Background

Mental disorders might be a risk factor for severe COVID-19. We aimed to assess the specific risks of COVID-19-related mortality, hospitalisation, and intensive care unit (ICU) admission associated with any pre-existing mental disorder, and specific diagnostic categories of mental disorders, and exposure to psychopharmacological drug classes.

Methods

In this systematic review and meta-analysis, we searched Web of Science, Cochrane, PubMed, and PsycINFO databases between Jan 1, 2020, and March 5, 2021, for original studies reporting data on COVID-19 outcomes in patients with psychiatric disorders compared with controls. We excluded studies with overlapping samples, studies that were not peer-reviewed, and studies written in languages other than English, Danish, Dutch, French, German, Italian, and Portuguese. We modelled random-effects meta-analyses to estimate crude odds ratios (OR) for mortality after SARS-CoV-2 infection as the primary outcome, and hospitalisation and ICU admission as secondary outcomes. We calculated adjusted ORs for available data. Heterogeneity was assessed using the I² statistic, and publication bias was tested with Egger regression and visual inspection of funnel plots. We used the GRADE approach to assess the overall strength of the evidence and the Newcastle Ottawa Scale to assess study quality. We also did subgroup analyses and meta-regressions to assess the effects of baseline COVID-19 treatment setting, patient age, country, pandemic phase, quality assessment score, sample sizes, and adjustment for confounders. This study is registered with PROSPERO, CRD42021233984.

Findings

841 studies were identified by the systematic search, of which 33 studies were included in the systematic review and 23 studies in the meta-analysis, comprising 1 469 731 patients with COVID-19, of whom 43 938 had mental disorders. The sample included 130 807 females (8·9% of the whole sample) and 130 373 males (8·8%). Nine studies provided data on patient race and ethnicity, and 22 studies were rated as high quality. The presence of any mental disorder was associated with an increased risk of COVID-19 mortality (OR 2·00 [95% CI 1·58–2·54]; I²=92·66%). This association was also observed for psychotic disorders (2·05 [1·37–3·06]; I²=80·81%), mood disorders (1·99 [1·46–2·71]; I²=68·32%), substance use disorders (1·76 [1·27–2·44]; I²=47·90%), and intellectual disabilities and developmental disorders (1·73 [1·29–2·31]; I²=90·15%) but not for anxiety disorders (1·07 [0·73–1·56]; I²=11·05%). COVID-19 mortality was associated with exposure to antipsychotics (3·71 [1·74–7·91]; I²=90·31%), anxiolytics (2·58 [1·22–5·44]; I²=96·42%), and antidepressants (2·23 [1·06–4·71]; I²=95·45%). For psychotic disorders, mood disorders, antipsychotics, and anxiolytics, the association remained significant after adjustment for age, sex, and other confounders. Mental disorders were associated with increased risk of hospitalisation (2·24 [1·70–2·94]; I²=88·80%). No significant associations with mortality were identified for ICU admission. Subgroup analyses and meta-regressions showed significant associations of baseline COVID-19 treatment setting (p=0·013) and country (p<0·0001) with mortality. No significant associations with mortality were identified for other covariates. No evidence of publication bias was found. GRADE assessment indicated high certainty for crude mortality and hospitalisation, and moderate certainty for crude ICU admission.

Interpretation

Pre-existing mental disorders, in particular psychotic and mood disorders, and exposure to antipsychotics and anxiolytics were associated with COVID-19 mortality in both crude and adjusted models. Although further research is required to determine the underlying mechanisms, our findings highlight the need for targeted approaches to manage and prevent COVID-19 in at-risk patient groups identified in this study.

Funding

None.

Translations

For the Italian, French and Portuguese translations of the abstract see Supplementary Materials section.

