{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T20:50:59Z","timestamp":1769633459764,"version":"3.49.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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, without a reduction in neutralization titer and with a modest increase in IgG2 to RBD and S.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:uri>https:\/\/www.clinicaltrials.gov\/<\/jats:uri>, identifier NCT04621123.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1647488","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T05:27:28Z","timestamp":1758778048000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Patient and donor antibody profiles in early COVID-19 convalescent plasma therapy in the COnV-ert 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