Azithromycin for sarcoidosis cough: an open label exploratory clinical trial

Background Chronic cough is a distressing symptom for many people with pulmonary sarcoidosis. Continuous treatment with a macrolide antibiotic may improve cough. We aimed to assess the potential efficacy of azithromycin in patients with sarcoidosis and self-reported cough.Methods We did a non-controlled, open label clinical trial of azithromycin 250 mg once daily for 3 months in patients with pulmonary sarcoidosis who reported a chronic cough. The primary outcome was number of coughs in 24 h. Secondary outcomes were cough visual analog scales and quality of life measured using the Leicester Cough Questionnaire and King's Sarcoidosis Questionnaire. Safety outcomes included QTc interval on ECG. Measurements were made at baseline and after one and 3 months of treatment.Results All 21 patients were white, median age 57 years, 9 males/12 females, median 3 years since diagnosis. Five were taking oral corticosteroids and none were taking other immunosuppressants. Twenty patients completed the trial. The median (range) number of coughs in 24 h was 228 (43–1950) at baseline, 122 (20–704) at 1 month, and 81 (16–414) at 3 months (p=0.002, Friedman's test). The median reduction in cough count at 3 months was 49.6%. There were improvements in all patient-reported outcomes. Azithromycin was well tolerated.Conclusion In a non-controlled open-label trial in people with sarcoidosis who reported a chronic cough, 3 months of treatment with azithromycin led to improvements in a range of cough metrics. Azithromycin should be tested as a treatment for sarcoidosis cough in a randomised placebo-controlled trial

Renal artery sympathetic denervation:observations from the UK experience

Background: Renal denervation (RDN) may lower blood pressure (BP); however, it is unclear whether medication changes may be confounding results. Furthermore, limited data exist on pattern of ambulatory blood pressure (ABP) response—particularly in those prescribed aldosterone antagonists at the time of RDN. Methods: We examined all patients treated with RDN for treatment-resistant hypertension in 18 UK centres. Results: Results from 253 patients treated with five technologies are shown. Pre-procedural mean office BP (OBP) was 185/102 mmHg (SD 26/19; n = 253) and mean daytime ABP was 170/98 mmHg (SD 22/16; n = 186). Median number of antihypertensive drugs was 5.0: 96 % ACEi/ARB; 86 % thiazide/loop diuretic and 55 % aldosterone antagonist. OBP, available in 90 % at 11 months follow-up, was 163/93 mmHg (reduction of 22/9 mmHg). ABP, available in 70 % at 8.5 months follow-up, was 158/91 mmHg (fall of 12/7 mmHg). Mean drug changes post RDN were: 0.36 drugs added, 0.91 withdrawn. Dose changes appeared neutral. Quartile analysis by starting ABP showed mean reductions in systolic ABP after RDN of: 0.4; 6.5; 14.5 and 22.1 mmHg, respectively (p < 0.001 for trend). Use of aldosterone antagonist did not predict response (p < 0.2). Conclusion: In 253 patients treated with RDN, office BP fell by 22/9 mmHg. Ambulatory BP fell by 12/7 mmHg, though little response was seen in the lowermost quartile of starting blood pressure. Fall in BP was not explained by medication changes and aldosterone antagonist use did not affect response

The Physical Relationship between Infectivity and Prion Protein Aggregates Is Strain-Dependent

Prions are unconventional infectious agents thought to be primarily composed of PrPSc, a multimeric misfolded conformer of the ubiquitously expressed host-encoded prion protein (PrPC). They cause fatal neurodegenerative diseases in both animals and humans. The disease phenotype is not uniform within species, and stable, self-propagating variations in PrPSc conformation could encode this ‘strain’ diversity. However, much remains to be learned about the physical relationship between the infectious agent and PrPSc aggregation state, and how this varies according to the strain. We applied a sedimentation velocity technique to a panel of natural, biologically cloned strains obtained by propagation of classical and atypical sheep scrapie and BSE infectious sources in transgenic mice expressing ovine PrP. Detergent-solubilized, infected brain homogenates were used as starting material. Solubilization conditions were optimized to separate PrPSc aggregates from PrPC. The distribution of PrPSc and infectivity in the gradient was determined by immunoblotting and mouse bioassay, respectively. As a general feature, a major proteinase K-resistant PrPSc peak was observed in the middle part of the gradient. This population approximately corresponds to multimers of 12–30 PrP molecules, if constituted of PrP only. For two strains, infectivity peaked in a markedly different region of the gradient. This most infectious component sedimented very slowly, suggesting small size oligomers and/or low density PrPSc aggregates. Extending this study to hamster prions passaged in hamster PrP transgenic mice revealed that the highly infectious, slowly sedimenting particles could be a feature of strains able to induce a rapidly lethal disease. Our findings suggest that prion infectious particles are subjected to marked strain-dependent variations, which in turn could influence the strain biological phenotype, in particular the replication dynamics

