Multiomics Approach Reveals Serum Biomarker Candidates for Congenital Zika Syndrome.

The Zika virus (ZIKV) can be vertically transmitted, causing congenital Zika syndrome (CZS) in fetuses. ZIKV infection in early gestational trimesters increases the chances of developing CZS. This syndrome involves several pathologies with a complex diagnosis. In this work, we aim to identify biological processes and molecular pathways related to CZS and propose a series of putative protein and metabolite biomarkers for CZS prognosis in early pregnancy trimesters. We analyzed serum samples of healthy pregnant women and ZIKV-infected pregnant women bearing nonmicrocephalic and microcephalic fetuses. A total of 1090 proteins and 512 metabolites were identified by bottom-up proteomics and untargeted metabolomics, respectively. Univariate and multivariate statistical approaches were applied to find CZS differentially abundant proteins (DAP) and metabolites (DAM). Enrichment analysis (i.e., biological processes and molecular pathways) of the DAP and the DAM allowed us to identify the ECM organization and proteoglycans, amino acid metabolism, and arachidonic acid metabolism as CZS signatures. Five proteins and four metabolites were selected as CZS biomarker candidates. Serum multiomics analysis led us to propose nine putative biomarkers for CZS prognosis with high sensitivity and specificity.

[Online survey on the reasons for vaccine hesitancy against COVID-19 in children and adolescents in Brazil]. / Inquérito online sobre os motivos para hesitação vacinal contra a COVID-19 em crianças e adolescentes do Brasil.

The objective is to unveil the reasons for vaccine hesitancy among parents and/or guardians of children and adolescents toward the prevention of COVID-19. This is a descriptive study, with a qualitative approach that seeks to analyze the answers to the open question "Why will you not vaccinate or have not vaccinated or are in doubt about vaccinating the children and adolescents under your responsibility, for the prevention of COVID-19?". The research included adult individuals, Brazilians, living in the country, responsible for children and adolescents under 18 years of age. Data collection took place electronically in November and December 2021. The answers were organized and processed with the support of the software Iramuteq. The textual corpus of this research was composed of the response of 1,896 participants, consisting of 87% who were hesitant (1,650) and 13% (246) of parents who intend to vaccinate but who outlined some doubts and considerations about the vaccination of children and adolescents. These are reasons why parents and/or guardians have not vaccinated or are in doubt about vaccinating the children and adolescents under their responsibility for the prevention of COVID-19: fears about vaccination regarding the conception that the vaccine is in the experimental phase, fear of adverse reactions and long-term effects. The reasons for the lack of intention to vaccinate stem from the understanding of the participants that COVID-19 in children is not serious, the risks of vaccination are greater than the benefits, and the right of choice not to vaccinate.

Objetiva-se desvelar os motivos para hesitação vacinal de pais e/ou responsáveis de crianças e adolescentes para prevenção da COVID-19. Trata-se de um estudo descritivo, de abordagem qualitativa, que busca analisar as respostas da pergunta aberta "por que você não vai vacinar, não vacinou ou está na dúvida em vacinar as crianças e os adolescentes sob sua responsabilidade para prevenção da COVID-19?". A pesquisa incluiu indivíduos adultos, brasileiros, residentes no país, responsáveis por crianças e adolescentes menores de 18 anos. A coleta de dados aconteceu de forma eletrônica entre os meses de novembro e dezembro de 2021. As respostas foram organizadas e processadas com suporte do software Iramuteq. O corpus textual desta pesquisa foi composto pela resposta de 1.896 participantes, constituído por 87% de hesitantes (1.650) e 13% (246) de pais que têm intenção de vacinar, mas que esboçaram algumas dúvidas e considerações a respeito da vacinação de crianças e adolescentes. São motivos pelos quais pais e/ou responsáveis não vacinaram ou estão na dúvida em vacinar as crianças e os adolescentes sob sua responsabilidade para prevenção da COVID-19: receio em razão de a vacina estar em fase experimental e medo das reações adversas e dos efeitos a longo prazo. Já os motivos para ausência de intenção de vacinar decorrem dos entendimentos dos participantes de que a COVID-19 em crianças não é grave, os riscos da vacinação são maiores do que os benefícios e o direito de escolha em não vacinar.

