Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19: an international, randomised, open-label trial.

• Tác giả: Friederike Bachmann, Daniel Bradshaw, Gaëlle Brunotte, Klemens Budde, Etienne Daguindau, Maxime Desmarets, Antoine Durrbach, Lise J Estcourt, Marita Führer, Jochen Greiner, Beate Grüner, Fabian Halleck, Simone Hoffmann, Henrike Hofmann, Bernd Jahrsdörfer, Nizar Joher, Sixten Körper, Carolin Ludwig, Jan Münch, Lynn Peters, Bart Rijnders, David J Roberts, Michael Schmidt, Eva Schrezenmeier, Hubert Schrezenmeier, Jens Schrezenmeier, Alina Seidel, Erhard Seifried, Pierre Tiberghien, Eric Toussirot, Anna-Teresa Tremmel, Charline Vauchy, Christiane Vieweg
• Ngôn ngữ: eng
• Thông tin xuất bản: Netherlands : EBioMedicine , 2025
• Bộ sưu tập: NCBI
• ID: 703230

Tóm tắt

 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.