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American Journal of Kidney Diseases

EPO in Patients With COVID-19: More Than an Erythropoietic Hormone

      To the Editor:
      In their editorial, Fishbane and Hirsh

      Fishbane S, Hirsch JS. Erythropoiesis-stimulating agent treatment in patients with COVID-19. Am J Kidney Dis. 2020;76(3):303–305.

      discuss associations between systemic inflammation and anemia in patients with coronavirus disease 2019 (COVID-19). This relationship, putatively attributed to hepcidin effects on iron availability, limits erythropoietin (EPO) efficacy. Despite this, the authors theorize that synergism between severe COVID-19 and erythropoiesis-stimulating agent use may produce dangerous thrombosis risks. They propose reduced hemoglobin level targets in maintenance dialysis patients with COVID-19 despite an association between anemia and more severe COVID-19.
      • Huang C.
      • Wang Y.
      • Li X.
      • et al.
      Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
      We contend that this approach, although reasonable, is potentially problematic.
      Disordered inflammatory responses underlie end-organ damage in patients with COVID-19. Increased levels of interleukins (eg, IL-1β and IL-6) are independently associated with disease severity/mortality, and therapies targeting IL-1β and IL-6 effects show promising results.
      • Ingraham N.E.
      • Lotfi-Emran S.
      • Thielen B.K.
      • et al.
      Immunomodulation in COVID-19.
      Our group and others showed that EPO immunoregulating effects include inhibiting IL-1β and IL-6 production by monocytes and promoting regulatory T-cell survival.
      • Cantarelli C.
      • Angeletti A.
      • Cravedi P.
      Erythropoietin, a multifaceted protein with innate and adaptive immune modulatory activity.
      In addition, growing evidence establishes global tissue-protective antiapoptotic effects of EPO, especially in organs targeted in COVID-19. Consistent with this, a recent case report attributed respiratory distress amelioration in an anemic 80-year-old man to EPO use.
      • Hadadi A.
      • Mortezazadeh M.
      • Kolahdouzan K.
      • Alavian G.
      Does recombinant human erythropoietin administration in critically ill COVID-19 patients have miraculous therapeutic effects?.
      Therefore, in COVID-19 patients, the benefits of erythropoiesis-independent EPO effects may far outweigh the risks. As such, further analysis and controlled studies are warranted to define how EPO treatment should be optimized in maintenance dialysis patients with COVID-19 and anemia.

      Article Information

      Support

      None.

      Financial Disclosure

      The authors declare that they have no relevant financial interests.

      Peer Review

      Received May 31, 2020. Accepted June 1, 2020, after editorial review by an Associate Editor and a Deputy Editor.

      References

      1. Fishbane S, Hirsch JS. Erythropoiesis-stimulating agent treatment in patients with COVID-19. Am J Kidney Dis. 2020;76(3):303–305.

        • Huang C.
        • Wang Y.
        • Li X.
        • et al.
        Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
        Lancet. 2020; 395: 497-506
        • Ingraham N.E.
        • Lotfi-Emran S.
        • Thielen B.K.
        • et al.
        Immunomodulation in COVID-19.
        Lancet Respir Med. 2020; 8: 544-546
        • Cantarelli C.
        • Angeletti A.
        • Cravedi P.
        Erythropoietin, a multifaceted protein with innate and adaptive immune modulatory activity.
        Am J Transplant. 2019; 19: 2407-2414
        • 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: 915-918

      Linked Article

      • Erythropoiesis-Stimulating Agent Treatment in Patients With COVID-19
        American Journal of Kidney DiseasesVol. 76Issue 3
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          The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting illness, coronavirus disease 2019 (COVID-19), developed in Wuhan, China, in late 2019.1 Within months, COVID-19 became a worldwide pandemic, with millions of cases reported.2 Nephrologists have been front and center, caring for infected dialysis patients while also treating hospitalized patients with COVID-19 and acute kidney injury (AKI). A controversial aspect of therapy in both settings has been the use of erythropoiesis-stimulating agents (ESAs) to treat anemia experienced by patients with COVID-19.
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