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

Inclusion Criteria:

• Patients between 18 and 70 years old
• COVID-19+ patients diagnosed upon biological testing (PCR Coronavirus SARS-CoV2)
• Hospitalized patients
• Obese individuals (BMI≥30kg/m²)
• Lymphocyte counts between 500 and 1500/mm3.
• Patients upon oxygen (either using mask or nasal cannula).
• Patients within their first 7 days after the beginning of symptoms.
• Women of childbearing potential: effective contraception for the duration of the study and 5 months after the administration of treatment.
• Patient who understands and accepts the need for a long term follow-up,
• Patients who agrees to be included in the study and who signs the informed consent form,
• Patients affiliated to a healthcare insurance plan.

Exclusion Criteria:

• CRITERIA LINKED TO THE DISEASE SEVERITY :

  • Patients hospitalized in ICU or constant care unit.
  • Patients with clinical symptoms requiring ICU admission (respiratory rate>30/min, oxygen requirement> 4Liters/min (using high concentration mask) to reach and maintain O2saturation>90%, qSOFA≥ 2(quick score of Sepsis-related Organ Failure Assessment), or associated multi-visceral failure.
  • Patients with high biological probability of macrophage activation syndrome (hemoglobin < 9.2 g/dl AND a blood platelets < 110000/mm3 AND AST > 30 U/l AND ferritin > 600 mg/l).

CRITERIA LINKED TO THE TREATMENT TOXICITY :

• Patients currently treated for cancer or with personal history of cancer within the last 3 years.
• Patients with Chronic Obstructive Pulmonary Disease (COPD) (GOLD 3 and 4 stages).
• Chronic respiratory insufficiency treated with oxygen.
• Patients aged above 70 years old.
• Active smoking.
• Personal history of thoracic radiotherapy.
• Patients with known sensibility to NIVOLUMAB or one of its component.
• Patients upon immunosuppressive dosage of corticoids.
• Patients upon immunosuppressive therapy or immunosuppressed patients.
• Patients already presenting severe autoimmune disease, for whom additional immunologic activation response would potentially precipitate lethal prognosis

GENERAL CRITERIA:

• Minor Patients
• Mentally unbalanced patients, under supervision or guardianship,
• Patient deprived of liberty,
• Patient who does not understand French/ is unable to give consent,
• Patient already included in a trial who may interfere with the study or in a period of exclusion following participation in a previous study.
• Pregnant (controlled by a pregnancy test) or lactating woman