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.

Characteristics and Specialization of the Immune Response in COVID-19 Abstract The outbreak of coronavirus pneumonia in Wuhan, China, became a pandemic on March 11, 2020. It has caused almost 4 million confirmed cases worldwide, with more than 270,000 deaths. Coronavirus is an enveloped RNA virus of the β-coronavirus genus distributed in birds, humans, and other mammals. The World Health Organization has named the new disease COVID-19. The scientific community is look http://doi.org/10.22201/fm.24484865e.2020.63.4.02 8 8 Revista de la Facultad de Medicina de la UNAM | ing for evidence that can lead to a better understanding of the infection and the immune response (IR), prognostic and therapeutic predictors, effective treatments and vaccines. The objective of this review was to compile updated scientific evidence of the IR to COVID-19, in order to guide professionals with solutions that have a clinical impact. The most important elements involve innate immunity with failures in the interferon system in the early stages of the infection and a sustained increase in proinflammatory interleukins. This can end in a potentially fatal cytokine storm. The infiltration of neutrophils and macrophages at the alveolar level, accompanied by neutrophilia, is very characteristic. Lymphopenia is evident at the adaptive immunity level, that, depending on the degree, can indicate the severity of the disease. Understanding the temporal sequence of the IR is crucial for choosing the appropriate and effective therapies, especially when selecting which type of anti-inflammatory drugs can be used and the frequency of the dosage. Due to the fact that it is difficult to determine when they will be clearly beneficial, not harmful to the IR and not too late, due to the irreversibility of the process. Key words: COVID-19; coronavirus; immune response

INTRODUCTION Advanced age and chronic disease comorbidities are indicators of poor prognosis in COVID-19 clinical progression. Fatal outcomes in patients with these characteristics are due to a dysfunctional immune response. Understanding COVID-19's immunopathogenesis helps in designing strategies to prevent and mitigate complications during treatment. OBJECTIVE Describe the main immunopathogenic alterations of COVID-19 in patients of advanced age or with chronic non-communicable diseases. DATA ACQUISITIONWe carried out a bibliographic search of primary references in PubMed, Elsevier, Science Direct and SciELO. A total of 270 articles met our initial search criteria. Duplicate articles or those unrelated to at least one chronic comorbidity, senescence or infl ammation and those that studied only patient clinical characteristics, laboratory tests or treatments were excluded. Finally, our selection included 124 articles for analysis: 10 meta-analyses, 24 original research articles, 67 review articles, 9 editorials, 9 comments, 3 books and 2 websites.DEVELOPMENT Hypertension and diabetes mellitus are the most common comorbidities in COVID-19 patients. Risk of developing severe manifestations of the disease, including death, is increased in senescent and obese patients and those with cardiovascular disease, cancer or chronic obstructive pulmonary disease. Low-grade chronic infl ammation is characteristic of all these conditions, refl ected in a proinfl ammatory state, endothelial dysfunction, and changes to innate immunity; mainly of the monocyte-macrophage system with changes in polarization, infl ammation, cytotoxicity and altered antigenic presentation. In the case of SARS-CoV-2 infection, mechanisms involved in acute infl ammation overlap with the patient's pro-infl ammatory state, causing immune system dysfunction. SARS-CoV-2 infection amplifi es already-existing alterations, causing failures in the immune system's control mechanisms. The resulting cytokine storm causes an uncontrolled systemic infl ammatory response marked by high serum levels of infl ammatory biomarkers and a pro-infl ammatory cytokine profi le with decompensation of underlying diseases. In asthma, chronic eosinophilic infl ammation protects against infection by producing a reduced interferon-mediated response and a reduced number of ACE2 receptors.CONCLUSIONS Low-grade chronic infl ammation present in advanced age and chronic diseases-but not in bronchial asthma-produces a pro-infl ammatory state that triggers a dysregulated immune response, favoring development of severe forms of COVID-19 and increasing lethality.

BackgroundThe COVID-19 pandemic presented an unprecedented challenge to identify effective drugs for prevention and treatment.ObjectiveTo characterize acute renal injury (AKI) in patients with COVID-19 and their relation with clinical outcomes within the framework of the SENTAD COVID clinical trial at the Abu Dhabi Stem Cells Center.MethodsAbu Dhabi Stem Cell Center (ADSCC) proposed a prospective clinical trial nebulization treatment with autologous stem cells (Non-Hematopoietic Peripheral Blood Stem Cells (NHPBSC)), at Abu Dhabi hospitals.Participants20 treated patients were compared with 23 not treated patients. Both groups received COVID 19 standard treatment.OutcomesAfter the results were collected, this study was created to determine the impact of the disease on the renal function and the efficacy of the therapy on patient’s outcomes.ResultsOne third of the critical patients studied suffered kidney failure. Patients in the treated group showed a favorable tendency to improve in contrast to those in the control group. Less patients from group A suffered from sepsis in comparison with the group B (25% vs 65%), HR=0.38, (95% Confidence Interval: 0.16 – 0.86), *p=0.0212. These results suggested a NNT=2.5. An improvement in lymphocyte count, CRP, and shorter hospital stay after treatment was evidenced, which led to less superinfection and sepsis in the treated group.ConclusionsThe proposed anti-inflammatory effect of the stem cells, offers a great promise for managing the illness, emerging as a crucial adjuvant tool in promoting healing and early recovery in severe COVID-19 infections and other supportive treatments.ARTICLE SUMMARYOur study had several strengths and limitation: It was a randomized trial.The treatment showed a positive result, providing evidence that this intervention is effective in routine practice.We found fewer complications related to prolonged hospital stay in the treated group.The is the small number of participants.It was carried out in 4 different hospitals, each with different criteria for the selection of the initial empirical antimicrobials, which can cause multiple resistant germs.

BackgroundCOVID-19 is the defining global crisis of our time. Secondary complication such as urinary tract infections and sepsis, worsen the already established problem, creating a new challenge.ObjectiveTo characterize the features and outcomes in COVID-19 patients with sepsis and urinary tract infection.MethodsAn observational and analytical study was conducted within the framework of the SENTAD COVID clinical trial at the Abu Dhabi Stem Cells Center, were the patients received a nebulization therapy with the use of autologous stem cells (group A). Those patients were compared with a not stem cells treated control arm (group B), and both received the UAE COVID 19 standard management. An analysis of the culture samples, antimicrobial agents and the efficacy of the therapy on patient’s outcomes was done.ResultsA significant difference between the groups was found in the UTI incidence (p=*0.0206). Patients in group A showed a lower tendency to sepsis in comparison with group B (7% vs 21%), HR=0.35, (95% Confidence Interval: 0.13 – 0.91), p=0.0175. It was calculated a NNT=7.3. Candida albicans was the most frequently agent causing sepsis and UTI. The massive use of broad-spectrum antimicrobials was striking.ConclusionsWe found a protective factor of stem cells against secondary infection in COVID 19 cases, in terms of sepsis and UTI. The suggested immunomodulatory effect of stem cells offers a therapeutic strategy to manage the disease and avoid several complications. Antimicrobial agents can lead to increased opportunistic infections, so a rational approach to these treatments must be considered.