The genetic landscape of mitochondrial diseases in the next-generation sequencing era: a Portuguese cohort study.

Introduction: Rare disorders that are genetically and clinically heterogeneous, such as mitochondrial diseases (MDs), have a challenging diagnosis. Nuclear genes codify most proteins involved in mitochondrial biogenesis, despite all mitochondria having their own DNA. The development of next-generation sequencing (NGS) technologies has revolutionized the understanding of many genes involved in the pathogenesis of MDs. In this new genetic era, using the NGS approach, we aimed to identify the genetic etiology for a suspected MD in a cohort of 450 Portuguese patients. Methods: We examined 450 patients using a combined NGS strategy, starting with the analysis of a targeted mitochondrial panel of 213 nuclear genes, and then proceeding to analyze the whole mitochondrial DNA. Results and Discussion: In this study, we identified disease-related variants in 134 (30%) analyzed patients, 88 with nuclear DNA (nDNA) and 46 with mitochondrial DNA (mtDNA) variants, most of them being pediatric patients (66%), of which 77% were identified in nDNA and 23% in mtDNA. The molecular analysis of this cohort revealed 72 already described pathogenic and 20 novel, probably pathogenic, variants, as well as 62 variants of unknown significance. For this cohort of patients with suspected MDs, the use of a customized gene panel provided a molecular diagnosis in a timely and cost-effective manner. Patients who cannot be diagnosed after this initial approach will be further selected for whole-exome sequencing. Conclusion: As a national laboratory for the study and research of MDs, we demonstrated the power of NGS to achieve a molecular etiology, expanding the mutational spectrum and proposing accurate genetic counseling in this group of heterogeneous diseases without therapeutic options.

The Effect of Colloidal Silica and Glaze Coatings on the Adhesion of Zirconia with Various Ytrria Concentration.

PURPOSE: This study evaluated the effect of coating traditional and translucent Y-TZP with an industrial nanometric colloidal silica or glaze before or after sintering on the adhesion of zirconia with various ytrria concentration. MATERIALS AND METHODS: Specimens of Y-TZP with 3% and 5% yttria were subdivided into 5 groups (n=10), according to the coating applied and moment of application (before or after Y-TZP sintering): Control (no coating), Colloidal Silica/Sintering, Sintering/Colloidal Silica, Glaze/Sintering, Sintering/ Glaze. Lithium disilicate (LD) was used as positive control. Except for Y-TZP controls, groups were conditioned with silane before cementation with a self-adhesive resin cement. After 24 hours, the shear bond strength and failure analysis were performed. Also, analysis of specimens' surface was accomplished with SEM-EDX. Kruskal-Wallis and Dunn tests were applied to analyze differences between groups (p⟨0.05). RESULTS: Overall, the worst and best values of shear bond strength test were control and glaze after sintering groups. Different morphological and chemical aspects were observed in SEM-EDX analysis. CONCLUSIONS: Coating Y-TZP with colloidal silica showed unsatisfactory results. In 3Y-TZP, the surface treatment associated with the best adhesion values was the application of glaze after zirconia sintering. However, in 5Y-TZP, glaze application can be performed before or after the zirconia sintering to optimize clinical steps.

Manejo anestésico perioperatorio de la deficiencia de acil-coenzima A deshidrogenasa de cadena muy larga / Perioperative anesthetic management of very long-chain acyl-coenzyme a dehydrogenase deficiency

La deficiencia de acil-coenzima A deshidrogenasa de cadena muy larga (VLCADD) es un trastorno infrecuente del metabolismo de β-oxidación de los ácidos grasos que origina susceptibilidad a hipoglucemia, fallo hepático, cardiomiopatía y rabdomiólisis durante las situaciones catabólicas. Reportamos el caso de un varón de 10 años de edad programado para la colocación de catéter venoso central totalmente implantado durante su hospitalización por rabdomiólisis, que fue exitosamente gestionada con anestesia general con óxido nitroso, sevoflurano y remifentanilo. No se produjo hipoglucemia y los niveles de creatina quinasa no se incrementaron durante el periodo perioperatorio. Describimos las dificultades a que nos enfrentamos, y las estrategias utilizadas para evitar mayor descompensación de la enfermedad debida al estrés quirúrgico.(AU)

Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare disorder of β-oxidation fatty acid metabolism that results in susceptibility to hypoglycemia, liver failure, cardiomyopathy and rhabdomyolysis during catabolic situations. We report the case of a 10-year-old male undergoing a totally implanted central venous catheter placement during hospitalization for rhabdomyolysis, who was successfully managed with general anesthesia with nitrous oxide, sevoflurane and remifentanil. No hypoglycemia occurred and creatine kinase levels did not increase in the perioperative period. We describe the challenges encountered and the strategies used to avoid further decompensation of the disease due to surgical stress.(AU)

Hypoglycemic effect of Coffea arabica leaf extracts and major bioactive constituents.

The present study focused on investigating the antioxidant, antiglycation activity, digestive enzymes inhibition, bioaccessibility and hypoglycemic effect of C. arabica leaves extracts. The extracts deactivated the O2•-, ROO•, H2O2, HOCl reactive oxygen species. Coffee leaves showed strong inhibition of α-glucosidase (IC50 = 40.30 µg mL-1) greater than the isolated metabolites and acarbose. There was also inhibition of pancreatic lipase (IC50 = 56.43 µg mL-1) in addition to a hypoglycemic effect in zebrafish similar to acarbose and metformin. With the exception of rutin, all biocompounds were detected at all stages of in vitro digestion. Finally, these results suggest that C. arabica leaf extracts possess antidiabetic and anti-obesity properties that can be attributed to the main metabolites and the synergistic action between them.Communicated by Ramaswamy H. Sarma.

Perioperative anesthetic management of very long-chain acyl-coenzyme a dehydrogenase deficiency.

Very long-chain acyl-coenzyme A dehydrogenase deficiency is a rare disorder of ß-oxidation fatty acid metabolism that results in susceptibility to hypoglycemia, liver failure, cardiomyopathy and rhabdomyolysis during catabolic situations. We report the case of a 10-year-old male undergoing a totally implanted central venous catheter placement during hospitalisation for rhabdomyolysis, who was successfully managed with general anesthesia with nitrous oxide, sevoflurane and remifentanil. No hypoglycemia occurred and creatine kinase levels did not increase in the perioperative period. We describe the challenges encountered and the strategies used to avoid further decompensation of the disease due to surgical stress.

Matteucinol combined with temozolomide inhibits glioblastoma proliferation, invasion, and progression: an in vitro, in silico, and in vivo study.

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 µg/mL Mat and 9.71 µg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.

Matteucinol combined with temozolomide inhibits glioblastoma proliferation, invasion, and progression: an in vitro, in silico, and in vivo study

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 μg/mL Mat and 9.71 μg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.

Multi-scale modeling of 2D GaSe FETs with strained channels.

Electronic devices based on bidimensional materials (2DMs) are the subject of an intense experimental research, that demands a tantamount theoretical activity. The latter must be hold up by a varied set of tools able to rationalize, explain and predict the operation principles of the devices. However, in the broad context of multi-scale computational nanoelectronics, there is currently a lack of simulation tools connecting atomistic descriptions with semi-classical mesoscopic device-level simulations and able to properly explain the performance of many state-of-the-art devices. To contribute to filling this gap we present a multi-scale approach that combines fine-level material calculations with a semi-classical drift-diffusion transport model. Its use is exemplified by assessing 2DM field effect transistors with strained channels, showing excellent capabilities to capture the changes in the crystal structure and their impact into the device performance. Interestingly, we verify the capacity of strain in monolayer GaSe to enhance the conduction of one type of carrier, enabling the possibility to mimic the effect of chemical doping on 2D materials. These results illustrate the great potential of the proposed approach to bridge levels of abstraction rarely connected before and thus contribute to the theoretical modeling of state-of-the-art 2DM-based devices.

