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Volume 6, Issue 1
  • ISSN: 2666-7967
  • E-ISSN: 2666-7975

Abstract

Objective

Ferroptosis is a form of programmed cell death characterized by the iron-dependent accumulation of lipid peroxides, leading to membrane damage and cell rupture. Several lines of evidence suggest that ferroptosis may contribute to the pathogenesis and severity of COVID-19. This study aimed to measure iron metabolism and lipid peroxidation markers in COVID-19 patients to establish a direct link between ferroptosis and COVID-19.

Methods

In the present cross-sectional study, the serum levels of hemoglobin (Hb), ferritin, and iron, total iron binding capacity (TIBC), malondialdehyde (MDA), and glutathione (GSH) were assessed in 100 COVID-19 patients diagnosed using Real-time PCR and compared to the levels in 100 healthy individuals.

Results

Our findings revealed a significant increase in serum levels of ferritin and MDA in COVID-19 patients compared to control subjects. Conversely, TIBC, Hb, Iron, and GSH levels were lower in COVID-19 patients than in control.

Conclusion

Our study provides further evidence supporting the significance of ferroptosis in the pathogenesis of COVID-19. Further research aimed at elucidating the exact role of ferroptosis in COVID-19 is warranted, as it may lead to improved strategies for mitigating multi-organ dysfunction associated with this disease.

© 2025 Bentham Science Publishers
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/content/journals/covid/10.2174/0126667975288661240123075201
2024-02-01
2025-01-06

