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.

中文翻译：

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SARS-CoV-2 受体 ACE2 的表达和一致的宿主反应特征因哮喘炎症表型而异。

 背景

超过 3 亿人被诊断患有哮喘，数据表明他们感染严重急性呼吸综合征冠状病毒 2 或产生不良后果的风险更高。哮喘具有显着的异质性，目前尚不清楚患者内在因素如何影响可能与 2019 年冠状病毒病有关。

 客观的

我们试图识别和描述严重急性呼吸综合征冠状病毒 2 感染风险较高的哮喘患者亚群。

 方法

使用临床相关参数对来自 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内血管紧张素转换酶 2 (ACE2) 表达相关的因素。 ACE-2 相关基因特征用于查询公开数据库，以确定上游信号事件和新的治疗靶点。

 结果

通过 2 型炎症生物标志物分层，我们确定了外周血嗜酸性粒细胞水平较低且支气管上皮中严重急性呼吸综合征冠状病毒 2 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 IFN 特征重叠，通常由病毒感染引起。 ACE2高的受试者的支气管肺泡灌洗细胞内的T细胞募集和激活也相应增加。这些患者表现出与2019年重症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

在 2 型低度哮喘患者中，ACE2 表达与病毒反应基因的上调有关，其特征类似于 2019 年严重冠状病毒病的已知危险因素。因此，针对 IFN 家族和 T 细胞激活因子的治疗可能有益在一部分患者中。