Human Ab Response & immunoMONItoring of COVID-19 Patients

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