Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19

Viruses. 2021 Sep 30;13(10):1966. doi: 10.3390/v13101966.

Abstract

Background: The immunological changes associated with COVID-19 are largely unknown.

Methods: Patients with COVID-19 showing moderate (n = 18; SpO2 > 93%, respiratory rate > 22 per minute, CRP > 10 mg/L) and severe (n = 23; SpO2 < 93%, respiratory rate >30 per minute, PaO2/FiO2 ≤ 300 mmHg, permanent oxygen therapy, qSOFA > 2) infection, and 37 healthy donors (HD) were enrolled. Circulating T- and B-cell subsets were analyzed by flow cytometry.

Results: CD4+Th cells were skewed toward Th2-like phenotypes within CD45RA+CD62L- (CM) and CD45RA-CD62L- (EM) cells in patients with severe COVID-19, while CM CCR6+ Th17-like cells were decreased if compared with HD. Within CM Th17-like cells "classical" Th17-like cells were increased and Th17.1-like cells were decreased in severe COVID-19 cases. Circulating CM follicular Th-like (Tfh) cells were decreased in all COVID-19 patients, and Tfh17-like cells represented the most predominant subset in severe COVID-19 cases. Both groups of patients showed increased levels of IgD-CD38++ B cells, while the levels of IgD+CD38- and IgD-CD38- were decreased. The frequency of IgD+CD27+ and IgD-CD27+ B cells was significantly reduced in severe COVID-19 cases.

Conclusions: We showed an imbalance within almost all circulating memory Th subsets during acute COVID-19 and showed that altered Tfh polarization led to a dysregulated humoral immune response.

Keywords: B-cell subsets; COVID-19; T-cell subsets; imbalanced immune response; multicolor flow cytometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1
  • Adult
  • Aged
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • COVID-19 / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunity*
  • Immunoglobulin D
  • Male
  • Middle Aged
  • Oxygen
  • Receptors, CCR6
  • SARS-CoV-2*
  • T-Lymphocytes / metabolism
  • Th17 Cells / immunology

Substances

  • CCR6 protein, human
  • Immunoglobulin D
  • Receptors, CCR6
  • ADP-ribosyl Cyclase 1
  • Oxygen