* Correspondence: a.koch@iem.unikiel.de Joint Section of Maritime Medicine, Naval Institute of Maritime Medicine and Christian-Albrechts-University Kiel, Kiel, Germany Full list of author information is available at the end of the article Introduction In the current pandemic of severe acute respiratory syndrome corona virus 2 (SARSCoV-2), the therapeutic administration of oxygen is a common procedure in order to mitigate patient’s hypoxia in the course of severe corona virus disease 2019 (COVID-19) pneumonia. However, additional oxygen causes a variety of well-known side-effects, impacting a number of systems regulating cardiovascular and respiratory homeostasis as well as reactive oxygen species (ROS)-production via oxidative stress. In this article, we want to focus on intermittent changes in lung and tissue oxygenation, as changes in local pO2 may be able to trigger one of the key effectors of cellular oxygen-sensing, hypoxia-inducible factor-1α (HIF-1α) and, in downstream, the expression of angiotensin-converting enzyme-2 (ACE2) and Furin. Recently, evidence has been found that the ACE2-receptor in lung tissue, in combination with Furin, is essential for the development of COVID-19 [1–3]. Besides, there is also new information, that in contrast a severe course of lung complication of COVID-19 is correlated with reduced ACE2 on the cell surface due to shedding of the ACE2-receptor from the cell surface [4] and thus, with an insufficient angiotensin-(2) (AT2)-conversion to angiotensin-(1-7) (AT1-7). This finding, that reduced ACE2 on lung cell surfaces is correlated with lung damage due to an uncontrolled renin-angiotensin system (RAS) cascade, is supported by recent data about effects of long-lasting hyperoxia on pulmonary tissue [5–10]. Thus, in the course of COVID-19, ACE2 plays a complex role: high levels of ACE2receptors on the cell surface in combination with Furin may facilitate SARS-Cov2-

中文翻译：

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在 COVID-19 治疗策略中使用高氧的难题：间歇性治疗性高氧能否通过触发 HIF-1α 在肺组织中表面受体 ACE2 和弗林蛋白酶的表达中发挥作用？

* 通讯：a.koch@iem.unikiel.de 海事医学联合科，海军海事医学研究所和基督教-阿尔布雷希特大学基尔，基尔，德国 完整的作者信息列表可在文章末尾获得在当前严重急性呼吸系统综合症冠状病毒 2 (SARSCoV-2) 大流行中，治疗性给氧是缓解患者在 2019 年严重冠状病毒病 (COVID-19) 肺炎过程中缺氧的常见程序。然而，额外的氧气会导致各种众所周知的副作用，影响许多调节心血管和呼吸稳态以及通过氧化应激产生活性氧 (ROS) 的系统。在本文中，我们希望关注肺和组织氧合的间歇性变化，因为局部 pO2 的变化可能能够触发细胞氧感应、缺氧诱导因子-1α (HIF-1α) 的关键效应物之一，以及在下游，血管紧张素转换酶-2 (ACE2) 和弗林。最近，有证据表明肺组织中的 ACE2 受体与弗林蛋白酶结合对 COVID-19 的发展至关重要 [1-3]。此外，还有新信息表明，相比之下，由于 ACE2 受体从细胞表面脱落 [4]，COVID-19 肺部并发症的严重过程与细胞表面 ACE2 的减少有关，因此，血管紧张素-(2) (AT2)-转化为血管紧张素-(1-7) (AT1-7) 不足。这一发现表明，肺细胞表面 ACE2 的减少与不受控制的肾素 - 血管紧张素系统 (RAS) 级联引起的肺损伤有关，最近关于长期高氧对肺组织影响的数据支持 [5-10]。因此，在 COVID-19 的过程中，ACE2 发挥着复杂的作用：细胞表面高水平的 ACE2 受体与弗林蛋白酶结合可能会促进 SARS-Cov2-