Single-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm

Nat Commun. 2020 Aug 6;11(1):3924. doi: 10.1038/s41467-020-17834-w.

Abstract

Several studies show that the immunosuppressive drugs targeting the interleukin-6 (IL-6) receptor, including tocilizumab, ameliorate lethal inflammatory responses in COVID-19 patients infected with SARS-CoV-2. Here, by employing single-cell analysis of the immune cell composition of two severe-stage COVID-19 patients prior to and following tocilizumab-induced remission, we identify a monocyte subpopulation that contributes to the inflammatory cytokine storms. Furthermore, although tocilizumab treatment attenuates the inflammation, immune cells, including plasma B cells and CD8+ T cells, still exhibit robust humoral and cellular antiviral immune responses. Thus, in addition to providing a high-dimensional dataset on the immune cell distribution at multiple stages of the COVID-19, our work also provides insights into the therapeutic effects of tocilizumab, and identifies potential target cell populations for treating COVID-19-related cytokine storms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Betacoronavirus / immunology*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19
  • Computational Biology
  • Coronavirus Infections / blood
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / virology
  • Cytokines / blood
  • Cytokines / immunology*
  • Humans
  • Inflammation / drug therapy
  • Macrophages / drug effects
  • Macrophages / immunology
  • Monocytes / immunology*
  • Pandemics
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / virology
  • Receptors, Interleukin-6 / immunology
  • SARS-CoV-2
  • Single-Cell Analysis / methods

Substances

  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • IL6R protein, human
  • Receptors, Interleukin-6
  • tocilizumab