Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Capital Medical University, Beijing, China; Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China; China-Japan Friendship Hospital, Beijing, China.
Department of COVID-19 Re-examination Clinic, Hubei Provincial Clinical Research Center for Infectious Diseases, Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences, Wuhan, China.
Lancet Respir Med. 2022 Sep;10(9):863-876. doi: 10.1016/S2213-2600(22)00126-6. Epub 2022 May 11.
BACKGROUND: With the ongoing COVID-19 pandemic, growing evidence shows that a considerable proportion of people who have recovered from COVID-19 have long-term effects on multiple organs and systems. A few longitudinal studies have reported on the persistent health effects of COVID-19, but the follow-up was limited to 1 year after acute infection. The aim of our study was to characterise the longitudinal evolution of health outcomes in hospital survivors with different initial disease severity throughout 2 years after acute COVID-19 infection and to determine their recovery status. METHODS: We did an ambidirectional, longitudinal cohort study of individuals who had survived hospitalisation with COVID-19 and who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. We measured health outcomes 6 months (June 16-Sept 3, 2020), 12 months (Dec 16, 2020-Feb 7, 2021), and 2 years (Nov 16, 2021-Jan 10, 2022) after symptom onset with a 6-min walking distance (6MWD) test, laboratory tests, and a series of questionnaires on symptoms, mental health, health-related quality of life (HRQoL), return to work, and health-care use after discharge. A subset of COVID-19 survivors received pulmonary function tests and chest imaging at each visit. Age-matched, sex-matched, and comorbidities-matched participants without COVID-19 infection (controls) were introduced to determine the recovery status of COVID-19 survivors at 2 years. The primary outcomes included symptoms, modified British Medical Research Council (mMRC) dyspnoea scale, HRQoL, 6MWD, and return to work, and were assessed in all COVID-19 survivors who attended all three follow-up visits. Symptoms, mMRC dyspnoea scale, and HRQoL were also assessed in controls. FINDINGS: 2469 patients with COVID-19 were discharged from Jin Yin-tan Hospital between Jan 7 and May 29, 2020. 1192 COVID-19 survivors completed assessments at the three follow-up visits and were included in the final analysis, 1119 (94%) of whom attended the face-to-face interview 2 years after infection. The median age at discharge was 57·0 years (48·0-65·0) and 551 (46%) were women. The median follow-up time after symptom onset was 185·0 days (IQR 175·0-197·0) for the visit at 6 months, 349·0 days (337·0-360·0) for the visit at 12 months, and 685·0 days (675·0-698·0) for the visit at 2 years. The proportion of COVID-19 survivors with at least one sequelae symptom decreased significantly from 777 (68%) of 1149 at 6 months to 650 (55%) of 1190 at 2 years (p<0·0001), with fatigue or muscle weakness always being the most frequent. The proportion of COVID-19 survivors with an mMRC score of at least 1 was 168 (14%) of 1191 at 2 years, significantly lower than the 288 (26%) of 1104 at 6 months (p<0·0001). HRQoL continued to improve in almost all domains, especially in terms of anxiety or depression: the proportion of individuals with symptoms of anxiety or depression decreased from 256 (23%) of 1105 at 6 months to 143 (12%) 1191 at 2 years (p<0·0001). The proportion of individuals with a 6MWD less than the lower limit of the normal range declined continuously in COVID-19 survivors overall and in the three subgroups of varying initial disease severity. 438 (89%) of 494 COVID-19 survivors had returned to their original work at 2 years. Survivors with long COVID symptoms at 2 years had lower HRQoL, worse exercise capacity, more mental health abnormality, and increased health-care use after discharge than survivors without long COVID symptoms. COVID-19 survivors still had more prevalent symptoms and more problems in pain or discomfort, as well as anxiety or depression, at 2 years than did controls. Additionally, a significantly higher proportion of survivors who had received higher-level respiratory support during hospitalisation had lung diffusion impairment (43 [65%] of 66 vs 24 [36%] of 66, p=0·0009), reduced residual volume (41 [62%] vs 13 [20%], p<0·0001), and total lung capacity (26 [39%] vs four [6%], p<0·0001) than did controls. INTERPRETATION: Regardless of initial disease severity, COVID-19 survivors had longitudinal improvements in physical and mental health, with most returning to their original work within 2 years; however, the burden of symptomatic sequelae remained fairly high. COVID-19 survivors had a remarkably lower health status than the general population at 2 years. The study findings indicate that there is an urgent need to explore the pathogenesis of long COVID and develop effective interventions to reduce the risk of long COVID.
