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鼻腔内给予恢复期血浆可预防仓鼠感染 SARS-CoV-2。

Intranasal administration of convalescent plasma protects against SARS-CoV-2 infection in hamsters.

机构信息

Transfusion Research Center, Belgian Red Cross-Flanders, Ghent, Belgium.

Transfusion Research Center, Belgian Red Cross-Flanders, Ghent, Belgium; Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.

出版信息

EBioMedicine. 2023 Jun;92:104597. doi: 10.1016/j.ebiom.2023.104597. Epub 2023 May 4.

Abstract

BACKGROUND

Convalescent plasma (CP) transfusion is an early option for treating infections with pandemic potential, often preceding vaccine or antiviral drug rollout. Heterogenous findings from randomized clinical trials on transfusion of COVID-19 CP (CCP) have been reported. However, meta-analysis suggests that transfusion of high titer CCP is associated with a mortality benefit for COVID-19 outpatients or inpatients treated within 5 days after symptom onset, indicating the importance of early administration.

METHODS

We tested if CCP is an effective prophylactic against SARS-CoV-2 infection by the intranasal administration of 25 μL CCP/nostril (i.e. 0.01-0.06 mg anti-RBD antibodies/kg) in hamsters exposed to infected littermates.

FINDINGS

In this model, 40% of CCP treated hamsters were fully protected and 40% had significantly reduced viral loads, the remaining 20% was not protected. The effect seems dose-dependent because high-titer CCP from a vaccinated donor was more effective than low-titer CCP from a donation prior to vaccine rollout. Intranasal administration of human CCP resulted in a reactive (immune) response in hamster lungs, however this was not observed upon administration of hamster CCP.

INTERPRETATION

We conclude that CCP is an effective prophylactic when used directly at the site of primary infection. This option should be considered in future prepandemic preparedness plans.

FUNDING

Flanders Innovation & Entrepreneurship (VLAIO) and the Foundation for Scientific Research of the Belgian Red Cross Flanders.

摘要

背景

恢复期血浆(CP)输注是治疗大流行潜力感染的早期选择,通常早于疫苗或抗病毒药物的推出。关于 COVID-19 CP(CCP)输注的随机临床试验报告了不一致的结果。然而,荟萃分析表明,输注高滴度 CCP 与 COVID-19 门诊或住院患者在症状出现后 5 天内接受治疗的死亡率降低相关,这表明早期给药的重要性。

方法

我们通过向暴露于感染同窝仔鼠的仓鼠的鼻腔内给予 25 μL CCP/鼻孔(即 0.01-0.06 mg 抗 RBD 抗体/公斤)来测试 CCP 是否是预防 SARS-CoV-2 感染的有效方法。

发现

在该模型中,40%的 CCP 治疗仓鼠完全受到保护,40%的仓鼠病毒载量显著降低,其余 20%的仓鼠未受到保护。该效果似乎呈剂量依赖性,因为来自接种疫苗供体的高滴度 CCP 比疫苗推出前的低滴度 CCP 更有效。人 CCP 的鼻腔内给药会导致仓鼠肺部产生反应性(免疫)反应,但在给予仓鼠 CCP 时未观察到这种反应。

结论

当直接在原发性感染部位使用时,CCP 是一种有效的预防措施。在未来的大流行准备计划中应考虑这种选择。

资助

佛兰德创新与创业(VLAIO)和比利时红十字佛兰德科学研究基金会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efad/10189094/3c6d0d901c6b/gr1.jpg

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