The severity of coronavirus disease 2019 (COVID-19) is linked to an increasing number of risk factors, including exogenous (environmental) stimuli such as air pollution, nicotine, and cigarette smoke. These three factors increase the expression of angiotensin I converting enzyme 2 (ACE2), a key receptor involved in the entry of SARS-CoV-2 -the etiological agent of COVID-19- into respiratory tract epithelial cells. Patients with severe COVID-19 are managed with oxygen support, as are at-risk individuals with chronic lung disease. To date, no study has examined whether an increased fraction of inspired oxygen (FiO₂) may affect the expression of SARS-CoV-2 entry receptors and co-receptors, including ACE2 and the transmembrane serine proteases TMPRSS1, TMPRSS2, and TMPRSS11D. To address this, steady-state mRNA levels for genes encoding these SARS-CoV-2 receptors were assessed in the lungs of mouse pups chronically exposed to elevated FiO₂, and in the lungs of preterm-born human infants chronically managed with an elevated FiO₂. These two scenarios served as models of chronic elevated FiO₂ exposure. Additionally, SARS-CoV-2 receptor expression was assessed in primary human nasal, tracheal, esophageal, bronchial and alveolar epithelial cells, as well as primary mouse alveolar type II cells exposed to elevated oxygen concentrations. Whilst gene expression of ACE2 was unaffected, gene and protein expression of TMPRSS11D was consistently upregulated by exposure to an elevated FiO₂. These data highlight the need for further studies that examine the relative contribution of the various viral co‑receptors on the infection cycle, and point to oxygen supplementation as a potential risk factor for COVID-19.

中文翻译：

---

FiO2 升高会增加呼吸道上皮细胞中 SARS-CoV-2 共受体的表达。

2019 年冠状病毒病 (COVID-19) 的严重程度与越来越多的风险因素有关，包括空气污染、尼古丁和香烟烟雾等外源性（环境）刺激。这三个因素增加了血管紧张素 I 转换酶 2 (ACE2) 的表达，ACE2 是参与 SARS-CoV-2（COVID-19 的病原体）进入呼吸道上皮细胞的关键受体。患有严重 COVID-19 的患者和患有慢性肺病的高危人群都接受氧气支持治疗。迄今为止，没有研究检查是否增加吸入氧气（FiO ₂) 可能影响 SARS-CoV-2 进入受体和辅助受体的表达，包括 ACE2 和跨膜丝氨酸蛋白酶 TMPRSS1、TMPRSS2 和 TMPRSS11D。_{为了解决这个问题，在长期暴露于升高的 FiO 2}的小鼠幼崽的肺部和长期使用升高的 FiO 管理的早产人类婴儿的肺部中评估了编码这些 SARS-CoV-2 受体基因的稳态 mRNA 水平₂ . 这两种情况作为慢性升高的 FiO _2的模型暴露。此外，还评估了 SARS-CoV-2 受体在原代人鼻、气管、食道、支气管和肺泡上皮细胞以及暴露于高氧浓度下的原代小鼠肺泡 II 型细胞中的表达。虽然 ACE2 的基因表达不受影响，但 TMPRSS11D 的基因和蛋白质表达通过暴露于升高的 FiO ₂持续上调。这些数据强调需要进一步研究，检查各种病毒共同受体对感染周期的相对贡献，并指出氧气补充是 COVID-19 的潜在风险因素。