Project description:The PREVAIL study was a Phase II/III randomized controlled trial examining the use of lactoferrin to prevent nosocomial infections in critically ill patients undergoing mechanical ventilation. Gene expression data was generated from a consecutive subset of patients at the lead study site. We used the Affymetrix PrimeView array to generate expression data at various time points during the ICU stay.
Project description:To determine whether differential expression of cellular microRNAs plays a role in the host response to Influenza A (H1N1) infection, we have employed the Agilent miRNA microarray (V3) as a discovery platform to identify microRNAs between the critically ill Patients with Influenza A (H1N1) and the healthy controls. Five critically ill patients with a diagnosis of 2009 Inflluenza A (H1N1) and three healthy controls were included in the study. The Peripheral Blood Mononuclear Cells (PBMCs) were isolated and total RNA was extracted respectively.
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.
Project description:Longitudinal Gene expression profiling of whole blood from critically ill influenza and bacterial pneumonia patients. In addition before vs 7 days post influenza vaccination volunteer samples are assayed.
Project description:Sepsis is a frequent complication in critically ill patients and highly heterogeneous that is associated with high morbidity and mortality rates, especially in the elderly population. Utilizing RNA-Sequencing (RNA-Seq) to analysis biological pathways is widely used in clinical and molecular genetics studies, but in elderly patients with sepsis are still lacking. Hence, we aim to investigate the mortality-relevant biological features and transcriptomic features in elderly patients who were admitted to intensive care unit (ICU) for sepsis.
Project description:Longitudinal Gene expression profiling of whole blood from critically ill influenza and bacterial pneumonia patients. In addition before vs 7 days post influenza vaccination volunteer samples are assayed. 3 groups of samples. First is bacterial pneumonia patients with 6 subjects sampled for up to 5 days. Second group is severe influenza infection with 4 subjects sampled for up to 5 days. Third group is influenza vaccination with 18 subjects sampled before and 7 days post vaccination.
Project description:It is known that about 60% of all human messenger RNAs (mRNAs) regulated by microRNAs, the role of mRNAs and microRNAs in the critically ill patients with Coronavirus Infection 2019 (COVID-19) is unknown. To evaluate mRNA and microRNA in whole blood of the critically ill patients with COVID-19 and to elucidate the pathogenesis of COVID-19 including the subsequent proteins profile following mRNA and microRNA integration analysis. RNA was extracted from the whole blood in 5 healthy controls and 10 critically ill patients with COVID-19 at the time of admission. mRNA and miRNA were measured by RNA sequence, and gene expression variation and pathway analysis were performed. As the IFNs proteins profile cohort, IFN-α2, IFN-β, IFN-γ, IL-27 and IFN-λ1 were measured on the day of admission (day 1, 181 critical and 22 non-critical patients) and day 6-8 (168 critical patients) in COVID19 patients and 19 healthy controls. Compared to healthy controls, 3488 mRNA and 31 miRNA genes were identified in the differentially expressed genes in the critically ill patients with COVID-19 (p-value<0.05, Log 2 fold change> |2|). In the canonical pathway analysis using Ingenuity Pathway Analysis (IPA), interferon signaling pathway was the most activated. In plasma interferon levels, IFN-β was elevated along with the increase of severity compared to healthy controls. IFN-λ1 was elevated in moderate disease compared to healthy controls, and conversely, IFN-λ1 was lower in severe disease than in moderate disease. Integration of mRNA and microRNA analysis showed activated interferon signaling. The plasma interferon proteins profile revealed that IFN-β (type I) and IFN-λ1 (type III) played an important role in the disease progression of COVID-19.