared to EGCG. The O-EGCG was shown to be strongly associated with the highest docking score and active site residues of IL-1, IL-6, and TNF- α, as well as the M^pro of SARS-CoV-2, according to in silico approach. The in vitro and in silico analyses indicate an improved therapeutic action of the oxidised form of EGCG. The effective inhibitory action of O-EGCG against SARS-CoV-2 suggests further exploration of the compound against COVID-19 and its efficacy. However, in vivo studies and understanding of the mechanism of action of O-EGCG may yield a better opinion on the use of O-EGCG and future human clinical trials. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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16 pages, 1768 KiB

Open AccessArticle

COVID-19 during Gestation: Maternal Implications of Evoked Oxidative Stress and Iron Metabolism Impairment

by Jorge Moreno-Fernandez, Julio J. Ochoa, Catalina De Paco Matallana, Africa Caño, Estefania Martín-Alvarez, Javier Sanchez-Romero, Juan M. Toledano, Maria Puche-Juarez, Sonia Prados, Susana Ruiz-Duran, Lucia Diaz-Meca, María Paz Carrillo and Javier Diaz-Castro

Antioxidants 2022, 11(2), 184; https://doi.org/10.3390/antiox11020184 - 18 Jan 2022

Cited by 9 | Viewed by 2880

Abstract

COVID-19 has reached pandemic proportions worldwide, with considerable consequences for both health and the economy. In pregnant women, COVID-19 can alter the metabolic environment, iron metabolism, and oxygen supply of trophoblastic cells, and therefore have a negative influence on essential mechanisms of fetal [...] Read more.

COVID-19 has reached pandemic proportions worldwide, with considerable consequences for both health and the economy. In pregnant women, COVID-19 can alter the metabolic environment, iron metabolism, and oxygen supply of trophoblastic cells, and therefore have a negative influence on essential mechanisms of fetal development. The purpose of this study was to investigate, for the first time, the effects of COVID-19 infection during pregnancy with regard to the oxidative/antioxidant status in mothers’ serum and placenta, together with placental iron metabolism. Results showed no differences in superoxide dismutase activity and placental antioxidant capacity. However, antioxidant capacity decreased in the serum of infected mothers. Catalase activity decreased in the COVID-19 group, while an increase in 8-hydroxy-2’-deoxyguanosine, hydroperoxides, 15-FT-isoprostanes, and carbonyl groups were recorded in this group. Placental vitamin D, E, and Coenzyme-Q10 also showed to be increased in the COVID-19 group. As for iron-related proteins, an up-regulation of placental DMT1, ferroportin-1, and ferritin expression was recorded in infected women. Due to the potential role of iron metabolism and oxidative stress in placental function and complications, further research is needed to explain the pathogenic mechanism of COVID-19 that may affect pregnancy, so as to assess the short-term and long-term outcomes in mothers’ and infants’ health. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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13 pages, 439 KiB

Open AccessArticle

Acute Lung Injury Biomarkers in the Prediction of COVID-19 Severity: Total Thiol, Ferritin and Lactate Dehydrogenase

by Alvaro Martinez Mesa, Eva Cabrera César, Elisa Martín-Montañez, Esther Sanchez Alvarez, Pilar Martinez Lopez, Yanina Romero-Zerbo, Maria Garcia-Fernandez and Jose Luis Velasco Garrido

Antioxidants 2021, 10(8), 1221; https://doi.org/10.3390/antiox10081221 - 29 Jul 2021

Cited by 22 | Viewed by 2536

Abstract

SARS-CoV-2 (COVID-19) patients who develop acute respiratory distress syndrome (ARDS) can suffer acute lung injury, or even death. Early identification of severe disease is essential in order to control COVID-19 and improve prognosis. Oxidative stress (OS) appears to play an important role in [...] Read more.

SARS-CoV-2 (COVID-19) patients who develop acute respiratory distress syndrome (ARDS) can suffer acute lung injury, or even death. Early identification of severe disease is essential in order to control COVID-19 and improve prognosis. Oxidative stress (OS) appears to play an important role in COVID-19 pathogenesis; we therefore conceived a study of the potential discriminative ability of serum biomarkers in patients with ARDS and those with mild to moderate disease (non-ARDS). 60 subjects were enrolled in a single-centre, prospective cohort study of consecutively admitted patients: 29 ARDS/31 non-ARDS. Blood samples were drawn and marker levels analysed by spectrophotometry and immunoassay techniques. C-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin were significantly higher in ARDS versus non-ARDS cases at hospital admission. Leukocytes, LDH, ferritin, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were also significantly elevated in ARDS compared to non-ARDS patients during the hospital stay. Total thiol (TT) was found to be significantly lower in ARDS. Conversely, D-dimer, matrix metalloproteinase-9 (MMP-9) and advanced glycosylated end products (AGE) were elevated. Leukocytes, LDH, CRP, ferritin and IL-6 were found to be significantly higher in non-survivors. However, lymphocyte, tumour necrosis factor beta (TGF-β), and TT were lower. In summary, our results support the potential value of TT, ferritin and LDH as prognostic biomarkers for ARDS development in COVID-19 patients, distinguishing non-ARDS from ARDS (AUCs = 0.92; 0.91; 0.89) in a fast and cost-effective manner. These oxidative/inflammatory parameters appear to play an important role in COVID-19 monitoring and can be used in the clinical management of patients. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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12 pages, 302 KiB

