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      Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

      research-article
      , PhD a , * , , MBBS a , , Prof, PhD d , , PhD a , , BSc a , , MSc a , , MRCP a , , PhD d , , PhD d , f , , PhD b , , MBChB d , , PhD e , f , , Prof, PhD g , , Prof, PhD j , , Prof, PhD l , m , , Prof, MD n , o , , PhD p , , Prof, MD q , v , , PhD a , , Prof, PhD w , , Prof, MD x , y , , Prof, DM z , , DPhil aa , , Prof, FRCP g , , MD h , i , , Prof, MD ab , , PhD k , , PhD e , , Prof, MD aa , ab , , Prof, MD ad , ae , af , , Prof, PhD ag , , Prof, MD c , ah , , Prof, MD q , r , , Prof, PhD ab , , PhD ag , ai , , PhD aj , ak , , Prof, DPhil s , , DPhil r , , PhD a , , DPhil t , , Prof, PhD al , am , , Prof, MD an , , Prof, PhD a , , Prof, MD d , , PhD ac , , MD ao , ap , , Prof, PhD aq , , Prof, PhD u , , PhD ar , , PhD as , at , , MA au , , Prof, PhD a , b , * , , Prof, PhD a , * , * , PHOSP-COVID Collaborative Group
      The Lancet. Respiratory Medicine
      The Author(s). Published by Elsevier Ltd.
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          Abstract

          Background

          The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes.

          Methods

          The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107).

          Findings

          We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity.

          Interpretation

          We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care.

          Funding

          UK Research and Innovation and National Institute for Health Research.

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          Most cited references36

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

            Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)
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              The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

              To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Validation study. A community clinic and an academic center. Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
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                Author and article information

                Journal
                Lancet Respir Med
                Lancet Respir Med
                The Lancet. Respiratory Medicine
                The Author(s). Published by Elsevier Ltd.
                2213-2600
                2213-2619
                7 October 2021
                7 October 2021
                Affiliations
                [a ]Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester, UK
                [b ]Department of Health Sciences, University of Leicester, Leicester, UK
                [c ]Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
                [d ]Usher Institute, University of Edinburgh, Edinburgh, UK
                [e ]Roslin Institute, University of Edinburgh, Edinburgh, UK
                [f ]Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK
                [g ]UCL Respiratory, Department of Medicine, University College London, London, UK
                [h ]Centre for Medical Image Computing, University College London, London, UK
                [i ]Lungs for Living Research Centre, University College London, London, UK
                [j ]Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
                [k ]Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
                [l ]Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
                [m ]Newcastle upon Tyne Teaching Hospitals Trust, Newcastle upon Tyne, UK
                [n ]Manchester Metropolitan University, Manchester, UK
                [o ]Salford Royal NHS Foundation Trust, Manchester, UK
                [p ]Infection Research Group, Hull University Teaching Hospitals, Hull, UK
                [q ]NIHR Oxford Health Biomedical Research Centre, University of Oxford, Oxford, UK
                [r ]Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
                [s ]Oxford Respiratory Trials Unit, University of Oxford, Oxford, UK
                [t ]Kadoorie Centre for Critical Care Research, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
                [u ]MRC Human Immunology Unit, University of Oxford, Oxford, UK
                [v ]Oxford Health NHS Foundation Trust, Oxford, UK
                [w ]Lane Fox Respiratory Service, Guy's and St Thomas' NHS Foundation Trust, London, UK
                [x ]Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
                [y ]Belfast Health & Social Care Trust, Belfast, UK
                [z ]Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
                [aa ]Imperial College Healthcare NHS Trust, London, UK, University College London, London, UK
                [ab ]National Heart and Lung Institute, Imperial College London, London, UK
                [ac ]Immunology and Inflammation, Imperial College London, London, UK
                [ad ]Hywel Dda University Health Board, Wales, UK
                [ae ]University of Swansea, Swansea, UK
                [af ]Respiratory Innovation Wales, Llanelli, UK
                [ag ]Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
                [ah ]Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester, UK
                [ai ]Department of Acute Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK
                [aj ]Barts Health NHS Trust, London, UK
                [ak ]Queen Mary University of London, London, UK
                [al ]NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
                [am ]Respiratory Medicine, Alder Hey Children's Hospital, Liverpool, UK
                [an ]King's College London British Heart Foundation Centre and King's College Hospital NHS Foundation Trust, London, UK
                [ao ]Cambridge NIHR Biomedical Research Centre, Cambridge, UK
                [ap ]NIHR Cambridge Clinical Research Facility, Cambridge, UK
                [aq ]University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
                [ar ]Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
                [as ]Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK
                [at ]Hospital for Tropical Diseases, University College London Hospital, London, UK
                [au ]Asthma UK and British Lung Foundation, London, UK
                Author notes
                [* ]Correspondence to: Prof Christopher E Brightling, Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester LE3 9QP, UK
                [*]

                Contributed equally

                [†]

                All Collaborative Group members are listed in appendix 1 (pp 1–9)

                Article
                S2213-2600(21)00383-0
                10.1016/S2213-2600(21)00383-0
                8497028
                34627560
                a639775b-ff21-4fe1-9b3c-bcc122777097
                © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

                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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