COVID-19 severity, miR-21 targets, and common human genetic variation. Letter regarding the article 'Circulating cardiovascular microRNAs in critically ill COVID-19 patients'.
Ontology highlight
ABSTRACT:
SUBMITTER: Dingsdag SA
PROVIDER: S-EPMC8427028 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
COVID-19 severity, miR-21 targets, and common human genetic variation. Letter regarding the article 'Circulating cardiovascular microRNAs in critically ill COVID-19 patients'.
Dingsdag Simon A SA Clay Oliver K OK Quintero Gustavo A GA
European journal of heart failure 20210809 11
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-02-28 | GSE197259 | GEO
Project description:AimsCoronavirus disease 2019 (COVID-19) is a still growing pandemic, causing many deaths and socio-economic damage. Elevated expression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry receptor angiotensin-converting enzyme 2 on cardiac cells of patients with heart diseases may be related to cardiovascular burden. We have thus analysed cardiovascular and inflammatory microRNAs (miRs), sensitive markers of cardiovascular damage, in critically ill, ventilated patients with COVID-19 or influenza-associated acute respiratory distress syndrome (Influenza-ARDS) admitted to the intensive care unit and healthy controls.Methods and resultsCirculating miRs (miR-21, miR-126, miR-155, miR-208a, and miR-499) were analysed in a discovery cohort consisting of patients with mechanically-ventilated COVID-19 (n = 18) and healthy controls (n = 15). A validation study was performed in an independent cohort of mechanically-ventilated COVID-19 patients (n = 20), Influenza-ARDS patients (n = 13) and healthy controls (n = 32). In both cohorts, RNA was isolated from serum and cardiovascular disease/inflammatory-relevant miR concentrations were measured by miR-specific TaqMan PCR analyses. In both the discovery and the validation cohort, serum concentration of miR-21, miR-155, miR-208a and miR-499 were significantly increased in COVID-19 patients compared to healthy controls. Calculating the area under the curve using receiver operating characteristic analysis miR-155, miR-208a and miR-499 showed a clear distinction between COVID-19 and Influenza-ARDS patients.ConclusionIn this exploratory study, inflammation and cardiac myocyte-specific miRs were upregulated in critically ill COVID-19 patients. Importantly, miR profiles were able to differentiate between severely ill, mechanically-ventilated Influenza-ARDS and COVID-19 patients, indicating a rather specific response and cardiac involvement of COVID-19.
| S-EPMC8014268 | biostudies-literature
Project description:Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit, to identify two clusters that, in spite of no major clinical differences, have different gene expression profiles that reveal different underlying pathogenetic mechanisms and ultimately have different ICU outcome. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding a similar result. These results illustrate the potential of transcriptomic profiles to identify patient endotypes and point to relevant pathogenetic mechanisms in COVID-19.
2023-04-29 | GSE206264 | GEO
Project description:Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit, to identify two clusters that, in spite of no major clinical differences, have different gene expression profiles that reveal different underlying pathogenetic mechanisms and ultimately have different ICU outcome. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding a similar result. These results illustrate the potential of transcriptomic profiles to identify patient endotypes and point to relevant pathogenetic mechanisms in COVID-19.
2022-02-28 | GSE197258 | GEO
Project description:Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit, to identify two clusters that, in spite of no major clinical differences, have different gene expression profiles that reveal different underlying pathogenetic mechanisms and ultimately have different ICU outcome. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding a similar result. These results illustrate the potential of transcriptomic profiles to identify patient endotypes and point to relevant pathogenetic mechanisms in COVID-19.
2022-02-28 | GSE197204 | GEO
Project description:Total plasma IgA glycosylation was compared between healthy volunteers and volunteers suffering fromo infections with either the influenza A virus or the severe acute respiratory syndrome corona virus 2. Data from functional assays of the same plasma samples, such as neutrophil extracellular trap formation is also available.
