Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)

Front Immunol. 2020 May 1;11:827. doi: 10.3389/fimmu.2020.00827. eCollection 2020.

Abstract

Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+ T cells or CD4+ T cells lower than 800, 300, or 400/μL, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-α concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-α concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.

Keywords: COVID-19; SARS- CoV-2; T cell exhaustion; T cell reduction; cytokine strom.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Betacoronavirus / physiology*
  • COVID-19
  • Coronavirus Infections / blood
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / pathology
  • Cytokines / blood
  • Humans
  • Lymphocyte Count
  • Pandemics
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / pathology
  • SARS-CoV-2
  • T-Lymphocytes / immunology

Substances

  • Cytokines