Department of Psychiatry, University of Oxford, Oxford, UK; Oxford Health NHS Foundation Trust, Oxford, UK; NIHR Oxford Health Biomedical Research Centre, Oxford, UK.
Department of Psychiatry, University of Oxford, Oxford, UK; NIHR Oxford Health Biomedical Research Centre, Oxford, UK.
Lancet Psychiatry. 2024 Sep;11(9):696-708. doi: 10.1016/S2215-0366(24)00214-1. Epub 2024 Jul 31.
BACKGROUND: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2-3 years, and whether symptoms at 2-3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2-3 years were associated with occupation change. People with lived experience were involved in the study. FINDINGS: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2-3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16-1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2-3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2-3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0-48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0-17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2-3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6-31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04-2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21-1·98] for every point increase in CCI-20). INTERPRETATION: Psychiatric and cognitive symptoms appear to increase over the first 2-3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. FUNDING: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research.
背景:已知 COVID-19 与疾病急性期后认知和精神方面的结局风险增加有关。我们旨在评估这些症状是否会在 COVID-19 住院后 1 年以上出现或持续存在,以确定 COVID-19 疾病的哪些早期方面可以预测长期症状,并确定这些症状与职业功能的关系。
方法:COVID-19 住院后研究(PHOSP-COVID)是一项前瞻性、纵向队列研究,纳入了在英国国民保健署医院住院的 COVID-19 临床诊断成年患者(年龄≥18 岁)。在 C-Fog 研究中,PHOSP-COVID 参与者的一个子集同意在住院后 2 至 3 年被重新联系进行其他研究,邀请他们完成计算机认知评估和临床量表。参与者完成了 Cognitron 电池的八项认知任务,涵盖八个认知领域,以及 9 项患者健康问卷抑郁量表、广义焦虑症 7 项量表、慢性疾病治疗疲劳量表功能评估和 20 项认知变化指数问卷(CCI-20),以评估主观认知下降。我们评估了症状在 6 个月、12 个月和 2-3 年的随访中绝对风险的演变,以及 2-3 年的症状是否由 COVID-19 疾病早期的方面预测。参与者完成了一份职业变化问卷,以确定他们的职业或工作状况是否发生了变化,如果发生了变化,原因是什么。我们评估了 2-3 年的哪些症状与职业变化有关。有过患病经历的人参与了这项研究。
发现:2469 名 PHOSP-COVID 参与者被邀请参加 C-Fog 研究,83 家医院中有 475 名参与者(女性 191 名[40.2%],男性 284 名[59.8%];平均年龄 58.26[11.13]岁)在 2-3 年的随访中提供了数据。与基于社会人口统计学特征的预期相比,参与者的认知评分较差,所有测试的认知领域平均得分低于均值 0.71 标准差(0.16-1.04;p<0.0001)。大多数参与者报告至少有轻度抑郁(353 人中的 263 人[74.5%])、焦虑(353 人中的 189 人[53.5%])、疲劳(353 人中的 220 人[62.3%])或主观认知下降(353 人中的 184 人[52.1%]),超过五分之一的人报告有严重抑郁(353 人中的 79 人[22.4%])、疲劳(353 人中的 87 人[24.6%])或主观认知下降(353 人中的 88 人[24.9%])。2-3 年的抑郁、焦虑和疲劳比 6 个月或 12 个月时更严重,既有现有症状的恶化,也有新症状的出现。2-3 年的症状与 COVID-19 疾病急性期的严重程度无关,但与 6 个月时的恢复程度密切相关(解释焦虑、抑郁、疲劳和主观认知下降的 35.0-48.8%的变异);与急性 D-二聚体与 C-反应蛋白比值升高相关的生物认知特征相关,该特征与 6 个月时的主观认知缺陷相关(解释焦虑、抑郁、疲劳和主观认知下降的 7.0-17.2%的变异);与 6 个月时的焦虑、抑郁、疲劳和主观认知缺陷有关。2-3 年的客观认知缺陷与测试的任何因素无关,除了 6 个月时的认知缺陷,其解释了 10.6%的变异。353 名参与者中有 95 名(26.9%[95%CI 22.6-31.8])报告了职业变化,健康状况不佳是这种变化的最常见原因。职业变化与客观认知缺陷(整体认知评分每降低 1 个标准差,比值比[OR]为 1.51[95%CI 1.04-2.22])和主观认知下降(CCI-20 每增加 1 分,OR 为 1.54[1.21-1.98])强烈且特异性相关。
解释:由于 6 个月时已有的症状恶化和新症状的出现,COVID-19 住院后 2-3 年内精神和认知症状似乎会增加。新症状主要出现在 6 个月时已经存在其他症状的人群中。因此,早期识别和管理症状可能是预防更复杂综合征发生的有效策略。职业变化很常见,主要与客观和主观认知缺陷有关。因此,需要促进认知恢复或预防认知下降的干预措施,以限制 COVID-19 的功能和经济影响。
资金:英国国家卫生与保健研究院牛津健康生物医学研究中心、沃尔夫森基金会、MQ 心理健康研究、英国医学研究理事会-英国创新署、英国国家卫生与保健研究院。
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