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:Circulatory shock affects approximately one-third of all patients in the Intensive Care Unit (ICU) and it is correlated with high mortality. Septic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock, with a different etiology. We aimed to assess in whole blood of CS and SS patients the transcriptomic alterations occurring over one week after ICU admission in order to identify the pathways that are modulated in circulatory shock irrespective of the etiology. We used Gene Set Enrichment Analysis (GSEA) to identify the biological processes and transcriptional regulators significantly enriched in both types of shock.
Project description:Interventions: case group:None;control group:None
Primary outcome(s): Admission to ICU after surgery
Study Design: Case-Control study
Project description:Objective: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill ICU patients positive for COVID19 vs. those negative for COVID19 to better understand the COVID19 associated host response. Design: Transcriptome profiling of buffy coat cells via ribonucleic acid sequencing (RNAseq) at the time of admission to the ICU. Setting: Tertiary care ICU and academic laboratory. Subjects: All patients admitted to the ICU suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Interventions: None. Measurement and Main Results: Age- and sex-matched ICU patients that were either COVID19+ (PCR positive, 2 genes) or COVID19- (PCR negative) were enrolled. Cohorts were well-balanced with the exception that COVID19- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19+ patients were more likely to suffer bilateral pneumonia compared to COVID19- patients. Further, the mortality rate for this cohort of COVID19+ ICU patients was 29%. Transcriptional analysis revealed that when compared to COVID19- patients, the altered transcriptional responses of leukocytes in critically ill COVID19+ ICU patients appeared to be associated with multiple interrelated outcomes, including but not limited to robust interferon (IFN)-associated transcriptional responses, a marked decrease in the transcriptional activity of genes contributing to protein synthesis and the dysregulated expression of genes that contribute to coagulation, platelet activation, Toll-like receptor activation, neurotrophin signaling, and protein SUMOylation/ubiquitination. Conclusions: COVID19+ patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19- patients. Identification of this profile provides guidance for future targeted studies exploring novel prognostic/therapeutic aspects of COVID19.