Open AccessArticle

Oxidative Stress Status in COVID-19 Patients Hospitalized in Intensive Care Unit for Severe Pneumonia. A Pilot Study

by Joël Pincemail, Etienne Cavalier, Corinne Charlier, Jean-Paul Cheramy–Bien, Eric Brevers, Audrey Courtois, Marjorie Fadeur, Smail Meziane, Caroline Le Goff, Benoît Misset, Adelin Albert, Jean-Olivier Defraigne and Anne-Françoise Rousseau

Antioxidants 2021, 10(2), 257; https://doi.org/10.3390/antiox10020257 - 07 Feb 2021

Cited by 94 | Viewed by 9385

Abstract

Background: A key role of oxidative stress has been highlighted in the pathogenesis of COVID-19. However, little has been said about oxidative stress status (OSS) of COVID-19 patients hospitalized in intensive care unit (ICU). Material and Methods: Biomarkers of the systemic OSS included [...] Read more.

Background: A key role of oxidative stress has been highlighted in the pathogenesis of COVID-19. However, little has been said about oxidative stress status (OSS) of COVID-19 patients hospitalized in intensive care unit (ICU). Material and Methods: Biomarkers of the systemic OSS included antioxidants (9 assays), trace elements (3 assays), inflammation markers (4 assays) and oxidative damage to lipids (3 assays). Results: Blood samples were drawn after 9 (7–11) and 41 (39–43) days of ICU stay, respectively in 3 and 6 patients. Vitamin C, thiol proteins, reduced glutathione, γ-tocopherol, β-carotene and PAOT^® score were significantly decreased compared to laboratory reference values. Selenium concentration was at the limit of the lower reference value. By contrast, the copper/zinc ratio (as a source of oxidative stress) was higher than reference values in 55% of patients while copper was significantly correlated with lipid peroxides (r = 0.95, p < 0.001). Inflammatory biomarkers (C-reactive protein and myeloperoxidase) were significantly increased when compared to normals. Conclusions: The systemic OSS was strongly altered in critically ill COVID-19 patients as evidenced by increased lipid peroxidation but also by deficits in some antioxidants (vitamin C, glutathione, thiol proteins) and trace elements (selenium). Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

Review

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17 pages, 3820 KiB

Open AccessReview

Cyanobacteria and Algae-Derived Bioactive Metabolites as Antiviral Agents: Evidence, Mode of Action, and Scope for Further Expansion; A Comprehensive Review in Light of the SARS-CoV-2 Outbreak

by Biswajita Pradhan, Rabindra Nayak, Srimanta Patra, Prajna Paramita Bhuyan, Soumya Ranjan Dash, Jang-Seu Ki, Siba Prasad Adhikary, Andrea Ragusa and Mrutyunjay Jena

Antioxidants 2022, 11(2), 354; https://doi.org/10.3390/antiox11020354 - 10 Feb 2022

Cited by 28 | Viewed by 3617

Abstract

COVID-19—a severe acute respiratory syndrome disease caused by coronavirus 2 (SARS-CoV-2)—has recently attracted global attention, due to its devastating impact, to the point of being declared a pandemic. The search for new natural therapeutic drugs is mandatory, as the screening of already-known antiviral [...] Read more.

COVID-19—a severe acute respiratory syndrome disease caused by coronavirus 2 (SARS-CoV-2)—has recently attracted global attention, due to its devastating impact, to the point of being declared a pandemic. The search for new natural therapeutic drugs is mandatory, as the screening of already-known antiviral drugs so far has led to poor results. Several species of marine algae have been reported as sources of bioactive metabolites with potential antiviral and immunomodulatory activities, among others. Some of these bioactive metabolites might be able to act as antimicrobial drugs and also against viral infections by inhibiting their replication. Moreover, they could also trigger immunity against viral infection in humans and could be used as protective agents against COVID-In this context, this article reviews the main antiviral activities of bioactive metabolites from marine algae and their potential exploitation as anti-SARS-CoV-2 drugs. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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13 pages, 1129 KiB

