Relationship between ferritin levels and the prognosis of COVID-19

Authors

DOI:

https://doi.org/10.11606/issn.1679-9836.v101i1e-190974

Keywords:

Ferritin, COVID-19, Inflammation, Hyperferritinemia, Treatments, Acute respiratory distress syndrome

Abstract

The high level of serum ferritin has been associated with severe COVID-19 due to its stimulation by cytokines related to the inflammatory process. Although this increase is expected, this review proposes to analyze how high ferritin can be related to this severeness. According to this premise, the hyperferritinemia on COVID-19 could be an important factor of prediction and another way to understand the complications of COVID-19 -coagulopathy, acute respiratory distress syndrome (ARDS). Furthermore, this correlation has been seen as a possible fifth syndrome among the other "hyperferritinemic syndromes", which are all characterized by high serum ferritin; this is an pertinent comparison and analyzation in terms of treatments.

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Author Biographies

  • Elson Cavalcante Silva de Sousa Júnior, Universidade de Pernambuco (UPE)

    Discente da Universidade de Pernambuco. Campus Garanhuns.

  • Artur Pereira de França Medeiros, Universidade de Pernambuco (UPE)

    Discente da Universidade de Pernambuco. Campus Garanhuns.

  • Igor Vasconcelos e Silva, Universidade de Pernambuco (UPE)

    Discente da Universidade de Pernambuco. Campus Garanhuns.

  • Rafael de Freitas e Silva, Universidade de Pernambuco (UPE)

    Docente da Universidade de Pernambuco. Campus Garanhuns. É o orientador deste manuscrito.

References

Shi Y, Wang G, Cai X, et al. An overview of COVID-19. J Zhejiang Univ-Sci B. 2020;21(5):343-360. doi: 10.1631/jzus.B2000083

Lin Z, Long F, Yang Y, Chen X, Xu L, Yang M. Serum ferritin as an independent risk factor for severity in COVID-19 patients. J Infect. 2020;81(4):647-79. doi: 10.1016/j.jinf.2020.06.053

Huang I, Pranata R, Lim MA, Oehadian A, Alisjahbana B. C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis. Ther Adv Respir Dis. 2020;14:175346662093717. doi: 10.1177/1753466620937175

Ruscitti P, Di Benedetto P, Berardicurti O, et al. Pro-inflammatory properties of H-ferritin on human macrophages, ex vivo and in vitro observations. Sci Rep. 2020;10(1):12232. doi: 10.1038/s41598-020-69031-w

Colafrancesco S, Alessandri C, Conti F, Priori R. COVID-19 gone bad: a new character in the spectrum of the hyperferritinemic syndrome? Autoimmun Rev. 2020;19(7):102573. doi: 10.1016/j.autrev.2020.102573

Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020;7(6):e438-e440. doi: 10.1016/S2352-3026(20)30145-9

Fontana P, Casini A, Robert-Ebadi H, Glauser F, Righini M, Blondon M. Venous thromboembolism in COVID-19: systematic review of reported risks and current guidelines. Swiss Med Wkly. 2020;150:w20301. doi: 10.4414/smw.2020.20301

Al-Samkari H, Karp Leaf RS, Dzik WH, et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 2020;136(4):489-500. doi: 10.1182/blood.2020006520

Cohen LA, Gutierrez L, Weiss A, et al. Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood. 2010;116(9):1574-84. doi: 10.1182/blood-2009-11-253815

Harrison PM, Arosio P. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta BBA - Bioenerg. 1996;1275(3):161-203. doi: 10.1016/0005-2728(96)00022-9

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):185. doi: 10.1186/1741-7015-11-185

Recalcati S, Invernizzi P, Arosio P, Cairo G. New functions for an iron storage protein: The role of ferritin in immunity and autoimmunity. J Autoimmun. 2008;30(1-2):84-89. doi:10.1016/j.jaut.2007.11.003

Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: Past, present and future. Biochim Biophys Acta. 2010;1800(8):760-9. doi: 10.1016/j.bbagen.2010.03.011

Torti FM, Torti SV. Regulation of ferritin genes and protein. Blood. 2002;99(10):3505-16. doi: 10.1182/blood.V99.10.3505

Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017;29(9):401-9. doi: 10.1093/intimm/dxx031

Worwood M, Dawkins S, Wagstaff M, Jacobs A. The purification and properties of ferritin from human serum. Biochem J. 1976;157(1):97-103. doi: 10.1042/bj1570097

Zacharski LR, Ornstein DL, Woloshin S, Schwartz LM. Association of age, sex, and race with body iron stores in adults: Analysis of NHANES III data. Am Heart J. 2000;140(1):98-104. doi: 10.1067/mhj.2000.106646

Grotto HZW. Diagnóstico laboratorial da deficiência de ferro. Rev Bras Hematol Hemoter. 2010;32:22-8. doi: 10.1590/S1516-84842010005000046

Cairo G, Pietrangelo A. Iron regulatory proteins in pathobiology. Biochem J. 2000;352 Pt 2:241-250.

