Inclusion Criteria:

• Age ≥ 18 years old
• Patient with laboratory-confirmed SARS-CoV-2 infection as determined by PCR < 96 h (at initial diagnosis or persistent carriage <96 h)
• Hospitalized patient with COVID-19 requiring oxygen therapy

And targeting in phase B :

• Patients under oxygen therapy such as nasal cannula/mask or non-invasive ventilation with paO2/FiO2 > 200 mmHg.
• Patients hospitalized for less than 7 days.
• Patients with symptoms for less than 10 days or RT-PCR (<96h) with Cycle Treshold < 25.
• Social security coverage
• signed informed consent (by patient or their legally authorized representative)

Exclusion Criteria:

• Hypersensitivity to natural or recombinant interferon-ß
• Hypersensitivity to human albumin or mannitol
• Recent suicide attempt
• Decompensation of liver failure
• age < 18 years
• Pregnant or nursing.
• Patients managed on an outpatient basis (i.e. not initially hospitalized).
• Parenteral IFN treatment. In periode B, addition of new exclusion criteria
• Patients with kidney transplant
• Immunocompromised patients
• Patients with severe systemic disease constantly threatening their vital prognosis (ASA ≥ IV: e.g. severe ARF, advanced cancer pathology, recent myocardial IDM, severe valvular dysfunction, dependence on parenteral nutrition on central line, shock, sepsis, trauma, ...).
• Patients in septic shock.
• Patients with documented fungal infection.
• Patients on mechanical ventilation.
• Patients hospitalized for COVID-19 for more than 7 days.