Epigenetic Changes in Long COVID Patients
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorIstituti Clinici Scientifici Maugeri SpA
About this trial
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 criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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).
Trial population
Post COVID-19 patients: Retrospective population of patients that manifested COVID-19 and recovered without sequelae. Long COVID-19 patients: Retrospective and prospective populations of patients that manifested COVID-19 and developed sequelae. The retrospective cohort includes subjects with long COVID-19 with or without cardio-pulmonary symptoms. The prospective cohort includes patients with long COVID-19 and gastrointestinal symptoms. Control Group: Retrospective population of subjects who never had SARS-CoV-2 infection.
Trial design
Design model
Case-control
Time perspective
Other
Treatments tested in this trial
Not listed
Trial groups
1,000 Participants
are grouped into 3 trial groupsGroup A: Post COVID-19 patients
Group B: Long COVID-19 patients
Group C: Control Group
Trial outcomes
Primary outcomes
1
Gene expression profile of peripheral blood cells
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.
Time frame
Baseline2
DNA methylation profile of peripheral blood cells
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.
Time frame
Baseline3
Frequency of peripheral blood immune cell populations
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.
Time frame
BaselineSecondary outcomes
1
Chromatin accessibility in peripheral blood leukocytes
Genome-wide chromatin accessibility will be measured through ATAC-seq in peripheral blood leukocytes and expressed as normalized chromatin accessibility signal.
Time frame
Baseline2
Gut microbiome composition
Gut microbiome composition will be assessed by 16S rRNA sequencing in residual intestinal biopsy samples obtained during clinically indicated endoscopy. Results will be expressed as the relative abundance (%) of bacterial taxa.
Time frame
BaselineOther outcomes
1
Predictive performance of integrated multi-omic models
Integrated predictive models based on clinical, transcriptomic, epigenomic and immunological data will be tested for Long COVID phenotypic stratification and prediction of symptom persistence. Model performance will be expressed as the area under the receiver operating characteristic curve (AUC).
Time frame
Baseline through 12 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Istituti Clinici Scientifici Maugeri SpA
Lead sponsor
IRCCS Ospedale San Raffaele
Collaborator
Istituto Auxologico Italiano
Collaborator
Source ClinicalTrials.gov
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