DEGUCHI Atsuko    Department   Graduate School of Medical Science, Graduate School of Medical Science    Position   Professor
Article types	Original article
Language	English
Peer review	Non peer reviewed
Title	S100A8 may govern hyper-inflammation in severe COVID-19.
Journal	Formal name：FASEB journal Abbreviation：FASEB J ISSN code：15306860/08926638
Domestic / Foregin	Foregin
Volume, Issue, Page	35(9),pp.e21798
Author and coauthor	Deguchi Atsuko, Yamamoto Tomoko, Shibata Noriyuki, Maru Yoshiro
Authorship	Lead author
Publication date	2021/09
Summary	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.
DOI	10.1096/fj.202101013
PMID	34339064