Identification of soluble biomarkers that associate with distinct manifestations of long COVID

Gao, Yu, Curtis, Cai, Adamo, Sarah, Biteus, Elsa, Kamal, Habiba, Dager, Lena, Miners, Kelly L., Llewellyn-Lacey, Sian, Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938, Amratia, Pragati, Bentley, Kirsten ORCID: https://orcid.org/0000-0002-6619-2098, Kollnberger, Simon, Wu, Jinghua, Akhirunnesa, Mily, Jones, Samantha, Julin, Per, Lidman, Christer, Stanton, Richard ORCID: https://orcid.org/0000-0002-6799-1182, Goepfert, Paul, Peluso, Michael, Deeks, Steven, Davies, Helen, Aleman, Soo, Buggert, Marcus and Price, David ORCID: https://orcid.org/0000-0001-9416-2737 2025. Identification of soluble biomarkers that associate with distinct manifestations of long COVID. Nature Immunology 26 , 692–705. 10.1038/s41590-025-02135-5

PDF - Published Version Available under License Creative Commons Attribution. Download (13MB)

Abstract

Long coronavirus disease (COVID) is a heterogeneous clinical condition of uncertain etiology triggered by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we used ultrasensitive approaches to profile the immune system and the plasma proteome in healthy convalescent individuals and individuals with long COVID, spanning geographically independent cohorts from Sweden and the United Kingdom. Symptomatic disease was not consistently associated with quantitative differences in immune cell lineage composition or antiviral T cell immunity. Healthy convalescent individuals nonetheless exhibited higher titers of neutralizing antibodies against SARS-CoV-2 than individuals with long COVID, and extensive phenotypic analyses revealed a subtle increase in the expression of some co-inhibitory receptors, most notably PD-1 and TIM-3, among SARS-CoV-2 nonspike-specific CD8+ T cells in individuals with long COVID. We further identified a shared plasma biomarker signature of disease linking breathlessness with apoptotic inflammatory networks centered on various proteins, including CCL3, CD40, IKBKG, IL-18 and IRAK1, and dysregulated pathways associated with cell cycle progression, lung injury and platelet activation, which could potentially inform the diagnosis and treatment of long COVID.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Nature Research
ISSN:	1529-2908
Date of First Compliant Deposit:	7 May 2025
Date of Acceptance:	14 March 2025
Last Modified:	07 May 2025 12:12
URI:	https://orca.cardiff.ac.uk/id/eprint/178027

Actions (repository staff only)

Edit Item