Kim S, Ponka P. Control of Transferrin Receptor Expression via Nitric Oxide-mediated Modulation of Iron-regulatory Protein 2. J Biol Chem. 1999;274(46):33035-42. doi: 10.1074/jbc.274.46.33035

Mikhael M, Kim SF, Schranzhofer M, et al. Iron regulatory protein-independent regulation of ferritin synthesis by nitrogen monoxide: IRP-independent effects of NO+ on Ft synthesis. FEBS J. 2006;273(16):3828-36. doi: 10.1111/j.1742-4658.2006.05390.x

Rogers J, Lacroix L, Durmowitz G, Kasschau K, Andriotakis J, Bridges KR. The role of cytokines in the regulation of ferritin expression. Adv Exp Med Biol. 1994;356:127-32. doi: 10.1007/978-1-4615-2554-7_14

Li JY, Paragas N, Ned RM, et al. Scara5 is a ferritin receptor mediating non-transferrin iron delivery. Dev Cell. 2009;16(1):35-46. doi: 10.1016/j.devcel.2008.12.002

Gray CP, Franco AV, Arosio P, Hersey P. Immunosuppressive effects of melanoma-derived heavy-chain ferritin are dependent on stimulation of IL-10 production. Int J Cancer. 2001;92(6):843-50. doi: 10.1002/ijc.1269

Li R, Luo C, Mines M, Zhang J, Fan G-H. Chemokine CXCL12 induces binding of ferritin heavy chain to the chemokine receptor CXCR4, Alters CXCR4 signaling, and induces phosphorylation and nuclear translocation of ferritin heavy chain. J Biol Chem. 2006;281(49):37616-27. doi: 10.1074/jbc.M607266200

Zhou P, Yang X-L, Wang X-G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3. doi: 10.1038/s41586-020-2012-7

Lan J, Ge J, Yu J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581(7807):215-20. doi: 10.1038/s41586-020-2180-5

Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363-74. doi: 10.1038/s41577-020-0311-8

Yang M. Cell pyroptosis, a potential pathogenic mechanism of 2019-nCoV infection. SSRN. 2020. doi: http://dx.doi.org/10.2139/ssrn.3527420

Zhang C, Wu Z, Li J-W, Zhao H, Wang G-Q. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020;55(5):105954. doi: 10.1016/j.ijantimicag.2020.105954

Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5

Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. J Infect. 2020;80(6):607-13. doi: 10.1016/j.jinf.2020.03.037

Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76(1):16-32. doi: 10.1128/MMBR.05015-11

Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;71(15):762-8. doi: 10.1093/cid/ciaa248

Wang F, Hou H, Luo Y, et al. The laboratory tests and host immunity of COVID-19 patients with different severity of illness. JCI Insight. 2020;5(10):e137799. doi: 10.1172/jci.insight.137799

Ni M, Tian F, Xiang D, Yu B. Characteristics of inflammatory factors and lymphocyte subsets in patients with severe COVID‐19. J Med Virol. 2020;92(11):2600-6. doi: 10.1002/jmv.26070

Ruddell RG, Hoang-Le D, Barwood JM, et al. Ferritin functions as a proinflammatory cytokine via iron-independent protein kinase C zeta/nuclear factor kappaB-regulated signaling in rat hepatic stellate cells. Hepatology. 2009;49(3):887-900. doi: 10.1002/hep.22716

Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int J Mol Sci. 2019;20(13):3328. doi: 10.3390/ijms20133328

Swanson KV, Deng M, Ting JP-Y. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19(8):477-89. doi: 10.1038/s41577-019-0165-0

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. doi: 10.1039/C3MT00347G

Ware LB, Matthay MA. The Acute Respiratory Distress Syndrome. N Engl J Med. 2000;342(18):1334-49. doi: 10.1056/NEJM200005043421806

Connelly KG, Moss M, Parsons PE, et al. Serum ferritin as a predictor of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1997;155(1):21-5. doi: 10.1164/ajrccm.155.1.9001283

Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-20. doi: 10.1056/NEJMoa2002032

Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020;135(23):2033-40. doi: 10.1182/blood.2020006000

Iba T, Levy JH. Inflammation and thrombosis: roles of neutrophils, platelets and endothelial cells and their interactions in thrombus formation during sepsis. J Thromb Haemost. 2018;16(2):231-41. doi: 10.1111/jth.13911

Pretorius E, Kell DB. Diagnostic morphology: biophysical indicators for iron-driven inflammatory diseases. Integr Biol. 2014;6(5):486-510. doi: 10.1039/C4IB00025K

