Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19: an international, randomised, open-label trial.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hoffmann Simone, Schrezenmeier Eva, Desmarets Maxime, Halleck Fabian, Durrbach Antoine, Peters Lynn, Tremmel Anna-Teresa, Seidel Alina, Führer Marita, Bachmann Friederike, Schrezenmeier Jens, Greiner Jochen, Körper Sixten, Hofmann Henrike, Ludwig Carolin, Vieweg Christiane, Jahrsdörfer Bernd, Budde Klemens, Schmidt Michael, Münch Jan, Joher Nizar, Daguindau Etienne, Grüner Beate, Brunotte Gaëlle, Vauchy Charline, Seifried Erhard, Bradshaw Daniel, Estcourt Lise J, Roberts David J, Toussirot Eric, Rijnders Bart, Tiberghien Pierre, Schrezenmeier Hubert
Аннотация
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.