22339c53-da2a-482d-9547-77ce15b36b11 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001006550 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:In a dual-center, two-cohort study, we performed single-cell RNA-sequencing of whole blood and peripheral blood mononuclear cells to determine changes in immune cell composition and activation in mild vs. severe COVID-19 over time. This study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.
| EGAS00001004571 | EGA
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections cause coronavirus disease 2019 (COVID-19) and are associated with inflammation and coagulopathy and high incidence of thrombosis. Myeloid cells (Mϕ) help coordinate the initial immune response in COVID-19. Although we appreciate that Mϕ lie at the nexus of inflammation and thrombosis, the mechanisms that unite the two in COVID-19 remain largely unknown. In this study, we employed systems biology approaches including proteomics, transcriptomics, and mass cytometry to define the circulating proteome and circulating immune cell phenotypes in subjects with COVID-19. In a cohort of COVID-19 subjects (n=35), circulating markers of inflammation (CCL23, IL-6) and vascular dysfunction (ACE2, tissue factor [TF]) were elevated in subjects with severe compared with mild COVID-19. Additionally, although the total white blood cell (WBC) counts were similar between COVID-19 groups, CD14+ monocytes from severe COVID-19 subjects expressed more TF. At baseline, transcriptomics demonstrated increased IL-6, CCL3, ACOD1, C5AR1, C5AR2, and TF in severe COVID-19 subjects compared with controls. Using “stress” transcriptomics, we found that circulating immune cells from severe COVID-19 subjects had evidence of profound immune paralysis with greatly reduced transcriptional activation and release of inflammatory markers in response to Toll-like receptor (TLR) activation. Finally, sera from severe (but not mild) COVID-19 subjects activated human monocytes and induced TF expression. Taken together, these observations further elucidate the pathological mechanisms that underlie immune dysfunction and coagulation abnormalities in COVID-19, contributing to our growing understanding of SARS-CoV-2 infections that could also be leveraged to develop novel diagnostic and therapeutic strategies.
2024-01-23 | GSE247186 | GEO
Project description:The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical manifestations in disease-ridden patients. Differences in the severity of COVID-19 ranges from asymptomatic infections and mild cases to the severe form, leading to acute respiratory distress syndrome (ARDS) and multiorgan failure with poor survival. MiRNAs can regulate various cellular processes, including proliferation, apoptosis, and differentiation, by binding to the 3′UTR of target mRNAs inducing their degradation, thus serving a fundamental role in post-transcriptional repression. Alterations of miRNA levels in the blood have been described in multiple inflammatory and infectious diseases, including SARS-related coronaviruses. We used microarrays to delineate the miRNAs and snoRNAs signature in the peripheral blood of severe COVID-19 cases (n=9), as compared to mild (n=10) and asymptomatic (n=10) patients, and identified differentially expressed transcripts in severe versus asymptomatic, and others in severe versus mild COVID-19 cases. A cohort of 29 male age-matched patients were selected. All patients were previously diagnosed with COVID-19 using TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Waltham, Massachusetts), or Cobas SARS-CoV-2 Test (Roche Diagnostics, Rotkreuz, Switzerland), with a CT value < 30. Additional criterion for selection was age between 35 and 75 years. Participants were grouped into severe, mild and asymptomatic. Classifying severe cases was based on requirement of high-flow oxygen support and ICU admission (n=9). Whereas mild patients were identified based on symptoms and positive radiographic findings with pulmonary involvement (n=10). Patients with no clinical presentation were labelled as asymptomatic cases (n=10).
2022-03-01 | E-MTAB-10970 | biostudies-arrayexpress
Project description:The objective of this experiment was to compare the transcriptomic profile (NanoString platform) of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild disease, and patients with severe COVID-19 with and without dexamethasone treatment, and healthy controls. We analyzed PBMCs from 4 mild COVID patients, 3 severe COVID patients,4 severe COVID patients treated with dexamethasone, and 5 healthy controls
2023-03-23 | GSE227341 | GEO
Project description:Although most SARS-CoV-2-infected individuals experience mild COVID-19, some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly upregulation of the TNF/IL-1beta-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1beta-driven inflammation, and this was not seen in patients with milder COVID-19 infection. Based on this, we propose that the type I IFN response exacerbates inflammation in patients with severe COVID-19 infection.
