Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes released by neutrophils to combat infections. However, when not properly regulated, NETs can contribute to inflammation and microvascular thrombosis, including in the lungs of patients with acute respiratory distress syndrome (ARDS). A study found that patients with severe coronavirus disease 2019 (COVID-19) had elevated levels of cell-free DNA, myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3) in their sera, which are specific markers of NETs. These markers correlated with acute-phase reactants such as C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count and platelet levels. Patients requiring mechanical ventilation had higher levels of cell-free DNA and MPO-DNA compared to those breathing room air. Additionally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. The study suggests that NETs may play a role in the inflammatory storm and thrombo-inflammatory processes in severe COVID-19. Future research should investigate the predictive power of circulating NETs in longitudinal cohorts and determine their potential as therapeutic targets. The study highlights the importance of understanding the role of neutrophil effector functions in the complications of COVID-19.Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes released by neutrophils to combat infections. However, when not properly regulated, NETs can contribute to inflammation and microvascular thrombosis, including in the lungs of patients with acute respiratory distress syndrome (ARDS). A study found that patients with severe coronavirus disease 2019 (COVID-19) had elevated levels of cell-free DNA, myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3) in their sera, which are specific markers of NETs. These markers correlated with acute-phase reactants such as C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count and platelet levels. Patients requiring mechanical ventilation had higher levels of cell-free DNA and MPO-DNA compared to those breathing room air. Additionally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. The study suggests that NETs may play a role in the inflammatory storm and thrombo-inflammatory processes in severe COVID-19. Future research should investigate the predictive power of circulating NETs in longitudinal cohorts and determine their potential as therapeutic targets. The study highlights the importance of understanding the role of neutrophil effector functions in the complications of COVID-19.