Human Ab Response & immunoMONItoring of COVID-19 Patients (HARMONICOV)

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

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome; SARS-CoV-2 Coronavirus
• Intervention / Treatment: Biological: Blood samples collection; Other: Saliva collection

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 Type: Interventional
• Enrollment (Actual): 71
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35033
    • CHU Rennes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: COVID-19 patients with associated ARDS	Biological: Blood samples collection; Blood sample collection at Day 1, day 7, day 14 for all patients. At month 4 for 25 survivors COVID-19 patients; Other: Saliva collection; Saliva collection at Month 4 for 25 survivors COVID-19 patients
Active Comparator: COVID-19 patients without associated ARDS	Biological: Blood samples collection; Blood sample collection at Day 1, day 7, day 14 for all patients. At month 4 for 25 survivors COVID-19 patients; Other: Saliva collection; Saliva collection at Month 4 for 25 survivors COVID-19 patients
Active Comparator: Patients with ARDS from other causes	Biological: Blood samples collection; Blood sample collection at Day 1, day 7, day 14 for all patients. At month 4 for 25 survivors COVID-19 patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of increased immune population	Blood sample	Month 4
Number of decreased immune population	Blood sample	Month 4
Number of statically different phenotypes compared to control patients	Blood sample	Month 4

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rennes University Hospital

Publications and helpful links

General Publications

• Hamzeh-Cognasse H, Mansour A, Reizine F, Mismetti P, Gouin-Thibault I, Cognasse F. Platelet-derived sCD40L: specific inflammatory marker for early-stage severe acute respiratory syndrome coronavirus 2 infection. Virol J. 2021 Oct 29;18(1):211. doi: 10.1186/s12985-021-01680-3.
• Pascal V, Dupont M, de Rouault P, Rizzo D, Rossille D, Jeannet R, Daix T, Francois B, Genebrier S, Cornic M, Monneret G, Venet F, Ferrant J, Roussel M, Reizine F, Le Souhaitier M, Tadie JM, Tarte K, Feuillard J, Cogne M. Demultiplexing Ig repertoires by parallel mRNA/DNA sequencing shows major differential alterations in severe COVID-19. iScience. 2023 Mar 17;26(3):106260. doi: 10.1016/j.isci.2023.106260. Epub 2023 Feb 21.
• Roussel M, Ferrant J, Reizine F, Le Gallou S, Dulong J, Carl S, Lesouhaitier M, Gregoire M, Bescher N, Verdy C, Latour M, Bezier I, Cornic M, Vinit A, Monvoisin C, Sawitzki B, Leonard S, Paul S, Feuillard J, Jeannet R, Daix T, Tiwari VK, Tadie JM, Cogne M, Tarte K. Comparative immune profiling of acute respiratory distress syndrome patients with or without SARS-CoV-2 infection. Cell Rep Med. 2021 Jun 15;2(6):100291. doi: 10.1016/j.xcrm.2021.100291. Epub 2021 May 6.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2020
• Primary Completion (Actual): March 9, 2021
• Study Completion (Actual): March 9, 2021

Study Registration Dates

• First Submitted: April 22, 2020
• First Submitted That Met QC Criteria: April 30, 2020
• First Posted (Actual): May 4, 2020

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; Acute Respiratory Distress Syndrome; SARS-CoV-2 coronavirus
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Coronavirus Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 35RC20_9795_HARMONICOV; 2020-A01100-39 (Other Identifier: ANSM (N°ID-RCB))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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