Clinical Impact and Risk Factors of Mortality in Hospitalized Children and Adolescents With Hematological Diseases and COVID-19: An Observational Retrospective Cohort Study.

This study aimed to evaluate the risk factors for COVID-19-related death in a large cohort of hospitalized children with hematological disorders. We performed an analysis of all pediatric patients with COVID-19 registered in a Brazilian nationwide surveillance database between February 2020 and May 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using the cumulative incidence function. Among 21,591 hospitalized pediatric patients with COVID-19, 596 cases (2.8%) had hematological diseases. Sixty-one children (27.4%) with malignant hematological diseases had a fatal outcome as compared with 4.2% and 7.4% of nonmalignant hematological and nonhematological cohorts, respectively (P<0.0001). Children with hematological diseases had a significant increased hazard of death compared with those without these conditions (hazard ratio [HR],=2.40, 95% confidence interval, 1.98 - 2.91). In multivariable analysis, the factors associated with death were the presence of malignant hematological disease (HR, 2.22, 95% CI 1.47 - 3.36), age >10 years (HR 2.19, 95% CI 1.46 - 3.19), male (HR 1.52, 95% CI 1.02 - 2.27), oxygen saturation <95% (HR 2.02, 95% CI 1.38 - 2.96), and abdominal pain at admission (HR 2.75, 95% CI 1.76 - 4.27). Children with malignant hematological diseases had a higher risk of death compared with those without these disorders.

Vaccine effectiveness against SARS-CoV-2 variants in adolescents from 15 to 90 days after second dose: a population-based test-negative case-control study.

OBJECTIVE: To estimate the vaccine effectiveness (VE) against hospitalization and severe illness in adolescents due to infection with SARS-CoV-2 variants (gamma, delta, and omicron). STUDY DESIGN: A test-negative, case-control analysis was conducted in Brazil from July 2021 to March 2022. We enrolled 8,458 eligible individuals (12 - 19 years of age) hospitalized with an acute respiratory syndrome, including 3,075 cases with laboratory-proven COVID-19 and 4,753 controls with negative tests for COVID-19. The primary exposure of interest was vaccination status. The primary outcome was SARS-CoV-2 infection during gamma/delta vs. omicron-predominant periods. The adjusted odds ratio for the association of prior vaccination and outcomes was used to estimate VE. RESULTS: In the pre-omicron period, VE against COVID-19 hospitalization was 88% (95%CI, 83% to 92%) and has dropped to 59% (95%CI, 49% to 66%) during the omicron period. For hospitalized cases of COVID-19, considering the entire period of the analysis, 2-dose schedule was moderately effective against ICU admission (46%, [95%CI, 27 to 60]), need of mechanical ventilation (49%, [95%CI, 32 to 70]), severe COVID-19 (42%, [95%CI, 17 to 60]), and death (46%, [95%CI, 8 to 67]). There was a substantial reduction of about 40% in the VE against all endpoints, except for death, during the omicron-predominant period. Among cases, 240 (6.6%) adolescents died; of fatal cases, 224 (93.3%) were not fully vaccinated. CONCLUSION: Among adolescents, the VE against all endpoints was substantially reduced during the omicron-predominant period. Our findings suggest that the two-dose regimen may be insufficient for SARS-CoV-2 variants and support the need for updated vaccines to provide better protection against severe COVID-19.

The use and role of telemedicine in maternal fetal medicine around the world: an up-to-date.

Purpose: The aim of this narrative review is to sumarize data about the use and role of telemedicine in maternal fetal medicine (MFM). Methods: We searched pubmed and scopus to find articles about telemedicine in MFM by using the terms telmedicine or telehealth and maternal fetal medicine. Results: Telehealth has been widely used for several medical specialties. During the coronavirus disease 2019 (COVID-19) pandemic, telehealth has gained investment and further research. Even though telemedicine in MFM has not been frequently applied, from 2020 onwards it has increased in both implementation and acceptance worldwide. The need to screen the patients in overloaded centers in a pandemic scenario required telemedicine in MFM, which has exhibited consistently good results concerning health and budget. The aim of this study was to review the telehealth programs and research focused on MFM around the world. Few studies have been applied to MFM and even fewer in developing and undeveloped countries. The majority of studies were concentrated in the USA and in Europe. Conclusion: Further research is needed, especially in non-developed countries, to comprehend the potential role of telemedicine in MFM for improving the life quality of the patients, health professionals, and to be cost-efficient.

