Project description:Individuals infected with SARS-CoV-2 vary greatly in their symptomatology and disease progression, likely as a result of numerous genetic, biological and environmental factors and their complex interactions. Meanwhile, the potential roles of microRNAs (miRNAs) in SARS-CoV-2 infection have not been fully described. MiRNAs have emerged as key post-transcriptional regulators of gene expression, and their dysregulation can be indicative of aberrant immune function. In this study, we characterize the potential roles of mIRNAs in early COVID-19 disease progression. We studied a diverse cohort of 259 patients admitted to hospitals in Abu Dhabi, United Arab Emirates to understand the clinical and biological factors associated with ICU admission during COVID-19 treatment, integrating electronic health records (EHR), global miRNA and RNA expression, and genotyping data. Using EHR, we identified 26 factors correlated with ICU admission, including 8 blood phenotypes such as neutrophil-to-lymphocyte ratio, Interleukin-6, and C-reactive protein levels. Using genome-wide miRNA expression data for a subset of 96 individuals from Southeast Asia and the Middle East and North Africa, we identified 27 miRNAs significantly associated with ICU admission (p < 0.01), and 97 miRNAs associated with at least one of the 8 blood phenotypes. [cross-cor] Integrating expression data for 632 miRNAs and genotyping data for ~260,000 SNPs, we identified 168 significant cis-expression quantitative trait loci (cis-eQTLs), of which 59 were associated with either ICU admission or one of the 8 blood phentoypes. Overall, our findings characterize the miRNA architecture of blood phenotypes during the early stages of COVID-19 infection, identify miRNAs associated with ICU admission and therefore COVID-19 disease severity, and suggest a potential genetic control of miRNA expression during early COVID-19 disease progression.
Project description:Individuals infected with SARS-CoV-2 vary greatly in their symptomatology and disease progression, likely as a result of numerous genetic, biological and environmental factors and their complex interactions. Meanwhile, the potential roles of microRNAs (miRNAs) in SARS-CoV-2 infection have not been fully described. MiRNAs have emerged as key post-transcriptional regulators of gene expression, and their dysregulation can be indicative of aberrant immune function. In this study, we characterize the potential roles of mIRNAs in early COVID-19 disease progression. We studied a diverse cohort of 259 patients admitted to hospitals in Abu Dhabi, United Arab Emirates to understand the clinical and biological factors associated with ICU admission during COVID-19 treatment, integrating electronic health records (EHR), global miRNA and RNA expression, and genotyping data. Using EHR, we identified 26 factors correlated with ICU admission, including 8 blood phenotypes such as neutrophil-to-lymphocyte ratio, Interleukin-6, and C-reactive protein levels. Using genome-wide miRNA expression data for a subset of 96 individuals from Southeast Asia and the Middle East and North Africa, we identified 27 miRNAs significantly associated with ICU admission (p < 0.01), and 97 miRNAs associated with at least one of the 8 blood phenotypes. [cross-cor] Integrating expression data for 632 miRNAs and genotyping data for ~260,000 SNPs, we identified 168 significant cis-expression quantitative trait loci (cis-eQTLs), of which 59 were associated with either ICU admission or one of the 8 blood phentoypes. Overall, our findings characterize the miRNA architecture of blood phenotypes during the early stages of COVID-19 infection, identify miRNAs associated with ICU admission and therefore COVID-19 disease severity, and suggest a potential genetic control of miRNA expression during early COVID-19 disease progression.
Project description:We isolated neutrophils from 11 healthy controls, 12 COIVD-19 patients in ICU and 12 COVID-19 patients from ward and submitted the isolated RNA for RNA sequencing. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cohorts. .
Project description:In this prospective observational cohort study, we found transcriptional evidence that persistent immune dysfunction was associated with 28-day mortality in both COVID-19 and non-COVID-19 septic patients. COVID-19 patients had an early antiviral response but became indistinguishable on a gene expression level from non-COVID-19 sepsis patients a week later. Early treatment of COVID-19 and non-COVID-19 sepsis ICU patients should focus on pathogen control, but both patient groups also require novel immunomodulatory treatments, particularly later during ICU hospitalization, independent of admission diagnosis. Some T1 samples were uploaded in GSE185263 and were not re-uploaded in this series.
