Abstract：
The infectious respiratory condition COVID-19 manifests a clinical course ranging from mild/moderate up-to critical systemic dysfunction and death linked to thromboinflammation. During COVID-19 infection, neutrophil extracellular traps participating in cytokine storm and coagulation dysfunction have emerged as diagnostic/prognostic markers. The characterization of NET identified that mainly histones, have the potential to initiate and propagate inflammatory storm and thrombosis, leading to increased disease severity and decreased patient survival. Baseline assessment and serial monitoring of blood histone concentration may be conceivably useful in COVID-19. We performed a literature review to explore the association among increased circulating levels of histones, disease severity/mortality in COVID-19 patients, and comparison of histone values between COVID-19 and non-COVID-19 patients. We carried out an electronic search in Medline and Scopus, using the keywords \"COVID-19\" OR \"SARS-CoV-2\" AND \"histone\" OR \"citrullinated histones\" OR \"hyperhistonemia\", between 2019 and present time (i.e., June 07th, 2022), which allowed to select 17 studies, totaling 1,846 subjects. We found that substantially elevated histone values were consistently present in all COVID-19 patients who developed unfavorable clinical outcomes. These findings suggest that blood histone monitoring upon admission and throughout hospitalization may be useful for early identification of higher risk of unfavorable COVID-19 progression. Therapeutic decisions in patients with SARS-CoV-2 based on the use of histone cut-off values may be driven by drugs engaging histones, finally leading to the limitation of cytotoxic, inflammatory, and thrombotic effects of circulating histones in viral sepsis.
摘要：
传染性呼吸道疾病COVID-19表现出从轻度/中度到严重的全身功能障碍和与血栓炎症相关的死亡的临床过程。在COVID-19感染期间，参与细胞因子风暴和凝血功能障碍的中性粒细胞胞外陷阱已成为诊断/预后标志物.NET的表征确定主要是组蛋白，有可能引发和传播炎症风暴和血栓形成，导致疾病严重程度增加和患者生存率降低。基线评估和连续监测血液组蛋白浓度可能对COVID-19有用。我们进行了文献综述，以探讨组蛋白循环水平增加之间的关联，COVID-19患者的疾病严重程度/死亡率，以及COVID-19和非COVID-19患者组蛋白值的比较。我们在Medline和Scopus进行了电子搜索，使用关键词\"COVID-19\"或\"SARS-CoV-2\"和\"组蛋白\"或\"瓜氨酸化组蛋白\"或\"高组织学血症\",在2019年和现在之间(即，6月07日,2022),允许选择17项研究，共1846个科目。我们发现，在所有出现不利临床结局的COVID-19患者中，组蛋白值一直显著升高。这些结果表明，入院时和整个住院期间的血液组蛋白监测可能有助于早期识别COVID-19不良进展的高风险。基于组蛋白截止值的SARS-CoV-2患者的治疗决策可能是由使用组蛋白的药物驱动的，最终导致细胞毒性的限制，炎症，和循环组蛋白在病毒性败血症中的血栓形成作用。
