Acute respiratory distress syndrome secondary to Sars-COV-2 infection: treatment with mesenchymal stromal cells (mscs) to prevent pulmonary complications

Abstract

In December 2019 in China, after a pneumonia outbreak of unknown etiology, a new RNA virus has been identified and called Sars-CoV-2. Sars-CoV-2 induced severe respiratory infections, with global and rapid epidemic diffusion, designated coronavirus disease 2019 (Covid-19).Sars-CoV-2 infection can lead to severe complications, such as acute respiratory distress syndrome (ARDS) with progression to pulmonary fibrosis.Recent clinical studies described that in patients with severe Covid-19, MSC infusions, promote regenerative and reparative effects with anti-inflammatory and anti-fibrotic action. MSCs do not express ACE2 and TMPRSS2, the two main human receptors for host-pathogen interaction, and are not permissive to in vitro Sars-CoV-2 infection, making them suitable for clinical application.The aim of our study was to evaluate the safety and efficacy of MSCs as cellular therapy in ARDS secondary to SarsCoV-2 in patients undergoing mechanical ventilation, in order to prevent pulmonary fibrosis.MSCs for infusions are thawed at 2x106/ml cellular concentration. The intravenous infusion protocol consists of two doses of third party allogenic MSCs at 1x106/Kg, 15 day apart. From April 2020, six adult patients median age 65 years, median body weight 80 Kg, in mechanical ventilation for ARDS secondary to Sars-CoV-2 infection have been treated. Early or late adverse events were not recorded. Four out six patients showed a significant gas exchange improvement with extubation within seven days from the first infusion.Our results underline the safety and efficacy of MSC infusions for ARDS patients in mechanical ventilation, supporting the need of a phase I/II clinical trial.