Xudong Cui,1,* Tiewei Li,2,* Jingping Yang,3 Xiaojuan Li,2 Pengfei Xuan,3 Hongyan Wang3 

1Respiratory and Critical Care Medicine Department, Inner Mongolia Baogang Hospital, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 2Department of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, People’s Republic of China; 3Respiratory and Critical Care Medicine Department, Inner Mongolia Baogang Hospital, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Tiewei Li; Jingping Yang, Email litieweind@163.com; yangron@sina.com

Background: Previous studies have demonstrated that neutrophil extracellular traps (NETs) are crucial in infectious diseases. This study aims to evaluate the clinical value of NET-related biomarkers in identifying the risk of COVID-19 and diagnosing the disease.
Methods: This study involved 32 patients who tested positive for COVID-19 via polymerase chain reaction (PCR) between April and August 2023. During the same period, 30 healthy volunteers were enrolled as a control group. The principal biomarkers related to NETs are citrullinated histone H3 (CitH3), double-stranded DNA (dsDNA), myeloperoxidase-DNA complex (MPO-DNA), and Nucleosome. Elevated levels in two or more of these biomarkers indicate raised NET concentrations. Multivariable logistic regression analysis was employed to assess whether NET-related biomarkers were the independent risk factor of COVID-19. The diagnostic value of NET-related biomarkers in COVID-19 was further evaluated using receiver operating characteristic (ROC) curve analysis. Statistical procedures were executed in SPSS software (version 24.0, USA).
Results: Compared with the control group, patients infected with COVID-19 had higher levels of dsDNA and nucleosomes (P < 0.001). Correlation analysis revealed a positive correlation between dsDNA levels and neutrophil count (r = 0.309, P = 0.015) as well as between nucleosome levels and neutrophil count (r = 0.446, P < 0.001). Further analysis showed that dsDNA and nucleosomes were independent risk factors for COVID-19 infection. ROC curve analysis showed that dsDNA area under the curve (AUC) = 0.777, 95% confidence interval (CI), 0.661– 0.893, P < 0.001, and nucleosomes (AUC = 0.884, 95% CI, 0.778– 0.991, P < 0.001) had well diagnostic value in the diagnosing COVID-19 infection.
Conclusion: NET-related biomarkers, dsDNA and nucleosomes, were independent risk factors of COVID-19 infection and potentially useful biomarkers in diagnosing COVID-19 infection in older patients.

Keywords: neutrophil extracellular traps, COVID-19, pneumonia, dsDNA, nucleosomes, older patient