Liew, F. et al. (2024) Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease. Nature Immunology, 25(4), pp. 607-621. (doi: 10.1038/s41590-024-01778-0) (PMID:38589621)
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Abstract
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 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.
| Item Type: | Articles (Letter) |
|---|---|
| Additional Information: | 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 (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 Medical Research Council (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference: C18616/A25153). Other grants which 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 (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU 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 (HDR UK) [grant code: 2021.0155], Medical Research Council [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 Medical Research Council (MRC) EMINENT Network (MR/R502121/1) which is co-funded by GSK; the Comprehensive Local Research Networks (CLRNs); the MRC HIC-Vac network (MR/R005982/1); RSV Consortium in Europe (RESCEU) Horizon 2020 Framework Grant 116019. FL is supported by an MRC clinical training fellowship [award MR/W000970/1]. CE is funded by NIHR [grant P91258-4]. LPH is supported by Oxford NIHR Biomedical Research Centre. AART is supported by a BHF Intermediate Clinical Fellowship (FS/18/13/33281). SLRJ receives support from UKRI, GCRF, Rosetrees Trust, BHIVA, EDCTP, Globvac. JDC has grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis and Insmed. RAE holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). AH is currently supported by UK Research and Innovation. NIHR and NIHR Manchester BRC. BR receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. DGW is supported by an NIHR Advanced Fellowship. AH has received support from MRC and for the Coronavirus Immunology Consortium (MR/V028448/1). LT is supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections (NIHR200907) at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. LVW has received support from UKRI, GSK/Asthma + Lung UK and NIHR for this study. MGS has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. JKB 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 DHSC, DID, NIHR, MRC, the Wellcome Trust, UK-HAS, the National Health Service, or the Department of Health. PJMO is supported by a NIHR Senior Investigator Award [award 201385]. |
| Keywords: | COVID-19, SARS-CoV-2, inflammation, post-viral sequelae, innate immunity, 73 complement, long COVID, PASC. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Scott, Dr Janet and Ho, Dr Antonia |
| Authors: | Liew, F., Efstathiou, C., Fontanella, S., Richardson, M., Saunders, R., Swieboda, D., Sidhu, J. K., Ascough, S., Moore, S. C., Mohamed, N., Nunag, J., King, C., Leavy, O. C., Elneima, O., McAuley, H. J.C., Shikotra, A., Singapuri, A., Sereno, M., Harris, V. C., Houchen-Wollof, L., Greening, N. J., Lone, N. I., Thorpe, M., Thompson, A. A. R., Rowland-Jones, S. L., Docherty, A. B., Chalmers, J. D., Ho, L.-P., Horsley, A., Raman, B., Poinasamy, K., Marks, M., Kon, O. M., Howard, L. S., Wootton, D. G., Quint, J. K., de Silva, T. I., Ho, A., Chiu, C., Harrison, E. M., Greenhalf, W., Baillie, J. K., Semple, M. G., Turtle, L., Evans, R. A., Wain, L. V., Brightling, C., Thwaites, R. S., Openshaw, P. J.M., PHOSP-COVID collaborative group, , and ISARIC4C Investigators, |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Nature Immunology |
| Publisher: | Nature Research |
| ISSN: | 1529-2908 |
| ISSN (Online): | 1529-2916 |
| Published Online: | 08 April 2024 |
| Copyright Holders: | Copyright © 2024 The Author(s) |
| First Published: | First published in Nature Immunology 25(4):607-621 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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