Medical Department, Jin Yin-tan Hospital, Wuhan, Hubei, China; Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences, Wuhan, Hubei, China.
Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Pulmonary and Critical Care Medicine, Capital Medical University, Beijing, China.
Lancet. 2021 Jan 16;397(10270):220-232. doi: 10.1016/S0140-6736(20)32656-8. Epub 2021 Jan 8.
The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity.
We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences.
In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0-65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0-199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·77 (1·05-2·97) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58-0·96) for scale 4 versus scale 3 and 2·69 (1·46-4·96) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m or more at acute phase had eGFR less than 90 mL/min per 1·73 m at follow-up.
At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery.
National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.
COVID-19 的长期健康后果在很大程度上仍不清楚。本研究旨在描述已从医院出院的 COVID-19 患者的长期健康后果,并调查相关的危险因素,特别是疾病严重程度。
我们对 2020 年 1 月 7 日至 5 月 29 日期间从金银潭医院出院的确诊 COVID-19 患者进行了双向队列研究。在随访前死亡、因精神障碍、痴呆或再次入院而难以随访、因并发骨关节炎或在出院前或后因中风或肺栓塞等疾病而无法自由活动、拒绝参加、无法联系以及居住在武汉以外或在护理院或福利院的患者均被排除在外。所有患者均接受一系列问卷评估症状和健康相关生活质量,进行体格检查和 6 分钟步行试验,并接受血液检查。根据患者在住院期间的最高七分类量表(3、4 和 5-6),采用分层抽样程序对患者进行抽样,以接受肺功能测试、高分辨率胸部 CT 和超声检查。参加中国洛匹那韦抑制 SARS-CoV-2 研究的入组患者接受严重急性呼吸综合征冠状病毒 2 抗体检测。使用多变量调整的线性或逻辑回归模型评估疾病严重程度与长期健康后果之间的关联。
在总共 2469 名出院 COVID-19 患者中,排除 736 名后,有 1733 名患者入组。患者的中位年龄为 57·0(IQR 47·0-65·0)岁,897 名(52%)为男性。随访研究于 2020 年 6 月 16 日至 9 月 3 日进行,症状出现后的中位随访时间为 186·0(175·0-199·0)天。疲劳或肌肉无力(63%,1655 例中有 1038 例)和睡眠困难(26%,1655 例中有 437 例)是最常见的症状。焦虑或抑郁在 1617 名患者中有 23%(367 例)报告。6 分钟步行距离低于正常范围下限的比例分别为严重程度量表 3 组的 24%、严重程度量表 4 组的 22%和严重程度量表 5-6 组的 29%。相应的弥散受损患者比例分别为严重程度量表 3 组的 22%、严重程度量表 4 组的 29%和严重程度量表 5-6 组的 56%,中位数 CT 评分分别为严重程度量表 3 组的 3·0(IQR 2·0-5·0)、严重程度量表 4 组的 4·0(3·0-5·0)和严重程度量表 5-6 组的 5·0(4·0-6·0)。多变量调整后,与严重程度量表 3 相比,严重程度量表 4 和 5-6 的患者发生弥散障碍的比值比(OR)分别为 1·61(95%CI 0·80-3·25)和 4·60(1·85-11·48);与严重程度量表 3 相比,严重程度量表 4 和 5-6 的患者发生焦虑或抑郁的 OR 分别为 0·88(0·66-1·17)和 1·77(1·05-2·97);与严重程度量表 3 相比,严重程度量表 4 和 5-6 的患者发生疲劳或肌肉无力的 OR 分别为 0·74(0·58-0·96)和 2·69(1·46-4·96)。在 94 名接受随访时血液抗体检测的患者中,与急性期相比,中和抗体的血清阳性率(96·2%比 58·5%)和中位数滴度(19·0 比 10·0)均显著降低。822 名无急性肾损伤且急性期估计肾小球滤过率(eGFR)≥90 mL/min/1.73 m2 的患者中,有 107 名患者在随访时 eGFR <90 mL/min/1.73 m2。
在急性感染后 6 个月,COVID-19 幸存者主要受疲劳或肌肉无力、睡眠困难和焦虑或抑郁困扰。住院期间病情较重的患者,其肺弥散能力受损更为严重,胸部影像学表现异常,是干预长期恢复的主要目标人群。
国家自然科学基金、中国医学科学院创新基金医学科学、国家重点研发计划、中国耐多药结核病新药创制重大专项和北京协和医学院基金会。