Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Department of Statistics, Federal University of Parana, Curitiba, Brazil.
Mediators Inflamm. 2022 Apr 22;2022:9339411. doi: 10.1155/2022/9339411. eCollection 2022.
: Neutrophil extracellular traps (NETs) release (i.e., NETosis) has been recently implicated in the pathomechanism underlying severe end-organ damage in Coronavirus Disease 2019 (COVID-19) and could present a novel therapeutic target. We aimed to determine whether circulating levels of cell-free DNA (cfDNA), a surrogate for NETosis, may be associated with the development of acute kidney injury (AKI), a major contributor to poor outcomes and mortality in COVID-19. : Blood samples were collected prospectively from adult patients infected with SARS-CoV-2 presenting to the emergency department (ED). Circulating levels of cfDNA were quantified from patients' serum. Further assessment of correlations between cfDNA levels and markers of AKI (i.e., serum creatinine (SCr), cystatin C, neutrophil gelatinase-associated lipocalin (NGAL)), biomarkers of thrombotic microangiopathy and of inflammation in patients' serum was performed. : Fifty-one COVID-19 patients were enrolled. cfDNA levels were found to be significantly higher in those who developed severe AKI ( < 0.001) and those needing renal replacement therapy ( = 0.020). cfDNA positively correlated with ED SCr, NGAL, cystatin C, neutrophil count, neutrophil-to-lymphocyte ratio, C3a, C5a, Scb5-9, IL-6, IL-8, IL-10, TNF-, LDH, CRP, ferritin, and fibrinogen and negatively correlated with ADAMTS13/von-Willebrand factor ratio and lymphocyte count. In a multivariate logistic regression, a one-unit increase in cfDNA value was associated with 4.6% increased odds of severe AKI (OR = 1.046; = 0.040). Finally, cfDNA significantly correlated with established NETs components, myeloperoxidase, and neutrophil elastase. : Intravascular NETosis could be an important contributing factor in the development of microthrombosis and COVID-19-associated AKI. Further research is urgently needed to understand the role of NETosis in COVID-19 and evaluate therapeutic avenues for targeting this process.
中性粒细胞胞外诱捕网（NETs）的释放（即 NETosis）最近被认为与 2019 年冠状病毒病（COVID-19）严重终末器官损伤的发病机制有关，并且可能成为一个新的治疗靶点。我们旨在确定循环游离 DNA（cfDNA）水平是否与急性肾损伤（AKI）的发生有关，AKI 是 COVID-19 患者预后不良和死亡率高的主要原因。
前瞻性采集因 SARS-CoV-2 感染而就诊于急诊科的成年患者的血液样本。从患者血清中定量循环 cfDNA 水平。进一步评估 cfDNA 水平与 AKI 标志物（即血清肌酐（SCr）、胱抑素 C、中性粒细胞明胶酶相关脂质运载蛋白（NGAL））、患者血清中血栓性微血管病和炎症的标志物之间的相关性。
共纳入 51 例 COVID-19 患者。结果发现，发生严重 AKI（<0.001）和需要肾脏替代治疗的患者（=0.020）cfDNA 水平显著升高。cfDNA 与 ED SCr、NGAL、胱抑素 C、中性粒细胞计数、中性粒细胞与淋巴细胞比值、C3a、C5a、Scb5-9、IL-6、IL-8、IL-10、TNF-、LDH、CRP、铁蛋白和纤维蛋白原呈正相关，与 ADAMTS13/血管性血友病因子比值和淋巴细胞计数呈负相关。在多变量逻辑回归中，cfDNA 值增加一个单位，严重 AKI 的几率增加 4.6%（OR=1.046；=0.040）。最后，cfDNA 与已建立的 NETs 成分（髓过氧化物酶和中性粒细胞弹性蛋白酶）显著相关。
血管内 NETosis 可能是 COVID-19 相关 AKI 微血栓形成的重要因素。迫切需要进一步研究以了解 NETosis 在 COVID-19 中的作用，并评估针对该过程的治疗途径。
