¹CHA University Ilsan Medical Center, Department of Psychiatry, Goyang, Korea, Republic of, ²National Traffic Injury Rehabilitation Hospital, Department of Psychiatry, Yangpyeong, Korea, Republic of, ³Seoul National University Hospital, Department of Neuropsychiatry, Seoul, Korea, Republic of, ⁴School of Medicine, CHA University, Department of Physiology, Pocheon-si, Korea, Republic of, ⁵CHA Bundang Medical Center, Department of Clinical Pharmacology and Therapeutics, Seongnam-si, Korea, Republic of

Background: Individuals with schizophrenia face markedly elevated risks of SARS-CoV-2 infection, hospitalization, and mortality compared to the general population due to biological vulnerability, cognitive impairment, and socioeconomic disadvantage. Recognizing these risks, international public health guidelines have designated people with severe mental illness (SMI) as a high-priority group for COVID-19 vaccination. However, vaccine uptake among patients with schizophrenia has been suboptimal, partly due to structural barriers (e.g., limited access, institutional mistrust) and psychiatric concerns—including fears of symptom exacerbation, affective instability, or adverse interactions with psychotropic medications. While isolated case reports of psychiatric decompensation post-vaccination exist, large-scale real-world data on the clinical impact of COVID-19 vaccination in schizophrenia populations remain limited.

Aims & Objectives: We aimed to evaluate the association of COVID-19 vaccination with treatment adherence, psychiatric stability, and SARS-CoV-2 infection risk in patients with schizophrenia.

Method: We conducted a nationwide, retrospective, propensity score-matched cohort study using linked data from the National Health Insurance Service and the Korea Disease Control and Prevention Agency databases in South Korea. We identified patients with schizophrenia aged 19–64 years and stratified them into vaccinated (three doses) and unvaccinated groups. A 1:1 propensity score matching was performed. The primary outcomes were schizophrenia-related hospitalisation and emergency department visits. Key secondary outcomes included medication adherence, measured by the proportion of days covered (PDC), and diagnosed SARS-CoV-2 infection.

Results: Between December 1, 2019 and December 31, 2022, a total of 6,662 unvaccinated and 52,063 vaccinated patients were identified. After matching, the final cohort included 4,629 matched pairs (N=9,258). No significant between-group differences were observed in schizophrenia-related hospitalization or ED visit rates, suggesting that vaccination was not associated with psychiatric destabilization. However, the vaccinated group demonstrated significantly better medication adherence over time, with a smaller decline in PDC compared to the unvaccinated group (mean change –3.49% vs. –10.19%; adjusted p<0.0001). Paradoxically, the vaccinated group had a higher incidence of confirmed COVID-19 diagnoses (adjusted hazard ratio [aHR] for unvaccinated vs. vaccinated: 0.47, 95% CI: 0.439–0.504, p<0.0001), likely reflecting differences in healthcare access, testing frequency, or behavioral risk compensation.

Discussion & Conclusions: Our findings indicate that COVID-19 vaccination is safe in patients with schizophrenia and is not associated with an increased risk of psychiatric decompensation or treatment escalation. Importantly, vaccination was linked to improved treatment adherence, suggesting potential benefits beyond infection prevention—such as enhanced clinical continuity and engagement with care. These results support ongoing efforts to prioritize individuals with SMI in public health vaccination strategies and counter unfounded concerns about psychiatric risks. Targeted outreach and psychoeducation may further improve vaccine uptake and reduce disparities in this vulnerable population.