6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

Abstract

Background: 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.

Methods: 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.

Findings: 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 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up.

Interpretation: 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.

Funding: 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.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Flow chart of patients with COVID-19 discharged from Jin Yin-tan Hospital between Jan 7, and May 29, 2020 HRCT=high resolution CT. LOTUS= Lopinavir Trial for Suppression of SARS-CoV-2 in China. *A series of questionnaires included a self-reported symptom questionnaire, the modified British Medical Research Council dyspnoea scale, the EuroQol five-dimension five-level questionnaire, the EuroQol Visual Analogue Scale, and an ischaemic stroke and cardiovascular event registration form. †Laboratory tests included a white cell count, lymphocyte count, serum creatinine, haemoglobin, and glycosylated haemoglobin.

Figure 2

Risk factors associated with diffusion impairment and CT score (A), and anxiety or depression and fatigue or muscle weakness (B) For associations of age, cigarette smoking, and education with outcome measure, the variables including age, gender, cigarette smoking, education, comorbidity, corticosteroids, antivirals, and intravenous immunoglobulin were all included in the models. For association of comorbidity with outcome, the aforementioned variables were all included together with comorbidity. For association of other factors including sex, corticosteroid, antiviral, and intravenous immunoglobulin with outcome, disease severity and the aforementioned variables were included in the model. OR (95% CI) or β (95% CI) for age indicates the risk of diffusion impairment, CT score, anxiety or depression, and fatigue or muscle weakness per 10-year age increase. OR=odds ratio.

Figure 3

Temporal changes of seropositivity and antibody titres against SARS-CoV-2 (A) Seropositivity of each antibody indicated by the y-axis. Violin plots show the distribution of each antibody feature N (B), RBD (C), S (D), and neutralising antibodies (E) split across baseline and follow-up plasma samples of 94 individuals. The horizontal lines are used to indicate the value used to diagnose positivity from the antibody test. The comparison of antibody test results at acute phase and follow-up was done with paired t tests for antibody titres and McNemar test for antibody positive rates. Plasma samples at acute phase were collected during hospital stay with a median duration of 23 (IQR 20–26) days from illness onset. OD=optical density. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. p values indicate a comparison between acute phase and follow-up. *p<0·0001. †p=0·29. ‡p=0·039. §p=1·00. ¶p=0·021.