Open AccessReview

Potential and Possible Therapeutic Effects of Melatonin on SARS-CoV-2 Infection

by Evgeny Shchetinin, Vladimir Baturin, Eduard Arushanyan, Albert Bolatchiev and Dmitriy Bobryshev

Antioxidants 2022, 11(1), 140; https://doi.org/10.3390/antiox11010140 - 09 Jan 2022

Cited by 7 | Viewed by 3627

Abstract

The absence of effective drugs for COVID-19 prevention and treatment requires the search for new candidates among approved medicines. Fundamental studies and clinical observations allow us to approach an understanding of the mechanisms of damage and protection from exposure to SARS-CoV-2, to identify [...] Read more.

The absence of effective drugs for COVID-19 prevention and treatment requires the search for new candidates among approved medicines. Fundamental studies and clinical observations allow us to approach an understanding of the mechanisms of damage and protection from exposure to SARS-CoV-2, to identify possible points of application for pharmacological interventions. In this review we presented studies on the anti-inflammatory, antioxidant, and immunotropic properties of melatonin. We have attempted to present scientifically proven mechanisms of action for the potential therapeutic use of melatonin during SARS-CoV-2 infection. A wide range of pharmacological properties allows its inclusion as an effective addition to the methods of prevention and treatment of COVID-19. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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24 pages, 3213 KiB

Open AccessReview

Implications of Vitamins in COVID-19 Prevention and Treatment through Immunomodulatory and Anti-Oxidative Mechanisms

by Juan M. Toledano, Jorge Moreno-Fernandez, María Puche-Juarez, Julio J. Ochoa and Javier Diaz-Castro

Antioxidants 2022, 11(1), 5; https://doi.org/10.3390/antiox11010005 - 21 Dec 2021

Cited by 9 | Viewed by 5504

Abstract

Since the appearance of the coronavirus disease 2019 (COVID-19) and its announcement as a global pandemic, the search for prophylactic and therapeutic options have become a priority for governments and the scientific community. The approval of several vaccines against SARS-CoV-2 is being crucial [...] Read more.

Since the appearance of the coronavirus disease 2019 (COVID-19) and its announcement as a global pandemic, the search for prophylactic and therapeutic options have become a priority for governments and the scientific community. The approval of several vaccines against SARS-CoV-2 is being crucial to overcome this situation, although the victory will not be achieved while the whole population worldwide is not protected against the virus. This is why alternatives should be studied in order to successfully support the immune system before and during a possible infection. An optimal inflammatory and oxidative stress status depends on an adequate diet. Poor levels of several nutrients could be related to an impaired immune response and, therefore, an increased susceptibility to infection and serious outcomes. Vitamins exert a number of anti-microbial, immunomodulatory, anti-inflammatory, and antioxidant activities, which can be of use to fight against this and several other diseases (especially vitamin D and C). Even though they cannot be considered as a definitive therapeutic option, in part owing to the lack of solid conclusions from well-designed clinical trials, currently available evidence from similar respiratory diseases may indicate that it would be rational to deeply explore the use of vitamins during this global pandemic. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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43 pages, 4925 KiB

Open AccessReview

The 15-Months Clinical Experience of SARS-CoV-2: A Literature Review of Therapies and Adjuvants

by Alessio Danilo Inchingolo, Gianna Dipalma, Angelo Michele Inchingolo, Giuseppina Malcangi, Luigi Santacroce, Maria Teresa D’Oria, Ciro Gargiulo Isacco, Ioana Roxana Bordea, Sebastian Candrea, Antonio Scarano, Benedetta Morandi, Massimo Del Fabbro, Marco Farronato, Gianluca Martino Tartaglia, Mario Giosuè Balzanelli, Andrea Ballini, Ludovica Nucci, Felice Lorusso, Silvio Taschieri and Francesco Inchingolo

Antioxidants 2021, 10(6), 881; https://doi.org/10.3390/antiox10060881 - 31 May 2021

