CHEST Guidelines-Neutrophil-Extracellular-Traps,-Local-IL-8-Express

Neutrophil-Extracellular-Traps,-Local-IL-8-Express

Pdf Summary

The study explores the role of neutrophil extracellular traps (NETs) in the severe inflammatory response observed in fatal COVID-19 cases. Researchers analyzed lung and liver tissue samples from 16 patients who died from COVID-19, using methods such as multiplexed immunofluorescence to assess NETs' presence and spatial distribution. The study found that NETs were abundant in the lungs but were unrelated to the local presence of SARS-CoV-2 virus, contrary to expectations. Instead, NET prevalence strongly correlated with high local levels of the chemokine IL-8, suggesting that IL-8 may induce NETosis, which is the process of NETs formation related to cell death.<br /><br />The study also noted a negative correlation between NETs presence and CD8+ T-cell infiltration in the lungs, implying that the presence of NETs might interfere with effective immune responses against the virus. In addition, NETs were noted in pulmonary thrombi, despite not being significantly present in the liver, indicating their specific association with lung pathology in COVID-19.<br /><br />The findings point to excessive inflammation, evidenced by NETs formation, as a significant contributor to lung damage in severe COVID-19, possibly more so than the direct effects of the virus itself. The opportunity for therapeutic intervention is suggested, targeting NET formation pathways using inhibitors of molecules like peptidyl arginine deiminase 4 or IL-8 via established drugs or antibodies currently in trial stages for various conditions. Overall, the study underscores NETs as potential key players in COVID-19 pathology, with IL-8 potentially as a causative agent, offering new avenues for treatment development aimed at reducing lung tissue damage in patients with severe COVID-19.

Keywords

neutrophil extracellular traps

NETs

COVID-19

inflammatory response

IL-8

NETosis

lung pathology

therapeutic intervention

peptidyl arginine deiminase 4

CD8+ T-cell