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

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiang-Na Zhao ◽  
Yue You ◽  
Xiao-Ming Cui ◽  
Hui-Xia Gao ◽  
Guo-Lin Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Nk Cells ◽  
Single Cell ◽  
Temporal Dynamics ◽  
Severe Disease ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
Peripheral Blood Mononuclear ◽  
Asymptomatic Patients

AbstractWhile 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 CD56briCD16− 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.

scholarly journals Single-cell multi-omics analysis of the immune response in COVID-19

2021 ◽  
Author(s):  
Emily Stephenson ◽  
◽  
Gary Reynolds ◽  
Rachel A. Botting ◽  
Fernando J. Calero-Nieto ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Single Cell ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Cross Sectional ◽  
Hematopoietic Stem ◽  
Symptomatic Disease

AbstractAnalysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

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

2020 ◽  
Author(s):  
Xiang-Na Zhao ◽  
Yue You ◽  
Guo-Lin Wang ◽  
Hui-Xia Gao ◽  
Xiao-Ming Cui ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Innate Immune Response ◽  
Clonal Expansion ◽  
Innate Immune ◽  
Type I ◽  
Severe Condition ◽  
Asymptomatic Patients

SUMMARYRecent 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.

scholarly journals The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres

2021 ◽  
Author(s):  
Emily Stephenson ◽  
Gary Reynolds ◽  
Rachel A Botting ◽  
Fernando J Calero-Nieto ◽  
Michael Morgan ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cell Surface ◽  
Single Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Surface Proteins ◽  
Peripheral Blood Mononuclear ◽  
Cell Surface Proteins

AbstractThe COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19. Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included: healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires have provided several insights into COVID-19: 1. a new non-classical monocyte state that sequesters platelets and replenishes the alveolar macrophage pool; 2. platelet activation accompanied by early priming towards megakaryopoiesis in immature haematopoietic stem/progenitor cells and expansion of megakaryocyte-primed progenitors; 3. increased clonally expanded CD8+ effector:effector memory T cells, and proliferating CD4+ and CD8+ T cells in patients with more severe disease; and 4. relative increase of IgA plasmablasts in asymptomatic stages that switches to expansion of IgG plasmablasts and plasma cells, accompanied with higher incidence of BCR sharing, as disease severity increases. All data and analysis results are available for interrogation and data mining through an intuitive web portal. Together, these data detail the cellular processes present in peripheral blood during an acute immune response to COVID-19, and serve as a template for multi-omic single cell data integration across multiple centers to rapidly build powerful resources to help combat diseases such as COVID-19.

scholarly journals Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David S. Fischer ◽  
Meshal Ansari ◽  
Karolin I. Wagner ◽  
Sebastian Jarosch ◽  
Yiqi Huang ◽  
...  
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Rna Sequencing ◽  
Ex Vivo ◽  
Severe Disease ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Single Cell Rna Sequencing

AbstractThe in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we use single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients. To do so, we induce transcriptional shifts by antigenic stimulation in vitro and take advantage of natural T cell receptor (TCR) sequences of clonally expanded T cells as barcodes for ‘reverse phenotyping’. This allows identification of SARS-CoV-2-reactive TCRs and reveals phenotypic effects introduced by antigen-specific stimulation. We characterize transcriptional signatures of currently and previously activated SARS-CoV-2-reactive T cells, and show correspondence with phenotypes of T cells from the respiratory tract of patients with severe disease in the presence or absence of virus in independent cohorts. Reverse phenotyping is a powerful tool to provide an integrated insight into cellular states of SARS-CoV-2-reactive T cells across tissues and activation states.

scholarly journals Single-Cell Transcriptomic Profiling of MAIT Cells in Patients With COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Jijing Shi ◽  
Jianglin Zhou ◽  
Xiaochang Zhang ◽  
Wei Hu ◽  
Jin-Fang Zhao ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Single Cell ◽  
Severe Disease ◽  
Lymphocyte Activation ◽  
Cell Receptor ◽  
Host Immune Response ◽  
Flow Cytometry Analysis ◽  
Transcriptomic Profiling ◽  
Mait Cells

