659 results for ""option,com_discussions"+y+19"

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• COVID-19 progression and convalescence in common variable immunodeficiency patients

  Longitudinal analysis of single-cell RNAseq datasets of PBMCs from COVID-19 CVID patients and controls.

  Study EGAS50000000368

• Single-cell RNA-seq of bronchoalveolar lavage (BAL) fluid of late stage severe COVID-19 patients

  COVID-19-induced ‘acute respiratory distress syndrome’ (ARDS) is associated with prolonged respiratory failure and high mortality, but the mechanistic basis of lung injury remains incompletely understood. Here, we analyzed pulmonary immune responses and lung pathology in two cohorts of patients with COVID-19 ARDS using functional single cell genomics, immunohistology and electron microscopy. We describe an accumulation of CD163-expressing monocyte-derived macrophages, that acquired a profibrotic transcriptional phenotype during COVID-19 ARDS. Gene set enrichment and computational data integration revealed a significant similarity between COVID-19-associated macrophages and profibrotic macrophage populations identified in idiopathic pulmonary fibrosis. COVID-19 ARDS was associated with clinical, radiographic, histopathological, and ultrastructural hallmarks of pulmonary fibrosis. Exposure of human monocytes to SARS-CoV-2, but not Influenza A virus or viral RNA analogs, was sufficient to induce a similar profibrotic phenotype in vitro. In conclusion, we demonstrate that SARS-CoV-2 triggers profibrotic macrophage responses and pronounced fibroproliferative ARDS.

  Study EGAS00001005634

• COVID-19 ACTIV-4 ACUTE: A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV4A)

  This is a randomized, open label, adaptive platform trial to compare the effectiveness of antithrombotic strategies for prevention of adverse outcomes in COVID-19 positive inpatients.

  Study phs002694

• Multimodal single-cell analyses of peripheral blood mononuclear cells in COVID-19 patients

  10x scRNA and 10X scVDJ analyses were performed using PBMCs collected from COVID-19 patients in Japan.

  Study JGAS000546

• Multimodal Immune Profiling to Determine Mechanisms of COVID-19 Clinical Trajectory in Uganda

  We conducted a prospective cohort study of adults (RESERVE-U-C19) admitted to Entebbe Regional Referral Hospital (ERRH), a national COVID-19 referral center, across three viral variant-driven phases of the pandemic in Uganda. In this cohort, which reflects the entire spectrum of SARS-CoV-2 infection, we integrated clinical data with serum proteomics (N=306) and whole-blood transcriptomics (N=100) to determine a range of host responses associated with COVID-19 severity, SARS-CoV-2/HIV co-infection, and circulating viral variants. Beyond the prognostic importance of myeloid cell-driven immune activation and lymphopenia, we show that multifaceted impairment of host protein synthesis and extensive redox imbalance define core metabolic signatures of severe COVID-19, with central roles for IL-7, IL-15, and lymphotoxin-α in COVID-19 respiratory failure. While prognostic signatures were generally consistent in SARS-CoV-2/HIV-coinfection, type I interferon responses uniquely scaled with COVID-19 severity in persons living with HIV. Throughout the pandemic, COVID-19 severity peaked during phases dominated by A.23/A.23.1 and Delta B.1.617.2/AY variants, with Delta phase COVID-19 distinguished by exaggerated pro-inflammatory myeloid cell and inflammasome activation, NK and CD8+ T-cell depletion, impaired host protein synthesis, and upregulation of viral cell entry and trafficking pathways. Data from this study available through dbGaP include raw RNA-Seq data from whole-blood of adult participants (N=100).

  Study phs003246

• Peripheral immunoprofiling of stratifies COVID-19 patients based on disease-specific neutrophil signatures

  The SARS-CoV-2 pandemic has led to increasing numbers of COVID-19 patients all over the world. Aetiopathologies range from no symptoms, mild flu-like to severe cases succumbing to respiratory failure. Reports on a dysregulated immune system in the severe cases, showing similarities to cytokine release syndrome, calls for better characterization and understanding of the changes in the immune system as well as their variance across COVID-19 patients in order to be able to design according to host-directed therapies. Here, we profiled blood transcriptomes of 39 COVID-19 patients and 10 control donors. Enriched granulocyte signatures in whole blood samples were verified in granulocyte samples from 49 COVID-19 patients in a second cohort.

