A Pilot Study on Oxidative Stress during the Recovery Phase in Critical COVID-19 Patients in a Rehabilitation Facility: Potential Utility of the PAOT® Technology for Assessing Total Anti-Oxidative Capacity
Joël Pincemail, Anne-Françoise Rousseau, Jean-François Kaux, Jean-Paul Cheramy-Bien, Christine Bruyère, Jeanine Prick, David Stern, Mouna-Messaouda Kaci, Benoît Maertens De Noordhout, Adelin Albert, Céline Eubelen, Caroline Le Goff, Benoît Misset, Etienne Cavalier, Corinne Charlier, Smail Meziane
Biomedicines, doi:10.3390/biomedicines11051308
Background: Oxidative stress (OS) could cause various COVID-19 complications. Recently, we have developed the Pouvoir AntiOxydant Total (PAOT®) technology for reflecting the total antioxidant capacity (TAC) of biological samples. We aimed to investigate systemic oxidative stress status (OSS) and to evaluate the utility of PAOT®for assessing TAC during the recovery phase in critical COVID-19 patients in a rehabilitation facility. Materials and Methods: In a total of 12 critical COVID-19 patients in rehabilitation, 19 plasma OSS biomarkers were measured: antioxidants, TAC, trace elements, oxidative damage to lipids, and inflammatory biomarkers. TAC level was measured in plasma, saliva, skin, and urine, using PAOT and expressed as PAOT-Plasma, -Saliva, -Skin, and -Urine scores, respectively. Plasma OSS biomarker levels were compared with levels from previous studies on hospitalized COVID-19 patients and with the reference population. Correlations between four PAOT scores and plasma OSS biomarker levels were analyzed. Results: During the recovery phase, plasma levels in antioxidants (γ-tocopherol, β-carotene, total glutathione, vitamin C and thiol proteins) were significantly lower than reference intervals, whereas total hydroperoxides and myeloperoxidase (a marker of inflammation) were significantly higher. Copper negatively correlated with total hydroperoxides (r = 0.95, p = 0.001). A similar, deeply modified OSS was already observed in COVID-19 patients hospitalized in an intensive care unit. TAC evaluated in saliva, urine, and skin correlated negatively with copper and with plasma total hydroperoxides. To conclude, the systemic OSS, determined using a large number of biomarkers, was always significantly increased in cured COVID-19 patients during their recovery phase. The less costly evaluation of TAC using an electrochemical method could potentially represent a good alternative to the individual analysis of biomarkers linked to pro-oxidants.
Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/biomedicines11051308/s1. Figure S1 : Individual plasma concentrations of antioxidants observed in COVID-19 patients as compared to CHU Liège reference intervals. LRV: lower reference value; URV: upper reference value.
Conflicts of Interest: The authors from academic institutions declare no conflict of interest. IEA had no role in the design of the study, the interpretation of data, or the decision to publish the results in Biomedicines.
References
Bartolini, Stabile, Bastianelli, Giustarini, Pierucci et al., SARS-2-CoV2 infection impairs the metabolism and redox function of cellular glutathione, Redox Biol
Bomer, Beverborg, Hoes, Streng, Vermeer et al., Selenium and outcome in heart failure, Eur. J. Heart Fail,
doi:10.1002/ejhf.1644Brainina, Gerasimova, Varzakova, Kazakov, Galperin, Noninvasive method of determining skin antioxidant/oxidant activity: Clinical and cosmetics applications, Anal. Bioanal. Electrochem
Butterworth, Baum, Porter, A modification of the Ellman procedure for the estimation of protein sulfhydryl groups, Arch. Biochem. Biophys,
doi:10.1016/0003-9861(67)90409-2Carrion-Garcia, Guerra-Hernandez, Garcia-Villanova, Serafini, Sanchez et al., Plasma non-enzymatic antioxidant capacity (NEAC) in relation to dietary NEAC, nutrient antioxidants and inflammation,
doi:10.3390/antiox9040301Cavezzi, Troiani, Corrao, COVID-19: Hemoglobin, iron, and hypoxia beyond inflammation. A narrative review, Clin. Pract,
doi:10.4081/cp.2020.1271Cecchini, Cecchini, SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression, Med. Hypotheses,
