Comprehensive Immune Profiling Reveals CD56+ Monocytes and CD31+ Endothelial Cells Are Increased in Severe COVID-19 Disease

J Immunol. 2022 Feb 1;208(3):685-696. doi: 10.4049/jimmunol.2100830. Epub 2022 Jan 5.

Abstract

Immune response dysregulation plays a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. In this study, we evaluated immune and endothelial blood cell profiles of patients with coronavirus disease 2019 (COVID-19) to determine critical differences between those with mild, moderate, or severe COVID-19 using spectral flow cytometry. We examined a suite of immune phenotypes, including monocytes, T cells, NK cells, B cells, endothelial cells, and neutrophils, alongside surface and intracellular markers of activation. Our results showed progressive lymphopenia and depletion of T cell subsets (CD3+, CD4+, and CD8+) in patients with severe disease and a significant increase in the CD56+CD14+Ki67+IFN-γ+ monocyte population in patients with moderate and severe COVID-19 that has not been previously described. Enhanced circulating endothelial cells (CD45-CD31+CD34+CD146+), circulating endothelial progenitors (CD45-CD31+CD34+/-CD146-), and neutrophils (CD11b+CD66b+) were coevaluated for COVID-19 severity. Spearman correlation analysis demonstrated the synergism among age, obesity, and hypertension with upregulated CD56+ monocytes, endothelial cells, and decreased T cells that lead to severe outcomes of SARS-CoV-2 infection. Circulating monocytes and endothelial cells may represent important cellular markers for monitoring postacute sequelae and impacts of SARS-CoV-2 infection during convalescence and for their role in immune host defense in high-risk adults after vaccination.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology
  • Biomarkers
  • CD56 Antigen / analysis
  • COVID-19 / blood
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • Child
  • Comorbidity
  • Endothelial Cells / chemistry
  • Endothelial Cells / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Hypertension / epidemiology
  • Hypertension / immunology
  • Immunophenotyping
  • Lymphocyte Activation
  • Lymphocyte Subsets / immunology
  • Lymphopenia / etiology
  • Lymphopenia / immunology
  • Male
  • Middle Aged
  • Monocytes / chemistry
  • Monocytes / immunology*
  • Neutrophils / immunology
  • Obesity / epidemiology
  • Obesity / immunology
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • SARS-CoV-2* / immunology
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / immunology
  • Young Adult

Substances

  • Antibodies, Viral
  • Biomarkers
  • CD56 Antigen
  • NCAM1 protein, human
  • PECAM1 protein, human
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2