A Review of Pleiotropic Potential of Erythropoietin as an Adjunctive Therapy for COVID-19

Coronavirus disease 2019 known as COVID-19 is a new high prevalence severe acute respiratory infectious disease. According to the research and statistical data, only in January 2021, about 10 million cases of COVID-19 and more than two million deaths have been confirmed. The main causing factor of this disease was introduced as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 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 have conducted a new systematic review of the published literature on the efficacy of erythropoietin (EPO) and recombinant human EPO as a safe stimulant and tissue protector in the treatment of COVID-19. We have briefly described the structure of coronavirus, its pathogenesis, and the structure of EPO and recombinant human EPO. All relevant articles which have published in the Science Direct, as well as PubMed, and Scholar-Google databases were explored. 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, antiinflammatory 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 or spinal-cord ischemic injuries. 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.