BackgroundMucosal-associated invariant T (MAIT) cells are considered to participate of the host immune response against acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, single-cell transcriptomic profiling of MAIT cells in patients with COVID-19 remains unexplored.MethodsWe performed single-cell RNA sequencing analyses on peripheral MAIT cells from 13 patients with COVID-19 and 5 healthy donors. The transcriptional profiles of MAIT cells, together with assembled T-cell receptor sequences, were analyzed. Flow cytometry analysis was also performed to investigate the properties of MAIT cells.ResultsWe identified that differentially expressed genes (DEGs) of MAIT cells were involved in myeloid leukocyte activation and lymphocyte activation in patients with COVID-19. In addition, in MAIT cells from severe cases, more DEGs were enriched in adaptive cellular and humoral immune responses compared with those in moderate cases. Further analysis indicated that the increase of cell cytotoxicity (killing), chemotaxis, and apoptosis levels in MAIT cells were consistent with disease severity and displayed the highest levels in patients with severe disease. Interestingly, flow cytometry analysis showed that the frequencies of pyroptotic MAIT cells, but not the frequencies of apoptotic MAIT cells, were increased significantly in patients with COVID-19, suggesting pyroptosis is one of leading causes of MAIT cell deaths during SARS-CoV-2 infection. Importantly, there were more clonal expansions of MAIT cells in severe cases than in moderate cases.ConclusionsThe results of the present study suggest that MAIT cells are likely to be involved in the host immune response against SARS-CoV-2 infection. Simultaneously, the transcriptomic data from MAIT cells provides a deeper understanding of the immune pathogenesis of the disease.

Analysis of the T-Cell Receptor Vα Gene Repertoire and Clonal Expansion in the Benzene-Exposed Group.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3874-3874
Author(s):  
Bo Li ◽  
Yangqiu Li ◽  
Shaohua Chen ◽  
Lijian Yang ◽  
Jiayu Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
Exposed Group ◽  
Skewed Distribution ◽  
Gene Repertoire ◽  
Peripheral Blood Mononuclear ◽  
Pcr Products ◽  
Expression Rate

Abstract Benzene is a potent human leukemogen, but its mechanism of hematotoxicity is uncertain. It is well know that benzene inhibit T cells proliferation. Several reports revealed that clonal expansion TCR Vβ T cells could be found in workers exposed to benzene. In this study we observe the distribution of TCR Vα gene repertoire and clonal expansion in peripheral blood mononuclear cells from 9 donors and 16 workers exposed to benzene. Complementarity determining region 3 (CDR3) of TCR Vα subfamily genes were amplified using RT-PCR. The PCR products were further analyzed by genescan to evaluating clonality of T cells. 29 Vα subfamily could be detected in 9 donors.1~11 Vα subfamilies were identified in all but one of the workers studied. The most frequently expressed Vα subfamily were Vα3, Vα12 and Vα19 (68.8%), Vα14(56.3%), with a lower expression rate found in Vα5,Vα15, Vα16, Vα 22, Vα 23 and Vα 24 (6.3%). Clonal expansion T cells in one or more Vα subfamily were found in 12 out of all workers studied, including oligoclonal, oligocolonal trend and bioclonal patterns. The frequency of clonal expansion T cells in Vα12, Vα14 and Vα19 subfamilies were higher than others. In conclusion, skewed distribution and clonal expansion of TCR Vα subfamily T cells could be found in workers exposed to benzene. Vα12, Vα14 and Vα19 subfamilies may be highly sensitive to benzene exposed. This is the first report of clonal expansion TCR Vα T cells in the benzene-exposed group. The bias pattern of TCR Vα T cells may be due to the immune cytotocicity from benzene. However, whether the oligoclonality in some Vα subfamilies reflect the phenomenon of clone absense or may be a response clone to benzene-related impairment during exposed to benzene, remains an open question.

scholarly journals Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians

2019 ◽  
Vol 116 (48) ◽  
pp. 24242-24251 ◽  
Author(s):  
Kosuke Hashimoto ◽  
Tsukasa Kouno ◽  
Tomokatsu Ikawa ◽  
Norihito Hayatsu ◽  
Yurina Miyajima ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Cd4 T Cells ◽  
Healthy Aging ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Cell Receptor ◽  
Peripheral Blood Mononuclear ◽  
Age Related

