eritoran and Cytokine-Release-Syndrome

The coronavirus disease 2019 (COVID-19) pandemic threatens human species with mortality rate of roughly 2%. We can hardly predict the time of herd immunity against and end of COVID-19 with or without success of vaccine. One way to overcome the situation is to define what delineates disease severity and serves as a molecular target. The most successful analogy is found in BCR-ABL in chronic myeloid leukemia, which is the golden biomarker, and simultaneously, the most effective molecular target. We hypothesize that S100 calcium-binding protein A8 (S100A8) is one such molecule. The underlying evidence includes accumulating clinical information that S100A8 is upregulated in severe forms of COVID-19, pathological similarities of the affected lungs between COVID-19 and S100A8-induced acute respiratory distress syndrome (ARDS) model, homeostatic inflammation theory in which S100A8 is an endogenous ligand for endotoxin sensor Toll-like receptor 4/Myeloid differentiation protein-2 (TLR4/MD-2) and mediates hyper-inflammation even after elimination of endotoxin-producing extrinsic pathogens, analogous findings between COVID-19-associated ARDS and pre-metastatic lungs such as S100A8 upregulation, pulmonary recruitment of myeloid cells, increased vascular permeability, and activation coagulation cascade. A successful treatment in an animal COVID-19 model is given with a reagent capable of abrogating interaction between S100A8/S100A9 and TLR4. In this paper, we try to verify our hypothesis that S100A8 governs COVID-19-associated ARDS.

Topics: Angiotensin-Converting Enzyme 2; Animals; Antiviral Agents; Calgranulin A; Chemokine CXCL11; COVID-19; Cytokine Release Syndrome; Disaccharides; Disease Models, Animal; Drug Discovery; Epithelial Cells; Humans; Inflammation; Lung; Lung Neoplasms; Lymphocyte Antigen 96; Macaca mulatta; Mice; Mice, Transgenic; Models, Biological; Mutation; Pandemics; Respiratory Distress Syndrome; SARS-CoV-2; Species Specificity; Sugar Phosphates; Toll-Like Receptor 4; Up-Regulation; Virus Internalization