Outcomes and risk factors for death among hospitalized children and adolescents with kidney diseases and COVID-19: an analysis of a nationwide database.

BACKGROUND: Patients with kidney diseases (KD) appear to be at particularly high risk for severe COVID-19. This study aimed to characterize the clinical outcomes and risk factors for COVID-19-related death in a large cohort of hospitalized pediatric patients with KD. METHODS: We performed an analysis of all pediatric patients with KD and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 16, 2020, and May 29, 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using cumulative incidence function. RESULTS: Among 21,591 hospitalized patients with COVID-19, 290 cases (1.3%) had KD. Of these, 59 (20.8%) had a fatal outcome compared with 7.5% of the non-KD cohort (P < 0.001). Pediatric patients with KD had an increased hazard of death compared with the non-KD cohort (Hazard ratio [HR] = 2.85, 95% CI 2.21-3.68, P < 0.0001). After adjustment, the factors associated with the death among KD patients were living in Northeast (HR 2.16, 95% CI 1.13-4.31) or North regions (HR 3.50, 95% CI 1.57-7.80), oxygen saturation < 95% at presentation (HR 2.31, 95% CI 1.30-4.10), and presence of two or more associated comorbidities (HR 2.10, 95% CI 1.08-4.04). CONCLUSIONS: Children and adolescents with KD had a higher risk of death compared with the non-KD cohort. The higher risk was associated with low oxygen saturation at admission, living in socioeconomically disadvantaged regions, and presence of other pre-existing comorbidities. A higher resolution version of the Graphical abstract is available as Supplementary information.

Imaging markers of neurologic damage in COVID-19: a systematic review.

BACKGROUND AND OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection commonly leads to neurologic manifestations. In the present review, we aimed to investigate potential neuroimaging markers of early diagnosis and prognosis of neurologic manifestations in COVID-19. METHODS: Our study was registered in the Prospective Register of Systematic Reviews (PROSPERO) under the protocol CDR42021265443. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we selected 51 studies for whole-manuscript analysis. RESULTS: Magnetic resonance imaging (MRI) was the most common imaging method. The pattern, sites of lesion, signs, and symptoms of neurologic injury varied. Such manifestations possibly resulted from a direct viral infection or, most likely, from indirect mechanisms including coagulation disturbances, hypoxemia, and immunological responses. CONCLUSION: The heterogeneity of the studies precludes any generalization of the findings. Brain MRI is the most informative imaging exam. Population studies including the entire spectrum of COVID-19 are missing. There is still a need for future population studies evaluating neurologic manifestations of all COVID-19 severities acutely and chronically.

Risk for Severe Illness and Death among Pediatric Patients with Down Syndrome Hospitalized for COVID-19, Brazil.

Down syndrome is the most common human chromosomal disorder. Whether Down syndrome is a risk factor for severe COVID-19 outcomes in pediatric patients remains unclear, especially in low-to-middle income countries. We gathered data on patients <18 years of age with SARS-CoV-2 infection from a national registry in Brazil to assess the risk for severe outcomes among patients with Down syndrome. We included data from 14,684 hospitalized patients, 261 of whom had Down syndrome. After adjustments for sociodemographic and medical factors, patients with Down syndrome had 1.8 times higher odds of dying from COVID-19 (odds ratio 1.82, 95% CI 1.22-2.68) and 27% longer recovery times (hazard ratio 0.73, 95% CI 0.61-0.86) than patients without Down syndrome. We found Down syndrome was associated with increased risk for severe illness and death among COVID-19 patients. Guidelines for managing COVID-19 among pediatric patients with Down syndrome could improve outcomes for this population.

Better healthcare can reduce the risk of COVID-19 in-hospital post-partum maternal death: evidence from Brazil.

OBJECTIVE: COVID-19 in post-partum women is commonly overlooked. The present study assessed whether puerperium is an independent risk factor of COVID-19 related in-hospital maternal death and whether fatality is preventable in the Brazilian context. METHODS: We retrospectively studied the clinical data of post-partum/pregnant patients hospitalized with COVID-19 gathered from a national database that registered severe acute respiratory syndromes (SIVEP-Gripe) in Brazil. Logistic regressions were used to examine the associations of in-hospital mortality with obstetric status and with the type of public healthcare provider, adjusting for socio-demographic, epidemiologic, clinical and healthcare-related measures. RESULTS: As of 30 November 2021, 1943 (21%) post-partum and 7446 (79%) pregnant patients of age between 15 and 45 years with COVID-19 that had reached the clinical endpoint (death or discharge) were eligible for inclusion. Case-fatality rates for the two groups were 19.8% and 9.2%, respectively. After the adjustment for covariates, post-partum patients had almost twice the odds of in-hospital mortality compared with pregnant patients. Patients admitted to private (not-for-profit) hospitals, those that had an obstetric centre or those located in metropolitan areas were less likely to succumb to SARS-CoV-2 infection. Those admitted to the Emergency Care Unit had similar mortality risk to those admitted to other public healthcare providers. CONCLUSION: We demonstrated that puerperium was associated with an increased odds of COVID-19-related in-hospital mortality. Only part of the risk can be reduced by quality healthcare such as non-profit private hospitals, those that have an obstetric centre or those located in urban areas.