2024-10-22 | PXD057019 | Pride
Project description:Here, we examined the dynamics of the gut and respiratory microbiomes in severe COVID-19 patients in need of mechanical ventilation in the intensive care unit (ICU). We recruited 85 critically ill patients (53 with COVID-19 and 32 without COVID-19) and 17 healthy controls (HCs) and monitored them for up to 4 weeks. We analyzed the bacterial and fungal taxonomic profiles and loads of 232 gut and respiratory samples and we measured the blood levels of Interleukin 6, IgG, and IgM in COVID-19 patients. Upon ICU admission, the bacterial composition and load in the gut and respiratory samples were altered in critically ill patients compared with HCs. During their ICU stay, the patients experienced increased bacterial and fungal loads, drastic decreased bacterial richness, and progressive changes in bacterial and fungal taxonomic profiles. In the gut samples, six bacterial taxa could discriminate ICU-COV(+) from ICU-COV(-) cases upon ICU admission and the bacterial taxa were associated according to age, PaO2/FiO2, and CRP levels. In the respiratory samples of the ICU-COV(+) patients, bacterial signatures including Pseudomonas and Streptococcus were found to be correlated with the length of ICU stay. Our findings demonstrated that the gut and respiratory microbiome dysbiosis and bacterial signatures associated with critical illness emerged as biomarkers of COVID-19 severity and could be a potential predictor of ICU length of stay. We propose using a high-throughput sequencing approach as an alternative to traditional isolation techniques to monitor ICU patient infection.
| S-EPMC9779860 | biostudies-literature
Project description:Single-cell RNA-sequencing reveals a shift from focused IFN alpha-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 – a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
2021-06-18 | GSE178404 | GEO
Project description:Background: COVID-19 has revealed novel pathological mechanisms, particularly hypercoagulability leading to increased thrombotic risk in critically ill patients. This study investigates transcriptional signatures associated with thrombosis development in COVID-19 intensive care unit (ICU) patients and evaluates their predictive potential. Methods: We performed whole blood transcriptional profiling of 57 mechanically ventilated COVID-19 patients, comparing those with thrombotic complications (TC, n=36) to those without (non-TC, n=21) using differential gene expression and machine learning approaches. Results: TC patients showed greater transcriptome disruption and 283 differentially expressed genes compared to non-TC patients. Key features included enhanced neutrophil activation, inflammatory responses, and monocyte activation alongside suppressed lymphocyte function. An OPLS-DA model achieved excellent classification performance (AUC=0.961, 95% CI: 0.905-0.997). The maltase-glucoamylase gene (MGAM) was the top discriminatory biomarker outperforming traditional clinical markers like D-dimer and C-reactive protein (AUC=0.94). Conclusions: Thrombotic complications in critically ill COVID-19 patients are characterized by distinct transcriptional signatures reflecting heightened neutrophil activation and inflammatory dysregulation. MGAM represents a novel potential biomarker that outperforms traditional clinical markers for identifying patients at high thrombotic risk, offering new opportunities for personalized risk stratification and management in severe COVID-19.
2025-06-18 | GSE300129 | GEO
Project description:Background: Outcomes in patients with severe SARS-CoV-2 infection (COVID-19) are conditioned by viral control and regulation of inflammation. Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. Methods: Patients admitted to an intensive care unit (ICU) with documented COVID-19 were prospectively included and IFIH1 rs1990760 genotypes determined. Peripheral blood gene expression, cell populations and immune mediators were measured during the first day after ICU admission before steroid therapy. Peripheral blood mononuclear cells from healthy volunteers were exposed ex-vivo to an MDA5 agonist and dexamethasone, and changes in gene expression assessed. ICU discharge and hospital death were modelled using rs1990760 variants and dexamethasone therapy as factors. Findings: 237 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a decrease in expression of inflammation-related pathways, an anti-inflammatory cell profile and a decrease in pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist ex-vivo showed an increase in FOXO3 and IL6 when dexamethasone was added. All patients with the TT variant not treated with steroids (n=14) survived their ICU stay (HR 2.49 95% confidence interval 1.29 – 4.79). Dexamethasone therapy in this subgroup (N=50) delayed ICU discharge and increased hospital mortality (HR 2.19, 95% confidence interval 1.01 – 4.87) and serum IL-6 concentrations. Interpretation: COVID-19 ICU patients with the IFIH1 rs1990760 TT variant show an ameliorated inflammatory response that results in better outcomes than CC/CT variants. Dexamethasone can reverse this anti-inflammatory phenotype, worsening the outcome. Funding: Instituto de Salud Carlos III.
2021-07-03 | GSE168400 | GEO