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

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

Comparative study with 3 cohorts of 25 adult patients: Cohort A: 25 COVID-19 associated ARDS Cohort B: 25 COVID-19 without ARDS Cohort C: 25 ARDS from other causes

Blood sample collection at Day 1, day 7, day 14 for all patients. At month 4 for 25 survivors COVID-19 patients

Qualitative identification of immune subpopulations showing a significant variation compared to controls and quantification of this variation (at D1 and/or D14)

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)

Qualitative identification of immune subpopulations showing a significant variation between acute stage and recovery (at 4 months) and quantification of this variation

Evaluation of V, D, J gene usage alterations in the immunoglobulin and T cell receptor (TCR) repertoires during ARDS linked to COVID-19

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

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.

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.