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纵向分析显示严重COVID-19患者的免疫功能失调
2020-07-29 22:37

美国耶鲁大学医学院Akiko Iwasaki小组揭示了严重COVID-19患者的免疫功能失调。2020年7月27日,《自然》杂志在线发表了这项成果。

研究人员连续分析了113例中度(非ICU)和重度(ICU)COVID-19患者的免疫应答。免疫分析显示,先天细胞谱系总体增加,同时T细胞数量减少。研究人员发现早期高水平的细胞因子和疾病恶化之间的关联。细胞因子早期增加之后,中度疾病的COVID-19患者显示出1型(抗病毒)和3型(抗真菌)反应的进行性降低。相反,患有严重疾病的患者在整个疾病过程中都保持了这些升高的反应。
 
此外,严重的疾病伴随着多种2型(抗蠕虫)效应物的增加,包括IL-5、IL-13、IgE和嗜酸性粒细胞。无监督聚类分析确定了4个免疫信号,分别代表(A)生长因子、(B)2/3型细胞因子、(C)混合的1/2/3型细胞因子和(D)与三种不同疾病轨迹相关的趋化因子。中度疾病患者的免疫特征富含组织修复性生长因子特征(A),而疾病轨迹恶化患者的所有四个标记水平均升高。
 
因此,研究人员确定了与严重COVID-19结果相关的不量免疫发展谱以及与不同疾病轨迹相关的早期免疫特征。
 
据悉,最近的研究提供了有关2019冠状病毒病(COVID-19)发病机理的见解。然而,疾病结果的纵向免疫学相关性仍不清楚。
 
附:英文原文

Title: Longitudinal analyses reveal immunological misfiring in severe COVID-19

Author: Carolina Lucas, Patrick Wong, Jon Klein, Tiago B. R. Castro, Julio Silva, Maria Sundaram, Mallory K. Ellingson, Tianyang Mao, Ji Eun Oh, Benjamin Israelow, Takehiro Takahashi, Maria Tokuyama, Peiwen Lu, Arvind Venkataraman, Annsea Park, Subhasis Mohanty, Haowei Wang, Anne L. Wyllie, Chantal B. F. Vogels, Rebecca Earnest, Sarah Lapidus, Isabel M. Ott, Adam J. Moore, M. Catherine Muenker, John B. Fournier, Melissa Campbell, Camila D. Odio, Arnau Casanovas-Massana, Roy Herbst, Albert C. Shaw, Ruslan Medzhitov, Wade L. Schulz, Nathan D. Grubaugh, Charles Dela Cruz, Shelli Farhadian, Albert I. Ko, Saad B. Omer, Akiko Iwasaki

Issue&Volume: 2020-07-27

Abstract: Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1–4. Yet, longitudinal immunological correlates of disease outcome remain unclear. Here, we serially analysed immune responses in 113 COVID-19 patients with moderate (non-ICU) and severe (ICU) disease. Immune profiling revealed an overall increase in innate cell lineages with a concomitant reduction in T cell number. We identify an association between early, elevated cytokines and worse disease outcomes. Following an early increase in cytokines, COVID-19 patients with moderate disease displayed a progressive reduction in type-1 (antiviral) and type-3 (antifungal) responses. In contrast, patients with severe disease maintained these elevated responses throughout the course of disease. Moreover, severe disease was accompanied by an increase in multiple type 2 (anti-helminths) effectors including, IL-5, IL-13, IgE and eosinophils. Unsupervised clustering analysis identified 4 immune signatures, representing (A) growth factors, (B) type-2/3 cytokines, (C) mixed type-1/2/3 cytokines, and (D) chemokines that correlated with three distinct disease trajectories of patients. The immune profile of patients who recovered with moderate disease was enriched in tissue reparative growth factor signature (A), while the profile for those with worsened disease trajectory had elevated levels of all four signatures. Thus, we identified development of a maladapted immune response profile associated with severe COVID-19 outcome and early immune signatures that correlate with divergent disease trajectories.

DOI: 10.1038/s41586-020-2588-y

Source: https://www.nature.com/articles/s41586-020-2588-y

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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