Crop Updates 2006 - Lupins and Pulses

This session covers sixty six papers from different authors: 2005 LUPIN AND PULSE INDUSTRY HIGHLIGHTS 1. Lupin Peter White, Department of Agriculture 2. Pulses Mark Seymour, Department of Agriculture 3. Monthly rainfall at experimental sites in 2005 4. Acknowledgements Amelia McLarty EDITOR 5. Contributors 6. Background Peter White, Department of Agriculture 2005 REGIONAL ROUNDUP 7. Northern agricultural region Wayne Parker, Department of Agriculture 8. Central agricultural region Ian Pritchard and Bob French, Department of Agriculture 9. Great southern and lakes Rodger Beermier, Department of Agriculture 10. South east region Mark Seymour, Department of Agriculture LUPIN AND PULSE PRODUCTION AGRONOMY AND GENETIC IMPROVEMENT 11. Lupin Peter White, Department of Agriculture 12. Narrow-leafed lupin breeding Bevan Buirchell, Department of Agriculture 13. Progress in the development of pearl lupin (Lupinus mutabilis) for Australian agriculture, Mark Sweetingham1,2, Jon Clements1, Geoff Thomas2, Roger Jones1, Sofia Sipsas1, John Quealy2, Leigh Smith1 and Gordon Francis1 1CLIMA, The University of Western Australia 2Department of Agriculture 14. Molecular genetic markers and lupin breeding, Huaan Yang, Jeffrey Boersma, Bevan Buirchell, Department of Agriculture 15. Construction of a genetic linkage map using MFLP, and identification of molecular markers linked to domestication genes in narrow-leafed lupin (Lupinus augustiflolius L) Jeffrey Boersma1,2, Margaret Pallotta3, Bevan Buirchell1, Chengdao Li1, Krishnapillai Sivasithamparam2 and Huaan Yang1 1Department of Agriculture, 2The University of Western Australia, 3Australian Centre for Plant Functional Genomics, South Australia 16. The first gene-based map of narrow-leafed lupin – location of domestication genes and conserved synteny with Medicago truncatula, M. Nelson1, H. Phan2, S. Ellwood2, P. Moolhuijzen3, M. Bellgard3, J. Hane2, A. Williams2, J. Fos‑Nyarko4, B. Wolko5, M. Książkiewicz5, M. Cakir4, M. Jones4, M. Scobie4, C. O’Lone1, S.J. Barker1, R. Oliver2, and W. Cowling1 1School of Plant Biology, The University of Western Australia, 2Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University, 3Centre for Bioinformatics and Biological Computing, Murdoch University, 4School of Biological Sciences and Biotechnology, SABC, Murdoch University,5Institute of Plant Genetics, Polish Academy of Sciences, Poznań, Poland 17. How does lupin optimum density change row spacing? Bob French and Laurie Maiolo, Department of Agriculture 18. Wide row spacing and seeding rate of lupins with conventional and precision seeding machines Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 19. Influence of row spacing and plant density on lupin competition with annual ryegrass, Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 20. Effect of timing and speed of inter-row cultivation on lupins, Martin Harries, Jo Walker and Steve Cosh, Department of Agriculture 21. The interaction of atrazine herbicide rate and row spacing on lupin seedling survival, Martin Harries and Jo Walker Department of Agriculture 22. The banding of herbicides on lupin row crops, Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 23. Large plot testing of herbicide tolerance of new lupin lines, Wayne Parker, Department of Agriculture 24. Effect of seed source and simazine rate of seedling emergence and growth, Peter White and Greg Shea, Department of Agriculture 25. The effect of lupin row spacing and seeding rate on a following wheat crop, Martin Harries, Jo Walker and Dirranie Kirby, Department of Agriculture 26. Response