The goal of this observational study is to improve the understanding of the biological mechanisms underlying long COVID and to identify molecular biomarkers that may support its diagnosis, prognosis, and future precision medicine approaches in adults with long COVID, adults who have fully recovered from COVID-19, and healthy control participants.
The main questions it aims to answer are:
* What molecular, immunological, epigenetic, and microbiome profiles distinguish individuals with long COVID from recovered COVID-19 participants and healthy controls?
* How are viral persistence, immune dysregulation, and alterations in the gut-immune axis associated with the development and clinical manifestations of long COVID?
* Which molecular biomarkers may improve disease diagnosis, patient stratification, and the identification of potential therapeutic targets?
Participants will:
* Undergo clinical evaluation and provide information about their medical history and symptoms.
* Provide biological samples, including blood and, when clinically indicated, intestinal biopsy tissue collected during routine colonoscopy procedures.
* Undergo comprehensive molecular analyses, including immunological, epigenetic, transcriptomic, proteomic, and microbiome profiling.
* Have their clinical and molecular data integrated using advanced computational approaches to identify biological signatures associated with long COVID.
The results of this study may improve the understanding of the biological mechanisms underlying long COVID and support the development of novel biomarkers and future precision medicine approaches for diagnosis, prognosis, patient stratification, and therapeutic target identification.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
Accepted
Inclusion Criteria (Post COVID-19 patients):
* Age ≥ 18 years.
* Previous SARS-CoV-2 infection documented by molecular or serological testing.
* Absence of persistent symptoms 2 months after acute infection.
* Willingness to provide written informed consent.
Inclusion Criteria (Long COVID-19 patients):
* Age ≥ 18 years.
* Previous SARS-CoV-2 infection documented by molecular or serological testing.
* Persistent symptoms at least 2 months after acute infection, according to the WHO definition of long COVID \[https://www.who.int/europe/news-room/fact-sheets/item/post-covid-19-condition\].
* Willingness to provide written informed consent.
Inclusion Criteria (Control Group):
* Age ≥ 18 years.
* No previous SARS-CoV-2 infection (documented by serology).
* Blood sample collected according to the COVID-BioVac protocol (NCT05276388) before the first administration of the SARS-CoV-2 vaccine.
* Willingness to provide written informed consent.
Exclusion Criteria:
* Inability to provide informed consent.
* Presence of severe systemic autoimmune diseases or congenital/acquired immunodeficiencies that may confound the interpretation of immunological data.
* Current systemic immunosuppressive therapy or treatment within the last 6 months prior to enrollment.
* Active malignancies or those treated within the last 12 months (except basal or squamous cell carcinomas in situ).
* Pregnancy or breastfeeding at the time of enrollment.
* Any other clinical condition that, in the investigator's opinion, could compromise the reliability of the data collected.
Primary outcome measure(s)
Gene expression profile of peripheral blood cells — Baseline Transcriptomic profiling will be performed in peripheral blood leukocytes using RNA sequencing. Gene expression will be expressed as normalized gene expression counts. Differential transcript abundance will be compared across participants with Long COVID with cardiopulmonary manifestations, Long COVID without cardiopulmonary manifestations, COVID-19 participants without persistent sequelae, and pre-pandemic healthy controls.
DNA methylation profile of peripheral blood cells — Baseline Genome-wide DNA methylation will be measured using the EPIC-v2 array and/or whole-genome bisulfite sequencing. Results will be expressed as DNA methylation β-values or methylation percentages (%). Methylation profiles will be compared across study groups.
Frequency of peripheral blood immune cell populations — Baseline Frequency of circulating immune cell subsets will be measured by multiparameter flow cytometry. Results will be expressed as the percentage (%) of the parent cell population. The analyses will include investigation of CD4+ T cells, CD8+ T cells, NK cells, B cells and regulatory T cells. Immune profiles will be compared among study groups.
Trial sites (3)
Facility
City
Region
Status
Istituto Auxologico Italiano
Cusano Milanino
Milano
Ospedale San Raffaele S.r.l.
Milan
Italy
Istituti Clinici Scientifici Maugeri
Pavia
Italy
More Istituti Clinici Scientifici Maugeri SpA trials in Italy
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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