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Abstract 


There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide1. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care2. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines3,4 that may be produced by a subset of inflammatory monocytes5,6, lymphopenia7,8 and T cell exhaustion9,10. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19.

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    Funding 


    Funders who supported this work.

    Agency for Science, Technology and Research

      Burroughs Wellcome Fund (1)

      • Grant ID: 1016687

      Burroughs Wellcome Fund (BWF) (1)

      • Grant ID: 1016687

      NHLBI NIH HHS (1)

      • Grant ID: K23 HL125663

      NIAID NIH HHS (2)

      • Grant ID: T32 AI007290

      • Grant ID: T32 AI007502

      NIDA NIH HHS (1)

      • Grant ID: DP1 DA046089

      NIGMS NIH HHS (2)

      • Grant ID: T32 GM007365

      • Grant ID: R25 GM086262

      National Science Foundation (1)

      • Grant ID: DGE-1656518

      National Science Foundation (NSF) (1)

      • Grant ID: DGE-1656518

      U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (1)

      • Grant ID: K23 HL125663

      U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (1)

      • Grant ID: DP1 DA04608902

      U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) (1)

      • Grant ID: DP1 DA04608902

      U.S. Department of Health & Human Services | National Institutes of Health (3)

      • Grant ID: AI007290-35

      • Grant ID: T32 GM007365-44

      • Grant ID: T32 AI007502-23

      U.S. Department of Health & Human Services | National Institutes of Health (NIH) (3)

      • Grant ID: T32 AI007502-23

      • Grant ID: T32 GM007365-44

      • Grant ID: AI007290-35

      Wellcome Trust

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