doi:10.1016/j.mehy.2020.110102Cekerevac, Turnic, Draginic, Andjic, Zivkovic et al., Predicting severity and intrahospital mortality in COVID-19; the place and role of oxidative stress, Oxidative Med. Cell. Longev,
doi:10.1155/2021/6615787Checa, Aran, Reactive oxygen species: Drivers of physiological and pathological processes, J. Inflamm. Res,
doi:10.2147/JIR.S275595D'oria, Schipani, Leonardi, Natalicchio, Perrini et al., The role of oxidative stress in cardiac disease: From physiological response to injury factor, Oxid. Med. Cell. Longev,
doi:10.1155/2020/5732956Da Silva Marques, Da Mata, Silveira, Marques, Amaral et al., Hydrogen peroxide release kinetics into saliva from different whitening products: A double-blind, randomized clinical trial, Clin. Oral. Investig
Daenen, Andries, Mekahli, Van Schepdael, Jouret et al., Oxidative stress in chronic kidney disease, Pediatr. Nephrol,
doi:10.1007/s00467-018-4005-4Davies, Hawkins, The role of myeloperoxidase in biomolecule modification, chronic inflammation, and disease, Antioxid. Redox Signal,
doi:10.1089/ars.2020.8030Deth, Clarke, Ni, Trivedi, Clinical evaluation of glutathione concentrations after consumption of milk containing different subtypes of β-casein: Results from a randomized, cross-over clinical trial, Nutr. J,
doi:10.1186/s12937-016-0201-xDuthie, Duthie, Russell, Kyle, Macdiarmid et al., Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change: A randomised trial, Eur. J. Nutr,
doi:10.1007/s00394-017-1469-0Ehrenwald, Chislom, Fox, Intact ceruloplasmin oxidatively modifies low density lipoprotein, J. Clin. Investig,
doi:10.1172/JCI117127Evan, Omaye, Use of saliva biomarkers to monitor efficacy of vitamin C in exercise-induced oxidative stress, Antioxidants,
doi:10.3390/antiox6010005Fernandes, De Brito, Silva Dos Reis, Sato, Pereir, SARS-CoV-2 and other respiratory viruses: What does oxidative stress have to do with it?, Oxid. Med. Cell. Longev,
doi:10.1155/2020/8844280Ganini, Canistro, Jang, Sadler, Mason et al., Ceruloplasmin (ferroxidase) oxidized hydroxylamine probes: Deceptive implications for free radical detection. Free Radic, Biol. Med,
doi:10.1016/j.freeradbiomed.2012.07.013Geng, Wei, Qian, Huay, Lodato et al., Pathophysiological characteristics and therapeutic approaches for pulmonary injury and cardiovascular complications of coronavirus disease, Cardiovasc. Pathol
Gey, Optimum plasma levels of antioxidant micronutrients-Ten years of antioxidant hypothesis on atherosclerosis, New Asp. Nutr. Status
Gianazza, Brioschi, Fernandez, Casalnuovo, Altomare et al., Lipid Peroxidation in Atherosclerotic Cardiovascular Diseases, Antioxid. Redox Signal,
doi:10.1089/ars.2019.7955Guo, Chen, Yeh, Der-Yun, Wang, Cu/Zn Ratios are associated with nutritional status, oxidative stress, inflammation and Immune abnormalities in patients on peritoneal dialysis, Clin. Biochem,
doi:10.1016/j.clinbiochem.2010.12.017Guo, Wang, Effects of zinc supplementation on plasma Copper/Zinc ratios, oxidative stress, and immunological status in hemodialysis patients, Int. J. Med. Sci,
doi:10.7150/ijms.5291Hajam, Rani, Ganie, Sheikh, Javaid et al., None, Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives. Cells,
doi:10.3390/cells11030552Holford, Carr, Zawari, Vizcaychipi, Vitamin C intervention for critical COVID-A pragmatic review of the current level of evidence, Life,
doi:10.3390/life11111166Holmes, O'connor, Perry, Tracey, Wessely et al., Multidisciplinary research priorities for the COVID-19 pandemic: A call for mental health science, Lancet Psychiatry,
doi:10.1016/S2215-0366(20)30168-1Huang, Rose, Hoffmann, The role of selenium in inflammation and immunity: From molecular mechanisms to therapeutic opportunities, Antioxid. Redox Signal,
doi:10.1089/ars.2011.4145Jarosz, Olbert, Wyszogrodzka, Młyniec, Librowski, Antioxidant and anti-inflammatory effects of zinc. Zincdependent NF-κB signaling, Inflammopharmacology,
doi:10.1007/s10787-017-0309-4Jiang, Natural forms of vitamin E: Metabolism, antioxidant and anti-inflammatory activities and the role in disease prevention 543 and therapy. Free Radic, Biol. Med,
doi:10.1016/j.freeradbiomed.2014.03.035Joris, Minguet, Colson, Joris, Fadeur et al., Cardiopulmonary exercise testing in critically ill coronavirus disease 2019 survivors: Evidence of a sustained exercise intolerance and hypermetabolism, Crit. Care Explor,
