tetano
Editor, Senior Moderator
J Microbiol Biotechnol
. 2025 Nov 26:35:e2509004.
doi: 10.4014/jmb.2509.09004. Circulating NET Biomarkers as Predictors of Inflammatory Storm Escalation and Critical Illness in COVID-19
Wenjuan Liu[SUP] 1 [/SUP], Xin Pan[SUP] 2 [/SUP], Ruyue Fan[SUP] 3 [/SUP], Ying Yang[SUP] 3 [/SUP], Na Sun[SUP] 3 [/SUP], Peibin Hou[SUP] 3 [/SUP], Zuowang Cheng[SUP] 4 [/SUP], Chuanjun Huang[SUP] 2 [/SUP], Shuai Liu[SUP] 2 [/SUP], Lili Su[SUP] 2 [/SUP]
Affiliations
COVID-19 demonstrates distinct clinical heterogeneity, ranging from mild symptoms to severe acute respiratory distress syndrome (ARDS). Neutrophil extracellular traps (NETs), which are web-like structures consisting of decondensed DNA adorned with cytotoxic proteins such as myeloperoxidase (MPO) and citrullinated histone H3 (CitH3), play a crucial role in pathogen containment. However, they may also promote immunothrombosis and tissue injury. This research aimed to explore the association between NET formation and the severity of COVID-19. Plasma samples were collected from 99 patients diagnosed between 2022 and 2023. NET remnants were quantified through cell-free DNA (cfDNA), MPO-DNA, neutrophil elastase (NE)-DNA complexes, histone-DNA complexes, and CitH3. The levels of all NET biomarkers were significantly increased in COVID-19 patients and were positively correlated with disease severity. Notably, patients who required mechanical ventilation or high-flow oxygen had significantly higher concentrations of cfDNA, histone-DNA, and CitH3, indicating a strong connection between NETs and respiratory deterioration. Specifically, the combined model incorporating three NETs-related biomarkers demonstrated superior performance in discriminating disease severity, as evidenced by receiver operating characteristic (ROC) analysis. These findings suggest that excessive NET formation contributes to the pathogenesis of COVID-19, potentially via pro-inflammatory and pro-thrombotic pathways. Consequently, the combined model (histone-DNA, MPO-DNA, and CitH3) is identified as a promising biomarker signature for reflecting neutrophil-mediated immunopathology.
Keywords: CitH3; NETs; cfDNA; disease severity; protein-DNA complexes; superior respiratory support.
. 2025 Nov 26:35:e2509004.
doi: 10.4014/jmb.2509.09004. Circulating NET Biomarkers as Predictors of Inflammatory Storm Escalation and Critical Illness in COVID-19
Wenjuan Liu[SUP] 1 [/SUP], Xin Pan[SUP] 2 [/SUP], Ruyue Fan[SUP] 3 [/SUP], Ying Yang[SUP] 3 [/SUP], Na Sun[SUP] 3 [/SUP], Peibin Hou[SUP] 3 [/SUP], Zuowang Cheng[SUP] 4 [/SUP], Chuanjun Huang[SUP] 2 [/SUP], Shuai Liu[SUP] 2 [/SUP], Lili Su[SUP] 2 [/SUP]
Affiliations
- PMID: 41309368
- DOI: 10.4014/jmb.2509.09004
COVID-19 demonstrates distinct clinical heterogeneity, ranging from mild symptoms to severe acute respiratory distress syndrome (ARDS). Neutrophil extracellular traps (NETs), which are web-like structures consisting of decondensed DNA adorned with cytotoxic proteins such as myeloperoxidase (MPO) and citrullinated histone H3 (CitH3), play a crucial role in pathogen containment. However, they may also promote immunothrombosis and tissue injury. This research aimed to explore the association between NET formation and the severity of COVID-19. Plasma samples were collected from 99 patients diagnosed between 2022 and 2023. NET remnants were quantified through cell-free DNA (cfDNA), MPO-DNA, neutrophil elastase (NE)-DNA complexes, histone-DNA complexes, and CitH3. The levels of all NET biomarkers were significantly increased in COVID-19 patients and were positively correlated with disease severity. Notably, patients who required mechanical ventilation or high-flow oxygen had significantly higher concentrations of cfDNA, histone-DNA, and CitH3, indicating a strong connection between NETs and respiratory deterioration. Specifically, the combined model incorporating three NETs-related biomarkers demonstrated superior performance in discriminating disease severity, as evidenced by receiver operating characteristic (ROC) analysis. These findings suggest that excessive NET formation contributes to the pathogenesis of COVID-19, potentially via pro-inflammatory and pro-thrombotic pathways. Consequently, the combined model (histone-DNA, MPO-DNA, and CitH3) is identified as a promising biomarker signature for reflecting neutrophil-mediated immunopathology.
Keywords: CitH3; NETs; cfDNA; disease severity; protein-DNA complexes; superior respiratory support.