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

Severe cases of coronavirus
disease 2019 (COVID-19), caused by
infection with SARS-CoV-2, are characterized by a hyperinflammatory
immune response that leads to numerous complications. Production of
proinflammatory neutrophil extracellular traps (NETs) has been suggested
to be a key factor in inducing a hyperinflammatory signaling cascade,
allegedly causing both pulmonary tissue damage and peripheral inflammation.
Accordingly, therapeutic blockage of neutrophil activation and NETosis,
the cell death pathway accompanying NET formation, could limit respiratory
damage and death from severe COVID-19. Here, we demonstrate that synthetic
glycopolymers that activate signaling of the neutrophil checkpoint
receptor Siglec-9 suppress NETosis induced by agonists of viral toll-like
receptors (TLRs) and plasma from patients with severe COVID-19. Thus,
Siglec-9 agonism is a promising therapeutic strategy to curb neutrophilic
hyperinflammation in COVID-19.