ABSTRACT
COVID-19, caused by SARS-CoV-2, has recently affected over 300,000 people and killed more than 10,000. The manner in which the key immune cell subsets change and their states during the course of COVID-19 remain unclear. Here, we applied single-cell technology to comprehensively characterize transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19. Compared with healthy controls, in patients in the early recovery stage (ERS) of COVID-19, T cells decreased remarkably, whereas monocytes increased. A detailed analysis of the monocytes revealed that there was an increased ratio of classical CD14++ monocytes with high inflammatory gene expression as well as a greater abundance of CD14++IL1B+ monocytes in the ERS. CD4+ 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 naive B cells decreased. Our study identified several novel B cell-receptor (BCR) changes, such as IGHV3-23 and IGHV3-7, and confirmed isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously used for virus vaccine development. The strongest pairing frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity. Furthermore, integrated analysis predicted that IL-1{beta} 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 that COVID-19 patients are still vulnerable after hospital discharge. Our identification of novel BCR signaling may lead to the development of vaccines and antibodies for the treatment of COVID-19. Highlights- The immune response was sustained for more than 7 days in the early recovery stage of COVID-19, suggesting that COVID-19 patients are still vulnerable after hospital discharge. - Single-cell analysis revealed a predominant subset of CD14++ IL1{beta}+ monocytes in patients in the ERS of COVID-19. - Newly identified virus-specific B cell-receptor changes, such as IGHV3-23, IGHV3-7, IGHV3-15, IGHV3-30, and IGKV3-11, could be helpful in the development of vaccines and antibodies against SARS-CoV-2. - IL-1{beta} and M-CSF were discovered as novel mediators of inflammatory cytokine storm, and TNFSF13, IL-2, IL-4, and IL-18 may be beneficial for recovery.
ABSTRACT
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)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , TranscriptomeABSTRACT
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)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , TranscriptomeABSTRACT
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)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , TranscriptomeABSTRACT
Objective To investigate the clinical factors and therapeutic tactic for rebleeding of hypertensive hemorrhage after minimally invasive craniopuncture.Methods Clinical data of 213 cases were reviewed retrospectively.8 possible factors were gathered to select the high-risk ones by multiple-factor Logistic regression analysis.Results 27 cases bled after minimally invasive craniopuncture therapy.By Logistic regression analysis,we found 4 high-risk factors of recurrence hemorrhage,including hematoma shape (β =2.236,P =0.002),systolic blood pressure on admission (β =1.877,P =0.001),operation time (β =-1.589,P =0.004) and hematoma clearance (β =1.280,P =0.010).Conclusion Paying more attention to the 4 factors and treating each patient by individual therapeutic tactic according to the 4 factors will help to decrease the incidence of bleeding after minimally invasive craniopuncture.