Humoral and cellular immune response after COVID-19 vaccination in patients with sickle cell disease on hydroxyurea
Open Access
- 12 February 2026
- journal article
- Published by American Society of Hematology in Blood Advances
- Vol. 10 (4) , 1068-1081
Abstract
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.Keywords
This publication has 49 references indexed in Scilit:
- Unswitched memory B cell deficiency in children with sickle cell disease and response to pneumococcal polysaccharide vaccineAmerican Journal of Hematology, 2024
- SARS‐CoV ‐2 mRNA vaccination of aplastic anemia patients is safe and effectiveAmerican Journal of Hematology, 2022
- Impact of adherence to hydroxyurea on health outcomes among patients with sickle cell diseaseAmerican Journal of Hematology, 2022
- Antibody Response in Immunocompromised Patients With Hematologic Cancers Who Received a 3-Dose mRNA-1273 Vaccination Schedule for COVID-19JAMA Oncology, 2022
- Increased CD8 T‐cell immunity after COVID‐19 vaccination in lymphoid malignancy patients lacking adequate humoral response: An immune compensation mechanism?American Journal of Hematology, 2022
- COVID-19 outcomes in sickle cell disease and sickle cell traitBest Practice & Research Clinical Haematology, 2022
- SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to OmicronCell, 2022
- Assessment of Clinical Outcomes Among Children and Adolescents Hospitalized With COVID-19 in 6 Sub-Saharan African CountriesJAMA Pediatrics, 2022
- Adaptive immunity to SARS-CoV-2 and COVID-19Cell, 2021
- Alteration of lymphocyte phenotype and function in sickle cell anemia: Implications for vaccine responsesAmerican Journal of Hematology, 2016