Albahari Dalia, Abdalla Oraib, Alqam Shatha Mahmud Ismail, Mohammed Mohammed Faisal Hamad, Ahmed Mohamed Ali Siddig, Wadoo Ovais
Department of Psychiatry, Hamad Medical Corporation, Doha, Qatar.
College of Medicine, Qatar University, Doha, Qatar.
Front Psychiatry. 2025 May 8;16:1527378. doi: 10.3389/fpsyt.2025.1527378. eCollection 2025.
Clozapine has immunomodulatory effects that raised concerns about its potential to exacerbate severe COVID-19. This study examines whether clozapine use is associated with worse COVID-19 outcomes in patients with schizophrenia.
This retrospective cohort study compared COVID-19 outcomes in SARS-CoV-2-infected patients on clozapine versus those on other antipsychotics. Primary outcomes included severe disease, hospitalization, ICU admission, and mortality. Descriptive statistics summarized the data, with categorical variables analyzed via Chi-square tests and exact Fisher test. The continuous variables were analyzed via Student's t-test. Logistic and linear regression analyses estimated odds ratios while adjusting for confounders.
Thirty-three patients on clozapine (29.7%) tested positive for SARS-CoV-2 and were compared to 132 SARS-CoV-2-positive patients on non-clozapine antipsychotics. Severe infection rates did not significantly differ (clozapine: 3%, non-clozapine: 7.69%, p = 0.340), nor did hospitalization rates (clozapine: 15.1%, non-clozapine: 16.9%, p = 0.807). All clozapine patients survived, while one death (0.7%) occurred in the non-clozapine group. The mean hospital stay was similar (clozapine: 8.8 days, SD = 2.2; non-clozapine: 11.5 days, SD = 1.9; p = 0.515). Logistic regression, correcting for age, sex, vaccination status, medical comorbidities, obesity, and smoking, found no significant associations: odds ratio for severe COVID-19 = 1.9 (95% CI: 0.1-12.0, p = 0.94); odds ratio for hospitalization = 0.96 (95% CI: 0.23-3.96, p = 0.953). Linear regression of hospital stay duration yielded a β-coefficient of 4.6 (95% CI: -9.4-18.7, p = 0.471). Peri- and post-infection white blood cell and neutrophil counts were not significantly different (p = 0.4298 and p = 0.1434, respectively).
Clozapine use was not associated with worse COVID-19 outcomes, supporting its relative safety during SARS-CoV-2 infection. These findings reassure clinicians regarding clozapine's continued use in treatment-resistant schizophrenia. However, the small clozapine sample size limits statistical power, warranting cautious interpretation and further research.
氯氮平具有免疫调节作用，这引发了人们对其可能加重重症 COVID-19 的担忧。本研究旨在探讨使用氯氮平是否与精神分裂症患者的 COVID-19 不良预后相关。
这项回顾性队列研究比较了服用氯氮平的 SARS-CoV-2 感染患者与服用其他抗精神病药物患者的 COVID-19 预后。主要结局包括重症疾病、住院、入住重症监护病房（ICU）和死亡率。描述性统计对数据进行了总结，分类变量通过卡方检验和精确 Fisher 检验进行分析。连续变量通过 Student t 检验进行分析。逻辑回归和线性回归分析在调整混杂因素后估计比值比。
33 名服用氯氮平的患者（29.7%）SARS-CoV-2 检测呈阳性，并与 132 名服用非氯氮平抗精神病药物的 SARS-CoV-2 阳性患者进行了比较。严重感染率无显著差异（氯氮平组：3%，非氯氮平组：7.69%，p = 0.340），住院率也无显著差异（氯氮平组：15.1%，非氯氮平组：16.9%，p = 0.807）。所有服用氯氮平的患者均存活，而非氯氮平组有 1 例死亡（0.7%）。平均住院时间相似（氯氮平组：8.8 天，标准差 = 2.2；非氯氮平组：11.5 天，标准差 = 1.9；p = 0.515）。在对年龄、性别、疫苗接种状况、合并症、肥胖和吸烟进行校正的逻辑回归分析中，未发现显著关联：重症 COVID-19 的比值比 = 1.9（95%置信区间：0.1 - 12.0，p = 0.94）；住院的比值比 = 0.96（95%置信区间：0.23 - 3.96，p = 0.953）。住院时间的线性回归得出β系数为 4.6（95%置信区间：-9.4 - 18.7，p = 0.471）。感染期间及感染后的白细胞和中性粒细胞计数无显著差异（分别为 p = 0.4298 和 p = 0.1434）。
使用氯氮平与 COVID-19 不良预后无关，这支持了其在 SARS-CoV-2 感染期间的相对安全性。这些发现让临床医生对氯氮平在难治性精神分裂症治疗中的持续使用放心。然而，氯氮平样本量较小限制了统计效力，需要谨慎解读并进一步研究。