Outcomes and risk factors of death among hospitalized children and adolescents with obesity and COVID-19 in Brazil: An analysis of a nationwide database.

BACKGROUND: Obesity is a well-recognized risk factor for critical illness and death among adult patients with SARS-CoV-2 infection. OBJECTIVE: This study aimed to characterize the clinical outcomes and risk factors of death related to obesity in a cohort of hospitalized paediatric patients with COVID-19. METHODS: We performed an analysis of all paediatric patients with obesity and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 2020 and May 2021. The primary outcome was time to death, which was evaluated by using cumulative incidence function. RESULTS: Among 21 591 hospitalized paediatric patients with COVID-19, 477 cases (2.2%) had obesity. Of them, 71 (14.9%) had a fatal outcome as compared with 7.5% for patients without obesity (hazard ratio [HR] = 2.0, 95% confidence interval [CI] 1.59-2.53, p < 0.001). After adjustment, the factors associated with death among patients with obesity were female gender (HR = 2.8, 95% CI 1.70-4.61), oxygen saturation < 95% (HR = 2.58, 95% CI 1.38-4.79), presence of one (HR = 1.91, 95% CI 1.11-3.26), and two or more comorbidities (HR = 4.0, 95% CI 2.21-7.56). CONCLUSIONS: Children and adolescents with obesity had higher risk of death compared with those without obesity. The higher risk of death was associated with female gender, low oxygen saturation at admission, and presence of other comorbidities.

Risk factors for COVID-19-related mortality in hospitalized children and adolescents with diabetes mellitus: An observational retrospective cohort study.

BACKGROUND: Diabetes has been recognized as a major comorbidity for COVID-19 severity in adults. This study aimed to characterize the clinical outcomes and risk factors for COVID-19-related death in a large cohort of hospitalized pediatric patients with diabetes. METHODS: We performed an analysis of all pediatric patients with diabetes and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 2020 and May 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using cumulative incidence function. RESULTS: Among 21,591 hospitalized pediatric patients with COVID-19, 379 (1.8%) had diabetes. Overall, children and adolescents with diabetes had a higher prevalence of ICU admission (46.6% vs. 26%), invasive ventilation (16.9% vs. 10.3%), and death (15% vs. 7.6%) (all P < 0.0001). Children with diabetes had twice the hazard of death compared with pediatric patients without diabetes (Hazard ratio [HR] = 2.0, 95% CI, 1.58-2.66). Among children with diabetes, four covariates were independently associated with the primary outcome, living in the poorest regions of the country (Northeast, HR, 2.17, 95% CI 1.18-4.01, and North, (HR 4.0, 95% CI 1.79-8.94), oxygen saturation < 95% at admission (HR 2.97, 95% CI 1.64-5.36), presence of kidney disorders (HR 3.39, 95% CI 1.42-8.09), and presence of obesity (HR 3.77, 95% CI 1.83-7.76). CONCLUSION: Children and adolescents with diabetes had a higher risk of death compared with patients without diabetes. The higher risk of death was associated with clinical and socioeconomic factors.

Renal Involvement in Pediatric Patients with COVID-19: An Up-to-date Review.

