Human Ab Response & immunoMONItoring of COVID-19 Patients

Not Applicable

Completed

• Conditions: SARS-CoV-2 Coronavirus; Acute Respiratory Distress Syndrome
• Interventions: Biological: Blood samples collection; Other: Saliva collection

• Registration Number: NCT04373200
• Lead Sponsor: Rennes University Hospital

Brief Summary

Prospective, mono centric study on COVID-19 patients with or without acute respiratory distress syndrome (ARDS) to analyse the dynamics of the immune response and to search for biomarkers of evolution

Detailed Description

Assessed by World Health Organisation as a pandemic on March 11, COVID-19 is caused by the SARS-CoV-2 coronavirus. The spectrum of its clinical manifestations is strikingly broad and extends from mild disease (resembling an ordinary bout of flu or even asymptomatic) to pneumonia. The latter cases convey a high risk of evolution towards acute respiratory distress syndrome (ARDS), eventually fatal when worsening with cytokine storm and multiple organ failure or with superinfection and sepsis. In the absence of overt variations of the virus itself, its interactions with the host immune system are likely crucial. Clinical features of patients with severe forms of COVID-19 were reported, but immunological description of biomarkers for exacerbation and mortality vs recovery remains superficial. Globally decreased white blood cells, notably T-cells, suggest that CoV-2 might trigger or exploit an immune defect. This could correspond to gaps in immune cell subpopulations, kinetics of activation or repertoires. Immune failure would then be responsible for exacerbations and a poor outcome in intensive care unit (ICU) patients. The objective of the study is to characterize the kinetics of the immune response and of immune dysregulation in ARDS patients. In addition to studying severe ARDS patients, an inverse image of immune repertoires should appear in healed up patients, after they have reached an undetectable viral load and acquired protective antibodies (Abs). Humoral immunity mediated by specific anti-viral Abs was a key factor for recovery from SARS-CoV-1 infection, and this is also expected for CoV-2, making the Ig repertoire also of special interest for its inclusion of anti-viral neutralizing Abs (nAbs).

Altogether, there is thus an urgent need for high-resolution characterization of the anti-CoV-2 immune response, correlating the dynamics of immune activation, cytokine production and immune repertoires with clinical evolution. In addition to providing biomarkers for prognosis evaluation and for monitoring innovative treatments this will also participate to the urgent quest of as many possible monoclonal antibodies (mAb) candidates for immunotherapy

Study Timeline

• Study First Submitted: 2020-04-22
• Study First Submitted QC: 2020-04-30
• Study First Posted: 2020-05-04
• Study Start: 2020-05-25
• Primary Completion: 2021-03-09
• Study Completion: 2021-03-09
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-19
• Last Update Posted: 2023-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

Inclusion Criteria

• Patient older than 18 years old

• Patients COVID-19 :

  • hospitalized for less than 48 hours in intensive care unit (ICU) with ARDS (PaO2/Fi02 < 200) or
  • hospitalized with respiratory syndrome without need of invasive mechanical ventilation

• Patients hospitalized for less than 48 hours in intensive care unit (ICU) with ARDS (PaO2/Fi02 < 200) from other causes

• Patients who have given their consent or included in an emergency situation

• Patients affiliated to medical care insurance

Exclusion Criteria

• Pregnant women
• Preexisting immune disorders (HIV-infection, malignancy, graft, treatment with immunosuppressive agents)
• Patients legally protected (under judicial protection, guardianship), persons deprived of liberty

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
COVID-19 patients with associated ARDS	Blood samples collection	-
Patients with ARDS from other causes	Blood samples collection	-
COVID-19 patients with associated ARDS	Saliva collection	-
COVID-19 patients without associated ARDS	Blood samples collection	-
COVID-19 patients without associated ARDS	Saliva collection	-

Primary Outcome Measures

Name	Time	Method
Number of increased immune population	Month 4	Blood sample
Number of decreased immune population	Month 4	Blood sample
Number of statically different phenotypes compared to control patients	Month 4	Blood sample

Secondary Outcome Measures

Name	Time	Method
Gain or loss of functional phenotypic markers between D1 and D14	Day 14	Qualitative identification of immune subpopulations showing a significant variation compared to controls and quantification of this variation (at D1 and/or D14)
Gain or loss of functional phenotypic markers between between acute and mild infections	Day 14	Qualitative identification of immune subpopulations showing a significant variation between acute and mild COVID-19 and quantification of this variation (at D1 and/or D14)
Gain or loss of functional phenotypic markers between D1 and month 4	Month 4	Qualitative identification of immune subpopulations showing a significant variation between acute stage and recovery (at 4 months) and quantification of this variation
Characterization of a new set of human antibodies from patients who have recovered of COVID-19	Month 4	Blood sample
Evaluation of V, D, J gene usage alterations in the immunoglobulin and T cell receptor (TCR) repertoires during ARDS linked to COVID-19	Day 14	Blood sample
Identification of the Ig classes and of V, D, J sequences of anti-CoV-2 antibodies	Month 4	Blood sample

Trial Locations

Locations (1)

CHU Rennes; 🇫🇷 Rennes, France