The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome.
The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome.
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DOI：
10.1186/s12967-020-02646-9
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发表时间：
2020-12-03
影响因子：
7.4
通讯作者：
LYMPHONIE study group
中科院分区：
文献类型：
--
作者：
Blot M;Bour JB;Quenot JP;Bourredjem A;Nguyen M;Guy J;Monier S;Georges M;Large A;Dargent A;Guilhem A;Mouries-Martin S;Barben J;Bouhemad B;Charles PE;Chavanet P;Binquet C;Piroth L;LYMPHONIE study group
尽管免疫调节是治疗冠状病毒病2019年(新冠肺炎)的一种有前景的治疗途径，但最相关的靶点仍有待发现。新冠肺炎具有特殊的特征和结果，提示一种独特的免疫发病机制。36名免疫功能正常的非新冠肺炎患者和27名患有重症肺炎的新冠肺炎患者前瞻性地在一个中心登记，其中大多数需要重症监护。比较两组患者的临床和生物学特征(包括T细胞表型和功能以及血浆中30种细胞因子的浓度)和预后。在相似的基线呼吸严重程度下，新冠肺炎患者需要机械通气的时间显著长于非新冠肺炎患者(15[7-22]天比4(0-15)天；p = 0.0049)。与非新冠肺炎患者比较，新冠肺炎患者大多数经典炎症细胞因子(G-CSFCCL20、IL-1β、IL-2、IL-6、IL-8、IL-15、肿瘤坏死因子-α、转化生长因子-β)水平降低，而血浆CXCL10、GM-CSFCCL5水平升高。新冠肺炎患者的T细胞耗竭与非新冠肺炎患者相似，但炎症/抗炎细胞因子反应(IL-6/IL-10和肿瘤坏死因子-α/IL-10比值)更不平衡。主成分分析确定了两种主要模式，并明确区分了非新冠肺炎和新冠肺炎患者。多因素回归分析证实GM-CSF、CXCL10和IL-10水平与机械通气时间独立相关。我们发现了一种独特的细胞因子反应，新冠肺炎患者血浆GM-CSF和CXCL10水平较高，与较长的机械通气时间独立相关。这些细胞因子可代表重症新冠肺炎患者的免疫反应紊乱，也可作为治疗的靶点。临床试验网站：NCT03505281。
Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis. Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared. At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7–22] vs. 4 (0–15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1β, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-β), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation. We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281.
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DOI：
10.1164/rccm.202005-1885oc
发表时间：
2020-12-01
影响因子：
24.7
作者：
Hue S;Beldi-Ferchiou A;Bendib I;Surenaud M;Fourati S;Frapard T;Rivoal S;Razazi K;Carteaux G;Delfau-Larue MH;Mekontso-Dessap A;Audureau E;de Prost N
通讯作者：
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影响因子：
100.3
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影响因子：
64.8
作者：
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通讯作者：
Flavell, RA
DOI：
10.1164/rccm.202005-1583oc
发表时间：
2020-09-15
影响因子：
24.7
作者：
McElvaney, Oliver J.;McEvoy, Natalie L.;McElvaney, Noel G.
通讯作者：
McElvaney, Noel G.
影响因子：
64.8
作者：
Carvelli, Julien;Demaria, Olivier;Vivier, Eric
通讯作者：
Vivier, Eric