{"title":"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。","authors":"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","doi":"10.1093/jac/dkae301","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The antiviral efficacy of Evusheld (AZD7442) in patients hospitalized for SARS-CoV-2 is unknown.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531825/pdf/","citationCount":"0","resultStr":"{\"title\":\"Antiviral effect of Evusheld in COVID-19 hospitalized patients infected with pre-Omicron or Omicron variants: a modelling analysis of the randomized DisCoVeRy trial.\",\"authors\":\"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\",\"doi\":\"10.1093/jac/dkae301\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The antiviral efficacy of Evusheld (AZD7442) in patients hospitalized for SARS-CoV-2 is unknown.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":14969,\"journal\":{\"name\":\"Journal of Antimicrobial Chemotherapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-11-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531825/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Antimicrobial Chemotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/jac/dkae301\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Antimicrobial Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jac/dkae301","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
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.
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.