Background The novel SARS-CoV-2 has caused the coronavirus disease 2019 (COVID-19) pandemic. Currently, with insufficient worldwide vaccination rates, identifying treatment solutions to reduce the impact of the virus is urgently needed. Method An adaptive, multicentric, open-label, and randomized controlled phase I/II clinical trial entitled the “SENTAD-COVID Study” was conducted by the Abu Dhabi Stem Cells Center under exceptional conditional approval by the Emirates Institutional Review Board (IRB) for COVID-19 Research Committee from April 4th to July 31st, 2020, using an autologous peripheral blood non-hematopoietic enriched stem cell cocktail (PB-NHESC-C) administered by compressor (jet) nebulization as a complement to standard care therapy. The primary endpoints include safety and efficacy assessments, adverse events, the mortality rate within 28 days, and the time to clinical improvement as measured by a 2-point reduction on a seven-category ordinal scale or discharge from the hospital whichever occurred first. Results The study included a total of 139 randomized COVID-19 patients, with 69 in the experimental group and 70 in the control group (standard care). Overall survival was 94.20% for the cocktail-treated group vs. 90.27% for the control group. Adverse events were reported in 50 (72.46%) patients receiving PB-NHESC-C and 51 (72.85%) in the control group (p = 0.9590), with signs and symptoms commonly found in COVID-19. After the first 9 days of the intervention, 67.3% of cocktail-treated patients recovered and were released from hospitals compared to 53.1% (RR = 0.84; 95% CI, 0.56–1.28) in the control group. Improvement, i.e., at least a 2-point reduction in the severity scale, was more frequently observed in cocktail-treated patients (42.0%) than in controls (17.0%) (RR = 0.69; 95% CI, 0.56–0.88). Conclusions Cocktail treatment improved clinical outcomes without increasing adverse events. Thus, the nebulization of PB-NHESC-C was safe and effective for treatment in most of these patients. Trial registration ClinicalTrials.gov. NCT04473170. It was retrospectively registered on July 16th, 2020.

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Critical limb ischemia (CLI) is considered the end-stage of peripheral arterial disease, with a prevalence between 2% and 4% in the general population and more than 15% in older adults. One-year major amputation rate can reach 30%, and diabetic patients are five times more likely to develop CLI than nondiabetics. The vascular damage and the complexity in the anatomical extension of the lesions are also worse in people with diabetes with poorer outcomes after vascularization attempts. Following the classifications suggested by international guidelines, we can define the presence of CLI and have a precise evaluation of the amputation risk and the best revascularization procedure for the patient. Nowadays, new endovascular techniques and devices make it possible to treat tibial vessels and even arteries below the ankle with promising initial results. Nevertheless, the re-occlusions rate and the need to re-do treatments at 1 year remain between 30% and 50%. The disease progression and hyperplasia can because it. However, the damage at the microcirculatory level can also lead to a decrease in tissue runoff and an increase in peripheral resistance, which determine the revascularization failure. In the last 20 years, several trials have been designed to avoid amputation in patients with no surgical options. The aim is to find a valid cellular base therapy to create a new vessel web in the ischemic tissue based on the angiogenetic power that stem cells have already demonstrated in vitro and animal studies. Different types of cells have been tested with different concentrations and administration routes with promising results. CD34+ Mononuclear cells, Mesenchymal stem cells, growth factors have demonstrated their contribution to the neo-angiogenesis in ischemic areas. At Abu Dhabi Stem Cells Center, we created a cellular cocktail as an adjunct treatment to surgical revascularization. We think that acting at the microcirculatory and immunological level. We may reduce postsurgery hyperplasia and increase tissue perfusion, ultimately prolonging the patency of revascularization procedures.