STREM-1 Predicts Disease Severity and Mortality in COVID-19 Patients: Involvement of Peripheral Blood Leukocytes and MMP-8 Activity.

Pedro Vieira Da Silva Neto ,Ruxana T Sadikot,Vinícius E Pimentel,Adriana Malheiro,Thais F C Fraga-Silva,Jonatan C S De Carvalho,Malena M Pérez,Fátima M Ostini,Leticia F Constant,Augusto M Degiovani,Ingryd Carmona‐Garcia ,Cristina Ribeiro De Barros Cardoso ,Víctor Alexandre Félix Bastos ,Camila Oliveira Silva Souza ,Marley Ribeiro Feitosa ,Talita Morais Fernandes ,Elisa Maria De Sousa Russo ,Antônio Luiz Boechat ,Sandra Regina Maruyama ,Lúcia Helena Faccioli ,Marcelo Dias‐Baruffi ,Fernando Crivelenti Vilar ,Diana Mota Toro ,Ana Paula Fernandes ,Isabel M Santos ,Carlos Alessandro Fuzo ,Omar Féres ,Camilla Narjara Simão Oliveira ,Vânia L D Bonato ,Jamille Guedes Malta Argolo ,Gilberto Gambero Gaspar ,Raquel Fernanda Gerlach ,Angelina Lettiere-Viana ,Rogério Serafim Parra ,Lílian Cataldi Rodrigues ,Carlos Artério Sorgi ,José Joaquim Ribeiro Da Rocha ,Fabiani Gai Frantz ,Nicola T Neto ,On Behalf Of The Imunocovid Study Group

doi:10.3390/v13122521

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.

Highlights

Coronavirus disease (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became a global public health problem due to the important frequencies of mortality
This study reported that plasma sTREM-1 concentration might serve as a predictive factor or biomarker for disease severity and mortality in a population of patients with COVID-19 in Ribeirão Preto, São
Our results suggest that plasma sTREM-1 levels at hospital admission can be used satisfactorily for evaluating disease severity and predicting adverse outcomes in patients with COVID-19

Summary

Introduction

Coronavirus disease (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became a global public health problem due to the important frequencies of mortality. 80% of patients infected with SARSCoV-2 will exhibit mild symptoms or remain asymptomatic. This infection may lead to serious clinical conditions, such as acute respiratory distress syndrome (ARDS), cardiovascular disorders, coagulopathy, and shock, which can result in multiorgan system dysfunction in certain patients [1,2,3]. To SARS, inflammation plays an important role in the pathophysiology of COVID-19, and patients with severe disease may have high serum concentrations of inflammatory markers such as IL-6, TNF, C-reactive protein (CRP), and D-dimer [6,7]. The immune responses to viral and bacterial infections are modulated by the activation of TREM-1 in macrophages [12]

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