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References

  1. DongE. DuH. GardnerL. An interactive web-based dashboard to track COVID-19 in real time.Lancet Infect. Dis.202020553353410.1016/S1473‑3099(20)30120‑1 32087114
     [Google Scholar]
  2. OchaniR. AsadA. YasminF. COVID-19 pandemic: From origins to outcomes. A comprehensive review of viral pathogenesis, clinical manifestations, diagnostic evaluation, and management.Infez. Med.20212912036 33664170
     [Google Scholar]
  3. AyalaA. MuñozM.F. ArgüellesS. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.Oxid. Med. Cell. Longev.2014201413110.1155/2014/360438 24999379
     [Google Scholar]
  4. HabibH.M. IbrahimS. ZaimA. IbrahimW.H. The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators.Biomed. Pharmacother.202113611122810.1016/j.biopha.2021.111228 33454595
     [Google Scholar]
  5. DixonS.J. LembergK.M. LamprechtM.R. Ferroptosis: An iron-dependent form of nonapoptotic cell death.Cell2012149510601072
     [Google Scholar]
  6. FarzipourS. Talebpour AmiriF. AlvandiM. ShaghaghiZ. YazdiA. Ferroptosis in cardiovascular disease: Basic mechanisms and implications for cardiovascular disease.J. Mazandaran Univ. Med. Sci.202131200199214
     [Google Scholar]
  7. KimS. KangS.W. JooJ. Characterization of ferroptosis in kidney tubular cell death under diabetic conditions.Cell Death Dis.202112216010.1038/s41419‑021‑03452‑x 33558472
     [Google Scholar]
  8. MenonA.V. LiuJ. TsaiH.P. Excess heme upregulates heme oxygenase 1 and promotes cardiac ferroptosis in mice with sickle cell disease.Blood2022139693694110.1182/blood.2020008455 34388243
     [Google Scholar]
  9. QiuY. CaoY. CaoW. JiaY. LuN. The application of ferroptosis in diseases.Pharmacol. Res.202015910491910.1016/j.phrs.2020.104919 32464324
     [Google Scholar]
  10. ChenY. LiN. WangH. Amentoflavone suppresses cell proliferation and induces cell death through triggering autophagy-dependent ferroptosis in human glioma.Life Sci.202024711742510.1016/j.lfs.2020.117425 32057904
     [Google Scholar]
  11. Fratta PasiniA.M. StranieriC. GirelliD. BustiF. CominaciniL. Is ferroptosis a key component of the process leading to multiorgan damage in COVID-19?Antioxidants20211011167710.3390/antiox10111677 34829548
     [Google Scholar]
  12. JacobsW. LammensM. KerckhofsA. Fatal lymphocytic cardiac damage in coronavirus disease 2019 (COVID‐19): Autopsy reveals a ferroptosis signature.ESC Heart Fail.2020763772378110.1002/ehf2.12958 32959998
     [Google Scholar]
  13. ChenY. XuY. ZhangK. ShenL. DengM. Ferroptosis in COVID-19-related liver injury: A potential mechanism and therapeutic target.Front. Cell. Infect. Microbiol.20221292251110.3389/fcimb.2022.922511 35967872
     [Google Scholar]
  14. ZhangR. SunC. ChenX. COVID-19-related brain injury: The potential role of ferroptosis.J. Inflamm. Res.2022152181219810.2147/JIR.S353467 35411172
     [Google Scholar]
  15. YazdiA. AlvandiM. ShaghaghiZ. Coronavirus disease in cardiovascular patients: Clinical characteristics and final prognosis.Avicenna J. Clin. Microbiol. Infect.2023101202610.34172/ajcmi.2023.3421
     [Google Scholar]
  16. HanY. ZhuJ. YangL. SARS-CoV-2 infection induces ferroptosis of sinoatrial node pacemaker cells.Circ. Res.2022130796397710.1161/CIRCRESAHA.121.320518 35255712
     [Google Scholar]
  17. OhkawaH. OhishiN. YagiK. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal. Biochem.197995235135810.1016/0003‑2697(79)90738‑3 36810
     [Google Scholar]
  18. Bellmann-WeilerR. LanserL. BarketR. Prevalence and predictive value of anemia and dysregulated iron homeostasis in patients with COVID-19 infection.J. Clin. Med.202098242910.3390/jcm9082429 32751400
     [Google Scholar]
  19. ShaoY. JiaH. LiS. Comprehensive analysis of ferroptosis-related markers for the clinical and biological value in gastric cancer.Oxid. Med. Cell. Longev.2021202112910.1155/2021/7007933 34745421
     [Google Scholar]
  20. MuL. WangD. DongZ. Abnormal levels of serum ferroptosis-related biomarkers in diabetic retinopathy.J. Ophthalmol.202220221710.1155/2022/3353740 36620526
     [Google Scholar]
  21. LanserL. BurkertF.R. Bellmann-WeilerR. Dynamics in anemia development and dysregulation of iron homeostasis in hospitalized patients with COVID-19.Metabolites2021111065310.3390/metabo11100653 34677368
     [Google Scholar]
  22. LiQ. ChenZ. ZhouX. LiG. ZhangC. YangY. Ferroptosis and multi-organ complications in COVID-19: Mechanisms and potential therapies.Front. Genet.202314118798510.3389/fgene.2023.1187985 37303950
     [Google Scholar]
  23. ZhangY. QianD. BaiX. SunS. Ferroptosis is a potential therapeutic target for pulmonary infectious diseases.Cell. Microbiol.2023202311410.1155/2023/3875897
     [Google Scholar]
  24. MuckenthalerM.U. RivellaS. HentzeM.W. GalyB. A red carpet for iron metabolism.Cell2017168334436110.1016/j.cell.2016.12.034 28129536
     [Google Scholar]
  25. NemethE. GanzT. Hepcidin-ferroportin interaction controls systemic iron homeostasis.Int. J. Mol. Sci.20212212649310.3390/ijms22126493 34204327
     [Google Scholar]
  26. SuriawinataE. MehtaK.J. Iron and iron-related proteins in COVID-19.Clin. Exp. Med.202223496999110.1007/s10238‑022‑00851‑y 35849261
