Expression of the membrane receptor mTREM-1 in peripheral blood cells and levels of soluble TREM-1 (sTREM-1) in children and adolescents with comorbidities and mild, moderate, severe or critical COVID-19.

• Grant number: 22/00831-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2022
• End date: April 30, 2023
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Thelma Suely Okay
• Grantee: Gabriel Acca Barreira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

There is still no consensus in the literature on the role of comorbidities, and whether all comorbidities influence the severity and prognosis of COVID-19 in children and adolescents. However, it is known that SARS-CoV-2 acts decisively on the innate immunity of the human host, using several strategies to subvert the control of the immune response. After birth, newborns and young infants have immature immune systems, increasing their susceptibility to infections. In this sense, innate immunity plays a key role in the first years of life, as the development of the adaptive immune response will only be completed after the first decade of life. In the present proposal we intend to evaluate the expression by Real Time PCR of TREM-1 receptors (Triggering Receptor Expressed on Myeloid cells-1) found on the surface of membranes (mTREM-1) of myeloid cells: neutrophils, monocytes, eosinophils and basophils, as well as tissue macrophages and mast cells, and lymphoid cells (T, B lymphocytes and NK cells), in the peripheral blood of pediatric patients with comorbidities, with or without COVID-19. This receptor plays a central role in the transduction of the signal generated in infectious processes and in the activation of transcription factors that stimulate the production of pro-inflammatory cytokines in the early stages of infection, and of anti-inflammatory cytokines in later stages. It is also intended to evaluate blood levels of the soluble form of TREM-1 (sTREM-1) that corresponds to the mTREM-1 ectodomain after cleavage by metalloproteinases. Our hypothesis is that in severe/critical cases of COVID-19 in children with comorbidities, we will find reduced expression of mTREM-1, leading to reduction of MCL-1 (a member of the intrinsic or mitochondrial pathway of cell death that has anti-apoptotic properties), therefore accelerating the death of immune cells at the infectious site. As for the concentrations of soluble TREM-1 (sTREM-1), they will be evaluated by ELISA and should be increased precisely due to the reduction of mTREM-1 that favors the production of sTREM-1. The greater availability of sTREM-1 in circulation will generate competition with mTREM-1 receptors for the binding with TREM-1 ligands, leading to an even greater reduction in the stimulation of the innate immune system and the release of pro-inflammatory cytokines in early infection, and of anti-inflammatory cytokines later, preventing the counter-regulation of the "cytokine storm", leading to cell death and perpetuation of irreversible tissue damage.