A Longitudinal Study of Immune Cells in Severe COVID-19 Patients

Front Immunol. 2020 Oct 23;11:580250. doi: 10.3389/fimmu.2020.580250. eCollection 2020.


Little is known about the time-dependent immune responses in severe COVID-19. Data of 15 consecutive patients were sequentially recorded from intensive care unit admission. Lymphocyte subsets and total monocyte and subsets counts were monitored as well as the expression of HLA-DR. For 5 patients, SARS-CoV-2-specific T-cell polyfunctionality was assessed against Spike and Nucleoprotein SARS-CoV-2 peptides. Non-specific inflammation markers were increased in all patients. Median monocyte HLA-DR expression was below the 8,000 AB/C threshold defining acquired immunodepression. A "V" trend curve for lymphopenia, monocyte numbers, and HLA-DR expression was observed with a nadir between days 11 and 14 after symptoms' onset. Intermediate CD14++CD16+ monocytes increased early with a reduction in classic CD14++CD16- monocytes. Polyfunctional SARS-Cov-2-specific CD4 T-cells were present and functional, whereas virus-specific CD8 T-cells were less frequent and not efficient. We report a temporal variation of both innate and adaptive immunity in severe COVID-19 patients, helpful in guiding therapeutic decisions (e.g. anti-inflammatory vs. immunostimulatory ones). We describe a defect in virus-specific CD8 T-cells, a potential biomarker of clinical severity. These combined data also provide helpful knowledge for vaccine design.

Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04386395.

Keywords: SARS-CoV-2; antigen-specific polyfunctional T-cells; immunity; intensive care unit; monocyte HLA-DR.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Biomarkers
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Female
  • GPI-Linked Proteins / metabolism
  • HLA-DR Antigens / immunology
  • Humans
  • Immunity, Cellular
  • Lipopolysaccharide Receptors / metabolism
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Prospective Studies
  • Receptors, IgG / metabolism
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • Severity of Illness Index*


  • Biomarkers
  • CD14 protein, human
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • HLA-DR Antigens
  • Lipopolysaccharide Receptors
  • Receptors, IgG

Associated data

  • ClinicalTrials.gov/NCT04386395