El objetivo es revelar los motivos de la indecisión a las vacunas de padres y/o responsables de niños y adolescentes para la prevención de COVID-19. Se trata de un estudio descriptivo con enfoque cualitativo, que busca analizar las respuestas a la pregunta abierta "¿Por qué no va a vacunar o no vacunó o tiene dudas en vacunar a los niños y los adolescentes bajo su responsabilidad para la prevención del COVID-19?". La investigación incluyó individuos adultos, brasileños, residentes en el país, responsables de niños y adolescentes menores de 18 años. La recolección de datos se realizó de forma electrónica entre los meses de noviembre y diciembre de 2021. Las respuestas se organizaron y procesaron con ayuda del software Iramuteq. El corpus textual de esta investigación fue compuesto por la respuesta de 1.896 participantes, siendo constituido por el 87% de indecisos (1.650) y el 13% (246) de padres que tienen la intención de vacunar, pero que esbozaron algunas dudas y consideraciones respecto a la vacunación de niños y adolescentes. Son motivos por los cuales los padres y/o responsables no vacunaron o están en duda en vacunar a los niños y adolescentes bajo su responsabilidad para prevención del COVID-19: temores con la vacunación en cuanto a la concepción de que la vacuna está en fase experimental, miedo a las reacciones adversas y los efectos a largo plazo. Los motivos de la ausencia de intención en vacunar se deben a que los participantes entienden que el COVID-19 en niños no es grave, que los riesgos de la vacunación son mayores que los beneficios y que tienen derecho a decidir no vacunarse.

Evaluation and monitoring of eye findings in children exposed to Zika virus during gestation: 3 years of follow-up.

INTRODUCTION: Congenital Zika syndrome (CZS) is a recently described disease. Our main objective was to evaluate and monitor, over 3 years, the ophthalmoscopic findings in children exposed to zika virus (ZIKV) during gestation. METHODS: This prospective observational study was conducted in Rio de Janeiro, Brazil, between April 2016 and May 2019. We evaluated two groups with exanthema serving as a proxy for viremia: (i) children whose mothers had exanthema during pregnancy and (ii) children who had microcephaly without maternal exanthema during pregnancy. We performed indirect ophthalmoscopy at recruitment and every 6 months thereafter. We also tested the association between ocular findings with maternal exanthema, microcephaly, CZS and maternal infection confirmed by reverse transcriptase quantitative polymerase chain reaction and gender. RESULTS: Of the 72 children included, 16 (22.2%) had optic nerve and/or retinal lesions. All 16 had CZS and 15 (93.7%) had microcephaly (14 at birth and 1 postnatally). The child with postnatally acquired microcephaly was born to a mother without exanthema during pregnancy. Fifty-six (77.8%) of the 72 children were followed for a median time of 24 months and none exhibited differences between admission and follow-up examinations. After logistic regression, only microcephaly at birth was associated with eye abnormalities (odds ratio, 77.015; 95% confidence interval, 8.85-670.38; p < 0.001). CONCLUSION: We observed that there was no progression of the lesions over the follow-up period. We also showed that the eye findings were associated only with microcephaly at birth. Attention should be paid to all children born during a ZIKV epidemic, regardless of maternal exanthema and/or microcephaly at birth.

Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study.

Introduction: Despite the existing data on the Multisystem Inflammatory Syndrome in Children (MIS-C), the factors that determine these patients evolution remain elusive. Answers may lie, at least in part, in genetics. It is currently under investigation that MIS-C patients may have an underlying innate error of immunity (IEI), whether of monogenic, digenic, or even oligogenic origin. Methods: To further investigate this hypothesis, 30 patients with MIS-C were submitted to whole exome sequencing. Results: Analyses of genes associated with MIS-C, MIS-A, severe covid-19, and Kawasaki disease identified twenty-nine patients with rare potentially damaging variants (50 variants were identified in 38 different genes), including those previously described in IFNA21 and IFIH1 genes, new variants in genes previously described in MIS-C patients (KMT2D, CFB, and PRF1), and variants in genes newly associated to MIS-C such as APOL1, TNFRSF13B, and G6PD. In addition, gene ontology enrichment pointed to the involvement of thirteen major pathways, including complement system, hematopoiesis, immune system development, and type II interferon signaling, that were not yet reported in MIS-C. Discussion: These data strongly indicate that different gene families may favor MIS- C development. Larger cohort studies with healthy controls and other omics approaches, such as proteomics and RNAseq, will be precious to better understanding the disease dynamics.

Biotechnological Advances in Gene Therapy of Hematopoietic Stem Cells: Systematic Review and Meta-Analysis.

