Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1781910.15789/2220-7619-SRD-17819ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИResearch ArticleSeverity-related differences on response of antioxidant defense system in COVID-19 patientsВлияние тяжести заболевания на ответ системы антиоксидантной защиты у пациентов с COVID-19ShohratiM.ШохратиМ.
Iran, Islamic Republic of

PhD, Professor of Pharmacology, Department of Clinical Pharmacy, Faculty of Pharmacy

кандидат наук, профессор фармакологии, кафедра клинической фармации, фармацевтический факультет

majidshohrati@yahoo.comJafariMahvashДжафариМахваш
Iran, Islamic Republic of

PhD, Professor of Biochemistry, Department of Biochemistry, Faculty of Medicine

PhD, профессор биохимии, кафедра биохимии, медицинский факультет

m.jafari145@gmail.comSadrzadehM.СадрзадеМ.
Iran, Islamic Republic of

Dr. in Pharmacology, Department of Clinical Pharmacy, Faculty of Pharmacy

доктор фармакологии, кафедра клинической фармации, фармацевтический факультет

masoudsadr5468@gmail.comEbrahiminezhadH.ЭбрахиминежадХ.
Iran, Islamic Republic of

Dr. in Pharmacology, Department of Clinical Pharmacy, Faculty of Pharmacy

доктор фармакологии, кафедра клинической фармации, фармацевтический факультет

hamidrezaebi@yahoo.comGhaneiM.ГанейМ.
Iran, Islamic Republic of

MD, Professor, Pulmonologist, Chemical Injuries Research Center

д.м.н., профессор, пульмонолог, Центр исследований химических поражений

mghaneister@gmail.comBaqiyatallah University of Medical SciencesУниверситет медицинских наук Бакияталлах11082025081220251558999051911202429072025Copyright ©; 2025, Shohrati M., Jafari M., Sadrzadeh M., Ebrahiminezhad H., Ghanei M.Copyright ©; 2025, Шохрати М., Джафари М., Садрзаде М., Эбрахиминежад Х., Ганей М.2025Shohrati M., Jafari M., Sadrzadeh M., Ebrahiminezhad H., Ghanei M.Шохрати М., Джафари М., Садрзаде М., Эбрахиминежад Х., Ганей М.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/17819

Background. COVID-19 is a major human infectious disease with devastating economic and public health impacts globally. Oxidative stress plays a pivotal role in the pathogenesis and progression of various viral infections. The aim of the present study was to evaluate oxidative stress biomarkers in COVID-19 patients with different severity to healthy participants. Materials and methods. This case-control study was conducted on 60 patients with COVID-19 infection (30 moderate and 30 severe) and 30 matched healthy controls referred to Baqiyatallah Hospital, Tehran from March until July 2020. Serum levels of total antioxidant capacity (TAC) and oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and levels of glutathione (GSH) and malondialdehyde (MDA) were measured using biochemical methods. Results. In terms of gender, the healthy control group consisted of 17 males and 13 females, and the group of moderate patients included 20 males and 10 females and severe COVID-19 patients included 14 males and 16 females, which were not statistically significant (p = 0.295). Also, the mean age in severe COVID-19 patients (46.6±12.8) was not significantly different from the healthy control (43.8±12; p = 0.683) and moderate (45.60±13.30; p = 0.953) groups. The results showed that SOD and CAT activities and MDA level in moderate and severe of COVID-19 patients were higher than the healthy individuals, while GPx and GR activities and GSH and TAC levels were significantly lower. SOD and GPx activities and MDA level in severe of COVID-19 patients were significantly different from moderate patients. However, CAT and GR activities and TAC level in severe cases was not significantly different from moderate patients. Conclusion. Oxidative stress plays an important role in the pathogenesis of COVID-19 infection as indicated by the enhancement of lipid peroxidation, depletion of GSH and alteration in antioxidant enzymes. The systemic oxidative stress is directly related to the severity of the pathogenesis. Therefore, substances with antioxidant properties may be a potential choice for the treatment of COVID-19 infection.