Cited by 22 | Viewed by 5772

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease of 2019 (COVID-19) that emerged in December 2019 in Wuhan, China, and rapidly spread worldwide, with a daily increase in confirmed cases and infection-related deaths. The World [...] Read more.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease of 2019 (COVID-19) that emerged in December 2019 in Wuhan, China, and rapidly spread worldwide, with a daily increase in confirmed cases and infection-related deaths. The World Health Organization declared a pandemic on the 11th of March 2020. COVID-19 presents flu-like symptoms that become severe in high-risk medically compromised subjects. The aim of this study was to perform an updated overview of the treatments and adjuvant protocols for COVID-19. Methods: A systematic literature search of databases was performed (MEDLINE PubMed, Google Scholar, UpToDate, Embase, and Web of Science) using the keywords: “COVID-19”, “2019-nCoV”, “coronavirus” and “SARS-CoV-2” (date range: 1 January 2019 to 31st October 2020), focused on clinical features and treatments. Results: The main treatments retrieved were antivirals, antimalarials, convalescent plasma, immunomodulators, corticosteroids, anticoagulants, and mesenchymal stem cells. Most of the described treatments may provide benefits to COVID-19 subjects, but no one protocol has definitively proven its efficacy. Conclusions: While many efforts are being spent worldwide in research aimed at identifying early diagnostic methods and evidence-based effective treatments, mass vaccination is thought to be the best option against this disease in the near future. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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20 pages, 1385 KiB

Open AccessReview

Type 1 Diabetes Mellitus in the SARS-CoV-2 Pandemic: Oxidative Stress as a Major Pathophysiological Mechanism Linked to Adverse Clinical Outcomes

by Aikaterini Kountouri, Emmanouil Korakas, Ignatios Ikonomidis, Athanasios Raptis, Nikolaos Tentolouris, George Dimitriadis and Vaia Lambadiari

Antioxidants 2021, 10(5), 752; https://doi.org/10.3390/antiox10050752 - 09 May 2021

Cited by 13 | Viewed by 3403

Abstract

Recent reports have demonstrated the association between type 1 diabetes mellitus (T1DM) and increased morbidity and mortality rates during coronavirus disease (COVID-19) infection, setting a priority of these patients for vaccination. Impaired innate and adaptive immunity observed in T1DM seem to play a [...] Read more.

Recent reports have demonstrated the association between type 1 diabetes mellitus (T1DM) and increased morbidity and mortality rates during coronavirus disease (COVID-19) infection, setting a priority of these patients for vaccination. Impaired innate and adaptive immunity observed in T1DM seem to play a major role. Severe, life-threatening COVID-19 disease is characterized by the excessive release of pro-inflammatory cytokines, known as a “cytokine storm”. Patients with T1DM present elevated levels of cytokines including interleukin-1a (IL), IL-1β, IL-2, IL-6 and tumor necrosis factor alpha (TNF-α), suggesting the pre-existence of chronic inflammation, which, in turn, has been considered the major risk factor of adverse COVID-19 outcomes in many cohorts. Even more importantly, oxidative stress is a key player in COVID-19 pathogenesis and determines disease severity. It is well-known that extreme glucose excursions, the prominent feature of T1DM, are a potent mediator of oxidative stress through several pathways including the activation of protein kinase C (PKC) and the increased production of advanced glycation end products (AGEs). Additionally, chronic endothelial dysfunction and the hypercoagulant state observed in T1DM, in combination with the direct damage of endothelial cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may result in endothelial and microcirculation impairment, which contribute to the pathogenesis of acute respiratory syndrome and multi-organ failure. The binding of SARS-CoV-2 to angiotensin converting enzyme 2 (ACE2) receptors in pancreatic b-cells permits the direct destruction of b-cells, which contributes to the development of new-onset diabetes and the induction of diabetic ketoacidosis (DKA) in patients with T1DM. Large clinical studies are required to clarify the exact pathways through which T1DM results in worse COVID-19 outcomes. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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Other

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37 pages, 2299 KiB

Open AccessSystematic Review

Molecular Mechanisms Related to Responses to Oxidative Stress and Antioxidative Therapies in COVID-19: A Systematic Review

by Evangelia Eirini Tsermpini, Una Glamočlija, Fulden Ulucan-Karnak, Sara Redenšek Trampuž and Vita Dolžan

Antioxidants 2022, 11(8), 1609; https://doi.org/10.3390/antiox11081609 - 19 Aug 2022

Cited by 20 | Viewed by 3702

Abstract

The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease’s progression is not entirely understood, but there are strong indications that oxidative stress and the defense against reactive oxygen species are crucial players. A big influx [...] Read more.

The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease’s progression is not entirely understood, but there are strong indications that oxidative stress and the defense against reactive oxygen species are crucial players. A big influx of immune cells to the site of infection is marked by the increase in reactive oxygen and nitrogen species. Our article aims to highlight the critical role of oxidative stress in the emergence and severity of COVID-19 and, more importantly, to shed light on the underlying molecular and genetic mechanisms. We have reviewed the available literature and clinical trials to extract the relevant genetic variants within the oxidative stress pathway associated with COVID-19 and the anti-oxidative therapies currently evaluated in the clinical trials for COVID-19 treatment, in particular clinical trials on glutathione and N-acetylcysteine. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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