Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19

ABSTRACT 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 profili...

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Vydané v:bioRxiv
Hlavní autori: Wilk, Aaron J, Lee, Madeline J, Wei, Bei, Parks, Benjamin, Pi, Ruoxi, Martínez-Colón, Giovanny J, Ranganath, Thanmayi, Zhao, Nancy Q, Taylor, Shalina, Becker, Winston, Stanford Covid-19 Biobank, Jimenez-Morales, David, Blomkalns, Andra L, Ruth O’hara, Ashley, Euan A, Nadeau, Kari C, Yang, Samuel, Holmes, Susan, Rabinovitch, Marlene, Rogers, Angela J, Greenleaf, William J, Blish, Catherine A
Médium: Paper
Jazyk:English
Vydavateľské údaje: Cold Spring Harbor Cold Spring Harbor Laboratory Press 18.12.2020
Cold Spring Harbor Laboratory
Vydanie:1.1
Predmet:
Coronaviruses
COVID-19
Immune response
Immunology
Inflammation
Innate immunity
Leukocytes (neutrophilic)
Monocytes
Myelopoiesis
Phenotypes
Proteomics
Severe acute respiratory syndrome coronavirus 2
ISSN:2692-8205, 2692-8205
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Shrnutí:ABSTRACT 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 a prominent neutrophil hyperactivation signature and monocytes with anti-inflammatory features. 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. One Sentence Summary Single-cell profiling demonstrates multifarious dysregulation of innate immune phenotype associated with COVID-19 severity. Competing Interest Statement C.A.B. is a member of the Scientific Advisory Board of Catamaran Bio. W.J.G. is a consultant for 10x Genomics and Guardant Health, Co-founder of Protillion Biosciences, and is named on patents describing ATAC-seq.
Bibliografia:SourceType-Working Papers-1
ObjectType-Working Paper/Pre-Print-1
content type line 50
Competing Interest Statement: C.A.B. is a member of the Scientific Advisory Board of Catamaran Bio. W.J.G. is a consultant for 10x Genomics and Guardant Health, Co-founder of Protillion Biosciences, and is named on patents describing ATAC-seq.
ISSN:2692-8205
2692-8205
DOI:10.1101/2020.12.18.423363