Characterization of the Immunometabolic Signature in Long COVID-19. (LoCo-ImMet)

The primary objective of this study is to identify immunometabolic signatures associated with Long COVID in plasma and peripheral blood mononuclear cells (PBMC).

Study Overview

• Status: Completed
• Conditions: Long COVID
• Intervention / Treatment: Biological: Blood sample (at inclusion and 6 months later); Other: Patient questionnaires (at inclusion and 6 months later)

Detailed Description

The mechanisms underlying Long COVID remain poorly understood. Among the symptoms most frequently reported by patients with long COVID, some (fatigue, neurocognitive disorders, muscular weakness) are similar to those reported by patients with innate or acquired abnormalities in energy metabolism, suggesting that metabolic changes could play a role in the disease. On the other hand, other studies have shown that COVID-19 induces an immune dysregulation that could persist after recovery.

The hypothesis of this study is that there are subtle but detectable immunometabolic changes in plasma and PBMC of patients with long COVID. The identification of these specific signatures would help to better understand the physiopathology of this disease and to identify possible therapeutic strategies .

The primary objective of this study is to identify immunometabolic signatures in plasma and peripheral blood mononuclear cells (PBMC) of patients with long COVID, as compared to patients who recovered from COVID-19 without prolonged symptoms.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • Angers University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

A/ Inclusion Criteria:

• For all patients:

  • Age > 18 years
  • Symptomatic COVID-19 diagnosed after 01JAN2021, confirmed by RT-PCR or Antigen test
  • Last SARS-CoV-2 infection diagnosed more than 12 weeks before inclusion
  • Patient covered by the French health insurance
  • Signature of the informed consent

• For patient with Long COVID :

  • At least one of the following symptoms during the week preceding inclusion: abnormal fatigue, dyspnoea sine materia, abnormal pain (chest, joint, muscle, headache), unusual neurocognitive disorders (concentration disorders, "brain fog", language/memory disorders, paraesthesia)
  • Absence of Return to Usual Health after SARS-CoV-2 infection (patient declaration)
  • Absence of alternative diagnosis for the symptoms

• For COVID-19 recovered patient (Control) :

  • None of the following symptoms in the 3 week before inclusion: abnormal fatigue, dyspnoea sine materia, abnormal pain (chest, joint, muscle, headache), unusual neurocognitive disorders (concentration disorders, "brain fog", language/memory disorders, paraesthesia)
  • Return to Usual Health after SARS-CoV-2 infection (patient declaration)

B/ Exclusion Criteria:

• History of severe COVID-19 (Hospitalization)
• Symptoms caused by sequelae of SARS-CoV-2 infection (in particular, persistence of lung parenchymal abnormalities : pulmonary fibrosis, persistent alveolitis on CT-Scan)
• Significant Depression or anxiety symptoms, as assessed by a > 10 score on the A or D items of the Hospital anxiety and depression scale (HAD)

• Presence of one of the following diseases:

  • Inborn errors of metabolism
  • estimated Glomerular filtration rate < 30 ml/min (MDRD)
  • Autoimmune disease
  • Immunosuppressive treatment or immune deficiency
  • Symptomatic heart failure
  • Respiratory failure (COPD stage ≥ 3 or oxygen therapy)
  • Solid cancer or active blood disease
  • Severe malnutrition (albumin < 30 g/L or weight loss ≥10% in 6 months)
  • Obesity with BMI ≥ 35 kg/m²
  • Diabetes not controlled by diet alone
• Pregnant, breastfeeding or parturient women
• Deprivation of liberty by judicial or administrative decision
• Mandatory Psychiatric Care
• Protected by decision of law
• Unable to express consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with Long COVID	Biological: Blood sample (at inclusion and 6 months later); (56ml of blood, 8 tubes) 3 heparin, 1 EDTA , 2 SST, 2 CPT; Other: Patient questionnaires (at inclusion and 6 months later); (4 questionnaires) Symptoms in the last week, Fatigue Impact Scale (FIS), Short-Form 36 (SF-36) and Nijmegen.
Active Comparator: COVID-19 recovered patients (Control)	Biological: Blood sample (at inclusion and 6 months later); (56ml of blood, 8 tubes) 3 heparin, 1 EDTA , 2 SST, 2 CPT; Other: Patient questionnaires (at inclusion and 6 months later); (4 questionnaires) Symptoms in the last week, Fatigue Impact Scale (FIS), Short-Form 36 (SF-36) and Nijmegen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of immunometabolic signatures specific of Long COVID in the plasma and mononuclear cells	Statistical analyzes (multivariate) by Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) (Q2Ycum > 0.5, P-value (CV-ANOVA) ≤0.05, Q2Ycum, test permutations <0) or the median (AUROC test sets) ≥ 0.8 and the median of the p-values associated with the AUROCs of the test sets ≤ 0.05 in the plasma and/or the PBMCs.	18 months
Concentration of metabolites and immune mediators in the plasma and mononuclear cells	Comparison of metabolites and immune mediators in the blood and PBMC of patients with long COVID will be compared with those of control patients using statistical tests after correction of the alpha risk.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in immuno-metabolic signatures 6 months after the initial assessment	Significant changes in concentration of metabolites and immune mediators 6 month after inclusion, in comparison with the initial assessment, will be identifed using paired statistical tests with correction of the alpha risk	18 months
Proportion of patients with clinical improvement (return to normal life) at 6 months with correction of the immuno-metabolic signature	The correlation between clinical signs of long COVID and the immuno-metabolic signature specific of long COVID identified in the study will be assessed 6 months after inclusion.	18 months

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Investigators: Principal Investigator: Vincent DUBEE, MD, PhD, Angers University Hospital; Principal Investigator: Valérie DUBUS, MD, Angers University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2023
• Primary Completion (Actual): May 7, 2025
• Study Completion (Actual): November 3, 2025

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Long COVID; immunometabolic; immunometabolic signatures
• Additional Relevant MeSH Terms: Post-Infectious Disorders; COVID-19; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; Post-Acute COVID-19 Syndrome; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: LoCo-ImMet

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared upon reasonable request. Only de-identified data will be shared. Any data collected during the study may be shared. The protocol will be shared initially. Other documents may be shared at a later date upon request (e.g., the CRF to allow a collaborator to select the data they wish to access). The recipients of the data will be researchers. The data will be available for any purpose deemed relevant by the study investigator, based on a protocol provided by the requester, after verification of the obtaining of regulatory approvals, including the favorable opinion of an ethics committee.
• IPD Sharing Time Frame: The data will be shared after signing a negotiated data transfer agreement ( data access agreement), for the duration specified in the agreement.
• IPD Sharing Access Criteria: The data will be made available via secure transfer (sharing platform approved by the university hospital: BlueFiles or Oodrive).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No