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A single-cell atlas of the peripheral immune response to severe COVID-19

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 3 million people worldwide. Approximately 20% of patients with COVID-19 develop severe disease and 5% require intensive care. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines that may be produced by a subset of inflammatory monocytes, lymphopenia, and T cell exhaustion. 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 7 patients hospitalized for COVID-19 and 6 healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) 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. Sample IDs used in the manuscript were shortened for clarity. They relate to the titles of deposited files as follows: covid_555_1: C1 A covid_555_2: C1 B covid_556: C2 covid_557: C3 covid_558: C4 covid_559: C5 covid_561: C7 HIP002: H1 HIP015: H2 HIP023: H3 HIP043: H4 HIP044: H5 HIP045: H6

ORGANISM(S): Homo sapiens

PROVIDER: GSE150728 | GEO | 2020/05/18

REPOSITORIES: GEO

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