Mental illness and antibody responses after COVID-19 vaccination in a prospective population-based study in Catalonia

Background Mental illnesses have been overlooked as a potential factor influencing antibody responses to COVID-19 vaccine. Associations between mental disorders and antibody response might vary by specific disorders, depend on the long-term course of the illness and relate to psychotropic treatment.

Methods: The association between mental illness diagnoses (mood affective disorders, anxiety disorders, other) over ten years and psychotropic drug prescription based on electronic health records with antibody levels (IgG and IgA) post COVID-19 vaccination was assessed in 939 vaccinated adults from Catalonia, Spain. We employed linear regression models to assess associations between specific mental illnesses and psychotropic drugs with antibody levels, correcting for demographics, comorbidities and lifestyle factors. In a genotyped subset (n = 247) we assessed the effect of polygenic risk scores (PRS) for mental illnesses and performed a two-sample mendelian randomization (MR) analysis to examine causality between mental illness and antibody responses.

Results: Mood affective disorders were associated with lower IgG to receptor binding domain (RBD) [percentage change = -26.37 (95 % CI, -42.00, -6.54)]. Diagnosis of anxiety disorders was not associated with the outcome. The group of other diagnoses (mainly including insomnia and nicotine dependence) were associated with lower IgG RBD levels [percentage change: -21.53 (95 % CI, -35.38, -4.71)] and recent onset cases (≤5 years ago) showed greater decline in antibody levels. Participants on second-generation antipsychotics and multiple classes of psychotropic drugs in the last 6 months exhibited lower antibody levels. In the genotyped population, higher genetic liability (higher PRS) to schizophrenia was associated with lower IgG RBD levels [percentage change = -35.49 (95 % CI, -56.55, -4.23)]. MR analysis revealed a causal relationship between major depression genetic instrumental variables and lower IgG RBD and S levels.

Conclusions: These findings raise concerns about the efficacy of COVID-19 vaccines and potentially of other vaccines as well, in individuals with mood affective disorders, current/recent insomnia and nicotine dependence and people on multiple psychotropic drugs. Whether these associations are translated into increased risk for breakthrough infections and immune mediated long-term sequels of the SARS-CoV-2 infection warrants further investigation.