ABSTRACT
Coronavirus disease 2019 (COVID-19), driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a global pandemic in March 2020. Pathogenic T cells and inflammatory monocytes are regarded as the central drivers of the cytokine storm associated with the severity of COVID-19. In this study, we explored the characteristic peripheral cellular profiles of patients with COVID-19 in both acute and convalescent phases by single-cell mass cytometry (CyTOF). Using a combination of algorithm-guided data analyses, we identified peripheral immune cell subsets in COVID-19 and revealed CD4+ T-cell depletion, T-cell differentiation, plasma cell expansion, and the reduced antigen presentation capacity of innate immunity. Notably, COVID-19 induces a dysregulation in the balance of monocyte populations by the expansion of the monocyte subsets. Collectively, our results represent a high-dimensional, single-cell profile of the peripheral immune response to SARS-CoV-2 infection.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , Leukocytes, Mononuclear/immunology , Monocytes/immunology , SARS-CoV-2/immunology , Adult , Aged , Antigen Presentation/immunology , CD4-Positive T-Lymphocytes/cytology , COVID-19/pathology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Cytokines/immunology , Dendritic Cells/cytology , Dendritic Cells/immunology , Female , Humans , Killer Cells, Natural/cytology , Killer Cells, Natural/immunology , Leukocytes, Mononuclear/cytology , Lymphocyte Depletion , Male , Middle Aged , Monocytes/cytology , Plasma Cells/cytology , Single-Cell AnalysisABSTRACT
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Subject(s)
Aging/immunology , Betacoronavirus , Coronavirus Infections/immunology , Immune System/immunology , Pandemics , Pneumonia, Viral/immunology , Single-Cell Analysis , Adult , Aged , Aged, 80 and over , Aging/genetics , CD4-Positive T-Lymphocytes/metabolism , COVID-19 , Cell Lineage , Chromatin Assembly and Disassembly , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokines/biosynthesis , Cytokines/genetics , Disease Susceptibility , Flow Cytometry/methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Humans , Immune System/cytology , Immune System/growth & development , Immunocompetence/genetics , Inflammation/genetics , Inflammation/immunology , Mass Spectrometry/methods , Middle Aged , SARS-CoV-2 , Sequence Analysis, RNA , Transcriptome , Young AdultABSTRACT
[This corrects the article DOI: 10.1038/s41421-020-0168-9.].
ABSTRACT
COVID-19, caused by SARS-CoV-2, has recently affected over 1,200,000 people and killed more than 60,000. The key immune cell subsets change and their states during the course of COVID-19 remain unclear. We sought to comprehensively characterize the transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19 by single-cell RNA sequencing technique. It was found that T cells decreased remarkably, whereas monocytes increased in patients in the early recovery stage (ERS) of COVID-19. There was an increased ratio of classical CD14++ monocytes with high inflammatory gene expression as well as a greater abundance of CD14++IL1ß+ monocytes in the ERS. CD4+ T cells and CD8+ T cells decreased significantly and expressed high levels of inflammatory genes in the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naïve B cells decreased. Several novel B cell-receptor (BCR) changes were identified, such as IGHV3-23 and IGHV3-7, and isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously used for virus vaccine development were confirmed. The strongest pairing frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity, which had not been reported yet. Furthermore, integrated analysis predicted that IL-1ß and M-CSF may be novel candidate target genes for inflammatory storm and that TNFSF13, IL-18, IL-2, and IL-4 may be beneficial for the recovery of COVID-19 patients. Our study provides the first evidence of an inflammatory immune signature in the ERS, suggesting COVID-19 patients are still vulnerable after hospital discharge. Identification of novel BCR signaling may lead to the development of vaccines and antibodies for the treatment of COVID-19.