Post by Nadica (She/Her) on Jun 23, 2024 0:04:41 GMT
Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment - Published Sept 17, 2020
Highlights
• SARS-CoV-2 infection induces profound alterations of the myeloid compartment
• Mild COVID-19 is marked by inflammatory HLA-DRhiCD11chi CD14+ monocytes
• Dysfunctional HLA-DRloCD163hi and HLA-DRloS100Ahi CD14+ monocytes in severe COVID-19
• Emergency myelopoiesis with immature and dysfunctional neutrophils in severe COVID-19
Summary
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.
Graphical Abstract
Highlights
• SARS-CoV-2 infection induces profound alterations of the myeloid compartment
• Mild COVID-19 is marked by inflammatory HLA-DRhiCD11chi CD14+ monocytes
• Dysfunctional HLA-DRloCD163hi and HLA-DRloS100Ahi CD14+ monocytes in severe COVID-19
• Emergency myelopoiesis with immature and dysfunctional neutrophils in severe COVID-19
Summary
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.
Graphical Abstract