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

Outcome

Met primary endpoint

Stopped (Enrollment): “Due to the significant decline in the number of newly diagnosed infections and the difficulties in opening new centers in the outgoing pandemic, recruitment declined. The Data Safety Monitoring Board recommended to stop the trial.”

paper 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% PMID 40020259 ↗

paper 95% confidence interval of difference -19% to -0.80%; p-value 0.027; Fisher's exact test PMID 40020259 ↗

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.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	COVID-19 convalescent plasma	Protein / enzyme biologic	2 unknown	Intravenous
Background	Current standard of care	Unknown	—	—
Background	Molnupiravir	Small molecule	—	—
Background	Nirmatrelvir	Small molecule	—	—
Background	Remdesivir	Small molecule	—	—
Background	Ritonavir	Other / unclassified	—	—
Background	Sotrovimab	Monoclonal antibody	—	—
Background	cilgavimab	Monoclonal antibody	—	—
Background	imdevimab	Monoclonal antibody	—	—
Background	tixagevimab	Monoclonal antibody	—	—

Indications