  Study EGAS00001004503

• Upper respiratory microbiome of COVID-19 patients

  Understanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 microbiome studies by analyzing the upper respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We found that time in the intensive care unit and the type of oxygen support explained the most variation within the upper respiratory tract microbiome, dwarfing (non-significant) effects from viral load, disease severity, and immune status. Specifically, mechanical ventilation was linked to altered community structure, lower species- and higher strain-level diversity, and significant shifts in oral taxa previously associated with COVID-19.

  Study EGAS00001004951

• Multi-omics integration reveals only minor long-term molecular and functional sequelae in immune cells of individuals recovered from COVID-19

  The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune system after recovery is less well known. To comprehensively investigate the post-SARS-CoV-2 infection sequelae on the immune system, we performed a multi-omics study by integrating single-cell RNA-sequencing, single-cell ATAC-sequencing, genome-wide DNA methylation profiling, and functional validation experiments in convalescent COVID-19 and healthy individuals. We showed that immune responses generally recover without major sequelae after COVID-19. However, subtle differences persist at the transcriptomic level in monocytes, with downregulation of the interferon pathway, while DNA methylation also displays moderate changes in convalescent COVID-19 individuals. However, these differences did not affect the cytokine production capacity of PBMCs upon different bacterial, viral, and fungal stimuli, although baseline release of IL-1RA and IFN?? was higher in convalescent individuals. In conclusion, despite minor differences in epigenetic and transcriptional programs, the immune system of convalescent COVID-19 patients largely recovers to the homeostatic level of healthy individuals.

  Study EGAS00001005529

• Genetic Determinants of Susceptibility to Severe COVID-19 Infection

  The goal of the project is to identify genetic susceptibility variants associated with acute COVID-19 infection susceptibility and severity using whole genome sequencing. The target of the project will include WGS data from whole blood samples of up to approximately 2000 COVID-19 patients (including critical/severe patient subgroup, asymptomatic/mild subgroup) from domestic and international medical institutions.

  Study phs002245

• SARS-CoV-2 host genetics and COVID-19 outcomes in admixed Brazilians with extreme phenotypes

  COVID-19 comprises clinical outcomes of SARS-CoV-2 infection and is highly heterogeneous, ranging from asymptomatic individuals to deceased young adults without comorbidities. There is growing evidence that host genetics play an important role in COVID-19 severity, including inborn errors of immunity, age-related inflammation and immunosenescence. This study proposes a strategy of subject’s ascertainment based on phenotypic extremes to take part in genomic studies and elucidate intrinsic risk factors involved in COVID-19 severe outcomes. Different cohorts were collected and submitted to Next-Generation Sequencing (Whole exome and whole genome sequencing).

  Study EGAS00001006376

• COVID19 Host Genetic Initiative

  The COVID-19 host genetics initiative is a bottom-up collaborative effort that has three main goals: 1. Provide an environment to foster the sharing of resources to facilitate COVID-19 host genetics research (e.g. protocols, questionnaires). 2. Organize analytical activities across studies to identify genetic determinants of COVID-19 susceptibility and severity. 3. Provide a platform to share the results from such activities, as well as the individual-level data where possible, to benefit the broader scientific community. Here, we release the harmonized individual-level data for the subset of individuals who participated in COVID-19 HGI. Please refer to this data dictionary: https://docs.google.com/spreadsheets/d/1whu_MjShXxbdoAJMCYxZ5C-vWOcRivwfWglTcBRNZgQ/edit#gid=470747846 Please cite both Nakanishi, T el al. J Clin Invest 2021 (PMID: 34597274) and COVID-19 Host Genetics Initiative, Nature 2021 (PMID: 34237774) when you use these data for your publications.

