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Fourth mRNA COVID-19 Vaccination in Immunocompromised Patients with Hematologic Malignancies

23 Pages Posted: 6 Mar 2023

See all articles by Quincy Hofsink

Quincy Hofsink

University of Amsterdam, Academic Medical Center, Department of Hematology

Sabine Haggenburg

University of Amsterdam, Academic Medical Center, Department of Hematology

Birgit I. Lissenberg-Witte

University of Amsterdam - Department of Clinical Epidemiology, Biostatistics and Bioinformation

Annoek E.C. Broers

Erasmus University Rotterdam (EUR) - Department of Hematology

Jaap A. van Doesum

University of Groningen - Department of Hematology and Oncology

Robert Samuel van Binnendijk

National Institute for Public Health and the Environment (RIVM) - Department for Immunology of Infectious Diseases and Vaccination (IIV)

Gerco den Hartog

National Institute for Public Health and the Environment (RIVM) - Department of Immune Surveillance

Michel S. Bhoekhan

University of Amsterdam, Academic Medical Center, Department of Hematology

Nienke J.E. Haverkate

University of Amsterdam - Amsterdam Institute for Infection and Immunity

Johan van Meerloo

Vrije Universiteit Amsterdam - Department of Hematology

Judith A. Burger

University of Amsterdam - Amsterdam Institute for Infection and Immunity

Joey H. Bouhuijs

University of Amsterdam - Amsterdam Institute for Infection and Immunity

Gaby Smits

National Institute of Public Health and the Environment

D. Wouters

University of Amsterdam - Central Diagnostic Laboratory

Ester M.M. van Leeuwen

University of Amsterdam - Amsterdam Institute for Infection and Immunity

Hetty J. Bontkes

Free University, Amsterdam - Medical Immunology Laboratory

Neeltje A. Kootstra

University of Amsterdam - Amsterdam Institute for Infection and Immunity

Sandra Vogels-Nooijen

Netherlands Comprehensive Cancer Organisation

Nynke Rots

National Institute for Public Health and the Environment (RIVM) - Centre for Infectious Disease Control

Josine van Beek

National Institute for Public Health and the Environment (RIVM) - Department for Immunology of Infectious Diseases and Vaccination (IIV)

Mirjam HM Heemskerk

Leiden University, Medical Center (LUMC), Department of Hematology

Kazimierz Groen

Vrije Universiteit Amsterdam - Department of Hematology

Tom van Meerten

University of Groningen - Department of Hematology and Oncology

Pim G. N. J. Mutsaers

Erasmus University Rotterdam (EUR) - Department of Hematology

Marit J. van Gils

University of Amsterdam - Department of Medical Microbiology and Infection Prevention

Abraham Goorhuis

University of Amsterdam - Department of Infectious Diseases

Caroline E. Rutten

University of Amsterdam, Academic Medical Center, Department of Hematology

Mette D. Hazenberg

University of Amsterdam, Academic Medical Center, Department of Hematology

Inger S. Nijhof

Vrije Universiteit Amsterdam - Department of Hematology

COBRA KAI Study Team

Independent

More...

Abstract

Background: Patients with hematologic malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality.

Methods: In this cohort study we quantified SARS-CoV-2-specific antibody concentration and neutralizing activity in SARS-CoV-2 naive, immunocompromised patients with hematologic malignancies who received 4 COVID-19 mRNA vaccinations.

Findings: 414 patients with hematologic malignancies were included in our analyses. Although S1 IgG concentrations significantly improved after the fourth dose, they remained significantly lower compared to those obtained by age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralizing antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in some patient groups with persistent immunodeficiencies. 19% of patients did not seroconvert despite 4 vaccinations. Patients who received their first 2 vaccinations when they were B cell depleted and the third and fourth vaccination during B cell recovery demonstrated similar antibody induction dynamics as patients with normal B cell numbers during the first 2 vaccinations. However, the neutralizing capacity of these antibodies was significantly better than that of patients with normal B cell numbers after two vaccinations.

Interpretation: A fourth mRNA COVID-19 vaccination improved S1 IgG concentrations in the majority of patients with a hematologic malignancy. Vaccination during B cell depletion may pave the way for better quality of antibody responses after B cell reconstitution.

Funding: The Netherlands Organisation for Health Research and Development and Amsterdam UMC.

Declaration of Interest: None of the authors declare competing financial interests.

Ethical Approval: Study protocols were approved by the Institutional Review Board of Amsterdam UMC location Vrije Universiteit and participating centers (COBRA-KAI study) and Utrecht University (VITAL cohort). All patients provided written informed consent.

