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Enya Daynes,1,2 Linzy Houchen-Wolloff,1,2 Amy C Barradell,1,2 Neil J Greening,1,2 Sally J Singh1,2 1Leicester NIHR Biomedical Research Centre Respiratory, Glenfield Hospital, Leicester, UK; 2Department of Respiratory Sciences, University of Leicester, Leicester, UKCorrespondence: Enya Daynes, NIHR Leicester Biomedical Research Centre- Respiratory, Glenfield Hospital, Groby Road, Leicester, UK, Email enya.daynes@uhl-tr.nhs.ukIntroduction: The High Frequency Airway Oscillating device (HFAO) was developed to help patients with COPD feel less breathless through flow resistive respiratory muscle training and fixed rate oscillations. Previous work has demonstrated that this device can improve inspiratory muscle strength over and above a sham device. Both groups improved their breathlessness and preserved clinical benefits though there were no statistically significant differences seen over and above the sham device. It is important to understand patient perceptions of using a device and how this may influence their treatment and therefore a qualitative analysis was conducted to understand participant experiences of a HFAO device.Methods: This was an exploratory qualitative analysis involving participants recruited to the Training to Improve Dyspnoea (TIDe) study. Participants completed a satisfaction survey and were invited to take part in a focus group. Focus groups were conducted by a researcher independent to the randomised controlled trial. Data was analysed independently by two researchers using inductive thematic analysis, and themes/sub-themes were agreed jointly. Data is presented in themes and sub themes and triangulated with survey response data.Results: Fourteen participants were recruited to two focus groups (71% male, mean [SD] age 64[9] years). The key themes were patient selection, device use, and investment. Patient selection explores the disease characteristics, emotional impact and management of care. Device use explores the device prescription and usage, routine and lifestyle and effectiveness. Investment covers accessibility, understanding, benefits vs participation and overall perceptions of the device.Conclusion: This research demonstrates the complexity of device interventions and that key considerations should be given to patient selection, the device use itself and, the time and cost investment required for participants to successfully implement the device into daily life.Keywords: COPD, breathlessness, qualitative

Sanjay Ramakrishnan,1– 3 Wim Janssens,4 Pierre-Regis Burgel,5 Marco Contoli,6 Frits ME Franssen,7 Neil J Greening,8 Timm Greulich,9 Iwein Gyselinck,4 Andreas Halner,1 Arturo Huerta,10 Rebecca L Morgan,11 Jennifer K Quint,12 Lowie EGW Vanfleteren,13 Kristina Vermeersch,4 Henrik Watz,14 Mona Bafadhel1 1Respiratory Medicine Unit, Nuffield Department of Medicine - Experimental Medicine, University of Oxford, Oxford, UK; 2 National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), University of Oxford, Oxford, UK; 3School of Medical and Health Sciences, Edith Cowan University, Perth, Australia; 4Department of Respiratory Diseases, UZ Leuven, Research Group BREATHE, KU Leuven, Leuven, Belgium; 5Faculty of Medicine, University of Paris and INSERM 1016 Institut Cochin, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; 6Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy; 7Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, Netherlands; 8Department of Respiratory Sciences, NIHR Leicester Biomedical Research Centre (Respiratory), Glenfield Hospital, Leicester, UK; 9Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Centre Giessen and Marburg, Philipps University, Member of the German Centre for Lung Research (DZL), Marburg, Germany; 10Pulmonary and Critical Care Division, Clinica Sagrada Familia, IDIBAPS August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain; 11Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada; 12National Heart & Lung Institute, Imperial College, London, UK; 13COPD Center, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Department of Internal Medicine and Clinical Nutrition at Institute of Medicine, SU Sahlgrenska, Göteborg, Sweden; 14Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, GermanyCorrespondence: Mona BafadhelRespiratory Medicine Unit, Nuffield Department of Medicine Experimental Medicine, University of Oxford, Oxford, UKTel +44 1865 612898Email mona.bafadhel@ndm.ox.ac.ukBackground: Despite hospitalization for exacerbation being a high-risk event for morbidity and mortality, there is little consensus globally regarding the assessment and management of hospitalised exacerbations of COPD. We aimed to establish a consensus list of symptoms, physiological measures, clinical scores, patient questionnaires and investigations to be obtained at time of hospitalised COPD exacerbation and follow-up.Methods: A modified Delphi online survey with pre-defined consensus of importance, feasibility and frequency of measures at hospitalisation and follow-up of a COPD exacerbation was undertaken.Findings: A total of 25 COPD experts from 18 countries contributed to all 3 rounds of the survey. Experts agreed that a detailed history and examination were needed. Experts also agreed on which treatments are needed and how soon these should be delivered. Experts recommended that a full blood count, renal function, C-reactive protein and cardiac blood biomarkers (BNP and troponin) should be measured within 4 hours of admission and that the modified Medical Research Council dyspnoea scale (mMRC) and COPD assessment test (CAT) should be performed at time of exacerbation and follow-up. Experts encouraged COPD clinicians to strongly consider discussing palliative care, if indicated, at time of hospitalisation.Interpretation: This Europe-wide consensus document is the first attempt to standardise the assessment and care of patients hospitalised for COPD exacerbations. This should be regarded as the starting point to build knowledge and evidence on patients hospitalised for COPD exacerbations.Keywords: COPD, disease exacerbation, hospitalisation, patient care, consensus development, expert opinion

Lorna E Latimer,1,2,* Despina Constantin,3–5,* Neil J Greening,1,2 Lori Calvert,6 Manoj K Menon,7 Michael C Steiner,1,2,* Paul L Greenhaff3–5,*1Department of Respiratory Sciences, University of Leicester, Leicester, UK; 2Institute for Lung Health, National Institute for Health Research (NIHR) Leicester Biomedical Research Centre - Respiratory, Glenfield Hospital, Leicester, UK; 3Medical Research Council/Arthritis Research UK (MRC/ARUK) Centre for Musculoskeletal Ageing Research, University of Nottingham, Nottingham, UK; 4Centre for Sport, Exercise and Osteoarthritis Research, University of Nottingham, Nottingham, UK; 5NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK; 6Peterborough and Stamford Hospitals NHS Foundation Trust, Peterborough City Hospital, Bretton, UK; 7Barking, Havering and Redbridge University Hospitals NHS Trust, Chest Clinic, King George Hospital, Ilford, UK*These authors contributed equally to this work Background: Voluntary resistance exercise (RE) training increases muscle mass and strength in patients with chronic obstructive pulmonary disease (COPD). Nonvolitional transcutaneous neuromuscular electrical stimulation (NMES) may be an alternative strategy for reducing ambulatory muscle weakness in patients unable to perform RE training, but little comparative data are available. This study, therefore, investigated changes in muscle mRNA abundance of a number of gene targets in response to a single bout of NMES compared with RE.Methods: Twenty-six patients with stable COPD (15 male; FEV1, 43±18% predicted; age, 64±8 years; fat free mass index, 16.6±1.8 kg/m2,) undertook 30 minutes of quadriceps NMES (50 Hz, current at the limit of tolerance) or 5×30 maximal voluntary isokinetic knee extensions. Vastus lateralis muscle biopsies were obtained at rest immediately before and 24 hours after intervention. Expression of 384 targeted mRNA transcripts was assessed by real time TaqMan PCR. Significant change in expression from baseline was determined using the ΔΔCT method with a false discovery rate (FDR) of

