Single-cell analysis of COVID-19, sepsis, and HIV infection reveals hyperinflammatory and immunosuppressive signatures in monocytes

Cell Rep. 2021 Oct 5;37(1):109793. doi: 10.1016/j.celrep.2021.109793. Epub 2021 Sep 17.


The mortality risk of coronavirus disease 2019 (COVID-19) patients has been linked to the cytokine storm caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the inflammatory responses shared between COVID-19 and other infectious diseases that feature cytokine storms may therefore help in developing improved therapeutic strategies. Here, we use integrative analysis of single-cell transcriptomes to characterize the inflammatory signatures of peripheral blood mononuclear cells from patients with COVID-19, sepsis, and HIV infection. We identify ten hyperinflammatory cell subtypes in which monocytes are the main contributors to the transcriptional differences in these infections. Monocytes from COVID-19 patients share hyperinflammatory signatures with HIV infection and immunosuppressive signatures with sepsis. Finally, we construct a "three-stage" model of heterogeneity among COVID-19 patients, related to the hyperinflammatory and immunosuppressive signatures in monocytes. Our study thus reveals cellular and molecular insights about inflammatory responses to SARS-CoV-2 infection and provides therapeutic guidance to improve treatments for subsets of COVID-19 patients.

Keywords: COVID-19; SARS-CoV-2; immunosuppression; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / blood*
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Cytokine Release Syndrome / blood
  • Cytokine Release Syndrome / immunology
  • Cytokines / blood
  • Data Analysis
  • Datasets as Topic
  • HIV Infections / blood*
  • HIV Infections / immunology
  • HIV-1 / immunology
  • Humans
  • Immunosuppression Therapy
  • Inflammation / blood
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • SARS-CoV-2 / immunology*
  • Sepsis / blood*
  • Sepsis / immunology
  • Single-Cell Analysis
  • Transcriptome*


  • Cytokines