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      3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study

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          Abstract

          Background

          The consequences of COVID-19 in those who recover from acute infection requiring hospitalisation have yet to be clearly defined. We aimed to describe the temporal trends in respiratory outcomes over 12 months in patients hospitalised for severe COVID-19 and to investigate the associated risk factors.

          Methods

          In this prospective, longitudinal, cohort study, patients admitted to hospital for severe COVID-19 who did not require mechanical ventilation were prospectively followed up at 3 months, 6 months, 9 months, and 12 months after discharge from Renmin Hospital of Wuhan University, Wuhan, China. Patients with a history of hypertension; diabetes; cardiovascular disease; cancer; and chronic lung disease, including asthma or chronic obstructive pulmonary disease; or a history of smoking documented at time of hospital admission were excluded at time of electronic case-note review. Patients who required intubation and mechanical ventilation were excluded given the potential for the consequences of mechanical ventilation itself to influence the factors under investigation. During the follow-up visits, patients were interviewed and underwent physical examination, routine blood test, pulmonary function tests (ie, diffusing capacity of the lungs for carbon monoxide [DLCO]; forced expiratory flow between 25% and 75% of forced vital capacity [FVC]; functional residual capacity; FVC; FEV 1; residual volume; total lung capacity; and vital capacity), chest high-resolution CT (HRCT), and 6-min walk distance test, as well as assessment using a modified Medical Research Council dyspnoea scale (mMRC).

          Findings

          Between Feb 1, and March 31, 2020, of 135 eligible patients, 83 (61%) patients participated in this study. The median age of participants was 60 years (IQR 52–66). Temporal improvement in pulmonary physiology and exercise capacity was observed in most patients; however, persistent physiological and radiographic abnormalities remained in some patients with COVID-19 at 12 months after discharge. We found a significant reduction in DLCO over the study period, with a median of 77% of predicted (IQR 67–87) at 3 months, 76% of predicted (68–90) at 6 months, and 88% of predicted (78–101) at 12 months after discharge. At 12 months after discharge, radiological changes persisted in 20 (24%) patients. Multivariate logistic regression showed increasing odds of impaired DLCO associated with female sex (odds ratio 8·61 [95% CI 2·83–26·2; p=0·0002) and radiological abnormalities were associated with peak HRCT pneumonia scores during hospitalisation (1·36 [1·13–1·62]; p=0·0009).

          Interpretation

          In most patients who recovered from severe COVID-19, dyspnoea scores and exercise capacity improved over time; however, in a subgroup of patients at 12 months we found evidence of persistent physiological and radiographic change. A unified pathway for the respiratory follow-up of patients with COVID-19 is required.

          Funding

          National Natural Science Foundation of China, UK Medical Research Council, and National Institute for Health Research Southampton Biomedical Research Centre.

          Translation

          For the Chinese translation of the abstract see Supplementary Materials section.

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          Most cited references35

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

          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.
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            ATS statement: guidelines for the six-minute walk test.

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              Mental health before and during the COVID-19 pandemic: a longitudinal probability sample survey of the UK population

              Summary Background The potential impact of the COVID-19 pandemic on population mental health is of increasing global concern. We examine changes in adult mental health in the UK population before and during the lockdown. Methods In this secondary analysis of a national, longitudinal cohort study, households that took part in Waves 8 or 9 of the UK Household Longitudinal Study (UKHLS) panel, including all members aged 16 or older in April, 2020, were invited to complete the COVID-19 web survey on April 23–30, 2020. Participants who were unable to make an informed decision as a result of incapacity, or who had unknown postal addresses or addresses abroad were excluded. Mental health was assessed using the 12-item General Health Questionnaire (GHQ-12). Repeated cross-sectional analyses were done to examine temporal trends. Fixed-effects regression models were fitted to identify within-person change compared with preceding trends. Findings Waves 6–9 of the UKHLS had 53 351 participants. Eligible participants for the COVID-19 web survey were from households that took part in Waves 8 or 9, and 17 452 (41·2%) of 42 330 eligible people participated in the web survey. Population prevalence of clinically significant levels of mental distress rose from 18·9% (95% CI 17·8–20·0) in 2018–19 to 27·3% (26·3–28·2) in April, 2020, one month into UK lockdown. Mean GHQ-12 score also increased over this time, from 11·5 (95% CI 11·3–11·6) in 2018–19, to 12·6 (12·5–12·8) in April, 2020. This was 0·48 (95% CI 0·07–0·90) points higher than expected when accounting for previous upward trends between 2014 and 2018. Comparing GHQ-12 scores within individuals, adjusting for time trends and significant predictors of change, increases were greatest in 18–24-year-olds (2·69 points, 95% CI 1·89–3·48), 25–34-year-olds (1·57, 0·96–2·18), women (0·92, 0·50–1·35), and people living with young children (1·45, 0·79–2·12). People employed before the pandemic also averaged a notable increase in GHQ-12 score (0·63, 95% CI 0·20–1·06). Interpretation By late April, 2020, mental health in the UK had deteriorated compared with pre-COVID-19 trends. Policies emphasising the needs of women, young people, and those with preschool aged children are likely to play an important part in preventing future mental illness. Funding None.
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                Author and article information

                Journal
                Lancet Respir Med
                Lancet Respir Med
                The Lancet. Respiratory Medicine
                Elsevier Ltd.
                2213-2600
                2213-2619
                5 May 2021
                5 May 2021
                Affiliations
                [a ]Department of Respiratory and Critical Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
                [b ]Department of Pulmonary and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
                [c ]Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK
                [d ]Institute for Life Sciences, University of Southampton, Southampton, UK
                [e ]Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
                [f ]Department of Respiratory and Critical Care Medicine, China–Japan Friendship Hospital, Beijing, China
                [g ]NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK
                Author notes
                [* ]Correspondence to: Dr Yihua Wang, Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK
                [** ]Prof Hanxiang Nie, Department of Respiratory and Critical Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
                [*** ]Dr Yi Hu, Department of Pulmonary and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
                [**** ]Dr Mark G Jones, NIHR Southampton Biomedical Research Centre, Southampton, UK
                [*]

                Authors contributed equally to this work

                [†]

                Senior authors contributed equally to this work

                Article
                S2213-2600(21)00174-0
                10.1016/S2213-2600(21)00174-0
                8099316
                33964245
                4fb30994-fef3-4f70-a218-d11c6baae5bc
                © 2021 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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