methylprednisolone for patients with covid-19 severe acute respiratory syndrome

Conditions: Severe Acute Respiratory Syndrome (SARS) Pneumonia; Coronavirus Infections; ARDS, Human

Summary: covid-19 infection is overwhelming italian healthcare. there is an urgent need for a solution to the lack of icu beds and increasing deaths day after day. a recent retrospective chinese paper (jama intern med, online march 13, 2020) showed impressive positive effect of methylprednisolone (mp) on survival of sars-cov-2 critically ill patients. moreover, the italian infectious disease leading institution guidelines for covid-19 clinical management included as an option for patients with "incipient worsening of respiratory functions" methylprednisolone treatment at an approximate dose of 80mg. the main objective of this multi-centre observational trial is to analyse the association of low dose prolonged infusion of methylprednisolone (mp) for patients with severe acute respiratory syndrome with composite primary end-point (icu referral, need for intubation, in-hospital death at day 28).

comparison of two groups of patients sars-cov-2 positive with severe acute respiratory syndrome: 1. exposed to low prolonged doses of methylprednisolone 2. not exposed to corticosteroids (standard of care alone) the two group will be weighted by means of a propensity score according to: 1. sex 2. age 3. c-reactive protein (crp) at baseline 4. sequential organ failure assessment (sofa) score at baseline 5. 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. 1. 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 \ 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. 2. unexposed patients will be selected from concurrent consecutive covid-19 patients with the same inclusion and exclusion criteria and blinded to outcome data.

Eligibility criteria:
inclusion criteria: 1. sars-cov-2 positive 2. age \>17 years and \< 80 years 3. p/f \< 250 mmhg 4. bilateral pneumonia (infiltrates/interstitial) 5. crp \>10mg/dl (or \>100mg/l) 6. 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

Keywords: sars-cov-2, sars ards methylprednisolone