2020-07-06 | GSE149689 | GEO
Project description:While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferon-stimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies that functionally block the production of the mild disease-associated ISG-expressing cells, by engaging conserved signaling circuits that dampen cellular responses to interferons. Overzealous and auto-directed antibody responses pit the immune system against itself in many COVID-19 patients and this defines targets for immunotherapies to allow immune systems to provide viral defense.
2021-01-22 | GSE163668 | GEO
Project description:Our understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including prominent hyperactivation signatures in neutrophils and monocytes with anti-inflammatory features. We also leverage epigenomic analysis to identify loss of accessibility at NF-kB binding sites within pro-inflammatory cytokine gene loci as a potential mechanism for the striking lack of cytokine production observed in monocytes in severe and fatal COVID-19. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.
2021-05-08 | GSE174072 | GEO
Project description:In children and younger adults up to 39 years of age, SARS-CoV-2 usually elicits mild symptoms that resemble the common cold. Disease severity increases with age starting at 30 and reaches astounding mortality rates that are ~330 fold higher in persons above 85 years of age compared to those 18-39 years old. To understand age-specific immune pathobiology of COVID-19 we have analyzed soluble mediators, cellular phenotypes, and transcriptome from over 80 COVID-19 patients of varying ages and disease severity, carefully controlling for age as a variable. We found that reticulocyte numbers and peripheral blood transcriptional signatures robustly correlated with disease severity. By contrast, decreased numbers and proportion of naïve T cells, reported previously as a COVID-19 severity risk factor, were found to be general features of aging and not of COVID-19 severity, as they readily occurred in older participants experiencing only mild or no disease at all. Single-cell transcriptional signatures across age and severity groups showed that severe but not moderate/mild COVID-19 causes cell stress response in different T cell populations, and some of that stress was unique to old severe participants, suggesting that in severe disease of older adults, these defenders of the organism may be disabled from performing immune protection. These findings shed new light on interactions between age and disease severity in COVID-19.
2023-01-11 | GSE212584 | GEO
Project description:Introduction: The crosstalk between immune cells through plasma extracellular vesicles (EVs) during SARS-CoV-2 infection may represent a significant determinant of clinical course in COVID-19 patients. EVs from SARS-CoV-2 virus-infected cells deliver their informational content to immune cells implicated in COVID-19 pathogenesis, thereby modulating pro-inflammatory immune responses during infection. γδ T cells are innate cells known for their pleiotropic properties spanning both innate and adaptive immunity and for their possible contribution to inflammation. This study aimed to characterize the biophysical profile and protein content of EVs derived from patients with severe and mild COVID-19, and to analyze their impact on the functional activity of Vδ2 T cells. Methods: Plasma samples from 42 COVID-19 hospitalized patients (17 severe and 25 mild) were enrolled at the National Institute for Infectious Diseases Lazzaro Spallanzani in Rome. Twenty-three healthy donors (HD) served as the control group. Plasma cytokines were quantified by ELISA assay. EVs were purified using nickel-based isolation (NBI) and analyzed by quantitative LC-MS proteomics. Characterization of EVs was performed using multiparametric flow cytometry, as well as the Vδ2 T cell functional assays. Peripheral blood mononuclear cells from 10 HD were utilized for immunological assays. Results: Cytometric characterization revealed that EVs from severe COVID-19 patients were enriched in platelet components compared to HD and mild patients. Protein expression of EVs from severe patients clustered differently in PCA and heatmap analyses with respect to HD and mild patients. A volcano plot revealed several proteins that were differentially expressed between EVs from mild and severe patients. A significant induction of several processes, including platelet degranulation, complement, coagulation, and innate immunity, was observed in the pathway analysis. EVs from severe COVID-19 patients enhanced the responsiveness of Vδ2 T cells to phosphoantigen, increasing their activation and proinflammatory cytokine production (TNF-α). Conclusions: Proteomic differential analysis reveals the expression/regulation of innate immune-related proteins in EVs from severe patients compared to mild patients/HD and supports their potential role in modulating innate immunity. Specifically, functional analysis of Vδ2 T cells suggests that EVs may contribute to the pathogenesis of severe COVID-19 by delivering molecular signals that exacerbate innate immune-driven inflammation.
2026-02-10 | PXD072061 | Pride
Project description:COVID-19 symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unraveling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. We carried out a multi-tissue (nasal, buccal and blood) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls.
2021-12-31 | GSE183071 | GEO