A single-cell atlas of the peripheral immune response in patients with severe COVID-19

By A. Wilk, A. Rustagi, Nancy Q. Zhao, J. Roque, Giovanny J. Martínez-Colón, J. McKechnie, Geoffrey T. Ivison, T. Ranganath, Rosemary Vergara, Taylor Hollis and 5 more. Nature Medicine, 2020

1,344 citations recorded by the source corpus.

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. Single-cell transcriptomic analysis identifies changes in peripheral immune cells in seven hospitalized patients with COVID-19, including HLA class II downregulation, a heterogeneous interferon-stimulated gene signature and low pro-inflammatory cytokine gene expression in monocytes and lymphocytes.

Subfields: Immunology, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2e500d6326a9c0cc05f9a0ec57df3da1dffd1bda

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Citations in the corpus

Dictionary learning for integrative, multimodal, and massively scalable single-cell analysis (2022, positive): “Data acquisition source: Supplementary Table 2 and PBMC scRNA datasets 4,62,63,102–112 .”
Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment (2020, positive): “Previousstudiesofperipheralblood mononuclear cell (PBMC) transcriptomes in a small number of patients with COVID-19 revealed changes in several cellular compartments, includingmonocytes, natural killer (NK) cells, dendritic cells (DCs), and T cells (Lee et al., 2020; Wilk et al., 2020).”
Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19 (2020, neutral): “Similar findings have been reported previously in the absence of specificity data (Huang et al., 2020; Thevarajan et al., 2020; Wilk et al., 2020).”