Background: In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge., Methods: Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium). HRQoL, assessed by the EuroQol-Five Dimensions-Five Levels utility index (EQ-5D-5L UI), pre-hospital and 1 year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient-reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias., Findings: Of the 1888 participants included in the primary analysis, 1149 received corticosteroids. There was no between-group difference in EQ-5D-5L UI at 1 year (mean difference 0.004, 95% CI -0.026-0.034). A similar reduction in EQ-5D-5L UI was seen at 1 year between corticosteroid exposed and nonexposed groups (mean±sd change -0.12±0.22 versus -0.11±0.22). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a cohort of 109 318 patients admitted to hospital with COVID-19, EQ-5D-5L UI at 1 year remained similar between the two groups., Interpretation: Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL 1 year after hospital discharge. Treatments to address the persistent reduction in HRQoL are urgently needed., Competing Interests: Conflict of interest: O.C. Leavy declares that their institute received joint funding from UKRI and NIHR (MR/V027859/1 and COV0319) to complete this work. A.B. Docherty declares that they were awarded funding from a Wellcome Clinical Research Career Development Fellowship (216606/Z/19/Z) to complete this work. A Sheikh declares that their institute was awarded grant funding from NIHR and UKRI to complete this work; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca's Thrombotic Thrombocytopenic Taskforce; and leadership or fiduciary roles for UK and Scottish Government COVID-19 advisory groups. C.E. Bolton declares that their institute received grant funding from NIHR/UKRI and NIHR to complete this work; and their institute received grant funding from Nottingham Hospitals Charity and University of Nottingham. G. Choudhury declares funding from GlaxoSmithKline and AstraZeneca; received honoraria for delivering talks from GSK, AZ, Chiesi and BI; participation on a Data Safety Monitoring Board or Advisory Board as Chair on the Act on COPD Programme for AZ in Scotland; and a leadership or fiduciary role as Chair for the Lothian Respiratory Managed Clinical Network. N.D. Bakerly declares they have received nonrestrictive educational grants from Chiesi, AZ and Teva for attending conferences; honoraria from Teva, AZ and GSK; support for attending meetings and/or travel from Chiesi and AZ; participation on a Data Safety Monitoring Board or Advisory Board for Teva; and receipt of equipment from Global Access Diagnostics (previously Mologic Inc). A. Shikotra declares that their institute was awarded joint funding from UKRI and the NIHR (MR/V027859/1 and COV0319) to complete this work. R. Aul declares lecture fees and support for attending a meeting from Boehringer Ingelheim. C. Echevarria declares a grant from GSK. J.R. Hurst declares funding from AstraZeneca; consulting fees from AstraZeneca and GSK; payment for lectures and presentations from AstraZeneca, Boehringer Ingelheim, Chiesi, Sanofi and Takeda; support for attending meetings and/or travel from AstraZeneca; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca; and receipt of equipment from Nonin. M. Jones declares funding from the MRC to complete this work; funding from the MRC, British Lung Foundation and Boehringer Ingelheim; consulting fees from Skyhawk Therapeutics; and a leadership or fiduciary role in the AAIR Charity Scientific Committee. P. Pfeffer declares funding from NIHR. S. Rowland-Jones declares that their institute received funding from UKRI to complete this work; and their institute received funding from NIHR Sheffield Biomedical Research centre, Bill and Melinda Gates Foundation, UKRI (MRC) and EDCTP. D. Parekh declares funding from NIHR and MRC; and a leadership or fiduciary role for the Faculty of Intensive Care Medicine Board. A.A.R. Thompson declares that their institute was awarded a fellowship from the British Heart Foundation, and grant funding from Heart Research UK and the National Institute for Health and Care Research; payment for lectures and presentations from Janssen-Cilag Ltd; and support for attending meetings from Janssen-Cilag Ltd. M.J. Davies declares grant funding from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, AstraZeneca and Janssen; consulting fees from Eli Lilly, Boehringer Ingelheim, Novo Nordisk and Sanofi; payment for speaking for Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, AstraZeneca, Amgen, Napp Pharmaceuticals and Novartis; and is an advisory board member for Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, Lexicon, Pfizer, Medtronic and ShouTi Pharma Inc., and Zealand Pharma. A. De Soyza declares that their institute was awarded grant funding from AstraZeneca, Bayer, GSK, Chiesi, Novartis and Pfizer, outside the submitted manuscript; consulting fees from AstraZeneca, Bayer, GSK, Chiesi, Novartis, Pfizer, Insmed and Gilead; payment for lectures and presentations from AstraZeneca, Bayer, GSK, Chiesi, Novartis, Pfizer, Insmed, Gilead and 30T; participation on a Data Safety Monitoring Board or Advisory Board for Bayer; and receipt of drugs from GSK outside the submitted manuscript. S. Heller declares consulting fees from NovoNordisk; and participation on a Data Safety Monitoring Board or Advisory Board for Eli Lilly with payments made to their institution. J. Jacob declares funding from Gilead, Microsoft Research and GlaxoSmithKline; consulting fees from Boehringer Ingelheim, Roche, GlaxoSmithKline and NHSX; payment for lectures and presentations received from Boehringer Ingelheim, Roche, GlaxoSmithKline and Takeda; support for attending meetings and/or travel from Boehringer Ingelheim; patents planned, issued or pending (UK patent application number 2113765.8 and UK patent application number GB2211487.0); and participation on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim and Roche. R.G. Jenkins declares that their institute received funding from AstraZeneca, Biogen, Galecto, GlaxoSmithKline, Nordic Biosciences, RedX and Pliant; consulting fees from AstraZeneca, Brainomix, Bristol Myers Squibb, Chiesi, Cohbar, Daewoong, GlaxoSmithKline, Veracyte, Resolution Therapeutics and Pliant; payment for lectures and presentations received from Boehringer Ingelheim, Chiesi, Roche, PatientMPower and AstraZeneca; payment for expert testimony from