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

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. 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. 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. 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. 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. 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.

因生物标志物有限导致的诊断延误与治疗不足，与新型冠状病毒肺炎（COVID-19）患者的预后密切相关。亟需筛选其他具有应用前景的生物标志物与候选靶点，以界定失调的炎症状态。本研究分别采用酶联免疫吸附试验（ELISA）与流式细胞术（flow cytometry），对住院COVID-19患者体内髓系细胞触发受体-1（triggering receptors expressed on myeloid cell，TREM-1）及TREM-2的表达水平进行了表征，并评估了其与疾病严重程度的相关性，同时与主要临床指标进行了对比分析。研究发现，相较于对照组，COVID-19患者血浆中的可溶性TREM-1与TREM-2表达水平显著升高；此外，COVID-19患者循环血液T细胞表面的膜结合型TREM-1与TREM-2表达亦呈上调趋势。相关性分析结果显示，可溶性TREM-2（sTREM-2）水平与动脉血氧分压/吸入氧分数比值（PaO2/FiO2）呈负相关，而与C反应蛋白（C-reactive protein，CRP）、降钙素原（procalcitonin，PCT）及白细胞介素-6（interleukin-6，IL-6）水平呈正相关。受试者工作特征曲线（Receiver operating characteristic curve，ROC）分析表明，sTREM-1与sTREM-2的预测效能与CRP、IL-6相当，在区分疾病严重程度方面略优于白细胞绝对计数、中性粒细胞绝对计数及PCT。综上，TREM-1与TREM-2是应对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的关键宿主免疫因子，可作为COVID-19潜在的诊断生物标志物与治疗靶点。