Schematic representation of the TREM-1/sTREM-1 pathway during the severity of COVID-19. SARS-CoV-2 activates innate immune receptors in infected cells and triggers the inflammatory transcription factor into the nucleus, where it induces several pro-inflammatory genes, including up-regulation of TREM-1. After binding to its ligand, TREM-1 associates with the adapter molecule DAP12, leading to a cascade of phosphorylation in a downstream kinase panel that, in turn, activates other transcription factors and amplifies the inflammatory response, as well as production of cytokines. It is speculated that high levels of circulating sTREM-1 were released from the surface of the peripheral blood leukocyte membrane related to MMP-8 activity. Therefore, individuals with high levels of sTREM-1 can indicate a dysregulated immune response (Created with BioRender.com, Agreement number: AZ238AM20F).