Pinsent Masons LLP; participation on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim, Galapagos and Vicore; and a leadership or fiduciary role for NuMedii and is president for Action for Pulmonary Fibrosis. W.D-C. Man declares that their institute received funding from National Institute for Health Research and NHS Accelerated Access Collaborative; and is Honorary President of the Association for Respiratory Technology and Physiology, and an associate editor of ERJ Open Research. G.P. McCann declares funding from NIHR (RP-2017-ST2-007) to complete this work; funding from the British Heart Foundation, Wellcome Trust and NIHR; and research support from Resonance Health, Circle CVi and Perspectum. S. Neubauer declares grant funding from Oxford NIHR Biomedical Research centre. P.J.M. Openshaw declares funding from UKRI-MRC/DHSC NIHR and UKRI-BEIS. M.J. Rowland declares support for attending meetings and/or travel from Novartis Pharmaceuticals; stock or stock options from Novartis Pharmaceuticals and Roche Pharmaceuticals; and is employed full time as a Senior Clinical Development Medical Director at Novartis Pharmaceuticals. J. Porter declares funding from Breathing Matters and UCL/H BRC (NIHR), and consulting fees from The Limbic. L.G. Heaney declares that their institute received funding from GSK, AstraZeneca and Roche/Genentech; payment for lectures received from AstraZeneca, Novartis, Roche/Genentech, Sanofi, Circassia, GlaxoSmithKline, Chiesi and Teva; support to travel to meetings from AstraZeneca and GSK; participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Roche/Genentech, GSK, Teva and Celltrion; and funding from the NIHR (RfPB grant PB-PG-0317-20032). J.T. Scott declares funding from UKRI. M.G. Semple declares grant funding from National Institute of Health Research UK, Medical Research Council UK and Health Protection Research Unit in Emerging and Zoonotic Infections, and University of Liverpool to complete this work; participation on a Data Safety Monitoring Board or Advisory Board for Pfizer; leadership or fiduciary roles as Chair of Infectious Disease Scientific Advisory Board Integrum Scientific LLC and Director of MedEx Solutions Ltd; stock or stock options as minority owner of Integrum Scientific LLC and majority owner of MedEx Solutions Ltd; receipt of equipment, materials, drugs, medical writing, gifts or other services from Chiesi Farmaceutici SpA; and is a nonremunerated independent member of HMG UK Scientific Advisory Group for Emergencies (SAGE), COVID-19 Response (March 2020 to March 2022) and a nonremunerated independent member of HMG UK New Emerging Respiratory Virus Threats Advisory Group (NERVTAG) (2014 to July 2023). S.J. Singh declares grants or contracts from NIHR (programme grant (NIHR 202020), Wellcome Doctoral Training Programme, HTA Project Grant (NIHR 131015), NIHR DHSC/UKRI COVID-19 Rapid Response Initiative, NIHR Global Research Group (NIHR 17/63/20)), Actegy Limited and NIHR Senior Investigator; payment for presentations for GSK, Ministry of Justice, CIPLA, Sherbourne Gibbs; participation on NICE Expert Adviser Panel (long COVID), Wales Long COVID Advisory Board and NHS-E Long Covid Your Covid Recovery working group; and leadership or fiduciary roles as ATS Pulmonary Rehabilitation Assembly Chair, Clinical Lead RCP Pulmonary Rehabilitation Accreditation Scheme and Clinical Lead NACAP Audit for Pulmonary Rehabilitation. M. Toshner declares grant funding from the NIHR Cambridge BRC and NIHR HTA to complete this work; consulting fees from Janssen; support for attending meetings and/or travel from GSK and Janssen; and participation on a Data Safety Monitoring Board or Advisory Board for ComCov and FluCov. A. Horsley declares that their institute was awarded funding from UK Research and Innovation (MR/V027859/1), the National Institute of Health Research (NIHR) (COV0319) and NIHR Manchester BRC; and is Chair for the NIHR Translational Research Collaboration. M. Marks declares that their institute received joint funding from UKRI and NIHR to complete this work. K. Poinasamy declares funding from UKRI and NIHR to complete this work. A. Briggs declares consulting fees from Roche, Merck, Sanofi and GSK. J.K. Quint declares that their institute received funding from the Industrial Strategy Challenge Fund, the Medical Research Council, Health Data Research, GSK, BI, Asthma+Lung UK and AZ; and consulting fees from GlaxoSmithKline, Evidera, Chiesi, AstraZeneca and Insmed. J.D. Chalmers declares funding from AstraZeneca, Boehringer Ingelheim, Grifols, Gilead Sciences, Insmed, Genentech and GlaxoSmithKline; consulting fees from AstraZeneca, Boehringer Ingelheim, Grifols, Gilead Sciences, Insmed, Genentech, Glaxosmithkline, Antabio, Zambon and Trudell; and leadership or fiduciary roles as Chief Editor of the European Respiratory Journal and associate editor of ERJ Open Research, Chair of the British Thoracic Society Science and Research Committee, and Trustee of the British Thoracic Society. L.V. Wain declares funding from UK Research and Innovation (MR/V027859/1), GSK/Asthma+Lung UK (Professorship (C17-1)) and National Institute of Health Research (COV0319) to complete this work; funding from Orion Pharma, GSK, Genentech, AstraZeneca, Nordic Bioscience and Sysmex (OGT); consulting fees Galapagos, Boehringer Ingelheim and GSK; support for attending meetings and/or travel Genentech; participation on Advisory Board for Galapagos; leadership or fiduciary roles as an associate editor for the European Respiratory Journal, and Medical Research Council Board member and Deputy Chair. C.E. Brightling declares that their institute received grant funding from MRC/NIHR and NIHR to complete this work; their institute received grant funding from GSK, AZ, Sanofi, Regeneron, Roche, Genentech, BI, Novartis, Chiesi, 4Dpharma and Mologic; and consulting fees from GSK, AZ, Sanofi, Regeneron, Roche, Genentech, BI, Novartis, Chiesi, 4Dpharma, Mologic and Areteia. R.A. Evans declares funding from UKRI/MRC/NIHR to complete this work; funding from Wolfson Foundation and Genentech/Roche; consulting fees from AstraZeneca/Evidera; speaking fees from Boehringer and Moderna; support for attending meetings from Chiesi; and leadership or fiduciary roles as ERS Group 01.02 Pulmonary Rehabilitation and Chronic Care Secretary, and ATS Pulmonary Rehabilitation Assembly Chair. All other authors declare no conflicts of interest., (Copyright ©The authors 2024.)

