Socio-economic status, iron deficiency anemia and COVID-19 disease burden – an appraisal
DOI:
https://doi.org/10.15584/ejcem.2021.1.8Keywords:
COVID-19, iron deficiency anemia, socio-economic statusAbstract
Introduction. Severe Acute Respiratory Syndrome-2, possesses varying degrees of susceptibility and lethality worldwide and WHO declared this as a pandemic of this century.
Aim. In this background, the aim of this present narrative is to provide a complementary overview of how low iron stores and mild anemia offers protection from infectious diseases like COVID-19 by restricting the viral replication and also to suggest some potential adjuvant therapeutic interventions.
Material and methods. Therefore, we performed a literature search reviewing pertinent articles and documents. PubMed, Google Scholar, Chemrxiv, MedRxiv, BioRxiv, Preprints and ResearchGate were investigated.
Analysis of the literature. Recent studies reported drastic systemic events taking place that contribute to the severe clinical outcomes such as decreased hemoglobin indicating anemia, hypoxia, altered iron metabolism, hypercoagulability, oxidative stress, cytokine storm, hyper-ferritinemia and thus Multi Organ Failure, reportedly hailed as the hallmark of the COVID-19 hyper-inflammatory state. Interestingly it is globally observed that, countries with higher Socio-economic status (SES) have considerably lower prevalence of Iron Deficiency Anemia (IDA) but higher Case Fatality Rate (CFR) rate due to COVID-19 while, low SES countries characterized by the higher prevalence of IDA, are less affected to COVID-19 infection and found to have less CFR, which is almost half to that of the higher SES counterpart.
Conclusion. Present review presumed that,low iron stores and mild anemia may play a beneficial role in some cases by offering protection from infectious diseases as low iron restricts the viral replication.Thus, suggested iron chelation or iron sequestration as an alternative beneficial adjuvant in treating COVID-19 infection.
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References
Gorbalenya AE, Baker SC, Baric RS, et al. The species Severe Acute Respiratory Syndrome-related Coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536-544.
Gemmati D, Bramanti B, Serino ML, Secchiero P, Zauli G, Tisato V. COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-Chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males? Int J Mol Sci. 2020;21(10):3474.
Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in coronavirus disease 2019 patients: A systematic review and meta-analysis. Int J Infect Dis. 2020;94:91-95.
Drosten C, Gunther S, Preiser W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003; 348:1967-1976.
Zaki AM, Van BS,Bestebroer TM, OsterhausAD,Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367(19): 1814-1820.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;95:497-506.
Bandyopadhyay AR, Chatterjee D, Ghosh K, Sarkar P. COVID 19: An Epidemiological and Host Genetics Appraisal. Asian J Med Sci. 2020;11(3):71-76.
Wan Y, Shang J, Graham R, et al. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS. J Virol. 2020;94(7):1-9.
Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. Covid-19 Does Not Lead to a "Typical" Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2020;201(10):1299-1300.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395:1054–1062.
Taneri PE, Gómez-Ochoa SA, Llanaj E, et al. Anemia and iron metabolism in COVID-19: a systematic review and meta-analysis. Eur J Epidemiol. 2020;35: 763–773.
Mehta D, McAuley DF, Brown M, et al. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395:1033-1034.
Phua J, Weng L, Ling L, et al. Intensive care management of coronavirus disease 2019 (COVID-19): Challenges and recommendations. Lancet Respir Med. 2020;8(5):506-517.
Zaim S, Chong JH, Sankaranarayanan V, Harky A. COVID-19 and multiorgan response (Epub 2020 Apr 28). Curr Probl Cardiol. 2020;45(8):1-22.
Kernan KF, Carcillo JA, Coffman LG, et al. Hyperferritinemia and Inflammation. Int Immunol. 2017;29(9):401-409.
Chan JF, Kok KH, Zhu Z, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microb Infect. 2020;9:221-236.
Cavezzi A, Troiani E, Corrao S. COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review. Clinics and Practice. 2020;10(2):24-30.
Ulrich H, Pillat MM. CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement. Stem Cell Rev Rep. 2020;20:1–7.
Li Y, Zhang Z, Yang L, et al. The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike. iScience. 2020;23(6):1-8.
Coste I, Gauchat JF, Wilson A, et al. Unavailability of CD147 leads to selective erythrocyte trapping in the spleen. Blood. 2001;97(12):3984–3988.
Lippi G, Mattiuzzi C. Hemoglobin value may be decreased in patients with severe coronavirus disease. Hematol Transfuse Cell Ther. 2020;42(2):116–117.
