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Cell ; 182(6): 1419-1440.e23, 2020 09 17.
Article in English | MEDLINE | ID: covidwho-694631

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DRhiCD11chi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DRlo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.


Subject(s)
Coronavirus Infections/immunology , Myeloid Cells/immunology , Myelopoiesis , Pneumonia, Viral/immunology , Adult , Aged , CD11 Antigens/genetics , CD11 Antigens/metabolism , COVID-19 , Cells, Cultured , Coronavirus Infections/blood , Coronavirus Infections/pathology , Female , HLA-DR Antigens/genetics , HLA-DR Antigens/metabolism , Humans , Male , Middle Aged , Myeloid Cells/cytology , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Proteome/genetics , Proteome/metabolism , Proteomics , Single-Cell Analysis
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