哮喘患者痰细胞COVID-19相关基因：与人口统计学特征及皮质类固醇的关系
2020/05/14
摘要
背景：2019年冠状病毒疾病（COVID-19）是由SARS冠状病毒2（SARS-CoV-2）引起。血管紧张素转换酶2（ACE2）和跨膜蛋白酶丝氨酸2（TMPRSS2）介导了宿主细胞的病毒感染。我们推测哮喘患者痰细胞ACE2或TMPRSS2基因表达的差异可能识别出有COVID19发病风险的亚群。
方法：我们分析了重症哮喘研究项目参3中330名患者和79名健康对照人群痰细胞中的ACE2和TMPRSS2，以及细胞间粘附分子1（ICAM-1）（鼻病毒受体作为对照）基因表达。
结果：ACE2基因表达低于TMPRSS2，两者在哮喘和健康人群中的表达水平相似。在哮喘患者中，男性、非裔美国人和糖尿病史与ACE2和TMPRSS2的高表达有关。吸入性皮质类固醇（ICS）与ACE2和TMPRSS2的表达降低有关，而氟羟氢化泼尼松（TA）治疗并没有降低两种基因的表达。这些发现与ICAM-1不同，ICAM-1基因在哮喘中表达增加，与性别、种族和ICS的使用相关的差异不太一致。
结论：ACE2和TMPRSS2在男性、非裔美国人和糖尿病患者中的高表达为监测这些哮喘亚组的COVID19不良预后提供了依据。使用ICS时，ACE2和TMPRSS2的低表达使ICS作为降低SARS-CoV-2易感性和降低COVID19发病率的预测因子的前瞻性研究成为可能。
COVID-19 Related Genes in Sputum Cells in Asthma: Relationship to Demographic Features and Corticosteroids.
Peters MC, Sajuthi S, Deford P, Christenson S, Rios CL, Montgomery MT, Woodruff PG, Mauger DT, Erzurum SC, Johansson MW, Denlinger LC, Jarjour NN, Castro M, Hastie AT, Moore W, Ortega VE, Bleecker ER, Wenzel SE, Israel E, Levy BD, Seibold MA, Fahy JV; National Heart, Lung, and Blood Institute Severe Asthma Research Program-3 Investigators.
Abstract
BACKGROUND:Coronavirus disease 2019 (COVID-19) is caused by SARS-coronavirus 2 (SARS-CoV-2). Angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among asthma patients may identify subgroups at risk for COVID19 morbidity.
METHODS:We analyzed gene expression for ACE2 and TMPRSS2, and for intercellular adhesion molecule 1 (ICAM-1)(rhinovirus receptor as a comparator), in sputum cells from 330 participants in the Severe Asthma Research Program-3 and 79 healthy controls.
RESULTS:Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes was similar in asthma and health. Among asthma patients, male gender, African Americans race, and history of diabetes mellitus, was 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 (TA) 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 gender, 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 COVID19 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 COVID19 morbidity.
背景：2019年冠状病毒疾病（COVID-19）是由SARS冠状病毒2（SARS-CoV-2）引起。血管紧张素转换酶2（ACE2）和跨膜蛋白酶丝氨酸2（TMPRSS2）介导了宿主细胞的病毒感染。我们推测哮喘患者痰细胞ACE2或TMPRSS2基因表达的差异可能识别出有COVID19发病风险的亚群。
方法：我们分析了重症哮喘研究项目参3中330名患者和79名健康对照人群痰细胞中的ACE2和TMPRSS2，以及细胞间粘附分子1（ICAM-1）（鼻病毒受体作为对照）基因表达。
结果：ACE2基因表达低于TMPRSS2，两者在哮喘和健康人群中的表达水平相似。在哮喘患者中，男性、非裔美国人和糖尿病史与ACE2和TMPRSS2的高表达有关。吸入性皮质类固醇（ICS）与ACE2和TMPRSS2的表达降低有关，而氟羟氢化泼尼松（TA）治疗并没有降低两种基因的表达。这些发现与ICAM-1不同，ICAM-1基因在哮喘中表达增加，与性别、种族和ICS的使用相关的差异不太一致。
结论：ACE2和TMPRSS2在男性、非裔美国人和糖尿病患者中的高表达为监测这些哮喘亚组的COVID19不良预后提供了依据。使用ICS时，ACE2和TMPRSS2的低表达使ICS作为降低SARS-CoV-2易感性和降低COVID19发病率的预测因子的前瞻性研究成为可能。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校 )
(Am J Respir Crit Care Med. 2020 Apr 29. doi: 10.1164/rccm.202003-0821OC.)
(Am J Respir Crit Care Med. 2020 Apr 29. doi: 10.1164/rccm.202003-0821OC.)
COVID-19 Related Genes in Sputum Cells in Asthma: Relationship to Demographic Features and Corticosteroids.
Peters MC, Sajuthi S, Deford P, Christenson S, Rios CL, Montgomery MT, Woodruff PG, Mauger DT, Erzurum SC, Johansson MW, Denlinger LC, Jarjour NN, Castro M, Hastie AT, Moore W, Ortega VE, Bleecker ER, Wenzel SE, Israel E, Levy BD, Seibold MA, Fahy JV; National Heart, Lung, and Blood Institute Severe Asthma Research Program-3 Investigators.
Abstract
BACKGROUND:Coronavirus disease 2019 (COVID-19) is caused by SARS-coronavirus 2 (SARS-CoV-2). Angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among asthma patients may identify subgroups at risk for COVID19 morbidity.
METHODS:We analyzed gene expression for ACE2 and TMPRSS2, and for intercellular adhesion molecule 1 (ICAM-1)(rhinovirus receptor as a comparator), in sputum cells from 330 participants in the Severe Asthma Research Program-3 and 79 healthy controls.
RESULTS:Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes was similar in asthma and health. Among asthma patients, male gender, African Americans race, and history of diabetes mellitus, was 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 (TA) 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 gender, 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 COVID19 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 COVID19 morbidity.
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