Gene therapy (GT) has emerged as a promising treatment option for disorders in the hematopoietic system, particularly primary immunodeficiencies (PID). Hematopoietic stem cells (HSCs) have gained attention due to their ability to support long-term hematopoiesis. In this study, we present a summary of research evaluating the most effective method of gene editing in HSCs for translational medicine. We conducted a systematic literature search in various databases, including Cochrane, LILACs, SciELO, and PubMed (MEDLINE), covering the period from January 1989 to June 10, 2023. The aim of this study was to identify articles that assessed the efficiency of gene editing in HSCs and clinical trials focusing on PID. Our research protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42022349850). Of the 470 studies identified in our search, 77 met the inclusion criteria. Among these, 61 studies were included in strategy 1 (gene therapy using HSC [GT-HSC]) of the systematic review (SR). We performed a meta-analysis on 17 of these studies. In addition, 16 studies were categorized under strategy 2 (clinical trials for PID). While clinical trials have demonstrated the potential benefits of GT-HSC, the safety and efficacy of gene editing still pose significant challenges. Various viral and nonviral approaches for gene delivery have been explored in basic and clinical research, with viral vectors being the most commonly used method in HSC therapeutics. Although promising, recent technologies such as CRISPR/Cas are not yet ready for efficient long-term restoration of the immune system as a whole.

Genetic screening in a Brazilian cohort with inborn errors of immunity.

BACKGROUND: Inherited genetic defects in immune system-related genes can result in Inborn Errors of Immunity (IEI), also known as Primary Immunodeficiencies (PID). Diagnosis of IEI disorders is challenging due to overlapping clinical manifestations. Accurate identification of disease-causing germline variants is crucial for appropriate treatment, prognosis, and genetic counseling. However, genetic sequencing is challenging in low-income countries like Brazil. This study aimed to perform genetic screening on patients treated within Brazil's public Unified Health System to identify candidate genetic variants associated with the patient's phenotype. METHODS: Thirteen singleton unrelated patients from three hospitals in Rio de Janeiro were enrolled in this study. Genomic DNA was extracted from the peripheral blood lymphocytes of each patient, and whole exome sequencing (WES) analyses were conducted using Illumina NextSeq. Germline genetic variants in IEI-related genes were prioritized using a computational framework considering their molecular consequence in coding regions; minor allele frequency ≤ 0.01; pathogenicity classification based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines gathered from the VarSome clinical database; and IEI-related phenotype using the Franklin tool. The genes classification into IEI categories follows internationally recognized guidelines informed by the International Union of Immunological Societies Expert Committee. Additional methods for confirmation of the variant included Sanger sequencing, phasing analysis, and splice site prediction. RESULTS: A total of 16 disease-causing variants in nine genes, encompassing six different IEI categories, were identified. X-Linked Agammaglobulinemia, caused by BTK variations, emerged as the most prevalent IEI disorder in the cohort. However, pathogenic and likely pathogenic variants were also reported in other known IEI-related genes, namely CD40LG, CARD11, WAS, CYBB, C6, and LRBA. Interestingly, two patients with suspected IEI exhibited pathogenic variants in non-IEI-related genes, ABCA12 and SLC25A13, potentially explaining their phenotypes. CONCLUSIONS: Genetic screening through WES enabled the detection of potentially harmful variants associated with IEI disorders. These findings contribute to a better understanding of patients' clinical manifestations by elucidating the genetic basis underlying their phenotypes.

Genotypic-Phenotypic Correlations of Hereditary Hyperferritinemia-Cataract Syndrome: Case Series of Three Brazilian Families.

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare, frequently misdiagnosed, autosomal dominant disease caused by mutations in the FTL gene. It causes bilateral pediatric cataract and hyperferritinemia without iron overload. The objective of this case series, describing three Brazilian families, is to increase awareness of HHCS, as well as to discuss possible phenotypic interactions with concurrent mutations in HFE, the gene associated with autosomal recessive inheritance hereditary hemochromatosis. Whole-exome sequencing was performed in eight individuals with HHCS from three different families, as well as one unaffected member from each family for trio analysis-a total of eleven individuals. Ophthalmological and clinical genetic evaluations were conducted. The likely pathogenic variant c.-157G>A in FTL was found in all affected individuals. They presented slowly progressing bilateral cataract symptoms before the age of 14, with a phenotype of varied bilateral diffuse opacities. Hyperferritinemia was present in all affected members, varying from 971 ng/mL to 4899 ng/mL. There were two affected individuals with one concurrent pathogenic variant in HFE (c.187C>G, p.H63D), who were also the ones with the highest values of serum ferritin in our cohort. Few publications describe individuals with pathogenic mutations in both FTL and HFE genes, and further studies are needed to assess possible phenotypic interactions causing higher values of hyperferritinemia.

