Reduced SARS-CoV-2 vaccine-specific antibody response associated with high clozapine doses in schizophrenia spectrum disorders.

Background: Schizophrenia, affecting approximately 1 % of the population worldwide, is associated with increased mortality rates and a reduced life expectancy of 10-20 years. Approximately 30 % of cases are resistant to conventional antipsychotic treatments, necessitating the use of clozapine. Recent evidence suggests that clozapine exerts immunomodulatory effects, with individuals undergoing chronic clozapine treatment exhibiting immune profiles resembling primary immunodeficiencies. Objective: To evaluate the immune response to vaccination with the spike protein of SARS-CoV-2 in schizophrenia patients treated with clozapine, compared to those receiving other antipsychotics. Methods: The study included 98 patients diagnosed with schizophrenia or schizoaffective disorder, of whom 69 were treated with clozapine. Demographic, clinical, and laboratory data were collected for all participants. Anti-spike protein antibodies were measured using the Elecsys® Anti-SARS-CoV-2 S assay. Results: No significant differences were observed in demographic, clinical, or laboratory parameters between the groups. Univariate analysis revealed that spike antibody levels were positively associated with smoking habits and more than two exposures to the virus, while they were negatively associated with the time elapsed since vaccination and clozapine dosage.In multivariate analysis, patients receiving clozapine doses >350 mg/day exhibited a significant reduction in anti-spike antibody levels compared to those not treated with clozapine (fold change = 0.49 [0.24-0.97], Conclusion: High doses of clozapine (>350 mg/day) in patients with schizophrenia and schizoaffective disorders are associated with a diminished immune response to SARS-CoV-2 spike protein vaccination.