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

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.

The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19

“…In another study, it was shown that AEA and 2-AG reduce pro-inflammatory cytokines and increase anti-inflammatory cytokines in individuals with HIV [ 55 ]. Indeed, we observed a positive association between 2-AG production and IL-10 and lymphocyte counts and a negative correlation with different COVID-19 markers of hyperinflammation, such as IL-6 [ 56 ], sTREM-1 [ 57 ] and neutrophil counts [ 56 ]. Although high levels of 2-AG did not prevent the severe course of COVID-19, they did demonstrate anti-inflammatory capabilities.…”

Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly

“…Corroborating this hypothesis, previous data from our group has shown an association between SNPs in TLR3 and TNFα involved in the decrease of antiviral immune response, with CZS occurrence and severity 19 . In contrast, higher levels of sTREM-1 have been described as indicative of poor prognosis in early stages of DENV arbovirus infection 46 , and recently, on the outcomes of SARS-CoV-2 infections 47 .…”

aMMP-8 Oral Fluid PoC Test in Relation to Oral and Systemic Diseases

“…This novel aMMP-8 chairside test also finds applicability in establishing the relationships between oral, general, and systemic health parameters, and aMMP-8 oral fluid PoCT has also been investigated namely, reproductive health parameters [40][41][42], diabetes [43,44], COVID-19-infection [45,46], and head and neck cancers' radiotherapy and its oral destructive immunodystrophic side effects [47]. Umeizudike and associates recently highlighted the potential usefulness of the aMMP-8 biomarker PoCT as a bridge between oral/periodontal and systemic diseases [48].…”