Volume 6, Issue 1 (Journal of Clinical and Basic Research (JCBR) 2022)                   jcbr 2022, 6(1): 11-27 | Back to browse issues page

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EmamiPari F, Kamali S, Nikzad G, Roosta Navi N, Soltani S, Kalani M R. A Review of Pleiotropic Potential of Erythropoietin as an Adjunctive Therapy for COVID-19. jcbr. 2022; 6 (1) :11-27
URL: http://jcbr.goums.ac.ir/article-1-324-en.html
1- Department of Animal Sciences, College of Life Sciences, Kharazmi University of Tehran, Tehran, Iran
2- Department of Molecular Cell Biology - Molecular Cell Science, Faculty of Basic Sciences, Mohaghegh Ardabili University, Ardabil, Iran
3- Department of Molecular Cell Biology - Molecular Cell Science, Payame Noor University of Talesh, Gilan, Iran
4- Department of Biology, Shahr-e-Quds Branch, Islamic Azad University, Tehran, Iran
5- Molecular Medicine Department, Golestan University of Medical Sciences, Gorgan, Iran , kalani@goums.ac.ir
Abstract:   (321 Views)
Coronavirus disease 2019 (COVID-19) is a severe acute respiratory disease with a high prevalence. According to the research and statistical data, in January 2021, there have been 92,262,621 confirmed cases of COVID-19 and more than two million deaths. Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the main cause of this disease. In addition to the respiratory system, the disease affects the gastrointestinal tract, central-peripheral nervous system, circulatory system, and kidneys. Therefore, any therapeutic action to reduce COVID-19-related symptoms and complications is essential. In this study, we conducted a systematic review of the published literature and preprints on the efficacy of erythropoietin (EPO) and recombinant human EPO as a safe stimulant and tissue protector in the treatment of COVID-19. We also briefly described the structure of coronavirus, its pathogenesis, and the structure of EPO and recombinant human EPO. All relevant articles published in the Science Direct, PubMed, and Google Scholar databases were searched.  According to the results, EPO is a cytoprotective cytokine induced by hypoxia. The pleiotropic effects of EPO are associated with its erythrocyte-forming, anti-apoptotic, anti-inflammatory activities. It also exerts protective effects on the heart, lungs, kidneys, arteries, and central and peripheral nervous systems. It has been demonstrated that EPO can increase hemoglobin levels, thereby increasing oxygen delivery to the tissues. Therefore, recombinant human EPO therapy can be used for counteracting the adverse effects of COVID-19 including hypoxic myocarditis, acute renal failure, pulmonary edema, and brain-spinal cord ischemic injury. Overall, the use of EPO and recombinant human EPO therapy increases blood coagulation, tumor growth, thromboembolism, and purification of red blood cells, which must be accompanied by anticoagulants such as heparin.
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Article Type: Review | Subject: Cellular and Molecular Biology
Received: 2021/08/9 | Accepted: 2022/01/9 | Published: 2022/02/2

1. World Health Organization [Internet]. 2021.
2. Alhogbani T. Acute myocarditis associated with novel Middle east respiratory syndrome coronavirus. Ann Saudi Med. 2016;36(1):78-80. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
3. Hadadi A, Mortezazadeh M, Kolahdouzan K, Alavian G. Does recombinant human erythropoietin administration in critically ill COVID-19 patients have miraculous therapeutic effects? J Med Virol. 2020;92(7):915-8. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
4. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nature Reviews Immunology. 2020;20(6):363-74. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
5. Kimáková P, Solár P, Solárová Z, Komel R, Debeljak N. Erythropoietin and Its Angiogenic Activity. Int J Mol Sci. 2017;18(7). [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
6. Soliz J, Schneider-Gasser EM, Arias-Reyes C, Aliaga-Raduan F, Poma-Machicao L, Zubieta-Calleja G, et al. Coping with hypoxemia: Could erythropoietin (EPO) be an adjuvant treatment of COVID-19? Respir Physiol Neurobiol. 2020;279:103476-. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
7. Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci. 2020;11(7):995-8. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
8. Lacombe C, Mayeux P. Biology of erythropoietin. Haematologica. 1998;83(8):724-32. [View at Publisher] [Google Scholar]
