Obesity, COVID-19 Infection Clinical Trial
Official title:
Study of the Efficiency and Security of NIVOLUMAB Therapy, Used in Immuno-stimulation, in Hospitalized Obese Individuals at Risk to Evolve Towards Severe Forms of COVID-19 Infection. Multicentric, Paralleled, Randomized, Controlled Trial
Although SARS-CoV-2 (Severe Acute Respiratory Syndrome-associated coronavirus) due to
COVID-19 evolves poorly towards ARDS (Acute Respiratory Distress Syndrome) and death, there
is to date no validated drug available for severe forms of COVID-19. Patients with COVID-19
undergo a drastic decrease of T lymphocytes (LT) count, while the remaining ones display an
"exhausted" phenotype, due to immunosuppressive pathway activation among which the Programed
cell Death 1 (PD1) receptor pathways. LT exhaustion is responsible for host anergy towards
viral infection and leads to increased risk of severe forms of COVID-19. Moreover, while the
number of systemic LT PD1+ correlates with poor prognosis clinical stages of COVID-19
infection, healing from COVID-19 associates with LT PD1 expression normalization. Chinese
epidemiologic data identified clinical risk factors of poor clinical evolution (i.e. ARDS or
death), among which is found obesity, similarly to observation previously obtained during
H1N1 infection (flu virus).
Obese persons display meta-inflammation and immune dysfunction, a condition similar to
ageing, thus termed "Inflamm-aging", thus also used during obesity. Inflamm-aging,
characterized by cytotoxic LT exhaustion and reduced NK cell (Natural Killer cell) cytotoxic
function secondary to PD1 pathway activation, could contribute to the poor prognosis observed
during cancer and infection in obese individuals. We hypothesize that the immunocompromised
profile observed during obesity contribute to their vulnerability towards COVID-19.
In cancer or certain infection diseases, NIVOLUMAB, an anti-PD1 monoclonal antibody, restores
exhausted LT immunity. We thus hypothesize that NIVOLUMAB-induced immunity normalization
could (i) stimulate anti-viral response also during COVID-19 infection and (ii) prevent ARDS
development, which has previously been associated with low LT count concomitant with
increased inflammatory cytokine production.
This randomized controlled therapeutic trial, using an add-on strategy to usual standard of
care, aims at demonstrating the efficacy and safety of NIVOLUMAB-induced cytotoxic LT
normalization, to improve clinical outcomes in hospitalized COVID-19+ adult obese individuals
with low LT, since they are at risk of poor prognosis. We postulate that NIVOLUMAB will
increase the number of individuals able to stop oxygen therapy at D15
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