Genetic identification of a rabies virus from an insectivorous bat in an urban area of Rio Grande do Sul, Brazil.

In Latin America, hematophagous bats are the main reservoirs of rabies virus (RABV) to livestock, to other mammals and, occasionally, to human. Nonetheless, reports of exposure of human and pets to RABV upon aggression by non-hematophagous bats are increasing, possibly facilitated by the synanthropic habits of these bats. We, herein, report the detection and genetic identification of a RABV recovered from an insectivorous bat found sick in a student housing building at the Federal University of Santa Maria, Southern Brazil. Taxonomic characterization identified the captured bat as a member of the genus Nyctinomops, family Molossidae, the group of insectivorous bats. Brain fragments of the bat were positive for RABV antigens by fluorescent antibody test (FAT) and for sequences of the nucleoprotein (N) gene by RT-PCR. The N amplicon was submitted to nucleotide sequencing and analysis, showing that the consensus sequences (SV 33/19) had high identity with RABV sequences of insectivorous bats deposited in GenBank. At phylogenetic tree, the N gene sequences of SV 33/19 clustered with RABV recovered from Nyctinomops laticaudatus, Molossus molossus, and Tadarida lauticaudata bats, and a part of RABV variant 3, 4, and 6, that correspond to Desmodus rotundus, Tadarida brasiliensis, and Lasiurus cinereus, respectively. Although no direct human or domestic animal exposure has been reported, this case strengthens the need for a continuous rabies vaccination in pets in the surrounding areas, since non-hematophagous bats may serve as source of infection for these animals. These findings also call attention for continuous monitoring of populations of synanthropic bats to avoid/prevent human exposure.

Prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm: a prospective cohort.

OBJECTIVE: To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks of gestation). DESIGN: The Extremely Low Gestational Age Newborn (ELGAN) Study, a prospective cohort. SETTING: Ten-year follow-up of extremely preterm infants born at 14 US hospitals between 2002 and 2004. METHODS: Prenatal tobacco smoke exposure was defined as a mother's report at enrolment of active (i.e. maternal) and passive smoking during pregnancy. Poisson regression with generalized estimating equations was used. Models adjusted for mother's age, race/ethnicity, education, insurance, pre-pregnancy body mass index, US region, multiple gestation and infant's sex; and in sensitivity analysis, gestational age at delivery and clinical subtype of preterm birth, given their classification as intermediate and non-confounding variables. MAIN OUTCOMES: Neurological impairment at 10 years, epilepsy, cerebral palsy and cognitive impairment. RESULTS: Of 1200 ELGAN study survivors, 856 were assessed at 10 years of age with neurological outcomes, of whom 14% (118/856) had active tobacco exposure during pregnancy and 24% (207/852) had passive tobacco exposure. Compared with children who were not exposed prenatally to tobacco, children exposed to active tobacco use during pregnancy had a higher risk of epilepsy (14% versus 5%; adjusted relative risk: 1.68, 95% CI 1.45-1.92). This risk remained after adjustment for gestational age at delivery and clinical subtype of preterm birth. Prenatal tobacco smoke exposure was not associated with other assessed neurological outcomes, including cerebral palsy and multiple measures of cognitive impairment. CONCLUSIONS: Among children born extremely preterm, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. TWEETABLE ABSTRACT: Among infants born before 28 weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life.

Generalizability of machine learning models and empirical equations for the estimation of reference evapotranspiration from temperature in a semiarid region.

