Lymphocyte Subset Alteration and Monocyte CD4 Expression Reduction in Patients with Severe COVID-19

Viral Immunol. 2021 Jun;34(5):342-351. doi: 10.1089/vim.2020.0166. Epub 2020 Nov 23.


The spectrum of coronavirus disease 2019 (COVID-19) severity, related to cellular immune functions, has not been fully clarified yet. Therefore, this study aimed to investigate the alteration of peripheral blood cells in patients with COVID-19. The flow cytometric characterization of immune cell subset was performed on 69 COVID-19 patients and 21 healthy controls. These data were evaluated based on the disease severity. A total of 69 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were classified as asymptomatic infection (n = 14), nonsevere (n = 39), and severe (n = 16) groups. Decreased lymphocytes and increased CD14 + 4- monocytes are found in patients with severe COVID-19. Decreased CD4 expression level was observed in the monocytes of patients with severe COVID-19. The total lymphocytes, B and T lymphocytes, CD4+ cells and CD8+ cells, and natural killer (NK) and natural killer T (NKT) cells were found to be decreased in patients with severe COVID-19. The CD4+/CD8+ ratio was not significantly different between patients with COVID-19 and healthy controls. The percentage of activated T cells (CD3+HLA-DR+) and B cells (CD19+CD38+) was lower in patients with severe COVID-19. Age and CD4- monocytes were independent predictors of disease severity. The SARS-CoV-2 infection may affect lymphocyte subsets, resulting in decreased T and B cells, monocytes, and NK and NKT cells. Decreased CD4 expression level by monocytes was significantly correlated with disease severity. Further studies on the host immune response to SARS-CoV-2 infection are necessary to predict the disease severity and protect against the virus.

Keywords: CD4; COVID-19; SARS-CoV-2; coronavirus; cytometry; lymphocyte; monocyte.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • CD4 Antigens / genetics*
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • Female
  • Flow Cytometry
  • Hospitalization / statistics & numerical data
  • Humans
  • Immunity, Cellular*
  • Lymphocyte Activation
  • Lymphocyte Count
  • Lymphocyte Subsets / immunology*
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Severity of Illness Index*
  • Young Adult


  • CD4 Antigens