Xie J, Covassin N, Fan Z, et al. Association between hypoxemia and mortality in patients with COVID-19. Mayo Clin Proc. 2020; 95(6):1138-1147.
Cui S, Chen S, Li X, et al. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost.2020;18(6):1421‐1424.
Abbaspour N, Hurrell R, Kelishadi R. Review on iron and its importance for human health. J Res Med Sci. 2014;19(2):164-174.
Khodour Y, Kaguni LS, Stiban J. Iron-sulfur clusters in nucleic acid metabolism: varyingroles of ancient cofactors. Enzymes. 2019;45:225–256.
Lieu PT, Heiskala M, Peterson PA, Yang Y. The roles of iron in health and disease. Mol Aspects Med. 2001;2:1-87.
Ganz T. Molecular control of iron transport. J Am Soc Nephrol. 2007;18(2):394–400.
Nemeth E, Tuttle MS, Powelson J, etal.Hepcidin Regulates Cellular iron Efflux by Binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090-2093.
Ganz T. Hepcidin and iron regulation, 10 years later. Blood. 2011;117:4425–4433.
Lavin Y, Mortha A, Rahman A, Merad M. Regulation of macrophage development and function in peripheral tissues. Nat Rev Immunol. 2015;15:731–744.
Ganz T, Nemeth E. Hepcidin and iron Homeostatis. Biochim Biophys Acta. 2012;1823(9):1434-1443.
Goddard GZ, Shoenfeld Y. Ferritin in autoimmune diseases. Autoimmun Rev. 2007;6(7): 457-463.
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.
Chaparro CM, Suchdev PM. Anemia epidemiology, pathophysiology, and etiology in low-and middle-income countries. Ann N Y Acad Sci. 2019;1450(1):15-31.
Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood. 2006;107(5):1747-1750.
Calis JC, Phiri KS, Faragher EB, et al. Severe anemia in Malawian children. N Engl J Med. 2008;358:888 –899.
WHO. Nutritional Anemia: tools for effective prevention. Geneva: World Health Organization, 2017.
World Health Organization. Iron Deficiency Anaemia: Assessment, Prevention And Control. A guide for programme managers. WHO: Geneva, 2001.
Conrad ME, Umbreit JN, Moore EG. Iron absorption and transport. Am J Med Sci. 1999; 318(4):213–229.
Kim JY, Shin S, Han K, et al. Relationship between socioeconomic status and anemia prevalence in adolescent girls based on the fourth and fifth Korea National Health and Nutrition Examination Surveys. Eur J Clin Nutr. 2014;68(2): 253–258.
Issaragrisil S, KaufmanDW, Anderson TE, et al. An association of aplastic anaemia in Thailand with low socioeconomic status. Aplastic Anemia Study Group. Br J Haematol. 1995;91(1):80–84.
Gompakis N, Economou M, Tsantali C, et al. The effect of dietary habits and socioeconomic status on the prevalence of iron deficiency in children of northern Greece. Acta Haematol. 2007;117(4):200–204.
Thankachan P, Muthayya S, Walczyk T, Kurpad AV, Hurrell RF. An analysis of the etiology of anemia and iron deficiency in young women of low socioeconomic status in Bangalore, India. Food Nutr Bull. 2007;28(3):328–336.
Animasahun BA, Temiye EO, Ogunkunle OO, Izuora AN, Njokanma OF. The influence of socioeconomic status on the hemoglobin level and anthropometry of sickle cell anemia patients in steady state at the Lagos University Teaching Hospital. Niger J Clin Pract. 2011;14(4):422–427.
Shilpa S, Biradar SPB, Alatagi AC, Wantamutte AS, Malur PR. Prevalence of anaemia among adolescent girls: a one year cross-sectional study. J Clin Diag Res. 2012;6(3): 372– 377.
Ifeanyi OE. International Journal of Advanced Multidisciplinary Research. Int J Adv Multidiscip Res. 2018;5(4):11-15.
COVID tracker (https://covid19.who.int/) Accessed 20 July, 2020.
https://howmuch.net/articles/gdp-per-capita-2018. International Monitory Fund-World Economic Outlook. Accesses on 13 July, 2020.
Benoist BD, McLean E, Egli I, Cogswell M. Worldwide prevalence of anemia 1993– 2005: WHO Global Database on Anemia. Geneva, Switzerland: World Health Organization; 2008.
Agostini ML, Andres EL, Sims AC, et al., Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio. 2018;9(2):1-15.
