Storm of soluble immune checkpoints associated with disease severity of COVID-19.
Ontology highlight
ABSTRACT:
SUBMITTER: Kong Y
PROVIDER: S-EPMC7475713 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description: Not available
| S-EPMC8521292 | biostudies-literature
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:In this study, we sought to identify circulating microRNA (miRNA) signatures associated with COVID-19 severity and outcome through small RNA-sequencing of serum samples from 89 COVID-19 patients and 45 healthy controls. As results, a set of miRNAs associated with lung disease, vascular damage and inflammation were upregulated in serum of COVID-19 patients vs controls, while miRNAs that inhibit pro-inflammatory cytokines and chemokines, angiogenesis and stress response were downregulated. In addition, patients with severe COVID-19 vs mild or moderate disease had a circulating miRNA signature associated with sepsis, hearth failure, tissue fibrosis, inflammation, and impairment of type I IFN and antiviral responses. A subset of the differentially expressed miRNAs predicted ICU admission, sequelae and mortality in COVID-19 patients. Investigation of the differentially expressed circulating miRNAs in relevant human cell types in vitro showed that some of these miRNAs were modulated directly by SARS-CoV-2 infection or indirectly by type I IFN stimulation.
2022-05-03 | GSE201790 | GEO
Project description:SARS-CoV-2 is an emerging mosquito-borne pathogen with increasing public health significance. To characterize interconnected immune responses to SARS-CoV-2, we here examined transcriptional signatures of CD4 and CD8 T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from three individuals with naturally-acquired SARS-CoV-2 infection. Whole transcriptome analysis demonstrated that all seven immune cells among PBMCs were clustered together with disease severity regardless of cell types. mDCs and pDCs gene signatures distinct disease severity. A distinct phenotype was observed in severe patients with or without plasma viremia, demonstrating a highly impaired induction of Interferon stimulated genes (ISGs) accompanied by imbalanced type I interferon sensing and an excessive inflammatory response. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in seven major immune cells in blood from different disease severe COVID-19 patients.
2022-11-11 | GSE216529 | GEO
Project description:The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T cell response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor Beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to the severity of the disease course. Clustering of highly similar TRB CDR3 amino acid sequences across COVID-19 patients yielded 785 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross-referenced to a publicly accessible dataset that mapped COVID-19 specific TCRs to the SARS-CoV-2 genome. We identified 140 SARS-CoV-2 specific TRB sequences belonging to 119 clusters in our COVID-19 patients. Next, we investigated 92 SARS-CoV-2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS-CoV-2 specific TRB sequences towards the nonstructural proteins (NSPs) of ORF1a/b of the SARS-CoV-2 genome was observed in clusters with critical disease course when compared to COVID-19 clusters with a severe disease course. These data imply that T-lymphocyte reactivity towards peptides from nonstructural proteins of SARS-CoV-2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity.
2021-07-07 | GSE161810 | GEO
Project description:Data suggest that interleukin (IL)-6 blockade could reduce mortality in severe COVID-19, yet IL-6 is only modestly elevated in most patients. Chen et al. describe the role of soluble interleukin-6 receptor (sIL-6R) in IL-6 trans-signaling and how understanding the IL-6:sIL-6R axis might help define and treat COVID-19 cytokine storm syndrome.
| S-EPMC8055165 | biostudies-literature
Project description:Viral strains, age, and host factors including genetics and proteins are associated with variable immune responses against SARS-CoV-2 and disease severity. We hypothesized that unique proteins/pathways are associated with COVID-19 disease severity in Puerto Rican Hispanics. A total of 121 men and women aged 21-80 years-old were recruited in Puerto Rico. Plasma samples were collected from unvaccinated COVID-19 infected subjects during acute disease (n=39) and compared to COVID-19 negative individuals (n=56) during acute disease using proteomics and cytokine expression. Infected individuals were stratified based on symptomatology as follows: mild (n=18), moderate (n=13), and severe (n=8). Quantitative proteomics was performed in plasma samples using Tandem Mass Tag (TMT) labeling. Cytokines in plasma were quantified using a human cytokine array. Proteomics analyses revealed 56 differentially regulated proteins and the top 3 pathways that were predicted to be inhibited in severe patients including LXR/RXR signaling, Production of NO and ROS in macrophages, and Synaptogenesis signaling. Decreased cadherin-13 validated by ELISA, which participates in synaptogenesis, is a novel protein is a novel protein not previously reported in other studies of COVID-19 severity and validated by ELISA. Cytokine analyses showed that TNF⍺ levels decreased with disease severity. This study uncovers potential host predictors of COVID-19 severity and new avenues for treatment in Puerto Rican Hispanics.
2024-06-16 | PXD046103 | Pride
Project description:Dysregulation of the immune system undoubtedly plays an important and, perhaps, determining role in the COVID-19 pathogenesis. While the main treatment of the COVID-19 intoxication is focused on neutralizing the excessive inflammatory response, it is worth considering an equally significant problem of the immunosuppressive conditions including immuno-paralysis, which lead to the secondary infection. Therefore, choosing a treatment strategy for the immune-mediated complications of coronavirus infection, one has to pass between Scylla and Charybdis, so that, in the fight against the "cytokine storm," it is vital not to miss the point of the immune silence that turns into immuno-paralysis.
| S-EPMC7465708 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-07-19 | GSE236017 | GEO
Project description:Certain serum proteins, including CRP and D-dimer, have prognostic value in patients with SARS-CoV-2 infection. Nonetheless, these factors are non-specific, and provide limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations which drive the pathogenesis of severe COVID-19. To identify novel cellular phenotypes associated with disease progression, we here describe a comprehensive, unbiased analysis of the total and plasma membrane proteomes of PBMCs from a cohort of 40 unvaccinated individuals with SARS-CoV-2 infection, spanning the whole spectrum of disease severity. Combined with RNA-seq and flow cytometry data from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing cumulative immune cell dysregulation in progressive disease. In particular, the cell surface proteins CEACAMs1, 6 and 8, CD177, CD63 and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3+CD4+CD177+ and CD16+CEACAM1/6/8+ mononuclear cells. Utilisation of these markers may facilitate real-time patient assessment by flow cytometry, and identify immune cell populations that could be targeted to ameliorate immunopathology.
2023-03-29 | PXD040703 | Pride