Donors for SARS-CoV-2 Convalescent Plasma for a Controlled Clinical Trial: Donor Characteristics, Content and Time Course of SARS-CoV-2 Neutralizing Antibodies

Sixten Körper; Bernd Jahrsdörfer; Victor M Corman; Jan Pilch; Patrick Wuchter; Rainer Blasczyk; Rebecca Müller; Torsten Tonn; Tamam Bakchoul; Richard Schäfer; David Juhl; Tatjana Schwarz; Nina Gödecke; Thomas Burkhardt; Michael Schmidt; Thomas Appl; Hermann Eichler; Harald Klüter; Christian Drosten; Erhard Seifried; Hubert Schrezenmeier

doi:10.1159/000515610

Donors for SARS-CoV-2 Convalescent Plasma for a Controlled Clinical Trial: Donor Characteristics, Content and Time Course of SARS-CoV-2 Neutralizing Antibodies

Transfus Med Hemother. 2021 May;48(3):137-147. doi: 10.1159/000515610. Epub 2021 Apr 21.

Authors

Sixten Körper^{1

2}, Bernd Jahrsdörfer^{1

2}, Victor M Corman³, Jan Pilch⁴, Patrick Wuchter⁵, Rainer Blasczyk⁶, Rebecca Müller⁵, Torsten Tonn⁷, Tamam Bakchoul⁸, Richard Schäfer⁹, David Juhl¹⁰, Tatjana Schwarz³, Nina Gödecke⁶, Thomas Burkhardt⁷, Michael Schmidt⁹, Thomas Appl^{1

2}, Hermann Eichler⁴, Harald Klüter⁵, Christian Drosten³, Erhard Seifried⁹, Hubert Schrezenmeier^{1

2}

Affiliations

¹ Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, Ulm, Germany.
² Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
³ Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health and German Centre for Infection Research, Berlin, Germany.
⁴ Institute of Clinical Hemostaseology and Transfusion Medicine, University Hospital and University of the Saarland, Homburg, Germany.
⁵ Institute of Transfusion Medicine and Immunology, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, Medical Faculty of Medicine Mannheim, University Mannheim, Mannheim, Germany.
⁶ Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany.
⁷ Experimental Transfusion Medicine, Technical University of Dresden, German Red Cross Blood Transfusion Service Nord-Ost gGmbH Dresden, Dresden, Germany.
⁸ Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany.
⁹ Institute of Transfusion Medicine and Immunohematology, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen, Frankfurt, Germany.
¹⁰ Institute of Transfusion Medicine, University Hospital Schleswig-Holstein, Kiel and Lübeck, Germany.

Abstract

Background: Convalescent plasma is one of the treatment options for COVID-19 which is currently being investigated in many clinical trials. Understanding of donor and product characteristics is important for optimization of convalescent plasma.

Methods: Patients who had recovered from CO-VID-19 were recruited as donors for COVID-19 convalescent plasma (CCP) for a randomized clinical trial of CCP for treatment of severe COVID-19 (CAPSID Trial). Titers of neutralizing antibodies were measured by a plaque-reduction neutralization test (PRNT). Correlation of antibody titers with host factors and evolution of neutralizing antibody titers over time in repeat donors were analysed.

Results: A series of 144 donors (41% females, 59% males; median age 40 years) underwent 319 plasmapheresis procedures providing a median collection volume of 850 mL and a mean number of 2.7 therapeutic units per plasmapheresis. The majority of donors had a mild or moderate course of COVID-19. The titers of neutralizing antibodies varied greatly between CCP donors (from <1:20 to >1:640). Donor factors (gender, age, ABO type, body weight) did not correlate significantly with the titer of neutralizing antibodies. We observed a significant positive correlation of neutralization titers with the number of reported COVID-19 symptoms and with the time from SARS-CoV-2 diagnosis to plasmapheresis. Neutralizing antibody levels were stable or increased over time in 58% of repeat CCP donors. Mean titers of neutralizing antibodies of first donation and last donation of repeat CCP donors did not differ significantly (1:86 at first compared to 1:87 at the last donation). There was a significant correlation of neutralizing antibodies measured by PRNT and anti-SARS-CoV-2 IgG and IgA antibodies which were measured by ELISA. CCP donations with an anti-SARS-CoV-2 IgG antibody content above the 25th percentile were substantially enriched for CCP donations with higher neutralizing antibody levels.

Conclusion: We demonstrate the feasibility of collection of a large number of CCP products under a harmonized protocol for a randomized clinical trial. Titers of neutralizing antibodies were stable or increased over time in a subgroup of repeat donors. A history of higher number of COVID-19 symptoms and higher levels of anti-SARS-CoV-2 IgG and IgA antibodies in immunoassays can preselect donations with higher neutralizing capacity.

Keywords: COVID-19; Convalescent plasma; Neutralizing antibody; Plasma donors; SARS-CoV-2.