Role of Oxidative Stress in Pathogenesis and Severity of COVID-19 Infection: Case-Control Study in Iraq


disease severity
oxidative stress
cytokine storm

How to Cite

Sadeq, H., & Daabo, H. (2022). Role of Oxidative Stress in Pathogenesis and Severity of COVID-19 Infection: Case-Control Study in Iraq. Journal of Life and Bio Sciences Research , 3(02), 40 - 45.


Coronavirus disease 2019 (COVID-19) has presented a significant threat to public health and has rapidly spread across the globe since its outbreak in Wuhan, China, in 2019. Clinical evidence suggests higher oxidative stress in COVID-19 patients, and this worsening redox status may contribute to disease progression. The present study aimed to investigate oxidative stress in patients with mild and severe COVID-19. A case-control study was conducted from September 2021 to January 2022 among eighty-eight COVID-19 patients (male: female, 35:53) and eighty-eight healthy volunteers as the control group (male: female, 53:35) with ages ranging from (18-45) years in Duhok city, Kurdistan Region-Iraq. According to the severity of infection, patients were divided into two groups (mild and severe). Serum levels of malondialdehyde (MDA) and 8-isoprostaglandin F2 alpha (8-iso-PGF2) were assessed as oxidative stress markers. In addition, serum activity of two main antioxidant enzymes, superoxide dismutase (SOD) and catalase were measured. Furthermore, their correlation with the most frequently used laboratory parameters, C-reactive protein (CRP) and D-dimer, were investigated. Serum levels of 8-iso-PGF2 and MDA were considerably higher in patients with COVID-19 compared to healthy individuals (p <0.001) and between severe and mild patients (p<0.001). The activity of CAT was greater in COVID-19 group than in controls (p=0.011), but the difference between severe and mild diseases was statistically insignificant (p>0.05). However, SOD activity showed an insignificant difference between control and case groups (p>0.05), as well as between mild and severe groups (p>0.05). Also, a significant correlation was found between oxidative stress biomarkers and laboratory parameters CRP and D-dimer (p<0.001; and p=0.020), respectively. COVID-19 patients show significantly increased oxidative stress parameters. This may play a crucial role in the disease pathophysiology and could be considered as a predictive marker for COVID19 severity.


Alamdari, D.H., Moghaddam, A.B., Amini, S., Keramati, M.R., Zarmehri, A.M., Alamdari, A.H., Koliakos, G. (2020). Application of methylene blue-vitamin CN-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial. European journal of pharmacology, 885, 173494.

Alwazeer, D., Liu, F.F.C., Wu, X.Y., LeBaron, T.W. (2021). Combating oxidative stress and inflammation in COVID-19 by molecular hydrogen therapy: Mechanisms and Perspectives. Oxidative Medicine and Cellular Longevity, 2021, 1-17.

Ballou, S.P., Kushner, I. (1992). C-reactive protein and the acute phase response. Advances in Internal Medicine, 37, 313-336.

BeltrGarc J., Osca-Verdegal, R., Pallard.V., Ferreres, J., Rodrez, M., Mulet, S., GarcGimz, J.L. (2020). Oxidative stress and inflammation in COVID-19-associated sepsis: the potential role of antioxidant therapy in avoiding disease progression. Antioxidants, 9(10), 936.

Camini, F.C., da Silva Caetano, C.C., Almeida, L.T., de Brito Magalh, C. L. (2017). Implications of oxidative stress on viral pathogenesis. Archives of Virology, 162(4), 907-917.

Cascella, M., Rajnik, M., Cuomo, A., Dulebohn, S.C., Di Napoli, R. (2020). Features, evaluation and treatment coronavirus (COVID-19). Treasure Island (FL): StatPearls. 2020.

Cecchini, R., Cecchini, A.L. (2020). SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression. Medical Hypotheses, 143, 110102.

Checconi, P., De Angelis, M., Marcocci, M. E., Fraternale, A., Magnani, M., Palamara, A. T., Nencioni, L. (2020). Redox-modulating agents in the treatment of viral infections. International Journal of Molecular Sciences, 21(11), 4084.

