Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19: an international, randomised, open-label trial

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clinical trial", "author": "Denkinger", "first-page": "96", "journal-title": "Nat Cancer", "key": "10.1016/j.ebiom.2025.105613_bib15", "volume": "4", "year": "2023" }, { "DOI": "10.1136/bmjmed-2022-000427", "article-title": "Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial", "author": "Lacombe", "doi-asserted-by": "crossref", "journal-title": "BMJ Med", "key": "10.1016/j.ebiom.2025.105613_bib16", "volume": "2", "year": "2023" }, { "DOI": "10.1136/bmjopen-2022-071277", "article-title": "Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial", "author": "Desmarets", "doi-asserted-by": "crossref", "journal-title": "BMJ Open", "key": "10.1016/j.ebiom.2025.105613_bib17", "volume": "13", "year": "2023" }, { "DOI": "10.1016/j.immuni.2022.09.006", "article-title": "SARS-CoV-2 in immunocompromised individuals", "author": "DeWolf", "doi-asserted-by": "crossref", "first-page": "1779", "journal-title": "Immunity", "key": "10.1016/j.ebiom.2025.105613_bib18", "volume": "55", "year": "2022" }, { "DOI": "10.1126/sciimmunol.abj1031", "article-title": "Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients", "author": "Rincon-Arevalo", "doi-asserted-by": "crossref", "journal-title": "Sci Immunol", "key": "10.1016/j.ebiom.2025.105613_bib19", "volume": "6", "year": "2021" }, { "DOI": "10.1038/s41586-021-03696-9", "article-title": "Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection", "author": "Wang", "doi-asserted-by": "crossref", "first-page": "426", "journal-title": "Nature", "key": "10.1016/j.ebiom.2025.105613_bib20", "volume": "595", "year": "2021" }, { "DOI": "10.3389/fimmu.2023.1170759", "article-title": "SARS-CoV-2 vaccination of convalescents boosts neutralization capacity against Omicron subvariants BA.1, BA.2 and BA.5 and can be predicted by anti-S antibody concentrations in serological assays", "author": "Seidel", "doi-asserted-by": "crossref", "journal-title": "Front Immunol", "key": "10.1016/j.ebiom.2025.105613_bib21", "volume": "14", "year": "2023" }, { "DOI": "10.1002/(SICI)1097-0258(19980430)17:8<873::AID-SIM779>3.0.CO;2-I", "article-title": "Interval estimation for the difference between independent proportions: comparison of eleven methods", "author": "Newcombe", "doi-asserted-by": "crossref", "first-page": "873", "journal-title": "Stat Med", "key": "10.1016/j.ebiom.2025.105613_bib22", "volume": "17", "year": "1998" }, { "DOI": "10.1001/jamanetworkopen.2022.50647", "article-title": "COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review and meta-analysis", "author": "Senefeld", "doi-asserted-by": "crossref", "journal-title": "JAMA Netw Open", "key": "10.1016/j.ebiom.2025.105613_bib23", "volume": "6", "year": "2023" }, { "DOI": "10.1038/s41579-023-00878-2", "article-title": "The evolution of SARS-CoV-2", "author": "Markov", "doi-asserted-by": "crossref", "first-page": "361", "journal-title": "Nat Rev Microbiol", "key": "10.1016/j.ebiom.2025.105613_bib24", "volume": "21", "year": "2023" }, { "DOI": "10.3389/fonc.2024.1389345", "article-title": "Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy", "author": "Pinana", "doi-asserted-by": "crossref", "journal-title": "Front Oncol", "key": "10.1016/j.ebiom.2025.105613_bib25", "volume": "14", "year": "2024" }, { "article-title": "Clinical feature of omicron infection in children with inborn errors of immunity in China", "author": "Yang", "journal-title": "Front Immunol", "key": "10.1016/j.ebiom.2025.105613_bib26", "volume": "15", "year": "2024" }, { "DOI": "10.20411/pai.v10i1.752", "article-title": "Escape of SARS-CoV-2 variants KP.1.1, LB.1, and KP3.3 from approved monoclonal antibodies", "author": "Planas", "doi-asserted-by": "crossref", "first-page": "1", "journal-title": "Pathog Immun", "key": "10.1016/j.ebiom.2025.105613_bib27", "volume": "10", "year": "2024" }, { "DOI": "10.3389/fimmu.2022.920210", "article-title": "BNT162b2 booster vaccination elicits cross-reactive immunity against SARS-CoV-2 variants B.1.1.529 and B.1.617.2 in convalescents of all ages", "author": "Jahrsdorfer", "doi-asserted-by": "crossref", "journal-title": "Front Immunol", "key": "10.1016/j.ebiom.2025.105613_bib28", "volume": "13", "year": "2022" }, { "DOI": "10.3389/ti.2022.10677", "article-title": "SARS-CoV2 mRNA vaccine-specific B-, T- and humoral responses in adolescents after kidney transplantation", "author": "Sattler", "doi-asserted-by": "crossref", "journal-title": "Transpl Int", "key": "10.1016/j.ebiom.2025.105613_bib29", "volume": "35", "year": "2022" }, { "DOI": "10.1172/jci.insight.157836", "article-title": 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"journal-title": "Nat Rev Immunol", "key": "10.1016/j.ebiom.2025.105613_bib43", "volume": "20", "year": "2020" }, { "DOI": "10.3390/v13081594", "article-title": "COVID-19 convalescent plasma is more than neutralizing antibodies: a narrative review of potential beneficial and detrimental co-factors", "author": "Focosi", "doi-asserted-by": "crossref", "first-page": "1594", "journal-title": "Viruses", "key": "10.1016/j.ebiom.2025.105613_bib44", "volume": "13", "year": "2021" }, { "DOI": "10.1111/trf.17701", "article-title": "Safety of COVID-19 convalescent plasma: a definitive systematic review and meta-analysis of randomized controlled trials", "author": "Franchini", "doi-asserted-by": "crossref", "first-page": "388", "journal-title": "Transfusion", "key": "10.1016/j.ebiom.2025.105613_bib45", "volume": "64", "year": "2024" } ], "reference-count": 44, "references-count": 44, "relation": {}, "resource": { "primary": { "URL": "https://linkinghub.elsevier.com/retrieve/pii/S235239642500057X" 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