This study uncovered a reversal of seasonal variation in hospitalised COPD exacerbation events after the COVID-19 pandemic. Investigation of updated seasonal exacerbation patterns and triggers can help initiate preventive strategies effectively. https://bit.ly/3wN71h0., Competing Interests: Conflict of interest: H. Aung, A. Aung, H.J.C. McAuley, O. Elneima, C. Flynn, T. Thornton and H. Evans have no potential conflicts of interest to disclose. C.E. Brightling has received grants and consultancy fees from 4D Pharma, AstraZeneca, Chiesi, Genentech, GlaxoSmithKline, Mologic, Novartis, Regeneron Pharmaceuticals, Roche and Sanofi. A. Wright has received grant income (paid to institution) from Sanofi. N.J. Greening has received honoraria for lectures, conference travel and advisory boards from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Pulmonx, and received grants and consultation fees (paid to institution) from Genentech, Roche and GlaxoSmithKline., (Copyright ©The authors 2024.)

Background: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning., Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2-3 years, and whether symptoms at 2-3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2-3 years were associated with occupation change. People with lived experience were involved in the study., Findings: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2-3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16-1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2-3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2-3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0-48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0-17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2-3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6-31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04-2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21-1·98] for every point increase in CCI-20)., Interpretation: Psychiatric and cognitive symptoms appear to increase over the first 2-3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19., Funding: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research., Competing Interests: Declaration of interests AHa is co-director and owner of H2CD, and owner and director of Future Cognition, which support online studies and develop custom cognitive assessment software, respectively. PJHe is director and CEO of H2CD. JDC declares grants from AstraZeneca, Boehringer Ingelheim, Insmed, Novartis, Gilead Sciences, and Genentech; and consulting fees from AstraZeneca, Boehringer Ingelheim, Insmed, Novartis, Gilead Sciences, Chiesi, Zambon, and Genentech. L-PH declares grants to their institution from UK Research and Innovation (UKRI), Regenerative Medicine Platform, Celgene, British Lung Foundation, and Oxford Boehringer Ingleheim; the author is on the advisory board for the CATALYST trial and acts as chair of the Respiratory Translational Research Collaboration. AHo declares a grant to their institution from UKRI and the UK National Institute for Health Research (NIHR) to complete this work, funding from NIHR Manchester Clinical Research Facility to support study delivery, and personal funding from NIHR Manchester Biomedical Research Centre (BRC). AHo declares institutional payments to support grant-funded research from NIHR, UK Medical Research Council (MRC), Cystic Fibrosis Trust, Cystic Fibrosis Foundation, North West Lung Centre Charity, and Moulton Trust; consulting fees from Mylan Pharmaceuticals for advisory board participation; and payment from Vertex Pharmaceuticals for educational presentation, participation on a clinical trials advisory board, and writing of a review article. AHo's non-paid roles include chair of the Cystic Fibrosis Clinical Trials Accelerator Program, deputy chair of the NIHR Respiratory Translational Research Collaboration, and director of a university spin-out company (Mi-trial). BR declares payments from the British Heart Foundation Oxford Centre of Research Excellence, NIHR Oxford BRC, and UKRI for grants and contracts; and consulting fees from Axcella Therapeutics. ASh, ASi, and MM declare a grant to their institution from UKRI and NIHR to complete this work. ASh declares unremunerated participation on the AstraZeneca Thrombotic Thrombocytopenic Taskforce and Scottish and UK Governments COVID-19 advisory groups. LH-W declares a grant from NIHR unrelated to the submitted work; acting as independent chair of the NIHR Health Technology Assessment Committee for Colour COPD trial; and membership of the American Thoracic Society Pulmonary Rehabilitation Assembly Web and Planning Committees. NIL declares acting as director of research at the Intensive Care Society UK. CEB declares a grant to their institution from UKRI and NIHR to complete this work; the author reports grants from GSK, AstraZeneca, Sanofi, Boehringer Ingelheim, Chiesi, Novartis, Roche, Genentech, Mologic, and 4DPharma; and consultancy fees paid to their institution from GSK, AstraZeneca, Sanofi, Boehringer Ingelheim, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma, and Teva. LVW declares research funding unrelated to the submitted work from GSK and Orion; consulting fees unrelated to the submitted work from Galapagos; a Wellcome Conference speaker honorarium; travel support from Genentech; advisory board participation for Galapagos; and an associate editor role for the European Respiratory Journal. RAE declares a grant to their institution from UKRI and NIHR to complete this work; the author declares speaker fees from Boehringer Ingelheim and unpaid roles as European Respiratory Society Assembly 01·02 Pulmonary Rehabilitation secretary and with the American Thoracic Society Pulmonary Rehabilitation Assembly programme committee. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Topic Importance: COVID-19 can cause ongoing and persistent symptoms (such as breathlessness and fatigue) that lead to reduced functional capacity. There are parallels in symptoms and functional limitations in adults with post-COVID symptoms and adults with chronic respiratory diseases. Pulmonary rehabilitation is a key treatment for adults with chronic respiratory diseases, with the aims to improve symptom management and increase functional capacity. Given the similarities in presentation and aims, a pulmonary rehabilitation program may be optimal to meet the needs of those with ongoing symptoms after COVID-19., Review Findings: Aerobic and strength training has shown benefit for adults living with long COVID, although there is little evidence on structured education in this population. Breathing pattern disorder is common in adults with long COVID, and considerations on treatment before rehabilitation, or alongside rehabilitation, are necessary. Considerations on postexertional malaise are important in this population, and evidence from the chronic fatigue syndrome literature supports the need for individualization of exercise programs, and considerations for those who have an adverse reaction to activity and/or exercise., Summary: This narrative review summarizes the current evidence on pulmonary rehabilitation programs in a long-COVID population. Where the evidence is lacking in long COVID the supporting evidence of these programs in chronic respiratory diseases has highlighted the importance of aerobic and strength training, considerations for fatigue, potential mechanisms for immunology improvement, and management of breathing pattern disorders in these programs., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: S. J. S. is a National Institute for Health Research Senior Investigator. None declared (E. D., G. M., J. H. H., N. C. B., M. B., C. B., H. J. C. M., N. J. G.)., (Copyright © 2024 American College of Chest Physicians. All rights reserved.)

Background: There is evidence to support COVID-19 rehabilitation programmes improving persistent COVID-19 symptoms; however, there is concern that therapies that include an exercise component may increase fatigue and post-exertional symptom exacerbation (PESE). The objectives of the present study were to determine the effect of a 6-week COVID-19 rehabilitation programme on fatigue and PESE in individuals with ongoing COVID-19 symptoms., Methods: After a routine medical assessment, individuals with persistent COVID-19 symptoms were enrolled on a 6-week COVID-19 specific rehabilitation programme. The programme included symptom-titrated exercise, education and self-management advice. Fatigue was assessed pre- and post-programme using the Functional Assessment Chronic Illness Therapy Fatigue questionnaire (FACIT). Exercise capacity (Incremental and Endurance Shuttle Walking Test (ISWT and ESWT)) and PESE (DePaul Symptom Questionnaire (DSQ)) were also assessed pre- and post-programme. Composite scores were calculated for the frequency and severity domains of the DSQ., Results: 148 patients (median (IQR) age 59 (49-72) years, 82 (55%) female, 81 (54%) hospitalised) completed the COVID-19 rehabilitation programme. FACIT score was reduced pre- to post-programme by a mean (CI) change of -5 (-7- -4); p<0.01. Exercise capacity increased by 82 (65-99) m for the ISWT and 398 (333-462) s for the ESWT (n=148). PESE was assessed in 44 patients. The DSQ frequency and severity composite score improved by 20 (13-28) and 19 (13-26) points, respectively (p<0.01, n=44)., Conclusion: These data demonstrate the potential benefits of a COVID-19 rehabilitation programme in improving fatigue, exercise capacity and symptom exacerbation in those with persistent COVID-19 symptoms., Competing Interests: Conflict of interest: There are no conflicts of interest to declare relating to this manuscript., (Copyright ©The authors 2024.)

Background: The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown., Methods: Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease ( i.e. , asthma, COPD or bronchiectasis) were compared to the non-airways group., Results: A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p<0.001), had higher burden of anxiety (29.1% versus 22.0%, p=0.002), depression (31.2% versus 24.7%, p=0.006), higher percentage of impaired mobility using short physical performance battery ≤10 (57.4% versus 45.2%, p<0.001) and 27% had a new disability (assessed by the Washington Group Short Set on Functioning) versus 16.6%, p=0.014. HRQoL assessed using EQ-5D-5L Utility Index was lower in the airways group (mean±SD 0.64±0.27 versus 0.73±0.25, p<0.001). Burden of breathlessness, fatigue and cough measured using a study-specific tool was higher in the airways group., Conclusion: Individuals with pre-existing airway diseases hospitalised due to COVID-19 were less likely to feel fully recovered, had lower physiological performance measurements, more burden of symptoms and reduced HRQoL up to 1 year post-hospital discharge., Competing Interests: Conflict of interest: J.R. Hurst has received support to attend meetings, research grants, and personal payment and payment to his employer from pharmaceutical companies that make medicines to treat airways diseases. J.K. Quint reports grants from Industrial Strategy Challenge Fund, the Medical Research Council, Health Data Research, GlaxoSmithKline (GSK), Boehringer Ingelheim (BI), Asthma+Lung UK and AstraZeneca (AZ), and consulting fees from GSK, Evidera, Chiesi, AZ and Insmed outside the submitted work. P.E. Pfeffer reports grants from NIHR and GSK, Honoraria payments for lectures from AZ, GSK, Sanofi and Chiesi and travel fees from AZ, GSK, Sanofi outside the submitted work. N.J. Greening reports grants from GSK and BioAge, and personal fees and travel grants from Genentech, Roche, Chiesi, AZ, GSK, Pulmonx and Chiesi outside the submitted work. J.D. Chalmers is an associate editor of this journal. A. Horsley reports grants from UKRI, NIHR and NIHR Manchester BRC during the conduct of this study and unenumerated role as the chair of NIHR Translational Research Collaboration. A. Sheikh has served on AZ's thrombotic thrombocytopenic taskforce, and on a number of UK and Scottish Government COVID-19 advisory bodies; all these roles were unremunerated. B. Raman reports grant from BHF Oxford CRE and speaker fees from Axcella Therapeutics. R.A. Evans reports grants from UKRI/MRC, DHSC/NIHR, Wolfson Foundation and Genentec/Roche during the conduct of this study, travel and speaker fees from AZ/Evidera, Boehringer Ingelheim (BI), Moderna and Chiesi, and unremunerated leadership roles in ERS/ATS outside the submitted work. C.E. Brightling declares that their institute was awarded a grant from UKRI/NIHR to complete this work; the author reports grants from GSK, AZ, Sanofi, Regeneron, BI, Chiesi, Novartis, Roche, Genentech, Mologic and 4DPharma; and consultancy fees paid to their institution from GSK, AZ, Sanofi, BI, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma and Areteia. A. De Soyza declares receiving personal consulting fees and travel grants from AZ, Bayer, GSK, Chiesi, Novartis, Pfizer, Insmed, Gilead and 30T outside the submitted work. All other authors declare no competing interests., (Copyright ©The authors 2024.)

