The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus' pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with
COVID-19 at different stages by using 5' gene expression,
T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell
mRNA sequencing (
scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with
COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with
COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The
type I interferon (IFN-I),
mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the
mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with
COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of
interferon-α (IFN-α) in the serum of patients with
COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with
COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of
COVID-19. TCR and BCR sequences analyses indicated that patients with
COVID-19 developed specific immune responses against SARS-CoV-2
antigens. Our study reveals a dynamic landscape of human blood immune responses to
SARS-CoV-2 infection, providing clues for therapeutic potentials in treating
COVID-19.