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Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/29394
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dc.contributor.authorLiew, F-
dc.contributor.authorEfstathiou, C-
dc.contributor.authorFontanella, S-
dc.contributor.authorRichardson, M-
dc.contributor.authorSaunders, R-
dc.contributor.authorSwieboda, D-
dc.contributor.authorSidhu, JK-
dc.contributor.authorAscough, S-
dc.contributor.authorMoore, SC-
dc.contributor.authorMohamed, N-
dc.contributor.authorNunag, J-
dc.contributor.authorKing, C-
dc.contributor.authorLeavy, OC-
dc.contributor.authorElneima, O-
dc.contributor.authorMcAuley, HJC-
dc.contributor.authorShikotra, A-
dc.contributor.authorSingapuri, A-
dc.contributor.authorSereno, M-
dc.contributor.authorHarris, VC-
dc.contributor.authorHouchen-Wolloff, L-
dc.contributor.authorGreening, NJ-
dc.contributor.authorLone, NI-
dc.contributor.authorThorpe, M-
dc.contributor.authorThompson, AAR-
dc.contributor.authorRowland-Jones, SL-
dc.contributor.authorDocherty, AB-
dc.contributor.authorChalmers, JD-
dc.contributor.authorHo, LP-
dc.contributor.authorHorsley, A-
dc.contributor.authorRaman, B-
dc.contributor.authorPoinasamy, K-
dc.contributor.authorMarks, M-
dc.contributor.authorKon, OM-
dc.contributor.authorHoward, LS-
dc.contributor.authorWootton, DG-
dc.contributor.authorQuint, JK-
dc.contributor.authorde Silva, TI-
dc.contributor.authorHo, A-
dc.contributor.authorChiu, C-
dc.contributor.authorHarrison, EM-
dc.contributor.authorGreenhalf, W-
dc.contributor.authorBaillie, JK-
dc.contributor.authorSemple, MG-
dc.contributor.authorTurtle, L-
dc.contributor.authorEvans, RA-
dc.contributor.authorWain, LV-
dc.contributor.authorBrightling, C-
dc.contributor.authorThwaites, RS-
dc.contributor.authorOpenshaw, PJM-
dc.contributor.authorAbel, K-
dc.contributor.authorAdamali, H-
dc.contributor.authorAdeloye, D-
dc.contributor.authorAdeyemi, O-
dc.contributor.authorAdrego, R-
dc.contributor.authorJimenez, LA-
dc.contributor.authorAhmad, S-
dc.contributor.authorHaider, NA-
dc.contributor.authorAhmed, R-
dc.contributor.authorAhwireng, N-
dc.contributor.authorAinsworth, M-
dc.contributor.authorAlamoudi, A-
dc.contributor.authorAli, M-
dc.contributor.authorAljaroof, M-
dc.contributor.authorAllan, L-
dc.contributor.authorAllen, R-
dc.contributor.authorAllerton, L-
dc.contributor.authorAllsop, L-
dc.contributor.authorAllt, AM-
dc.contributor.authorAlmeida, P-
dc.contributor.authorAl-Sheklly, B-
dc.contributor.authorAltmann, D-
dc.contributor.authorCorral, MA-
dc.contributor.authorAmoils, S-
dc.contributor.authorAnderson, D-
dc.contributor.authorAntoniades, C-
dc.contributor.authorArbane, G-
dc.contributor.authorArias, AM-
dc.contributor.authorArmour, C-
dc.contributor.authorArmstrong, L-
dc.contributor.authorArmstrong, N-
dc.contributor.authorArnold, D-
dc.contributor.authorArnold, H-
dc.contributor.authorAshish, A-
dc.contributor.authorAshworth, A-
dc.contributor.authorAshworth, M-
dc.contributor.authorAslani, S-
dc.contributor.authorAssefa-Kebede, H-
dc.contributor.authorAtkin, P-
dc.contributor.authorAtkin, C-
dc.contributor.authorAul, R-
dc.contributor.authorAung, H-
dc.contributor.authorAustin, L-
dc.contributor.authorAvram, C-
dc.contributor.authorAvramidis, N-
dc.contributor.authorAyoub, A-
dc.contributor.authorBabores, M-
dc.contributor.authorBaggott, R-
dc.contributor.authorBagshaw, J-
dc.contributor.authorBaguley, D-
dc.contributor.authorBailey, E-
dc.contributor.otherPHOSP-COVID collaborative group-
dc.contributor.otherISARIC investigators-
dc.date.accessioned2024-07-21T15:58:52Z-
dc.date.available2024-07-21T15:58:52Z-
dc.date.issued2024-04-08-
dc.identifierORCiD: Claudia Efstathiou https://orcid.org/0000-0001-6125-8126-
dc.identifierORCiD: Shona C. Moore https://orcid.org/0000-0001-8610-2806-
dc.identifierORCiD: Jose Nunag https://orcid.org/0000-0002-4218-0500-
dc.identifierORCiD: Amisha Singapuri https://orcid.org/0009-0002-4711-7516-
dc.identifierORCiD: Marco Sereno https://orcid.org/0000-0003-4573-9303-
dc.identifierORCiD: Linzy Houchen-Wolloff https://orcid.org/0000-0003-4940-8835-
dc.identifierORCiD: Neil J. Greening https://orcid.org/0000-0003-0453-7529-