Введение. COVID-19 является серьезным инфекционным заболеванием, оказывая разрушительное воздействие на экономику и общественное здравоохранение во всем мире. Окислительный стресс играет ключевую роль в патогенезе и прогрессировании различных вирусных инфекций. Целью настоящего исследования была оценка биомаркеров окислительного стресса у пациентов с COVID-19 различной степени тяжести и у волонтеров. Материалы и методы. Настоящее исследование случай–контроль было проведено с участием 60 пациентов с COVID-19 (по 30 человек со среднетяжелым и тяжелым течением) и 30 здоровых лиц контрольной группы, поступивших в больницу «Бакияталлах» в Тегеране с марта по июль 2020 г. Биохимические методы использовались для оценки сывороточных уровней общей антиоксидантной активности (ОАС) и биомаркеров окислительного стресса, таких как супероксиддисмутаза (СОД), каталаза (КАТ), глутатионпероксидаза (ГП) и глутатионредуктаза (ГР), а также уровни глутатиона (GSH) и малонового диальдегида (МДА). Результаты. В контрольную группу вошли 17 мужчин и 13 женщин, в группу пациентов средней степени тяжести COVID-19 — 20 мужчин и 10 женщин, в группу с тяжелым течением COVID-19 — 14 мужчин и 16 женщин (p = 0,295). Кроме того, средний возраст у пациентов с тяжелым течением COVID-19 (46,6±12,8 лет) существенно не отличался от возраста обследованных в группе контроля (43,8±12 лет; p = 0,683) и пациентов со средней степенью тяжести (45,60±13,30 лет; p = 0,953). Результаты показали, что активность СОД и КAT, а также уровень МДА у пациентов со среднетяжелым и тяжелым течением COVID-19 были выше, чем у здоровых лиц, в то время как активность ГП и ГР, а также уровни GSH и ОАС были значительно ниже. Активность СОД и ГП, а также уровень МДА у пациентов с тяжелым течением COVID-19 существенно отличались от показателей пациентов со средней степенью тяжести. Однако активность КAT и ГР, а также уровень ОАС у пациентов с тяжелым течением заболевания достоверно не отличались от таковых у среднетяжелых пациентов. Заключение. Окислительный стресс играет важную роль в патогенезе инфекции COVID-19, о чем свидетельствуют усиление перекисного окисления липидов, истощение GSH и изменение активности антиоксидантных ферментов. Системный окислительный стресс напрямую связан с тяжестью патогенеза COVID-19. Следовательно, вещества с антиоксидантными свойствами могут быть потенциальным выбором для лечения COVID-19.