Supercentenarians, people who have reached 110 y of age, are a great model of healthy aging. Their characteristics of delayed onset of age-related diseases and compression of morbidity imply that their immune system remains functional. Here we performed single-cell transcriptome analysis of 61,202 peripheral blood mononuclear cells (PBMCs), derived from 7 supercentenarians and 5 younger controls. We identified a marked increase of cytotoxic CD4 T cells (CD4 cytotoxic T lymphocytes [CTLs]) as a signature of supercentenarians. Furthermore, single-cell T cell receptor sequencing of 2 supercentenarians revealed that CD4 CTLs had accumulated through massive clonal expansion, with the most frequent clonotypes accounting for 15 to 35% of the entire CD4 T cell population. The CD4 CTLs exhibited substantial heterogeneity in their degree of cytotoxicity as well as a nearly identical transcriptome to that of CD8 CTLs. This indicates that CD4 CTLs utilize the transcriptional program of the CD8 lineage while retaining CD4 expression. Indeed, CD4 CTLs extracted from supercentenarians produced IFN-γ and TNF-α upon ex vivo stimulation. Our study reveals that supercentenarians have unique characteristics in their circulating lymphocytes, which may represent an essential adaptation to achieve exceptional longevity by sustaining immune responses to infections and diseases.

scholarly journals Single-cell RNA sequencing reveals in vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’

2020 ◽  
Author(s):  
David S. Fischer ◽  
Meshal Ansari ◽  
Karolin I. Wagner ◽  
Sebastian Jarosch ◽  
Yiqi Huang ◽  
...  
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Rna Sequencing ◽  
Severe Disease ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Phenotypic Profile ◽  
Single Cell Rna Sequencing

ABSTRACTThe in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we used single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients. To do so, we induced transcriptional shifts by antigenic stimulation in vitro and took advantage of natural T cell receptor (TCR) sequences of clonally expanded T cells as barcodes for ‘reverse phenotyping’. This allowed identification of SARS-CoV-2-reactive TCRs and revealed phenotypic effects introduced by antigen-specific stimulation. We characterized transcriptional signatures of currently and previously activated SARS-CoV-2-reactive T cells, and showed correspondence with phenotypes of T cells from the respiratory tract of patients with severe disease in the presence or absence of virus in independent cohorts. Reverse phenotyping is a powerful tool to provide an integrated insight into cellular states of SARS-CoV-2-reactive T cells across tissues and activation states.

scholarly journals H-Ras gene takes part to the host immune response to COVID-19

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Salvatore Sciacchitano ◽  
Andrea Sacconi ◽  
Claudia De Vitis ◽  
Giovanni Blandino ◽  
Giulia Piaggio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Severe Disease ◽  
Host Immune Response ◽  
Severe Form ◽  
Ras Gene ◽  
Peripheral Blood Mononuclear ◽  
Ras Genes

AbstractRas gene family members play a relevant role in cancer, especially when they are mutated. However, they may play additional roles in other conditions beside cancer. We performed gene expression analysis using the NanoString PanCancer IO 360 panel in the peripheral blood mononuclear cell (PBMC) of six COVID-19 patients and we found that H-Ras gene was significantly upregulated, while both K-Ras and N-Ras genes were downregulated. In particular, H-Ras gene upregulation was more evident in COVID-19 patients with a more severe disease. We compared our results with those obtained by analyzing two different and independent datasets, including a total of 53 COVID-19 patients, in which the gene expression analysis was performed using the Immunology_V2 panel. Comparative analysis of the H-Ras gene expression in these patients confirmed our preliminary results. In both of them, in fact, we were able to confirm the upregulation of the expression of the H-Ras gene. The exact role of this specific upregulation of the H-Ras gene in response to SARS-CoV-2 infection and its possible role in cancer still remains to be elucidated. In conclusion, H-Ras gene participates to the host immune response to SARS-CoV-2 virus infection, especially in patients affected by the most severe form of the COVID-19.

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