The Effect of Deferoxamine and Vitamin C Supplementation on Ferritin and CRP Levels in COVID-19 Patients
Abstract
Background: Today, the COVID19 pandemic is one of the most important health system challenges in the world, which doesn’t have specific treatment yet. It includes a wide range of respiratory and non-respiratory signs and symptoms, that lead to hospitalization and intensive care units.
Methods: In this study, 78 patients in two groups of 39 patients were included. The case group included 39 COVID19 patients who had specified sign in CT scans and factors of viral infection, high serum ferritin, increased inflammatory factor in the blood. There were two intervention groups (receiving deferoxamine and vitamin C) and the control group (receiving only official protocol drugs of the country). All patients were admitted to the ICU of Shohada-e-Tajrish Hospital and underwent complete cardiorespiratory monitoring. All changes in Spo2, hemodynamics, serum ferritin and CRP were recorded before the study.
Results: This study presented that improved patient had lower ferritin levels than those who were still ill. In addition, prescribing deferoxamine as an adjunct to vitamin C can prevent cytokine storms that was effective for improving the patients with COVID19.
Conclusion: In conclusion. According to the role of deferoxamine and vitamin C in significantly reducing inflammatory factors of ferritin and CRP, they can be used as an adjunctive therapy in patients with COVID19.
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[2] Adedeji AO, Lazarus H. Biochemical characterization of Middle East respiratory syndrome coronavirus helicase. Msphere. 2016; 1(5).
[3] Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan. China. JAMA. 2020; 323(11):1061-9.
[4] Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020; 382(18):1708-20.
[5] Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The lancet. 2020; 395(10223):507-13.
[6] Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020; 395(10223):497-506.
[7] Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020; 323(20):2052-9.
[8] Wu C, Chen X, Cai Y, Zhou X, Xu S, Huang H, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA internal medicine. 2020; 180(7):934-43.
[9] Blanco-Melo D, Nilsson-Payant BE, Liu W-C, Uhl S, Hoagland D, Møller R, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020; 181(5):1036-45. e9.
[10] Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LF. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020; 20(6):363-74.
[11] Hui DS, Chan PK. Severe acute respiratory syndrome and coronavirus. Infectious Disease Clinics. 2010; 24(3):619-38.
[12] Manne BK, Denorme F, Middleton EA, Portier I, Rowley JW, Stubben C, et al. Platelet gene expression and function in patients with COVID-19. Blood. 2020; 136(11):1317-29.
[13] Li Y, Hu Y, Yu J, Ma T. Retrospective analysis of laboratory testing in 54 patients with severe-or critical-type 2019 novel coronavirus pneumonia. Lab Invest. 2020; 100(6):794-800.
[14] Baraboutis IG, Gargalianos P, Aggelonidou E, Adraktas A. Initial real-life experience from a designated COVID-19 centre in Athens, Greece: a proposed therapeutic algorithm. SN Compr Clin Med. 2020; 2(6):689-93.
[15] Velavan TP, Meyer CG. Mild versus severe COVID-19: laboratory markers. Int J Infect Dis. 2020; 95:304-7.
[16] Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020; 27(6):992-1000. e3.
[17] Torti FM, Torti SV. Regulation of ferritin genes and protein. Blood. 2002; 99(10):3505-16.
[18] Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017; 29(9):401-9.
[19] Kell DB. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics. 2009; 2(1):1-79.
[20] Pretorius E, Vermeulen N, Bester J, Lipinski B, Kell DB. A novel method for assessing the role of iron and its functional chelation in fibrin fibril formation: the use of scanning electron microscopy. Toxicol Mech Methods. 2013; 23(5):352-9.
[21] Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 2014; 6(4):748-73.
[22] Lipinski B, Pretorius E, Oberholzer HM, van der Spuy WJ. Interaction of fibrin with red blood cells: the role of iron. Ultrastruct Pathol. 2012; 36(2):79-84.
[23] Bennett TD, Hayward KN, Farris RW, Ringold S, Wallace CA, Brogan TV. Very high serum ferritin levels are associated with increased mortality and critical care in pediatric patients. Pediatr Crit Care Med. 2011; 12(6):e233-e6.
