While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56^briCD16⁻ natural killer (NK) cells and upregulation of interferon-gamma in effector CD4⁺ and CD8⁺ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4⁺ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.

虽然一些被严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 感染的个体呈现轻到重度的疾病，但许多 SARS-CoV-2 感染的个体是无症状的。我们试图确定无症状和中度患者之间免疫反应的区别。我们对来自健康对照的无症状、中度和重度患者的 37 个纵向收集的外周血单核细胞样本进行了单细胞转录组和 T 细胞/B 细胞受体 (TCR/BCR) 测序。无症状患者表现出 CD56 ^bri CD16 ^-自然杀伤 (NK) 细胞增加和效应子 CD4 ⁺和 CD8 ⁺中干扰素-γ 的上调T细胞和NK细胞。他们表现出更强大的 TCR 克隆扩增，尤其是在效应 CD4 ⁺ T 细胞中，但与中度患者相比缺乏强大的 BCR 克隆扩增。此外，无症状患者的干扰素刺激基因 (ISG) 表达一般较低，但患者间变异性较大，而中度患者在多个细胞群中显示出 ISG 表达的不同幅度和时间动态，但低于严重疾病患者。我们的数据提供了无症状感染中 SARS-CoV-2 不同免疫特征的证据。