Abstract
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.
Keywords: Coronavirus disease 2019; S100A8; Toll-like receptor; acute respiratory distress syndrome; myeloid-derived suppressor cells.
【저자키워드】 Coronavirus disease 2019, acute respiratory distress syndrome, Toll-like receptor, S100A8, myeloid-derived suppressor cells., 【초록키워드】 COVID-19, Treatment, coronavirus disease, Inflammation, Respiratory distress syndrome, Coronavirus disease 2019, ARDS, Vaccine, coronavirus, pandemic, Biomarker, acute respiratory distress syndrome, Immunity, TLR4, disease severity, myeloid cells, lung, vascular permeability, Toll-like receptor, Elimination, Coagulation, cells, herd immunity, hyper-inflammation, Pathogens, receptor, mortality rate, recruitment, disease, predict, leukemia, calcium, acute respiratory distress, S100A8, coagulation cascade, endotoxin, Evidence, Ligand, Interaction, Hypothesis, similarity, chronic myeloid leukemia, respiratory distress, Activation, calcium-binding protein, situation, clinical information, syndrome, upregulation, severe forms of COVID-19, molecular target, reagent, S100A9, effective, COVID-19-associated ARDS, increased vascular permeability, affected, include, form, overcome, to define, upregulated, extrinsic, accumulating, homeostatic, 【제목키워드】 severe COVID-19,