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      Does recombinant human erythropoietin administration in critically ill COVID‐19 patients have miraculous therapeutic effects?

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          Abstract

          An 80‐year‐old man with multiple comorbidities presented to the emergency department with tachypnea, tachycardia, fever, and critically low O 2 saturation and definitive chest computerized tomography scan findings in favor of COVID‐19 and positive PCR results in 48 hours. He received antiviral treatment plus recombinant human erythropoietin (rhEPO) due to his severe anemia. After 7 days of treatment, he was discharged with miraculous improvement in his symptoms and hemoglobin level. We concluded that rhEPO could attenuate respiratory distress syndrome and confront the severe acute respiratory syndrome coronavirus 2 virus through multiple mechanisms including cytokine modulation, antiapoptotic effects, leukocyte release from bone marrow, and iron redistribution away from the intracellular virus.

          Highlights

          • Recombinant human erythropoietin can rapidly correct anemia and symptoms associated with COVID‐19

          • Through cytokine modulation, rhEPO exerts its cytoprotective and anti‐apoptotic effects in COVID pneumonia.

          • rhEPO takes iron away from intracellular virus into the bone marrow, undermining the viral enzymatic requirements.

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          Most cited references15

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          Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

          Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.
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            Viral infection and iron metabolism.

            Fundamental cellular operations, including DNA synthesis and the generation of ATP, require iron. Viruses hijack cells in order to replicate, and efficient replication needs an iron-replete host. Some viruses selectively infect iron-acquiring cells by binding to transferrin receptor 1 during cell entry. Other viruses alter the expression of proteins involved in iron homeostasis, such as HFE and hepcidin. In HIV-1 and hepatitis C virus infections, iron overload is associated with poor prognosis and could be partly caused by the viruses themselves. Understanding how iron metabolism and viral infection interact might suggest new methods to control disease.
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              Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis.

              Recombinant human erythropoietin is commonly used for treatment of anaemia. Our aim was to determine whether targeting different haemoglobin concentrations with such treatment is associated with altered all-cause mortality and cardiovascular events in patients with anaemia caused by chronic kidney disease. We did a meta-analysis of randomised controlled clinical trials that were identified in medical databases and trial registration websites. Trials were eligible for inclusion if they assessed the effects of targeting different haemoglobin concentrations in patients with anaemia caused by chronic disease who were randomly assigned to treatment with recombinant human erythropoietin, recruited at least 100 patients, and had a minimum follow-up of 12 weeks. We analysed nine randomised controlled trials that enrolled 5143 patients. There was a significantly higher risk of all-cause mortality (risk ratio 1.17, 95% CI 1.01-1.35; p=0.031) and arteriovenous access thrombosis (1.34, 1.16-1.54; p=0.0001) in the higher haemoglobin target group than in the lower haemoglobin target group in the fixed effects model without heterogeneity between studies. There was a significantly higher risk of poorly controlled blood pressure (1.27, 1.08-1.50; p=0.004) in the higher haemoglobin target group than in the lower target haemoglobin group with the fixed effects model; however, this was not significant in the random effects model (1.31, 0.97-1.78; p=0.075). The incidence of myocardial infarction was much the same in the two groups. To target higher haemoglobin concentrations when treating patients with anaemia caused by chronic kidney disease with recombinant human erythropoietin puts such patients at increased risk of death. Current guidelines do not include an upper limit for the target haemoglobin concentration; such an upper limit should be considered in future recommendations.
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                Author and article information

                Contributors
                masoudmm1990@yahoo.com
                Journal
                J Med Virol
                J. Med. Virol
                10.1002/(ISSN)1096-9071
                JMV
                Journal of Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                0146-6615
                1096-9071
                19 April 2020
                : 10.1002/jmv.25839
                Affiliations
                [ 1 ] Department of Infectious Diseases, Sina Hospital Tehran University of Medical Sciences Tehran Iran
                [ 2 ] Internal Medicine Department Tehran University of Medical Sciences Tehran Iran
                [ 3 ] Radiation Oncology Department Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Tehran Iran
                [ 4 ] Pharmacotherapy Department, Faculty of Pharmacy Tehran University of Medical Sciences Tehran Iran
                Author notes
                [*] [* ] Correspondence Masoud Mortezazadeh, MD, Internal Medicine Department, Sina Hospital, Hasan Abad Square, Tehran 1136746911, Iran.

                Email: masoudmm1990@ 123456yahoo.com

                Author information
                http://orcid.org/0000-0001-5080-6887
                http://orcid.org/0000-0003-3585-9379
                http://orcid.org/0000-0003-1522-5619
                Article
                JMV25839
                10.1002/jmv.25839
                7262240
                32270515
                1d6aa77c-daf2-49af-988b-bfff9864a8c4
                © 2020 Wiley Periodicals, Inc.

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 27 March 2020
                : 03 April 2020
                : 04 April 2020
                Page count
                Figures: 2, Tables: 1, Pages: 4, Words: 2447
                Categories
                Short Communication
                Short Communications
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.3 mode:remove_FC converted:01.06.2020

                Microbiology & Virology
                acute respiratory distress syndrome,covid‐19,cytokine,erythropoietin
                Microbiology & Virology
                acute respiratory distress syndrome, covid‐19, cytokine, erythropoietin

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