9. Kobayashi H, Liu J, Urrutia AA, Burmakin M, Ishii K, Rajan M, et al. Hypoxia-inducible factor prolyl-4-hydroxylation in FOXD1 lineage cells is essential for normal kidney development. Kidney Int. 2017;92(6):1370-83. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
10. Ehrenreich H, Weissenborn K, Begemann M, Busch M, Vieta E, Miskowiak KW. Erythropoietin as candidate for supportive treatment of severe COVID-19. Mol Med. 2020;26(1):58. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
11. Dame C, Fahnenstich H, Freitag P, Hofmann D, Abdul-Nour T, Bartmann P, et al. Erythropoietin mRNA expression in human fetal and neonatal tissue Blood. 1998;92(9):3218-25. [View at Publisher] [DOI] [PMID] [Google Scholar]
12. Ghezzi P, Brines M. Erythropoietin as an anti-apoptotic, tissue-protective cytokine. Cell Death & Differentiation. 2004;11(1):S37-S44. [View at Publisher] [DOI] [PMID] [Google Scholar]
13. Shanmugaraj B, Siriwattananon K, Wangkanont K, Phoolcharoen W. Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Asian Pac J Allergy Immunol. 2020;38(1):10-8. [Google Scholar]
14. Li H, Liu SM, Yu XH, Tang SL, Tang CK. Coronavirus disease 2019 (COVID-19): current status and future perspectives. Int J Antimicrob Agents. 2020;55(5):105951. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
15. Mousavizadeh L, Ghasemi S. Genotype and phenotype of COVID-19: Their roles in pathogenesis. J Microbiol Immunol Infect. 2021;54(2):159-63. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
16. Vellingiri B, Jayaramayya K, Iyer M, Narayanasamy A, Govindasamy V, Giridharan B, et al. COVID-19: A promising cure for the global panic. Sci Total Environ. 2020;725:138277. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
17. Zhang R, Wang X, Ni L, Di X, Ma B, Niu S, et al. COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020;250:117583. [View at Publisher] [DOI:10.1016/j.lfs.2020.117583] [PMID] [PMCID] [Google Scholar]
18. Asselah T, Durantel D, Pasmant E, Lau G, Schinazi RF. COVID-19: Discovery, diagnostics and drug development. J Hepatol. 2021;74(1):168-84. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
19. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787-99. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
20. Dai M, Liu D, Liu M, Zhou F, Li G, Chen Z, et al. Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak. Cancer Discov. 2020;10(6):783-91. https://doi.org/10.2139/ssrn.3558017 [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
21. Zhu FC, Li YH, Guan XH, Hou LH, Wang WJ, Li JX, et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet. 2020;395(10240):1845-54. [View at Publisher] [DOI] [Google Scholar]
22. 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. Lancet. 2020;395(10223):497-506. [View at Publisher] [DOI] [Google Scholar]
23. Hu K, Patel J, Swiston C, Patel BC. Ophthalmic Manifestations Of Coronavirus (COVID-19). StatPearls. Treasure Island (FL): StatPearls Publishing [Google Scholar]
24. Brier ME, Bunke CM, Lathon PV, Aronoff GR. Erythropoietin-induced antinatriuresis mediated by angiotensin II in perfused kidneys. J Am Soc Nephrol. 1993;3(9):1583-90. [View at Publisher] [DOI] [PMID] [Google Scholar]
25. Geier MR, Geier DA. Respiratory conditions in coronavirus disease 2019 (COVID-19): Important considerations regarding novel treatment strategies to reduce mortality. Med Hypotheses. 2020;140:109760. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
26. Hui DS, E IA, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020;91:264-6. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
27. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;588(7836):E6. [View at Publisher] [DOI] [PMID] [Google Scholar]
28. Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, et al. Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol. 2020;11:827. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
29. Broxmeyer HE. Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration. J Exp Med. 2013;210(2):205-8. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
30. Genc S, Koroglu TF, Genc K. Erythropoietin and the nervous system. Brain Res. 2004;1000(1-2):19-31. [View at Publisher] [DOI] [PMID] [Google Scholar]
31. Sun Y, Zhou C, Polk P, Nanda A, Zhang JH. Mechanisms of erythropoietin-induced brain protection in neonatal hypoxia-ischemia rat model. J Cereb Blood Flow Metab. 2004;24(2):259-70. [View at Publisher] [DOI] [PMID] [Google Scholar]
