Center for Infectious Disease, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
Sci Immunol. 2020 Jun 26;5(48). doi: 10.1126/sciimmunol.abd2071.
SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients the infection results in moderate to severe acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. High serum levels of IL-6, IL-10 and an immune hyperresponsiveness referred to as a 'cytokine storm' have been associated with poor clinical outcome. Despite the large numbers of COVID-19 cases and deaths, information on the phenotype and kinetics of SARS-CoV-2-specific T cells is limited. Here, we studied 10 COVID-19 patients who required admission to an intensive care unit and detected SARS-CoV-2-specific CD4 and CD8 T cells in 10 out of 10 and 8 out of 10 patients, respectively. We also detected low levels of SARS-CoV-2-reactive T cells in 2 out of 10 healthy controls not previously exposed to SARS-CoV-2, which is indicative of cross-reactivity due to past infection with 'common cold' coronaviruses. The strongest T-cell responses were directed to the spike (S) surface glycoprotein, and SARS-CoV-2-specific T cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected. Furthermore, we studied T-cell kinetics and showed that SARS-CoV-2-specific T cells are present relatively early and increase over time. Collectively, these data shed light on the potential variations in T-cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in the disease, and also inform vaccine design and evaluation.
严重急性呼吸综合征冠状病毒 2 已被确定为导致全球呼吸道疾病(COVID-19)爆发的病原体。在某些患者中,感染导致中度至重度急性呼吸窘迫综合征(ARDS),需要进行有创机械通气。高水平的白细胞介素 6(IL-6)、白细胞介素 10(IL-10)和被称为“细胞因子风暴”的免疫高反应性与不良临床结局相关。尽管 COVID-19 病例和死亡人数众多,但有关 SARS-CoV-2 特异性 T 细胞表型和动力学的信息有限。在这里,我们研究了 10 名需要入住重症监护病房的 COVID-19 患者,在 10 名患者中的 10 名和 8 名患者中的 8 名患者中检测到了 SARS-CoV-2 特异性 CD4 和 CD8 T 细胞。我们还在 2 名未接触过 SARS-CoV-2 的健康对照者中检测到低水平的 SARS-CoV-2 反应性 T 细胞,这表明由于过去感染了“普通感冒”冠状病毒而发生了交叉反应。最强的 T 细胞反应针对刺突(S)表面糖蛋白,SARS-CoV-2 特异性 T 细胞主要产生效应和 Th1 细胞因子,尽管也检测到 Th2 和 Th17 细胞因子。此外,我们研究了 T 细胞动力学,并表明 SARS-CoV-2 特异性 T 细胞相对较早出现,并随时间增加。总之,这些数据揭示了 T 细胞反应作为疾病严重程度的函数的潜在变化,这是了解免疫病理学在疾病中潜在作用的关键问题,也为疫苗设计和评估提供了信息。