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. 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. 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). 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. 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.

中文翻译：

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COVID-19 入院后 2-3 年的认知和精神症状轨迹：英国的一项纵向前瞻性队列研究


已知 COVID-19 与疾病急性期后认知和精神结果风险增加有关。我们的目的是评估这些症状是否会在因 COVID-19 住院后出现或持续超过 1 年，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。住院后 COVID-19 研究 (PHOSP-COVID) 是一项前瞻性纵向队列研究，研究对象是在英国参与的国家卫生服务医院中因临床诊断为 COVID-19 住院的成年人（年龄≥18 岁）。在 C-Fog 研究中，同意重新联系进行其他研究的 PHOSP-COVID 参与者子集被邀请在入院后 2 到 3 年内完成计算机化认知评估和临床量表。参与者通过 Cognitron 电池完成了涵盖 8 个认知领域的 8 项认知任务，此外还包括 9 项抑郁症患者健康问卷、7 项广泛性焦虑症量表、慢性病治疗疲劳量表的功能评估和20 项认知变化指数 (CCI-20) 问卷，用于评估主观认知能力下降。我们评估了 6 个月、12 个月和 2-3 年随访期间症状的绝对风险如何演变，以及 2-3 年的症状是否可以通过 COVID-19 疾病的早期方面进行预测。参与者完成了一份职业变化调查问卷，以确定他们的职业或工作状态是否发生了变化，如果有，原因是什么。我们评估了 2-3 岁时哪些症状与职业变化相关。有生活经验的人参与了这项研究。 2469 名 PHOSP-COVID 参与者受邀参加 C-Fog 研究，其中 475 名参与者（191 [40·2%] 女性和 284 [59·8%] 男性；平均年龄 58·26 [SD 11·13] 岁）从 83 家医院之一出院的患者提供了 2-3 年随访数据。参与者的认知得分比根据所有测试的认知领域的社会人口统计学特征所预期的要差（平均得分低于平均值 0·71 SD [IQR 0·16–1·04]；p<0·0001）。大多数参与者至少报告有轻度抑郁（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%]）或主观认知能力下降。 184 人 [353 人中的 52·1%]），超过五分之一的人报告严重抑郁（353 人中的 79 人 [22·4%]）、疲劳（353 人中的 87 人 [24·6%]）或主观认知能力下降（88 人） [24·9%] 共 353)。抑郁、焦虑和疲劳在 2-3 岁时比 6 个月或 12 个月时更严重，有证据表明现有症状恶化并出现新症状。 2-3 岁时的症状并不能通过急性 COVID-19 疾病的严重程度来预测，但可以通过 6 个月时的恢复程度来强烈预测（解释了焦虑、抑郁、疲劳等方面 35·0–48·8% 的差异）和主观认知能力下降）；通过生物认知特征将相对于 C 反应蛋白急剧升高的 D-二聚体与 6 个月时的主观认知缺陷联系起来（解释了焦虑、抑郁、疲劳和主观认知下降的 7·0–17·2% 的差异）；以及 6 个月时的焦虑、抑郁、疲劳和主观认知缺陷。除 6 个月时的认知缺陷外，任何测试因素都无法预测 2-3 岁时的客观认知缺陷，这解释了其方差的 10·6%。 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（整体认知评分每下降一个 SD，比值比 [OR] 1·51 [95% CI 1·04–2·22]）和主观认知衰退（OR 1·54）密切相关。 CCI-20 每增加一点 [1·21–1·98]）。由于 6 个月时已经出现的症状恶化以及新症状的出现，精神和认知症状似乎在住院后的前 2-3 年内有所增加。新症状大多发生在 6 个月时已经出现其他​​症状的人中。因此，早期识别和管理症状可能是预防复杂综合征后期发作的有效策略。职业变化很常见，主要与客观和主观认知缺陷有关。因此，需要采取促进认知恢复或预防认知能力下降的干预措施，以限制 COVID-19 的功能和经济影响。国家健康与护理研究所牛津健康生物医学研究中心、沃尔夫森基金会、MQ 心理健康研究所、MRC-UK 研究与创新以及国家健康与护理研究所。