BACKGROUND: In pediatric patients, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has been mostly associated with mild symptoms. However, as in adults, renal involvement has been reported in children and adolescents with Coronavirus Disease 2019 (COVID-19). OBJECTIVE: This review aimed to report data about renal involvement in pediatric COVID-19 patients. The focuses were on the pathophysiology of acute kidney injury in Pediatric Inflammatory Multisystem Syndrome Temporally Associated (PIMS-TS) with SARS-CoV-2 and the possible impact of SARS-CoV-2 infection upon kidney function, as well as data concerning patients with previous kidney diseases, including Nephrotic Syndrome and Chronic Renal Disease. The implications for COVID-19 outcomes in pediatric patients were also discussed. METHODS: This integrative review searched for articles on renal involvement in pediatric COVID-19 patients. The databases evaluated were PubMed and Scopus. RESULTS: The emergence of PIMS-TS with SARS-CoV-2 has shown that pediatric patients are at risk of severe COVID-19, with multi-organ involvement and dysfunction. In addition to intense inflammation, several systems are affected in this syndrome, collectively creating a combination of factors that results in acute kidney injury. Several studies have proposed that kidney cells, including the podocytes, might be at risk of direct infection by SARS-CoV-2, as high levels of ACE2, the virus receptor, are expressed on the membrane of such cells. Some cases of glomerular diseases triggered by SARS-CoV-2 infection and relapses of previous renal diseases have been reported. CONCLUSION: Further studies are necessary to establish risk factors for renal involvement in pediatric COVID-19 and to predict disease outcomes.

Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux.

BACKGROUND: Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood. METHODS: A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR. A GWAS was performed in 1395 patients and 5366 controls, of European ancestry. RESULTS: Altogether, 3% of VUR patients harbored an undiagnosed rare CNV disorder, such as the 1q21.1, 16p11.2, 22q11.21, and triple X syndromes ((OR, 3.12; 95% CI, 2.10 to 4.54; P=6.35×10-8) The GWAS identified three study-wide significant and five suggestive loci with large effects (ORs, 1.41-6.9), containing canonical developmental genes expressed in the developing urinary tract (WDPCP, OTX1, BMP5, VANGL1, and WNT5A). In particular, 3.3% of VUR patients were homozygous for an intronic variant in WDPCP (rs13013890; OR, 3.65; 95% CI, 2.39 to 5.56; P=1.86×10-9). This locus was associated with multiple genitourinary phenotypes in the UK Biobank and eMERGE studies. Analysis of Wnt5a mutant mice confirmed the role of Wnt5a signaling in bladder and ureteric morphogenesis. CONCLUSIONS: These data demonstrate the genetic heterogeneity of VUR. Altogether, 6% of patients with VUR harbored a rare CNV or a common variant genotype conferring an OR >3. Identification of these genetic risk factors has multiple implications for clinical care and for analysis of outcomes in VUR.

COVID-19 pandemic and the answer of science: a year in review.

The world is looking forward to a prompt response by the scientific community in order to overcome the first pandemic of the 21st century. This study aimed to provide an overview of scientific output on COVID-19 during its first year. We assembled information regarding 60,830 articles related to COVID-19 indexed in the WoS database from January 24 to December 13, 2020. Only 4 countries accounted for about 60% of the articles (USA, China, Italy, and England) and 12 countries accounted for about 95% of the world scientific output on COVID-19 (USA, China, Italy, England, India, Canada, Germany, Spain, Australia, Brazil, Iran, and Turkey). 25 research centers around the world contributed with more than 500 papers on COVID-19. Papers were scattered throughout 6,133 journals, with 12 journals with > 250 articles. 20 articles (0.03%) have already received more than the 1,000 citations. The response of the scientific endeavor to this acute global public health emergency has been fast and robust. The overview provided by the analysis of the scientific response to the pandemic may contribute to further studies aiming to evaluate the impact and changes in the scientific endeavor for the next years in light of the forthcoming new world framework.

The Impact of Vaccination Worldwide on SARS-CoV-2 Infection: A Review on Vaccine Mechanisms, Results of Clinical Trials, Vaccinal Coverage and Interactions with Novel Variants.

BACKGROUND: The COVID-19 pandemic demanded a global effort towards quickly developing safe and effective vaccines against SARS-CoV-2. OBJECTIVE: This review aimed to discuss the main vaccines available, their mechanisms of action, results of clinical trials, and epidemiological behavior. The implications of viral variants were also debated. METHODS: A non-systematic literature review was performed between February and March 2021 by searching the Pubmed, Scopus, and SciELO databases, using different combinations of the following terms: "vaccines", "clinical trials" , "SARS-CoV-2", "Coronavirus", "COVID-19", "mechanisms of action". Data regarding clinical trials of SARS-CoV-2 vaccines and epidemiological information were also searched. RESULTS: The mechanisms of action included vector-virus, mRNA and inactivated virus vaccines. The vaccines showed positive results in phases 2/3 clinical trials. The efficacy of the mRNA 1273 and of mRNA BNT 162b2 vaccines were 94.1% and 95%, respectively. The effectiveness of the ChAdOx1 nCoV-19 vaccine varied according to the scheme, with an overall value of 70.4%. The Gam-COVID-Vac vaccine had an efficacy of 91.6%. Regarding the Ad26.COV2.S vaccine, 99% or more of seroconversion was observed in all subgroups 29 days after vaccination. The CoronaVac vaccine induced an immune response in 92% of the volunteers receiving 3ug and in 98% with 6ug, in comparison to 3% in the placebo group. CONCLUSION: Global efforts have resulted in vaccines being available in record time, with good safety and immunogenicity profile. However, only long-term studies can provide more information on the duration of immunity and the need for additional doses.