[24] Carcillo JA, Sward K, Halstead ES, Telford R, Jimenez-Bacardi A, Shakoory B, et al. A systemic inflammation mortality risk assessment contingency table for severe sepsis. Pediatr Crit Care Med. 2017; 18(2):143-50.
[25] Mehta P, Cron RQ, Hartwell J, Manson JJ, Tattersall RS. Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome. Lancet Rheumatol. 2020.
[26] Rosário C, Zandman-Goddard G, Meyron-Holtz EG, D’Cruz DP, Shoenfeld Y. The hyperferritinemic syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med. 2013; 11(1):1-11.
[27] Su L-J, Zhang J-H, Gomez H, Murugan R, Hong X, Xu D, et al. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev. 2019; 2019.
[28] Emara A, El Kelany R, Moustafa K. Comparative study of the protective effect between deferoxamine and deferiprone on chronic iron overload induced cardiotoxicity in rats. Hum Exp Toxicol. 2006; 25(7):375-85.
[29] Sarantos K, Evans P, Garbowski M, Davis B, Porter JB. Vitamin C Deficiency in Patients on Long-Term Deferasirox without Supplementation. American Society of Hematology; 2008.
[30] Cheng L, Li H, Li L, Liu C, Yan S, Chen H, et al. Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis. J Clin Lab Anal. 2020; 34(10):e23618.
[31] Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet. 2020; 395(10229):1054-62.
[32] Meyer D. Iron chelation as therapy for HIV and Mycobacterium tuberculosis co-infection under conditions of iron overload. Curr Pharm Des. 2006; 12(16):1943-7.
[33] Khodour Y, Kaguni LS, Stiban J. Iron–sulfur clusters in nucleic acid metabolism: Varying roles of ancient cofactors. The Enzymes. 2019; 45:225-56.
[34] Romeo AM, Christen L, Niles EG, Kosman DJ. Intracellular chelation of iron by bipyridyl inhibits DNA virus replication: ribonucleotide reductase maturation as a probe of intracellular iron pools. J Biol Chem. 2001; 276(26):24301-8.
[35] Chen L, Xiong S, She H, Lin SW, Wang J, Tsukamoto H. Iron causes interactions of TAK1, p21ras, and phosphatidylinositol 3-kinase in caveolae to activate IκB kinase in hepatic macrophages. J Biol Chem. 2007; 282(8):5582-8.
[36] Xiong S, She H, Sung CK, Tsukamoto H. Iron-dependent activation of NF-κB in Kupffer cells: a priming mechanism for alcoholic liver disease. Alcohol. 2003; 30(2):107-13.
[37] Li B, Espósito BP, Wang S, Zhang J, Xu M, Zhang S, et al. Desferrioxamine-caffeine shows improved efficacy in chelating iron and depleting cancer stem cells. J Trace Elem Med Biol. 2019; 52:232-8.
[38] Debebe Z, Ammosova T, Breuer D, Lovejoy DB, Kalinowski DS, Karla PK, et al. Iron chelators of the di-2-pyridylketone thiosemicarbazone and 2-benzoylpyridine thiosemicarbazone series inhibit HIV-1 transcription: identification of novel cellular targets—iron, cyclin-dependent kinase (CDK) 2, and CDK9. Mol Pharmacol. 2011; 79(1):185-96.
[39] Kumari N, Iordanskiy S, Kovalskyy D, Breuer D, Niu X, Lin X, et al. Phenyl-1-Pyridin-2yl-ethanone-based iron chelators increase IκB-α expression, modulate CDK2 and CDK9 activities, and inhibit HIV-1 transcription. Antimicrob Agents Chemother. 2014; 58(11):6558-71.
[40] Costagliola DG, Montalembert Md, Lefrère JJ, Briand C, Rebulla P, Baruchel S, et al. Dose of desferrioxamine and evolution of HIV‐1 infection in thalassaemic patients. Br J Haematol. 1994; 87(4):849-52.
[41] Drakesmith H, Prentice A. Viral infection and iron metabolism. Nat Rev Microbiol. 2008; 6(7):541-52.
[42] Haider BA, Spiegelman D, Hertzmark E, Sando D, Duggan C, Makubi A, et al. Anemia, iron deficiency, and iron supplementation in relation to mortality among HIV-infected patients receiving highly active antiretroviral therapy in Tanzania. Am J Trop Med Hyg. 2019; 100(6):1512-20.
