Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.

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Liew, Felicity, Efstathiou, Claudia, Fontanella, Sara, Richardson, Matthew, Saunders, Ruth, Swieboda, Dawid, Sidhu, Jasmin K, Ascough, Stephanie, Moore, Shona C ORCID: 0000-0001-8610-2806, Mohamed, Noura et al (show 41 more authors) , Nunag, Jose, King, Clara, Leavy, Olivia C, Elneima, Omer, McAuley, Hamish JC, Shikotra, Aarti, Singapuri, Amisha, Sereno, Marco, Harris, Victoria C, Houchen-Wolloff, Linzy, Greening, Neil J, Lone, Nazir I, Thorpe, Matthew, Thompson, AA Roger, Rowland-Jones, Sarah L, Docherty, Annemarie B, Chalmers, James D, Ho, Ling-Pei, Horsley, Alexander, Raman, Betty, Poinasamy, Krisnah, Marks, Michael, Kon, Onn Min, Howard, Luke S, Wootton, Daniel G ORCID: 0000-0002-5903-3881, Quint, Jennifer K, de Silva, Thushan I, Ho, Antonia, Chiu, Christopher, Harrison, Ewen M, Greenhalf, William ORCID: 0000-0002-1865-3195, Baillie, J Kenneth, Semple, Malcolm G ORCID: 0000-0001-9700-0418, Turtle, Lance, Evans, Rachael A, Wain, Louise V, Brightling, Christopher, Thwaites, Ryan S, Openshaw, Peter JM, PHOSP-COVID collaborative group, and ISARIC investigators, (2024) Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease. Nature immunology, 25 (4). pp. 607-621.

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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:	Article
Uncontrolled Keywords:	ISARIC investigators, PHOSP-COVID collaborative group
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	19 Apr 2024 10:36
Last Modified:	26 Apr 2024 16:41
DOI:	10.1038/s41590-024-01778-0
Open Access URL:	https://doi.org/10.1038/s41590-024-01778-0
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3180457