A single-cell atlas of the peripheral immune response in patients with severe COVID-19 was analyzed using single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven hospitalized patients with COVID-19 and six healthy controls. The study identified significant changes in immune cell composition and phenotype in patients with severe COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation, and a developing neutrophil population. These neutrophils showed characteristics of plasmablasts and were associated with severe disease. The study also found that peripheral monocytes and lymphocytes did not express substantial amounts of pro-inflammatory cytokines, suggesting that they may not be the primary contributors to the cytokine storm observed in severe COVID-19. Additionally, the study identified a depletion of several innate immune cell subsets in patients with COVID-19, including γδ T cells, plasmacytoid dendritic cells, conventional dendritic cells, CD16+ monocytes, and NK cells. The study also found that CD56dim NK cells were primarily depleted in ventilator-dependent patients, while CD56bright NK cells were significantly depleted in all patients with COVID-19. The study also identified a cluster of proliferative lymphocytes that appeared to be increased in most patients with COVID-19. The study found that T and NK cells did not express significant levels of pro-inflammatory cytokine genes, suggesting that they may not be the primary contributors to the cytokine storm. The study also identified a novel cell population that was significantly increased only in patients with ARDS, which was annotated as 'developing neutrophils'. These cells expressed several genes encoding neutrophil granule proteins but did not express canonical neutrophil markers. The study also found that these cells occupied a similar space as plasmablasts rather than canonical neutrophils in the UMAP embedding. The study also identified that these cells may represent neutrophils at various developmental stages. The study also found that the expression of pro-inflammatory cytokine genes was not uniform across all patients with COVID-19, and that the expression of these genes was not explained by ventilation or ARDS. The study also found that the expression of these genes was correlated with age and time-distance from fever onset. The study also found that the expression of these genes was not consistent between most patients with COVID-19. The study also found that the expression of these genes was not consistent between most patients with COVID-19. The study also found that the expression of these genes was not consistent between most patients with COVID-19. The study also found that the expression of these genes was not consistent between most patients with COVID-19. The study also found that the expression of these genes was not consistent between most patients with COVID-19. The study also found that the expression ofA single-cell atlas of the peripheral immune response in patients with severe COVID-19 was analyzed using single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven hospitalized patients with COVID-19 and six healthy controls. The study identified significant changes in immune cell composition and phenotype in patients with severe COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation, and a developing neutrophil population. These neutrophils showed characteristics of plasmablasts and were associated with severe disease. The study also found that peripheral monocytes and lymphocytes did not express substantial amounts of pro-inflammatory cytokines, suggesting that they may not be the primary contributors to the cytokine storm observed in severe COVID-19. Additionally, the study identified a depletion of several innate immune cell subsets in patients with COVID-19, including γδ T cells, plasmacytoid dendritic cells, conventional dendritic cells, CD16+ monocytes, and NK cells. The study also found that CD56dim NK cells were primarily depleted in ventilator-dependent patients, while CD56bright NK cells were significantly depleted in all patients with COVID-19. The study also identified a cluster of proliferative lymphocytes that appeared to be increased in most patients with COVID-19. The study found that T and NK cells did not express significant levels of pro-inflammatory cytokine genes, suggesting that they may not be the primary contributors to the cytokine storm. The study also identified a novel cell population that was significantly increased only in patients with ARDS, which was annotated as 'developing neutrophils'. These cells expressed several genes encoding neutrophil granule proteins but did not express canonical neutrophil markers. The study also found that these cells occupied a similar space as plasmablasts rather than canonical neutrophils in the UMAP embedding. The study also identified that these cells may represent neutrophils at various developmental stages. The study also found that the expression of pro-inflammatory cytokine genes was not uniform across all patients with COVID-19, and that the expression of these genes was not explained by ventilation or ARDS. The study also found that the expression of these genes was correlated with age and time-distance from fever onset. The study also found that the expression of these genes was not consistent between most patients with COVID-19. The study also found that the expression of these genes was not consistent between most patients with COVID-19. The study also found that the expression of these genes was not consistent between most patients with COVID-19. The study also found that the expression of these genes was not consistent between most patients with COVID-19. The study also found that the expression of these genes was not consistent between most patients with COVID-19. The study also found that the expression of