Lipinski B, Pretorius E, Oberholzer HM, Van Der Spuy WJ. Iron enhances generation of fibrin fibers in human blood: Implications for pathogenesis of stroke. Microsc Res Tech. 2012;75(9):1185-90. doi: 10.1002/jemt.22047

Eckly A, Hechler B, Freund M, et al. Mechanisms underlying FeCl3-induced arterial thrombosis: Characterization of the FeCl3-induced thrombosis model. J Thromb Haemost. 2011;9(4):779-89. doi: 10.1111/j.1538-7836.2011.04218.x

Perricone C, Bartoloni E, Bursi R, et al. COVID-19 as part of the hyperferritinemic syndromes: the role of iron depletion therapy. Immunol Res. 2020;68(4):213-24. doi: 10.1007/s12026-020-09145-5

Levi M, van der Poll T. Coagulation and sepsis. Thromb Res. 2017;149:38-44. doi: 10.1016/j.thromres.2016.11.007

Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure. Cell Host Microbe. 2020;27(6):992-1000.e3. doi: 10.1016/j.chom.2020.04.009

Zhang Y, Xiao M, Zhang S, et al. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. N Engl J Med. 2020;382(17):e38. doi: 10.1056/NEJMc2007575

National Institutes of Health. COVID-19 Treatment. Coronavirus disease 2019 (COVID-19) treatment guidelines. Bethesda, Maryland; s.d. [cited 2021 June 14]. Available from: https://www.covid19treatmentguidelines.nih.gov/.

Xie Y, Cao S, Dong H, et al. Effect of regular intravenous immunoglobulin therapy on prognosis of severe pneumonia in patients with COVID-19. J Infect. 2020;81(2):318-56. doi: 10.1016/j.jinf.2020.03.044

Mohtadi N, Ghaysouri A, Shirazi S, et al. Recovery of severely ill COVID-19 patients by intravenous immunoglobulin (IVIG) treatment: A case series. Virology. 2020;548:1-5. doi: 10.1016/j.virol.2020.05.006

Shi H, Zhou C, He P, et al. Successful treatment with plasma exchange followed by intravenous immunoglobulin in a critically ill patient with COVID-19. Int J Antimicrob Agents. 2020;56(2):105974. doi: 10.1016/j.ijantimicag.2020.105974

Khamis F, Al-Zakwani I, Al Hashmi S, et al. Therapeutic plasma exchange in adults with severe COVID-19 infection. Int J Infect Dis. 2020;99:214-18. doi: 10.1016/j.ijid.2020.06.064

Ma J, Xia P, Zhou Y, et al. Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19. Clin Immunol. 2020;214:108408. doi: 10.1016/j.clim.2020.108408

Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335(1):2-13. doi:10.1016/j.mce.2010.04.005

Nguyen AA, Habiballah SB, Platt CD, Geha RS, Chou JS, McDonald DR. Immunoglobulins in the treatment of COVID-19 infection: Proceed with caution! Clin Immunol. 2020;216:108459. doi: 10.1016/j.clim.2020.108459

Jawhara S. Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients? Int J Mol Sci. 2020;21(7):2272. doi: 10.3390/ijms21072272

Shum HP, Yan WW, Chan TM. Extracorporeal blood purification for sepsis. Hong Kong Med J. 2016;22(5):478-85. doi: 10.12809/hkmj164876

Keith P, Day M, Perkins L, Moyer L, Hewitt K, Wells A. A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care. 2020;24(1):128,s13054-020-2836-4. doi: 10.1186/s13054-020-2836-4

Castañeda S, Blanco R, González-Gay MA. Adult-onset Still’s disease: advances in the treatment. Best Pract Res Clin Rheumatol. 2016;30(2):222-38. doi: 10.1016/j.berh.2016.08.003

Mavragani CP, Spyridakis EG, Koutsilieris M. Adult-Onset Still’s disease: From pathophysiology to targeted therapies. Int J Inflamm. 2012;2012:1-10. doi: 10.1155/2012/879020

The REMAP-CAP Investigators. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. N Engl J Med. 2021;384(16):1491-502. doi: 10.1056/NEJMoa2100433

Abani O, Abbas A, Abbas F, et al. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637-45. doi: 10.1016/S0140-6736(21)00676-0

Huet T, Beaussier H, Voisin O, et al. Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol. 2020;2(7):e393-e400. doi: 10.1016/S2665-9913(20)30164-8

Cavalli G, De Luca G, Campochiaro C, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2(6):e325-e331. doi: 10.1016/S2665-9913(20)30127-2

Published

2022-02-23

Issue

Section

Artigos de Revisão/Review Articles

How to Cite

Sousa Júnior, E. C. S. de, Medeiros, A. P. de F., & Silva, R. de F. e . (2022). Relationship between ferritin levels and the prognosis of COVID-19 (I. V. e Silva, Trans.). Revista De Medicina, 101(1), e-190974. https://doi.org/10.11606/issn.1679-9836.v101i1e-190974