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Humoral and cellular responses to mRNA vaccines against SARS-CoV2 in patients with a history of CD20-B-cell depleting therapy
Matthias B. Moor; Franziska Suter-Riniker; Michael P. Horn; Daniel Aeberli; Jennifer Amsler; Burkhard Moeller; Linet M. Njue; Cesare Medri; Anne Angelillo-Scherrer; Luca Borradori; Susanne Radonjic-Hoesli; Morteza Seyed Jafari; Andrew Chan; Robert Hoepner; Vera Ulrike Bacher; Laila-Yasmin Mani; Joseena Mariam Iype; Cedric Hirzel; Britta Maurer; Daniel Sidler.
Afiliación
  • Matthias B. Moor; Department of Nephrology and Hypertension, Inselspital, Bern University Hospital and Department of Biomedical Research, University of Bern, Bern, Switzerland
  • Franziska Suter-Riniker; Department of Infectious Diseases, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
  • Michael P. Horn; Department of Clinical Chemistry, Inselspital University Hospital, Bern, Switzerland
  • Daniel Aeberli; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital and Department of Biomedical Research, University of Bern, Bern, Switzerland
  • Jennifer Amsler; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital and Department of Biomedical Research, University of Bern, Bern, Switzerland
  • Burkhard Moeller; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital and Department of Biomedical Research, University of Bern, Bern, Switzerland
  • Linet M. Njue; Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • Cesare Medri; Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • Anne Angelillo-Scherrer; Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • Luca Borradori; Department of Dermatology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
  • Susanne Radonjic-Hoesli; Department of Dermatology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
  • Morteza Seyed Jafari; Department of Dermatology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
  • Andrew Chan; Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
  • Robert Hoepner; Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
  • Vera Ulrike Bacher; Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • Laila-Yasmin Mani; Department of Nephrology and Hypertension, Inselspital, Bern University Hospital and Department of Biomedical Research, University of Bern, Bern, Switzerland
  • Joseena Mariam Iype; Department of Clinical Chemistry, Inselspital University Hospital, Bern, Switzerland
  • Cedric Hirzel; Department of Infectious Diseases, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
  • Britta Maurer; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital and Department of Biomedical Research, University of Bern, Bern, Switzerland
  • Daniel Sidler; Department of Nephrology and Hypertension, Inselspital, Bern University Hospital and Department of Biomedical Research, University of Bern, Bern, Switzerland
Preprint en En | PREPRINT-MEDRXIV | ID: ppmedrxiv-21259848
ABSTRACT
BackgroundB-cell depleting therapies increase COVID19 morbidity and mortality. For this specific population, evidence-based vaccination strategies are lacking. Here, we investigated humoral and cell mediated immune responses to SARS-CoV2 mRNA-based vaccines in patients receiving CD20-B-cell depleting agents for autoimmune disease, malignancy, or transplantation. MethodsPatients at the Bern University Hospital with a treatment history of anti-CD20 depleting agents (rituximab or ocrelizumab) were enrolled for analysis of humoral and cell-mediated immune responses (by interferon-{gamma} release assay) after completing vaccination against SARS-CoV2. Primary outcome was the the anti-spike antibody response in anti-CD20-treated patients (n=96) in comparison to immunocompetent controls (n=29). ResultsAnti-spike IgG antibodies were detected in 49% of patients 1.79 months after the second vaccine dose (interquartile range, IQR 1.16-2.48) compared to 100% of controls (p<0.001). SARS-CoV2 specific interferon-{gamma} release was detected in 20% of patients and 75% of healthy controls (p<0.001). Only 11% of patients, but 75%of healthy controls showed positive reactions in both assays, respectively (p<0.001). Time since last anti-CD20 therapy (7.6 months), peripheral CD19+ (>27/{micro}l), and CD4+ lymphocyte count (>653/{micro}l) predicted humoral vaccine response (area under the curve [AUC] 67% [CI 56-78], 67% [CI 55-80] and 66% [CI 54-79], (positive predictive value [PPV] 0.78, 0.7 and 0.71). ConclusionThis study provides evidence for blunted humoral and cell-mediated immune responses elicited by SARS-CoV2 mRNA vaccines in patients with CD20-depleting treatment history. Lymphocyte subpopulation counts are associated with vaccine response in this highly vulnerable population. (Funded by Bern University Hospital, ClinicalTrials.gov number, NCT04877496)
Licencia
cc_by_nc
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2021 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2021 Tipo del documento: Preprint