Journal Article

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

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

2025

Overview

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.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Adult / Aged / Asymptomatic / Biomarkers / Biomarkers - blood / Chronic illnesses / COVID-19 - blood / COVID-19 - immunology / COVID-19 - pathology / Cytokines / Cytokines - blood / Dyspnea / Enzyme-linked immunosorbent assay / Female / Females / Health aspects / Hospital patients / Hospitalization / Humans / Immune response / Infection / Infections / Inflammation - blood / Inflammation - immunology / Intercellular Adhesion Molecule-1 - blood / Interleukin-6 - blood / Long COVID / Male / Middle Aged / Pantoprazole / Patients / Rites, ceremonies and celebrations / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Spallanzani, Lazzaro / T cells / T-Lymphocytes - immunology / Tumor necrosis factor / Tumor necrosis factor-TNF