Alterations in T and B cell function persist in convalescent COVID-19 patients.
Alterations in T and B cell function persist in convalescent COVID-19 patients.
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DOI：
10.1016/j.medj.2021.03.013
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发表时间：
2021-06-11
期刊：
影响因子：
--
通讯作者：
Menon M
中科院分区：
文献类型：
--
作者：
Shuwa HA;Shaw TN;Knight SB;Wemyss K;McClure FA;Pearmain L;Prise I;Jagger C;Morgan DJ;Khan S;Brand O;Mann ER;Ustianowski A;Bakerly ND;Dark P;Brightling CE;Brij S;CIRCO;Felton T;Simpson A;Grainger JR;Hussell T;Konkel JE;Menon M
最新研究表明，一些 2019 年冠状病毒病 (COVID-19) 患者存在持续症状，包括呼吸困难和慢性疲劳；然而，这些患者的长期免疫反应目前仍不清楚。在这里，我们描述了住院的 COVID-19 患者在急性疾病期间和恢复期 3-6 个月时 B 细胞和 T 细胞的表型和功能特征。我们报告说，在急性 COVID-19 患者中观察到的 B 细胞亚群的变化在恢复期患者中基本上得到了恢复。相比之下，恢复期患者的 T 细胞表现出持续的变化，CD8+ T 细胞中明显存在细胞毒性程序，并且 1 型细胞因子和白细胞介素 17 (IL-17) 的产生增加。有趣的是，急性 COVID-19 患者的 B 细胞响应 Toll 样受体激活而表现出 IL-6/IL-10 细胞因子失衡，偏向促炎表型。尽管无论临床结果如何，恢复期患者中 IL-6+ B 细胞的频率都会恢复，但 IL-10+ B 细胞的恢复与肺部病理学的缓解相关。我们的数据详细介绍了既往住院的 COVID-19 患者出院后 6 个月内的淋巴细胞变化，并根据不同的淋巴细胞表型确定了 3 个恢复期患者亚组，其中 1 个亚组与较差的临床结果相关。我们认为，因 COVID-19 住院后 B 细胞和 T 细胞功能的改变可能会影响长期免疫力，并导致恢复期 COVID-19 患者出现一些持续症状。由 UKRI、李斯特预防医学研究所、Wellcome Trust、肯尼迪风湿病研究信托基金和 3M Global Giving 提供。在 COVID-19 期间对淋巴细胞进行了检查，在急性 COVID-19 期间观察到的恢复期长达 6 个月的 B 细胞变化在恢复期 COVID-19 患者的恢复期 T 细胞中大部分恢复，显示出持续的变化。淋巴细胞特征定义了 3 个恢复期患者组，其中一组结果较差。由一种新型冠状病毒株引起的 2019 年冠状病毒病 (COVID-19) 大流行已导致全球超过 1 亿人感染。新证据表明，一些 COVID-19 患者存在持续症状，包括疲劳、纤维化肺病和肌痛；然而，这些患者的长期免疫反应仍然不明确。在这里，我们进行了一项观察性研究，检查了 COVID-19 患者住院期间和恢复期长达 6 个月的淋巴细胞群。我们发现了恢复期患者中持续存在的一些淋巴细胞改变。此外，对恢复期 COVID-19 患者淋巴细胞参数的汇编确定了 3 个不同的患者亚组，其中 1 个亚组与较差的临床结果相关。我们的研究概述了 COVID-19 恢复期患者的淋巴细胞变化与对后续健康的负面影响相关。舒瓦等人。检查急性和恢复期 COVID-19 患者的淋巴细胞特征，详细说明出院后 6 个月内淋巴细胞表型的持续变化。在这份报告中，他们根据不同的淋巴细胞特征确定了 3 个恢复期患者亚组，其中 1 个亚组与较差的临床结果相关。
Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these patients presently remains ill-defined. Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3–6 months of convalescence. We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic program evident in CD8+ T cells as well as elevated production of type 1 cytokines and interleukin-17 (IL-17). Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to Toll-like receptor activation, skewed toward a pro-inflammatory phenotype. Whereas the frequency of IL-6+ B cells was restored in convalescent patients irrespective of clinical outcome, the recovery of IL-10+ B cells was associated with the resolution of lung pathology. Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with 1 subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalization with COVID-19 could affect longer-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients. Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving. Lymphocytes were examined during COVID-19 and at up to 6 months of convalescence B cell changes seen during acute COVID-19 were largely restored in convalescence T cells from convalescent COVID-19 patients displayed persistent changes Lymphocyte signatures defined 3 convalescent patient groups, one with poorer outcomes The coronavirus disease 2019 (COVID-19) pandemic, caused by a novel coronavirus strain, has resulted in >100 million infections worldwide. Emerging evidence suggests that some COVID-19 patients suffer persistent symptoms, including fatigue, fibrotic lung disease, and myalgia; however, the long-term immune response in these patients remains ill-defined. Here, we conducted an observational study examining lymphocyte populations in COVID-19 patients during hospitalization and at up to 6 months of convalescence. We identified a number of lymphocyte alterations that persisted in convalescent patients. Moreover, the compilation of lymphocyte parameters in convalescent COVID-19 patients identified 3 distinct patient subgroups, with 1 subgroup associated with poorer clinical outcome. Our study outlines lymphocyte changes in convalescent COVID-19 patients associated with negative effects on subsequent health. Shuwa et al. examine lymphocyte characteristics in acute and convalescent COVID-19 patients, detailing persistent alterations in lymphocyte phenotype up to 6 months following hospital discharge. In this report, they identify 3 subgroups of convalescent patients based on distinct lymphocyte signatures, with 1 subgroup associated with poorer clinical outcomes.
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