Cosmi, B., Legnani, C., Cini, M., Favaretto, E., Palareti, G. (2008). D-dimer and factor VIII are independent risk factors for recurrence after anticoagulation withdrawal for a first idiopathic deep vein thrombosis. Thrombosis Research, 122(5), 610-617.

Delgado-Roche, L., Mesta, F. (2020). Oxidative stress a key player in severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Archives of Medical Research, 51(5), 384-387.

Deore, D.N., Surwase, S.P., Masroor, S., Khan, S.T., Kathore, V. (2012). A cross sectional study on the relationship between the body mass index (BMI) and the audiovisual reaction time (ART). Journal of Clinical and Diagnostic Research, 6(9), 1466.

Fuentes, E., Gibbins, J.M., Holbrook, L.M., Palomo, I. (2018). NADPH oxidase 2 (NOX2): A key target of oxidative stress-mediated platelet activation and thrombosis. Trends in Cardiovascular Medicine, 28(7), 429-434.

Gjyshi, O., Bottero, V., Veettil, M.V., Dutta, S., Singh, V.V., Chikoti, L., Chandran, B. (2014). Kaposi's sarcoma-associated herpesvirus induces Nrf2 during de novo infection of endothelial cells to create a microenvironment conducive to infection. PLoS Pathogens, 10(10), e1004460.

Goud, P.T., Bai, D., Abu-Soud, H.M. (2021). A multiple-hit hypothesis involving reactive oxygen species and myeloperoxidase explains clinical deterioration and fatality in COVID-19. International Journal of Biological Sciences, 17(1), 62.

Hosakote, Y.M., Liu, T., Castro, S.M., Garofalo, R.P., Casola, A. (2009). Respiratory syncytial virus induces oxidative stress by modulating antioxidant enzymes. American Journal of Respiratory Cell and Molecular Biology, 41(3), 348-357.

Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223), 497-506.

Ivanov, A. V., Bartosch, B., Isaguliants, M. G. (2017). Oxidative stress in infection and consequent disease. Oxidative Medicine and Cellular Longevity. 2017, 3496043.

Jain, S.K., Parsanathan, R., Levine, S.N., Bocchini, J.A., Holick, M.F., Vanchiere, J.A. (2020). The potential link between inherited G6PD deficiency, oxidative stress, and vitamin D deficiency and the racial inequities in mortality associated with COVID-19. Free Radical Biology and Medicine, 161, 84-91.

Jara-Palomares, L., Solier-Lopez, A., Elias-Hernandez, T., Asensio-Cruz, M. I., Blasco-Esquivias, I., Sanchez-Lopez, V., Otero-Candelera, R. (2018). D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis. British Journal of Cancer, 119(8), 915-921.

Johns Hopkins University. (2022). Johns Hopkins Coronavirus Resource Center. Johns Hopkins Coronavirus Resource Center; Johns Hopkins University & Medicine.

Khomich, O.A., Kochetkov, S.N., Bartosch, B., Ivanov, A.V. (2018). Redox biology of respiratory viral infections. Viruses, 10(8), 392.

Kim, H.J., Kim, C.H., Ryu, J.H., Kim, M.J., Park, C.Y., Lee, J.M., Yoon, J.H. (2013). Reactive oxygen species induce antiviral innate immune response through IFN- regulation in human nasal epithelial cells. American Journal of Respiratory Cell and Molecular Biology, 49(5), 855-865.

Komaravelli, N., Casola, A. (2014). Respiratory viral infections and subversion of cellular antioxidant defenses. Journal of Pharmacogenomics & Pharmacoproteomics, 5(4).

Lehmann, A., Prosch, H., Zehetmayer, S., Gysan, M. R., Bernitzky, D., Vonbank, K., Gompelmann, D. (2021). Impact of persistent D-dimer elevation following recovery from COVID-19. PLoS One, 16(10), e0258351.

Mehri, F., Rahbar, A., Ghane, E., Souri, B., & Esfahani, M. (2021). The comparison of oxidative markers between Covid-19 patients and healthy subjects: Oxidative stress and Covid-19. Archives of medical research.

