Simone Hoffmann, Eva Schrezenmeier, Maxime Desmarets, Fabian Halleck, Antoine Durrbach, Lynn Peters, Anna-Teresa Tremmel, Alina Seidel, Marita Führer, Friederike Bachmann, Jens Schrezenmeier, Jochen Greiner, Sixten Körper, Henrike Hofmann, Carolin Ludwig, Christiane Vieweg, Bernd Jahrsdörfer, Klemens Budde, Michael Schmidt, Jan Münch, Nizar Joher, Etienne Daguindau, Beate Grüner, Gaëlle Brunotte, Charline Vauchy, Erhard Seifried, Daniel Bradshaw, Lise J Estcourt, David J Roberts, Eric Toussirot, Bart Rijnders, Pierre Tiberghien, Hubert Schrezenmeier
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引用次数: 0
摘要
背景：COVID-19恢复期血浆（CCP）是治疗COVID-19的一种选择。本研究探讨了早期高滴度CCP治疗轻度COVID-19免疫功能低下患者的安全性和有效性。方法：这项随机、对照、开放标签的试验在德国、法国和荷兰的10个临床试验中心评估了轻度COVID-19免疫功能低下患者（n = 120）的CCP。患者按1:1随机分组，接受单独的标准护理（SoC组）或SoC和2个单位的CCP。大多数患者（89.7%）接种了3次以上的SARS-CoV-2疫苗。主要终点是随机分组后第28天因进展性COVID-19症状住院或死亡，以改良意向治疗基础（117例患者）进行分析。安全性分析包括完整的分析集。该试验已注册EudraCT 2021-006621-22， ClinicalTrials.gov注册号NCT05271929。研究结果：在2022年4月11日至2023年11月27日期间，120名患者入组。CCP组患者在症状出现后的中位4天内接受了来自恢复期、接种过SARS-CoV-2抗体水平非常高（中位为81,810 IU/ml）的供体的中位559 ml CCP。主要结局发生在SoC组的5/58例患者（8.6%）和CCP组的0/59例患者（0%），差异为-8.6%(95%可信区间差异为-19%至-0.80%；假定值0.027;费雪精确检验)。患者体内的SARS-CoV-2抗体过程显示CCP对抗体的被动转移，特别是对新的SARS-CoV-2变体的中和作用。随访期间患者的SARS-CoV-2全基因组测序结果显示宿主内病毒进化显著，但组间无差异。CCP被很好地容忍。解释：早期给予高滴度CCP可预防轻度COVID-19免疫功能低下患者住院或死亡。资助：支助e项目（欧洲联盟“地平线2020方案”）、德国联邦教育和研究部、ZonMw、荷兰卫生研究与发展组织。
Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19: an international, randomised, open-label trial.
Background: COVID-19 convalescent plasma (CCP) is a treatment option for COVID-19. This study investigated the safety and efficacy of early, very high-titre CCP in immunocompromised individuals with mild COVID-19.
Methods: This randomised, controlled, open-label trial assessed CCP in immunocompromised patients (n = 120) with mild COVID-19 in 10 clinical trial centres across Germany, France, and the Netherlands. Patients were randomised 1:1 to receive either standard of care (SoC) alone (SoC group) or SoC and 2 units of CCP. Most patients (89.7%) had received ≥3 SARS-CoV-2 vaccinations. The primary endpoint was hospitalisation for progressive COVID-19 symptoms or death by day 28 after randomisation, analysed on a modified intention-to-treat basis (117 patients). The safety analysis included the full analysis set. The trial is registered with EudraCT 2021-006621-22, and ClinicalTrials.gov, NCT05271929.
Findings: Between April 11, 2022 and November 27, 2023, 120 patients were enrolled. Patients in the CCP group received a median of 559 ml CCP from convalescent, vaccinated donors with very high levels of SARS-CoV-2 antibodies (median 81,810 IU/ml) at a median 4 days after symptom onset. The primary outcome occurred in 5/58 patients (8.6%) in the SoC group and in 0/59 patients (0%) in the CCP group, difference -8.6% (95% confidence interval of difference -19% to -0.80%; p-value 0.027; Fisher's exact test). The course of SARS-CoV-2 antibodies in the patients demonstrated a passive transfer of antibodies by the CCP, in particular neutralising effects against new SARS-CoV-2 variants. Whole genome sequencing of SARS-CoV-2 in patients during follow-up showed significant intra-host viral evolution, but without differences between groups. CCP was well tolerated.
Interpretation: Early administration of high-titre CCP can prevent hospitalisation or death in immunocompromised patients with mild COVID-19.
Funding: Support-e project (European Union's Horizon 2020 Programme), German Federal Ministry of Education and Research, ZonMw, the Netherlands Organisation for Health Research and Development.
EBioMedicineBiochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍：
eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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