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.

中文翻译：

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纵向分析揭示严重 COVID-19 中的免疫失灵

最近的研究深入了解了 2019 年冠状病毒病 (COVID-19) 1 – 4 的发病机制。然而，疾病结果的纵向免疫相关性仍不清楚。在这里，我们连续分析了 113 名中度或重度 COVID-19 患者的免疫反应。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。细胞因子水平的早期升高与更糟糕的疾病结果相关。随着细胞因子的早期增加，中度 COVID-19 患者的 1 型（抗病毒）和 3 型（抗真菌）反应逐渐减少。相比之下，重症 COVID-19 患者在整个疾病过程中都保持了这些较高的反应。此外，严重的 COVID-19 还伴随着多种 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。无监督聚类分析确定了四种免疫特征，分别代表生长因子 (A)、2/3 型细胞因子 (B)、混合 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 COVID-19 中恢复的患者的免疫特征富含组织修复生长因子特征 A，而患有严重疾病的患者的免疫特征所有四种特征的水平均升高。因此，我们发现了与严重的 COVID-19 和不良临床结果相关的不适应的免疫反应特征，以及与不同疾病轨迹相关的早期免疫特征。对中度或重度 COVID-19 患者免疫反应的纵向分析确定了与严重疾病相关的不适应的免疫反应特征。