Prognostic value of sTREM-1 in COVID-19 patients: a biomarker for disease severity and mortality
Authors: da Silva Neto Pedro V. , de Carvalho Jonatan C. S. , Pimentel Vinícius E. , Pérez Malena M. , Carmona-Garcia Ingryd , Neto Nicola T. , Toro Diana M. , Oliveira Camilla N. S. , Fraga-Silva Thais F. C. , Milanezi Cristiane M. , Rodrigues Lilian C. , Dias Cassia F. S. L. , Xavier Ana C. , Porcel Giovanna S. , Guarneri Isabelle C. , Zaparoli Kamila , Garbato Caroline T. , Argolo Jamille G. M. , Júnior Ângelo A. F. , de Amorim Alessandro P. , Degiovani Augusto M. , da Silva Dayane P. , Nepomuceno Debora C. , da Silva Rafael C. , Constant Leticia F. , Ostini Fátima M. , Feitosa Marley R. , Parra Rogerio S. , Vilar Fernando C. , Gaspar Gilberto G. , da Rocha José J. R. , Feres Omar , Barbieri Rita C. C. , Frantz Fabiani G. , Maruyama Sandra R. , Russo Elisa M. S. , Viana Angelina L. , Fernandes Ana P. M. , Santos Isabel K. F. M. , Bonato Vânia L. D. , Dias-Baruffi Marcelo , Malheiro Adriana , Sadikot Ruxana T. , Cardoso Cristina R. B. , Faccioli Lúcia H. , Sorgi Carlos A. 
Published: September 2020

Background

The uncontrolled inflammatory response plays a critical role in the novel coronavirus disease (COVID-19) and triggering receptor expressed on myeloid cells-1 (TREM-1) is thought to be intricate to inflammatory signal amplification. This study aims to investigate the association between soluble TREM-1 (sTREM-1) and COVID-19 as a prognostic biomarker to predict the disease severity, lethality and clinical management.

Methods

We enrolled 91 patients with COVID-19 in domiciliary care (44 patients) or in hospital care (47 patients), who were classified after admission into mild, moderate, severe and critical groups according to their clinical scores. As non-COVID-19 control, 30 healthy volunteers were included. Data on demographic, comorbidities and baseline clinical characteristics were obtained from their medical and nurse records. Peripheral blood samples were collected at admission and after hospitalization outcome to assess cytokine profile and sTREM-1 level by specific immunoassays.

Results

Within COVID-19 patients, the highest severity was associated with the most significant elevated plasma levels sTREM-1. Using receiver operating curve analysis (ROC), sTREM-1 was found to be predictive of disease severity (AUC= 0.988) and the best cut-off value for predicting in-hospital severity was ≥ 116.5 pg/mL with the sensitivity for 93.3% and specificity for 95.8%. We also described the clinical characteristics of these patients and explored the correlation with markers of the disease aggravation. The levels of sTREM-1 were positively correlated with IL-6, IL-10, blood neutrophils counts, and critical disease scoring (r= 0.68,p<0.0001). On the other hand, sTREM-1 level was significantly negative correlated with lymphocytes counting, and mild disease (r= −0.42,p<0.0001). Higher levels of sTREM-1 were related to poor outcome and death, patients who received dexamethasone tended to have lower sTREM-1 levels.

Conclusion

Our results indicated that sTREM-1 in COVID-19 is associated with severe disease development and a prognostic marker for mortality. The use of severity biomarkers such as sTREM-1 together with patients clinical scores could improve the early recognition and monitoring of COVID-19 cases with higher risk of disease worsening.