Human Ab Response & immunoMONItoring of COVID-19 Patients

Acute Respiratory Distress Syndrome Clinical Trial

— HARMONICOV  

Official title:

Human Ab Response & immunoMONItoring of COVID-19 Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04373200
• Other study ID #: 35RC20_9795_HARMONICOV
• Secondary ID: 2020-A01100-39
• Status: Completed
• Phase: N/A
• Start date: May 25, 2020
• Est. completion date: March 9, 2021

Study information

• Verified date: May 2023
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: March 9, 2021
• Est. primary completion date: March 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Coronavirus Infections
• COVID-19
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• SARS-CoV-2 Coronavirus

Intervention

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

Locations

Country	Name	City	State
France	CHU Rennes	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

References & Publications (2)

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 p — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of increased immune population	Blood sample	Month 4
Primary	Number of decreased immune population	Blood sample	Month 4
Primary	Number of statically different phenotypes compared to control patients	Blood sample	Month 4
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Identification of the Ig classes and of V, D, J sequences of anti-CoV-2 antibodies	Blood sample	Month 4
Secondary	Characterization of a new set of human antibodies from patients who have recovered of COVID-19	Blood sample	Month 4