Aims Anticoagulation was associated with improved survival of hospitalized coronavirus disease 2019 (COVID-19) patients in large-scale studies. Yet, the development of COVID-19-associated coagulopathy (CAC) and the mechanism responsible for improved survival of anticoagulated patients with COVID-19 remain largely elusive. This investigation aimed to explore the effects of anticoagulation and low-molecular-weight heparin (LMWH) in particular on patient outcome, CAC development, thromboinflammation, cell death, and viral persistence. Methods and results Data of 586 hospitalized COVID-19 patients from three different regions of Austria were evaluated retrospectively. Of these, 419 (71.5%) patients received LMWH and 62 (10.5%) received non-vitamin-K oral anticoagulants (NOACs) during hospitalization. Plasma was collected at different time points in a subset of 106 patients in order to evaluate markers of thromboinflammation (H3Cit-DNA) and the cell death marker cell-free DNA (cfDNA). Use of LMWH was associated with improved survival upon multivariable Cox regression (hazard ratio = 0.561, 95% confidence interval: 0.348–0.906). Interestingly, neither LMWH nor NOAC was associated with attenuation of D-dimer increase over time, or thromboinflammation. In contrast, anticoagulation was associated with a decrease in cfDNA during hospitalization, and curtailed viral persistence was observed in patients using LMWH leading to a 4-day reduction of virus positivity upon quantitative polymerase chain reaction [13 (interquartile range: 6–24) vs. 9 (interquartile range: 5–16) days, P = 0.009]. Conclusion Time courses of haemostatic and thromboinflammatory biomarkers were similar in patients with and without LMWH, indicating either no effects of LMWH on haemostasis or that LMWH reduced hypercoagulability to levels of patients without LMWH. Nonetheless, anticoagulation with LMWH was associated with reduced mortality, improved markers of cell death, and curtailed viral persistence, indicating potential beneficial effects of LMWH beyond haemostasis, which encourages use of LMWH in COVID-19 patients without contraindications.

中文翻译：

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在 2019 年冠状病毒病中使用低分子量肝素与减少病毒持续性有关：一项回顾性多中心观察研究

在大规模研究中，抗凝与 2019 年住院冠状病毒病 (COVID-19) 患者的生存率提高有关。然而，COVID-19 相关凝血病 (CAC) 的发展以及导致 COVID-19 抗凝患者生存率提高的机制在很大程度上仍然难以捉摸。本研究旨在探讨抗凝剂和低分子肝素 (LMWH) 对患者预后、CAC 发展、血栓炎症、细胞死亡和病毒持续存在的影响。方法和结果 对来自奥地利三个不同地区的 586 例 COVID-19 住院患者的数据进行了回顾性评估。其中，419 名 (71.5%) 患者在住院期间接受了 LMWH，62 名 (10.5%) 患者在住院期间接受了非维生素 K 口服抗凝剂 (NOAC)。在不同时间点收集 106 名患者的血浆，以评估血栓炎症标志物 (H3Cit-DNA) 和细胞死亡标志物游离 DNA (cfDNA)。使用 LMWH 与多变量 Cox 回归后生存率的提高相关（风险比 = 0.561，95% 置信区间：0.348-0.906）。有趣的是，LMWH 和 NOAC 均与 D-二聚体随时间增加的减弱或血栓炎症无关。相比之下，抗凝与住院期间 cfDNA 的减少有关，并且在使用 LMWH 的患者中观察到病毒持续时间减少，导致定量聚合酶链反应后病毒阳性减少 4 天 [13（四分位距：6-24）vs . 9（四分位距：5-16）天，P = 0.009]。结论 有和没有 LMWH 的患者的止血和血栓炎症生物标志物的时间过程相似，表明 LMWH 对止血没有影响，或者 LMWH 将高凝状态降低到没有 LMWH 的患者的水平。尽管如此，LMWH 抗凝与降低死亡率、改善细胞死亡标志物和减少病毒持续存在相关，这表明 LMWH 除了止血之外的潜在有益作用，这鼓励在没有禁忌症的 COVID-19 患者中使用 LMWH。