Individual patient and donor seroprofiles in convalescent plasma treatment of COVID-19 in REMAP-CAP clinical trial

Visa Nurmi; Richard Mayne; Chanice Knight; Hannia L Almonacid-Mendoza; Shannah Secret; Lise Estcourt; Jussi Hepojoki; Tonći Šuštić; Abigail A Lamikanra; Hoi Pat Tsang; David K Menon; Manu Shankar-Hari; C Ellen van der Schoot; Gestur Vidarsson; David J Roberts; Peter Simmonds; Klaus Hedman; Heli Harvala

doi:10.1016/j.jinf.2025.106412

Individual patient and donor seroprofiles in convalescent plasma treatment of COVID-19 in REMAP-CAP clinical trial

J Infect. 2025 Jan 9:106412. doi: 10.1016/j.jinf.2025.106412. Online ahead of print.

Authors

Visa Nurmi¹, Richard Mayne², Chanice Knight², Hannia L Almonacid-Mendoza³, Shannah Secret⁴, Lise Estcourt⁵, Jussi Hepojoki⁶, Tonći Šuštić⁷, Abigail A Lamikanra⁵, Hoi Pat Tsang³, David K Menon⁸, Manu Shankar-Hari⁹, C Ellen van der Schoot¹⁰, Gestur Vidarsson⁷, David J Roberts⁵, Peter Simmonds², Klaus Hedman¹¹, Heli Harvala¹²

Affiliations

¹ Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK; Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Electronic address: [email protected].
² Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
³ Clinical Services, NHS Blood and Transplant, Oxford, UK.
⁴ Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK; Clinical Services, NHS Blood and Transplant, Oxford, UK.
⁵ Clinical Services, NHS Blood and Transplant, Oxford, UK; Radcliffe Department of Medicine and BRC Haematology Theme, University of Oxford, Oxford, UK.
⁶ Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Institute of Veterinary Pathology, Vetsuisse faculty, University of Zürich, Zürich, Switzerland.
⁷ Department of Experimental Immunohematology, Sanquin Research, Amsterdam, the Netherlands; Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Centre for Biomolecular Research, Utrecht University, Utrecht, the Netherlands.
⁸ Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.
⁹ Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK.
¹⁰ Department of Experimental Immunohematology, Sanquin Research, Amsterdam, the Netherlands; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
¹¹ Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Helsinki University Hospital Diagnostics Centre, Helsinki, Finland.
¹² Radcliffe Department of Medicine and BRC Haematology Theme, University of Oxford, Oxford, UK; Microbiology Services, NHS Blood and Transplant, Colindale, UK; Infection and Immunity, University College of London, London, UK.

PMID: 39798805
DOI: 10.1016/j.jinf.2025.106412

Abstract

Objectives: Convalescent plasma (CP) treatment of COVID-19 has shown significant therapeutic effect only when administered early. We investigated the importance of patient and CP seroprofiles on treatment outcome in REMAP-CAP CP trial.

Methods: We evaluated neutralising antibodies (nAb), anti-spike (S) IgM, IgG, IgG avidity, IgG fucosylation and respiratory viral loads in a sub-set of patients (n=80) and controls (n=51) before and after transfusion, comparing them to those in the CP units (n=157) they received.

Results: Most patients were SARS-CoV-2 seropositive pre-transfusion (72% nAb; 89% S-IgG seropositivity). The majority (80%) had higher pre-transfusion S-IgG levels (median 1.7×10⁶ arbitrary units (AU); 56%) or S-IgG production rates (median 1.1×10⁶AU/day; 64%) than they received from CP (median 2.2×10⁵AU). Only 22% of the patients demonstrated significant (median 24-fold) increase in their S-IgG levels acquired from transfusion. Better outcomes, measured by organ support-free days, were associated with increase in S-IgM levels (p=0.007), decreased S-IgG fucosylation (p<0.001), lower patient age (p<0.001) but not with receiving CP (p=0.337).

Conclusions: Based on our data, increased S-antibody levels linked to transfused CP were only observed in pre-seroconversion or immunodeficient patients lacking their own SARS-CoV-2 antibodies, representing the groups where CP treatment has previously shown most benefit.

Keywords: Antibodies; COVID-19, SARS-CoV-2; Convalescent plasma treatment; Critical care; Infectious diseases; Serology; Transfusion medicine; Virology.