S100A8 may govern hyper‐inflammation in severe COVID‐19

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.

Characterization of Early Peripheral Immune Responses in Patients with Sepsis and Septic Shock

“…P-selectin has been proposed as a central mediator of platelet aggregation and thrombus formation in sepsis [67]. Moreover, S100A8 is derived from neutrophils and can also promote coagulation through a mechanism involving the activation of platelets [68,69], a process which is also facilitated by P-selectin expression in the surface of platelets (Figure 8). Importantly E-selectin and P-selectin showed a moderate positive correlation in our study.…”

LeLISA: a new lectin-based immunoassay for evaluation of mucins and pancreatic cystic lesions (PCL)

“…The binding of S100A8 to GNA (data not shown) opens a link to a better understanding of many different types of disease since the former may cause severe Covid-19 disease (15), may promote epithelialmesenchymal transition and metastasis in colorectal cancer (16), may protect alveolar cells against injury and emphysema development (17), may cause poor prognosis in mammary cancer (18) while appearance of S100A8 on stromal cells may be bene cial in colorectal cancer (19). Theoretically, treatment with lectins binding S100A8 might in uence such phenomena.…”

Circulating Calprotectin as a Predictive and Severity Biomarker in Patients with COVID-19

“…Interest in calprotectin as a biomarker of inflammation has surged with its increasing availability on ELISA and automated platforms, and with better understanding of the important pre-analytical requirements for reproducible measurement [ 13 , 18 , 19 , 20 ]. Recognition that changes in calprotectin levels can indicate increasing or decreasing inflammatory changes in diverse inflammatory conditions has led to growing interest in cCP as a practical and clinically useful biomarker for patient management, and as a potential therapeutic target [ 4 , 20 , 21 , 22 , 23 , 24 ]. However, despite multiple recent studies showing that cCP levels correlate better with the severity of COVID-19 than a host of other biomarkers—including IL-6 and CRP—cCP is seldom used to assess and follow COVID-19 patients, likely due to unfamiliarity and, until recently, the unavailability of automated, quantitative practical assays [ 7 , 8 , 9 , 23 , 24 , 25 ].…”