ABSTRACT
INTRODUCTION: The acute respiratory distress syndrome (ARDS) resulting from coronavirus disease 2019 (COVID-19) is associated with a massive release of inflammatory cytokines and high mortality. Preliminary mortality rates of those who require mechanical ventilation ranges from 31-66%. Mesenchymal stromal cells (MSCs) have anti-inflammatory properties and are being studied as a potential treatment for steroid-resistant graft-vs-host disease, which is characterized by excessive immune activation and tissue damage. Furthermore, MSCs have shown activity in pre-clinical studies in treating acute lung injury. We aimed to determine the safety and feasibility of MSC in mechanically ventilated patients with COVID-19 moderate to severe ARDS. METHODS: Eleven patients were treated with remestemcel-L, an allogeneic cryopreserved MSC product, under individual patient emergency investigational new drug (eIND) applications. Patients were eligible if they had COVID-19 disease with moderate to severe ARDS and had been receiving mechanical ventilation for less than 72 hours prior to the first infusion. Patients with pre-existing lung disease requiring supplemental oxygen or severe liver or kidney injury were excluded. Each patient received two infusions of remestemcel-L at a dose of 2 million cells/kg/ infusion, 48-120 hours apart. RESULTS: Remestemcel-L infusions were well-tolerated in all eleven patients. After 28 days of follow-up, ten patients (91%) were extubated, nine (82%) remained liberated from mechanical ventilation and were discharged from the ICU and two (18%) died. The median time to extubation was ten days. Eight patients (73%) were discharged from the hospital. C reactive protein levels significantly declined within five days of MSC infusion. Five patients developed secondary infections and one patient experienced pulmonary embolism, which were thought to be attributable to their underlying disease. CONCLUSIONS: Remestemcel-L infusions to treat COVID-19 associated moderate to severe ARDS were safe and associated with substantial clinical and laboratory improvement. A randomized controlled trial based on these results is underway.