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Dynamic Activity in cis-Regulatory Elements of Leukocytes Identifies Transcription Factor Activation and Stratifies COVID-19 Severity in ICU Patients

ABSTRACT: Dynamic Activity in cis-Regulatory Elements of Leukocytes Identifies Transcription Factor Activation and Stratifies COVID-19 Severity in ICU Patients

PROVIDER: PRJNA912692 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22752300_1.fastq.gz	Fastqsanger.gz
	SRR22752300_2.fastq.gz	Fastqsanger.gz
	SRR22752500.fastq.gz	Fastqsanger.gz
	SRR22752600.fastq.gz	Fastqsanger.gz
	SRR22752700.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.

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Dynamic Activity in cis-Regulatory Elements of Leukocytes Identifies Transcription Factor Activation and Stratifies COVID-19 Severity in ICU Patients

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