Mironova, G.D., Belosludtseva, N.V., Ananyan, M.A. (2020). Prospects for the use of regulators of oxidative stress in the comprehensive treatment of the novel Coronavirus Disease 2019 (COVID-19) and its complications. Eur Rev Med Pharmacol Sci., 24(16), 8585-8591.

Muhammad, Y., Kani, Y.A., Iliya, S., Muhammad, J.B., Binji, A., El-Fulaty Ahmad, A., Ahmed, A.U. (2021). Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria. SAGE Open Medicine, 9, 2050312121991246.

Nanduri, J., Yuan, G., Kumar, G.K., Semenza, G.L., Prabhakar, N.R. (2008). Transcriptional responses to intermittent hypoxia. Respiratory Physiology & Neurobiolog, 164(1-2), 277-281.

Paracha, U.Z., Fatima, K., Alqahtani, M., Chaudhary, A., Abuzenadah, A., Damanhouri, G., Qadri, I. (2013). Oxidative stress and hepatitis C virus. Virology Journal, 10(1), 1-9.

Pham-Huy, L.A., He, H., Pham-Huy, C. (2008). Free radicals, antioxidants in disease and health. International journal of biomedical science: IJBS, 4(2), 89.

Pincemail, J., Cavalier, E., Charlier, C., CheramyBien, J.P., Brevers, E., Courtois, A., Rousseau, A.F. (2021). Oxidative stress status in COVID-19 patients hospitalized in intensive care unit for severe pneumonia. A pilot study. Antioxidants, 10(2), 257.

Poggi, C., Dani, C. (2014). Antioxidant strategies and respiratory disease of the preterm newborn: an update. Oxidative Medicine and Cellular Longevity, 2014.

Polonikov, A. (2020). Endogenous deficiency of glutathione as the most likely cause of serious manifestations and death in COVID-19 patients. ACS Infectious Diseases, 6(7), 1558-1562.

Schwarz, K. B. (1996). Oxidative stress during viral infection: a review. Free Radical Biology and Medicine, 21(5), 641-649.

Suhail, S., Zajac, J., Fossum, C., Lowater, H., McCracken, C., Severson, N., Hati, S. (2020). Role of oxidative stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) infection: a review. The Protein Journal, 39(6), 644-656.

Valencia, D.N. (2020) Brief Review on COVID-19: The 2020 Pandemic Caused by SARS-CoV-2. Cureus 12(3): e7386.

Voicu, S., Ketfi, C., Sté°¡nian, A., Chousterman, B. G., Mohamedi, N., Siguret, V., Bonnin, P. (2021). Pathophysiological processes underlying the high prevalence of deep vein thrombosis in critically ill COVID-19 patients. Frontiers in Physiology, 608788.

Volanakis, J.E. (2001). Human C-reactive protein: expression, structure, and function. Molecular Immunology, 38(2-3), 189-197.

World Health Organization (2022). WHO COVID-19 dashboard. [online] World Health Organization. Available at:

World Health Organization. (2020). Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance, 13 March 2020 (No. WHO/2019-nCoV/clinical/2020.4). World Health Organization.

Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., Wang, F.S. (2020). Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine, 8(4), 420-422.

Yaghoubi, N., Youssefi, M., Jabbari Azad, F., Farzad, F., Yavari, Z., Zahedi Avval, F. (2022). Total antioxidant capacity as a marker of severity of COVID19 infection: Possible prognostic and therapeutic clinical application. Journal of Medical Virology, 94(4), 1558-1565.

Zheng, L., Fei, J., Feng, C.M., Xu, Z., Fu, L., Zhao, H. (2021). Serum 8-iso-PGF2 predicts the severity and prognosis in patients with community-acquired pneumonia: a retrospective cohort study. Frontiers in Medicine, 8, 633442.

Zhu, Z., Cai, T., Fan, L., Lou, K., Hua, X., Huang, Z., Gao, G. (2020). Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019. Int J Infect Dis., 95:332-339.

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