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.