Elevated plasma sTIM-3 levels in patients with severe COVID-19

J Allergy Clin Immunol. 2021 Jan;147(1):92-98. doi: 10.1016/j.jaci.2020.09.007. Epub 2020 Sep 21.


Background: The pathogenesis of coronavirus disease 2019 (COVID-19) is still incompletely understood, but it seems to involve immune activation and immune dysregulation.

Objective: We examined the parameters of activation of different leukocyte subsets in COVID-19-infected patients in relation to disease severity.

Methods: We analyzed plasma levels of myeloperoxidase (a marker of neutrophil activation), soluble (s) CD25 (sCD25) and soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) (markers of T-cell activation and exhaustion), and sCD14 and sCD163 (markers of monocyte/macrophage activation) in 39 COVID-19-infected patients at hospital admission and 2 additional times during the first 10 days in relation to their need for intensive care unit (ICU) treatment.

Results: Our major findings were as follows: (1) severe clinical outcome (ICU treatment) was associated with high plasma levels of sTIM-3 and myeloperoxidase, suggesting activated and potentially exhausted T cells and activated neutrophils, respectively; (2) in contrast, sCD14 and sCD163 showed no association with need for ICU treatment; and (3) levels of sCD25, sTIM-3, and myeloperoxidase were inversely correlated with degree of respiratory failure, as assessed by the ratio of Pao2 to fraction of inspired oxygen, and were positively correlated with the cardiac marker N-terminal pro-B-type natriuretic peptide.

Conclusion: Our findings suggest that neutrophil activation and, in particular, activated T cells may play an important role in the pathogenesis of COVID-19 infection, suggesting that T-cell-targeted treatment options and downregulation of neutrophil activation could be of importance in this disorder.

Keywords: COVID-19; T cell; TIM-3; neutrophil; outcome.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Antigens, CD / blood
  • Antigens, Differentiation, Myelomonocytic / blood
  • COVID-19 / blood*
  • Female
  • Hepatitis A Virus Cellular Receptor 2 / blood*
  • Humans
  • Interleukin-2 Receptor alpha Subunit / blood
  • Lipopolysaccharide Receptors / blood
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Receptors, Cell Surface / blood
  • SARS-CoV-2 / metabolism*
  • Severity of Illness Index
  • T-Lymphocytes / metabolism
  • Time Factors


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Lipopolysaccharide Receptors
  • Receptors, Cell Surface