Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine

Julian Stumpf; Torsten Siepmann; Tom Lindner; Claudia Karger; Jörg Schwöbel; Leona Anders; Robert Faulhaber-Walter; Jens Schewe; Heike Martin; Holger Schirutschke; Kerstin Barnett; Jan Hüther; Petra Müller; Torsten Langer; Thilo Pluntke; Kirsten Anding-Rost; Frank Meistring; Thomas Stehr; Annegret Pietzonka; Katja Escher; Simon Cerny; Hansjörg Rothe; Frank Pistrosch; Harald Seidel; Alexander Paliege; Joachim Beige; Ingolf Bast; Anne Steglich; Florian Gembardt; Friederike Kessel; Hannah Kröger; Patrick Arndt; Jan Sradnick; Kerstin Frank; Anna Klimova; René Mauer; Xina Grählert; Moritz Anft; Arturo Blazquez-Navarro; Timm H Westhoff; Ulrik Stervbo; Torsten Tonn; Nina Babel; Christian Hugo

doi:10.1016/j.lanepe.2021.100178

Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine

Lancet Reg Health Eur. 2021 Oct:9:100178. doi: 10.1016/j.lanepe.2021.100178. Epub 2021 Jul 23.

Authors

Julian Stumpf^{1

2}, Torsten Siepmann³, Tom Lindner⁴, Claudia Karger⁵, Jörg Schwöbel⁶, Leona Anders⁷, Robert Faulhaber-Walter⁸, Jens Schewe⁹, Heike Martin¹⁰, Holger Schirutschke¹¹, Kerstin Barnett¹², Jan Hüther¹³, Petra Müller¹⁴, Torsten Langer¹⁵, Thilo Pluntke¹⁶, Kirsten Anding-Rost¹⁷, Frank Meistring¹⁸, Thomas Stehr¹⁹, Annegret Pietzonka²⁰, Katja Escher²¹, Simon Cerny²², Hansjörg Rothe²³, Frank Pistrosch²⁴, Harald Seidel²⁵, Alexander Paliege¹, Joachim Beige^{5

26}, Ingolf Bast⁷, Anne Steglich¹, Florian Gembardt¹, Friederike Kessel¹, Hannah Kröger¹, Patrick Arndt¹, Jan Sradnick¹, Kerstin Frank²⁷, Anna Klimova²⁸, René Mauer²⁹, Xina Grählert³⁰, Moritz Anft³¹, Arturo Blazquez-Navarro³¹, Timm H Westhoff³², Ulrik Stervbo³¹, Torsten Tonn^{33