Background: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known., Objectives: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors., Methods: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health., Results: From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86)., Conclusion: Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need., Trail Registration Number: ISRCTN10980107., Competing Interests: Competing interests: KK is chair of the ethnicity subgroup of the UK Scientific Advisory Group for Emergencies (SAGE) and is a member of SAGE. KK (Chair) and RE are members of the Long COVID Epidemiological Research Group that reports to the CMO. CB is an author of the COVID-19 rapid guideline: managing the long-term effects of COVID-19 NICE guideline (NG188) https://www.nice.org.uk/guidance/ng188/history. CB is a member of the NHS National Services Scotland Long COVID group and his employer, the University of Glasgow, holds a research agreement with AstraZeneca and Somalogic for research in COVID-19. AJM is an employee of AstraZeneca., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood 1 . Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials., (© 2024. The Author(s).)

Objective: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies., Design/patients: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study)., Measurements: Plasma steroids were quantified by liquid chromatography-mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD)., Results: In the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow-up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121-192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in-hospital severity, perception of recovery, or patient-reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in-hospital severity, perception of recovery or symptom scores., Conclusions: Circulating glucocorticoids in patients hospitalised with COVID-19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post-COVID symptoms suggests steroid insufficiency does not play a causal role in this condition., (© 2024 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Rationale: As the prevalence of multimorbidity increases, understanding the impact of isolated comorbidities in people COPD becomes increasingly challenging. A simplified model of common comorbidity patterns may improve outcome prediction and allow targeted therapy., Objectives: To assess whether comorbidity phenotypes derived from routinely collected clinical data in people with COPD show differences in risk of hospitalisation and mortality., Methods: Twelve clinical measures related to common comorbidities were collected during annual reviews for people with advanced COPD and k-means cluster analysis performed. Cox proportional hazards with adjustment for covariates was used to determine hospitalisation and mortality risk between clusters., Measurements and Main Results: In 203 participants (age 66 ± 9 years, 60 % male, FEV 1 %predicted 31 ± 10 %) no comorbidity in isolation was predictive of worse admission or mortality risk. Four clusters were described: cluster A (cardiometabolic and anaemia), cluster B (malnourished and low mood), cluster C (obese, metabolic and mood disturbance) and cluster D (less comorbid). FEV 1 %predicted did not significantly differ between clusters. Mortality risk was higher in cluster A (HR 3.73 [95%CI 1.09-12.82] p = 0.036) and B (HR 3.91 [95%CI 1.17-13.14] p = 0.027) compared to cluster D. Time to admission was highest in cluster A (HR 2.01 [95%CI 1.11-3.63] p = 0.020). Cluster C was not associated with increased risk of mortality or hospitalisation., Conclusions: Despite presence of advanced COPD, we report striking differences in prognosis for both mortality and hospital admissions for different co-morbidity phenotypes. Objectively assessing the multi-system nature of COPD could lead to improved prognostication and targeted therapy for patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls., Results: We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3-5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28 -ve CD57 +ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57 +ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ([Formula: see text] = 0.174, p = 0.043), with a major influence being disease severity ([Formula: see text] = 0.188, p = 0.01)., Conclusions: Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease., (© 2024. The Author(s).)

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury., Competing Interests: H.Z. has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). I.K. declares grant fundind and speaker fees from Novo Nordisk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Coronavirus disease 2019 (COVID-19) can lead to ongoing symptoms such as breathlessness, fatigue and muscle pain, which can have a substantial impact on an individual. Exercise-based rehabilitation programmes have proven beneficial in many long-term conditions that share similar symptoms. These programmes have favourably influenced breathlessness, fatigue and pain, while also increasing functional capacity. Exercise-based rehabilitation may benefit those with ongoing symptoms following COVID-19. However, some precautions may be necessary prior to embarking on an exercise programme. Areas of concern include ongoing complex lung pathologies, such as fibrosis, cardiovascular abnormalities and fatigue, and concerns regarding post-exertional symptom exacerbation. This article addresses these concerns and proposes that an individually prescribed, symptom-titrated exercise-based intervention may be of value to individuals following infection with severe acute respiratory syndrome coronavirus 2., Competing Interests: Conflict of interest: S.J. Singh reports grants from NIHR (NIHR Programme Grant (NIHR 202020), HTA Project Grant (NIHR: 131015), NIHR DHSC/UKRI COVID-19 Rapid Response Initiative, NIHR Global Research Group (NIHR 17/63/20), NIHR Senior Investigator), Wellcome Doctoral Training Programme and Actegy Limited; lecture honoraria from GSK, Ministry of Justice, CIPLA and Sherbourne Gibbs; advisory board membership with NICE Expert Adviser Panel – Long COVID, and Wales Long COVID Advisory Board (expired); leadership roles with ATS as Pulmonary Rehabilitation Assembly Chair, Clinical Lead for the RCP Pulmonary Rehabilitation Accreditation Scheme, and Clinical Lead for the NACAP Audit for Pulmonary Rehabilitation, outside the submitted work. E. Daynes reports lecture honoraria from Clinical Physio, outside the submitted work. B. Raman reports grants from BHF Oxford Centre of Research Excellence transition fellowship, NIHR Oxford, Oxford BRC; and lecture honoraria from Axcella Therapeutics, outside the submitted work. N.J. Greening reports grants from GSK, Genentech and Roche; consulting fees from Genentech and Roche; lecture honoraria from AstraZeneca, Chiesi, GSK and PulmonX; travel support from Chiesi and AstraZeneca; and is a member of a number of DSMCs, including rehabilitation, exercise and supplementation trials in COPD, outside the submitted work. T. Chalder reports grants from Guy's and St Thomas’ Charity, National Institute for Health Research (NIHR) Biomedical Research Centre, NIHR and UKRI; royalties, consulting fees for workshops, travel expenses, accommodation costs, and honorarium for lectures; was on the Expert Advisory Panel for COVID-19 Rapid Guidelines, and on the scientific committee of the British Association of Cognitive Behavioural Psychotherapy, outside the submitted work. R.A. Evans reports grants from NIHR/UKRI/Wolfson Foundation; consulting fees from AstraZeneca; lecture honoraria from Boehringer; travel support from Chiesi; and a leadership role as ERS Group 01.02 Pulmonary Rehabilitation Secretary, outside the submitted work. C.E. Bolton reports grants from UKRI/MRC, NIHR Nottingham BRC, Nottingham Hospitals Charity and University of Nottingham, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2023.)

Competing Interests: Competing interests: None declared.

Post-COVID cognitive deficits, including 'brain fog', are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits., (© 2023. The Author(s).)

