Transcriptional Changes in CD16+ Monocytes May Contribute to the Pathogenesis of COVID-19

Front Immunol. 2021 May 24;12:665773. doi: 10.3389/fimmu.2021.665773. eCollection 2021.

Abstract

The COVID-19 pandemic has caused more than three million deaths globally. The severity of the disease is characterized, in part, by a dysregulated immune response. CD16+ monocytes are innate immune cells involved in inflammatory responses to viral infections, and tissue repair, among other functions. We characterized the transcriptional changes in CD16+ monocytes from PBMC of people with COVID-19, and from healthy individuals using publicly available single cell RNA sequencing data. CD16+ monocytes from people with COVID-19 compared to those from healthy individuals expressed transcriptional changes indicative of increased cell activation, and induction of a migratory phenotype. We also analyzed COVID-19 cases based on severity of the disease and found that mild cases were characterized by upregulation of interferon response and MHC class II related genes, whereas the severe cases had dysregulated expression of mitochondrial and antigen presentation genes, and upregulated inflammatory, cell movement, and apoptotic gene signatures. These results suggest that CD16+ monocytes in people with COVID-19 contribute to a dysregulated host response characterized by decreased antigen presentation, and an elevated inflammatory response with increased monocytic infiltration into tissues. Our results show that there are transcriptomic changes in CD16+ monocytes that may impact the functions of these cells, contributing to the pathogenesis and severity of COVID-19.

Keywords: SARS-CoV-2; cell movement; inflammation; non-classical monocytes; single-cell transcriptomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • COVID-19 / genetics
  • COVID-19 / immunology
  • COVID-19 / metabolism
  • COVID-19 / virology*
  • Case-Control Studies
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • GPI-Linked Proteins / metabolism
  • Gene Expression Profiling
  • Host-Pathogen Interactions
  • Humans
  • Inflammation Mediators / metabolism
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism
  • Male
  • Middle Aged
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / virology*
  • RNA-Seq
  • Receptors, IgG / metabolism*
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity*
  • Severity of Illness Index
  • Single-Cell Analysis
  • Transcription, Genetic*
  • Transcriptome*
  • Young Adult

Substances

  • Apoptosis Regulatory Proteins
  • Cytokines
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Inflammation Mediators
  • Interferon Regulatory Factors
  • Mitochondrial Proteins
  • Receptors, IgG