Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19

Respiratory immune characteristics associated with Coronavirus Disease 2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid immune cells from patients with varying severity of COVID-19 and from healthy people by using single-cell RNA sequencing. Proinflammatory monocyte-derived macrophages were abundant in the bronchoalveolar lavage fluid from patients with severe COVID-9. Moderate cases were characterized by the presence of highly clonally expanded CD8 + T cells. This atlas of the bronchoalveolar immune microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19. Single-cell transcriptome and T cell receptor analysis of bronchoalveolar lavage fluid suggests enrichment of proinflammatory macrophages in patients with severe COVID-19 and the presence of clonally expanded CD8 + T cells in patients with moderate COVID-19.

[1]  Guangchuang Yu,et al.  clusterProfiler: an R package for comparing biological themes among gene clusters. , 2012, Omics : a journal of integrative biology.

[2]  Xuetao Cao.  COVID-19: immunopathology and its implications for therapy , 2020, Nature Reviews Immunology.

[3]  S. Farhadian,et al.  Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19 , 2020, BMC Neurology.

[4]  P. Khong,et al.  COVID-19 pneumonia: what has CT taught us? , 2020, The Lancet Infectious Diseases.

[5]  S. Kaveri,et al.  Adjunct Immunotherapies for the Management of Severely Ill COVID-19 Patients , 2020, Cell Reports Medicine.

[6]  E. Vieta,et al.  Erythropoietin as candidate for supportive treatment of severe COVID-19 , 2020, Molecular medicine.

[7]  Eric Song,et al.  Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling , 2020, bioRxiv.

[8]  Thomas R. Gingeras,et al.  STAR: ultrafast universal RNA-seq aligner , 2013, Bioinform..

[9]  F. Kittrell,et al.  From Mice to Humans , 2004, Cancer Research.

[10]  Paul J. Hoffman,et al.  Comprehensive Integration of Single-Cell Data , 2018, Cell.

[11]  Jincun Zhao,et al.  Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus Infection , 2014, Journal of Virology.

[12]  Y. Hu,et al.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China , 2020, The Lancet.

[13]  G. Gao,et al.  T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV , 2016, Antiviral Research.

[14]  M. Guilliams,et al.  Developmental control of macrophage function. , 2018, Current opinion in immunology.

[15]  Pierre Geurts,et al.  SCENIC: Single-cell regulatory network inference and clustering , 2017 .

[16]  P. Linsley,et al.  MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data , 2015, Genome Biology.

[17]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. Shilatifard,et al.  Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis , 2019, American journal of respiratory and critical care medicine.

[19]  Jincun Zhao,et al.  T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice , 2010, Journal of Virology.

[20]  Yufeng Shen,et al.  Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites. , 2017, Cell reports.

[21]  T. Willinger,et al.  Origin and ontogeny of lung macrophages: from mice to humans , 2019, Immunology.

[22]  Chuan Qin,et al.  Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. , 2019, JCI insight.

[23]  S. Heyman,et al.  The Lung Macrophage in SARS-CoV-2 Infection: A Friend or a Foe? , 2020, Frontiers in Immunology.

[24]  David K. Meyerholz,et al.  Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice , 2016, Cell Host & Microbe.

[25]  J. Aerts,et al.  SCENIC: Single-cell regulatory network inference and clustering , 2017, Nature Methods.

[26]  P. Benos,et al.  Proliferating SPP1/MERTK-expressing macrophages in idiopathic pulmonary fibrosis , 2019, European Respiratory Journal.

[27]  Yuanliang Xie,et al.  COVID-19 with spontaneous pneumomediastinum , 2020, The Lancet Infectious Diseases.

[28]  J. Mesirov,et al.  The Molecular Signatures Database Hallmark Gene Set Collection , 2015 .

[29]  G. Lauer,et al.  Hepatitis C virus-specific CD4+ T cell phenotype and function in different infection outcomes. , 2020, The Journal of clinical investigation.

[30]  M. Tosolini,et al.  Single-Cell Signature Explorer for comprehensive visualization of single cell signatures across scRNA-seq datasets , 2019, bioRxiv.