During hospitalisation with COVID-19, individuals may experience prolonged periods of immobilisation. Combined with the inflammatory effects of the virus, this may lead to a significant reduction in both muscle mass and strength. Data from several long-term studies suggest that these symptoms may not fully resolve within one year. Owing to its effectiveness at inducing muscle fibre hypertrophy and improving neuromuscular efficiency, resistance training is of great interest in the rehabilitation of this population. This narrative review aims to identify the rationale and potential efficacy of resistance training for restoring physical function following infection with SARS-CoV-2, as well as evidence of its use in clinical practice. The studies included in this narrative review consisted mostly of multi-component rehabilitation trials. Of these, widespread improvements in muscle strength were reported using intensities of up to 80% of participants' 1-repetition-maximum. Evidence thus far indicates that resistance training may be safe and effective in patients following COVID-19, although its individual contribution is difficult to discern. Future exercise intervention studies investigating the efficacy of resistance training as a sole modality are needed., (Copyright: © 2023 Hylonome Publications.)

Although the exact prevalence of post-COVID-19 condition (also known as long COVID) is unknown, more than a third of patients with COVID-19 develop symptoms that persist for more than 3 months after SARS-CoV-2 infection. These sequelae are highly heterogeneous in nature and adversely affect multiple biological systems, although breathlessness is a frequently cited symptom. Specific pulmonary sequelae, including pulmonary fibrosis and thromboembolic disease, need careful assessment and might require particular investigations and treatments. COVID-19 outcomes in people with pre-existing respiratory conditions vary according to the nature and severity of the respiratory disease and how well it is controlled. Extrapulmonary complications such as reduced exercise tolerance and frailty might contribute to breathlessness in post-COVID-19 condition. Non-pharmacological therapeutic options, including adapted pulmonary rehabilitation programmes and physiotherapy techniques for breathing management, might help to attenuate breathlessness in people with post-COVID-19 condition. Further research is needed to understand the origins and course of respiratory symptoms and to develop effective therapeutic and rehabilitative strategies., Competing Interests: Declaration of interests SJS has received project funding from the UK National Institute for Health Research (NIHR), UK Research and Innovation, the Department of Health and Social Care, and Actegy. She has received funding for a doctoral training programme from the Wellcome Trust, and reports funding for presentations from GSK, the UK Ministry of Justice, Cipla, and Sherbourne Gibbs. SJS is the American Thoracic Society Pulmonary Rehabilitation Assembly Chair, clinical lead for the Royal College of Physicians Pulmonary Rehabilitation Accreditation Scheme, clinical lead for the National Asthma and COPD Audit Programme for Pulmonary Rehabilitation, and is on the National Institute for Health and Care Excellence expert advisory panel for long COVID. CEB has received funding to his institution for consultancy and investigator roles from GSK, AstraZeneca, Genentech, Roche, Sanofi, Regeneron, Boehringer Ingelheim, Chiesi, Mologic, and 4DPharma. RAE reports research funding from the NIHR, UKRI, and the Wolfson Foundation. She has received payment for a consultancy role from AstraZeneca, for invited lectures from Boehringer Ingelheim, and for conference attendance from Chiesi. RAE is secretary of the European Respiratory Society Group 01.02 Rehabilitation and Chronic Care. RGJ has received grants to his institution from AstraZeneca, Biogen, Galecto, GSK, Nordic Biosciences, RedX, and Pilant. He reports consultancy fees from AstraZeneca, Brainomix, Bristol Myers Squibb, Chiesi, Cohbar, Daewoong, GSK, Pliant, Resolution Therapeutics, Roche, and Veracyte, and lecture fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Roche, and PatientMPower. RGJ is on data safety monitoring boards for Boehringer Ingelheim, Galapagos, and Vicore, and is on the advisory board of NuMedii. RGJ is the current president of Action for Pulmonary Fibrosis. MT has received funding from MorphogenIX and Jansen for taking part in advisory boards and has received support from GSK and Jansen to travel and attend meetings. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea., Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107)., Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect., Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition., Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council., Competing Interests: Declaration of interests IDS declares a statistical editor honoraria role with Thorax. TP declares support from the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre (BRC) to complete the work. ALH declares an editor-in-chief role for Computer Physics Communications. RA declares speaker fees and travel support from Boehringer Ingelheim. CEB declares their institute was awarded a grant from the UK Research and Innovation (UKRI)/NIHR and institutional support from NIHR Nottingham BRC to complete this work; the author reports grants from Nottingham Hospitals Charity and Nottingham University Hospitals Research and Innovation Department. TC declares support from the NIHR South London and Maudsley NHS Foundation Trust, King's College London BRC to complete the work; the author reports grants from Guy's and St Thomas' Charity, NIHR, and UKRI; the author has published self-help books on chronic fatigue for which she receives royalties; the author has received ad-hoc payments for workshops carried out in long-term conditions; the author declares travel and accommodation support; the author is part of the scientific committee of the British Association for Behavioural and Cognitive Psychotherapies (BABCP) and she is on the expert advisory panel for COVID-19 Rapid Guidelines. JDC declares grants from AstraZeneca, Novartis, Boehringer Ingelheim, Genentech, Gilead Sciences, Insmed, GlaxoSmithKline, and Grifols; the author reports consulting fees from AstraZeneca, Insmed, Boehringer Ingelheim, Janssen, Antabio, Chiesi, Novartis, Pfizer, Zambon, GlaxoSmithKline, and Grifols. GD declares support from the NIHR Imperial BRC, Royal Brompton and Harefield NGS Foundation Trust, Royal Brompton & Harefield Hospitals Charity, Imperial College Healthcare NHS Trust, and the Medical Research Council (MRC) to complete this work; the author reports grants from Genentech, AstraZeneca, British Lung Foundation (BLF) Early Cohort, GlaxoSmithKline, Novartis, Chiesi, and Boehringer Ingelheim; the author has a published chapter in a textbook for which he receives payment; the author declares a role in the advisory boards for AstraZeneca and Novartis and as honorarium as deputy editor of the American Journal of Respiratory and Critical Care Medicine (AJRCCM). L-PH declares grants from NIHR Oxford BRC. MGJ declares grants from the Royal Society, MRC, BLF, Boehringer Ingelheim, and the Asthma, Allergy and Inflammatory Research Charity. BR declares support from the British Heart Foundation (BHF) Oxford Centre of Research Excellence (CRE) to complete this work. SLR-J declares support for her institute from UKRI to complete the work; the author reports grants from UKRI, The European and Developing Countries Clinical Trials Partnership (EDCTP), MRC, Rosetrees Trust, and the Global Challenges Research Fund (GCRF); the author reports an honorarium for chapter contribution from the Federation of European Academies of Medicine; the author is Data and Safety Monitoring Board (DSMB) Chair for a Bexsero trial funded by Wellcome Trust; the author declares an editor role for AIDS journal. AVR declares support from NIHR Leicester BRC to complete the work. MS declares support for his institute from MRC/Department of Health and Social Care (DHSC) to complete the work. ASi declares support for her institute from UKRI/NIHR to complete the work. DGW declares an advanced Fellowship grant from NIHR; the author receives an honorarium from bioMérieux to present. TY declares support from the NIHR Leicester BRC to complete the work. RGJ declares grants from AstraZeneca, Biogen, Galecto, GlaxoSmithKline, Nordic Biosciences, RedX, Pliant; the author received consulting fees from AstraZeneca, Brainomix, Bristol Myers Squibb, Chiesi, Cohbar, Daewoong, GlaxoSmithKline, Veracyte, Resolution Therapeutics, and Pliant; the author has received payments from Boehringer Ingelheim, Chiesi, Roche, patientMpower, and AstraZeneca; the author was paid for expert testimony by Pinsent Masons LLP; the author has participated on a DSMB for Boehringer Ingelheim, Galapagos, and Vicore; the author has held a leadership role at NuMedii and is President of Action for Pulmonary Fibrosis. SJS declares grants from NIHR, Wellcome Doctoral Training Programme (DTP), the Human Tissue Authority, NIHR DHSC/UKRI COVID-19 Rapid Response Initiative, NIHR Global Research Group, Actegy Limited, and as an NIHR Senior Investigator; the author has presented for