VACCINE RESPONSE AND IMMUNITY IN PATIENTS WITH PSYCHOTIC DISORDERS: PROSPECTIVE STUDY OF SARS-COV-2 AND PNEUMOCOCCAL VACCINATION
Authors: Arumuham *Atheeshaan , Mizuno Yuya , O'brien Oisin , Lobo Maria , Parmar Sita , Baxter Luke , Jolles Stephen , Howes Oliver D 
Published: February 2025

Abstract

Background
Schizophrenia is associated with excess mortality compared to the general population for both COVID-19 and pneumonia (1,2). Immune dysfunction may play a role in poorer outcomes. Schizophrenia has been associated with altered serum cytokine levels (3) and blunted response to vaccines relative to healthy controls (4). Patients with psychotic disorders have an increased risk of COVID-19 infection despite vaccination (5).

Aims & Objectives
We tested the hypothesis that COVID-19 vaccine response is lower in schizophrenia relative to controls. With clozapine reported to have immunosuppressant effects, we also tested the hypothesis that patients treated with clozapine have a significantly lower response to Pneumococcal vaccination compared to healthy volunteers.

Methods
We employed an open-label prospective study involving 4 cohorts. First, patients with psychotic disorders on any antipsychotic medication and matched healthy controls received the COVID- 19 vaccine. A separate cohort of patients on clozapine treatment and matched healthy controls received the Pneumovax-23 vaccine. Patients were recruited from adult mental health teams in South London and Maudsley NHS Foundation Trust. Controls with no history of psychosis were recruited from the same region. All participants provided baseline blood samples prior to receiving either the COVID-19 or Pneumovax-23 vaccine. Samples were then obtained 1-month post-vaccination, including SARS-CoV-2 spike protein IgG and anti-Pneumococcal total IgG (according to received vaccine). Also, in participants receiving Pneumovax-23, cytokines (IL-5, IL-6, IL-10, TNF-α, IFN-γ) and immunoglobulins (IgM, IgA, and IgG) were analysed at baseline and 6-hours post-vaccination to assess acute immune response.

Results
24 patients and 33 controls received the COVID-19 vaccine. Changes in SARS-CoV-2 spike protein IgG levels were significantly lower in patients (mean [SD]: +2.94 [1.80]) versus controls (+3.95 [1.64]; t55=-2.20, p=0.03). All controls positively seroconverted while 3 patients, who were all prescribed clozapine, did not. Collection of Pneumovax-23 response data is ongoing. Currently, 21 clozapine-treated patients and 13 controls have received the vaccine. Baseline general IgG levels were significantly lower in patients (8.82 [2.59]) compared to controls (12.40 [2.77], t31=-4.4, p&lt;0.001). Of these, 16 patients and 12 controls had baseline negative immunity to Pneumococcus. Changes in anti- Pneumococcal total IgG was significantly lower in patients (+33.93 [30.57]) compared to controls (+59.79 [23.59], t26=-2.43, p=0.02). All but 1 control positively seroconverted, while 8 patients on clozapine did not reach protective anti-Pneumococcal antibody levels. Changes in cytokines or immunoglobulins at 6-hours post Pneumovax-23 did not differ between groups.

Discussion & Conclusions
COVID-19 vaccine response was lower in patients with psychotic disorders relative to controls, suggesting an impaired immune response to the SARS-CoV-2 spike protein. Clozapine-treated patients had an impaired Pneumococcal vaccine response compared to healthy volunteers, with 50% not achieving protective antibody levels. Our findings indicate that patients with psychotic disorders, particularly those treated with clozapine, are at risk of inadequate immunity despite vaccination efforts. Future studies should aim to control for demographic confounders and examine long-term vaccine response.

References
1)De Hert, M. et al. (2022) “COVID-19-related mortality risk in people with severe mental illness: A systematic and critical review,” Frontiers in psychiatry, 12. doi: 10.3389/fpsyt.2021.798554.
2)Chou, F. H.-C., Tsai, K.-Y. and Chou, Y.-M. (2013) “The incidence and all-cause mortality of pneumonia in patients with schizophrenia: A nine-year follow-up study,” Journal of psychiatric research, 47(4), pp. 460–466. doi: 10.1016/j.jpsychires.2012.12.007.
3)Pillinger, T. et al. (2019) “A meta-analysis of immune parameters, variability, and assessment of modal distribution in psychosis and test of the immune subgroup hypothesis,” Schizophrenia bulletin, 45(5), pp. 1120–1133. doi: 10.1093/schbul/sby160.
4)Xiao, K. et al. (2022) “Immune response to vaccination in adults with mental disorders: A systematic review,” Journal of affective disorders, 304, pp. 66–77. doi: 10.1016/j.jad.2022.02.025.
5)Nishimi, K. et al. (2022) “Association of psychiatric disorders with incidence of SARS-CoV-2 breakthrough infection among vaccinated adults,” JAMA network open, 5(4), p. e227287. doi: 10.1001/jamanetworkopen.2022.7287.