説明
<jats:title>Abstract</jats:title><jats:p>Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (<jats:italic>CD16</jats:italic><jats:sup><jats:italic>+</jats:italic></jats:sup><jats:italic>C1QA/B/C</jats:italic><jats:sup><jats:italic>+</jats:italic></jats:sup>) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34<jats:sup>+</jats:sup>hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8<jats:sup>+</jats:sup>T cells and an increased ratio of CD8<jats:sup>+</jats:sup>effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.</jats:p>
収録刊行物
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- Nature Medicine
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Nature Medicine 27 (5), 904-916, 2021-04-20
Springer Science and Business Media LLC