dc.identifierORCiD: Nazir I. Lone https://orcid.org/0000-0003-2707-2779-
dc.identifierORCiD: A. A. Roger Thompson https://orcid.org/0000-0002-0717-4551-
dc.identifierORCiD: Claire M Nolan https://orcid.org/0000-0001-9067-599X-
dc.identifier.citationLiew, F. et al. for the PHOSP-COVID collaborative group and the ISARIC investigators (2024) 'Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease', Nature Immunology, 2024, 25 (4), pp. 607 - 621. doi: 10.1038/s41590-024-01778-0.en_US
dc.identifier.issn1529-2908-
dc.identifier.urihttps://bura.brunel.ac.uk/handle/2438/29394-
dc.descriptionData availability: This is an open access article under the CC BY 4.0 license. The PHOSP-COVID protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online at ref. 76. Access to these materials can be granted by contacting phosp@leicester.ac.uk and Phospcontracts@leicester.ac.uk. The ISARIC4C protocol, data sharing and publication policy are available at https://isaric4c.net. ISARIC4C’s Independent Data and Material Access Committee welcomes applications for access to data and materials (https://isaric4c.net). The datasets used in the study contain extensive clinical information at an individual level that prevent them from being deposited in an public depository due to data protection policies of the study. Study data can only be accessed via the ODAP, a protected research environment. All data used in this study are available within ODAP and accessible under reasonable request. Data access criteria and information about how to request access is available online at ref. 76. If criteria are met and a request is made, access can be gained by signing the eDRIS user agreement.en_US
dc.descriptionCode availability: Code was written within the ODAP, using R v4.2.0 and publicly available packages (‘data.table v1.14.2’, ‘EnvStats v2.7.0’, ‘tidyverse v1.3.2’, ‘lme4 v1.1-32’, ‘caret v6.0-93’, ‘glmnet v4.1-6’, ‘mdatools v0.14.0’, ‘ggpubbr v0.4.0’, ‘ggplot2 v3.3.6’, ‘bootnet v1.5.6’ and ‘qgraph v1.9.8’ packages). No new algorithms or functions were created and code used in-built functions in listed packages available on CRAN. The code used to generate data and to analyze data is publicly available at https://github.com/isaric4c/wiki/wiki/ISARIC; https://github.com/SurgicalInformatics/cocin_cc and https://github.com/ClaudiaEfstath/PHOSP_Olink_NatImm.-
dc.description.abstractOne 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 understood1. 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.en_US
dc.description.sponsorshipThis research used data assets made available by ODAP as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref. MC_PC_20058). This work is supported by the following grants: the PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research (NIHR; grant references MR/V027859/1 and COV0319). ISARIC4C is supported by grants from the National Institute for Health and Care Research (award CO-CIN-01) and the MRC (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference C18616/A25153). Other grants that have supported this work include the UK Coronavirus Immunology Consortium (funder reference 1257927), the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant IS-BRC-1215-20013), the Health Protection Research Unit in Respiratory Infections at Imperial College London and NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, (NIHR award 200907), Wellcome Trust and Department for International Development (215091/Z/18/Z), Health Data Research UK (grant code 2021.0155), MRC (grant code MC_UU_12014/12) and NIHR Clinical Research Network for providing infrastructure support for this research. We also acknowledge the support of the MRC EMINENT Network (MR/R502121/1), which is cofunded by GSK, the Comprehensive Local Research Networks, the MRC HIC-Vac network (MR/R005982/1) and the RSV Consortium in Europe Horizon 2020 Framework Grant 116019. F.L. is supported by an MRC clinical training fellowship (award MR/W000970/1). C.E. is funded by NIHR (grant P91258-4). L.-P.H. is supported by Oxford NIHR Biomedical Research Centre. A.A.R.T. is supported by a British Heart Foundation (BHF) Intermediate Clinical Fellowship (FS/18/13/33281). S.L.R.