Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19
| Autor: | Marlene Rabinovitch, Angela J. Rogers, Madeline J. Lee, Nancy Q. Zhao, Samuel Yang, Catherine A. Blish, Bei Wei, Benjamin Parks, Ruoxi Pi, Ruth O'Hara, Winston R. Becker, Euan A. Ashley, Kari C. Nadeau, Giovanny J Martínez-Colón, Susan Holmes, Shalina Taylor, Aaron J. Wilk, Thanmayi Ranganath, David Jimenez-Morales, William J. Greenleaf, Andra L. Blomkalns, Stanford Covid Biobank |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Proteomics 0301 basic medicine Neutrophils medicine.medical_treatment Innate Immunity and Inflammation Immunology macromolecular substances Disease Severity of Illness Index Monocytes Article Virus Epigenesis Genetic Infectious Disease and Host Defense Transcriptome 03 medical and health sciences 0302 clinical medicine Immune system Immunity medicine Humans Immunology and Allergy Aged Epigenomics Innate immune system business.industry NF-kappa B COVID-19 Middle Aged Phenotype Immunity Innate Hematopoiesis Killer Cells Natural 030104 developmental biology Cytokine Case-Control Studies Cytokines Female Myelopoiesis Single-Cell Analysis business 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20210582 |
| Popis: | Single-cell profiling demonstrates multifarious dysregulation of innate immune phenotype associated with COVID-19 severity. Severe COVID-19 is associated with hyperactivation of neutrophils and NK cells, while monocytes take on tolerogenic phenotypes. Meanwhile, mild COVID-19 is associated with limited, or rapidly resolved, immune perturbation. Our understanding of protective versus pathological 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 revealed widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, including prominent hyperactivation signatures in neutrophils and NK cells. We also identified chromatin accessibility changes at NF-κB binding sites within cytokine gene loci as a potential mechanism for the striking lack of pro-inflammatory cytokine production observed in monocytes in severe and fatal COVID-19. We further demonstrated 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. Graphical Abstract |
| Databáze: | OpenAIRE |
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