GlaxoSmithKline, Ministry of Justice, CIPLA, and Sherbourne Gibbs; the author is on the National Institute for Health and Care Excellence (NICE) Expert Advisor Panel for Long COVID and was on the Wales Long COVID Advisory Board; the author is the American Thoracic Society (ATS) Pulmonary Rehabilitation Assembly Chair, Clinical Lead Royal Society of Physicians (RSP) Pulmonary Rehabilitation Accreditation Scheme, and Clinical Lead Nation Asthma and COPD Audit Programme (NACAP) for Pulmonary Rehabilitation. WD-CM declares grants for his institution from NIHR, National Health Service (NHS) Accelerated Access Collaborative, and BLF; the author is the honorary President of the Association for Respiratory Technology and Physiology but receives no payment. CEBr declares support from UKRI/DHSC and NIHR Leicester BRC to complete the work; the author reports grants from GlaxoSmithKline, AstraZeneca, Sanofi, CI, Chiesi, Novartis, Roche, Genentech, Mologic, and 4DPharma; the author received consulting fees paid to his institution from GlaxoSmithKline, AstraZeneca, Sanofi, BI, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma, and TEVA. LVW declares support from UKRI, GlaxoSmithKline/Asthma + Lung UK, and NIHR to complete this work; the author receives grants from Orion Pharma, GlaxoSmithKline, Genentech, and AstraZeneca; the author received consulting fees paid to her institution from Galapagos and Boehringer Ingelheim; the author received support for attending a meeting from Genentech. JCP received consulting fees from Istesso and The Limbic; the author participated on a DSMB for Vicore. AART declares a fellowship grant from BHF and a grant from NIHR to his institution; the author received an honorarium for lectures from Janssen-Cilag Ltd; the author received support for attending meetings from Janssen-Cilag Ltd. AH declares support from UKRI, NIHR, and NIHR Manchester BRC to complete the work; the author is Chair NIHR Translational Research Collaboration (unpaid). PLM declares a grant for his institution from AstraZeneca; the author received consulting fees from Hoffmann-La Roche, Boehringer Ingelheim, AstraZeneca, Trevi, and Qureight; the author received speaker fees from Boehringer Ingelheim and Hoffmann-La Roche. RAE declares support from UKRI/MRC to complete the work; the author reports a grant from NIHR/Wolfson Foundation; the author received consulting fees from AstraZeneca for Long COVID; the author received a speaker fee from Boehringer Ingelheim for a lecture on Long COVID; the author received support to attend BTS conference virtually from Chiesi; the author is the European Respiratory Society Group 01.02 Pulmonary Rehabilitation Secretary (unpaid). JFB declares support to his institute from an MRC Transition Fellowship, Asthma + Lung UK, NIHR Manchester BRC, and UKRI; the author reports grants paid to his institution from the Small Business Research Initiative Home Spirometer and the National Institute of Academic Anaesthesia; the author has received support for attending meetings from TEVA and Therakos; the author is a committee member of the Royal Society of Medicine (RSM). All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Identify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19., Design: Multicentre prospective observational cohort study using questionnaire data at visit 1 (2-7 months post discharge) and visit 2 (10-14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations., Setting: 64 UK acute hospital Trusts., Participants: Adults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19., Main Outcome Measures: Self-reported swallow, communication, voice and cognitive compromise., Results: Compromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001)., Conclusion: Swallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues., Competing Interests: Competing interests: CEB has a UKRI PHOSP grant through NIHR Nottingham Biomedical Research Centre for support to conduct the PHOSP study, and Nottingham Hospital Trust Charity donations to support her research. JC has grants/contracts with AstraZeneca, Boehringer Ingelheim, Insmed, Gilead Sciences, Grifols and has received consulting fees from AstraZeneca, Boehringer Ingelheim, Insmed, Gilead Sciences, Grifols, Pfizer, Zambon, Antabio, Janssen. LVW holds a UK Research and Innovation GSK/Asthma + Lung UK National Institute of Health Research Grant and Orion Pharma GSK Genentech AstraZeneca research funding and has received consulting fees from Galapagos Boehringer Ingelheim and travel fees from Greentech, is on the advisory board for Galapagos and is the Associate Editor for European Respiratory Journal. MR has received consulting fees from Galapagos Boehringer Ingelheim. ASi received joint funding UKRI & NIHR grant references: MR/V027859/1 and COV031. CB has received UKRI/DHSC PHOSP-COVID grant via NIHR Leicester BRC, grants from GSK, AZ, Sanofi, BI, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma, consultancy paid to institution from GSK, AZ, Sanofi, BI, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma, TEVA. RAE has received NIHR/UKRI/Wolfson Foundation grants, consulting fees from AstraZeneca for long COVID, honoraria payment from Boeringher, support from Chiesi to attend BTS, and is ERS Group 01.02 Pulmonary Rehabilitation Secretary. JKQ is on the Thorax editorial board., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea., Methods: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up., Findings: We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01-1.03), male (1.54, 1.16-2.04), neither obese nor severely obese (1.82, 1.06-3.13 and 4.19, 2.14-8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09-2.22) or cardiovascular disease (1.33, 1.00-1.79), and shorter hospital admission (1.01 per day, 1.00-1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission)., Interpretation: Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19., Funding: PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care.COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders., Competing Interests: Aziz Sheikh received research grant to Institution from the National Institute of Health and Care Research (NIHR); participated in AstraZeneca's Thrombotic Thrombocytopenic TaskForce (unremunerated); served as an adviser to UK and Scottish Government COVID bodies (unremunerated). LGH received project grant funding to Institution from MedImmune, Novartis UK, Roche/Genentech and GlaxoSmithKline (GSK); payment for lectures from AstraZeneca, Novartis, Roche/Genentech, Sanofi, Circassia, GSK, Chiesi, Teva; travel funding from AstraZeneca, Chiesi, Novartis, Boehringer Ingelheim, Teva and GSK; attended advisory boards/lectures of Novartis, Roche/Genentech, GSK, Evelo Biosciences, Teva, Theravance and Vectura. ADS received grants unrelated to the current work from AstraZeneca, Bayer, GSK, Pfizer, Novartis; consulting fees from AstraZeneca, GSK, Insmed and Bayer; travel support from Chiesi, AstraZeneca and GSK; attended advisory board of Insmed. AH received funding from UK Research and Innovation, National Institute of Health Research, NIHR Manchester BRC; chair NIHR Translational Research Collaboration (unpaid). JDC received funding from AstraZeneca, Genentech, Gilead Sciences, GSK, Insmed, Grifols, Novartis, Boehringer Ingelheim; consulting fees from Astrazeneca, Chiesi, GSK, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio, Zambon. RAE received funding from NIHR, UKRI, Wolfson Foundation; consulting fees from AstraZeneca; payment for lecture from Boeringher; support for attending meetings from Chiesi; served as ERS Group 01.02 Pulmonary Rehabilitation Secretary (unpaid). AM received funding to Institution from Barts Charity, Pharma Nord, Fischer Family Foundation, DSM Nutritional Products, The Exilarch's Foundation, The Karl R Pfleger Foundation, The AIM Foundation, Synergy Biologics, Cytoplan Ltd, UK NIHR Clinical Research Network, Health Data Research UK BREATHE Hub, UK Research and Innovation Industrial Strategy Challenge Fund, Thornton & Ross, Warburtons, Matthew Isaacs (personal donation), Barbara Boucher (personal donation), Hyphens Pharma. Amisha Singapuri received funding to Institution from UKRI and NIHR. BR received funding from BHF Oxford CRE Transition Intermediate Clinical Research Fellowship; payment for lecture from Axcella Therapeutics. CEB received funding to Institution from MRC, NIHR, Leicester NIHR BRC, GSK, AstraZeneca, Sanofi, Regeneron, Roche, Genentech, BI, Novartis, Chiesi, 4Dpharma, Mologic; consulting fees to institution from GSK, AstraZeneca, Sanofi, Regeneron, Roche, Genentech, BI, Novartis, Chiesi, 4Dpharma, Mologic. MS received funding to Institution from UKRI-MRC and DHSC-NIHR. LVW received funding from UK Research and Innovation, GSK/Asthma + Lung UK, NIHR, Orion Pharma, GSK, Genentech, AstraZeneca; consulting fees to institution from Galapagos, Boehringer Ingelheim; travel support from Genentech; attended Advisory Board for Galapagos; served as Associate Editor for European Respiratory Journal. PEP received funding from NIHR. JKQ received funding to Institution from MRC, HDR UK, GSK, BI, asthma + lung UK, AstraZeneca; consulting fees from GSK, AstraZeneca, Insmed. MM received funding from the PHOSP Covid grant. Other authors declare no conflict of interests., (© 2023 The Author(s).)

