Variation in anti-SARS-CoV-2 spike antibody responses by variants in patients with severe mental illness after COVID-19 vaccination.

Research has shown that patients with psychiatric disorders are more susceptible to contracting SARS-CoV-2 and tend to experience worse outcomes from COVID-19. Therefore, vaccination is strongly suggested for these patients to enhance protection. However, there is limited research on how COVID-19 vaccines induce antibody responses, specifically in individuals with psychiatric conditions. Furthermore, the situation has become more complex with the emergence of variants of concern (VOCs), and the effectiveness of antibody responses against these variants is still poorly understood. To determine whether patients with severe mental illness (SMI) mount an adequate immune reaction to COVID-19 vaccination, we studied the immunization effect of two widely used vaccines, ChAdOx1-S (AstraZeneca) and mRNA-1273 (Moderna), in patients with SMI compared to healthy controls. We enrolled 163 patients with SMI (mainly schizophrenia) and 66 healthy controls, all of whom were negative for previous SARS-CoV-2 infection. We analyzed anti-SARS-CoV-2 spike antibody titers against wild-type (WT), Delta, and Omicron variants after full (two-dose) vaccination with either the ChAdOx1-S or mRNA-1273 COVID-19 vaccines. Patients with SMI exhibited significantly lower mean anti-SARS-CoV-2 spike antibody titers. These results were consistent across different vaccine types and VOCs. Vaccination with ChAdOx1-S consistently induced lower spike-binding antibodies against WT, Delta, and Omicron variants compared to the mRNA-1273 vaccine. While the antibody activities against Omicron are well preserved, they are weaker than those against the WT and Delta variants. Our findings explain why patients with SMI are particularly susceptible to SARS-CoV-2 infection, breakthrough infections, and poorer COVID-19 outcomes.