Social Representations of Hesitant Brazilians about Vaccination against COVID-19.

BACKGROUND: The control of the COVID-19 pandemic has been a great challenge. Understanding the thoughts and beliefs underlying vaccine hesitancy can help in the formulation of public policies. The present study aimed to analyze the social representations of hesitant Brazilians about vaccination against COVID-19. METHODS: Qualitative research guided by the Theory of Social Representations, carried out through an online survey among Brazilian adults living in Brazil. The data were analyzed using the IRaMuTeQ software. RESULTS: Of the 173,178 respondents, 10,928 were hesitant and declared reasons for vaccination hesitation. The analysis generated three classes: mistrust of the vaccine and underestimation of the severity of the pandemic; (dis)information and distrust of political involvement; and fear of adverse reactions to COVID-19 vaccines. CONCLUSIONS: Social knowledge, presented by the representations apprehended in this study, demonstrates difficulty in discerning the reliability of information and a social imagination full of doubts and uncertainties. Understanding the internal dynamics of these groups, with their representations of the world, is important to propose policies and actions that echo and cause changes in the understanding of the role of immunization. It is essential to shed light on the sociological imagination so that gaps filled with false information can be dismantled and confronted with scientific knowledge accessible to the population.

Assessing whole-exome sequencing data from undiagnosed Brazilian patients to improve the diagnostic yield of inborn errors of immunity.

OBJECTIVES: Inborn error of immunity (IEI) comprises a broad group of inherited immunological disorders that usually display an overlap in many clinical manifestations challenging their diagnosis. The identification of disease-causing variants from whole-exome sequencing (WES) data comprises the gold-standard approach to ascertain IEI diagnosis. The efforts to increase the availability of clinically relevant genomic data for these disorders constitute an important improvement in the study of rare genetic disorders. This work aims to make available WES data of Brazilian patients' suspicion of IEI without a genetic diagnosis. We foresee a broad use of this dataset by the scientific community in order to provide a more accurate diagnosis of IEI disorders. DATA DESCRIPTION: Twenty singleton unrelated patients treated at four different hospitals in the state of Rio de Janeiro, Brazil were enrolled in our study. Half of the patients were male with mean ages of 9 ± 3, while females were 12 ± 10 years old. The WES was performed in the Illumina NextSeq platform with at least 90% of sequenced bases with a minimum of 30 reads depth. Each sample had an average of 20,274 variants, comprising 116 classified as rare pathogenic or likely pathogenic according to American College of Medical Genetics and Genomics and the Association (ACMG) guidelines. The genotype-phenotype association was impaired by the lack of detailed clinical and laboratory information, besides the unavailability of molecular and functional studies which, comprise the limitations of this study. Overall, the access to clinical exome sequencing data is limited, challenging exploratory analyses and the understanding of genetic mechanisms underlying disorders. Therefore, by making these data available, we aim to increase the number of WES data from Brazilian samples despite contributing to the study of monogenic IEI-disorders.

Obesity Induces an Impaired Placental Antiviral Immune Response in Pregnant Women Infected with Zika Virus.

Obesity is increasing in incidence worldwide, especially in women, which can affect the outcome of pregnancy. During this period, viral infections represent a risk to the mother, the placental unit, and the fetus. The Zika virus (ZIKV) outbreak in Brazil has been the cause of congenital Zika syndrome (CZS), with devastating consequences such as microcephaly in newborns. Herein, we analyzed the impact of maternal overweight/obesity on the antiviral factors' expression in the placental tissue of Zika-infected mothers. We accessed placentas from women with and without obesity from 34 public health units (São Paulo) and from Zika-infected mothers with and without obesity from the Clinical Cohort Study of ZIKV pregnant women (Rio de Janeiro, Brazil). We first verified that obesity, without infection, did not alter the constitutive transcriptional expression of antiviral factors or IFN type I/III expression. Interestingly, obesity, when associated with ZIKV infection, showed a decreased transcriptional expression of RIG-I and IFIH1 (MDA-5 protein precursor gene). At the protein level, we also verified a decreased RIG-I and IRF-3 expression in the decidual placenta from the Zika-infected obese group, regardless of microcephaly. This finding shows, for the first time, that obesity associated with ZIKV infection leads to an impaired type I IFN downstream signaling pathway in the maternal-fetal interface.

Trustworthiness of information sources on vaccines for COVID-19 prevention among Brazilians.

