TREM-1, TREM-2 and their association with disease severity in patients with COVID-19

Ann Med. 2023;55(2):2269558. doi: 10.1080/07853890.2023.2269558. Epub 2023 Oct 17.

Abstract

Background: Delayed diagnosis and inadequate treatment caused by limited biomarkers are associated with the outcomes of COVID-19 patients. It is necessary to identify other promising biomarkers and candidate targets for defining dysregulated inflammatory states.

Methods: The triggering receptors expressed on myeloid cell (TREM)-1 and TREM-2 expression from hospitalized COVID-19 patients were characterized using ELISA and flow cytometry, respectively. Their correlation with disease severity and contrast with the main clinical indicators were evaluated.

Results: Increased expression of soluble TREM-1 and TREM-2 in the plasma of COVID-19 patients was found compared to the control group. Moreover, membrane-bound TREM-1 and TREM-2 expression was upregulated on the cell surface of circulating blood T cells from COVID-19 patients. Correlation analysis showed that sTREM-2 levels were negatively correlated with PaO2/FiO2, but positively correlated with C-reactive protein (CRP), procalcitonin (PCT) and interleukin (IL)-6 levels. Receiver operating characteristic curve analysis indicated that the predictive efficacy of sTREM-1 and sTREM-2 was equivalent to CRP and IL-6, and a little better than absolute leukocyte or neutrophil count and PCT in distinguishing disease severity.

Conclusion: TREM-2 and TREM-1 are critical host immune factors that response to SARS-COV-2 infection and could serve as potential diagnostic biomarkers and therapeutic targets for COVID-19.

Keywords: COVID-19; TREM-1; TREM-2; disease severity.

Plain language summary

The expression of soluble TREM-1 and TREM-2 in plasma and membrane-bound TREM-1 and TREM-2 on the cell surface was upregulated in COVID-19 patients.sTREM-2 level was negatively correlated with PaO2/FiO2, but positively correlated with CRP, PCT and IL-6 level, respectively.sTREM-1 and sTREM-2 exhibited potential predictive abilities, and their expression was equivalent to CRP and IL-6, and better than the absolute leukocytes or neutrophil counts and PCT in distinguishing disease severity.

MeSH terms

  • Biomarkers
  • C-Reactive Protein / metabolism
  • COVID-19* / diagnosis
  • Humans
  • Interleukin-6
  • Membrane Glycoproteins*
  • Myeloid Cells / metabolism
  • Patient Acuity
  • Procalcitonin
  • Receptors, Immunologic / metabolism
  • SARS-CoV-2 / metabolism
  • Triggering Receptor Expressed on Myeloid Cells-1

Substances

  • Triggering Receptor Expressed on Myeloid Cells-1
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Biomarkers
  • C-Reactive Protein
  • Procalcitonin
  • Interleukin-6

Grants and funding

This work was funded by the Natural Science Foundation of China [No. 82200014], Natural Science Foundation of Shandong Province [ZR2022QH216], Funding Statement Taishan Scholars Program of Shandong Province [No. tsqn202103196], and teachers’ research at Jining Medical University [No. JYFC2019FKJ169].