Abstract
Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.
【초록키워드】 COVID-19, Neutrophils, Inflammatory diseases, SARS-CoV-2, neutrophil, lung, Cytokine storm syndrome, in vitro, angiotensin-converting enzyme 2, Autopsy, Cohort, pathophysiology, death, organ dysfunction, Neutrophil extracellular trap, virus replication, plasma, cell death, NETs, COVID-19 patients, acute respiratory distress, Concentration, detrimental, COVID-19 patient, tissue, tissue damage, healthy control, syndrome, serine protease, potential therapeutic target, NET, lung epithelial, enrolled, described, develop, involved, healthy, investigated, hospitalized patient, promote, induce, triggered, tracheal, released, diagnosis of COVID-19, 【제목키워드】 Neutrophil extracellular trap, COVID-19 pathology,