The Penman-Monteith equation is recommended for the estimation of reference evapotranspiration (ETo). However, it requires meteorological data that are commonly unavailable. Thus, this study evaluates artificial neural network (ANN), multivariate adaptive regression splines (MARS), and the original and calibrated Hargreaves-Samani (HS) and Penman-Monteith temperature (PMT) equations for the estimation of daily ETo using temperature. Two scenarios were considered: (i) local, models were calibrated/developed and evaluated using data from individual weather stations; (ii) regional, models were calibrated/developed using pooled data from several stations and evaluated independently in each one. Local models were also evaluated outside the calibration/training station. Data from 9 stations were used. The original PMT outperformed the original HS, but after local or regional calibrations, they performed similarly. The locally calibrated equations and the local machine learning models exhibited higher performances than their regional versions. However, the regional models had higher generalization capacity, with a more stable performance between stations. The machine learning models performed better than the equations evaluated. When comparing the ANN models with the HS equation, mean RMSE reduced from 0.96 to 0.87 and from 0.84 to 0.73, in regional and local scenarios, respectively. ANN and MARS performed similarly, with a slight advantage for ANN.

Influence of dietary Chlorella vulgaris and carbohydrate-active enzymes on growth performance, meat quality and lipid composition of broiler chickens.

Herein, we investigated the effect of Chlorella vulgaris as ingredient (10% of incorporation) in broiler diets, supplemented or not with 2 formulations of Carbohydrate-Active enZymes (CAZymes; Rovabio Excel AP and a mixture of recombinant CAZymes, composed by an exo-ß-glucosaminidase, an alginate lyase, a peptidoglycan N-acetylmuramic acid deacetylase and a lysozyme), on growth performance, meat quality, fatty acid composition, oxidative stability, and sensory traits. One hundred twenty 1-day-old Ross 308 male birds were randomly assigned to one of the 4 experimental diets (n = 30): corn-soybean meal-basal diet (control), basal diet with 10% C. vulgaris (CV), CV supplemented with 0.005% of a commercial CAZyme cocktail (Rovabio Excel AP), (CV + R), and CV supplemented with 0.01% of a 4-CAZyme mixture previously selected (CV + M) during the experimental period lasted from day 21 to day 35. Body weight gain and feed conversion rate of broilers were not affected by C. vulgaris but digesta viscosity increased more than 2-fold (P < 0.001) relative to the control. In addition, neither cooking loss, shear force, juiciness, flavor nor off-flavor was impaired by dietary treatments (P > 0.05). By contrast, the dietary C. vulgaris increased tenderness, yellowness (b∗) and total carotenoids in breast and thigh meats. However, no additional protective effect against lipid oxidation was observed in meat with the inclusion of microalga. Chlorella vulgaris, independently of CAZymes, had a minor impact on meat fatty acid composition but improved the proportion of some beneficial fatty acids. In summary, our data indicate a slight improvement of broiler meat quality and lipid nutritional value, without impairment of broilers' growth performance, thus supporting the usefulness of this microalga in poultry diets, up to this high level of incorporation. By contrast, the selected CAZyme mixtures used do not significantly improve the release of microalga nutrients in poultry diets, through the disruption of microalga cell wall, which warrants further research.

Ecology and spatial distribution of sand fly species in low endemic areas for American Tegumentary Leishmaniasis in the municipality of Seropédica, Rio de Janeiro, Brazil.

Due to the fundamental role that sand flies (Diptera: Psychodidae) have in Leishmania spp. (Kinetoplastida: Trypanosomatidae) transmission, the objective of this study was to evaluate the ecology and spatial distribution of species circulating in the municipality of Seropédica, Rio de Janeiro, Brazil. A total of 17 371 specimens were collected between August 2016 and July 2017, and five species were identified: Nyssomyia intermedia (Lutz & Neiva, 1912), Migonemyia migonei (França, 1920), Nyssomyia whitmani (Antunes & Coutinho, 1939), Pintomyia pessoai (Coutinho & Barretto, 1940), and Pintomyia fischeri (Pinto, 1926). In relation to the number of sand flies collected, we observed a significant difference between rural and periurban areas and between the neighbourhoods. We observed that N. intermedia has a relatively greater adaptation to the peridomiciliary environment. This is the first report of Pi. pessoai and Pi. fischeri (only females) in Seropédica as well as the first record of the frequency of phlebotomine species focusing on some ecological indices and the spatial distribution of sand flies. The results presented here aimed to provide an insight into the spatial population dynamics of phlebotomine species in low endemic areas of American Tegumentary Leishmaniasis (ATL) in Seropédica, highlighting important areas for entomological surveillance.

