Université Paris Cité et Université Sorbonne Paris Nord, Inserm, IAME, F-75018 Paris, France.
Hospices Civils de Lyon, Laboratoire de Virologie, Institut des Agents Infectieux de Lyon, Centre National de Référence des virus respiratoires France Sud, F-69317 Lyon, France.
J Antimicrob Chemother. 2024 Nov 4;79(11):2887-2895. doi: 10.1093/jac/dkae301.
The antiviral efficacy of Evusheld (AZD7442) in patients hospitalized for SARS-CoV-2 is unknown.
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.
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).
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.
Evusheld（AZD7442）在因 SARS-CoV-2 住院的患者中的抗病毒疗效尚不清楚。
我们分析了 199 名因感染 SARS-CoV-2 病毒而住院的患者（109 名接受 Evusheld 治疗，90 名接受安慰剂治疗）的鼻咽病毒载量和血清中和活性对感染变异体的演变情况，这些患者均纳入了随机、双盲、试验性 DisCoVeRy（NCT04315948）。我们使用一种机制数学模型，重建了病毒动力学轨迹以及 Evusheld 治疗期间血清中和活性增加如何调节病毒动力学轨迹。
我们的模型确定了中和活性与病毒动力学有关。反映 Evusheld 对变异体的依赖型中和活性，Evusheld 的抗病毒活性在感染前 Omicron 或 Omicron BA.2 变异体的患者中大于感染 Omicron BA.1 变异体的患者。具体而言，该模型预测，与安慰剂治疗组相比，Evusheld 可使感染前 Omicron（中位数：5.9；80%置信区间[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 变异体的患者中，效果更为温和，将病毒清除的中位时间缩短 2 天（中位数：2.2；80%PI：0.4-8.9）。
接受 Evusheld 治疗的住院患者的 SARS-CoV-2 病毒清除中位时间更短。由于 Evusheld 的抗病毒活性是由中和活性水平介导的，因此其对病毒清除的影响在很大程度上取决于感染的变异体。
