The emergence of SARS-CoV-2/human/Wuhan/X1/2019, a virus belonging to the species Severe acute respiratory syndrome-related coronavirus, and the recognition of Coronavirus Disease 2019 (COVID-19) as a pandemic have highly increased the scientific research regarding the pathogenesis of COVID-19. The Renin Angiotensin System (RAS) seems to be involved in COVID-19 natural course, since studies suggest the membrane-bound Angiotensin-converting enzyme 2 (ACE2) works as SARS-CoV-2 cellular receptor. Besides the efforts of the scientific community to understand the virus' molecular interactions with human cells, few studies summarize what has been so far discovered about SARS-CoV-2 signaling mechanisms and its interactions with RAS molecules. This review aims to discuss possible SARS-CoV-2 intracellular signaling pathways, cell entry mechanism and the possible consequences of the interaction with RAS components, including Angiotensin II (Ang II), Angiotensin-(1-7) [Ang-(1-7)], Angiotensin-converting enzyme (ACE), ACE2, Angiotensin II receptor type-1 (AT1), and Mas Receptor. We also discuss ongoing clinical trials and treatment based on RAS cascade intervention. Data were obtained independently by the two authors who carried out a search in the PubMed, Embase, LILACS, Cochrane, Scopus, SciELO and the National Institute of Health databases using Medical Subject Heading terms as "SARS-CoV-2," "COVID-19," "Renin Angiotensin System," "ACE2," "Angiotensin II," "Angiotensin-(1-7)," and "AT1 receptor." Similarly to other members of Coronaviridae family, the molecular interactions between the pathogen and the membrane-bound ACE2 are based on the cleavage of the spike glycoprotein (S) in two subunits. Following the binding of the S1 receptor-binding domain (RBD) to ACE2, transmembrane protease/serine subfamily 2 (TMPRSS2) cleaves the S2 domain to facilitate membrane fusion. It is very likely that SARS-CoV-2 cell entry results in downregulation of membrane-bound ACE2, an enzyme that converts Ang II into Ang-(1-7). This mechanism can result in lung injury and vasoconstriction. In addition, Ang II activates pro-inflammatory cascades when binding to the AT1 Receptor. On the other

The last decade was crucial for our understanding of the renin-angiotensin-aldosterone system (RAAS) as a two-axis, counterregulatory system, divided into the classical axis, formed by angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the angiotensin type 1 receptor (AT1R), and the alternative axis comprising angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) (Ang-(1-7)), and the Mas receptor. Breakthrough discoveries also took place, with other RAAS endopeptides being described, including alamandine and angiotensin A. In this review, we characterize the two RAAS axes and the role of their components in pediatric kidney diseases, including childhood hypertension (HTN), pediatric glomerular diseases, congenital abnormalities of the kidney and urinary tract (CAKUT), and chronic kidney disease (CKD). We also present recent findings on potential interactions between the novel coronavirus, SARS-CoV-2, and components of the RAAS, as well as potential implications of coronavirus disease 2019 (COVID-19) for pediatric kidney diseases.

Background: Pediatric tumors remain the highest cause of death in developed countries. Research on novel therapeutic strategies with lesser side effects is of utmost importance. In this scenario, the role of Renin Angiotensin System (RAS) axes, the classical one formed by angiotensin converting enzyme (ACE), Angiotensin II and AT1 receptor and the alternative axis composed by ACE2, Angiotensin-(1-7) and Mas receptor, have been investigated in cancer. Objective: This review aimed to summarize the pathophysiological role of RAS in cancer, evidence for anti-tumor effects of ACE2/Angiotensin-(1-7)/Mas receptor axis and future therapeutic perspectives for pediatric cancer. Methods: Pubmed, Scopus and Scielo were searched in regard to RAS molecules in human cancer and in pediatric patients. The search terms were “RAS”, “ACE”, “Angiotensin-(1-7)”, “ACE2”, “Angiotensin II”, “AT1 receptor”, “Mas receptor”, “Pediatric”, “Cancer”. Results: Experimental studies have shown that Angiotensin-(1-7) inhibits the growth of tumors cells and reduces local inflammation and angiogenesis in several types of cancer. Clinical trials with Angiotensin-(1-7) or TXA127, a pharmaceutical grade formulation of the naturally occurring peptide, have reported promising findings, but not enough to recommend medical use in human cancer. In regard to pediatric cancer, only three articles that marginally investigated RAS components were found and none of them evaluated molecules of the alternative RAS axis. Conclusion: Despite the potential applicability of Angiotensin-(1-7) in pediatric tumors, the role of this molecule was never tested. Further clinical trials are necessary, also including pediatric patients, to confirm safety and efficiency and to define therapeutic targets.

Introduction: Preventing and fighting COVID-19 are of the utmost importance. In this context, the importance of using telemedicine tools has grown, including teleconsultations, epidemiological telemonitoring, remote diagnosis, support, and training of health professionals. Objective: This article aims to report the results of a distance-training course on SARS-CoV-2 and COVID-19. We analyze the course adherence, the students’ profile, pre, and post-test proficiency index and satisfaction with the course. Methods: This is a cross-sectional study that evaluated data from the course on SARS-CoV-2 and COVID-19. The data were analyzed in terms of distribution and comparisons of means and frequencies. A paired t-test was used to compare the pre and post-test grades. A p-value <0.05 was considered significant. Data were collected from the Moodle teaching platform, without identifying the participants. Results: From March 23 to May 14, the course was offered to 1,008 medical students and health care providers. Most were from the state of Minas Gerais, some from other Brazilian states, and Mozambique. The majority completed the course, with an 89.8% adherence. The evaluations related to the course, the tutors, the degree of satisfaction, and the security for the professional performance after the course obtained maximum scores. The comparison between the pre and post grades showed proficiency gain (p<0.0001). Conclusion: The course has contributed to the training of medical students and health professionals from Brazil and Mozambique. The organizing committee was able to prepare students and provide knowledge to professionals with difficulty to access good technical and evidence-based information. After the training, the students were selected to work on university projects aiming at supporting city halls, health departments, and the community.

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