Skip to content
2000
Volume 21, Issue 3
  • ISSN: 1573-398X
  • E-ISSN: 1875-6387

Abstract

Objective

This study aimed to elucidate the association between iron dysregulation and the severity of COVID-19, examining serum levels of iron-related biomarkers in hospitalized patients. The primary objective was to identify reliable predictors for disease severity, specifically focusing on the role of ferritin, Hemoglobin (Hb), Total Iron-binding Capacity (TIBC), and iron.

Materials and Methods

The study enrolled 117 consecutive COVID-19 patients, classified into mild, severe, and critical groups. Serum levels of Hb, TIBC, iron, and ferritin were measured using standardized methods. Data were analyzed using ROC analysis, logistic regression models, and correlation assessments. The study adhered to ethical guidelines, obtaining informed consent from all participants.

Results

Results revealed a consistent elevation in iron and ferritin levels as disease severity increased, accompanied by a reciprocal decline in Hb and TIBC. Ferritin emerged as a robust predictor for disease prognosis, with an AUC of 0.808, providing a sensitivity of 62.50% and a specificity of 91.74%. Age and education were identified as exacerbating factors influencing patient outcomes. The findings have been found to align with previous studies linking higher ferritin levels to adverse outcomes, supporting ferritin’s utility as a prognostic marker.

Conclusion

The intricate relationship between iron metabolism and COVID-19 severity has been highlighted in this study, emphasizing elevated ferritin levels as potential predictors for severe outcomes and indicators of inflammation-induced cellular damage. These findings may contribute valuable insights into personalized patient management strategies and the potential for targeted interventions in severe COVID-19 cases. Further research involving larger populations is essential to validate these observations and enhance our understanding of the complex host response to SARS-CoV-2.

Loading

Article metrics loading...

/content/journals/crmr/10.2174/011573398X306178240816054525
2024-08-29
2025-06-22
Loading full text...

Full text loading...

