S100A8 may govern hyper-inflammation in severe COVID-19

Area of Science:

• Immunology
• Molecular Biology
• Pathology

Background:

• The COVID-19 pandemic presents a significant global health threat with a notable mortality rate.
• Predicting herd immunity and the pandemic's end remains challenging, necessitating identification of disease severity markers and therapeutic targets.
• BCR-ABL in chronic myeloid leukemia serves as a successful model for a dual biomarker and molecular target.

Purpose of the Study:

• To investigate the hypothesis that S100 calcium-binding protein A8 (S100A8) is a critical molecule in COVID-19 pathogenesis.
• To explore S100A8 as a potential biomarker and therapeutic target for severe COVID-19, particularly COVID-19-associated acute respiratory distress syndrome (ARDS).

Main Methods:

• Review of clinical data showing S100A8 upregulation in severe COVID-19.
• Comparison of lung pathology in COVID-19 with S100A8-induced ARDS models.
• Analysis of S100A8's role in homeostatic inflammation via Toll-like receptor 4/Myeloid differentiation protein-2 (TLR4/MD-2) pathway.
• Examination of analogous findings between COVID-19 ARDS and pre-metastatic lung conditions.

Main Results:

• S100A8 is clinically observed to be upregulated in severe COVID-19 cases.
• Pathological similarities exist between COVID-19 lungs and S100A8-induced ARDS models.
• S100A8 mediates hyper-inflammation through the TLR4/MD-2 pathway, potentially independent of extrinsic pathogens.
• Therapeutic strategies targeting S100A8/S100A9 interaction with TLR4 showed success in an animal COVID-19 model.

Conclusions:

• S100A8 is strongly implicated in the development of COVID-19-associated ARDS.
• S100A8 represents a promising molecular target for therapeutic intervention in severe COVID-19.
• Further research into S100A8's role could lead to novel treatments for hyper-inflammatory responses in COVID-19.