"In another animal study of lipopolysaccharide (LPS) inducedsepsis model,7EPO effect on hepatic mitochondrial damage was as-sessed and it was shown that EPO suppressed the LPS effect on theincrease of IL‐1β and reactive oxygen species levels, mitochondrialDNA copy number, and also decreased protein expressions ofcaspase‐1, and NLRP3 (NLR Family Pyrin Domain Containing 3) gene.EPO alleviated LPS‐induced cellular edema in hepatic lobules, lym-phocytic infiltration, and hepatocellular necrosis.Renoprotective effects of EPO in mice with septic acute kidneyinjury has been observed and has been linked to attenuation ofmicrovascular damage, reducing renal inflammatory response and im-provement of renal tissue oxygenation through the decrease of hypoxia‐inducible factor‐1 alpha, inducible nitric oxide synthase, and NF‐κBandalso enhancement of erythropoietin receptor (EPO‐R), PeCAM‐1, vas-cular endothelial growth factor, and VEGFR‐2 expression.8Another study conducted earlier by Heitrich et al9on a murinemodel of sepsis‐caused acute lung injury and acute kidney injurydemonstrated beneficial protective EPO effects on pulmonary andrenal outcomes through EPO‐R and VEGF/VEGFR‐2 expression.Moreover, it has been shown that EPO has cardioprotective effectsby reducing the myocardial inflammatory response in septic rats andattenuates the reduction in mitochondrial membrane potential andinhibits myocardial cell apoptosis through mitochondrial pathwayand by reducing NF‐κB p65 expression.10NF‐κB is a principle factor of multiple inflammatory pathways,and according to the above‐mentioned studies, it can be consideredan important target for treatment. Blocking the activation of NF‐κBby EPO may prevent further deterioration caused by the COVID‐19disease through cytokine modulation and its regenerative and anti-apoptotic effectsAnother mechanism for an explanation of EPO effect on the im-provement of the clinical condition of the presented case could berooted to the findings of Ito et al11on an animal study that revealed tha t24 hours after EPO administration, the number of IgDlowimmature Bcells and mature B cells, as well as CD4+ and CD8+ T cells in the bonemarrow, decreased significantly due to their egress into the peripheralblood. This backup leukocyte release into the peripheral bloodstream might be a reason for the optimized viral confrontation of the immune system. Thus in the presented case, after the first dose of rhEPO andpacked RBC transfusion, abso lute lymphocyte count increased from 333to 933/μL of blood; a rise quite larger than to be elucidated only by250 mL of packed RBCs transfusion.During inflammation, serum Hepcidin levels increase the followingstimulation by IL‐6, downregulating cellular ferroportin and this leads todecreased iron absorption and its detainment in liver and spleen mac-rophages12which could promote the survival of intracellular micro-organisms. EPO by downregulating IL‐6 and Hepcidin levels could lead toan increased release of iron from macrophages and increased absorptionof iron by the bone marrow, thus decreasing iron availability for in-tracellular organisms like Coronavirus for their required enzymatic ac-tivities. This antiviral strategy of keeping iron out of infected cells haspreviously been explored and considered to be potentially effective inhuman infections by hepatitis C virus, human immunodeficiency virus‐1,hepatitis B virus, and cytomegalovirus viral infections.13Although the above‐mentioned novel mechanisms of EPO effectin septic states could elaborate the rapid clinical improvement of thepresented COVID‐19 case, we should not underestimate the defini-tive effects of rising hemoglobin from 6.7 to 9 g/dL in the improve-ment of pulmonary oxygenation and thus relieving the existingrespiratory symptoms. However, the 2.3 g/dL rise in hemoglobin levelin only 7 days with the mentioned dose of rhEPO is both profoundand questionable considering the reported peak effects of rhEPO in2 to 6 weeks after the starting dose."