sTREM-1 Predicts Disease Severity and Mortality in COVID-19 Patients: Involvement of Peripheral Blood Leukocytes and MMP-8 Activity
Pedro V. da Silva‐Neto, Jonatan C. S. de Carvalho, Vinícius E. Pimentel, Malena M. Pérez, Diana Mota Toro, Thais Fernanda de Campos Fraga‐Silva, Carlos Alessandro Fuzo, Camilla N. S. Oliveira, Lílian Cataldi Rodrigues, Jamille Guedes Malta Argolo, Ingryd Carmona‐Garcia, Nicola T. Neto, Camila Oliveira Silva Souza, Talita Morais Fernandes, Víctor Alexandre Félix Bastos, Augusto M. Degiovani, Leticia F. Constant, Fátima M. Ostini, Marley Ribeiro Feitosa, Rogério Serafim Parra, Fernando Crivelenti Vilar, Gilberto Gambero Gaspar, José Joaquim Ribeiro da Rocha, Omar Féres, Fabiani Gai Frantz, Raquel F. Gerlach, Sandra Regina Maruyama, Elisa Maria de Sousa Russo, Angelina Lettiere-Viana, Ana Paula Fernandes, Isabel Kinney Ferreira de Miranda Santos, Vânia Luiza Deperon Bonato, Antônio Luiz Boechat, Adriana Malheiro, Ruxana T. Sadikot, Marcelo Dias‐Baruffi, Cristina Ribeiro de Barros Cardoso, Lúcia Helena Faccioli, Carlos A. Sorgi, on behalf of the IMUNOCOVID Study Group
Abstract
Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.