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.
【저자키워드】 COVID-19, Neutrophils, Monocytes, SARS-CoV-2, immune profiling, scRNA-seq, mass cytometry, dysfunctional neutrophils, emergency myelopoiesis, 【초록키워드】 Coronavirus disease 2019, Pathogenesis, Respiratory failure, severe COVID-19, SARS-COV-2 infection, neutrophil, respiratory tract infection, protective immunity, Patient, Mild, moderate, mechanism, Evidence, Immune cell, severe disease, systemic immune response, mononuclear cell, Activation, alteration, neutrophil count, precursors, dysregulated immune response, Single-cell RNA-sequencing, interferon-stimulated gene, myeloid cell, inflammatory monocyte, Occurrence, form, elevated, provide, determine, changes in, individuals, reveal, subset, single-cell proteomics, 【제목키워드】 myeloid, compartment,