doi:10.1097/CCE.0000000000000491Kaci, Belhaffef, Meziane, Dostert, Menu et al., Arab-Tehranv, E. Nanoemulsions and topical creams for the safe and effective delivery of lipophilic antioxidant coenzyme Q10, J. Food Process Technol,
doi:10.1016/j.colsurfb.2018.04.010Karkhanei, Ghane, Mehri, Evaluation of oxidative stress level: Total antioxidant capacity, total oxidant status and glutathione activity in patients with COVID-19. New Microbes New Infect,
doi:10.1016/j.nmni.2021.100897Kumar, Singh, Maniar, Chawdhary, Bhattacharyya et al., Plasma hydrogen peroxide: A myth or reality?, Int. J. Clin. Biochem,
doi:10.1007/s12291-018-0746-xLafaurie, Zaror, Díaz-Báez, Castillo, De Ávila et al., Evaluation of substantivity of hypochlorous acid as an antiplaque agent: A randomized controlled trial, Int. J. Dent. Hyg,
doi:10.1111/idh.12342Lindblad, Tveden-Nyborg, Lykkesfeldt, Regulation of vitamin C homeostasis during deficiency, Nutrients,
doi:10.3390/nu5082860Lindstrom, Murray, Schaum's Easy Outline of Statistics
Macieczyk, Zalewska, Ladny, Salivary antioxidant barrier, redox status, and oxidative damage to proteins and lipids in healthy children, adults, and the elderly, Oxid. Med. Cell. Longev,
doi:10.1155/2019/4393460Maciejczyk, Szulimowska, Taranta-Janusz, Werbel, Wasileewska et al., Salivary FRAP as a marker of chronic kidney disease progression in children, Antioxidants,
doi:10.3390/antiox8090409Martín-Fernandez, Aller, Heredia-Rodríguez, Gomez-Sanchez, Martínez-Paz et al., Lipid peroxidation as a hallmark of severity in COVID-19 patients, Redox Biol,
doi:10.1016/j.redox.2021.102181Mckay, Lyner, Linden, Kee, Moitry et al., Association of low plasma antioxidant levels with all-cause mortality and coronary events in healthy middle-aged men from France and Northern Ireland in the PRIME study, Eur. J. Nutr,
doi:10.1007/s00394-020-02455-2Mezzetti, Pierdomenico, Costantini, Romano, De Cesare et al., Copper/zinc ratio and systemic oxidant load: Effect of aging and aging-related degenerative diseases. Free Radic, Biol. Med,
doi:10.1016/S0891-5849(98)00109-9Milleriii, Appel, Risby, Effect of dietary patterns on measures of lipid peroxidation. Results from a randomized Clinical trial, Circulation,
doi:10.1161/01.CIR.98.22.2390Moghaddam, Heller, Sun, Seelig, Cherkezov et al., Selenium deficiency is associated with mortality risk from COVID-19, Nutrients,
doi:10.3390/nu12072098Muhammad, Kani, Iliya, Muhammad, Binji et al., Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria, SAGE Open Med,
doi:10.1177/2050312121991246Mukaka, A guide to appropriate use of correlation coefficient in medical research, Malawi Med. J
Munteanu, Apetre, Analytical methods U-used in D-determining antioxidant activity: A review, Int. J. Mol. Sci,
doi:10.3390/ijms22073380Nitti, Marengo, Furfaro, Pronzato, Marinari et al., Hormesis and oxidative distress: Pathophysiology of reactive oxygen species and the open question of antioxidant modulation and supplementation, Antioxidants,
doi:10.3390/antiox11081613Omaye, Tumbull, Sauerlich, Selected methods for the determination of ascorbic acid in animal cells, tissues and fluids, Methods Enzym
Ozgünes, Gürer, Tuner, Correlation between plasma malondialdehyde and ceruloplasmin activity values in rheumatoid arthritis, Clin. Biochem,
doi:10.1016/0009-9120(94)00081-6Ozturk, Kurutos, Ataseven, Copper/zinc and copper/selenium ratios, and oxidative stress as biochemical markers in recurrent aphthous stomatitis, J. Trace Elem. Med. Biol,
doi:10.1016/j.jtemb.2013.04.002Peluso, Raguzzini, Salivary and urinary total antioxidant capacity as biomarkers of oxidative stress in humans, Pathol. Res. Int,
doi:10.1155/2016/5480267Pincemail, Cavalier, Charlier, Cheramy-Bien, Brevers et al., Oxidative stress status in COVID-19 patients hospitalized in intensive care unit for severe pneumonia. A pilot study, Antioxidants,
doi:10.3390/antiox10020257Pincemail, Cillard, Nève, Defraigne, Mesure de la capacité antioxydante globale du plasma: Une revue critique, Ann. Biol. Clin
Pincemail, Defraigne, Cheramy-Bien, Dardenne, Donneau et al., On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm, Redox Rep,