Cardiac magnetic resonance in the assessment of pericardial abnormalities: a case series.

BACKGROUND: Cardiac magnetic resonance (CMR) has a unique role in evaluating pericardial disease, permitting non-invasive tissue analysis, and haemodynamic assessment. CASE SUMMARY: In Case 1 of recurrent pericarditis, CMR confirmed reactivation of inflammation with late gadolinium enhancement and native T1/T2 mapping techniques, prompting therapeutic changes. In constrictive pericarditis, CMR is the only modality capable of differentiating a subacute potentially reversible form (Case 2), from a chronic, burnt out irreversible phase characterized by constrictive physiology (Case 3). DISCUSSION: Cardiac magnetic resonance is an effective tool to tailor individual therapy, particularly in cases of recurrent and constrictive pericarditis. Late gadolinium enhancement provides diagnostic and prognostic information, and multiparametric mapping has emerged as a promising tool with incremental diagnostic value.

Trimers Conjugated to Fibrin Hydrogels Promote Salivary Gland Function.

New strategies for tissue engineering have great potential for restoring and revitalizing impaired tissues and organs, including the use of smart hydrogels that can be modified to enhance organization and functionality of the salivary glands. For instance, monomers of laminin-111 peptides chemically conjugated to fibrin hydrogel (L1pM-FH) promote cell cluster formation in vitro and salivary gland regeneration in vivo when compared with fibrin hydrogel (FH) alone; however, L1pM-FH produce only weak expression of acinar differentiation markers in vivo (e.g., aquaporin-5 and transmembrane protein 16). Since previous studies demonstrated that a greater impact can be achieved when trimeric forms were used as compared with monomeric or dimeric forms, we investigated the extent to which trimers of laminin-111 chemically conjugated to FH (L1pT-FH) can increase the expression of acinar differentiation markers and elevate saliva secretion. In vitro studies using Par-C10 acinar cells demonstrated that when compared with L1pM-FH, L1pT-FH induced similar levels of acinar-like cell clustering, polarization, lumen formation, and calcium signaling. To assess the performance of the trimeric complex in vivo, we compared the ability of L1pM-FH and L1pT-FH to increase acinar differentiation markers and restore saliva flow rate in a salivary gland wound model of C57BL/6 mice. Our results show that L1pT-FH applied to wounded mice significantly improved the expression of the acinar differentiation markers and saliva secretion when compared with the monomeric form. Together, these positive effects of L1pT-FH warrant its future testing in additional models of hyposalivation with the ultimate goal of applying this technology in humans.

Probiotic supplementation containing Bacillus velezensis enhances expression of immune regulatory genes against pigeon circovirus in pigeons (Columba livia).

AIMS: In this study, we aimed to isolate and evaluate the efficacy of Bacillus velezensis as a probiotic and to assess its activity towards pigeons infected with pigeon circovirus (PiCV). METHODS AND RESULTS: Bacillus velezensis, isolated from pigeon faeces, was orally administered to pigeons for 60 days. After pigeons were challenged with PiCV, the PiCV viral load and expression of indicator genes for innate immunity were detected in spleen tissue and faeces of pigeons. Bacillus velezensis significantly reduced the PiCV viral load in the faeces and spleen of pigeons 5 days post-challenge (dpc). The mRNA expression levels of treated pigeons showed that interferon-gamma (IFN-γ), myxovirus resistance 1 (Mx1), and signal transducers and activators of transcription 1 (STAT1) genes were upregulated, whereas no expression of interleukin-4 (IL-4) was detected. Moreover, toll-like receptor 2 (TLR2) and 4 (TLR4) were significantly upregulated in probiotic-treated pigeons (P < 0·05). CONCLUSIONS: This is the first report showing that probiotic supplementation can effectively enhance the T-helper type 1 immune response and decrease the PiCV viral loads in pigeons. SIGNIFICANCE AND IMPACT OF THE STUDY: This study proposes that the administration of a probiotic strain, B. velezensis, to pigeons can protect against PiCV infection.