of crop lupin species to row spacing, Leigh Smith1, Kedar Adhikari1, Jon Clements2 and Patrizia Guantini3, 1Department of Agriculture, 2CLIMA, The University of Western Australia, 3University of Florence, Italy 27. Response of Lupinus mutabilis to lime application and over watering, Peter White, Leigh Smith and Mark Sweetingham, Department of Agriculture 28. Impact of anthracnose on yield of Andromeda lupins, Geoff Thomas, Kedar Adhikari and Katie Bell, Department of Agriculture 29. Survey of lupin root health (in major production areas), Geoff Thomas, Ken Adcock, Katie Bell, Ciara Beard and Anne Smith, Department of Agriculture 30. Development of a generic forecasting and decision support system for diseases in the Western Australian wheatbelt, Tim Maling1, Art Diggle1,2, Debbie Thackray1, Kadambot Siddique1 and Roger Jones1,2 1CLIMA, The University of Western Australia, 2Department of Agriculture 31.Tanjil mutants highly tolerant to metribuzin, Ping Si1, Mark Sweetingham1,2, Bevan Buirchell1,2 and Huaan Yang l,2 1CLIMA, The University of Western Australia, 2Department of Agriculture 32. Precipitation pH vs. yield and functional properties of lupin protein isolate, Vijay Jayasena1, Hui Jun Chih1 and Ken Dods2 1Curtin University of Technology, 2Chemistry Centre 33. Lupin protein isolation with the use of salts, Vijay Jayasena1, Florence Kartawinata1,Ranil Coorey1 and Ken Dods2 1Curtin University of Technology, 2Chemistry Centre 34. Field pea, Mark Seymour, Department of Agriculture 35. Breeding highlights Kerry Regan1,2, Tanveer Khan1,2, Stuart Morgan1 and Phillip Chambers1 1Department of Agriculture, 2CLIMA, The University of Western Australia 36. Variety evaluation, Kerry Regan1,2, Tanveer Khan1,2, Jenny Garlinge1 and Rod Hunter1 1Department of Agriculture, 2CLIMA, The University of Western Australia 37. Days to flowering of field pea varieties throughout WA Mark Seymour1, Ian Pritchard1, Rodger Beermier1, Pam Burgess1 and Dr Eric Armstrong2 Department of Agriculture, 2NSW Department of Primary Industries, Wagga Wagga 38. Semi-leafless field peas yield more, with less ryegrass seed set, in narrow rows, Glen Riethmuller, Department of Agriculture 39. Swathing, stripping and other innovative ways to harvest field peas, Mark Seymour, Ian Pritchard, Rodger Beermier and Pam Burgess, Department of Agriculture 40. Pulse demonstrations, Ian Pritchard, Wayne Parker, Greg Shea, Department of Agriculture 41. Field pea extension – focus on field peas 2005, Ian Pritchard, Department of Agriculture 42. Field pea blackspot disease in 2005: Prediction versus reality, Moin Salam, Jean Galloway, Pip Payne, Bill MacLeod and Art Diggle, Department of Agriculture 43. Pea seed-borne mosaic virus in pulses: Screening for seed quality defects and virus resistance, Rohan Prince, Brenda Coutts and Roger Jones, Department of Agriculture, and CLIMA, The University of Western Australia 44. Yield losses from sowing field peas infected with pea seed-borne mosaic virus, Rohan Prince, Brenda Coutts and Roger Jones, Department of Agriculture, and CLIMA, The University of Western Australia 45. Desi chickpea, Wayne Parker, Department of Agriculture 46. Breeding highlights, Tanveer Khan 1,2, Pooran Gaur3, Kadambot Siddique2, Heather Clarke2, Stuart Morgan1and Alan Harris1, 1Department of Agriculture2CLIMA, The University of Western Australia, 3International Crop Research Institute for Semi Arid Tropics (ICRISAT), India 47. National chickpea improvement program, Kerry Regan1, Ted Knights2 and Kristy Hobson3,1Department of Agriculture, 2Agriculture New South Wales 3Department of Primary Industries, Victoria 