OBJECTIVE: This study aims to assess the trustworthiness of information sources, perception of clear information about the vaccine, and strategies to increase adherence to vaccination to provide managers with information that helps establish effective communication with the population about vaccination. METHOD: This is an online survey conducted between January 22 and 29, 2021, preceded by an Informed Consent, that aims to assess vaccine hesitancy, which corresponded to the first week of vaccination initiation to prevent COVID-19 in Brazil. Data were obtained from a questionnaire made available through a free platform and stored in Google Forms and later exported to the SPSS statistical package for analysis. The sample consisted of all questionnaires from participants who self-declared as age 18 or older, Brazilian, and residing in Brazil at the time of the survey. Incomplete records with more than 50% of blank items and duplicates were excluded. All categorical variables were analyzed from their absolute and relative frequencies. Multivariate logistic regression was performed to verify the relationship between dependent variables and independent variables. RESULTS: The results show that trust in information sources diverges between hesitant and non-hesitant. They also showed that some participants show an overall distrust that seems to have deeper foundations than issues related only to the source of information. The high rejection of television and the WHO as sources of information among hesitant suggests that integrated actions with research institutes, public figures vaccinating, and religious leaders can help to combat vaccine hesitation. Two actors become particularly important in this dynamic, both for good and bad, and their anti-vaxxer behavior must be observed: the doctor and the Ministry of Health. CONCLUSION: This study contributes to gathering valuable information to help understand the behavior and thinking relevant to the adherence to vaccination recommendations.

Longitudinal Evaluation of Antibody Persistence in Mother-Infant Dyads After Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy.

BACKGROUND: There are limited data on how coronavirus disease 2019 (COVID-19) severity, timing of infection, and subsequent vaccination impact transplacental transfer and persistence of maternal and infant antibodies. METHODS: In a longitudinal cohort of pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, maternal/infant sera were collected at enrollment, delivery/birth, and 6 months. Anti-SARS-CoV-2 spike immunoglobulin (Ig)G, IgM, and IgA were measured by enzyme-linked immunosorbent assay. RESULTS: Two-hundred fifty-six pregnant women and 135 infants were enrolled; 148 maternal and 122 neonatal specimens were collected at delivery/birth; 45 maternal and 48 infant specimens were collected at 6 months. Sixty-eight percent of women produced all anti-SARS-CoV-2 isotypes at delivery (IgG, IgM, IgA); 96% had at least 1 isotype. Symptomatic disease and vaccination before delivery were associated with higher maternal IgG at labor and delivery. Detectable IgG in infants dropped from 78% at birth to 52% at 6 months. In the multivariate analysis evaluating factors associated with detectable IgG in infants at delivery, significant predictors were 3rd trimester infection (odds ratio [OR] = 4.0), mild/moderate disease (OR = 4.8), severe/critical disease (OR = 6.3), and maternal vaccination before delivery (OR = 18.8). No factors were significant in the multivariate analysis at 6 months postpartum. CONCLUSIONS: Vaccination in pregnancy post-COVID-19 recovery is a strategy for boosting antibodies in mother-infant dyads.

Willingness of Brazilian caregivers in having their children and adolescents vaccinated against Covid-19.

BACKGROUND: The vaccination of children and adolescents for the prevention of Covid-19 is important to:decrease in deaths and hospitalizations, prevent multisystem inflammatory syndrome, avoid long-term complications and decrease the suspension of on-site classes. Despite of these benefits, some studies have shown that some caregivers are still hesitancy. METHODS: This is a voluntary and anonymous online survey conducted from November 17 to December 14, 2021, in Brazil, through a free-of-charge platform with a link provided on social networks. A bivariate analysis was conducted with the independent variables, with vaccine hesitancy as the outcome variable, and a multivariate logistic model was used to calculated adjusted odds ratios. RESULTS: The sample included 15,297 respondents. Approximately 13.3 % (2,028) of the caregivers were hesitant to vaccinate their children and adolescents against Covid-19 in at least one age group. The vaccination hesitanty rate of caregivers of children aged 0-4 years, 5-11 years and adolescents were 16 %, 13 %, 15 %, respectively. The principal factors associated with vaccine hesitancy were the following: belief that they need to wait longer, belief that children that had natural infection doesn't need to vaccinate and belief that vaccine has long term adverse effects. INTERPRETATION: The present study showed that the willingness of caregivers to have their children and adolescents vaccinated in Brazil is high compared to data from adult and pediatric international studies. This study provides a profile of the hesitant caregivers considering their perspectives and beliefs regarding vaccines that can help the elaboration of strategies to increase vaccine adherence.

