Single-cell immune profiling reveals distinct immune response in asymptomatic COVID-19 patients

Zhao, Xiang-Na; You, Yue; Cui, Xiao-Ming; Gao, Hui-Xia; Wang, Guo-Lin; Zhang, Sheng-Bo; Yao, Lin; Duan, Li-Jun; Zhu, Ka-Li; Wang, Yu-Ling; Li, Li; Lu, Jian-Hua; Wang, Hai-Bin; Fan, Jing-Fang; Zheng, Huan-Wei; Dai, Er-Hei; Tian, Lu-Yi; Ma, Mai-Juan

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(bri)CD16(−) 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.