32. Kuhrt D, Wojchowski DM. Emerging EPO and EPO receptor regulators and signal transducers. Blood. 2015;125(23):3536-41. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
33. Krantz SB. Erythropoietin. Blood. 1991;77(3):419-34. https://doi.org/10.1182/blood.V77.3.419.419 [View at Publisher] [DOI] [PMID] [Google Scholar]
34. Marti HH, Wenger RH, Rivas LA, Straumann U, Digicaylioglu M, Henn V, et al. Erythropoietin gene expression in human, monkey and murine brain. Eur J Neurosci. 1996;8(4):666-76. [View at Publisher] [DOI] [PMID] [Google Scholar]
35. Jelkmann W. Physiology and pharmacology of erythropoietin. Transfus Med Hemother. 2013;40(5):302-9. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
36. Wu H, Liu X, Jaenisch R, Lodish HF. Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell. 1995;83(1):59-67. [View at Publisher] [DOI] [Google Scholar]
37. Lin CS, Lim SK, D'Agati V, Costantini F. Differential effects of an erythropoietin receptor gene disruption on primitive and definitive erythropoiesis. Genes Dev. 1996;10(2):154-64. [View at Publisher] [DOI] [PMID] [Google Scholar]
38. Suresh S, Rajvanshi PK, Noguchi CT. The Many Facets of Erythropoietin Physiologic and Metabolic Response. Front Physiol. 2019;10:1534. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
39. Liu L, Damen JE, Cutler RL, Krystal G. Multiple cytokines stimulate the binding of a common 145-kilodalton protein to Shc at the Grb2 recognition site of Shc. Mol Cell Biol. 1994;14(10):6926-35. [View at Publisher] [DOI] [PMID] [PMCID]
40. Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, et al. JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell. 1993;74(2):227-36. [View at Publisher] [DOI] [Google Scholar]
41. Juul SE, Yachnis AT, Christensen RD. Tissue distribution of erythropoietin and erythropoietin receptor in the developing human fetus. Early Hum Dev. 1998;52(3):235-49. [View at Publisher] [DOI] [Google Scholar]
42. Livnah O, Stura EA, Middleton SA, Johnson DL, Jolliffe LK, Wilson IA. Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation. Science. 1999;283(5404):987-90. [View at Publisher] [DOI] [PMID] [Google Scholar]
43. Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, et al. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A. 2003;100(10):5807-12. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
44. Watowich SS. The erythropoietin receptor: molecular structure and hematopoietic signaling pathways. J Investig Med. 2011;59(7):1067-72. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
45. Jacobs K, Shoemaker C, Rudersdorf R, Neill SD, Kaufman RJ, Mufson A, et al. Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature. 1985;313(6005):806-10. [View at Publisher] [DOI] [PMID] [Google Scholar]
46. Erythropoietins, Erythropoietic Factors, and Erythropoiesis. 2 ed. Steven G. Elliott MF, Graham Molineux, editor. Birkhäuser Basel 2009: Birkhäuser Basel; 2009. XVIII, 330 p.
47. Egrie JC, Browne J, Lai P, Lin FK. Characterization of recombinant monkey and human erythropoietin. Prog Clin Biol Res. 1985;191:339-50. [View at Publisher] [Google Scholar]
48. Wei Y, Zhou J, Yu H, Jin X. AKT phosphorylation sites of Ser473 and Thr308 regulate AKT degradation. Biosci Biotechnol Biochem. 2019;83(3):429-35. [View at Publisher] [DOI] [PMID] [Google Scholar]
49. Thomas R. Gelzleichter. Chapter 7 - Early Characterization of Biosimilar Therapeutics. M. Plitnick DJH, editor. In : Lisa Nonclinical Development of Novel Biologics, Biosimilars, Vaccines and Specialty Biologics, Academic Press, ; 2013. [View at Publisher] [DOI] [Google Scholar]
50. Brines M, Cerami A. Emerging biological roles for erythropoietin in the nervous system. Nat Rev Neurosci. 2005;6(6):484-94. [View at Publisher] [DOI] [PMID] [Google Scholar]
51. Arcasoy MO. The non-haematopoietic biological effects of erythropoietin. Br J Haematol. 2008;141(1):14-31. [View at Publisher] [DOI] [PMID] [Google Scholar]
52. Alley W, Tao L, Shion H, Yu YQ, Rao C, Chen W. UPLC-MS assessment on the structural similarity of recombinant human erythropoietin (rhEPO) analogues from manufacturers in China for attribute monitoring. Talanta. 2020;220:121335. [View at Publisher] [DOI] [PMID] [Google Scholar]
53. Fisher JW. Landmark advances in the development of erythropoietin. Experimental Biology and Medicine. 2010 Dec;235(12):1398-411. [View at Publisher] [DOI] [PMID] [Google Scholar]
