Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

Comparison of two groups of patients SARS-CoV-2 positive with severe acute respiratory syndrome:

• Exposed to low prolonged doses of Methylprednisolone
• Not exposed to corticosteroids (standard of care alone)

The two group will be weighted by means of a propensity score according to:

• Sex
• Age
• C-reactive protein (CRP) at baseline
• Sequential Organ Failure Assessment (SOFA) score at baseline
• PaO2/FiO2 ratio at baseline (ratio of arterial oxygen partial pressure to fractional inspired oxygen)

Anti-viral agents, chloroquine, respiratory support (any), and antibiotics (any) are allowed in each study group. Corticosteroids use, other than per-protocol Methylprednisolone in the exposed group is a reason for dropout.

• The exposed group is treated with Methylprednisolone at study entry (baseline) according to a protocol based on the Italian national recommendations for COVID-19 management: a loading dose of 80 mg IV, followed by an infusion of 80 mg/day in 240 mL normal saline at 10 mL/h. The infusion is continued for at least eight days and until achieving either a PaO2:FiO2 > 350 mmHg or a CRP < 20 mg/L. Treatment is then switched to oral administration of Methylprednisolone 16 mg or 20 mg IV twice daily until CRP returns to < 20% of normal range and/or PaO2:FiO2 > 400 or SatHbO2 ≥ 95%. The decision to apply the protocol to Covid-19 is left to the discretion of the treating team for each individual patient.
• Unexposed patients will be selected from concurrent consecutive COVID-19 patients with the same inclusion and exclusion criteria and blinded to outcome data.

Inclusion criteria

• SARS-CoV-2 positive
• Age >17 years and < 80 years
• P/F < 250 mmHg
• Bilateral pneumonia (infiltrates/interstitial)
• CRP >10mg/dL (or >100mg/L)
• Alternatively to 4-5-6 criteria a diagnosis of ARDS according to the Berlin definition (Ranieri M, et al. JAMA 2012)

Exclusion criteria

• Heart failure as predominant cause of acute respiratory failure
• Decompensated liver cirrhosis
• Cancer
• Organ transplantation
• HIV+
• dialysis
• long-term oxygen therapy, home mechanical ventilation
• Idiopathic pulmonary fibrosis
• Progressive neuromuscular disorders (e.g. Duchenne, Pompe, ALS)
• Dementia or decompensated psychiatric diseases
• immunosuppressive treatments
• Chronic use of corticosteroids
• Use of Tocilizumab
• pregnancy