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Single-cell multi-omics analysis of the immune response in COVID-19.

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Stephenson, Emily 
Reynolds, Gary 
Botting, Rachel A 
Calero-Nieto, Fernando J  ORCID logo


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 (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ 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.



COVID-19, Cross-Sectional Studies, Humans, Monocytes, Proteome, Receptors, Antigen, B-Cell, Receptors, Antigen, T-Cell, SARS-CoV-2, Single-Cell Analysis, T-Lymphocytes, Transcriptome

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Nat Med

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Springer Science and Business Media LLC
Wellcome Trust (206328/Z/17/Z)
Medical Research Council (MR/S036113/1)
Medical Research Council (MR/S035842/1)
Arthritis Research UK (21777)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Cambridge University Hospitals NHS Foundation Trust (CUH) (BRC 2012-2017)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cancer Research UK (S_3517)
NHS Blood and Transplant Trust Fund (WP15-02)
Medical Research Council (MR/P008801/1)
NHS Blood and Transplant (NHSBT) (WP15-02)
Medical Research Council (MC_PC_17230)
MRC (MR/W014556/1)
Medical Research Council (MR/R015635/1)
Wellcome Trust (107630/Z/15/Z)
Biotechnology and Biological Sciences Research Council (BB/P002293/1)
Wellcome Trust (203151/Z/16/Z)