[43] Liu W, Zhang S, Nekhai S, Liu S. Depriving iron supply to the virus represents a promising adjuvant therapeutic against viral survival. Curr Clin Microbiol Rep. 2020; 7(2):13-9.
[2] Adedeji AO, Lazarus H. Biochemical characterization of Middle East respiratory syndrome coronavirus helicase. Msphere. 2016; 1(5).
[3] Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan. China. JAMA. 2020; 323(11):1061-9.
[4] Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020; 382(18):1708-20.
[5] Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The lancet. 2020; 395(10223):507-13.
[6] Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020; 395(10223):497-506.
[7] Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020; 323(20):2052-9.
[8] Wu C, Chen X, Cai Y, Zhou X, Xu S, Huang H, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA internal medicine. 2020; 180(7):934-43.
[9] Blanco-Melo D, Nilsson-Payant BE, Liu W-C, Uhl S, Hoagland D, Møller R, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020; 181(5):1036-45. e9.
[10] Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LF. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020; 20(6):363-74.
[11] Hui DS, Chan PK. Severe acute respiratory syndrome and coronavirus. Infectious Disease Clinics. 2010; 24(3):619-38.
[12] Manne BK, Denorme F, Middleton EA, Portier I, Rowley JW, Stubben C, et al. Platelet gene expression and function in patients with COVID-19. Blood. 2020; 136(11):1317-29.
[13] Li Y, Hu Y, Yu J, Ma T. Retrospective analysis of laboratory testing in 54 patients with severe-or critical-type 2019 novel coronavirus pneumonia. Lab Invest. 2020; 100(6):794-800.
[14] Baraboutis IG, Gargalianos P, Aggelonidou E, Adraktas A. Initial real-life experience from a designated COVID-19 centre in Athens, Greece: a proposed therapeutic algorithm. SN Compr Clin Med. 2020; 2(6):689-93.
[15] Velavan TP, Meyer CG. Mild versus severe COVID-19: laboratory markers. Int J Infect Dis. 2020; 95:304-7.
[16] Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020; 27(6):992-1000. e3.
[17] Torti FM, Torti SV. Regulation of ferritin genes and protein. Blood. 2002; 99(10):3505-16.
[18] Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017; 29(9):401-9.
[19] Kell DB. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics. 2009; 2(1):1-79.
[20] Pretorius E, Vermeulen N, Bester J, Lipinski B, Kell DB. A novel method for assessing the role of iron and its functional chelation in fibrin fibril formation: the use of scanning electron microscopy. Toxicol Mech Methods. 2013; 23(5):352-9.
[21] Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 2014; 6(4):748-73.
[22] Lipinski B, Pretorius E, Oberholzer HM, van der Spuy WJ. Interaction of fibrin with red blood cells: the role of iron. Ultrastruct Pathol. 2012; 36(2):79-84.
[23] Bennett TD, Hayward KN, Farris RW, Ringold S, Wallace CA, Brogan TV. Very high serum ferritin levels are associated with increased mortality and critical care in pediatric patients. Pediatr Crit Care Med. 2011; 12(6):e233-e6.
[24] Carcillo JA, Sward K, Halstead ES, Telford R, Jimenez-Bacardi A, Shakoory B, et al. A systemic inflammation mortality risk assessment contingency table for severe sepsis. Pediatr Crit Care Med. 2017; 18(2):143-50.
[25] Mehta P, Cron RQ, Hartwell J, Manson JJ, Tattersall RS. Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome. Lancet Rheumatol. 2020.
[26] Rosário C, Zandman-Goddard G, Meyron-Holtz EG, D’Cruz DP, Shoenfeld Y. The hyperferritinemic syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med. 2013; 11(1):1-11.
[27] Su L-J, Zhang J-H, Gomez H, Murugan R, Hong X, Xu D, et al. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev. 2019; 2019.
[28] Emara A, El Kelany R, Moustafa K. Comparative study of the protective effect between deferoxamine and deferiprone on chronic iron overload induced cardiotoxicity in rats. Hum Exp Toxicol. 2006; 25(7):375-85.
