Transcriptional Profiling of Leukocytes in Critically Ill COVID19 Patients
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ABSTRACT:
PROVIDER: PRJNA648120 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR12313439.fastq.gz | Fastqsanger.gz | |||
| SRR12313440.fastq.gz | Fastqsanger.gz | |||
| SRR12313441.fastq.gz | Fastqsanger.gz | |||
| SRR12313442.fastq.gz | Fastqsanger.gz | |||
| SRR12313443.fastq.gz | Fastqsanger.gz |
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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.
2020-10-01 | GSE154998 | GEO
Project description:Genome-wide gene expression profiling of whole blood leukocytes in critically ill patients with sepsis or non-infectious disease has been used extensively in search of diagnostic biomarkers, as well as prognostic signatures reflecting diseases severity and outcome. Through technological advances in genomics it has become clear that transcription is not limited to protein-coding regions of the genome. Here, we describe a comprehensive analysis of RNA expression in blood leukocytes of critically ill patients with sepsis, a non-infectious condition and healthy subjects
2021-01-11 | GSE134347 | GEO
Project description:Genome-wide gene expression profiling of whole blood leukocytes in critically ill patients with sepsis or non-infectious disease has been used extensively in search of diagnostic biomarkers, as well as prognostic signatures reflecting diseases severity and outcome. Through technological advances in genomics it has become clear that transcription is not limited to protein-coding regions of the genome. Here, we describe a comprehensive analysis of small non-coding RNA expression in blood leukocytes of critically ill patients with sepsis, a non-infectious condition, healthy subjects and experimental human endotoxemia
2021-01-11 | GSE134358 | GEO
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.
2022-06-22 | GSE182152 | GEO
Project description:The host response in critically ill patients with sepsis, septic shock remains poorly defined. Considerable research has been conducted to accurately distinguish patients with sepsis from those with non-infectious causes of disease. Technological innovations have positioned systems biology at the forefront of biomarker discovery. Analysis of the whole-blood leukocyte transcriptome enables the assessment of thousands of molecular signals beyond simply measuring several proteins in plasma, which for use as biomarkers is important since combinations of biomarkers likely provide more diagnostic accuracy than the measurement of single ones or a few. Evidence suggests that genome-wide transcriptional profiling of blood leukocytes can assist in differentiating between infection and non-infectious causes of severe disease. Of importance, RNA biomarkers have the potential advantage that they can be measured reliably in rapid quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)-based point of care tests. PAXgene blood RNA was isolated at intensive-care unit (ICU) admission and throughout ICU length-of-stay. Through the use of genome-wide microarrays we aimed to identify molecular features that enbale the adequate discrimination of infectious and non-infectious sources of critical illness. Moreover, biological pathway analysis was used to tease out the most relevant biological units in sepsis and septic shock.
2015-07-06 | E-GEOD-65682 | biostudies-arrayexpress
Project description:The host response in critically ill patients with sepsis, septic shock remains poorly defined. Considerable research has been conducted to accurately distinguish patients with sepsis from those with non-infectious causes of disease. Technological innovations have positioned systems biology at the forefront of biomarker discovery. Analysis of the whole-blood leukocyte transcriptome enables the assessment of thousands of molecular signals beyond simply measuring several proteins in plasma, which for use as biomarkers is important since combinations of biomarkers likely provide more diagnostic accuracy than the measurement of single ones or a few. Evidence suggests that genome-wide transcriptional profiling of blood leukocytes can assist in differentiating between infection and non-infectious causes of severe disease. Of importance, RNA biomarkers have the potential advantage that they can be measured reliably in rapid quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)-based point of care tests.
2015-07-06 | GSE65682 | GEO
Project description:BackgroundCOVID19 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 patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (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. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and differentially expressed genes as well as significantly enriched gene sets were identified.ResultsWe enrolled seven COVID19 + (PCR positive, 2 SARS-CoV-2 genes) and seven age- and sex-matched COVID19- (PCR negative) control ICU patients. 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. The mortality rate for this cohort of COVID19 + ICU patients was 29%. As indicated by both single-gene based and gene set (GSEA) approaches, the major disease-specific transcriptional responses of leukocytes in critically ill COVID19 + ICU patients were: (i) a robust overrepresentation of interferon-related gene expression; (ii) a marked decrease in the transcriptional level of genes contributing to general protein synthesis and bioenergy metabolism; and (iii) the dysregulated expression of genes associated with coagulation, platelet function, complement activation, and tumour necrosis factor/interleukin 6 signalling.ConclusionsOur findings demonstrate that critically ill COVID19 + patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19- patients, providing guidance for future targeted studies exploring novel prognostic and therapeutic aspects of COVID19.
| S-EPMC7729690 | biostudies-literature
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.
2012-12-28 | E-GEOD-24956 | biostudies-arrayexpress
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.
2018-08-22 | GSE118657 | GEO
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.
2011-06-30 | GSE20346 | GEO