34}, Nina Babel^{31

35}, Christian Hugo^{1

2}

Affiliations

¹ Medizinische Klinik und Poliklinik III, Universitätsklinikum, Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
² KfH-Nierenzentrum Dresden, Dresden, Germany.
³ KfH-Nierenzentrum am Klinikum Chemnitz, Krankenhaus Küchwald, Chemnitz, Germany.
⁴ Division of Nephrology, University Hospital Leipzig, Leipzig, Germany.
⁵ KfH-Nierenzentrum am Klinikum St. Georg, Leipzig, Germany.
⁶ Dialysezenturm Chemnitz, Chemnitz, Germany.
⁷ Dialysepraxis Leipzig, Leipzig, Germany.
⁸ Nephrologisches Zentrum Freiberg, Freiberg, Germany.
⁹ Dialyse- und Nierenambulanz Sebnitz, Sebnitz, Germany.
¹⁰ Nephrologisches Zentrum Zwickau, Zwickau, Germany.
¹¹ PHV Dialysezentrum Dresden Friedrichstadt, Dresden, Germany.
¹² Dialyse Heidenau, Heidenau, Germany.
¹³ Nephrocare GmbH Döbeln, Döbeln, Germany.
¹⁴ PHV Dialysezentrum Dresden-Johannstadt, Dresden, Germany.
¹⁵ Dialysezentrum Annaberg, Annaberg-Buchholz, Germany.
¹⁶ KfH-Nierenzentrum Grimma, Grimma, Germany.
¹⁷ KfH-Nierenzentrum Bischofswerda, Bischofswerda, Germany.
¹⁸ KfH-Nierenzentrum am Städtischen Klinikum Görlitz, Görlitz, Germany.
¹⁹ KfH-Nierenzentrum Bautzen, Bautzen, Germany.
²⁰ Via medis Nierenzentrum Dresden MVZ GmbH, Dresden, Germany.
²¹ KfH-Gesundheitszentrum Aue, Aue-Bad-Schlema, Germany.
²² ELBLAND Dialyse Großenhain, Großenhain, Germany.
²³ Dialyse-Praxis Weißwasser, Weißwasser, Germany.
²⁴ Nephrologisches Zentrum Hoyerswerda, Hoyerswerda, Germany.
²⁵ KfH-Nierenzentrum am Vogtland Krankenhaus Plauen, Plauen, Germany.
²⁶ Department of Nephrology und Rheumatology, Internal Medicine II, Martin-Luther-University Halle/Wittenberg, Halle, Germany.
²⁷ Institut für Transfusionsmedizin Plauen, DRK-Blutspendedienst Nord-Ost gemeinnützige GmbH, Plauen, Germany.
²⁸ National Center for Tumor Diseases (NCT) Partner Site Dresden, Dresden, Germany.
²⁹ Faculty of Medicine Carl Gustav Carus, Institute for Medical Informatics and Biometry (IMB), Technische Universität, Dresden, Germany.
³⁰ Coordinating Centre for Clinical Trials, Dresden, Germany.
³¹ Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Germany.
³² Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany.
³³ Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Dresden, Germany.
³⁴ Faculty of Medicine Carl Gustav Carus, Transfusion Medicine, Technische Universität, Dresden, Germany.
³⁵ Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, and Institute of Medical Immunology, Germany.

Abstract

Background: Dialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality.

Methods: We conducted a prospective study exploring the eight week time course of specific cellular (interferon-γ release assay and flow cytometry) or/and humoral immune responses (ELISA) to SARS-CoV-2 boost vaccination in more than 3100 participants including medical personnel, dialysis patients and kidney transplant recipients using mRNA vaccines BNT162b2 or mRNA-1273.

Results: SARS-CoV-2-vaccination induced seroconversion efficacy in dialysis patients was similar to medical personnel (> 95%), but markedly impaired in kidney transplant recipients (42%). T-cellular immunity largely mimicked humoral results. Major risk factors of seroconversion failure were immunosuppressive drug number and type (belatacept, MMF-MPA, calcineurin-inhibitors) as well as vaccine type (BNT162b2 mRNA). Seroconversion rates induced by mRNA-1273 compared to BNT162b2 vaccine were 97% to 88% (p < 0.001) in dialysis and 49% to 26% in transplant patients, respectively. Specific IgG directed against the new binding domain of the spike protein (RDB) were significantly higher in dialysis patients vaccinated by mRNA-1273 (95%) compared to BNT162b2 (85%, p < 0.001). Vaccination appeared safe and highly effective demonstrating an almost complete lack of symptomatic COVID-19 disease after boost vaccination as well as ceased disease incidences during third pandemic wave in dialysis patients.

Conclusion: Dialysis patients exhibit a remarkably high seroconversion rate of 95% after boost vaccination, while humoral response is impaired in the majority of transplant recipients. Immunosuppressive drug number and type as well as vaccine type (BNT162b2) are major determinants of seroconversion failure in both dialysis and transplant patients suggesting immune monitoring and adaption of vaccination protocols.

Keywords: BNT162b2; COVID-19; SARS-CoV-2 vaccination; clinical decision-making; dialysis patients; epidemiology; guidelines; humoral and cellular immune response; kidney transplant recipients; mRNA-1273; medical personnel; tozinameran.