Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19.
Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19.
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纵向免疫分析揭示了与Covid-19相关的关键髓样特征。
DOI：
10.1126/sciimmunol.abd6197
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发表时间：
2020-09-17
影响因子：
24.8
通讯作者：
Hussell T
中科院分区：
文献类型：
--
作者：
Mann ER;Menon M;Knight SB;Konkel JE;Jagger C;Shaw TN;Krishnan S;Rattray M;Ustianowski A;Bakerly ND;Dark P;Lord G;Simpson A;Felton T;Ho LP;NIHR Respiratory TRC,;Feldmann M;CIRCO,;Grainger JR;Hussell T
对 COVID-19 患者免疫反应的纵向分析确定了与严重疾病相关的骨髓特征。 COVID-19 发病机制与过度的免疫反应有关。然而，驱动不同临床疾病结果的特定细胞介质和炎症成分仍然知之甚少。我们在英国 COVID-19 大流行高峰期间对住院患者的全血和外周血单核细胞 (PBMC) 进行了纵向免疫分析。在这里，我们报告了入院后不久出现的与 COVID-19 严重程度相关的关键免疫特征。免疫特征与中性粒细胞与 T 细胞比例的变化、血清 IL-6、MCP-1 和 IP-10 升高以及最引人注目的 CD14+ 单核细胞表型和功能的调节有关。 CD14+单核细胞的修饰特征包括前列腺素生成酶COX-2的诱导较差，以及细胞周期标记物Ki-67的表达增强。纵向分析显示，患者的一些免疫特征恢复到健康中位水平，最终结果良好。这些发现确定了 COVID-19 患者先天免疫区室中以前未被认识到的改变，并支持了以下观点：针对这种疾病应考虑针对从骨髓中释放髓样细胞的治疗策略。此外，他们证明，入院后早期就出现了过度免疫反应的特征，这表明免疫调节疗法在早期时间点是最有益的。
Longitudinal analysis of the immune response in COVID-19 patients identifies a myeloid signature associated with severe disease. COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints.
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影响因子：
8
作者：
Cole SL;Dunning J;Kok WL;Benam KH;Benlahrech A;Repapi E;Martinez FO;Drumright L;Powell TJ;Bennett M;Elderfield R;Thomas C;MOSAIC investigators;Dong T;McCauley J;Liew FY;Taylor S;Zambon M;Barclay W;Cerundolo V;Openshaw PJ;McMichael AJ;Ho LP
通讯作者：
Ho LP
影响因子：
10.5
作者：
O'Shea JJ;Schwartz DM;Villarino AV;Gadina M;McInnes IB;Laurence A
通讯作者：
Laurence A
DOI：
10.1096/fj.13-241760
发表时间：
2014-07
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Coward WR;Feghali-Bostwick CA;Jenkins G;Knox AJ;Pang L
通讯作者：
Pang L
COVID-19 患者支气管肺泡免疫细胞的单细胞景观。
影响因子：
82.9
作者：
Liao, Mingfeng;Liu, Yang;Zhang, Zheng
通讯作者：
Zhang, Zheng
影响因子：
15.9
作者：
Chen, Guang;Wu, Di;Ning, Qin
通讯作者：
Ning, Qin