Inquérito online sobre os motivos para hesitação vacinal contra a COVID-19 em crianças e adolescentes do Brasil / Online survey on the reasons for vaccine hesitancy against COVID-19 in children and adolescents in Brazil / Encuesta en línea sobre los motivos de la indecisión a las vacunas contra COVID-19 en niños y adolescentes de Brasil

Resumo: Objetiva-se desvelar os motivos para hesitação vacinal de pais e/ou responsáveis de crianças e adolescentes para prevenção da COVID-19. Trata-se de um estudo descritivo, de abordagem qualitativa, que busca analisar as respostas da pergunta aberta "por que você não vai vacinar, não vacinou ou está na dúvida em vacinar as crianças e os adolescentes sob sua responsabilidade para prevenção da COVID-19?". A pesquisa incluiu indivíduos adultos, brasileiros, residentes no país, responsáveis por crianças e adolescentes menores de 18 anos. A coleta de dados aconteceu de forma eletrônica entre os meses de novembro e dezembro de 2021. As respostas foram organizadas e processadas com suporte do software Iramuteq. O corpus textual desta pesquisa foi composto pela resposta de 1.896 participantes, constituído por 87% de hesitantes (1.650) e 13% (246) de pais que têm intenção de vacinar, mas que esboçaram algumas dúvidas e considerações a respeito da vacinação de crianças e adolescentes. São motivos pelos quais pais e/ou responsáveis não vacinaram ou estão na dúvida em vacinar as crianças e os adolescentes sob sua responsabilidade para prevenção da COVID-19: receio em razão de a vacina estar em fase experimental e medo das reações adversas e dos efeitos a longo prazo. Já os motivos para ausência de intenção de vacinar decorrem dos entendimentos dos participantes de que a COVID-19 em crianças não é grave, os riscos da vacinação são maiores do que os benefícios e o direito de escolha em não vacinar.

Abstract: The objective is to unveil the reasons for vaccine hesitancy among parents and/or guardians of children and adolescents toward the prevention of COVID-19. This is a descriptive study, with a qualitative approach that seeks to analyze the answers to the open question "Why will you not vaccinate or have not vaccinated or are in doubt about vaccinating the children and adolescents under your responsibility, for the prevention of COVID-19?". The research included adult individuals, Brazilians, living in the country, responsible for children and adolescents under 18 years of age. Data collection took place electronically in November and December 2021. The answers were organized and processed with the support of the software Iramuteq. The textual corpus of this research was composed of the response of 1,896 participants, consisting of 87% who were hesitant (1,650) and 13% (246) of parents who intend to vaccinate but who outlined some doubts and considerations about the vaccination of children and adolescents. These are reasons why parents and/or guardians have not vaccinated or are in doubt about vaccinating the children and adolescents under their responsibility for the prevention of COVID-19: fears about vaccination regarding the conception that the vaccine is in the experimental phase, fear of adverse reactions and long-term effects. The reasons for the lack of intention to vaccinate stem from the understanding of the participants that COVID-19 in children is not serious, the risks of vaccination are greater than the benefits, and the right of choice not to vaccinate.

Resumen: El objetivo es revelar los motivos de la indecisión a las vacunas de padres y/o responsables de niños y adolescentes para la prevención de COVID-19. Se trata de un estudio descriptivo con enfoque cualitativo, que busca analizar las respuestas a la pregunta abierta "¿Por qué no va a vacunar o no vacunó o tiene dudas en vacunar a los niños y los adolescentes bajo su responsabilidad para la prevención del COVID-19?". La investigación incluyó individuos adultos, brasileños, residentes en el país, responsables de niños y adolescentes menores de 18 años. La recolección de datos se realizó de forma electrónica entre los meses de noviembre y diciembre de 2021. Las respuestas se organizaron y procesaron con ayuda del software Iramuteq. El corpus textual de esta investigación fue compuesto por la respuesta de 1.896 participantes, siendo constituido por el 87% de indecisos (1.650) y el 13% (246) de padres que tienen la intención de vacunar, pero que esbozaron algunas dudas y consideraciones respecto a la vacunación de niños y adolescentes. Son motivos por los cuales los padres y/o responsables no vacunaron o están en duda en vacunar a los niños y adolescentes bajo su responsabilidad para prevención del COVID-19: temores con la vacunación en cuanto a la concepción de que la vacuna está en fase experimental, miedo a las reacciones adversas y los efectos a largo plazo. Los motivos de la ausencia de intención en vacunar se deben a que los participantes entienden que el COVID-19 en niños no es grave, que los riesgos de la vacunación son mayores que los beneficios y que tienen derecho a decidir no vacunarse.

