Expression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype
Expression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype
复制标题
DOI：
10.1016/j.jaci.2020.05.051
复制
发表时间：
2020-08-01
影响因子：
14.2
通讯作者：
Wenzel, Sally E.
中科院分区：
文献类型：
--
作者：
Camiolo, Matthew;Gauthier, Marc;Wenzel, Sally E.
背景：超过3亿人被诊断为哮喘，有数据表明他们感染严重急性呼吸综合征冠状病毒2型的风险更高。哮喘具有明显的异质性，目前尚不清楚患者内在因素如何与冠状病毒疾病2019年相关。目的：我们试图识别和表征哮喘患者亚群的严重急性呼吸综合征冠状病毒2感染风险增加。方法：根据临床相关参数对2个大型哮喘队列的参与者进行分层，以确定与支气管上皮血管紧张素转换酶-2(ACE2)表达相关的因素。结果：根据2型炎症生物标志物的分层，我们确定了外周血嗜酸性粒细胞减少并伴有严重急性呼吸综合征冠状病毒2型受体ACE2表达增加的受试者。与ACE2高度相关的基因与1型和2型干扰素信号重叠，通常由病毒感染诱导。ACE2高表达受试者支气管肺泡灌洗液细胞内T细胞募集和活化程度呈递增趋势。这些患者表现出与2019年严重冠状病毒病危险因素相对应的特征，包括男性、高血压病史、外周血低和支气管肺泡灌洗淋巴细胞升高。结论：ACE2表达与2019年严重冠状病毒病已知危险因素相似的2型低度哮喘患者亚群的病毒反应基因上调有关。因此，针对干扰素家族和T细胞激活因子的治疗可能对部分患者有益。
Background: More than 300 million people carry a diagnosis of asthma, with data to suggest that they are at a higher risk for infection or adverse outcomes from severe acute respiratory syndrome coronavirus 2. Asthma is remarkably heterogeneous, and it is currently unclear how patient-intrinsic factors may relate to coronavirus disease 2019.Objective: We sought to identify and characterize subsets of patients with asthma at increased risk for severe acute respiratory syndrome coronavirus 2 infection.Methods: Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to angiotensin-converting enzyme-2 (ACE2) expression within bronchial epithelium. ACE-2 correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets.Results: Stratifying by type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the severe acute respiratory syndrome coronavirus 2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with type 1 and 2 IFN signatures, normally induced by viral infections. T-cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe coronavirus disease 2019, including male sex, history of hypertension, low peripheral blood, and elevated bronchoalveolar lavage lymphocytes.Conclusions: ACE2 expression is linked to upregulation of viral response genes in a subset of type 2 low patients with asthma with characteristics resembling known risk factors for severe coronavirus disease 2019. Therapies targeting the IFN family and T-cell activating factors may therefore be of benefit in a subset of patients.