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Successful treatment of COVID-19 infection with convalescent plasma in B-cell-depleted patients may promote cellular immunity
Authors:Andreas E. Kremer  Anita N. Kremer  Carsten Willam  Simon Völkl  Johan Verhagen  Susanne Achenbach  Edith D. van der Meijden  Vanessa Lang  Michael Aigner  Clara Maier  Matthias Tenbusch  Klaus Korn  Gloria Lutzny-Geier  Silvia Spoerl  Richard Strauß  Marcel Vetter  Klaus Überla  Markus F. Neurath  Andreas Mackensen  Mario Schiffer  Holger Hackstein
Affiliation:1. Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland;2. Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany

These authors contributed equally to this work.;3. Department of Internal Medicine 4, Nephrology and Hypertension, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany

These authors contributed equally to this work.;4. Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany;5. Department of Transfusion Medicine and Haemostaseology, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany;6. Institute of Virology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany;7. Department of Internal Medicine 1, Gastroenterology, Pneumology and Endocrinology, University Hospital Erlangen and Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany;8. Department of Transfusion Medicine and Haemostaseology, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany

These authors contributed equally to this work.

Abstract:Treatment with convalescent plasma has been shown to be safe in coronavirus disease in 2019 (COVID-19) infection, although efficacy reported in immunocompetent patients varies. Nevertheless, neutralizing antibodies are a key requisite in the fight against viral infections. Patients depleted of antibody-producing B cells, such as those treated with rituximab (anti-CD20) for hematological malignancies, lack a fundamental part of their adaptive immunity. Treatment with convalescent plasma appears to be of general benefit in this particularly vulnerable cohort. We analyzed clinical course and inflammation markers of three B-cell-depleted patients suffering from COVID-19 who were treated with convalescent plasma. In addition, we measured serum antibody levels as well as peripheral blood CD38/HLA-DR-positive T-cells ex vivo and CD137-positive T-cells after in vitro stimulation with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides in these patients. We observed that therapy with convalescent plasma was effective in all three patients and analysis of CD137-positive T-cells after stimulation with SARS-CoV-2 peptides showed an increase in peptide-specific T-cells after application of convalescent plasma. In conclusion, we here demonstrate efficacy of convalescent plasma therapy in three B-cell-depleted patients and present data that suggest that while application of convalescent plasma elevates systemic antibody levels only transiently, it may also boost specific T-cell responses.
Keywords:B-cell deficiency  convalescent plasma  COVID-19  SARS-CoV-2  T-cell immunity
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