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