Study of Immune Response During SARS-CoV-2 Infection - (COVID-19)

Since March 2020, Europe has been facing the spread of Coronavirus disease 2019 (COVID-19),
an emerging infectious disease of viral zoonosis type, caused by the coronavirus SARS-CoV-21.
This virus is responsible for an epidemic in Wuhan in November 2019 and a pandemic in March
2020. The mode of transmission, both respiratory and by contact, carried by microdroplets
emitted by an infected person and inhaled by a person nearby, induces a very high
contagiousness rate2. In the majority of cases, CoV-2-SARS infection is not very symptomatic,
but some evolve into severe forms, particularly in frail people: elderly subjects, those
affected by chronic diseases (diabetes, obesity or cancer) or those undergoing
immunosuppressive treatments. There is still little information on the reasons why some will
develop a severe form while others will remain asymptomatic. The immune response is little
studied in this context.

Functional study of the cellular immune response has shown its interest in predicting the
risk of infection in different cohorts, particularly in renal insufficiency subjects awaiting
transplantation with an over-risk of developing an infection within a year in patients with a
low level of gamma interferon (INFγ: main anti-viral cytokine) after non-specific stimulation
of T lymphocytes.

A study published the clinical characteristics of 41 patients infected with coronavirus at
the Huanan seafood market (first contact cases). Despite a similar clinical symptomatology:
cough (76%) and fever (98%), some patients required rapid ventilatory assistance. These
patients had an increased production of inflammatory cytokines: IL2, IL7, IL10, GSCF, IP10,
MCP1, MIP1A, and TNFα3.

Here, the objective is to identify cytokine profiles in subjects exposed to or infected with
SARS-CoV-2 that can predict their risk of developing a severe pauci-symptomatic form at the
time of exposure or during the development of a severe form. the team believes that the
immune response to this infection is a major factor in the risk of developing an asymptomatic
infection, a flu-like symptomatology or a respiratory failure syndrome (ARDS).3,4 The team
believes that the immune response to this infection is a major factor in the risk of
developing an asymptomatic infection, a flu-like symptomatology or a respiratory failure
syndrome (ARDS). The team thus wishes to better direct patients to appropriate care
structures to optimise the care pathway (ambulatory, infectiology, intensive care),
respirators and number of beds so as not to overload the staff) and to enable treatments to
be personalised and adapted as best as possible: corticosteroids, immunomodulators,
antivirals.

The study will be based on 2 axes: a first clinical axis (i) and a cellular axis (ii).

In its clinical part (i), the intensity of the immune response in COVID19 subjects presenting
different forms of the disease (asymptomatic, moderate and severe forms) will be measured.
These subjects will be recruited from two different patient populations:

- Subjects at risk of infection with CoV-2-SARS. We will test the Th1 response of
caregivers at the time of their entry into a COVID-19 service by measuring the level of
INFγ released after non-specific T-cell stimulation. The hypothesis is that a high level
of INFγ at the time of exposure prevents the risk of developing severe disease and
directs the patient towards less symptomatic forms. Thus, thanks to serological tests,
it will be possible to determine retrospectively in this group how many subjects
presented an asymptomatic form and thus to determine with the help of a functional test
mimicking a viral infection the level of IFNγ measured after stimulation.

- Patients with CoV-2-SARS infection hospitalized in the Infectious Diseases Department
with a moderate form or in resuscitation with a severe form of COVID.19 The evaluation
of these patients on admission using a functional test mimicking a viral infection the
rate of IFNγ measured after stimulation will be carried out.

The levels of IFNγ measured after stimulation will be compared in these 3 groups of COVID19
patients if the evolution towards inflammatory cytokinic profiles at D0, D5 and D10 can
predict the risk of developing ARDS...

Then, the impact of different therapeutic interventions on the secretion of INFγ will be
tested in vitro in an ancillary study (ii): anti-inflammatory, corticosteroids, anti-IL6,
IL2, IL7, chloroquine on their capacity to produce anti-viral cytokines of the type INFγ on
different T cells while limiting the production of pro-inflammatory cytokines by cells of
innate immunity, from healthy subjects, COVID-19 subjects with a mildly symptomatic form or
COVID-19 subjects with ARDS.