Renin Angiotensin System (RAS) and Immune System Profile in Specific Subgroups with COVID-19.

BACKGROUND: The identification of vulnerable subgroups and risk factors associated with the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) infection and coronavirus disease 2019 (COVID-19) is of utmost importance in a pandemic scenario. Potential interactions between renin-angiotensin system (RAS), immune markers and COVID-19 play a role in disease outcome in specific groups of patients. OBJECTIVE: This review aimed to describe the particularities of the RAS and the immune system profile of particular subgroups of patients. METHODS: This non-systematic review summarizes evidence on SARS-CoV-2 infection in specific subgroups of patients and possible relationships between immune system, RAS and the pathophysiology of COVID-19. RESULTS: The RAS and the immune system exert a role in the pathogenesis and prognosis of COVID-19, mainly in cases of hypertension, diabetes, obesity and other chronic diseases. The overactivation of the ACE/Ang II/AT1R axis and the enhancement of inflammation contribute to deleterious effects of COVID-19. Likewise, pregnant women and elderly patients usually display immune responses that are less effective in withstanding exposition to viruses, while children are relatively protected against severe complications of COVID-19. Women, conversely, exhibit stronger antiviral responses and are less sensitive to the effects of increased Ang II. Future Perspectives: The recognition of vulnerable subgroups and risk factors for disease severity is essential to better understand the pandemic. Precision medicine tools, including proteomics and metabolomics approaches, identified metabolic patterns of the severe form of disease and might be the alternative to diagnose, evaluate and predict the prognosis and the efficiency of therapies.

Clinical characteristics and risk factors for death among hospitalised children and adolescents with COVID-19 in Brazil: an analysis of a nationwide database.

BACKGROUND: COVID-19 is usually less severe and has lower case fatality in children than in adults. We aimed to characterise the clinical features of children and adolescents hospitalised with laboratory-confirmed SARS-CoV-2 infection and to evaluate the risk factors for COVID-19-related death in this population. METHODS: We did an analysis of all patients younger than 20 years who had quantitative RT-PCR-confirmed COVID-19 and were registered in the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe, a nationwide surveillance database of patients admitted to hospital with severe acute respiratory disease in Brazil), between Feb 16, 2020, and Jan 9, 2021. The primary outcome was time to recovery (discharge) or in-hospital death, evaluated by competing risks analysis using the cumulative incidence function. FINDINGS: Of the 82 055 patients younger than 20 years reported to SIVEP-Gripe during the study period, 11 613 (14·2%) had available data showing laboratory-confirmed SARS-CoV-2 infection and were included in the sample. Among these patients, 886 (7·6%) died in hospital (at a median 6 days [IQR 3-15] after hospital admission), 10 041 (86·5%) patients were discharged from the hospital, 369 (3·2%) were in hospital at the time of analysis, and 317 (2·7%) were missing information on outcome. The estimated probability of death was 4·8% during the first 10 days after hospital admission, 6·7% during the first 20 days, and 8·1% at the end of follow-up. Probability of discharge was 54·1% during the first 10 days, 78·4% during the first 20 days, and 92·0% at the end of follow-up. Our competing risks multivariate survival analysis showed that risk of death was increased in infants younger than 2 years (hazard ratio 2·36 [95% CI 1·94-2·88]) or adolescents aged 12-19 years (2·23 [1·84-2·71]) relative to children aged 2-11 years; those of Indigenous ethnicity (3·36 [2·15-5·24]) relative to those of White ethnicity; those living in the Northeast region (2·06 [1·68-2·52]) or North region (1·55 [1·22-1·98]) relative to those in the Southeast region; and those with one (2·96 [2·52-3·47]), two (4·96 [3·80-6·48]), or three or more (7·28 [4·56-11·6]) pre-existing medical conditions relative to those with none. INTERPRETATION: Death from COVID-19 was associated with age, Indigenous ethnicity, poor geopolitical region, and pre-existing medical conditions. Disparities in health care, poverty, and comorbidities can contribute to magnifying the burden of COVID-19 in more vulnerable and socioeconomically disadvantaged children and adolescents in Brazil. FUNDING: National Council for Scientific and Technological Development, Research Support Foundation of Minas Gerais.

