6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.
6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.
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DOI：
10.1016/s0140-6736(23)00810-3
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发表时间：
2023-06-17
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COVID-19 对健康的长期影响在很大程度上仍不清楚。本研究的目的是描述已出院的 COVID-19 患者的长期健康后果，并调查相关的风险因素，特别是疾病的严重程度。我们对2020年1月7日至5月29日期间从金银潭医院（中国武汉）出院的确诊的COVID-19患者进行了双向队列研究。由于精神障碍、痴呆或再次入院而难以进行随访的患者；因合并骨关节病而无法自由活动或因中风或肺栓塞等疾病在出院前后无法活动的人；那些拒绝参加的人；无法联系到的人；居住在武汉以外、居住在疗养院、福利院的人均被排除在外。所有患者均接受了一系列问卷调查，以评估症状和健康相关的生活质量，接受体检和 6 分钟步行测试，并接受血液检查。采用分层抽样程序，按照患者住院期间最高七级量表3级、4级、5-6级进行抽样，进行肺功能检查、胸部高分辨率CT和超声检查。参与中国洛匹那韦抑制 SARS-CoV-2 试验的入组患者接受了 SARS-CoV-2 抗体检测。使用多变量调整线性或逻辑回归模型来评估疾病严重程度与长期健康后果之间的关联。总共有 2469 名出院的 COVID-19 患者被排除，其中 1733 名患者被排除。患者的中位年龄为 57·0 岁 (IQR 47·0–65·0)，其中 897 名 (52%) 为男性，836 名 (48%) 为女性。随访时间为2020年6月16日至9月3日，症状出现后中位随访时间为186·0天（175·0-199·0）。疲劳或肌肉无力（52%，1654 人中的 855 人）和睡眠困难（26%，1655 人中的 437 人）是最常见的症状。 23%（1616 名患者中的 367 名）报告存在焦虑或抑郁。 6 分钟步行距离低于正常范围下限的比例，严重程度为 3 级的患者为 17%，严重程度为 4 级的患者为 13%，严重程度为 5-6 级的患者为 28%。 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.经过多变量调整后，对于扩散障碍，患者的优势比 (OR) 为 4 级与 3 级相比为 1·61 (95% CI 0·80–3·25)，5-6 级与 3 级相比为 4·60 (1·85–11·48)；对于焦虑或抑郁，4级与3级相比为OR 0·88 (0·66–1·17)；对于焦虑或抑郁，5-6级与3级相比为OR 1·76 (1·05–2·96)；对于疲劳或肌肉无力，4级与3级相比为0·87 (0·68–1·11)；对于疲劳或肌肉无力，5-6级与3级相比为2·75 (1·61–4·69)。 94例随访时检测血液抗体的患者中，中和抗体血清阳性率（96·2% vs 58·5%）和中和抗体滴度中位值（19·0 vs 10·0）均显着低于急性期。 822 名没有急性肾损伤且急性期估计肾小球滤过率 (eGFR) 为每 1·73 m2 或以上 90 mL/min 的参与者中，有 107 名参与者在随访时 eGFR 低于每 1·73 m2 90 mL/min。急性感染后 6 个月，COVID-19 幸存者主要出现疲劳或肌肉无力、睡眠困难、焦虑或抑郁等问题。住院期间病情较重的患者，肺弥散能力受损更严重，胸部影像学表现异常，是长期康复干预的主要目标人群。国家自然科学基金委、中国医学科学院医学科学创新基金、国家重点研发计划、国家肺结核新药创制重大科技专项、北京协和医学院基金资助。
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 and May 29, 2020. Patients who died before follow-up; patients for whom follow-up would be difficult because of psychotic disorders, dementia, or readmission 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 SARS-CoV-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 years (IQR 47·0–65·0) and 897 (52%) were male and 836 (48%) were female. 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 days (175·0–199·0). Fatigue or muscle weakness (52%, 855 of 1654) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1616) of patients. The proportions of 6-min walking distance less than the lower limit of the normal range were 17% for those at severity scale 3, 13% for severity scale 4, and 28% 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) of 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 1·76 (1·05–2·96) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·87 (0·68–1·11) for scale 4 versus scale 3 and 2·75 (1·61–4·69) 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 an estimated glomerular filtration rate (eGFR) of 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 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.