54. Jubinsky PT, Krijanovski OI, Nathan DG, Tavernier J, Sieff CA. The beta chain of the interleukin-3 receptor functionally associates with the erythropoietin receptor. Blood. 1997;90(5):1867-73. [View at Publisher] [DOI] [PMID] [Google Scholar]
55. Brines M, Cerami A. The receptor that tames the innate immune response. Mol Med. 2012;18(1):486-96. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
56. Anusornvongchai T, Nangaku M, Jao TM, Wu CH, Ishimoto Y, Maekawa H, et al. Palmitate deranges erythropoietin production via transcription factor ATF4 activation of unfolded protein response. Kidney Int. 2018;94(3):536-50. [View at Publisher] [DOI] [PMID] [Google Scholar]
57. Nairz M, Haschka D, Dichtl S, Sonnweber T, Schroll A, Aßhoff M, et al. Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis. Scientific Reports. 2017;7(1):13012. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
58. Erbayraktar S, Grasso G, Sfacteria A, Xie QW, Coleman T, Kreilgaard M, et al. Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo. Proc Natl Acad Sci U S A. 2003;100(11):6741-6. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
59. Fiordaliso F, Chimenti S, Staszewsky L, Bai A, Carlo E, Cuccovillo I, et al. A nonerythropoietic derivative of erythropoietin protects the myocardium from ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2005;102(6):2046-51. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
60. Bonnas C, Wüstefeld L, Winkler D, Kronstein-Wiedemann R, Dere E, Specht K, et al. EV-3, an endogenous human erythropoietin isoform with distinct functional relevance. Sci Rep. 2017;7(1):3684. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
61. Robertson CS, Garcia R, Gaddam SSK, Grill RJ, Cerami Hand C, Tian TS, et al. Treatment of mild traumatic brain injury with an erythropoietin-mimetic peptide. J Neurotrauma. 2013;30(9):765-74. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
62. Simon F, Floros N, Ibing W, Schelzig H, Knapsis A. Neurotherapeutic potential of erythropoietin after ischemic injury of the central nervous system. Neural Regen Res. 2019;14(8):1309-12. [DOI] [PMID] [PMCID] [Google Scholar]
63. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
64. MacRedmond R, Singhera GK, Dorscheid DR. Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute lung injury. Eur Respir J. 2009;33(6):1403-14. [View at Publisher] [DOI] [PMID] [Google Scholar]
65. Hu H, Ma F, Wei X, Fang Y. Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin. Eur Heart J. 2021;42(2):206. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
66. Olsen NV, Aachmann-Andersen N-J, Oturai P, Munch-Andersen T, Bornø A, Hulston C, et al. Erythropoietin down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate in humans. J Physiol. 2011;589(Pt 6):1273-81. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
67. Al-Samkari H, Karp Leaf RS, Dzik WH, Carlson JCT, Fogerty AE, Waheed A, et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 2020;136(4):489-500. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
68. Sahebnasagh A, Mojtahedzadeh M, Najmeddin F, Najafi A, Safdari M, Rezai Ghaleno H, et al. A Perspective on Erythropoietin as a Potential Adjuvant Therapy for Acute Lung Injury/Acute Respiratory Distress Syndrome in Patients with COVID-19. Arch Med Res. 2020;51(7):631-5. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
69. Shimaoka M, Park EJ. Advances in understanding sepsis. Eur J Anaesthesiol Suppl. 2008;42:146-53. [DOI] [PMID] [PMCID]
70. Fishbane S, Hirsch JS. Erythropoiesis-Stimulating Agent Treatment in Patients With COVID-19. Am J Kidney Dis. 2020;76(3):303-5. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
71. Leventhal J, Angeletti A, Cravedi P. EPO in Patients With COVID-19: More Than an Erythropoietic Hormone. Am J Kidney Dis. 2020;76(3):441. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
72. Farmer S, Horváth-Puhó E, Vestergaard H, Hermann AP, Frederiksen H. Chronic myeloproliferative neoplasms and risk of osteoporotic fractures; a nationwide population-based cohort study. Br J Haematol. 2013;163(5):603-10. [View at Publisher] [DOI] [PMID] [Google Scholar]
73. Sukhomlin T. Could an acute respiratory distress syndrome in COVID-19 infected patients be calmed down simply by iron withdrawal from lung tissues? J Med Virol. 2021;93(2):577-8. [View at Publisher] [DOI] [PMID] [Google Scholar]
74. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):811-8. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
