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

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.

KEY MESSAGES

• 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.

Keywords:

• TREM-1
• TREM-2
• disease severity
• COVID-19

Acknowledgements

The authors thank the National Natural Science Foundation of China for its support.

Authors contributions

Ruyue Fan, Zuowang Cheng and Shuai Liu conceived of the project. Ruyue Fan, Zuowang Cheng, Zhisheng Huang, Bo Liu and Shuai Liu discussed and designed the experiments. Ying Yang, Peibin Hou and Ruyue Fan conducted experiments. Shuai Liu, Na Sun, Bin Hu and Chuanjun Huang performed statistical analyses. Ruyue Fan and Shuai Liu prepared the manuscript. All authors interpreted the results and edited the manuscript accordingly. All authors have read and approved the final manuscript.

Ethics statement

Experiments involving human participants were conducted in accordance with the Declaration of Helsinki and approved by the Shandong Provincial Hospital Affiliated to Shandong First Medical University Ethics Committee (Approval No. 2023-805) in accordance with the guidelines for the protection of human volunteers. All participants provided written informed consent to participate in the study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data used in the current study are accessible from the corresponding authors upon reasonable request.

Additional information

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].