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Emergence of Low-density Inflammatory Neutrophils Correlates with Hypercoagulable State and Disease Severity in COVID-19 Patients
medRxiv - Allergy and Immunology Pub Date : 2020-05-26 , DOI: 10.1101/2020.05.22.20106724
Samantha M Morrissey , Anne E Geller , Xiaoling Hu , David Tieri , Elizabeth A Cooke , Chuanlin Ding , Matthew Woeste , Huang-ge Zhange , Rodrigo Cavallazi , Sean P Clifford , James Chen , Maiying Kong , Corey T Watson , Jiapeng Huang , Jun Yan

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Approximately 20% of infected patients experience a severe manifestation of the disease, causing bilateral pneumonia and acute respiratory distress syndrome. Severe COVID-19 patients also have a pronounced coagulopathy with approximately 30% of patients experiencing thromboembolic complications. However, the etiology driving the coagulopathy remains unknown. Here, we explore whether the prominent neutrophilia seen in severe COVID-19 patients contributes to inflammation-associated coagulation. We found in severe patients the emergence of a CD16IntCD44lowCD11bInt low-density inflammatory band (LDIB) neutrophil population that trends over time with changes in disease status. These cells demonstrated spontaneous neutrophil extracellular trap (NET) formation, phagocytic capacity, enhanced cytokine production, and associated clinically with D-dimer and systemic IL-6 and TNF-α levels, particularly for CD40+ LDIBs. We conclude that the LDIB subset contributes to COVID-19-associated coagulopathy (CAC) and could be used as an adjunct clinical marker to monitor disease status and progression. Identifying patients who are trending towards LDIB crisis and implementing early, appropriate treatment could improve all-cause mortality rates for severe COVID-19 patients.

中文翻译:

低密度炎症性中性粒细胞的出现与COVID-19患者的高凝状态和疾病严重程度相关

严重急性呼吸综合症冠状病毒2(SARS-CoV-2)是一种新型病毒病原体,可导致称为冠状病毒病2019(COVID-19)的临床疾病。大约20%的感染患者经历了该病的严重表现,引起双侧肺炎和急性呼吸窘迫综合征。严重的COVID-19患者也有明显的凝血病,约30%的患者出现血栓栓塞并发症。然而,导致凝血病的病因仍然未知。在这里,我们探讨在严重的COVID-19患者中看到的显着嗜中性粒细胞是否有助于炎症相关的凝血。我们发现在严重的患者中出现了CD16IntCD44lowCD11bInt低密度炎性带(LDIB)中性粒细胞群,其随着疾病状况的变化而随时间变化。这些细胞表现出自发的中性粒细胞胞外陷阱(NET)形成,吞噬能力,​​增强的细胞因子产生,并在临床上与D-二聚体和全身性IL-6和TNF-α水平相关,尤其是CD40 + LDIBs。我们得出的结论是,LDIB子集可导致COVID-19相关性凝血病(CAC),并可用作监测疾病状态和进展的辅助临床标志物。识别出倾向于LDIB危机并尽早实施适当治疗的患者可以提高重症COVID-19患者的全因死亡率。我们得出的结论是,LDIB子集可导致COVID-19相关性凝血病(CAC),并可用作监测疾病状态和进展的辅助临床标志物。识别出倾向于LDIB危机并尽早实施适当治疗的患者可以提高重症COVID-19患者的全因死亡率。我们得出的结论是,LDIB子集可导致COVID-19相关性凝血病(CAC),并可用作监测疾病状态和进展的辅助临床标志物。识别出倾向于LDIB危机并尽早实施适当治疗的患者可以提高重症COVID-19患者的全因死亡率。
更新日期:2020-05-26
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