CLINICAL TRIAL article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1647488
Patient and donor antibody profiles in early COVID-19 convalescent plasma therapy in the COnV-ert trial
Provisionally accepted
Andrea Alemany Ortiz1*
Dan Ouchi1
Edwards Pradenas2
Ruth Aguilar3
Marta Vidal Costa3
Alfons Jimenez Morera3
Pere Millat Martínez3
Marc Corbacho-Monné4Clara Suñer3
Quique Bassat3Bàrbara Baro3
Gemma Moncunill3Oriol Mitjà5
Julià Blanco2
Carlota Dobano3- 1Instituto Salud Global Barcelona (ISGlobal), Barcelona, Spain
- 2IrsiCaixa, Badalona, Spain
- 3Instituto de Salud Global de Barcelona, Barcelona, Spain
- 4Fundacio Parc Tauli, Sabadell, Spain
- 5Fundacio Lluita contra les Infeccions, Badalona, Spain
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Negative efficacy results of COVID-19 convalescent plasma (CCP) as early treatment in the COnV-ert trial have been attributed to the use of methylene blue (MB). We characterized immune responses after MB-treated CCP infusion and impact of MB in antibodies of CCP units infused. We measured antibody isotypes (IgG, IgM, IgA) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) against SARS-CoV-2 nucleocapsid and spike (S) antigens, neutralizing antibody titers, and IgG avidity in 128 participants of the COnV-ert trial 7 and 60 days after infusion, and in paired CCP units before and after MB treatment. Treatment with CCP significantly increased levels of IgG and IgG1 to receptor binding domain [RBD] and S, IgG3 to S and S2, and IgG avidity in recipients 7 days after infusion, without an increase in IgA, IgM, IgG2, IgG4, or neutralization. At day 7 post-infusion, recipients exhibited lower IgG, all IgG subclasses, and avidity, higher IgA and IgM, and comparable neutralization, relative to paired CCP units. MB was associated with a significant decrease in cytophilic subclasses IgG1 and IgG3 to S and S2 and IgA to RBD, S and S2 in CCP units, without a reduction in neutralization titer, and with a modest increase in IgG2 to RBD and S. Our study shows a modest impact of a single intravenous infusion of MB-treated high-titer CCP on circulating antibody levels compared to those generated by the host by day 7, and an adverse effect of MB on IgG1 and IgG3, which are essential for effector functions.
Keywords: High-titer Convalescent Plasma, COVID-19, Antibody immune response, Methyleneblue, Immunology & Infectious Diseases
Received: 15 Jun 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 Alemany Ortiz, Ouchi, Pradenas, Aguilar, Vidal Costa, Jimenez Morera, Millat Martínez, Corbacho-Monné, Suñer, Bassat, Baro, Moncunill, Mitjà, Blanco and Dobano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Andrea Alemany Ortiz, Instituto Salud Global Barcelona (ISGlobal), Barcelona, Spain
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