Fig 3.
eNAMPT is a novel DAMP in COVID-19 infection and in the development of ARDS. In response to a variety of injurious ARDS-relevant stimuli, including trauma, hypoxia, mechanical stress (generated by mechanical ventilation) and SARS-CoV2 infection, the NAMPT gene is activated, primarily in epithelial cells, leukocytes and vascular endothelial cells, to generate and secrete eNAMPT into the blood.10,73 Circulating eNAMPT functions as a damage-associated molecular pattern protein or DAMP via ligation of pathogen-recognition receptor, TLR4, eliciting NFkB-mediated gene expression and activation of systemic inflammatory cascades.73 The elaborated cytokines, that is, the “cytokine storm,” produce systemic inflammation with increases in vascular permeability, organ edema and multiorgan failure, the main contributor to ARDS mortality. ARDS, acute respiratory distress syndrome; DAMP, damage-associated molecular pattern protein; eNAMPT, extracellularly-secreted nicotinamide phosphoribosyl-transferase.