Department of Laboratory Medicine, Seoul National University College of Medicine.
Department of Laboratory Medicine, Yonsei University College of Medicine.
Ann Clin Lab Sci. 2022 May;52(3):374-381.
Exploration of biomarkers to predict the severity of COVID-19 is important to reduce mortality. Upon COVID-19 infection, neutrophil extracellular traps (NET) are formed, which leads to a cytokine storm and host damage. Hence, the extent of NET formation may reflect disease progression and predict mortality in COVID-19.
We measured 4 NET parameters - cell-free double stranded DNA (cell-free dsDNA), neutrophil elastase, citrullinated histone H3 (Cit-H3), and histone - DNA complex - in 188 COVID-19 patients and 20 healthy controls. Survivors (n=166) were hospitalized with or without oxygen supplementation, while non-survivors (n=22) expired during in-hospital treatment.
Cell-free dsDNA was significantly elevated in non-survivors in comparison with survivors and controls. The survival rate of patients with high levels of cell-free dsDNA, neutrophil elastase, and Cit-H3 was significantly lower than that of patients with low levels. These three markers significantly correlated with inflammatory markers (absolute neutrophil count and C-reactive protein).
Since the increase in NET parameters indicates the unfavourable course of COVID-19 infection, patients predisposed to poor outcome can be rapidly managed through risk stratification by using these NET parameters.
探索预测 COVID-19 严重程度的生物标志物对于降低死亡率非常重要。在 COVID-19 感染后,会形成中性粒细胞胞外诱捕网(NET),导致细胞因子风暴和宿主损伤。因此,NET 形成的程度可能反映疾病的进展,并预测 COVID-19 的死亡率。
我们测量了 188 名 COVID-19 患者和 20 名健康对照者的 4 个 NET 参数-无细胞双链 DNA(cell-free dsDNA)、中性粒细胞弹性蛋白酶、瓜氨酸化组蛋白 H3(Cit-H3)和组蛋白-DNA 复合物。幸存者(n=166)在住院时需要或不需要补充氧气,而非幸存者(n=22)在住院期间死亡。
与幸存者和对照组相比,非幸存者的无细胞 dsDNA 明显升高。高水平无细胞 dsDNA、中性粒细胞弹性蛋白酶和 Cit-H3 的患者生存率明显低于低水平患者。这三个标志物与炎症标志物(中性粒细胞计数和 C 反应蛋白)显著相关。
由于 NET 参数的增加表明 COVID-19 感染的不良进程,因此可以通过使用这些 NET 参数进行风险分层,快速对预后不良的患者进行管理。