COVID-19severity of disease oxidative stressantioxidant enzymeslipid peroxidationserumCOVID-19тяжесть заболеванияокислительный стрессантиоксидантные ферментыперекисное окисление липидовсыворотка кровиChemical Damage Research Center of Medical Sciences Tehran, Iran (grant)Центр исследований химических поражений г.Тегеран, Иран (грант)99000289Atanasovska E., Petrusevska M., Zendelovska D., Spasovska K., Stevanovikj M., Kasapinova K., Gjorgjievska K., Labachevski N. Vitamin D levels and oxidative stress markers in patients hospitalized with COVID-19. Redox Rep., 2021, vol. 26, no. 1, pp. 184–189. doi: 10.1080/13510002.2021.1999126Badawy M.A., Yasseen B.A., El-Messiery R.M., Abdel-Rahman E.A., Elkhodiry A.A., Kamel A.G., El-Sayed H., Shedra A.M., Hamdy R., Zidan M., Al-Raawi D., Hammad M., Elsharkawy N., El Ansary M., Al-Halfawy A., Elhadad A., Hatem A., Abouelnaga S., Dugan L.L., Ali S.S. Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality. Elife, 2021, vol. 10: e69417. doi: 10.7554/eLife.69417Beltrán-García J., Osca-Verdegal R., Pallardó F.V., Ferreres J., Rodríguez M., Mulet S., Sanchis-Gomar F., Carbonell N., García-Giménez J.L. Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression. Antioxidants (Basel), 2020, vol. 9, no. 10, pp. 936–953. doi: 10.3390/antiox9100936Chernyak B.V., Popova E.N., Prikhodko A.S., Grebenchikov O.A., Zinovkina L.A., Zinovkin R.A. COVID-19 and Oxidative Stress. Biochemistry (Mosc.), 2020, vol. 85, no. 12, pp. 1543–1553. doi: 10.1134/S0006297920120068Chiscano-Camón L., Ruiz-Rodriguez J.C., Ruiz-Sanmartin A., Roca O., Ferrer R. Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome. Crit. Care, 2020, vol. 24, no. 1, pp. 522–530. doi: 10.1186/s13054-020-03249-yCullen S. Oxidative Marker Changes in COVID-19 Patients. J. Health Med. Res., 2022, vol. 4, no. 1: 102. doi: 10.35248/jhmr.22.04(01).102Eshrati R., Jafari M., Gudarzi S., Nazari A., Samizadeh E., Ghafourian Hesami M. Comparison of ameliorative effects of Taraxacum syriacum and N-acetylcysteine against acetaminophen-induced oxidative stress in rat liver and kidney. J. Biochem., 2021, vol. 169, no. 3, pp. 337–350. doi: 10.1093/jb/mvaa107Forcados G.E., Muhammad A., Oladipo O.O., Makama S., Meseko C.A. Metabolic Implications of Oxidative Stress and Inflammatory Process in SARS-CoV-2 Pathogenesis: Therapeutic Potential of Natural Antioxidants. Front. Cell. Infect. Microbiol., 2021, vol. 11: 654813. doi: 10.3389/fcimb.2021.654813Golabi S., Ghasemi S., Adelipour M., Bagheri R., Suzuki K., Wong A., Seyedtabib M., Naghashpour M. Oxidative Stress and Inflammatory Status in COVID-19 Outpatients: A Health Center-Based Analytical Cross-Sectional Study. Antioxidants (Basel), 2022, vol. 11, no. 4, pp. 606–620. doi: 10.3390/antiox11040606Gudarzi S., Jafari M., Pirzad Jahromi G., Eshrati R., Asadollahi M., Nikdokht P. Evaluation of modulatory effects of saffron (Crocus sativus L.) aqueous extract on oxidative stress in ischemic stroke patients: a randomized clinical trial. Nutr. Neurosci., 2022, vol. 25, no. 6, pp. 1137–1146. doi: 10.1080/1028415X.2020.1840118Guloyan V., Oganesian B., Baghdasaryan N., Yeh C., Singh M., Guilford F., Ting Y.S., Venketaraman V. Glutathione Supplementation as an Adjunctive Therapy in COVID-19. Antioxidants (Basel), 2020, vol. 9, no. 10, pp. 914–927. doi: 10.3390/antiox9100914Handu D., Moloney L., Rozga M., Cheng F.W. Malnutrition Care During the COVID-19 Pandemic: Considerations for Registered Dietitian Nutritionists. J. Acad. Nutr. Diet., 2021, vol. 121, no. 5, pp. 979–987. doi: 10.1016/j.jand.2020.05.012Heydari J., Jafari M., Khazaie S., Goosheh H., Ghanei M., Karbasi A. The role of oxidative stress in severity of obstructive pulmonary complications in sputum of sulfur mustard-injured patients. Iran J. Toxicol., 2017, vol. 11, no. 5, pp. 5–11.Jafari M., Salehi M., Shirbazou S., Abasian L., Talebi-Meymand F. Evaluation of gender-related differences in response to oxidative stress in Toxoplasma gondii positive serum. Ann. Mil. Health Sci. Res., 2014, vol. 12, no. 2: e63369.Jaiswal N., Bhatnagar M., Shah H. N-acetycysteine: A potential therapeutic agent in COVID-19 infection. Med. Hypotheses, 2020, vol. 144: 110133. doi: 10.1016/j.mehy.2020.110133Karkhanei B., Talebi Ghane E., Mehri F. Evaluation of oxidative stress level: total antioxidant capacity, total oxidant status and glutathione activity in patients with COVID-19. New Microbes New Infect., 2021, vol. 42: 100897. doi: 10.1016/j.nmni.2021.100897Khan S., Faisal S., Usman H., Zainab R., Taj F., Amrani R., Tayyeb M. COVID-19: a brief overview on the role of vitamins specifically vitamin C as immune modulators and in prevention and treatment of SARS-Cov-2 infections. Biomed. J. Sci. Tech. Res., 