Safety and efficiency of inhalation method for administration of small extracellular vesicles derived from multipotent mesenchymal stromal cells of human umbilical cord in SARS- CoV-2 associated pneumonia

Abstract

The coronavirus infection (COVID-19), an acute viral disease with predominant affection of the upper respiratory tract, is a challenge for modern medicine. Considering the fact that in the pathogenesis of coronavirus pneumonia there is violation of the immune response (hyper-response, cytokine storm) the drugs that locally regulate it may be promising in the pneumonia treatment. Biological activity of exosomes is widely investigated in the world. Small extracellular vesicles of mesenchymal cells have the following effects: anti-apoptotic, proliferation stimulation, anti-inflammatory and immunomodulatory. Objective: to evaluate the safety and efficacy of the method of inhalation administration of small extracellular vesicles in bilateral pneumonia caused by a new SARS-CoV-2 coronavirus infection. To study these effects an interventional, prospective, randomized, double-blind, placebo-controlled study has been conducted to evaluate the safety and efficacy of inhaled small extracellular vesicles administration to the patients with bilateral pneumonia caused by the new coronavirus infection SARS-CoV-2. Altogether 36 patients with confirmed new coronavirus infection COVID-19, complicated by bilateral pneumonia of moderate severity (12 patients each in study groups 1 and 2, depending on the type of given small extracellular vesicles, and the control group) participated in the study. Small extracellular vesicles were inhaled twice a day in the dose of 2-10х1010 particles. The efficacy and safety of the method were assessed judging by the patients' general state, assessment of the disease severity, general and biochemical blood tests, coagulogram, saturation, CT scan of the lungs before and after 1 0 days of treatment. The observation period was 30 days after hospitalization. During the study the safety of the method was proved, all the patients recovered. Reliable differences of the blood CRP index, which normalized by day 10 of treatment in groups 1 and 2, but remained elevated in the control group. No significant differences were found in other assessed parameters.