Avaliação do potencial de TREM-1 como biomarcador da Covid-19 e sua correlação com a patogenicidade da doença

Abstract

Coronavirus 2019 (Covid-19) is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system, characterized by severe inflammatory conditions. In this context, the receptor expressed in myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals. Thus, to elucidate how this receptor contributes to the immunopathology or dysregulation of the immune response observed in Covid-19, we determined the expression of TREM-1 and its soluble counterpart (sTREM-1) during disease severity and in the pulmonary microenvironment, correlating these data with other clinical, molecular and cellular parameters. Based on clinical scores, we included Covid-19-positive patients classified into specific symptom severity groups (mild, moderate, severe, and critical) in our cohort. In peripheral blood, we observed that the production of sTREM-1 was significantly higher among patients with severe disease, showing positive correlations with inflammatory parameters, clinical progression and mortality. Furthermore, their systemic levels were positively correlated with elevated MMP-8 expression, suggesting a mechanism for TREM-1 release from the surface of peripheral blood cells. In the lung microenvironment, we related the high diversity of MMPs to the severity of Covid-19. Our results indicated a strong enzymatic activity of MMP-2 in aspirated tracheal fluid (TAF) samples from patients who died. Furthermore, we observed an increase in neutrophil infiltration, production of reactive oxygen species (ROS) and lipid peroxidation, in cooperation with the expression of MMP-8 and MMP-2, also favorable for the release of sHLA-G and sTREM-1 in lung tissue. Network analysis showed that miRNAs related to the TREM-1 pathway may favor regulatory processes during disease severity. Together, we suggest that TREM-1 can be used as a predictive tool for the progression and outcome of Covid-19, as well as participating in the pathogenicity mechanism by increasing hyperinflammation in Covid-19, via the action of endoproteinases and in the regulation of the response. miRNA immune.