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Series GSE174072 Query DataSets for GSE174072
Status Public on May 08, 2021
Title Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Our understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including prominent hyperactivation signatures in neutrophils and monocytes with anti-inflammatory features. We also leverage epigenomic analysis to identify loss of accessibility at NF-kB binding sites within pro-inflammatory cytokine gene loci as a potential mechanism for the striking lack of cytokine production observed in monocytes in severe and fatal COVID-19. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.
 
Overall design Single-cell RNA and single-cell ATAC sequencing of peripheral blood mononuclear cells (PBMCs) from 8 samples from COVID-19 patients and 6 healthy controls.
 
Contributor(s) Wilk AJ, Parks B, Greenleaf WJ, Blish CA
Citation(s) 34128959, 38578283
Submission date May 07, 2021
Last update date Jun 06, 2024
Contact name Aaron James Wilk
E-mail(s) awilk@stanford.edu
Organization name Stanford University
Street address 300 Pasteur Dr Bldg S131, Grant
City Stanford
State/province California
ZIP/Postal code 94305
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (70)
GSM5285683 PBMCs from COVID-19 patient 562
GSM5285684 PBMCs from COVID-19 patient 563
GSM5285685 PBMCs from COVID-19 patient 564_A
Relations
BioProject PRJNA728100
SRA SRP318911

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Supplementary file Size Download File type/resource
GSE174072_RAW.tar 55.1 Gb (http)(custom) TAR (of RDS, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
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