Longitudinal analyses reveal immunological misfiring in severe COVID-19
Longitudinal analyses reveal immunological misfiring in severe COVID-19
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DOI：
10.1038/s41586-020-2588-y
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发表时间：
2020-07-27
期刊：
影响因子：
64.8
通讯作者：
Iwasaki, Akiko
中科院分区：
文献类型：
--
作者：
Lucas, Carolina;Wong, Patrick;Iwasaki, Akiko
最近的研究为冠状病毒病2019(新冠肺炎)的发病机制提供了见解(1-4)。然而，疾病结局的纵向免疫学相关性仍不清楚。在这里，我们连续分析了113例中重度新冠肺炎患者的免疫反应。免疫图谱显示先天细胞谱系的总体增加，伴随而来的是T细胞数量的减少。早期细胞因子水平升高与较差的疾病结局相关。随着早期细胞因子的增加，中度新冠肺炎的患者表现出1型(抗病毒)和3型(抗真菌)反应的进行性降低。相比之下，严重新冠肺炎的患者在整个病程中保持这些升高的反应。此外，重度新冠肺炎伴随多种2型(抗蠕虫)效应物的增加，包括白细胞介素5(IL-5)、IL-13、免疫球蛋白E和嗜酸性粒细胞。非监督聚类分析确定了四个免疫特征，分别代表生长因子(A)、2/3型细胞因子(B)、混合型1/2/3型细胞因子(C)和趋化因子(D)，它们与三种不同的疾病轨迹相关。从中度新冠肺炎康复的患者的免疫图谱中，组织修复生长因子签名A丰富，而那些患有严重疾病的患者的免疫图谱中，所有四个签名的水平都升高了。因此，我们发现了与严重新冠肺炎和不良临床结果相关的适应不良免疫反应谱，以及与不同疾病轨迹相关的早期免疫特征。对中重度新冠肺炎患者的免疫反应进行纵向分析发现，适应不良免疫反应谱与严重疾病有关。
Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)(1-4). However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.A longitudinal analysis of immune responses in patients with moderate or severe COVID-19 identifies a maladapted immune response profile linked to severe disease.