COVID-19-related Genes in Sputum Cells in Asthma Relationship to Demographic Features and Corticosteroids
COVID-19-related Genes in Sputum Cells in Asthma Relationship to Demographic Features and Corticosteroids
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DOI：
10.1164/rccm.202003-0821oc
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发表时间：
2020-07-01
影响因子：
24.7
通讯作者：
Fahy, John, V
中科院分区：
文献类型：
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作者：
Peters, Michael C.;Sajuthi, Satria;Fahy, John, V
理由：冠状病毒病 (COVID-19) 是由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的。 ACE2（血管紧张素转换酶2）和TMPRSS2（跨膜蛋白酶丝氨酸2）介导宿主细胞的病毒感染。我们推断，哮喘患者痰细胞中 ACE2 或 TMPRSS2 基因表达的差异可能会识别出有 COVID-19 发病风险的亚组。 目的：确定哮喘患者的人口统计学特征与痰中 ACE2 和 TMPRSS2 基因表达之间的关系。 方法：我们分析了 ACE2 和 TMPRSS2 以及 ICAM-1（细胞间质细胞间质细胞间质细胞间质细胞间质细胞间质细胞）的基因表达。 粘附分子1）（鼻病毒受体作为比较）来自330名SARP3（严重哮喘研究计划-3）参与者和79名健康对照受试者的痰细胞。测量和主要结果：ACE2的基因表达低于TMPRSS2，并且两种基因的表达水平在哮喘和健康中相似。在哮喘患者中，男性、非裔美国人种族和糖尿病史与 ACE2 和 TMPRSS2 的较高表达相关。使用吸入皮质类固醇 (ICS) 与 ACE2 和 TMPRSS2 表达降低相关，但曲安奈德治疗并未降低任一基因的表达。这些研究结果与 ICAM-1 的研究结果不同，ICAM-1 的基因表达在哮喘中增加，并且与性别、种族和 ICS 使用相关的差异不太一致。结论：男性、非裔美国人和糖尿病患者中 ACE2 和 TMPRSS2 的较高表达为监测这些哮喘亚组的 COVID-19 不良结局提供了依据。使用 ICS 时 ACE2 和 TMPRSS2 的表达较低，因此需要对 ICS 的使用进行前瞻性研究，将其作为 SARS-CoV-2 感染易感性降低和 COVID-19 发病率降低的预测因子。
Rationale: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 (angiotensin-converting enzyme 2), and TMPRSS2(transmembrane protease serine 2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among patients with asthma may identify subgroups at risk for COVID-19 morbidity.Objectives: To determine the relationship between demographic features and sputum ACE2 and TMPRSS2 gene expression in asthma.Methods: We analyzed gene expression for ACE2 and TMPRSS2, and for ICAM-1 (intercellular adhesion molecule 1) (rhinovirus receptor as a comparator) in sputum cells from 330 participants in SARP3 (Severe Asthma Research Program-3) and 79 healthy control subjects.Measurements and Main Results: Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes were similar in asthma and health. Among patients with asthma, male sex, African American race, and history of diabetes mellitus were associated with higher expression of ACE2 and TMPRSS2. Use of inhaled corticosteroids (ICS) was associated with lower expression of ACE2 and TMPRSS2, but treatment with triamcinolone acetonide did not decrease expression of either gene. These findings differed from those for ICAM-1, where gene expression was increased in asthma and less consistent differences were observed related to sex, race, and use of ICS.Conclusions: Higher expression of ACE2 and TMPRSS2 in males, African Americans, and patients with diabetes mellitus provides rationale for monitoring these asthma subgroups for poor COVID-19 outcomes. The lower expression of ACE2 and TMPRSS2 with ICS use warrants prospective study of ICS use as a predictor of decreased susceptibility to SARS-CoV-2 infection and decreased COVID-19 morbidity.