75. Tang YD, Rinder HM, Katz SD. Effects of recombinant human erythropoietin on antiplatelet action of aspirin and clopidogrel in healthy subjects: results of a double-blind, placebo-controlled randomized trial. Am Heart J. 2007;154(3):494.e1-7. [View at Publisher] [DOI] [PMID] [Google Scholar]
76. Sarkisian L, Saaby L, Poulsen TS, Gerke O, Jangaard N, Hosbond S, et al. Clinical Characteristics and Outcomes of Patients with Myocardial Infarction, Myocardial Injury, and Nonelevated Troponins. Am J Med. 2016;129(4):446.e5-.e21. [View at Publisher] [DOI] [PMID] [Google Scholar]
77. Tavazzi G, Pellegrini C, Maurelli M, Belliato M, Sciutti F, Bottazzi A, et al. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail. 2020;22(5):911-5. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
78. Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-73. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
79. Heitrich M, García DM, Stoyanoff TR, Rodríguez JP, Todaro JS, Aguirre MV. Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation. Biomed Pharmacother. 2016;82:606-13. [View at Publisher] [DOI] [PMID] [Google Scholar]
80. Du Y, Tu L, Zhu P, Mu M, Wang R, Yang P, et al. Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study. Am J Respir Crit Care Med. 2020;201(11):1372-9. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
81. Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75(23):2950-73. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
82. Kakavas S, Demestiha T, Vasileiou P, Xanthos T. Erythropoetin as a novel agent with pleiotropic effects against acute lung injury. Eur J Clin Pharmacol. 2011;67(1):1-9. [View at Publisher] [DOI] [PMID] [Google Scholar]
83. Lundby C, Olsen NV. Effects of recombinant human erythropoietin in normal humans. J Physiol. 2011;589(Pt 6):1265-71. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
84. Uversky VN, Redwan EM. Erythropoietin and co.: intrinsic structure and functional disorder. Mol Biosyst. 2016;13(1):56-72. [View at Publisher] [DOI] [PMID] [Google Scholar]
85. Masuda S, Okano M, Yamagishi K, Nagao M, Ueda M, Sasaki R. A novel site of erythropoietin production. Oxygen-dependent production in cultured rat astrocytes. J Biol Chem. 1994;269(30):19488-93. [View at Publisher] [DOI] [Google Scholar]
86. Zhang X, Dong S, Qin Y, Bian X. Protective effect of erythropoietin against myocardial injury in rats with sepsis and its underlying mechanisms. Mol Med Rep. 2015;11(5):3317-29. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
87. Lechuga GC, Souza-Silva F, Sacramento CQ, Trugilho MRO, Valente RH, Napoleão-Pêgo P, et al. SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites. Int J Mol Sci. 2021;22(16):9035. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
88. Pugh CW, Ratcliffe PJ. New horizons in hypoxia signaling pathways. Exp Cell Res. 2017;356(2):116-21. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
89. Khoo A, McLoughlin B, Cheema S, Weil RS, Lambert C, Manji H, et al. Postinfectious brainstem encephalitis associated with SARS-CoV-2. J Neurol Neurosurg Psychiatry. 2020;91(9):1013-4. [View at Publisher] [DOI] [PMID] [Google Scholar]
90. Luo H-C, You C-Y, Lu S-W, Fu Y-Q. Characteristics of coagulation alteration in patients with COVID-19. Ann Hematol. 2021;100(1):45-52. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
91. Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089-98. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
92. Elliott S, Pham E, Macdougall IC. Erythropoietins: a common mechanism of action. Exp Hematol. 2008;36(12):1573-84. [View at Publisher] [DOI] [PMID] [Google Scholar]
93. Liongue C, Sertori R, Ward AC. Evolution of Cytokine Receptor Signaling. J Immunol. 2016;197(1):11-8. [View at Publisher] [DOI] [PMID] [Google Scholar]
94. Bazan JF. Structural design and molecular evolution of a cytokine receptor superfamily. Proceedings of the National Academy of Sciences of the United States of America. 1990;87(18):6934-8. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]
95. Miura Y, Miura O, Ihle JN, Aoki N. Activation of the mitogen-activated protein kinase pathway by the erythropoietin receptor. J Biol Chem. 1994;269(47):29962-9. [View at Publisher] [DOI] [Google Scholar]
96. Brines M, Grasso G, Fiordaliso F, Sfacteria A, Ghezzi P, Fratelli M, et al. Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc Natl Acad Sci U S A. 2004;101(41):14907-12. [View at Publisher] [DOI] [PMID] [PMCID] [Google Scholar]

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