-J. receives support from UK Research and Innovation (UKRI), Global Challenges Research Fund (GCRF), Rosetrees Trust, British HIV association (BHIVA), European & Developing Countries Clinical Trials Partnership (EDCTP) and Globvac. J.D.C. has grants from AstraZeneca, Boehringer Ingelheim, GSK, Gilead Sciences, Grifols, Novartis and Insmed. R.A.E. holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). A. Horsley is currently supported by UK Research and Innovation, NIHR and NIHR Manchester BRC. B.R. receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. D.G.W. is supported by an NIHR Advanced Fellowship. A. Ho has received support from MRC and for the Coronavirus Immunology Consortium (MR/V028448/1). L.T. is supported by the US Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085 and the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections (NIHR200907) at the University of Liverpool in partnership with UK Health Security Agency (UK-HSA), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. L.V.W. has received support from UKRI, GSK/Asthma and Lung UK and NIHR for this study. M.G.S. has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool. J.K.B. is supported by the Wellcome Trust (223164/Z/21/Z) and UKRI (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1 and MC_PC_20029). The funders were not involved in the study design, interpretation of data or writing of this manuscript. The views expressed are those of the authors and not necessarily those of the Department of Health and Social Care (DHSC), the Department for International Development (DID), NIHR, MRC, the Wellcome Trust, UK-HSA, the National Health Service or the Department of Health. P.J.M.O. is supported by a NIHR Senior Investigator Award (award 201385). We thank all the participants and their families. We thank the many research administrators, health-care and social-care professionals who contributed to setting up and delivering the PHOSP-COVID study at all of the 65 NHS trusts/health boards and 25 research institutions across the United Kingdom, as well as those who contributed to setting up and delivering the ISARIC4C study at 305 NHS trusts/health boards. We also thank all the supporting staff at the NIHR Clinical Research Network, Health Research Authority, Research Ethics Committee, Department of Health and Social Care, Public Health Scotland and Public Health England. We thank K. Holmes at the NIHR Office for Clinical Research Infrastructure for her support in coordinating the charities group. The PHOSP-COVID industry framework was formed to provide advice and support in commercial discussions, and we thank the Association of the British Pharmaceutical Industry as well the NIHR Office for Clinical Research Infrastructure for coordinating this. We are very grateful to all the charities that have provided insight to the study: Action Pulmonary Fibrosis, Alzheimer’s Research UK, Asthma and Lung UK, British Heart Foundation, Diabetes UK, Cystic Fibrosis Trust, Kidney Research UK, MQ Mental Health, Muscular Dystrophy UK, Stroke Association Blood Cancer UK, McPin Foundations and Versus Arthritis. We thank the NIHR Leicester Biomedical Research Centre patient and public involvement group and Long Covid Support. We also thank G. Khandaker and D. C. Newcomb who provided valuable feedback on this work. Extended Data Fig. 10 was created using Biorender.en_US
dc.format.extent607 - 621-
dc.format.mediumPrint-Electronic-
dc.language.isoen_USen_US
dc.publisherNature Research (part of Springer Nature)en_US
dc.rightsCopyright © 2024 The Authors. Rights and permissions: Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.-
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.subjectinflammasomeen_US
dc.subjectinflammationen_US
dc.subjectinnate immunityen_US
dc.titleLarge-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of diseaseen_US
dc.typeArticleen_US
dc.date.dateAccepted2024-02-06-
dc.identifier.doihttps://doi.org/10.1038/s41590-024-01778-0-
dc.relation.isPartOfNature Immunology-
pubs.issue4-
pubs.publication-statusPublished-
pubs.volume25-
dc.identifier.eissn1529-2916-
dc.rights.licensehttps://creativecommons.org/licenses/by/4.0/lealcode.en-
dc.rights.holderThe Authors-
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