People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden.

危重的 COVID - 19 患者表现出预测死亡率和反映肺部 SARS - CoV - 2 病毒负担的外周免疫谱。

• 影响指数: 16.988
• 发表时间: 12 2021 21
• 来源期刊: Cell Rep Med
• DOI: 10.1016/j.xcrm.2021.100476
• PMID: 34873589
• 文章类型: Journal Article
• 作者列表: Cillo AR,Somasundaram A,Shan F,Cardello C,Workman CJ,Kitsios GD,Ruffin AT,Kunning S,Lampenfeld C,Onkar S,Grebinoski S,Deshmukh G,Methe B,Liu C,Nambulli S,Andrews LP,Duprex WP,Joglekar AV,Benos PV,Ray P,Ray A,McVerry BJ,Zhang Y,Lee JS,Das J,Singh H,Morris A,Bruno TC,Vignali DAA

关键词: COVID-19; COVID-19 outcome; gene modules; inflammatory cytokines; inflammatory monocytes; machine learning; severe COVID-19; single-cell RNA-seq; type I interferon

Mesh: Aged; COVID-19 / blood immunology mortality virology; Critical Illness; Cytokines / blood; Gene Regulatory Networks; Humans; Inflammation; Lung / immunology virology; Models, Theoretical; Monocytes / immunology; Myeloid Cells / immunology; Reproducibility of Results; SARS-CoV-2 / pathogenicity; Viral Load

Abstract

Despite extensive analyses, there remains an urgent need to delineate immune cell states that contribute to mortality in people critically ill with COVID-19. Here, we present high-dimensional profiling of blood and respiratory samples from people with severe COVID-19 to examine the association between cell-linked molecular features and mortality outcomes. Peripheral transcriptional profiles by single-cell RNA sequencing (RNA-seq)-based deconvolution of immune states are associated with COVID-19 mortality. Further, persistently high levels of an interferon signaling module in monocytes over time lead to subsequent concerted upregulation of inflammatory cytokines. SARS-CoV-2-infected myeloid cells in the lower respiratory tract upregulate CXCL10, leading to a higher risk of death. Our analysis suggests a pivotal role for viral-infected myeloid cells and protracted interferon signaling in severe COVID-19.

摘要

尽管进行了广泛的分析，仍然迫切需要描述导致重症冠状病毒病2019(COVID-19)患者死亡的免疫细胞状态.这里,我们对重症COVID-19患者的血液和呼吸道样本进行了高维分析,以检查细胞连锁分子特征与死亡结局之间的关联.基于单细胞RNAseq的免疫状态去卷积的外周转录谱与COVID-19死亡率相关。Further,随着时间的推移,单核细胞中持续高水平的干扰素信号传导模块导致随后的炎性细胞因子的协同上调.SARS-CoV-2感染的下呼吸道骨髓细胞上调CXCL10，导致更高的死亡风险。我们的分析表明，在严重的COVID-19中，病毒感染的骨髓细胞和延长的干扰素信号传导具有关键作用。