2020 update on the renin–angiotensin–aldosterone system in pediatric kidney disease and its interactions with coronavirus

The last decade was crucial for our understanding of the renin–angiotensin–aldosterone system (RAAS) as a two-axis, counter-regulatory 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.

Renin-Angiotensin System in Central Nervous System Diseases and its Interaction with COVID-19.

BACKGROUND: The Renin-Angiotensin System (RAS) comprises a complex molecular cascade with two counter-regulatory axes, the classical and the alternative. Angiotensin II and Angiotensin-(1-7), the main peptides of the RAS, exert opposite effects in multiple organs and systems, including the cardiovascular, renal, pulmonary, and immune systems. Strong evidence supports the hypothesis of a local RAS in the Central Nervous System (CNS) and its modulatory roles in neuroendocrinology and neurotransmission. OBJECTIVE: In this narrative review, we provide a comprehensive approach to experimental and clinical data regarding RAS molecule expression and their possible roles in the physiology and physiopathology of CNS diseases. METHODS: This non-systematic review summarizes evidence on RAS implications in CNS diseases and their possible relationships with COVID-19. RESULTS: We divided the possible RAS mechanisms in distinct conditions during the lifespan, approaching from congenital infections to neurodegenerative alterations, passing through mood disorders and cerebrovascular diseases. We also gathered current evidence about the possible effects of RAS in Covid-19, particularly in cases with neurological manifestations. CONCLUSION: Although there are limitations and controversies, the analysis of RAS mechanisms in the CNS certainly represents an interesting field of research. However, further investigation is necessary to support the noteworthy interactions and provide a better comprehension of the cross-talk between RAS and the CNS. Investigations in this research field may shed light on the novel therapeutic targets.

How is COVID-19 pandemic impacting mental health of children and adolescents?

The coronavirus disease (COVID-19) affected virtually all countries. Uncertain about the health risk and an increasing financial loss will contribute to widespread emotional distress and an increased risk of psychiatric disorders shortly. Posttraumatic, anxiety, and depression disorders are expected during and aftermath of the pandemic. Some groups, like children, have more susceptibility to having long term consequences in mental health. Herein, we made a comprehensive and non-systematic search in four databases (PubMed, Scopus, SciELO, and Google Scholars) to answer the question: What are children's and adolescents' mental health effects of the pandemic? Furthermore, which features are essential for mental health in a pandemic? Results: Seventy-seven articles were selected for full text read, and 51 were included. Children answer stress differently, depending on the development stage. High rates of anxiety, depression, and post-traumatic symptoms were identified among children. Discussion: Symptoms were as expected. New supportive strategies have appeared during this pandemic, but there is no measure of its effectiveness. Some groups seem to be more vulnerable to the mental health burden of the COVID-19 pandemic, and the mitigation actions should prioritize them. The school's role appears to be revalued by society. This review seems to pick good targets to prioritize mitigation actions aiming to spare children not only from the severe cases of COVID-19 but also to help them to deal with the mental health burden of the pandemics.

Emotional, Behavioral, and Psychological Impact of the COVID-19 Pandemic.

The emergence of SARS-CoV-2 in December 2019 prompted consternation in many parts of the world. Due to its fast dissemination, the World Health Organization declared a pandemic in March 2020. Aiming to contain the spread of the virus, leaders of many countries restrained social movement, targeting to flatten the curve of contamination with social distancing. This review aimed to analyze how human behavior has changed throughout this period. We also approached the key components of the emotional reaction to the pandemic, how internal and external factors, such as personality traits, gender, the media, the economy and the governmental response, influence the social perception of the pandemic and the psychological outcomes of the current scenario. Moreover, we explored in depth the groups at increased risk of suffering mental health burden secondary to these circumstances. These include the healthcare professionals, elderly individuals, children, college students, black subjects, latin and LGBTQ+ communities, economically disadvantaged groups, the homeless, prisoners, the rural population and psychiatric patients. We also discussed several measures that might minimize the emotional impact derived from this scenario. It is crucial that the health authorities, the government and the population articulate to assist the vulnerable groups and promote emotional and psychological support strategies. Moreover, it is fundamental that the population is provided with accurate information concerning the COVID-19 pandemic.