Keywords: Humoral immunogenicity, Antibody response, SARS-CoV-2, COVID-19 vaccination, Booster vaccination, Hematologic malignancies, Immunocompromised

Suggested Citation

Hofsink, Quincy and Haggenburg, Sabine and Lissenberg-Witte, Birgit I. and Broers, Annoek E.C. and van Doesum, Jaap A. and van Binnendijk, Robert Samuel and den Hartog, Gerco and Bhoekhan, Michel S. and Haverkate, Nienke J.E. and van Meerloo, Johan and Burger, Judith A. and Bouhuijs, Joey H. and Smits, Gaby and Wouters, D. and van Leeuwen, Ester M.M. and Bontkes, Hetty J. and Kootstra, Neeltje A. and Vogels-Nooijen, Sandra and Rots, Nynke and van Beek, Josine and Heemskerk, Mirjam HM and Groen, Kazimierz and van Meerten, Tom and Mutsaers, Pim G. N. J. and van Gils, Marit J. and Goorhuis, Abraham and Rutten, Caroline E. and Hazenberg, Mette D. and Nijhof, Inger S. and Team, COBRA KAI Study, Fourth mRNA COVID-19 Vaccination in Immunocompromised Patients with Hematologic Malignancies. Available at SSRN: https://ssrn.com/abstract=4375614 or http://dx.doi.org/10.2139/ssrn.4375614

Quincy Hofsink

University of Amsterdam, Academic Medical Center, Department of Hematology ( email )

Sabine Haggenburg

University of Amsterdam, Academic Medical Center, Department of Hematology ( email )

Birgit I. Lissenberg-Witte

University of Amsterdam - Department of Clinical Epidemiology, Biostatistics and Bioinformation ( email )

PO Box 22700
Amsterdam, 1100 DD
Netherlands

Annoek E.C. Broers

Erasmus University Rotterdam (EUR) - Department of Hematology ( email )

Jaap A. Van Doesum

University of Groningen - Department of Hematology and Oncology ( email )

Robert Samuel Van Binnendijk

National Institute for Public Health and the Environment (RIVM) - Department for Immunology of Infectious Diseases and Vaccination (IIV) ( email )

Bilthoven
Netherlands

Gerco Den Hartog

National Institute for Public Health and the Environment (RIVM) - Department of Immune Surveillance ( email )

Michel S. Bhoekhan

University of Amsterdam, Academic Medical Center, Department of Hematology ( email )

Nienke J.E. Haverkate

University of Amsterdam - Amsterdam Institute for Infection and Immunity ( email )

Johan Van Meerloo

Vrije Universiteit Amsterdam - Department of Hematology ( email )

Judith A. Burger

University of Amsterdam - Amsterdam Institute for Infection and Immunity ( email )

Joey H. Bouhuijs

University of Amsterdam - Amsterdam Institute for Infection and Immunity ( email )

Gaby Smits

National Institute of Public Health and the Environment ( email )

D. Wouters

University of Amsterdam - Central Diagnostic Laboratory ( email )

Ester M.M. Van Leeuwen

University of Amsterdam - Amsterdam Institute for Infection and Immunity ( email )

Hetty J. Bontkes

Free University, Amsterdam - Medical Immunology Laboratory ( email )

Neeltje A. Kootstra

University of Amsterdam - Amsterdam Institute for Infection and Immunity ( email )

Sandra Vogels-Nooijen

Netherlands Comprehensive Cancer Organisation ( email )

Nynke Rots

National Institute for Public Health and the Environment (RIVM) - Centre for Infectious Disease Control ( email )

Bilthoven
Netherlands

Josine Van Beek

National Institute for Public Health and the Environment (RIVM) - Department for Immunology of Infectious Diseases and Vaccination (IIV) ( email )

Mirjam HM Heemskerk

Leiden University, Medical Center (LUMC), Department of Hematology ( email )

Netherlands

Kazimierz Groen

Vrije Universiteit Amsterdam - Department of Hematology ( email )

Tom Van Meerten

University of Groningen - Department of Hematology and Oncology ( email )

Netherlands

Pim G. N. J. Mutsaers

Erasmus University Rotterdam (EUR) - Department of Hematology ( email )

Marit J. Van Gils

University of Amsterdam - Department of Medical Microbiology and Infection Prevention ( email )

Amsterdam
Netherlands

Abraham Goorhuis

University of Amsterdam - Department of Infectious Diseases ( email )

Caroline E. Rutten

University of Amsterdam, Academic Medical Center, Department of Hematology ( email )

Mette D. Hazenberg (Contact Author)

University of Amsterdam, Academic Medical Center, Department of Hematology ( email )

Inger S. Nijhof

Vrije Universiteit Amsterdam - Department of Hematology ( email )

COBRA KAI Study Team

Independent

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