Evusheld对COVID-19住院病人感染前欧米克龙或欧米克龙变体的抗病毒效果:随机DisCoVeRy试验的模型分析。

IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES
Maxime Beaulieu, Alexandre Gaymard, Clément Massonnaud, Nathan Peiffer-Smadja, Maude Bouscambert-Duchamp, Guislaine Carcelain, Guillaume Lingas, France Mentré, Florence Ader, Maya Hites, Pascal Poignard, Jérémie Guedj
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引用次数: 0

摘要

背景: Evusheld(AZD7442)对 SARS-CoV-2 住院患者的抗病毒疗效尚不清楚:Evusheld(AZD7442)对SARS-CoV-2住院患者的抗病毒疗效尚不清楚:我们分析了199例感染SARS-CoV-2病毒的住院患者(109例接受Evusheld治疗,90例接受安慰剂治疗)的鼻咽病毒载量和血清中和活性的变化情况,这些患者被纳入随机双盲试验DisCoVeRy(NCT04315948)。我们利用一个机理数学模型重建了病毒动力学轨迹,以及在埃武塞治疗过程中血清中和活性的增加是如何调节病毒动力学的:结果:我们的模型发现中和活性与病毒动力学相关。Evusheld的抗病毒活性在感染前Omicron或Omicron BA.2变体的患者中比在感染Omicron BA.1变体的患者中更大,这反映了Evusheld的中和活性与变体相关。更具体地说,根据模型预测,与安慰剂治疗的患者相比,Evusheld可使感染前Omicron(中位数:5.9;80% PI:2.1-13.6)或Omicron BA.2(中位数:5.4;80% PI:2.0-12.4)的患者的病毒清除中位时间缩短5天以上。在感染 Omicron BA.1 变异株的患者中,效果较为温和,病毒清除时间的中位数缩短了 2 天(中位数:2.2;80% PI:0.4-8.9):结论:接受 Evusheld 治疗的住院病人清除 SARS-CoV-2 病毒的中位时间更短。由于 Evusheld 的抗病毒活性是由中和活性水平介导的,因此它对病毒清除的影响很大程度上取决于感染的变体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Antiviral effect of Evusheld in COVID-19 hospitalized patients infected with pre-Omicron or Omicron variants: a modelling analysis of the randomized DisCoVeRy trial.

Background: The antiviral efficacy of Evusheld (AZD7442) in patients hospitalized for SARS-CoV-2 is unknown.

Methods: We analysed the evolution of both the nasopharyngeal viral load and the serum neutralization activity against the variant of infection in 199 hospitalized patients (109 treated with Evusheld, 90 treated with placebo) infected with the SARS-CoV-2 virus and included in the randomized, double-blind, trial DisCoVeRy (NCT04315948). Using a mechanistic mathematical model, we reconstructed the trajectories of viral kinetics and how they are modulated by the increase in serum neutralization activity during Evusheld treatment.

Results: Our model identified that the neutralization activity was associated with viral kinetics. Reflecting the variant-dependent neutralization activity of Evusheld, the antiviral activity of Evusheld was larger in patients infected with pre-Omicron or Omicron BA.2 variants than in patients infected with Omicron BA.1 variant. More specifically, the model predicted that Evusheld reduced the median time to viral clearance compared with placebo-treated patients by more than 5 days in patients infected by pre-Omicron (median: 5.9; 80% PI: 2.1-13.6) or Omicron BA.2 (median: 5.4; 80% PI: 2.0-12.4), respectively. The effect was more modest in patients infected by the Omicron BA.1 variant, reducing the median time to viral clearance by 2 days (median: 2.2; 80% PI: 0.4-8.9).

Conclusions: Hospitalized patients treated with Evusheld had a shorter median time to SARS-CoV-2 viral clearance. As Evusheld antiviral activity is mediated by the level of neutralization activity, its impact on viral clearance varies largely according to the variant of infection.

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来源期刊
CiteScore
9.20
自引率
5.80%
发文量
423
审稿时长
2-4 weeks
期刊介绍: The Journal publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents. The Journal publishes primarily in human medicine, and articles in veterinary medicine likely to have an impact on global health.
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