Single-cell landscape of immunological responses in patients with COVID-19

Single-cell landscape of immunological responses in patients with COVID-19
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DOI:
10.1038/s41590-020-0762-x
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发表时间:
2020-08-12
期刊:
影响因子:
30.5
通讯作者:
Wang, Fu-Sheng
Wang, Fu-Sheng
中科院分区:
医学1区
文献类型:
--
作者:
Zhang, Ji-Yuan;Wang, Xiang-Ming;Wang, Fu-Sheng

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在由严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)感染引起的冠状病毒病2019 (COVID-19)中,疾病严重程度与宿主免疫反应之间的关系尚不完全清楚。在这里,我们对5名健康献血者和13名COVID-19患者(包括中、重度和恢复期病例)的外周血样本进行了单细胞RNA测序。通过测定免疫细胞的转录谱,结合组装的T细胞受体和B细胞受体序列,我们分析了免疫细胞的功能特性。COVID-19患者的大多数细胞类型表现出强烈的干扰素- α反应和总体急性炎症反应。此外,高细胞毒性效应T细胞亚群(如CD4(+)效应- gnly(颗粒蛋白)、CD8(+)效应- gnly和NKT CD160)的密集扩增与中度患者的康复有关。在重症患者中,免疫景观表现为紊乱的干扰素反应,严重的免疫衰竭,扭曲的T细胞受体库和广泛的T细胞扩增。这些发现说明了疾病进展过程中免疫反应的动态性质。严重的COVID-19的特征之一是高炎症状态。Wang及其同事描述了中、重度和恢复期COVID-19患者的单细胞转录图景。
In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-alpha response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4(+)effector-GNLY (granulysin), CD8(+)effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.Severe COVID-19 is characterized-among other things-by a hyperinflammatory state. Wang and colleagues describe the single-cell transcriptional landscape of moderate, severe and convalescent cases of patients with COVID-19.