Antifungal and antibiofilm activities of the essential oil of leaves from Lippia gracilis Schauer against phytopathogenic fungi.

AIMS: This study aimed to evaluate the antifungal and antibiofilm effects of essential oil (EO) from leaves of Lippia gracilis and its major constituents, thymol and carvacrol, against phytopathogenic fungi. METHODS AND RESULTS: The leaves of L. gracilis were hydrodistilled to obtain the EO and the chemical composition was determined by GC/MS analysis. The antifungal activity of EO of L. gracilis was evaluated on the vegetative and mycelial growth of Colletotrichum gloeosporioides, Colletotrichum lindemuthianum, Fusarium oxysporum and Fusarium solani. In addition, the ability of the oil to inhibit fungal biofilm formation was assessed by total biomass quantification using crystal violet staining, analysis of metabolic activity, and scanning electron microscopy (SEM). Moreover the antifungal and antibiofilm activities of the monoterpenes, thymol and carvacrol, present in EO of L. gracilis were evaluated against F. oxysporum. The analysis of the chemical composition of EO extracted from L. gracilis, revealed the presence of monoterpenes (94·13%), which included carvacrol (48·57%) and thymol (7·78%), and 4 sesquiterpenes (3·74%). In general, EO showed significant antifungal activity and inhibited the formation of fungal biofilms. Furthermore, thymol and carvacrol showed significant antifungal and antibiofilm activities against F. oxysporum. SEM images showed structural changes in fungal morphology upon treatment with EO of L. gracilis. CONCLUSION: The results presented in this study showed promising antifungal and antibiofilm effects of EO of L. gracilis and its major components, carvacrol and thymol. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings indicate that the EO extracted from L. gracilis, and the monoterpenes, carvacrol and thymol have a great potential as antifungal and antibiofilm agents. Furthermore, this is the first report of the antibiofilm activity of the EO of L. gracilis and its major components against phytopathogenic fungi.

Socio-economic inequalities and COVID-19 incidence and mortality in Brazilian children: a nationwide register-based study.

OBJECTIVES: This study aimed to estimate the incidence and mortality rates of coronavirus disease 2019 (COVID-19) in Brazilian children and to analyze its relationship with socio-economic inequalities in a state-level analysis. STUDY DESIGN: This is a nationwide register-based study. METHODS: To estimate the incidence and mortality rates of COVID-19 in Brazilian children aged 0-19 years, we extracted data of confirmed cases and deaths from the de-identified microdata catalog and official bulletins of the 27 Brazilian states' health department websites until September 3, 2020. Social and economic inequalities were evaluated using the Social Vulnerability Index and Gini coefficient, respectively. The relationship between COVID-19 rates in Brazilian children and socio-economic vulnerability at the state level was analyzed using Spearman's rank correlation. RESULTS: Of the 3,998,055 individuals with COVID-19 included in our database, 335,279 (8.4%) were children aged 0-19 years. Eight hundred deaths in children were registered, which accounts for about 0.7% of the deaths related to COVID-19 in the country. There were important differences in the incidence and mortality rates among Brazilian regions, and a correlation between mortality rates and social (ρ = 0.519; P-value = 0.007; effect magnitude: moderate) and economic (ρ = 0.615; P-value < 0.001; effect magnitude: strong) inequalities was found in a state-level analysis. CONCLUSIONS: This population-based study showed important regional differences in COVID-19 estimates for children in Brazil and a relationship between mortality rates and socio-economic inequalities. The knowledge of sociogeographic differences in the estimates of COVID-19 is crucial to planning societal strategies and local decision-making to mitigate the effects of disease in the pediatric population.