48. Chickpea breeding lines in CVT exhibit excellent ascochyta blight resistance, Tanveer Khan1,2, Alan Harris1, Stuart Morgan1 and Kerry Regan1,2, 1Department of Agriculture, 2CLIMA, The University of Western Australia 49. Variety evaluation, Kerry Regan1,2, Tanveer Khan1,2, Jenny Garlinge2 and Rod Hunter2, 1CLIMA, The University of Western Australia 2Department of Agriculture 50. Desi chickpeas for the wheatbelt, Wayne Parker and Ian Pritchard, Department of Agriculture 51. Large scale demonstration of new chickpea varieties, Wayne Parker, MurrayBlyth, Steve Cosh, Dirranie Kirby and Chris Matthews, Department of Agriculture 52. Ascochyta management with new chickpeas, Martin Harries, Bill MacLeod, Murray Blyth and Jo Walker, Department of Agriculture 53. Management of ascochyta blight in improved chickpea varieties, Bill MacLeod1, Colin Hanbury2, Pip Payne1, Martin Harries1, Murray Blyth1, Tanveer Khan1,2, Kadambot Siddique2, 1Department of Agriculture, 2CLIMA, The University of Western Australia 54. Botrytis grey mould of chickpea, Bill MacLeod, Department of Agriculture 55. Kabuli chickpea, Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 56. New ascochyta blight resistant, high quality kabuli chickpea varieties, Kerry Regan1,2, Kadambot Siddique2, Tim Pope2 and Mike Baker1, 1Department of Agriculture, 2CLIMA, The University of Western Australia 57. Crop production and disease management of Almaz and Nafice, Kerry Regan and Bill MacLeod, Department of Agriculture, and CLIMA, The University of Western Australia 58. Faba bean,Mark Seymour, Department of Agriculture 59. Germplasm evaluation – faba bean, Mark Seymour1, Tim Pope2, Peter White1, Martin Harries1, Murray Blyth1, Rodger Beermier1, Pam Burgess1 and Leanne Young1,1Department of Agriculture, 2CLIMA, The University of Western Australia 60. Factors affecting seed coat colour of faba bean during storage, Syed Muhammad Nasar-Abbas1, Julie Plummer1, Kadambot Siddique2, Peter White 3, D. Harris4 and Ken Dods4.1The University of Western Australia, 2CLIMA, The University of Western Australia, 3Department of Agriculture, 4Chemistry Centre 61. Lentil,Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 62. Variety and germplasm evaluation, Kerry Regan1,2, Tim Pope2, Leanne Young1, Phill Chambers1, Alan Harris1, Wayne Parker1 and Michael Materne3, 1Department of Agriculture 2CLIMA, The University of Western Australia, 3Department of Primary Industries, Victoria Pulse species 63. Land suitability for production of different crop species in Western Australia, Peter White, Dennis van Gool, and Mike Baker, Department of Agriculture 64. Genomic synteny in legumes: Application to crop breeding, Huyen Phan1, Simon Ellwood1, J. Hane1, Angela Williams1, R. Ford2, S. Thomas3 and Richard Oliver1,1Australian Centre of Necrotrophic Plant Pathogens, Murdoch University 2BioMarka, School of Agriculture and Food Systems, ILFR, University of Melbourne 3NSW Department of Primary Industries 65. ALOSCA – Development of a dry flow legume seed inoculant, Rory Coffey and Chris Poole, ALOSCA Technologies Pty Ltd 66. Genetic dissection of resistance to fungal necrotrophs in Medicago truncatula, Simon Ellwood1, Theo Pfaff1, Judith Lichtenzveig12, Lars Kamphuis1, Nola D\u27Souza1, Angela Williams1, Emma Groves1, Karam Singh2 and Richard Oliver1 1Australian Centre of Necrotrophic Plant Pathogens, Murdoch University, 2CSIRO Plant Industry APPENDIX I: LIST OF COMMON ACRONYM

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

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

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research