早期给予低分子量肝素与新冠病毒拭子转阴时间缩短有关。

Early low-molecular-weight heparin administration is associated with shorter time to SARS-CoV-2 swab negativity.

作者信息

Trunfio Mattia, Salvador Elena, Gaviraghi Alberto, Audagnotto Sabrina, Marinaro Letizia, Motta Ilaria, Casciaro Riccardo, Ghisetti Valeria, Fava Carmen, Bonora Stefano, Di Perri Giovanni, Calcagno Andrea

机构信息

Department of Medical Sciences, University of Turin at the Unit of Infectious Diseases, "Amedeo di Savoia" Hospital, Turin, Italy.

Microbiology and Molecular Biology Laboratory, "Amedeo di Savoia" Hospital, ASL Città di Turin, Turin, Italy.

出版信息

Antivir Ther. 2020;25(6):327-333. doi: 10.3851/IMP3377.

DOI:10.3851/IMP3377

PMID:33506810

Abstract

BACKGROUND

Antiviral and immune-modulating properties of low-molecular-weight heparin (LMWH) against Coronaviridae have been reported by in vitro studies, but no in vivo evidence is yet available. We sought to know whether the timing of prophylactic doses of LMWH during the course of COVID-19 may affect the time to SARS-CoV-2 nasal-oropharyngeal swab negativization.

METHODS

Retrospective monocentric cross-sectional study on patients requiring sub-intensive ward admission due to first SARS-CoV-2 infection and undergoing early (EH; within 7 days from COVID-19 signs and symptoms onset) versus delayed prophylactic LMWH (DH; after 7 days). SARS-CoV-2 RNA was measured by reverse transcription real-time PCR according to scheduled time points: first swab after 2 weeks from COVID-19 onset, then at 1-week intervals until negativity.

RESULTS

Time to SARS-CoV-2 swab negativity was shorter in EH (38 patients) compared with DH (55 patients): 22 versus 37 days (P=0.004). The number of confirmative negative swabs in EH was significantly higher compared with DH at week 2 (21.1% versus 3.6%; P=0.017) and 4 (60.0% versus 19.6%; P<0.001). At univariate, EH differed from DH for several disease severity and clinical management parameters. Nevertheless, after accounting for the differences, Cox regression showed early LMWH administration (hazard ratio [HR] 2.91 [1.51, 5.63]; P=0.002) and higher lymphocytes nadir (HR 1.04 [1.01, 1.08]; P=0.020) as predictors of shorter time to swab negativity.

CONCLUSIONS

This potential antiviral and/or immune-modulating activity of LMWH needs further in vivo confirmations by randomized controlled trials.

摘要

背景

体外研究报道了低分子量肝素（LMWH）对冠状病毒科的抗病毒和免疫调节特性，但尚无体内证据。我们试图了解在COVID-19病程中预防性使用LMWH的时机是否会影响SARS-CoV-2鼻咽拭子转阴的时间。

方法

对因首次感染SARS-CoV-2而需要入住亚重症病房的患者进行回顾性单中心横断面研究，这些患者接受早期（EH；在COVID-19体征和症状出现后7天内）与延迟预防性LMWH（DH；7天后）治疗。根据预定时间点通过逆转录实时PCR检测SARS-CoV-2 RNA：在COVID-19发病后2周进行首次拭子检测，然后每隔1周检测一次直至转阴。

结果

与DH组（55例患者）相比，EH组（38例患者）的SARS-CoV-2拭子转阴时间更短：分别为22天和37天（P=0.004）。在第2周（21.1%对3.6%；P=0.017）和第4周（60.0%对19.6%；P<0.001）时，EH组的确诊阴性拭子数量显著高于DH组。单因素分析显示，EH组和DH组在几个疾病严重程度和临床管理参数方面存在差异。然而，在考虑这些差异后，Cox回归显示早期给予LMWH（风险比[HR] 2.91 [1.51, 5.63]；P=0.002）和更低的淋巴细胞最低点（HR 1.04 [1.01, 1.08]；P=0.020）是拭子转阴时间较短的预测因素。