Background: Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months., Methods: This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population., Results: 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 versus BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) versus BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm., Conclusion: Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments., Competing Interests: Conflict of interest: D. Waller reports lecture honoraria from PulmonX Ltd, outside the submitted work. N.J. Greening reports grants from GSK, consulting fees from Genentech, lecture honoraria from AstraZeneca and Chiesi, travel support from Chiesi, outside the submitted work. P.L. Shah reports lecture honoraria from PulmonX Ltd, outside the submitted work. R. Bilancia reports lecture honoraria and travel support from Intuitive, outside the submitted work. R. Lawson is a Member of British Thoracic Society COPD Specialist Advisory group, a Member of South Yorkshire Clinical Senate, and a Member of South Yorkshire and Bassetlaw Respiratory Clinical Network, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2023.)

Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage. Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post-COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata. Methods: The PHOSP-COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP-COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up. Measurements and Main Results: The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83-155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05-1.40), percent predicted Dl CO less than 80% (RR, 1.25; 95% CrI, 1.00-1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07-1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6-9.5), rising to 11.7% (95% CrI, 10.3-13.1) in the sensitivity analysis. Conclusions: Residual lung abnormalities were estimated in up to 11% of people discharged after COVID-19-related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications.

Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty., Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group-robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)-at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107., Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered., Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required., Funding: UK Research and Innovation and National Institute for Health Research., Competing Interests: RAE declares speaker fees or support from Boeringher Ingelheim and 10.13039/100019719Chiesi as well as their role as ERS Group 01.02 Pulmonary Rehabilitation Secretary. CEBo and AG declare support from 10.13039/501100020624NIHR Nottingham BRC and Nottingham university Hospitals Trust R&I and Nottingham Hospitals Charity. CEB declares grants and consultancy paid to institution from GSK, AZ, 10.13039/100004339Sanofi, 10.13039/100001003Boeringher Ingelheim, Chiesi, 10.13039/100004336Novartis, 10.13039/100004337Roche, 10.13039/100004328Genentech, Mologic, 4DPharma outside of this work. JDC declares grants from 10.13039/100004337Roche, Insmed, 10.13039/100001003Boehringer Ingelheim, 10.13039/100004336Novartis, GSK, 10.13039/100005564Gilead Sciences and 10.13039/501100016387Grifols as well as consulting fees from 10.13039/100004325Astrazeneca, Insmed, 10.13039/100001003Boehringer Ingelheim, Janssen, Chiesi, 10.13039/100004336Novartis, Grifols, Zambon, Pfizer and GSK outside of this work. AH declares institutional and individual support from the NIHR Manchester BRC as well as their role as Deputy Chair NIHR Translational Research Collaboration. WD-CM declares grants or contracts from National Institute for Health Research, Asthma + Lung UK and NHSX as well as payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Mundipharma, 10.13039/100004336Novartis and European Conference and Incentive Services and participation on a Data Safety Monitoring Board or Advisory Board for Jazz Pharmaceuticals and receipt of equipment, materials, drugs, medical writing, gifts or other services from GSK for funds for blood analysis outside of this work. JKQ declares grants paid to institution from the Medical Research Council, HDR UK, GSK, Bayer, 10.13039/100001003Boehringer Ingelheim, Asthma + Lung UK, 10.13039/100019719Chiesi and 10.13039/100004325AstraZeneca as well as advisory bord participation or speaking fees from 10.13039/100004330GlaxoSmithKline, 10.13039/100001003Boehringer Ingelheim, 10.13039/100004325AstraZeneca, 10.13039/100019719Chiesi, Teva, Insmed and 10.13039/100004326Bayer. BR declares consulting fees from Axcella Therapeutics outside of this work. SJS declares grants from the NIHR programme grant (NIHR 202020) as an NIHR Senior Investigator, the Wellcome Doctoral Training Programme, HTA Project Grant (NIHR: 131015), NIHR DHSC/UKRI COVID-19 Rapid Response Initiative, NIHR Global Research Group (NIHR 17/63/20) and Actegy Limited, honoraria paid by GSK, Ministry of Justice, CIPLA and Sherbourne Gibbs for presentations, participation on the NICE Expert Adviser Panel - Long COVID and Wales Long COVID Advisory Board (expired) and a role as ATS Pulmonary Rehabilitation Assembly Chair, Clinical Lead RCP Pulmonary Rehabilitation Accreditation Scheme and Clinical Lead NACAP Audit for Pulmonary Rehabilitation. LVW declares additional support from GSK and 10.13039/501100000362Asthma + Lung UK (Professorship (C17-1)) relating to this work as well as research funding from Orion Pharma and GSK, research collaboration contracts from Genentech and 10.13039/100004325AstraZeneca, consulting fees paid to institution from Galapagos for participation in an advisory board, support for travel from Genentech and their role as Associate Editor for European Respiratory Journal outside of this work. JW declares grants from the 10.13039/501100009130NIHR programme development grant and 10.13039/100015544King’s College Hospital Charity as well as participation on the trial steering group for “Falls in Care Homes (FinCH)” and programme steering group member for “Promoting Activity, Independence and Stability in Early Dementia (PrAISED) research programme” as their role as Clinical lead for national audit of inpatient falls (Royal College of Physicians) outside of this work. NJG declares grants or contracts from the NIHR, GSK and MRC, consulting fees paid to institution from Genentech, lecture fees from 10.13039/100004325AstraZeneca and 10.13039/100001003Boehringer Ingelheim as well as both lecture fees and support for travel from 10.13039/100019719Chiesi outside of this work. HJCM, ABD, OE, PLG, VCH, EMH, L-PH, LH-W, CJJ, OCL, NIL, MM, DP, KP, MR, RMS, MSe, AShi, ASi, MSt, ALT, CW, MDW and JML declare no competing interests., (© 2023 The Author(s).)