Portable wide-field digital imaging for screening of neonatal visual impairment causes in Rio de Janeiro, Brazil: a budget impact analysis.

OBJECTIVE: To estimate the budget impact of portable wide-field digital imaging incorporation on screening neonatal causes of childhood blindness and visual impairment in Rio de Janeiro, Brazil. DESIGN: Budget impact analysis. SETTING: Rio de Janeiro, Brazil. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the direct cost of indirect binocular ophthalmoscopy, red reflex test and portable wide-field digital image screening comprising all babies born in Rio de Janeiro's government maternity wards. The secondary outcome was the budget impact of implementing portable wide-field digital image screening in Rio de Janeiro, Brazil. RESULTS: Considering 100% coverage of maternity wards, the total budget impact between 2020 and 2024 would be US$3 820 706.04, ranging from US$3 139 844.34 to US$6 099 510.35. The additional cost would be US$3 124 457.28, ranging from US$2 714 492.26 to US$4 880 608.63. CONCLUSION: The cost of universal digital imaging screening corresponds to less than 1% of the government health budget of the city of Rio de Janeiro. The information provided in this study may help government decision-makers evaluate the feasibility of implementing this new strategy in the municipal setting. Further health economic evaluations should be performed to verify the affordability of the implementation of this screening strategy in the Brazilian scenario, taking into account scarce human resources.

Anthropometric Parameters of Children with Congenital Zika Virus Exposure in the First Three Years of Life.

Little is known about the impact of congenital Zika virus (ZIKV) exposure on growth in the first years of life. In this prospective cohort study,201 ZIKV antenatally-exposed children were followed at a tertiary referral center in Rio de Janeiro, Brazil. Eighty-seven were classified as congenital Zika syndrome (CZS) patients and 114 as not congenital Zika syndrome (NCZS); growth parameters were described and compared between groups and with WHO standard growth curves. Thirty-four (39%) newborns with CZS and seven (6%) NCZS were small for gestational age (p < 0.001). NCZS mean weight measures ranged from −0.45 ± 0.1 to 0.27 ± 0.2 standard deviations (SD) from the WHO growth curve median during follow-up, versus −1.84 ± 0.2 to −2.15 ± 0.2 SD for the CZS group (p < 0.001). Length mean z-scores varied from −0.3 ± 0.1 at 1 month to 0.17 ± 0.2 SD between 31 and 36 months in the NCZS group, versus −2.3 ± 0.3 to −2.0 ± 0.17 SD in the CZS group (p < 0.001). Weight/height (W/H) and BMI z-scores reached -1.45 ± 0.2 SD in CZS patients between 31 and 36 months, versus 0.23 ± 0.2 SD in the NCZS group (p < 0.01). Between 25 and 36 months of age, more than 50% of the 70 evaluated CZS children were below weight and height limits; 36 (37.1%) were below the W/H cut-off. Gastrostomy was performed in 23 (26%) children with CZS. During the first three years of life, CZS patients had severe and early growth deficits, while growth of NCZS children was normal by WHO standards.

Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report.

BACKGROUND: X-linked agammaglobulinemia (XLA) is an Inborn Errors of Immunity (IEI) characterized by pan-hypogammaglobulinemia and low numbers of B lymphocytes due to mutations in BTK gene. Usually, XLA patients are not susceptible to respiratory tract infections by viruses and do not present interstitial lung disease (ILD) such as bronchiolitis obliterans (BO) as a consequence of acute or chronic bacterial infections of the respiratory tract. Although many pathogenic variants have already been described in XLA, the heterogeneous clinical presentations in affected patients suggest a more complex genetic landscape underlying this disorder. CASE PRESENTATION: We report two pediatric cases from male siblings with X-Linked Agammaglobulinemia and bronchiolitis obliterans, a phenotype not often observed in XLA phenotype. The whole-exome sequencing (WES) analysis showed a rare hemizygous missense variant NM_000061.2(BTK):c.1751G>A(p.Gly584Glu) in BTK gene of both patients. We also identified a gain-of-function mutation in TGFß1 (rs1800471) previously associated with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. TGFß1 plays a key role in the regulation of immune processes and inflammatory response associated with pulmonary impairment. CONCLUSIONS: Our report illustrates a possible role for WES in patients with known inborn errors of immunity, but uncommon clinical presentations, providing a personalized understanding of genetic basis, with possible implications in the identification of potential treatments, and prognosis for patients and their families.

Early Predictors of Poor Neurologic Outcomes in a Prospective Cohort of Infants With Antenatal Exposure to Zika Virus.

