The Inflammatory Factors Associated with Disease Severity to Predict COVID-19 Progression

J Immunol. 2021 Apr 1;206(7):1597-1608. doi: 10.4049/jimmunol.2001327. Epub 2021 Feb 12.

Abstract

Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. Exploring the immune-inflammatory characteristics of COVID-19 patients is essential to reveal pathogenesis and predict progression. In this study, COVID-19 patients showed decreased CD3+, CD4+, and CD8+ T cells but increased neutrophils in circulation, exhibiting upregulated neutrophil-to-lymphocyte and neutrophil-to-CD8+ T cell ratio. IL-6, TNF-α, IL-1β, IL-18, IL-12/IL-23p40, IL-10, Tim-3, IL-8, neutrophil extracellular trap-related proteinase 3, and S100A8/A9 were elevated, whereas IFN-γ and C-type lectin domain family 9 member A (clec9A) were decreased in COVID-19 patients compared with healthy controls. When compared with influenza patients, the expressions of TNF-α, IL-18, IL-12/IL-23p40, IL-8, S100A8/A9 and Tim-3 were significantly increased in critical COVID-19 patients, and carcinoembryonic Ag, IL-8, and S100A8/A9 could serve as clinically available hematologic indexes for identifying COVID-19 from influenza. Moreover, IL-6, IL-8, IL-1β, TNF-α, proteinase 3, and S100A8/A9 were increased in bronchoalveolar lavage fluid of severe/critical patients compared with moderate patients, despite decreased CD4+ T cells, CD8+ T cells, B cells, and NK cells. Interestingly, bronchoalveolar IL-6, carcinoembryonic Ag, IL-8, S100A8/A9, and proteinase 3 were found to be predictive of COVID-19 severity and may serve as potential biomarkers for predicting COVID-19 progression and potential targets in therapeutic intervention of COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • COVID-19* / blood
  • COVID-19* / immunology
  • Calgranulin A / blood
  • Calgranulin A / immunology
  • Calgranulin B / blood
  • Calgranulin B / immunology
  • Cytokines / blood
  • Cytokines / immunology
  • Disease Progression
  • Female
  • Hepatitis A Virus Cellular Receptor 2 / blood
  • Hepatitis A Virus Cellular Receptor 2 / immunology
  • Humans
  • Inflammation Mediators* / blood
  • Inflammation Mediators* / immunology
  • Leukocyte Count
  • Male
  • Middle Aged
  • Myeloblastin / blood
  • Myeloblastin / immunology
  • Retrospective Studies
  • SARS-CoV-2* / immunology
  • SARS-CoV-2* / metabolism
  • Severity of Illness Index*

Substances

  • Calgranulin A
  • Calgranulin B
  • Cytokines
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Inflammation Mediators
  • S100A8 protein, human
  • S100A9 protein, human
  • Myeloblastin