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恢复期 COVID-19 患者中 SARS-CoV-2 抗体血清学阴性的反应性 T 细胞。

Reactive T Cells in Convalescent COVID-19 Patients With Negative SARS-CoV-2 Antibody Serology.

机构信息

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, Berlin, Germany.

Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, and German Centre for Infection Research (DZIF), associated partner, Charitéplatz 1, Berlin, Germany.

出版信息

Front Immunol. 2021 Jul 12;12:687449. doi: 10.3389/fimmu.2021.687449. eCollection 2021.

Abstract

Despite RT-PCR confirmed COVID-19, specific antibodies to SARS-CoV-2 spike are undetectable in serum in approximately 10% of convalescent patients after mild disease course. This raises the question of induction and persistence of SARS-CoV-2-reactive T cells in these convalescent individuals. Using flow cytometry, we assessed specific SARS-CoV-2 and human endemic coronaviruses (HCoV-229E, -OC43) reactive T cells after stimulation with spike and nucleocapsid peptide pools and analyzed cytokine polyfunctionality (IFN, TNFα, and IL-2) in seropositive and seronegative convalescent COVID-19 patients as well as in unexposed healthy controls. Stimulation with SARS-CoV-2 spike and nucleocapsid (NCAP) as well as HCoV spike peptide pools elicited a similar T cell response in seropositive and seronegative post COVID-19 patients. Significantly higher frequencies of polyfunctional cytokine nucleocapsid reactive CD4+ T cells (triple positive for IFN, TNFα, and IL-2) were observed in both, seropositive (p = 0.008) and seronegative (p = 0.04), COVID-19 convalescent compared to healthy controls and were detectable up to day 162 post RT-PCR positivity in seronegative convalescents. Our data indicate an important role of NCAP-specific T cells for viral control.

摘要

尽管经过 RT-PCR 确诊为 COVID-19,但在轻症患者康复后,约 10%的患者血清中无法检测到针对 SARS-CoV-2 刺突蛋白的特异性抗体。这就提出了一个问题,即在这些康复个体中,SARS-CoV-2 反应性 T 细胞的诱导和持续存在情况如何。我们使用流式细胞术,在使用刺突蛋白和核衣壳肽池进行刺激后,评估了特异性 SARS-CoV-2 和人类地方性冠状病毒(HCoV-229E、-OC43)反应性 T 细胞,并分析了血清阳性和血清阴性 COVID-19 康复患者以及未暴露的健康对照者中细胞因子的多功能性(IFN、TNFα 和 IL-2)。SARS-CoV-2 刺突蛋白和核衣壳(NCAP)以及 HCoV 刺突肽池的刺激在血清阳性和血清阴性的 COVID-19 后患者中引发了相似的 T 细胞反应。在血清阳性(p=0.008)和血清阴性(p=0.04)的 COVID-19 康复患者中,均观察到更高频率的多功能细胞因子核衣壳反应性 CD4+T 细胞(IFN、TNFα 和 IL-2 三重阳性),与健康对照组相比,这在两者中均更为显著,并且在血清阴性的康复患者中,可检测到 RT-PCR 阳性后长达 162 天。我们的数据表明 NCAP 特异性 T 细胞在病毒控制中具有重要作用。

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