Synthetic Siglec-9 Agonists Inhibit Neutrophil Activation Associated with COVID-19

Area of Science:

• Immunology
• Virology
• Pharmacology

Background:

• Severe COVID-19 involves a hyperinflammatory immune response.
• Neutrophil extracellular traps (NETs) contribute to inflammation and tissue damage in COVID-19.
• Blocking neutrophil activation and NETosis is a potential therapeutic strategy.

Approach:

• Investigated synthetic glycopolymers designed to activate the Siglec-9 receptor on neutrophils.
• Tested the effect of Siglec-9 agonists on NETosis induced by viral toll-like receptor (TLR) agonists.
• Evaluated Siglec-9 agonist efficacy using plasma from patients with severe COVID-19.

Key Points:

• Synthetic glycopolymers activating Siglec-9 effectively suppress NETosis.
• This suppression occurs even when NETosis is triggered by viral TLR agonists.
• Siglec-9 agonism mitigates NET formation induced by severe COVID-19 patient plasma.

Conclusions:

• Siglec-9 agonism represents a promising therapeutic strategy for severe COVID-19.
• Targeting Siglec-9 can mitigate the detrimental effects of neutrophilic hyperinflammation.
• This approach may help reduce pulmonary tissue damage and improve outcomes in critical COVID-19 cases.