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.


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 http://creativecommons.org/licenses/by/4.0/.

Cite as

Liew, F., Efstathiou, C., Fontanella, S., Richardson, M., Saunders, R., Swieboda, D., Sidhu, J., Ascough, S., Moore, S., Mohamed, N., Nunag, J., King, C., Leavy, O., Elneima, O., McAuley, H., Shikotra, A., Singapuri, A., Sereno, M., Harris, V., Houchen-Wollof, L., Greening, N., Lone, N., Thorpe, M., Thompson, A., Rowland-Jones, S., Docherty, A., Chalmers, J., Ho, L., Horsley, A., Raman, B., Poinasamy, K., Marks, M., Kon, O., Howard, L., Wootton, D., Quint, J., de Silva, T., Ho, A., Chiu, C., Harrison, E., Greenhalf, W., Baillie, J., Semple, M., Turtle, L., Evans, R., Wain, L., Brightling, C., Thwaites, R., Openshaw, P., The PHOSP-COVID Collaborative Group & ISARIC Investigators 2024, 'Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease', Nature Immunology, 25, pp. 607-621. https://doi.org/10.1038/s41590-024-01778-0

Downloadable citations

Download HTML citationHTML Download BIB citationBIB Download RIS citationRIS
Last updated: 23 May 2024
Was this page helpful?