BACKGROUND: Identify early predictors of poor neurodevelopment in infants with antenatal Zika virus (ZIKV) exposure. METHODS: Analysis of a prospective cohort of infants with antenatal ZIKV exposure confirmed by maternal or infant RT-PCR or IgM during the epidemic in Rio de Janeiro, Brazil. Clinical findings before 3 months of age were associated with Bayley-III Scales of Infant and Toddler Development conducted after 6 months of age. RESULTS: ZIKV exposure was confirmed in 219 cases; 162 infants were normocephalic, 53 were microcephalic, 4 had no head circumference recorded because of perinatal death/LTFU. Seven of the 112 normocephalic infants developed secondary microcephaly between 3 weeks and 8 months of age. Among the normocephalic at birth cohort, the mean HCZ among normal, at risk, and developmentally delayed children was significantly different (ANOVA, P = 0.02). In particular, the mean HCZ of the developmentally delayed group was significantly lower than that of the normal group (Tukey's test, P = 0.014). HCZ was more strongly associated with lower expressive language scores (P = 0.04) than receptive language scores (P = 0.06). The rate of auditory abnormalities differed among the normal, at risk, and developmentally delayed groups (Chi-squared test, P = 0.016), which was driven by the significant difference between the normal and at risk groups (post hoc test, P = 0.011, risk ratio 3.94). Auditory abnormalities were associated with both expressive and receptive language delays (P = 0.02 and P = 0.02, respectively). CONCLUSIONS: Clear predictors of neurodevelopment in normocephalic ZIKV-exposed children have not been previously identified. Our findings demonstrate that smaller HCZ and auditory abnormalities in these infants correlate with poor neurodevelopment as toddlers. Language delay is the most prominent developmental concern among these children, who will require frequent auditory and speech evaluations throughout childhood.

SARS-CoV-2 seroprevalence and social inequalities in different subgroups of healthcare workers in Rio de Janeiro, Brazil.

BACKGROUND: COVID-19 has exacerbated health inequalities worldwide. Yet, such a perspective has not been investigated in specific healthcare workers and their resulting inclusion as a priority group for vaccination have been an important focus of political and social discussion. This study aimed at investigating whether SARS-CoV-2-seropositivity in healthcare workers in a public hospital in Rio de Janeiro, Brazil, was influenced by social determinants of health and the social vulnerability in subgroups of workers. METHODS: A serological survey was conducted in 1,154 healthcare workers in June and July 2020. The association between the serological test results for detection of IgG antibodies to SARS-CoV-2 and socioeconomic, occupational characteristics and transportation used by the workers to commute was assessed using the Pearson´s chi-square test and Cramer's V. FINDINGS: Overall, the serum prevalence for the virus in the healthcare workers was 30% (342/1141). Non-white workers (208/561) with lower income (169/396) and schooling (150/353), as well as users of the mass transportation system (157/246) showed the highest infection rates. Importantly they mostly corresponded to hospital support workers (131/324), in particular the cleaning personnel (42/70). Accordingly, income, schooling and work modality appeared as negative predictors, as ascertained by forest plot analysis. INTERPRETATIONS: The data clearly illustrate the inequality in SARS-CoV-2 infection in the Brazilian population, comprising even healthcare workers of the Brazilian unified health system.

Repercussions of the COVID-19 pandemic on health professionals in the state of Rio de Janeiro / Brazil.

Brazil has been severely affected by the COVID-19 pandemic. The high numbers of confirmed cases and deaths have continued unabated since the first reported case, with no flattening or downward turn in the curve. In this context, healthcare workers have been exposed uninterruptedly to stress factors throughout a year of the pandemic. The study´s aim was to identify and analyze healthcare workers´ perceptions of their feelings and concerns that have surfaced in responding to the pandemic. METHOD: This was a cross-sectional online qualitative survey study of 554 healthcare personnel working in the state of Rio de Janeiro during the COVID-19 pandemic. Recruitment occurred from July 20 to September 30, 2020, using an online survey, preceded byfree informed consent term. Data were analyzed with the Iramuteq software. RESULTS: Through a dendrogram, the words with the highest chi-square were highlighted and grouped into four classes: healthcare workers´ fear of falling ill to COVID-19 and infecting their family members; work/labor issues; feelings of powerlessness and need for public policies for government action; and fatigue and burnout in the pandemic. Each word class was also illustrated by a similarity tree. CONCLUSION: The study revealed healthcare workers´ exacerbated fear of infection and transmission of COVID-19 to their family members, besides financial losses and feelings of powerlessness and abandonment.