doi:10.1179/1351000212Y.0000000012Pincemail, Kaci, Cheramy-Bien, Defraigne, Electrochemical methodology for evaluating skin oxidative stress status (OSS). Diseases,
doi:10.3390/diseases7020040Pincemail, Kaci, Kevers, Tabart, Elle et al., An easy electrochemical method for evaluating antioxidant capacity of wines, Diseases,
doi:10.3390/diseases7010010Pincemail, Le Goff, Charlier, Gillion, Cheramy-Bien et al., Evaluation biologique du stress oxydant. Application en routine clinique, Nutr. Et Endocrinol
Pincemail, Vanbelle, Gaspard, Collette, Haleng et al., Effect of different contraceptive methods on the oxidative stress status in women aged 40-48 years from the ELAN study in the province of Liège, Hum. Reprod,
doi:10.1093/humrep/dem146Polizzi, Torrisi, Santonocito, Di Stefano, Indelicato et al., Influence of myeloperoxidase levels on periodontal disease: An applied clinical study, App. Sci,
doi:10.3390/app10031037Poljšak, Dahmane, Godic, Intrinsic skin aging: The role of oxidative stress, Acta Derm. Alp. Pannonica Adriat
Prasad, Tyagi, Aggarwal, Detection of inflammatory biomarkers in saliva and urine: Potential in diagnosis, prevention, and treatment for chronic diseases, Exp. Biol. Med,
doi:10.1177/1535370216638770Ran, Zhao, Tan, Wang, Mizuno et al., Association between serum vitamin C and the blood pressure: A systematic review and meta-analysis of observational studies, Cardiovasc. Ther,
doi:10.1155/2020/4940673Rousseau, Minguet, Colson, Kellens, Chaabane et al., Post-intensive care syndrome after a critical COVID-19: Cohort study from a Belgian follow-up clinic, Ann. Intensive Care. 2021,
doi:10.1186/s13613-021-00910-9Savic-Radojevic, Pljesa-Ercegovac, Matic, Simic, Radovanovic et al., Chapter Four-Novel Biomarkers of Heart Failure, Adv. Clin. Chem
Shi, Puto, N-Acetylcysteine to combat COVID-19: An evidence review, Ther. Clin. Risk Manag
Siegel, Nonparametric Statistics for the Behavioral Sciences
Sies, Oxidative stress: Introductory remarks
Sinclair, Taylor, Lunec, Girling, Barnett, Low plasma ascorbate levels in patients with type 2 diabetes mellitus consuming adequate dietary vitamin C, Diabet. Med,
doi:10.1111/j.1464-5491.1994.tb00375.xSteinbrenner, Duntas, Rayman, The role of selenium in type-2 diabetes mellitus and its metabolic comorbidities, Redox Biol,
doi:10.1016/j.redox.2022.102236Steven, Frenis, Oelze, Kalinovic, Kuntic et al., Vascular inflammation and oxidative stress: Major triggers for cardiovascular disease, Oxid. Med. Cell. Longev,
doi:10.1155/2019/7092151Sturup, Hayes, Peters, Development and application of a simple routine for the determination of selenium in serum by octopole reaction with ICPMS, Anal. Bioanal. Chem,
doi:10.1007/s00216-004-2946-xTsimikas, Brilakis, Lennon, Miller, Witztum et al., Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events, J. Lipid Res,
doi:10.1194/jlr.M600361-JLR200Turki, Hayot, Carnac, Pillard, Passerieux et al., Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction. Free Radic, Biol. Med,
doi:10.1016/j.freeradbiomed.2012.06.041Virella, Carter, Saad, Crosswell, Game et al., Distribution of IgM and IgG antibodies to oxidized LDL in immune complexes isolated from patients with type 1 diabetes and its relationship with nephropathy. Distribution of IgM and IgG antibodies to oxidized LDL in immune complexes isolated from patients with type 1 diabetes and its relationship with nephropathy, Clin. Immunol
Vlasova, Sokolov, Kostevich, Mikhalchik, Vasilyev, Myeloperoxidase-induced oxidation of albumin and ceruloplasmin: Role of Tyrosines, Biochemistry,
doi:10.1134/S0006297919060087Wayner, Burton, Ingold, Barclay, Locke, The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant capacity of human blood plasma, BBA
Zhang, Penninger, Li, Zhong, Slutsky, Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: Molecular mechanisms and potential therapeutic target, Intensive Care Med,
doi:10.1007/s00134-020-05985-9Zhao, Tham, Lu, Lai, Lee et al., Simultaneous determination of vitamins C, E and carotene in human plasma by high-performance liquid chromatography with photodiode-array detection, J. Pharm. Pharm. Sci
Zuo, Prather, Stetskiv, Garrison, Meade et al., Inflammaging and oxidative stress in human diseases: From molecular mechanisms to novel treatments, Int. J. Mol. Sci,
doi:10.3390/ijms20184472
