# Inflammatory Milieu and Specific T-Cell Response Observed Three Months and One Year After SARS-CoV-2 Infection in Long COVID Subjects

**Authors:** Eleonora Cimini, Alessandra Vergori, Claudia Cimaglia, Eleonora Tartaglia, Stefania Notari, Francesca Colavita, Giulia Matusali, Ilaria Mastrorosa, Valentina Mazzotta, Pierangelo Chinello, Paola Mencarini, Maria Letizia Giancola, Amina Abdeddaim, Rita Casetti, Germana Grassi, Simona Gili, Flavia Cristofanelli, Fabrizio Maggi, Pierluca Piselli, Enrico Girardi, Andrea Antinori, Marta Camici

PMC · DOI: 10.3390/ijms262110412 · International Journal of Molecular Sciences · 2025-10-27

## TL;DR

This study finds that long COVID is linked to persistent inflammation and T-cell responses up to a year after SARS-CoV-2 infection.

## Contribution

The study identifies long-term immune changes in long COVID patients, including persistent T-cell memory and altered inflammatory markers.

## Key findings

- LC patients showed elevated IL-8 and TNF-α at three months post-infection.
- SARS-CoV-2-specific T-cell responses persisted at one year, indicating memory T-cell formation.
- Inflammatory and coagulation markers were altered at three months, with some changes lasting up to one year.

## Abstract

Long COVID (LC) is characterized by a wide range of symptoms, the causes of which remain unclear. We investigated associations between inflammatory and coagulation factors, adaptive immune response to SARS-CoV-2, and LC. We enrolled 196 unvaccinated individuals with SARS-CoV-2 (March–June 2020). Blood samples were collected at three (T3M) and twelve (T12M) months post infection. Plasma concentrations of coagulation factors (D-Dimer, E-Selectin, ICAM-1, VCAM-1) and inflammatory markers (IL-6, IL-8, TNF-α, IL-1β) were measured by ELISA, and SARS-CoV-2-specific T-cell response was assessed by Elispot. LC occurred in 66/196 patients (34%); 77.8% had been hospitalized. Respiratory symptoms were present in 54%, fatigue in 30%, and neuropsychological symptoms in 14%. At T3M, hospitalized patients exhibited higher levels of ICAM-1, VCAM-1, and IL-6, along with increased immunoreactivity. LC patients exhibited elevated IL-8 and TNF-α and enhanced immunoreactivity at T3M, though these differences were not observed at T12M. Inflammatory and coagulation markers were altered at three months after acute infection, with some changes persisting at one year, suggesting a long-term immunological impact of SARS-CoV-2 on the inflammatory response. A SARS-CoV-2-specific T-cell response was still detectable at T12M, albeit at a lower level than at T3M, suggesting the persistence of protective memory T-cells beyond the acute phase.

## Linked entities

- **Proteins:** Sele (selectin, endothelial cell), ICAM1 (intercellular adhesion molecule 1), VCAM1 (vascular cell adhesion molecule 1), IL6 (interleukin 6), CXCL8 (C-X-C motif chemokine ligand 8), TNF (tumor necrosis factor), IL1B (interleukin 1 beta)
- **Diseases:** SARS-CoV-2 (MONDO:0100096)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, SELE (selectin E) [NCBI Gene 6401] {aka CD62E, ELAM, ELAM1, ESEL, LECAM2, selectin-e}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}
- **Diseases:** fatigue (MESH:D005221), Respiratory symptoms (MESH:D012818), Inflammatory (MESH:D007249), coagulation (MESH:D001778), neuropsychological symptoms (MESH:D012816), LC (MESH:D000094024), infection (MESH:D007239), SARS-CoV-2 Infection (MESH:D000086382)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** T12M

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12607545/full.md

## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC12607545/full.md

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Source: https://tomesphere.com/paper/PMC12607545