Soluble E-selectin is a significant biomarker for ARDS. Soluble E-selectin also has pro-inflammatory properties further releasing cytokines and promoting its synthesis and the continued influx of neutrophils. Small molecule glycomimetic antagonists of E-selectin (rivipansel and uproleselan) are 500- to 1000-fold more potent inhibitors of E-selectin and have shown activity and no measurable toxicity in human clinical trials for other indications. Treatment with these E-selectin inhibitors reduced the levels of soluble E-selectin in the bloodstream which occurs during recovery of ARDS. Thus antagonists of E-selectin which include glycomimetic antagonists and more specifically, rivipansel (GMI-1070) and uproleselan (GMI-1271), may be used to treat COVID-19 patients with respiratory symptoms that may lead to ARDS~Primary Objective:~Safety of uproleselan in patients with severe COVID-19 pneumonia.~Secondary Objectives:~To evaluate if treatment with uproleselan administered intravenously in addition to the best available therapy according to institutional guidelines is able to reduce the progression of acute respiratory failure, in patients with severe COVID-19 pneumonia.~To evaluate proportion of patients alive and free of respiratory failure through Day 28~To evaluate overall survival and all-cause mortality at day 15 and 28.~To evaluate changes in the COVID ordinal outcomes scale.~To assess adverse events to evaluate the safety of uproleselan.~To assess ventilator-free days, ICU-free days, oxygen, vasopressor free days.~To evaluate changes in D-dimer.~Exploratory Objectives:~To examine the correlation of plasma soluble E-selectin concentrations with clinical outcomes.~To examine the correlations of other biomarkers of interest with clinical outcome.
The purpose of this study is to find out whether the drug uproleselan can help patients with severe COVID-19 pneumonia. Investigators will study both the side effects of the drug and assess if the drug will help patients recover more quickly and slow down the progression of acute respiratory failure.