Characterization of the Immunometabolic Signature in Long COVID-19.

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.

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