References

  1. 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.2022.92251135967872
    [Google Scholar]
  2. Thi Hong NguyenN. OuT.Y. HuyL.D. ShihC.L. ChangY.M. PhanT.P. HuangC.C. A global analysis of COVID-19 infection fatality rate and its associated factors during the Delta and Omicron variant periods: An ecological study.Front. Public Health202311114513810.3389/fpubh.2023.114513837333556
    [Google Scholar]
  3. ChungJ.Y. ThoneM.N. KwonY.J. COVID-19 vaccines: The status and perspectives in delivery points of view.Adv. Drug Deliv. Rev.202117012510.1016/j.addr.2020.12.01133359141
    [Google Scholar]
  4. ČepelakI DodigS Ferroptosis-a link between iron biology, aging and COVID-19?Rad Hrvatske akademije znanosti i umjetnosti. Medicinske Znanosti 2022; 552: 58-9.
    [Google Scholar]
  5. Martín-FernándezM. AllerR. Heredia-RodríguezM. Gómez-SánchezE. Martínez-PazP. Gonzalo-BenitoH. Sánchez-de PradaL. GorgojoÓ. Carnicero-FrutosI. TamayoE. Tamayo-VelascoÁ. Lipid peroxidation as a hallmark of severity in COVID-19 patients.Redox Biol.20214810218110.1016/j.redox.2021.10218134768063
    [Google Scholar]
  6. HenryB.M. de OliveiraM.H.S. BenoitS. PlebaniM. LippiG. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): A meta-analysis.Clin Chem Lab Med (CCLM)20205871021102810.1515/cclm‑2020‑036932286245
    [Google Scholar]
  7. YangM. LaiC.L. SARS-CoV-2 infection: Can ferroptosis be a potential treatment target for multiple organ involvement?Cell Death Discov.20206113010.1038/s41420‑020‑00369‑w33251029
    [Google Scholar]
  8. CavezziA. TroianiE. CorraoS. COVID-19: Hemoglobin, iron, and hypoxia beyond inflammation. A narrative review.Clin. Pract.2020102127110.4081/cp.2020.127132509258
    [Google Scholar]
  9. DrakesmithH. PrenticeA. Viral infection and iron metabolism.Nat. Rev. Microbiol.20086754155210.1038/nrmicro193018552864
    [Google Scholar]
  10. LepantoM.S. RosaL. PaesanoR. ValentiP. CutoneA. Lactoferrin in aseptic and septic inflammation.Molecules2019247132310.3390/molecules2407132330987256
    [Google Scholar]
  11. ValkoM. LeibfritzD. MoncolJ. CroninM.T.D. MazurM. TelserJ. Free radicals and antioxidants in normal physiological functions and human disease.Int. J. Biochem. Cell Biol.2007391448410.1016/j.biocel.2006.07.00116978905
    [Google Scholar]
  12. PizzinoG IrreraN CucinottaM PallioG ManninoF ArcoraciV Oxidative stress: Harms and benefits for human health.Oxid Med Cell Longev.20172017841676310.1155/2017/8416763
    [Google Scholar]
  13. CullisJ.O. FitzsimonsE.J. GriffithsW.J.H. TsochatzisE. ThomasD.W. Investigation and management of a raised serum ferritin.Br. J. Haematol.2018181333134010.1111/bjh.1516629672840
    [Google Scholar]
  14. ForcadosG.E. MuhammadA. OladipoO.O. MakamaS. MesekoC.A. Metabolic implications of oxidative stress and inflammatory process in SARS-CoV-2 pathogenesis: Therapeutic potential of natural antioxidants.Front. Cell. Infect. Microbiol.20211165481310.3389/fcimb.2021.65481334123871
    [Google Scholar]
  15. TauseefM. KnezevicN. ChavaK.R. SmithM. SukritiS. GianarisN. ObukhovA.G. VogelS.M. SchraufnagelD.E. DietrichA. BirnbaumerL. MalikA.B. MehtaD. TLR4 activation of TRPC6-dependent calcium signaling mediates endotoxin-induced lung vascular permeability and inflammation.J. Exp. Med.2012209111953196810.1084/jem.2011135523045603
    [Google Scholar]
  16. NikiE. Biomarkers of lipid peroxidation in clinical material.Biochim. Biophys. Acta, Gen. Subj.20141840280981710.1016/j.bbagen.2013.03.020
    [Google Scholar]
  17. GuptaY. MaciorowskiD. MedernachB. BeckerD.P. DurvasulaR. LibertinC.R. KempaiahP. Iron dysregulation in COVID-19 and reciprocal evolution of SARS-CoV-2: Natura nihil frustra facit.J. Cell. Biochem.2022123360161910.1002/jcb.3020734997606
    [Google Scholar]
  18. GirelliD. MarchiG. BustiF. VianelloA. Iron metabolism in infections: Focus on COVID-19. Semin Hematol. 2021; 58(3): 182-187.10.1053/j.seminhematol.2021.07.001
  19. HanL ZhangE YinD KongR XuT ChenW Low expression of long noncoding RNA PANDAR predicts a poor prognosis of non-small cell lung cancer and affects cell apoptosis by regulating Bcl-2.Cell Death Dis201562e166510.1038/cddis.2015.30
    [Google Scholar]
  20. SastryS. CuomoF. MuthusamyJ. COVID-19 and thrombosis: The role of hemodynamics.Thromb. Res.2022212515710.1016/j.thromres.2022.02.01635219932
    [Google Scholar]
  21. LagadinouM SolomouEE ZareifopoulosN MarangosM GogosC VelissarisD Prognosis of COVID-19: Changes in laboratory parameters.Infez Med.202028suppl 18995
    [Google Scholar]
  22. EdeasM. SalehJ. PeyssonnauxC. Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis?Int. J. Infect. Dis.20209730330510.1016/j.ijid.2020.05.11032497811
    [Google Scholar]
  23. LvY. ChenL. LiangX. LiuX. GaoM. WangQ. WeiQ. LiuL. Association between iron status and the risk of adverse outcomes in COVID-19.Clin. Nutr.20214053462346910.1016/j.clnu.2020.11.03333380357
    [Google Scholar]
