Longitudinal single-cell immune profiling revealed distinct innate immune response in asymptomatic COVID-19 patients

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

Recent studies have characterized the single-cell immune landscape of host immune response of coronavirus disease 2019 (COVID-19), specifically focus on the severe condition. However, the immune response in mild or even asymptomatic patients remains unclear. Here, we performed longitudinal single-cell transcriptome sequencing and T cell/B cell receptor sequencing on 3 healthy donors and 10 COVID-19 patients with asymptomatic, moderate, and severe conditions. We found asymptomatic patients displayed distinct innate immune responses, including increased CD56briCD16− NK subset, which was nearly missing in severe condition and enrichment of a new Th2-like cell type/state expressing a ciliated cell marker. Unlike that in moderate condition, asymptomatic patients lacked clonal expansion of effector CD8+ T cells but had a robust effector CD4+ T cell clonal expansion, coincide with previously detected SARS-CoV-2-reactive CD4+ T cells in unexposed individuals. Moreover, NK and effector T cells in asymptomatic patients have upregulated cytokine related genes, such as IFNG and XCL2. Our data suggest early innate immune response and type I immunity may contribute to the asymptomatic phenotype in COVID-19 disease, which could in turn deepen our understanding of severe COVID-19 and guide early prediction and therapeutics.