tetano
Editor, Senior Moderator
Front Immunol
. 2025 Sep 25:16:1647488.
doi: 10.3389/fimmu.2025.1647488. eCollection 2025. Patient and donor antibody profiles in early COVID-19 convalescent plasma therapy in the COnV-ert trial
Andrea Alemany[SUP] 1 2 3 4 [/SUP], Dan Ouchi[SUP] 1 3 [/SUP], Edwards Pradenas[SUP] 5 [/SUP], Ruth Aguilar[SUP] 3 [/SUP], Marta Vidal[SUP] 3 [/SUP], Alfons Jimenez[SUP] 3 [/SUP], Pere Millat-Martinez[SUP] 3 4 [/SUP], Marc Corbacho-Monné[SUP] 1 2 6 [/SUP], Clara Suñer[SUP] 3 [/SUP], Quique Bassat[SUP] 3 4 7 8 9 10 [/SUP], Bàrbara Baro[SUP] 3 4 [/SUP], Gemma Moncunill[SUP] 3 11 [/SUP], Oriol Mitjà[SUP] 1 2 12 [/SUP]; COnV-ert Group of Authors; Julià Blanco[SUP] #[/SUP][SUP] 5 11 12 13 [/SUP], Carlota Dobaño[SUP] #[/SUP][SUP] 3 11 [/SUP]
Affiliations
Introduction: The negative efficacy results of coronavirus disease 2019 (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 the impact of MB on antibodies of the infused CCP units.
Methods: We measured antibody isotypes (IgG, IgM, and IgA) and IgG subclasses (IgG1, IgG2, IgG3, and 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.
Results: Treatment with CCP significantly increased the 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 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.
Discussion: 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.
Clinical trial registration: https://www.clinicaltrials.gov/, identifier NCT04621123.
Keywords: COVID-19; antibody immune response; high-titer convalescent plasma; immunology & infectious diseases; methylene blue.
. 2025 Sep 25:16:1647488.
doi: 10.3389/fimmu.2025.1647488. eCollection 2025. Patient and donor antibody profiles in early COVID-19 convalescent plasma therapy in the COnV-ert trial
Andrea Alemany[SUP] 1 2 3 4 [/SUP], Dan Ouchi[SUP] 1 3 [/SUP], Edwards Pradenas[SUP] 5 [/SUP], Ruth Aguilar[SUP] 3 [/SUP], Marta Vidal[SUP] 3 [/SUP], Alfons Jimenez[SUP] 3 [/SUP], Pere Millat-Martinez[SUP] 3 4 [/SUP], Marc Corbacho-Monné[SUP] 1 2 6 [/SUP], Clara Suñer[SUP] 3 [/SUP], Quique Bassat[SUP] 3 4 7 8 9 10 [/SUP], Bàrbara Baro[SUP] 3 4 [/SUP], Gemma Moncunill[SUP] 3 11 [/SUP], Oriol Mitjà[SUP] 1 2 12 [/SUP]; COnV-ert Group of Authors; Julià Blanco[SUP] #[/SUP][SUP] 5 11 12 13 [/SUP], Carlota Dobaño[SUP] #[/SUP][SUP] 3 11 [/SUP]
Affiliations
- PMID: 41080591
- PMCID: PMC12507808
- DOI: 10.3389/fimmu.2025.1647488
Introduction: The negative efficacy results of coronavirus disease 2019 (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 the impact of MB on antibodies of the infused CCP units.
Methods: We measured antibody isotypes (IgG, IgM, and IgA) and IgG subclasses (IgG1, IgG2, IgG3, and 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.
Results: Treatment with CCP significantly increased the 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 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.
Discussion: 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.
Clinical trial registration: https://www.clinicaltrials.gov/, identifier NCT04621123.
Keywords: COVID-19; antibody immune response; high-titer convalescent plasma; immunology & infectious diseases; methylene blue.