Coping with hypoxemia: Could erythropoietin (EPO) be an adjuvant treatment of COVID-19?

Abstract A very recent epidemiological study provides preliminary evidence that living in habitats located at 2500 m above sea level and higher might protect from the development of severe respiratory symptoms following infection with the novel SARS-CoV-2 virus. This epidemiological finding raises the question of whether physiological mechanisms underlying the acclimatization to high altitude identifies therapeutic targets for the effective treatment of severe acute respiratory syndrome pivotal to the reduction of global mortality during the COVID-19 pandemic. This article compares the symptoms of acute mountain sickness (AMS) with those of SARS-CoV-2 infection and explores overlapping patho-physiological mechanisms of the respiratory system including impaired oxygen transport, pulmonary gas exchange and brainstem circuits controlling respiration. In this context, we also discuss the potential impact of SARS-CoV-2 infection on oxygen sensing in the carotid body. Finally, since erythropoietin (EPO) is an effective treatment for AMS, this article reviews the potential benefits of implementing FDA-approved erythropoietin-based (EPO) drug therapies to counteract a variety of acute respiratory and non-respiratory (e.g. excessive inflammation of vascular beds) symptoms of SARS-CoV-2 infection. High-altitude environments of 2500 m above sea level (masl) are characterized by barometric hypoxia. Chronic exposure to hypobaric hypoxia in such extreme and adverse environments evokes short- and long-term physiologic adaptations to maintain tissue oxygen levels at high altitude in animals and humans. Recent work suggests that high altitude dewellers, in particular in American countries and Tibet ( Arias-Reyes et al., 2020 ; Ortiz-Prado et al., 2020 ), may present with lower infection rates and/or less severe symptoms of COVID-19 compared to lowlanders ( Arias-Reyes et al., 2020 ; Lei et al., 2020 ; Ortiz-Prado et al., 2020 ). This epidemiologic finding raises the question of whether physiological mechanisms underlying the acclimatization to high altitude or in turn the development of acute mountain sickness (AMS), may provide potential avenues for understanding the severity of symptoms and treatment of SARS-CoV-2 infection. Here, we provide a survey of similarities of acute mountain sickness to COVID-19 and suggest that the physiologic response to high altitude, characterized by an increase in erythropoietin (EPO), may provide a framework to develop an adjuvant therapy in COVID-19. Indeed, a recently published case study from Iran supports EPO as an effective treatment of severe COVID-19 patho-physiology ( Hadadi et al., 2020 ).