  24. ZhaoK. HuangJ. DaiD. FengY. LiuL. NieS. Serum iron level as a potential predictor of Coronavirus Disease 2019 severity and mortality: A retrospective study.Open Forum Infect Dis.202077ofaa25010.1093/ofid/ofaa250
    [Google Scholar]
  25. BolondiG. RussoE. GamberiniE. CircelliA. MecaM.C.C. BrogiE. ViolaL. BissoniL. PolettiV. AgnolettiV. Iron metabolism and lymphocyte characterisation during COVID-19 infection in ICU patients: An observational cohort study.World J. Emerg. Surg.20201514110.1186/s13017‑020‑00323‑232605582
    [Google Scholar]
  26. DollS. ConradM. Iron and ferroptosis: A still ill-defined liaison.IUBMB Life201769642343410.1002/iub.161628276141
    [Google Scholar]
  27. 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.2021.11122833454595
    [Google Scholar]
  28. BenyaminB. EskoT. RiedJ.S. RadhakrishnanA. VermeulenS.H. TragliaM. GögeleM. AndersonD. BroerL. PodmoreC. LuanJ. KutalikZ. SannaS. van der MeerP. TanakaT. WangF. WestraH.J. FrankeL. MihailovE. MilaniL. HälldinJ. WinkelmannJ. MeitingerT. ThieryJ. PetersA. WaldenbergerM. RendonA. JolleyJ. SambrookJ. KiemeneyL.A. SweepF.C. SalaC.F. SchwienbacherC. PichlerI. HuiJ. DemirkanA. IsaacsA. AminN. SteriM. WaeberG. VerweijN. PowellJ.E. NyholtD.R. HeathA.C. MaddenP.A.F. VisscherP.M. WrightM.J. MontgomeryG.W. MartinN.G. HernandezD. BandinelliS. van der HarstP. UdaM. VollenweiderP. ScottR.A. LangenbergC. WarehamN.J. van DuijnC. BeilbyJ. PramstallerP.P. HicksA.A. OuwehandW.H. OexleK. GiegerC. MetspaluA. CamaschellaC. TonioloD. SwinkelsD.W. WhitfieldJ.B. Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis.Nat. Commun.201451492610.1038/ncomms592625352340
    [Google Scholar]
  29. XuZ. ShiL. WangY. ZhangJ. HuangL. ZhangC. LiuS. ZhaoP. LiuH. ZhuL. TaiY. BaiC. GaoT. SongJ. XiaP. DongJ. ZhaoJ. WangF.S. Pathological findings of COVID-19 associated with acute respiratory distress syndrome.Lancet Respir. Med.20208442042210.1016/S2213‑2600(20)30076‑X32085846
    [Google Scholar]
  30. SferaA. BullockK. PriceA. InderiasL. OsorioC. Ferrosenescence: The iron age of neurodegeneration?Mech. Ageing Dev.2018174637510.1016/j.mad.2017.11.01229180225
    [Google Scholar]
  31. DalamagaM. KarampelaI. MantzorosC.S. Commentary: Could iron chelators prove to be useful as an adjunct to COVID-19 Treatment Regimens?Metabolism202010815426010.1016/j.metabol.2020.15426032418885
    [Google Scholar]
  32. BastinA. ShiriH. ZanganehS. FooladiS. Momeni MoghaddamM.A. MehrabaniM. Iron chelator or iron supplement consumption in COVID-19? The role of iron with severity infection.Biol. Trace Elem. Res.202111134825316
    [Google Scholar]
  33. GongT. LiuL. JiangW. ZhouR. DAMP-sensing receptors in sterile inflammation and inflammatory diseases.Nat. Rev. Immunol.20202029511210.1038/s41577‑019‑0215‑731558839
    [Google Scholar]
  34. FoxS.E. AkmatbekovA. HarbertJ.L. LiG. QuincyB.J. Vander HeideR.S. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from new orleans.Lancet Respir. Med.20208768168610.1016/S2213‑2600(20)30243‑532473124
    [Google Scholar]
  35. Bellmann-WeilerR. LanserL. BarketR. RanggerL. SchapflA. SchaberM. FritscheG. WöllE. WeissG. Prevalence and predictive value of anemia and dysregulated iron homeostasis in patients with COVID-19 infection.J. Clin. Med.202098242910.3390/jcm908242932751400
    [Google Scholar]
  36. MeradM. MartinJ.C. Pathological inflammation in patients with COVID-19: A key role for monocytes and macrophages.Nat. Rev. Immunol.202020635536210.1038/s41577‑020‑0331‑432376901
    [Google Scholar]
  37. ShahA. FrostJ.N. AaronL. DonovanK. DrakesmithH. McKechnieS.R. StanworthS.J. Systemic hypoferremia and severity of hypoxemic respiratory failure in COVID-19.Crit. Care202024132010.1186/s13054‑020‑03051‑w32517773
    [Google Scholar]
  38. SmailS.W. BabaeiE. AminK. Hematological, inflammatory, coagulation, and oxidative/antioxidant biomarkers as predictors for severity and mortality in COVID-19: A prospective cohort-study.Int. J. Gen. Med.20231656558010.2147/IJGM.S40220636824986
    [Google Scholar]
  39. WangD. YinY. HuC. LiuX. ZhangX. ZhouS. JianM. XuH. ProwleJ. HuB. LiY. PengZ. Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China.Crit. Care202024118810.1186/s13054‑020‑02895‑632354360
    [Google Scholar]
  40. DoerreA. DoblhammerG. The influence of gender on COVID-19 infections and mortality in Germany: Insights from age- and gender-specific modeling of contact rates, infections, and deaths in the early phase of the pandemic.PLoS One2022175e026811910.1371/journal.pone.026811935522614
    [Google Scholar]
  41. JinJ.M. BaiP. HeW. WuF. LiuX.F. HanD.M. LiuS. YangJ.K. Gender differences in patients with COVID-19: Focus on severity and mortality.Front. Public Health2020815210.3389/fpubh.2020.0015232411652
    [Google Scholar]
/content/journals/crmr/10.2174/011573398X306178240816054525
Loading
/content/journals/crmr/10.2174/011573398X306178240816054525
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test