Journal Article Epublish
PubMed: 40519925 DOI: 10.3389/fimmu.2025.1578208
Markers of T cell activation and exhaustion in plasma are associated with persistent symptoms up to 18 months following mild SARS-CoV-2 infection.
Front Immunol 16:1578208
Authors: Thor Ueland, Rebecca Jane Cox, Annika E Michelsen, Elisabeth Berg Fjelltveit, Kari Otterdal, Tuva Dahl, Fan Zhou, Rebecca Elyanow, Pål Aukrust, Bjørn Blomberg, Bente E Halvorsen, Nina Langeland
Affiliations
- Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
- Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
- Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.
- Department of Clinical Science, University of Bergen, Bergen, Norway.
- Adaptive Biotechnologies, Seattle, WA, United States.
- Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
- National Advisory Unit for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway.
Abstract
Background
Persistent symptoms following SARS-CoV-2 is an increasing problem after COVID-19 disease. The pathogenesis of this persistent post Covid-19 Condition (PCC) is, however, largely unknown. We hypothesized that persistent T cell activation and exhaustion play a role in PCC development.
Methods
We examined plasma levels of soluble (s) CD25, TIM-3 and LAG-3, all markers of T cell activation/exhaustion, by enzyme immunoassays in 170 home-isolated and 53 hospitalized patients for up to 18 months after COVID-19 in relation to persistent symptomatology.
Results
Our major findings were: (i) Cases with persistent dyspnea and fatigue had markedly higher sCD25 at 6-18 months with a more modest increase in sTIM-3. (ii) Cases with memory problems at 12-18 months had increased sLAG-3 iii) sCD25 correlated with SARS-CoV-2 antibody titers and microneutralization titers only in cases with PCC while sTIM-3 correlated with these parameters irrespectively of symptoms. iv) Although hospitalized patients had markedly elevated levels of T cell activation/exhausting markers during follow-up, there was no relation to PCC symptoms.
Conclusion
Our study indicates a role for T cell activation/exhaustion in PCC following home isolated COVID-19 infection, with somewhat different patterns of sCD25, sTIM-3 and sLAG-3, but not in hospitalized COVID-19 patients where disease severity may be more important.
MeSH
Cells, Sars-Cov-2, Signs And Symptoms, Covid-19, Immune System Diseases, Severe Acute Respiratory Syndrome-Related Coronavirus, T-Lymphocytes, Infections, Plasma