Neutrophil extracellular traps in COVID-19.
By Y. Zuo, S. Yalavarthi, Huirong Shi, K. Gockman, M. Zuo, J. Madison, C. Blair, Andrew Weber, B. Barnes, M. Egeblad and 3 more. JCI Insight, 2020
1,366 citations recorded by the source corpus.
In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have potential to propagate inflammation and microvascular thrombosis - including in the lungs of patients with acute respiratory distress syndrome. While elevated levels of blood neutrophils predict worse outcomes in COVID-19, the role of NETs has not been investigated. We now report that sera from patients with COVID-19 (n = 50 patients, n = 84 samples) have elevated levels of cell-free DNA, myeloperoxidase(MPO)-DNA, and citrullinated histone H3 (Cit-H3); the latter two are highly specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute phase reactants including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. In summary, these data reveal high levels of NETs in many patients with COVID-19, where they may contribute to cytokine release and respiratory failure. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts, and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.
Subfields: Epidemiology, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/4740e7948f7171d599ad50c5513e1819cec6b5ec
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Citations in the corpus
- Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis (2020, background): “NETs appear to be involved in COVID-19 as well (9).”
- The cytokine storm and COVID‐19 (2020, background): “extracellular nets released by neutrophils, may contribute to cytokine release.(36) The cytokine storm in COVID‐19 is characterized by a high expression of IL‐6 and TNF‐α.”
- COVID-19 update: Covid-19-associated coagulopathy (2020, background): “[47] reported high levels of circulating cf-DNA and DNA-myeloperoxidase complexes in patients with Covid-19.”
- Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment (2020, neutral): “The transcriptional programs induced in immature neutrophils, including pro- and pre-neutrophils, as well as in COVID-19-associated mature neutrophil clusters, align with other observations in severe COVID-19 patients, including increased NET formation (Barnes et al., 2020; Zuo et al., 2020), coagul”
- COVID-19 and multisystem inflammatory syndrome in children and adolescents (2020, positive): “…un controlled manner, leading to an exaggerated systemic inflammatory response, 84 similar to hyperinflammation seen in MISC. Zuo and colleagues 85 have shown that NETs are increased in the plasma of patients infected with SARSCoV2, and higher concentrations of NETs are seen in those with…”
- Mechanisms of SARS-CoV-2 Transmission and Pathogenesis (2020, neutral): “From another angle, formation of neutrophil extracellular traps (NETs) inside microvessels is pronounced in patients with severe relative to mild COVID-19, implicating NETs as possible potentiators of COVID-19 pathogenesis [89].”