中文翻译：

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精神障碍和 COVID-19 相关死亡率、住院和重症监护病房入院的风险：系统回顾和荟萃分析

背景

精神障碍可能是严重 COVID-19 的危险因素。我们旨在评估与 COVID-19 相关的死亡率、住院和重症监护病房 (ICU) 入院与任何先前存在的精神障碍、精神障碍的特定诊断类别以及接触精神药理学药物类别相关的特定风险。

方法

在此系统评价和荟萃分析中，我们搜索了 2020 年 1 月 1 日至 2021 年 3 月 5 日期间的 Web of Science、Cochrane、PubMed 和 PsycINFO 数据库，以寻找原始研究报告精神疾病患者 COVID-19 结果的数据，并与之进行比较与控制。我们排除了样本重叠的研究、未经同行评审的研究以及使用英语、丹麦语、荷兰语、法语、德语、意大利语和葡萄牙语以外的语言撰写的研究。我们对随机效应荟萃分析进行建模，以估计 SARS-CoV-2 感染后死亡率的粗比值比 (OR) 作为主要结果，将住院和入住 ICU 作为次要结果。我们计算了可用数据的调整后 OR。使用I ²评估异质性统计数据和发表偏倚通过 Egger 回归和漏斗图的目视检查进行了测试。我们使用 GRADE 方法来评估证据的整体强度，并使用 Newcastle Ottawa 量表来评估研究质量。我们还进行了亚组分析和元回归，以评估基线 COVID-19 治疗环境、患者年龄、国家、大流行阶段、质量评估评分、样本量和混杂因素调整的影响。本研究已在 PROSPERO 注册，CRD42021233984。

发现

通过系统检索确定了 841 项研究，其中 33 项研究纳入系统评价，23 项研究纳入荟萃分析，包括 1 469 731 名 COVID-19 患者，其中 43 938 名患有精神障碍。样本包括 130 807 名女性（占整个样本的 8·9%）和 130 373 名男性（8·8%）。9 项研究提供了患者种族和种族的数据，22 项研究被评为高质量。任何精神障碍的存在都与 COVID-19 死亡风险增加相关（OR 2·00 [95% CI 1·58–2·54]；I ² =92·66%）。在精神障碍 (2·05 [1·37–3·06]; I ² =80·81%)、情绪障碍 (1·99 [1·46–2·71]; I ²=68·32%）、物质使用障碍（1·76 [1·27–2·44]；I ² =47·90%）、智力障碍和发育障碍（1·73 [1·29–2· 31]；I ² =90·15%）但不适用于焦虑症（1·07 [0·73–1·56]；I ² =11·05%）。COVID-19 死亡率与抗精神病药 (3·71 [1·74–7·91]；I ² =90·31%)、抗焦虑药 (2·58 [1·22–5·44]；I ² =96·42%), 和抗抑郁药 (2·23 [1·06–4·71]; I ²=95·45%）。对于精神障碍、情绪障碍、抗精神病药和抗焦虑药，在调整年龄、性别和其他混杂因素后，这种关联仍然显着。精神障碍与住院风险增加相关 (2·24 [1·70–2·94]; I ² =88·80%)。未发现入住 ICU 与死亡率有显着关联。亚组分析和元回归显示基线 COVID-19 治疗环境 (p=0·013) 和国家 (p<0·0001) 与死亡率显着相关。未发现其他协变量与死亡率有显着关联。没有发现发表偏倚的证据。GRADE 评估表明粗死亡率和住院率具有高度确定性，粗略进入 ICU 具有中等确定性。

解释

在原始模型和调整后的模型中，预先存在的精神障碍，特别是精神病和情绪障碍，以及抗精神病药和抗焦虑药的暴露与 COVID-19 死亡率相关。尽管需要进一步研究以确定潜在机制，但我们的研究结果强调需要有针对性的方法来管理和预防本研究中确定的高危患者群体中的 COVID-19。

资金

没有任何。

翻译

有关摘要的意大利语、法语和葡萄牙语翻译，请参阅补充材料部分。