     [Google Scholar]
  27. KunoT. MiyamotoY. IwagamiM. The association of hemoglobin drop with in-hospital outcomes in COVID-19 patients, QJM.Int. J. Med.202111411789794
     [Google Scholar]
  28. LippiG. MattiuzziC. Hemoglobin value may be decreased in patients with severe coronavirus disease 2019.Hematol. Transfus. Cell Ther.202042211611710.1016/j.htct.2020.03.001 32284281
     [Google Scholar]
  29. EdeasM. SalehJ. PeyssonnauxC. Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis?Int. J. Infect. Dis.20209730330510.1016/j.ijid.2020.05.110 32497811
     [Google Scholar]
  30. RuanQ. YangK. WangW. JiangL. SongJ. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China.Intensive Care Med.202046584684810.1007/s00134‑020‑05991‑x 32125452
     [Google Scholar]
  31. Gómez-PastoraJ. WeigandM. KimJ. Hyperferritinemia in critically ill COVID-19 patients - Is ferritin the product of inflammation or a pathogenic mediator?Clin. Chim. Acta202050924925110.1016/j.cca.2020.06.033 32579952
     [Google Scholar]
  32. ColafrancescoS. AlessandriC. ContiF. PrioriR. COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome?Autoimmun. Rev.202019710257310.1016/j.autrev.2020.102573 32387470
     [Google Scholar]
  33. WeissG. GanzT. GoodnoughL.T. Anemia of inflammation.Blood20191331405010.1182/blood‑2018‑06‑856500 30401705
     [Google Scholar]
  34. NemethE. RiveraS. GabayanV. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin.J. Clin. Invest.200411391271127610.1172/JCI200420945 15124018
     [Google Scholar]
  35. ShahA. FrostJ.N. AaronL. Systemic hypoferremia and severity of hypoxemic respiratory failure in COVID-19.Crit. Care202024132010.1186/s13054‑020‑03051‑w 32517773
     [Google Scholar]
  36. EhsaniA.H. NasimiM. BigdeloZ. Pityriasis rosea as a cutaneous manifestation of COVID‐19 infection.J. Eur. Acad. Dermatol. Venereol.2020349e436e43710.1111/jdv.16579 32359180
     [Google Scholar]
  37. EhsaniS. COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein.Biol. Direct20201511910.1186/s13062‑020‑00275‑2 33066821
     [Google Scholar]
  38. XiongS. SheH. TsukamotoH. Signaling role of iron in NF-kappa B activation in hepatic macrophages, comparative hepatology.Comp. Hepatol.200414
     [Google Scholar]
  39. YadavD. PvsnK.K. TomoS. Association of iron-related biomarkers with severity and mortality in COVID-19 patients.J. Trace Elem. Med. Biol.20227412707510.1016/j.jtemb.2022.127075 36174458
     [Google Scholar]
  40. OgunA. AdeyinkaA. Biochemistry, transferrin.In: StatPearls.Treasure Island, FL, USAStatPearls Publishing LLC2022
     [Google Scholar]
  41. BianconiV. MannarinoM.R. FigorilliF. The detrimental impact of elevated ferritin to iron ratio on in-hospital prognosis of patients with COVID-19.Expert Rev. Mol. Diagn.202222446947810.1080/14737159.2022.2052047 35260036
     [Google Scholar]
  42. FlorezA.F. AlborziniaH. Ferroptosis: Mechanism and diseases.Springer202110.1007/978‑3‑030‑62026‑4
     [Google Scholar]
  43. YinH. XuL. PorterN.A. Free radical lipid peroxidation: mechanisms and analysis.Chem. Rev.2011111105944597210.1021/cr200084z 21861450
     [Google Scholar]
  44. YangWS SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4.Cell20141561-231733110.1016/j.cell.2013.12.010 24439385
     [Google Scholar]
  45. DerouicheS. Oxidative stress associated with SARS-Cov-2 (COVID-19) increases the severity of the lung disease-a systematic review.J Infect Dis Epidemiol202063121126
     [Google Scholar]
  46. MuhammadY. KaniY.A. IliyaS. Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria.SAGE Open Med.2021910.1177/2050312121991246 33614035
     [Google Scholar]
  47. ChenX. ComishP.B. TangD. KangR. Characteristics and biomarkers of ferroptosis.Front. Cell Dev. Biol.2021963716210.3389/fcell.2021.637162 33553189
     [Google Scholar]
  48. MehriF. RahbarA.H. GhaneE.T. SouriB. EsfahaniM. Changes in oxidative markers in COVID-19 patients.Arch. Med. Res.202152884384910.1016/j.arcmed.2021.06.004 34154831
     [Google Scholar]
  49. Avila-NavaA. Pech-AguilarA.G. LugoR. Medina-VeraI. Guevara-CruzM. Gutiérrez-SolisA.L. Oxidative stress biomarkers and their association with mortality among patients infected with SARS-CoV-2 in mexico.Oxid. Med. Cell. Longev.202220221810.1155/2022/1058813 35746958
     [Google Scholar]
  50. PerriconeC. BartoloniE. BursiR. COVID-19 as part of the hyperferritinemic syndromes: The role of iron depletion therapy.Immunol. Res.202068421322410.1007/s12026‑020‑09145‑5 32681497
     [Google Scholar]
/content/journals/covid/10.2174/0126667975288661240123075201
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Role of Ferroptosis in COVID-19 Pathogenesis: Insights from Iron Metabolism and Lipid Peroxidation Markers
Coronaviruses 6, E010224226642 (2025); https://doi.org/10.2174/0126667975288661240123075201
/content/journals/covid/10.2174/0126667975288661240123075201
/content/journals/covid/10.2174/0126667975288661240123075201
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  • Article Type:     Research Article
Keyword(s): COVID-19; Ferroptosis; glutathione; hemoglobin; malondialdehyde; stress oxidative
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