The mechanisms underlying the immune remodeling and severity response in coronavirus disease 2019 (COVID-19) are yet to be fully elucidated. Our comprehensive integrative analyses of single-cell RNA sequencing (scRNAseq) data from four published studies, in patients with mild/moderate and severe infections, indicate a robust expansion and mobilization of the innate immune response and highlight mechanisms by which low-density neutrophils and megakaryocytes play a crucial role in the cross talk between lymphoid and myeloid lineages. We also document a marked reduction of several lymphoid cell types, particularly natural killer cells, mucosal-associated invariant T (MAIT) cells, and gamma-delta T (γδT) cells, and a robust expansion and extensive heterogeneity within plasmablasts, especially in severe COVID-19 patients. We confirm the changes in cellular abundances for certain immune cell types within a new patient cohort. While the cellular heterogeneity in COVID-19 extends across cells in both lineages, we consistently observe certain subsets respond more potently to interferon type I (IFN-I) and display increased cellular abundances across the spectrum of severity, as compared with healthy subjects. However, we identify these expanded subsets to have a more muted response to IFN-I within severe disease compared to non-severe disease. Our analyses further highlight an increased aggregation potential of the myeloid subsets, particularly monocytes, in COVID-19. Finally, we provide detailed mechanistic insights into the interaction between lymphoid and myeloid lineages, which contributes to the multisystemic phenotype of COVID-19, distinguishing severe from non-severe responses.
【저자키워드】 COVID-19, MDSC, plasmablast, aggregation, immune-remodeling, low-density neutrophils, megakaryocyte, cDC2, 【초록키워드】 coronavirus disease, Monocytes, innate immune response, severity, neutrophil, interferon, heterogeneity, immune, Single-cell RNA sequencing, cells, plasmablasts, Patient, phenotype, IFN-I, Natural killer cells, disease, lineages, mechanism, cellular, Interaction, Analysis, severe disease, cell types, reduction, healthy subjects, type I, severe COVID-19 patients, severe infections, multisystemic, low-density, lymphoid, patient cohort, while, scRNAseq, responses, Cell, highlight, robust, observé, identify, changes in, contribute, subset, respond, cross talk, immune cell type, 【제목키워드】 response, landscape,