  Study EGAS00001005304

• Rapid Acceleration of Diagnostics - Underserved Populations (RADx-UP): CO-CREATE-Ex: Community-engaged Optimization of COVID-19 Rapid Evaluation And TEsting Experiences

  Cases of COVID-19 infection in San Diego have persistently remained high in the county's central and southern communities near the US/Mexico border, home to primarily Latino residents who have been one of the ethnic minority communities most impacted by COVID-19. To address this, our Phase I RADx-UP project partnered with San Ysidro Health (SYH), a federally qualified health center, and the Global Action Research Center (Global ARC), a social change organization, to co-create and demonstrate the impact of a PCR-based COVID-19 testing program in San Ysidro. To date, we have administered approximately 15,000 PCR tests for >10,000 community members (92% Latino) and received requests from SYH to scale-out the testing program to additional primary care clinic sites. Responsive to RFA-OD-22-006, we will continue working with our community (Global ARC) and clinical (SYH) partners to refine, specify, implement, and evaluate an implementation strategy bundle that optimizes COVID-19 testing, expanding beyond current PCR testing to focus on FDA-authorized COVID-19 rapid antigen testing. Use of self-administered rapid antigen tests will allow participants to build capacity to self-test and use health information technology to access additional clinic services. Based on initial implementation mapping with the project's established Community and Scientific Advisory Board, three implementation strategies were prioritized to accelerate sustained uptake of rapid COVID-19 testing. These three strategies include: (1) current, walk-up onsite free testing; (2) promotores-led COVID-19 test counseling and preventive care reminders; (3) vending machines that dispense FDA-authorized self-testing kits. Our primary objectives are to: 1) refine and operationalize our multi-component implementation strategy bundle and a related set of measures of success for rapid FDA- authorized COVID-19 testing and 2) implement and evaluate impact of our innovative, multilevel, and multicomponent implementation strategy bundle to optimize COVID-19 rapid testing among underserved, Latino communities using a roll-out implementation optimization study design across four clinics over 18 months. The COVID-19 pandemic has underscored the urgent and essential need to engage invested community parties continuously and meaningfully in public health research to reduce health disparities. This proposal is well-positioned to provide a set of strategies and measures of success that can be used in settings serving underserved communities while maintaining flexibility to adjust to the changing COVID-19 landscape.

  Study phs003686

• Single-cell RNA-sequencing for peripheral blood mononuclear cells from COVID-19 patients and healthy controls of Japanese

  We performed single-cell RNA-sequencing of peripheral blood mononuclear cells obtained from COVID-19 patients and healthy controls.

  Study JGAS000593

• Single-cell RNA-sequencing for peripheral blood mononuclear cells from COVID-19 patients and healthy controls of Japanese

  We performed single-cell RNA-sequencing of peripheral blood mononuclear cells obtained from COVID-19 patients and healthy controls.

  Study JGAS000543

• NIDDK IBD Genetics Consortium Repository Exome Chip

  The Illumina Infinium HumanExome+ BeadChip contains putative functional exonic variants selected from individual exome and whole-genome sequences from diverse populations. It includes nonsynonymous variants, splice variants and stop-altering variants. It also includes tags for previous GWAS-identified loci, ancestry informative markers, markers designed for identity by descent analyses, synonymous variants, fingerprint SNPs common to major genotyping platforms, mitochondrial SNPs, chromosome Y SNPs, and HLA tag SNPs. For more information as well as a detailed description of the variant calling and QC procedures, see Li et al. (2016). Li, D., et al. (2016) A pleiotropic missense variant in SLC39A8 is associated with Crohn's disease and human gut microbiome composition. Gastroenterology, 151, 1-9. PMID: 27492617.

  Study phs001723

• Single-Cell TCR/BCR Sequencing for Korean COVID-19 Vaccinated and Patient Samples

  We conducted longitudinal single-cell TCR/BCR sequencing for COVID-19 vaccinated cases (297 samples from 112 cases) and COVID-19 infected cases classified as Asymptomatic (26 samples from 12 cases), Mild (82 samples from 37 cases), Moderate (123 samples from 50 cases), Severe (216 samples from 58 cases), and Critical (142 samples from 41 cases) according to the NIH guideline.

  Study phs003341

• The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation

  Assessment of dexamethasone response in human lung through scRNA-seq analysis of bronchoalveolar lavage (BAL) samples from patients with severe COVID-19.

  Study EGAS50000000203

• RNA-sequencing of PBMCs from COVID-19 patients experiencing different degrees of the disease (mild and critical), and control patients

  Bulk RNA-sequencing of peripheral blood mononuclear cells collected from mild COVID-19 (n = 4), critical COVID-19 (n = 12) and control (n = 8) patients. Sequencing data is provided as FASTQ files.

