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Background Treatment options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) are desperately needed. Allogeneic human umbilical cord derived mesenchymal stromal cells (hCT-MSCs) have potential therapeutic benefits in these critically ill patients, but feasibility and safety data are lacking. Materials and Methods In this phase I multisite study, 10 patients with COVID-19-related ARDS were treated with 3 daily intravenous infusions of hCT-MSCs (1 million cells/kg, maximum dose 100 million cells). The primary endpoint assessed safety. Results Ten patients (7 females, 3 males; median age 62 years (range 39-79)) were enrolled at 2 sites and received a total of 30 doses of study product. The average cell dose was 0.93 cells/kg (range 0.56-1.45 cells/kg and total dose range 55-117 million cells) with 5/30 (17%) of doses lower than intended dose. Average cell viability was 85% (range 63%-99%) with all but one meeting the >70% release criteria. There were no infusion-related reactions or study-related adverse events, 28 non-serious adverse events in 3 unique patients, and 2 serious adverse events in 2 unique patients, which were expected and unrelated to the study product. Five patients died: 3 by day 28 and 5 by day 90 of the study (median 27 days, range 7-76 days). All deaths were determined to be unrelated to the hCT-MSCs. Conclusion We were able to collect relevant safety outcomes for the use of hCT-MSCs in patients with COVID-19-related ARDS. Future studies to explore their safety and efficacy are warranted.

Introduction SARS-CoV-2 infection results in the COVID-19 disease that caused a global pandemic. In severe cases, COVID-19 leads to acute respiratory distress syndrome (ARDS), due to direct lung injury and hyperinflammatory response. COVID-related ARDS treatment now includes remdesivir, dexamethasone, and anti-inflammatory monoclonal antibodies, which have decreased the mortality rate, yet patients continue to die from sepsis or multiorgan failure and new treatments are needed. The use of mesenchymal stromal cells (MSC) offers a unique therapeutic option that may shorten time to lung injury resolution through anti-inflammatory, immune-modulatory, and regenerative mechanisms. Objective The aim of this study was to test the safety of human cord tissue-derived MSCs (hCT-MSC) in patients with COVID-related ARDS. This study was funded by The Marcus Foundation. Methods In this phase I multisite study, 10 adults with COVID- related ARDS were treated with 3 daily intravenous infusions of hCT-MSCs (1 million cells/kg/dose, maximum dose 100 million cells with a post thaw viability ≥70%). Patients were excluded if they had evidence of multiorgan failure, immunodeficiency, or were receiving extracorporeal membrane oxygenation or not expected to survive more than 24 hours. The primary endpoint was short-term safety of hCT-MSC infusions. The secondary endpoints included 28-day survival and changes in the Murray Lung Injury Score. Results From August to November 2020, 10 patients (7 females, 3 males; 2 Black, 6 White, 2 other; 3 Hispanic or Latino), with a median age of 61.5 years (range 39-97), were enrolled at 2 sites. There were no infusion-related or study-related adverse events. The average cell dose administered was 0.94 ± 0.29 cells/kg, and average cell viability was 85% ± 11%; 5 of 30 (17%) doses were less than the study dose, and 29 of 30 (97%) met the ≥70% viability criteria. There were 28 non-serious adverse events in 3 unique patients and 2 serious adverse events in 2 unique patients, which were expected and deemed unrelated to the study product. Five patients died: 3 by day 28 and 2 by day 90. All deaths were determined to be unrelated to the hCT-MSCs. The Murray Lung Injury Score did not appear to change over the 28-day study period. Discussion hCT-MSCs infusions are safe in patients with COVID-related ARDS. Future studies determining their efficacy are warranted.

Aviation is one of the world's great connectors of people, trade and tourism. It enhances the prosperity of communities serves, provides jobs, skills and opportunities. It is the real world wide web– a network of airlines, airports and air traffic control organisations that link the major cities and small communities of the world 24 hours a day with very advanced aircraft. Aviation is remarkable for giant technological leaps it has made over the last century. This progress would not have been possible without parallel achievements in the control and reduction of aviation's safety hazards. Aviation is interdependent. The consequences of a major air disaster can affect many of the stakeholders. Mutual concern over damage to the industry's reputation, goodwill and public confidence trends to promote collective action over the parochial pursuit of special interest A natural disaster is a major adverse event resulting from natural processes of the Earth; examples include floods, volcanic eruptions, earthquakes, tsunamis, and other geologic processes. A natural disaster can cause loss of life or property damage,(http://www.ncdc.noaa.gov/billions), and typically leaves some economic damage in its wake, the severity of which depends on the affected population's resilience, or ability to recover .