Background Coronavirus disease 2019 (COVID-19) can progress to severe pneumonia with respiratory failure and is aggravated by the deregulation of the immune system causing an excessive inflammation including the cytokine storm. Methods In this study, we report that severe acutely infected patients have high levels of both type-1 and type-2 cytokines. Results Our results show abnormal cytokine levels upon T-cell stimulation, in a nonpolarized profile. Furthermore, our findings indicate that this hyperactive cytokine response is associated with a significantly increased frequency of late-differentiated T cells with particular phenotype of effector exhausted/senescent CD28−CD57+ cells. Of note, we demonstrated for the first time an increased frequency of CD3+CD4+CD28−CD57+ T cells with expression of programmed death 1, one of the hallmarks of T-cell exhaustion. Conclusions These findings reveal that COVID-19 is associated with acute immunodeficiency, especially within the CD4+ T-cell compartment, and points to possible mechanisms of loss of clonal repertoire and susceptibility to viral relapse and reinfection events.

中文翻译：

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2019 年冠状病毒病重症患者表现出与急性感染中效应器耗尽的衰老 T 细胞相关的过度活跃的细胞因子反应

背景 2019 年冠状病毒病 (COVID-19) 可发展为伴有呼吸衰竭的严重肺炎，并因免疫系统失调导致包括细胞因子风暴在内的过度炎症而加剧。方法 在这项研究中，我们报告严重急性感染患者具有高水平的 1 型和 2 型细胞因子。结果 我们的结果显示 T 细胞刺激后细胞因子水平异常，处于非极化状态。此外，我们的研究结果表明，这种过度活跃的细胞因子反应与晚期分化 T 细胞的频率显着增加有关，这些细胞具有效应器耗竭/衰老 CD28-CD57+ 细胞的特定表型。值得注意的是，我们首次证明了表达程序性死亡 1 的 CD3+CD4+CD28-CD57+ T 细胞频率增加，T 细胞衰竭的标志之一。结论 这些发现表明，COVID-19 与急性免疫缺陷有关，尤其是在 CD4+ T 细胞区室中，并指出了克隆库丢失以及病毒复发和再感染事件易感性的可能机制。