  Dataset EGAD50000001405

• miRNA-sequencing of PBMCs from COVID-19 patients experiencing different degrees of the disease (mild and critical), and control patients

  micro RNA-sequencing of peripheral blood mononuclear cells collected from mild COVID-19 (n = 6), critical COVID-19 (n = 13) and control (n = 8) patients. Sequencing data is provided as FASTQ files.

  Dataset EGAD50000001406

• Single-cell RNA sequencing of bronchoalveolar lavages from COVID-19 patients

  Discriminating mild-moderate from critical COVID-19 disease by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.

  Study EGAS00001004717

• Long-read single-cell RNA-seq in COVID-19

  We report the first application of long-read single-cell RNA sequencing on nasopharyngeal swabs from COVID-19 patients and healthy controls to resolve transcript-level changes across cell types. Samples were collected from three patients with moderate COVID-19, six patients with critical COVID-19, and three healthy controls. Single-cell libraries were generated using the 10x Genomics Chromium 3' protocol, producing unfragmented cDNA. Libraries were sequenced on the Oxford Nanopore Technologies PromethION platform. Basecalling was performed with Guppy (v1.6), generating a single FASTQ file per sample.

  Dataset EGAD50000001836

• Elucidation of the association between viruses and autoimmune diseases and COVID-19

  We determined the presence of endogenous human herpesvirus 6 (eHHV-6) and calculated anellovirus load from whole-genome sequencing data of 1,164 patients with COVID-19.

  Study JGAS000739

• Transcriptional_reprogramming_from_innate_immune_functions_to_a_pro_thrombotic_signature_upon_SARS_CoV_2_sensing_by_monocytes_in_COVID_19

  Alterations in the myeloid immune compartment have been observed in COVID-19, but the specific mechanisms underlying these impairments are not completely understood. Here we examined the functionality of classical CD14+ monocytes as a main myeloid cell component in well-defined cohorts of patients with mild and moderate COVID-19 during the acute phase of infection and compared them to that of healthy individuals. We found that ex vivo isolated CD14+ monocytes from mild and moderate COVID-19 patients display specific expression patterns of costimulatory and inhibitory receptors that clearly distinguish them from healthy monocytes, as well as an altered metabolic profile. In addition, decreased NFB activation in COVID-19 monocytes ex vivo is accompanied by an intact type I IFN antiviral response. Secondary pathogen sensing ex vivo led to a state of functional unresponsiveness characterized by a defect in pro-inflammatory cytokine expression, NFB-driven cytokine responses and defective type I IFN response in moderate COVID-19 monocytes, together with defects in the metabolic reprogramming that innate immune cells usually undergo upon pathogen sensing. Transcriptionally and functionally, COVID-19 monocytes switched their gene expression signature from canonical innate immune functions to a pro-thrombotic phenotype characterized by enrichment of pathways involved in hemostasis, immunothrombosis, platelet aggregation and other accessory pathways to platelet activation, accumulation and clot formation, including extracellular matrix reorganization, integrin cell surface interactions and signaling by PDGF. These results provide a potential mechanism by which innate immune dysfunction in COVID-19 may contribute to disease pathology

  Study EGAS00001006788

• COVID-19 PBMC single-cell transcriptomics, multiplexed

  COVID-19 PBMC single-cell transcriptomics, multiplexed

  Dataset EGAD50000000188

• Transcriptome changes in circulating immune cells of critical COVID-19 patients predict a specific metabolic and epigenetic imprint

  The progression to severe COVID-19 arises predominantly from a dysregulated host immune response, although the underlying regulatory mechanisms still remain partially elusive. This limits a prompt prediction of disease progression and restrains our understanding of “long COVID”. Here, we analyzed the transcriptomes of peripheral blood mononuclear cells collected from COVID-19 patients experiencing different degrees of the disease and control patients. In critical COVID-19 patients, we found an altered regulatory network involving microRNAs, long non-coding RNAs, and coding genes that control mRNA translation-related genes, epigenetics, and metabolism. We also observed an upregulation of tRNA aminoacylation genes and increased expression of coding genes enriched for the cognate amino acids. Collectively, our findings indicate a broad perturbation of the gene expression landscape that characterizes the aberrant host immune response in critical COVID-19 patients and is potentially coordinated by alterations in microRNA expression and tRNA metabolism.

  Study EGAS50000000965