6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records.
6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records.
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DOI：
10.1016/s2215-0366(21)00084-5
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发表时间：
2021-05
期刊：
影响因子：
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通讯作者：
Harrison PJ
中科院分区：
文献类型：
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作者：
Taquet M;Geddes JR;Husain M;Luciano S;Harrison PJ
已有报告称COVID-19会导致神经和精神方面的后遗症，但还需要更多数据来充分评估COVID-19对大脑健康的影响。我们的目的是提供对COVID-19诊断后6个月内患者神经和精神疾病诊断的发病率和相对风险的可靠估计。对于这项回顾性队列研究和事件发生时间分析，我们使用了从TriNetX电子健康记录网络（超过8100万患者）获得的数据。我们的主要队列包括诊断为COVID-19的患者;一个匹配的对照队列包括诊断为流感的患者，另一个匹配的对照队列包括同期诊断为任何呼吸道感染（包括流感）的患者。诊断为COVID-19或SARS-CoV-2检测阳性的患者被排除在对照组之外。所有队列均包括在2020年1月20日或之后发生索引事件且在2020年12月13日仍然存活的10岁以上患者。我们估计了确诊COVID-19后6个月内14种神经和精神疾病结局的发生率：颅内出血;缺血性卒中;帕金森综合征;格林-巴利综合征;神经、神经根和神经丛疾病;肌神经接头和肌肉疾病;脑炎;痴呆;精神病、情绪和焦虑障碍（分组和单独）;物质使用障碍;失眠。使用考克斯模型，我们比较了流感或其他呼吸道感染患者的倾向评分匹配队列的发生率。我们调查了这些估计值如何受到COVID-19严重程度的影响，如住院、重症治疗病房（ITU）入院和脑病（谵妄和相关疾病）。我们通过在不同情景下重复分析，评估了队列之间结局差异的稳健性。为了提供神经和精神后遗症的发生率和风险的基准，我们将我们的主要队列与同期诊断的四个队列的患者进行了比较，这些患者具有额外的指标事件：皮肤感染、尿石症、大骨骨折和肺栓塞。在236379名确诊为COVID-19的患者中，在随后6个月内神经系统或精神疾病诊断的估计发生率为33.62%（95%CI 33.17 - 34.07），其中12.84%（12.36 - 13.33）首次接受此类诊断。对于已入住ITU的患者，诊断的估计发生率为46.42%（44.78 - 48.09），首次诊断为25.79%（23.50 - 28.25）。关于研究结果的个体诊断，整个COVID-19队列的估计发病率为0.56%（0.50 - 0.63）颅内出血，2.10%（1.97 - 2.23）缺血性卒中，0.11%帕金森综合征为0.08 ~ 0.14，痴呆为0.67%（0.59 ~ 0.75），焦虑症为17.39%（17.04 ~ 17.74），精神病性障碍为1.40%（1.30 ~ 1.51）。在ITU入院组中，估计发生率为2.66%颅内出血（2.24 - 3.16），6.92%（6·17-7·76）缺血性卒中，0·26%痴呆1.74%（1.31 ~ 2.30），焦虑症19.15%（17.90 ~ 20.48），精神病性障碍2.77%（2.31 ~ 3.33）。大多数诊断类别在COVID-19患者中比流感患者更常见（风险比[HR] 1.44，95% CI 1.40 - 1.47，任何诊断; 1.78，1.68 - 1.89，任何首次诊断）和患有其他呼吸道感染的患者（1·16，1·14-1·17，任何诊断; 1·32，1·27-1·36，任何首次诊断）。与发病率一样，患有更严重COVID-19的患者的HR更高（例如，与未接受ITU的患者相比：任何诊断为1·58，1·50-1·67;任何首次诊断为2·87，2·45-3·35）。结果是强大的各种敏感性分析和基准对四个额外的指数健康事件。我们的研究为COVID-19感染后6个月内大量神经和精神疾病的发病率提供了证据。在患有严重COVID-19的患者中，风险最大，但不限于此。这些信息有助于服务规划和确定研究优先事项。需要补充研究设计，包括前瞻性队列，以证实和解释这些发现。国家卫生研究所（NIHR）牛津健康生物医学研究中心。
Neurological and psychiatric sequelae of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis. For this retrospective cohort study and time-to-event analysis, we used data obtained from the TriNetX electronic health records network (with over 81 million patients). Our primary cohort comprised patients who had a COVID-19 diagnosis; one matched control cohort included patients diagnosed with influenza, and the other matched control cohort included patients diagnosed with any respiratory tract infection including influenza in the same period. Patients with a diagnosis of COVID-19 or a positive test for SARS-CoV-2 were excluded from the control cohorts. All cohorts included patients older than 10 years who had an index event on or after Jan 20, 2020, and who were still alive on Dec 13, 2020. We estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root, and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders (grouped and separately); substance use disorder; and insomnia. Using a Cox model, we compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections. We investigated how these estimates were affected by COVID-19 severity, as proxied by hospitalisation, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders). We assessed the robustness of the differences in outcomes between cohorts by repeating the analysis in different scenarios. To provide benchmarking for the incidence and risk of neurological and psychiatric sequelae, we compared our primary cohort with four cohorts of patients diagnosed in the same period with additional index events: skin infection, urolithiasis, fracture of a large bone, and pulmonary embolism. Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17–34·07), with 12·84% (12·36–13·33) receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42% (44·78–48·09) and for a first diagnosis was 25·79% (23·50–28·25). Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50–0·63) for intracranial haemorrhage, 2·10% (1·97–2·23) for ischaemic stroke, 0·11% (0·08–0·14) for parkinsonism, 0·67% (0·59–0·75) for dementia, 17·39% (17·04–17·74) for anxiety disorder, and 1·40% (1·30–1·51) for psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% (2·24–3·16) for intracranial haemorrhage, 6·92% (6·17–7·76) for ischaemic stroke, 0·26% (0·15–0·45) for parkinsonism, 1·74% (1·31–2·30) for dementia, 19·15% (17·90–20·48) for anxiety disorder, and 2·77% (2·31–3·33) for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio [HR] 1·44, 95% CI 1·40–1·47, for any diagnosis; 1·78, 1·68–1·89, for any first diagnosis) and those who had other respiratory tract infections (1·16, 1·14–1·17, for any diagnosis; 1·32, 1·27–1·36, for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not: 1·58, 1·50–1·67, for any diagnosis; 2·87, 2·45–3·35, for any first diagnosis). Results were robust to various sensitivity analyses and benchmarking against the four additional index health events. Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings. National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre.