TREM-1, TREM-2 and Their Association with Disease Severity in Patients with COVID-19

Overview

Journal Ann Med

Publisher Informa Healthcare

Specialty General Medicine

Date 2023 Oct 17

PMID 37848000

Authors

Ruyue Fan

Zuowang Cheng

Zhisheng Huang

Ying Yang

Na Sun

Bin Hu

Peibin Hou

Bo Liu

Chuanjun Huang

Shuai Liu

Affiliations

Soon will be listed here.

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 PaO/FiO, 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.

Citing Articles

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References

Zhu Z, Zhang X, Dong W, Wang X, He S, Zhang H . TREM2 suppresses the proinflammatory response to facilitate PRRSV infection via PI3K/NF-κB signaling. PLoS Pathog. 2020; 16(5):e1008543. PMC: 7250469. DOI: 10.1371/journal.ppat.1008543. View

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z . Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229):1054-1062. PMC: 7270627. DOI: 10.1016/S0140-6736(20)30566-3. View

Tan C, Huang Y, Shi F, Tan K, Ma Q, Chen Y . C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early. J Med Virol. 2020; 92(7):856-862. PMC: 7262341. DOI: 10.1002/jmv.25871. View

Williams P, McWilliams C, Soomro K, Harding I, Gurney S, Thomas M . The dynamics of procalcitonin in COVID-19 patients admitted to Intensive care unit - a multi-centre cohort study in the South West of England, UK. J Infect. 2021; 82(6):e24-e26. PMC: 7970419. DOI: 10.1016/j.jinf.2021.03.011. View

Ruan Q, Yang K, Wang W, Jiang L, Song J . Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020; 46(5):846-848. PMC: 7080116. DOI: 10.1007/s00134-020-05991-x. View

Jiyong J, Tiancha H, Wei C, Huahao S . Diagnostic value of the soluble triggering receptor expressed on myeloid cells-1 in bacterial infection: a meta-analysis. Intensive Care Med. 2008; 35(4):587-95. DOI: 10.1007/s00134-008-1333-z. View

Colonna M . The biology of TREM receptors. Nat Rev Immunol. 2023; 23(9):580-594. PMC: 9904274. DOI: 10.1038/s41577-023-00837-1. View

Wilson J, Simpson L, Ferreira A, Rustagi A, Roque J, Asuni A . Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis. JCI Insight. 2020; 5(17). PMC: 7526438. DOI: 10.1172/jci.insight.140289. View

Donlan A, Sutherland T, Marie C, Preissner S, Bradley B, Carpenter R . IL-13 is a driver of COVID-19 severity. JCI Insight. 2021; 6(15). PMC: 8410056. DOI: 10.1172/jci.insight.150107. View

10.

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y . Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223):497-506. PMC: 7159299. DOI: 10.1016/S0140-6736(20)30183-5. View

11.

Lippi G, Plebani M . Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Clin Chim Acta. 2020; 505:190-191. PMC: 7094472. DOI: 10.1016/j.cca.2020.03.004. View

12.

Liu D, Dong Y, Liu Z, Niu B, Wang Y, Gao X . Impact of TREM-2 gene silencing on inflammatory response of endotoxin-induced acute lung injury in mice. Mol Cell Biochem. 2014; 394(1-2):155-61. DOI: 10.1007/s11010-014-2091-6. View

13.

Zhang J, Wang X, Xing X, Xu Z, Zhang C, Song J . Single-cell landscape of immunological responses in patients with COVID-19. Nat Immunol. 2020; 21(9):1107-1118. DOI: 10.1038/s41590-020-0762-x. View

14.

Wiersinga W, Rhodes A, Cheng A, Peacock S, Prescott H . Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020; 324(8):782-793. DOI: 10.1001/jama.2020.12839. View

15.

Wang T, Feng J, Shu C, Shin-Jung Lee S, Chen C, Wei Y . Plasma Concentrations of sTREM-1 as Markers for Systemic Adverse Reactions in Subjects Treated With Weekly Rifapentine and Isoniazid for Latent Tuberculosis Infection. Front Microbiol. 2022; 13:821066. PMC: 8927064. DOI: 10.3389/fmicb.2022.821066. View

16.

Sun G, Guan C, Zhou Y, Liu Y, Li S, Zhou H . Vasoactive intestinal peptide re-balances TREM-1/TREM-2 ratio in acute lung injury. Regul Pept. 2010; 167(1):56-64. DOI: 10.1016/j.regpep.2010.11.008. View

17.

Hiremath J, Renu S, Tabynov K, Renukaradhya G . Pulmonary inflammatory response to influenza virus infection in pigs is regulated by DAP12 and macrophage M1 and M2 phenotypes. Cell Immunol. 2020; 352:104078. DOI: 10.1016/j.cellimm.2020.104078. View

18.

Qin R, He L, Yang Z, Jia N, Chen R, Xie J . Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis. Clin Rev Allergy Immunol. 2022; 64(1):33-65. PMC: 8763427. DOI: 10.1007/s12016-021-08908-8. View

19.

Hoogendijk A, Blok D, Garcia Laorden M, Kager L, Lede I, Rahman W . Soluble and cell-associated triggering receptor expressed on myeloid cells-1 and -2 in patients with pulmonary tuberculosis. J Infect. 2015; 71(6):706-9. DOI: 10.1016/j.jinf.2015.09.002. View

20.

Singer M, Deutschman C, Seymour C, Shankar-Hari M, Annane D, Bauer M . The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315(8):801-10. PMC: 4968574. DOI: 10.1001/jama.2016.0287. View