Covid 19 Clinical Trials

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

NCT04413838 Obesity, COVID-19 Infection Drug: NIVOLUMAB Other: Routine standard of care

MeSH:Infection Communicable Diseases

Primary Outcomes

Description: Patient's clinical state will be evaluated by the proportion of patients able to be weaned of oxygen at D15 after randomization (randomization date is the day where the experimental treatment (i.e. NIVOLUMAB) is administered).

Measure: Patient's clinical state

Time: 15 days after randomization

Secondary Outcomes

Description: Proportion of in-coming patients in ICU at D7 and D15 post-randomization

Measure: Readmission

Time: 7 days and 15 days after randomization

Description: Proportion of death at D7 and D15 post-randomization

Measure: Mortality

Time: 7 days and 15 days after randomization

Description: Proportion of patients weaned out of oxygen at D7 post-randomization

Measure: Oxygen flow needs

Time: 7 days after randomization

Description: Mean oxygen flow needed

Measure: Requirement of oxygen

Time: 7 days and 15 days after randomization

Description: Proportion of out-coming patients from hospitalization at D7 and D15 post-randomization

Measure: Discharge from hospital

Time: 7 days and 15 days after randomization

Description: Report of all adverse events linked or not to experimental treatment during the study

Measure: Adverse events

Time: Within 15 days post-randomization and 90 days and 6 months after randomization

Description: Presence or not of nasopharyngeal SARS-CoV-2 determined by PCR response

Measure: Presence of nasopharyngeal SARS-CoV-2