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).
Project description:The purpose of this study was to identify miRNAs that were dysregulated after the onset of COVID-19 and thus potentially be used for risk stratification (i.e., mortality). Therefore, we conducted a multi-center, retrospective longitudinal cohort study enrolling 142 patients with laboratory-confirmed SARS-CoV-2 infection who presented to two Canadian hospitals from May 2020 – December 2020 along with a cohort of 27 SARS-CoV-2 patients with mild upper respiratory tract symptoms and 69 SARS-CoV-2-negative patients from the ICU. Blood was biobanked from SARS-CoV-2 positive patients in the emergency department (mild), ward (moderate) or intensive care unit (severe). Assessment of miRNA expression and co-regulatory network generation revealed significant transcriptome dyregulation in pateints with severe COVID-19 that was largely different from SARS-CoV-2 negative patients in the ICU.
Project description:Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia was associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). In longitudinal comparisons, COVID-19 ICU patients had a distinct proteomic trajectory associated with RNAemia and mortality. Among COVID-19-enriched proteins, galectin-3 binding protein (LGALS3BP) and proteins of the complement system were identified as interaction partners of SARS-CoV-2 spike glycoprotein. Finally, machine learning identified ‘Age, RNAemia’ and ‘Age, pentraxin-3 (PTX3)’ as the best binary signatures associated with 28-day ICU mortality.
Project description:Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia was associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). In longitudinal comparisons, COVID-19 ICU patients had a distinct proteomic trajectory associated with RNAemia and mortality. Among COVID-19-enriched proteins, galectin-3 binding protein (LGALS3BP) and proteins of the complement system were identified as interaction partners of SARS-CoV-2 spike glycoprotein. Finally, machine learning identified ‘Age, RNAemia’ and ‘Age, pentraxin-3 (PTX3)’ as the best binary signatures associated with 28-day ICU mortality.
Project description:The acute respiratory distress syndrome (ARDS) is a common complications of severe COVID-19 and contributes to patient morbidity and mortality. ARDS is a heterogeneous syndrome caused by various insults, and results in acute hypoxemic respiratory failure. Patients with ARDS from COVID-19 may represent a subgroup of ARDS patients with distinct molecular profiles that drive disease outcomes. Here, we hypothesized that longitudinal transcriptomic analysis may identify distinct dynamic pathobiological pathways during COVID-19 ARDS. We identified a patient cohort from an existing ICU biorepository and established three groups for comparison: 1) patients with COVID-19 ARDS that survived hospitalization (COVID survivors, n = 4), 2) patients with COVID-19 ARDS that did not survive hospitalization (COVID non-survivors, n = 5), and 3) patients with ARDS from other causes as a control group (ARDS controls, n = 4). RNA was extracted from peripheral blood mononuclear cells (PBMCs) at 4 time points (Days 1, 3, 7, and 10 following ICU admission) and prepared for RNA sequencing with rRNA depletion and library generation for Illumina. An Illumina NovaSeq X Plus instrument was used to generate 150 base pair paired-end reads, which were aligned to the hg GRCh38.96 reference genome using HiSAT2. Differential expression analysis was performed with DESeq2.
Project description:The pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is required. COVID-19 subjects (n=64) and control subjects (n=19) were enrolled, and blood was drawn within 72 hours of diagnosis. Serum multiplex assay and buffy coat cell mRNA sequencing was performed. Oxidant/free radical (electron paramagnetic resonance (EPR) spectroscopy, nitrite-nitrate assay) and antioxidant (ferrous reducing ability of serum assay and high-performance liquid chromatography) were performed. Multivariate analyses were performed to evaluate potential of indicated parameters to predict clinical outcome. Significantly greater levels of multiple inflammatory and vascular markers were quantified in the subjects admitted to the ICU compared to non-ICU subjects. Gene set enrichment analyses indicated significant enhancement of oxidant related pathways and biochemical assays confirmed a significant increase in free radical production and uric acid reduction in COVID-19 subjects. Multivariate analyses confirmed a positive association between serum levels of VCAM-1, ICAM-1 and a negative association between the abundance of one electron oxidants (detected by ascorbate radical formation) and mortality in COVID subjects while IL-17c and TSLP levels predicted need for intensive care in COVID-19 subjects.