2020, vol. 28, no. 3, pp. 21580–21586. doi: 10.26717/BJSTR.2020.28.004648Khazaie S., Jafari M., Heydari J., Asgari A., Tahmasebi K., Salehi M., Abedini M.S. Modulatory effects of vitamin C on biochemical and oxidative changes induced by acute exposure to diazinon in rat various tissues: Prophylactic and therapeutic roles. J. Anim. Physiol. Anim. Nutr. (Berl)., 2019, vol. 103, no. 5, pp. 1619–1628. doi: 10.1111/jpn.13144Liao Q.J., Ye L.B., Timani K.A., Zeng Y.C., She Y.L., Ye L., Wu Z.H. Activation of NF-kappaB by the full-length nucleocapsid protein of the SARS coronavirus. Acta Biochim. Biophys. Sin. (Shanghai), 2005, vol. 37, no. 9, pp. 607–612. doi: 10.1111/j.1745-7270.2005.00082.xMartín-Fernández M., Aller R., Heredia-Rodríguez M., Gómez-Sánchez E., Martínez-Paz P., Gonzalo-Benito H., Sánchez-de Prada L., Gorgojo Ó., Carnicero-Frutos I., Tamayo E., Tamayo-Velasco Á. Lipid peroxidation as a hallmark of severity in COVID-19 patients. Redox Biol., 2021, vol. 48: 102181. doi: 10.1016/j.redox.2021.102181Meftahi G.H., Bahari Z., Jangravi Z., Iman M. A vicious circle between oxidative stress and cytokine storm in acute respiratory distress syndrome pathogenesis at COVID-19 infection. Ukr. Biochem. J., 2021, vol. 93, no. 1, pp. 18–29. doi: 10.15407/ubj93.01.018Mehri F., Rahbar A.H., Ghane E.T., Souri B., Esfahani M. Changes in oxidative markers in COVID-19 patients. Arch. Med. Res., 2021, vol. 52, no. 8, pp. 843–849. doi: 10.1016/j.arcmed.2021.06.004Mousavi S.R., Jafari M., Rezaei S., Agha-Alinejad H., Sobhani V. Evaluation of the effects of different intensities of forced running wheel exercise on oxidative stress biomarkers in muscle, liver and serum of untrained rats. Lab. Anim. (NY), 2020, vol. 49, no. 4, pp. 119–125. doi: 10.1038/s41684-020-0503-7Muhammad Y., Kani Y.A., Iliya S., Muhammad J.B., Binji A., El-Fulaty Ahmad A., Kabir M.B., Umar Bindawa K., Ahmed A. Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria. SAGE Open Med., 2021, vol. 9: 2050312121991246. doi: 10.1177/2050312121991246Naghashpour M., Ghiassian H., Mobarak S., Adelipour M., Piri M., Seyedtabib M., Golabi S. Profiling serum levels of glutathione reductase and interleukin-10 in positive and negative-PCR COVID-19 outpatients: A comparative study from southwestern Iran. J. Med. Virol., 2022, vol. 94, no. 4, pp. 1457–1464. doi: 10.1002/jmv.27464Poe F.L., Corn J. N-Acetylcysteine: A potential therapeutic agent for SARS-CoV-2. Med. Hypotheses, 2020, vol. 143: 109862. doi: 10.1016/j.mehy.2020.109862Polonikov A. Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients. ACS Infect. Dis., 2020, vol. 6, no. 7, pp. 1558–1562. doi: 10.1021/acsinfecdis.0c00288Qin M., Cao Z., Wen J., Yu Q., Liu C., Wang F., Zhang J., Yang F., Li Y., Fishbein G., Yan S., Xu B., Hou Y., Ning Z., Nie K., Jiang N., Liu Z., Wu J., Yu Y., Li H., Zheng H., Li J., Jin W., Pang S., Wang S., Chen J., Gan Z., He Z., Lu Y. An Antioxidant Enzyme Therapeutic for COVID-19. Adv. Mater., 2020, vol. 32, no. 43: e2004901. doi: 10.1002/adma.202004901Shakoor H., Feehan J., Al Dhaheri A.S., Ali H.I., Platat C., Ismail L.C., Apostolopoulos V., Stojanovska L. Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19? Maturitas, 2021, vol. 143, pp. 1–9. doi: 10.1016/j.maturitas.2020.08.003Strycharz-Dudziak M., Kiełczykowska M., Drop B., Świątek Ł., Kliszczewska E., Musik I., Polz-Dacewicz M. Total Antioxidant Status (TAS), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) in Oropharyngeal Cancer Associated with EBV Infection. Oxid. Med. Cell. Longev., 2019, vol. 2019: 5832410. doi: 10.1155/2019/5832410Suhail S., Zajac J., Fossum C., Lowater H., McCracken C., Severson N., Laatsch B., Narkiewicz-Jodko A., Johnson B., Liebau J., Bhattacharyya S., Hati S. Role of Oxidative Stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) Infection: A Review. Protein J., 2020, vol. 39, no. 6, pp. 644–656. doi: 10.1007/s10930-020-09935-8Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L., Tai Y., Bai C., Gao T., Song J., Xia P., Dong J., Zhao J., Wang F.S. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med., 2020, vol. 8, no. 4, pp. 420–422. doi: 10.1016/S2213-2600(20)30076-XYaghoubi N., Youssefi M., Jabbari Azad F., Farzad F., Yavari Z., Zahedi Avval F. Total antioxidant capacity as a marker of severity of COVID-19 infection: Possible prognostic and therapeutic clinical application. J. Med. Virol., 2022, vol. 94, no. 4, pp. 1558–1565. doi: 10.1002/jmv.27500Zhang Y., Xu C., Agudelo Higuita N.I., Bhattacharya R., Chakrabarty J.H., Mukherjee P. Evaluation of I-TAC as a potential early plasma marker to differentiate between critical and non-critical COVID-19. Cell Stress, 2021, vol. 6, no. 1, pp. 6–16. doi: 10.15698/cst2022.01.262