Humoral and cellular immune response after COVID-19 vaccination in patients with sickle cell disease on hydroxyurea Open Access

• Normal spike-specific antibody and memory B cell concentrations in two-dose COVID-19 mRNA vaccinated patients with sickle cell disease;

• Spike-specific T cell frequencies were normal, but their capacity to produce type 1 cytokines was reduced in these patients.

Patients with sickle cell disease (SCD) are at increased risk of COVID-19-related mortality compared to healthy individuals, also after vaccination. To what extent impaired vaccine-induced immunity contributes to this risk is unknown. We prospectively investigated vaccine immunogenicity in 31 COVID-19 mRNA vaccinated patients with SCD. All patients used hydroxyurea. We quantified humoral and cellular immune responses four weeks after second and third vaccination and compared results with age-, sex- and vaccine-matched healthy individuals. Irrespective of higher naive and lower memory subsets of B cells, serum neutralizing spike glycoprotein 1 (S1) IgG antibody concentrations and frequencies of spike-specific memory B cells were similar to healthy individuals at each timepoint. Frequencies of CD4+ and CD8+ T cells in patients with SCD were also comparable to 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 the use of hydroxyurea. Whereas a third vaccination improved neutralizing antibody and memory B cell responses, Th1 cytokine production tended to remain lower in patients compared to controls. Our data point towards delayed or reduced vaccine-induced immunity, in line with previous reports, which may contribute to the increased risk for COVID-19 related mortality reported in these patients. Clinical Trial: NL-OMON51241, CCMO.nl