背景:随着 COVID-19 大流行的持续,越来越多的证据表明,相当一部分 COVID-19 康复患者的多个器官和系统存在长期影响。一些纵向研究报告了 COVID-19 的持续健康影响,但随访仅限于急性感染后 1 年。我们的研究目的是描述不同初始疾病严重程度的医院幸存者在急性 COVID-19 感染后 2 年内健康结局的纵向演变,并确定他们的恢复状况。
方法:我们对 2020 年 1 月 7 日至 5 月 29 日从武汉金银潭医院出院的 COVID-19 住院幸存者进行了双向、纵向队列研究。我们在症状发作后 6 个月(2020 年 6 月 16 日至 9 月 3 日)、12 个月(2020 年 12 月 16 日至 2021 年 2 月 7 日)和 2 年(2021 年 11 月 16 日至 2022 年 1 月 10 日)时使用 6 分钟步行距离(6MWD)测试、实验室检查和一系列症状、心理健康、健康相关生活质量(HRQoL)、重返工作岗位和出院后医疗保健使用的问卷进行健康结局评估。部分 COVID-19 幸存者在每次就诊时接受肺功能检查和胸部影像学检查。引入与 COVID-19 幸存者年龄匹配、性别匹配和共病匹配的无 COVID-19 感染参与者(对照组),以确定 COVID-19 幸存者在 2 年内的恢复状况。主要结局包括症状、改良英国医学研究理事会(mMRC)呼吸困难量表、HRQoL、6MWD 和重返工作岗位,所有参加全部 3 次随访的 COVID-19 幸存者都进行了评估。对照组也评估了症状、mMRC 呼吸困难量表和 HRQoL。
结果:2020 年 1 月 7 日至 5 月 29 日,从武汉金银潭医院出院的 COVID-19 患者有 2469 例。1192 例 COVID-19 幸存者完成了 3 次随访评估,其中 1119 例(94%)参加了感染后 2 年的面对面访谈。出院时的中位年龄为 57.0 岁(48.0-65.0),551 例(46%)为女性。症状发作后中位随访时间为 6 个月时 185.0 天(IQR 175.0-197.0),12 个月时 349.0 天(337.0-360.0),2 年时 685.0 天(675.0-698.0)。至少有 1 种后遗症症状的 COVID-19 幸存者比例从 6 个月时的 1149 例中的 777 例(68%)显著下降到 2 年时的 1190 例中的 650 例(55%)(p<0.0001),且疲劳或肌肉无力始终是最常见的症状。2 年时,mMRC 评分至少为 1 的 COVID-19 幸存者比例为 1191 例中的 168 例(14%),明显低于 6 个月时的 1104 例中的 288 例(26%)(p<0.0001)。在几乎所有领域,HRQoL 持续改善,尤其是焦虑或抑郁:焦虑或抑郁症状的个体比例从 6 个月时的 1105 例中的 256 例(23%)下降到 2 年时的 1191 例中的 143 例(12%)(p<0.0001)。COVID-19 幸存者的 6MWD 低于正常范围下限的比例在整体和不同初始疾病严重程度的亚组中持续下降。438 例(89%)COVID-19 幸存者在 2 年后已返回原来的工作岗位。在 2 年时患有长 COVID 症状的幸存者的 HRQoL 较低,运动能力较差,心理健康异常较多,出院后医疗保健使用增加,与无长 COVID 症状的幸存者相比。此外,在 2 年时,幸存者比对照组更常见症状,且疼痛或不适、焦虑或抑郁问题更严重。幸存者的呼吸困难(43[65%]例 vs 24[36%]例,p=0.0009)、残气量(41[62%]例 vs 13[20%]例,p<0.0001)和肺总量(26[39%]例 vs 4[6%]例,p<0.0001)受损的比例显著高于对照组。
解释:无论初始疾病严重程度如何,COVID-19 幸存者的身心健康均呈纵向改善,大多数在 2 年内恢复到原来的工作岗位;然而,有症状后遗症的负担仍然相当高。与一般人群相比,COVID-19 幸存者在 2 年内的健康状况明显较差。研究结果表明,迫切需要探索长 COVID 的发病机制,并开发有效的干预措施,以降低长 COVID 的风险。
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