Early High-Titre Convalescent Plasma in Clinically Vulnerable Individuals With Mild COVID-19

Summary

* Research Question: Does convalescent plasma (CCP) collected from donors who have recovered from COVID-19 and who have a very high titre of anti-SARS-CoV-2 antibodies reduce the risk of hospitalisation (for COVID-19) or death in patients with early symptoms of acute COVID-19 who are vulnerable to this disease compared to standard of care? * Study product: Very high antibody titre COVID-19 convalescent plasma collected more than 15 days after end of symptoms in COVID-19 patients who also had received at least one dose of a SARS-CoV-2 vaccine. * Methodology: Multicentre, randomised, open-label, adaptive superiority trial: COVID-19 very high neutralizing Ab titre convalescent plasma vs standard care in 2 cohorts of vulnerable patients (cohort 1: elderly (≥ 70 years) and younger with comorbidities, cohort 2: immunosuppressed patients). * Study phase: Phase 3 * Intervention: Two units of high antibody titre COVID-19 convalescent plasma to individuals randomised to the intervention group, 2 units from 2 different donors, preferably transfused on the same day. Plasma provided by convalescent vaccinated donors with a minimum antibody titre of 1:640 against delta variant (B1.617.2) or antibody concentration \>=4.000 BAU/ml in the QuantiVac anti-SARS-CoV-2 IgG ELISA or \>=20.000 U/ml in the Elecsys anti-SARS-CoV-2 CLIA * Randomisation: 1:1 (standard of care + convalescent plasma vs. standard of care) stratified by centre (cohorts 1 and 2)

Timeline

Start

2022-04-01

Primary completion

2024-01-18

Completion

2024-06-17

Publications

• Hoffmann S, Seidel A, Ludwig C, Vieweg C, Muller R, Hofmann H, Jahrsdorfer B, Wuchter P, Kluter H, Schmidt M, Johnsen M, Burkhardt T, Appl T, Schrezenmeier E, Munch J, Tiberghien P, Schrezenmeier H, Korper S. SARS-CoV-2 convalescent plasma for the controlled clinical trial "COVIC-19": Experience from collection of very high-titer plasma from superimmunized individuals. Transfusion. 2025 Oct;65(10):1888-1902. doi: 10.1111/trf.18394. Epub 2025 Sep 12.
• Hoffmann S, Schrezenmeier E, Desmarets M, Halleck F, Durrbach A, Peters L, Tremmel AT, Seidel A, Fuhrer M, Bachmann F, Schrezenmeier J, Greiner J, Korper S, Hofmann H, Ludwig C, Vieweg C, Jahrsdorfer B, Budde K, Schmidt M, Munch J, Joher N, Daguindau E, Gruner B, Brunotte G, Vauchy C, Seifried E, Bradshaw D, Estcourt LJ, Roberts DJ, Toussirot E, Rijnders B, Tiberghien P, Schrezenmeier H. Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19: an international, randomised, open-label trial. EBioMedicine. 2025 Mar;113:105613. doi: 10.1016/j.ebiom.2025.105613. Epub 2025 Feb 27.
• Desmarets M, Hoffmann S, Vauchy C, Rijnders BJA, Toussirot E, Durrbach A, Korper S, Schrezenmeier E, van der Schoot CE, Harvala H, Brunotte G, Appl T, Seifried E, Tiberghien P, Bradshaw D, Roberts DJ, Estcourt LJ, Schrezenmeier H. Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial. BMJ Open. 2023 Apr 27;13(4):e071277. doi: 10.1136/bmjopen-2022-071277.

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