[29] Sarantos K, Evans P, Garbowski M, Davis B, Porter JB. Vitamin C Deficiency in Patients on Long-Term Deferasirox without Supplementation. American Society of Hematology; 2008.
[30] Cheng L, Li H, Li L, Liu C, Yan S, Chen H, et al. Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis. J Clin Lab Anal. 2020; 34(10):e23618.
[31] Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet. 2020; 395(10229):1054-62.
[32] Meyer D. Iron chelation as therapy for HIV and Mycobacterium tuberculosis co-infection under conditions of iron overload. Curr Pharm Des. 2006; 12(16):1943-7.
[33] Khodour Y, Kaguni LS, Stiban J. Iron–sulfur clusters in nucleic acid metabolism: Varying roles of ancient cofactors. The Enzymes. 2019; 45:225-56.
[34] Romeo AM, Christen L, Niles EG, Kosman DJ. Intracellular chelation of iron by bipyridyl inhibits DNA virus replication: ribonucleotide reductase maturation as a probe of intracellular iron pools. J Biol Chem. 2001; 276(26):24301-8.
[35] Chen L, Xiong S, She H, Lin SW, Wang J, Tsukamoto H. Iron causes interactions of TAK1, p21ras, and phosphatidylinositol 3-kinase in caveolae to activate IκB kinase in hepatic macrophages. J Biol Chem. 2007; 282(8):5582-8.
[36] Xiong S, She H, Sung CK, Tsukamoto H. Iron-dependent activation of NF-κB in Kupffer cells: a priming mechanism for alcoholic liver disease. Alcohol. 2003; 30(2):107-13.
[37] Li B, Espósito BP, Wang S, Zhang J, Xu M, Zhang S, et al. Desferrioxamine-caffeine shows improved efficacy in chelating iron and depleting cancer stem cells. J Trace Elem Med Biol. 2019; 52:232-8.
[38] Debebe Z, Ammosova T, Breuer D, Lovejoy DB, Kalinowski DS, Karla PK, et al. Iron chelators of the di-2-pyridylketone thiosemicarbazone and 2-benzoylpyridine thiosemicarbazone series inhibit HIV-1 transcription: identification of novel cellular targets—iron, cyclin-dependent kinase (CDK) 2, and CDK9. Mol Pharmacol. 2011; 79(1):185-96.
[39] Kumari N, Iordanskiy S, Kovalskyy D, Breuer D, Niu X, Lin X, et al. Phenyl-1-Pyridin-2yl-ethanone-based iron chelators increase IκB-α expression, modulate CDK2 and CDK9 activities, and inhibit HIV-1 transcription. Antimicrob Agents Chemother. 2014; 58(11):6558-71.
[40] Costagliola DG, Montalembert Md, Lefrère JJ, Briand C, Rebulla P, Baruchel S, et al. Dose of desferrioxamine and evolution of HIV‐1 infection in thalassaemic patients. Br J Haematol. 1994; 87(4):849-52.
[41] Drakesmith H, Prentice A. Viral infection and iron metabolism. Nat Rev Microbiol. 2008; 6(7):541-52.
[42] Haider BA, Spiegelman D, Hertzmark E, Sando D, Duggan C, Makubi A, et al. Anemia, iron deficiency, and iron supplementation in relation to mortality among HIV-infected patients receiving highly active antiretroviral therapy in Tanzania. Am J Trop Med Hyg. 2019; 100(6):1512-20.
[43] Liu W, Zhang S, Nekhai S, Liu S. Depriving iron supply to the virus represents a promising adjuvant therapeutic against viral survival. Curr Clin Microbiol Rep. 2020; 7(2):13-9.
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| Issue | Vol 10 No 3 (2024): Summer |
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| Section | Research Article(s) | |
| DOI | https://doi.org/10.18502/aacc.v10i3.15691 | |
| Keywords | ||
| COVID19 Deferral Vitamin C Ferritin | ||
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How to Cite
1.
Behnaz F, Sadeghzadeh Sadat SE, Mohseni G, Ghasemi M. The Effect of Deferoxamine and Vitamin C Supplementation on Ferritin and CRP Levels in COVID-19 Patients. Arch Anesth & Crit Care. 2023;10(3):232-238.
