Humoral and cellular immune response after COVID-19 vaccination in patients with sickle cell disease on hydroxyurea
Patients with sickle cell disease (SCD) are at increased risk of COVID-19-related mortality compared with healthy individuals, even after vaccination. To what extent impaired vaccine-induced immunity contributes to this risk is unknown. We prospectively investigated vaccine immunogenicity in 31 patients with SCD who received COVID-19 mRNA vaccines. All patients used hydroxyurea. We quantified humoral and cellular immune responses 4 weeks after the second and third vaccinations and compared the results with those of age-, sex-, and vaccine-matched healthy individuals. Irrespective of higher naïve and lower memory B-cell subsets, serum neutralizing spike glycoprotein 1 immunoglobulin G antibody concentrations and frequencies of spike-specific memory B cells were similar to those in healthy individuals at each time point. Frequencies of CD4+ and CD8+ T cells in patients with SCD were also comparable with controls; however, type 1 cytokine production by spike-specific T cells was reduced. Reduced cytokine production and lower antibody production correlated with higher serum fetal hemoglobin levels, suggesting an association with hydroxyurea use. Although a third vaccination improved neutralizing antibody and memory B-cell responses, T helper 1 cytokine production tended to remain lower in patients than in controls. Our data point toward delayed or reduced vaccine-induced immunity, in line with previous reports, which may contribute to the increased risk of COVID-19-related mortality reported in these patients. This trial was registered at www.ccmo.nl as NL-OMON51241.
Authors
- Marit J. van Gils (ORCID: https://orcid.org/0000-0003-3422-8161)
- Nienke J.E. Haverkate (ORCID: https://orcid.org/0000-0002-3701-4735)
- Quincy Hofsink (ORCID: https://orcid.org/0009-0004-0216-7071)
- Gerco den Hartog (ORCID: https://orcid.org/0000-0002-2103-6315)
- Pim G. N. J. Mutsaers (ORCID: https://orcid.org/0000-0002-3924-8578)
- Rory D. de Vries (ORCID: https://orcid.org/0000-0003-2817-0127)
- Corine H. GeurtsvanKessel (ORCID: https://orcid.org/0000-0002-7678-314X)
- Birgit I. Lissenberg‐Witte (ORCID: https://orcid.org/0000-0001-9448-1826)
- Rob van Binnendijk (ORCID: https://orcid.org/0000-0002-5808-1443)
- Sabine Haggenburg (ORCID: https://orcid.org/0000-0003-4095-9307)
- Erfan Nur (ORCID: https://orcid.org/0000-0002-7069-930X)
- Abraham Goorhuis (ORCID: https://orcid.org/0000-0001-7423-6217)
- Mathieu Claireaux (ORCID: https://orcid.org/0000-0003-1890-9493)
- Mette D. Hazenberg (ORCID: https://orcid.org/0000-0002-5113-0249)
- Charlotte F.J. Van Tuijn (ORCID: https://orcid.org/0000-0003-4278-5267)
- Annoek E. C. Broers (ORCID: https://orcid.org/0000-0003-0118-0966)
- Bart J. Biemond (ORCID: https://orcid.org/0000-0002-4426-5743)
- Inger S. Nijhof
- Michel S. Bhoekhan
- Cilia R. Pothast (ORCID: https://orcid.org/0000-0002-9761-3123)
- Caroline E. Rutten
- Mirjam H.M. Heemskerk (ORCID: https://orcid.org/0000-0001-6320-9133)
Institutions
- Radboud University Nijmegen (NL)
- Leiden University Medical Center (NL)
- Erasmus MC (NL)
- Radboud University Medical Center (NL)
- Sanquin (NL)
- Netherlands Center for Occupational Diseases (NL)
- St. Antonius Ziekenhuis (NL)
- National Institute for Public Health and the Environment (NL)
- Amsterdam Neuroscience (NL)
- Erasmus MC Cancer Institute (NL)
- Amsterdam University Medical Centers (NL)
- Vrije Universiteit Amsterdam (NL)
- University of Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Erasmus University Rotterdam (NL)
Publication Details
- Journal
- Blood Advances
- Published
- 2025-11-26
- DOI
- https://doi.org/10.1182/bloodadvances.2025017239
- Primary Topic
- Blood groups and transfusion
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Amsterdam University Medical Centers
- ZonMw
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek