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. In COVID-19, viral pathogen associated molecular patterns and viral-induced cytokines can induce NETosis of neutrophils at the site of infection and in the periphery. Siglec-9 agonists inhibit COVID-19 plasma-induced NETosis, potentially preventing deleterious hyperinflammatory responses.
【초록키워드】 COVID-19, coronavirus disease, Production, Inflammation, immune response, severe COVID-19, neutrophil, Infection, TLRs, cytokine, Toll-like receptor, proinflammatory, hyperinflammation, therapeutic, Patient, death, pathway, Neutrophil extracellular trap, NETosis, complications, plasma, receptor, cell death, NETs, therapeutic strategy, Signaling, Deleterious, neutrophil activation, tissue damage, hyperinflammatory responses, key factor, agonist, cascade, neutrophilic, viral pathogen, Hyperinflammatory, NET, limit, caused, inhibit, characterized, suggested, induce, activate, suppress, viral-induced, infection with SARS-CoV-2, molecular pattern, 【제목키워드】 synthetic, agonist, with COVID-19,