Yao TT, Qian JD, Zhu WY, Wang Y, Wang GQ. A Systematic review of lopinavir therapy for SARS Coronavirus and MERS Coronavirus-a possible reference for Coronavirus Disease-19 treatment option. J Med Virol. 2020;92(6):556-563.
Lester M, Sahin A, Pasyar A. The use of Dexamethsone in the treatment of COVID-19. Ann Med Surg (Lond). 2020;56:218-219.
Huang L, Chen Y, Xiao J, et al. Progress in the Research and Development of Anti-COVID-19 Drugs. Front Public Health. 2020;365(8):1-8
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):24301–24308.
Adedeji A, Lazarus H. Biochemical characterization of Middle East respiratory syndrome coronavirus helicase. mSphere. 2016;1(5):e00235–16.
Jia Z, Liming Y, Ren Z, et al. Delicate structural coordination of the severe acute respiratory syndrome coronavirus Nsp13 upon ATP hydrolysis. Nucleic Acids Res. 2019;47(12):6538-6550.
Liu W, Zhang S, Nekhai S, et al. Depriving Iron Supply to the Virus Represents a Promising Adjuvant Therapeutic Against Viral Survival. Current Clinical Microbiology Reports. 2020;7:13-19.
Cassat JE, Skaar EP. Iron in infection and immunity. Cell Host Microbe. 2013;13(5):509– 519.
Drakesmith H, Prentice A. Viral infection and iron metabolism. Nat Rev Microbiol. 2008;6(7):541–552.
Pereira LA, Bentley K, Peeters A, Churchill MJ, Deacon NJ. A compilation of cellular transcription factor interactions with the HIV-1 LTR promoter. Nucleic Acids Res. 2000;28(3):663–668.
Xiong S, She H, Takeuchi H, et al. Signaling role of intracellular Iron in NF-κB activation. J Biol Chem. 2003;278(20):17646–17654.
Xiong S, She H, Sung CK, Tsukamoto H. Iron-dependent activation of NF-kappaB in Kupffer cells: a priming mechanism for alcoholic liver disease. Alcohol. 2003;30(2):107–113.
Hoque M, Hanauske-Abel HM, Palumbo P, et al. InhibitionofHIV-1geneexpressionby Ciclopirox and Deferiprone, drugs that prevent hypusination of eukaryotic initiation factor 5A. Retrovirology. 2009;6:90.
Zimmerman C, Klein K, Kiser P, et al. Identification of a host protein essential for assembly of immature HIV-1 capsids. Nature. 2002;415(6867):88–92.
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):213–224.
Zandman-Goddard G, Shoenfeld Y. Ferritin in autoimmune diseases. Autoimmun Rev. 2007;6(7):457–463.
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):e233–236.
Arieh S, Laham-Karam N, Schechter C, et al. A single viral protein HCMV US2 affects antigen presentation and intracellular iron homeostasis by degradation of classical HLA class I and HFE molecules. Blood. 2003;101(7):2858–2864.
Hariyanto TI, Kurniawan A. Anemia is associated with severe coronavirus disease 2019 (COVID-19) infection. Transfus Apher Sci. 2020;59(6):102926.
Moalem S, Weinberg ED, Percy ME. Hemochromatosis and the enigma of misplaced iron: implications for infectious disease and survival. Biometals. 2004;17(2):135-139.
Scindia Y, Dey P, Thirunagari A, et al. Hepcidin mitigates renal ischemia-reperfusion injury by modulating systemic iron homeostasis. J Am Soc Nephrol. 2015;26(11):2800–2814.
Thursz M. Iron, hemochromatosis and thalassemia as risk factors for fibrosis in hepatitis C virus infection. Gut. 2007;56(5):613–614.
Galli A, Svegliati-Baroni G, Ceni E, et al. Oxidative stress stimulates proliferation and invasiveness of hepatic stellate cells via a MMP2-mediated mechanism. Hepatology. 2005;41(5):1074–1084.
Debebe Z, Ammosova T, Jerebtsova M, et al. Iron chelators ICL670 and 311 inhibit HIV-1 transcription. Virology. 2007;367(2):324–333.
Mobarra N, Shanaki M, Ehteram H, et al. A Review on Iron Chelators in Treatment of Iron Overload Syndromes. Int J Hematol Oncol Stem Cell Res. 2016;10(4):239–247.
Weinberg ED. Iron availability and infection. Biochim Biophys Acta. 2009;1790(7):600–605.
Ganz T, Nemeth E. Iron homeostasis in host defense and inflammation. Nat Rev Immunol. 2015;15(8):500–510.
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