Re-analysis of Single Cell Transcriptome Reveals That the NR3C1-CXCL8-Neutrophil Axis Determines the Severity of COVID-19

Front Immunol. 2020 Aug 28:11:2145. doi: 10.3389/fimmu.2020.02145. eCollection 2020.

Abstract

SARS-CoV-2 infection has recently been declared a pandemic. Some patients showing severe symptoms exhibit drastic inflammation and airway damage. In this study, we re-analyzed published scRNA-seq data of COVID-19 patient bronchoalveolar lavage fluid to further classify and compare immunological features according to the patient's disease severity. Patients with severe symptoms showed DNA damage and apoptotic features of epithelial cells. Our results suggested that epithelial damage was associated with neutrophil infiltration. Myeloid cells of severe patients showed higher expression of proinflammatory cytokines and chemokines such as CXCL8. As a result, neutrophils were abundant in lungs of patients from the severe group. Furthermore, recruited neutrophils highly expressed genes related to neutrophil extracellular traps. Neutrophil-mediated inflammation was regulated by glucocorticoid receptor expression and activity. Based on these results, we suggest that severe COVID-19 symptoms may be determined by differential expression of glucocorticoid receptors and neutrophils.

Keywords: BAL; COVID-19; CXCL8; SARS-CoV-2; glucocorticoid; neutrophil; scRNA-seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Betacoronavirus / immunology*
  • Bronchoalveolar Lavage Fluid / immunology
  • COVID-19
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / virology
  • Epithelial Cells / pathology
  • Extracellular Traps / immunology
  • Female
  • Gene Expression Profiling / methods
  • Humans
  • Inflammation / immunology
  • Interleukin-8 / genetics*
  • Interleukin-8 / metabolism
  • Male
  • Middle Aged
  • Myeloid Cells / immunology
  • Neutrophil Infiltration / immunology
  • Neutrophils / immunology*
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / virology
  • RNA-Seq
  • Receptors, Glucocorticoid / genetics*
  • Receptors, Glucocorticoid / metabolism
  • SARS-CoV-2
  • Severity of Illness Index*
  • Single-Cell Analysis / methods
  • Transcriptome*

Substances

  • CXCL8 protein, human
  • Interleukin-8
  • NR3C1 protein, human
  • Receptors, Glucocorticoid