[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.

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.

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.

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.

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.

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.

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.

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.

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 preventive health services in Brazil.

INTRODUCTION: The increasing burden of non-communicable diseases and limited public financing are major challenges facing health care systems in Latin America. Although COVID-19 severely impacted the Brazilian health care system, it is crucial to further characterize the degree of disruption caused to public health efforts, in order to address and manage long term effects of this pandemic. We therefore quantified the demand for preventive and treatment services from the Brazilian Unified Health System (Sistema Único de Saúde/SUS) in 2020 to evaluate potential repercussions of COVID-19 in this setting. METHODS: Using the SUS database, we compared preventative and treatment services rendered in 2020 to the same services rendered from 2017 to 19. We also evaluated the frequency of respiratory infection (RI) diagnoses during the pandemic, relative to the preceding years. RESULTS: Compared to 2017-19, in 2020 non-urgent medical appointments decreased 1.4-fold (p = 0.0017), dental consultations 2.8-fold (p = 0.05), and immunization coverage 1.5 fold (p = 0.0005). The number of RI visits to SUS ambulatory care units in 2020 was 4.2 times higher than in preceding years (p = 0.0014), with a peak of 280,898 diagnoses in July 2020. CONCLUSION: The COVID-19 pandemic appears to have led to a dramatic decline in preventative and treatment services provided by SUS to the Brazilian population. Our findings may aid decision-makers in formulating policies to increase the availability of outpatient services in the aftermath of the pandemic. Counter measures will be critical to avoid a resurgence in vaccine-preventable diseases and complications stemming from non-communicable, chronic health conditions.

Low COVID-19 vaccine hesitancy in Brazil.

BACKGROUND: The COVID-19 pandemic has affected the entire world, and the vaccine has emerged as a source of hope for return to normal life. Still, various countries have reported high vaccine hesitancy rates. It is important to know the vaccine hesitancy profile in Brazil to help design adequate communication strategies. METHODS: A voluntary, anonymous online survey was conducted from January 22 to 29, 2021, including resident Brazilian adults to assess factors related to vaccine hesitancy. Sociodemographic and epidemiological data were analyzed. 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 173,178 respondents, and vaccine hesitancy was found in 10.5%. The principal factors associated with vaccine hesitancy were the following: assigning importance to the vaccinés efficacy (AOR = 16.39), fear of adverse reactions (AOR = 11.23), and assigning importance to the vaccinés country of origin (AOR = 3.72). Other risk factors were the following: male gender (AOR = 1.62), having children (AOR = 1.29), 9 years of schooling or less (AOR = 1.31), living in the Central-West region (AOR = 1.19), age ≥ 40 years (AOR = 1.17), and monthly income < U$788.68 (AOR = 1.13). The two vaccines available in Brazil, Covishield and CoronaVac, showed similar confidence, 80.13% and 76.36%, respectively, despite the higher rejection of the latter vaccinés Chinese origin. INTERPRETATION: This online survey confirms the low vaccine hesitancy rate among Brazilians and allowed the identification of a profile that can assist the elaboration of communication strategies to increase vaccine adherence. FUNDING: National Institute of Women, Children and Adolescents Health Fernandes Figueira, FIOCRUZ, Rio de Janeiro, Brazil.

The clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations.

Since the 2015 to 2016 outbreak in America, Zika virus (ZIKV) infected almost 900,000 patients. This international public health emergency was mainly associated with a significant increase in the number of newborns with congenital microcephaly and abnormal neurologic development, known as congenital Zika syndrome (CZS). Furthermore, Guillain-Barré syndrome (GBS), a neuroimmune disorder of adults, has also been associated with ZIKV infection. Currently, the number of ZIKV-infected patients has decreased, and most of the cases recently reported present as a mild and self-limiting febrile illness. However, based on its natural history of a typical example of reemerging pathogen and the lack of specific therapeutic options against ZIKV infection, new outbreaks can occur worldwide, demanding the attention of researchers and government authorities. Here, we discuss the clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations. Several studies have confirmed the tropism of ZIKV for neural progenitor stem cells by demonstrating the presence of ZIKV in the central nervous system (CNS) during fetal development, eliciting a deleterious inflammatory response that compromises neurogenesis and brain formation. Of note, while the neuropathology of CZS can be due to a direct viral neuropathic effect, adults may develop neuroimmune manifestations such as GBS due to poorly understood mechanisms. Antiganglioside autoantibodies have been detected in multiple patients with ZIKV infection-associated GBS, suggesting a molecular mimicry. However, further additional immunopathological mechanisms remain to be uncovered, paving the way for new therapeutic strategies.

Children's Multisystem inflammatory syndrome with myopathy.

This report describes a case of multisystem inflammatory syndrome in a child that evolved with a pattern of toxic shock syndrome with coronary artery ectasia and neurological involvement, documented by magnetic resonance imaging, with changes in the corpus callosum and myopathy in the pelvic girdle and paravertebral musculature.

Children's Multisystem inflammatory syndrome with myopathy

Abstract This report describes a case of multisystem inflammatory syndrome in a child that evolved with a pattern of toxic shock syndrome with coronary artery ectasia and neurological involvement, documented by magnetic resonance imaging, with changes in the corpus callosum and myopathy in the pelvic girdle and paravertebral musculature.

A newborn screening pilot study using methylation-sensitive high resolution melting on dried blood spots to detect Prader-Willi and Angelman syndromes.

Prader-Willi (PWS) and Angelman (AS) syndromes are two clinically distinct imprinted disorders characterized by genetic abnormalities at 15q11-q13. Early diagnosis of both syndromes provides improved treatment and accurate genetic counseling. Whole blood (WB) is the most common DNA source of many methodologies to detect PWS and AS, however, the need of WB makes a massive screening difficult in newborns due to economic and technical limitations. The aim of this study was to adapt a Methylation-sensitive High-Resolution Melting (MS-HRM) approach from dried blood spot (DBS) samples, assessing the different DNA isolation techniques and diagnostic performance. Over a 1-year period, we collected 125 DBS cards, of which 45 had already been diagnosed by MS-HRM (20 PWS, 1 AS, and 24 healthy individuals). We tested three different DBS-DNA extraction techniques assessing the DNA concentration and quality, followed by MS-HRM and statistical comparison. Each DBS-DNA extraction method was capable of accuracy in detecting all PWS and AS individuals. However, the efficiency to detect healthy individuals varied according to methodology. In our experience, DNA extracted from DBS analyzed by the MS-HRM methodology provides an accurate approach for genetic screening of imprinting related disorders in newborns, offering several benefits compared to traditional whole blood methods.

Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients.

Background: Visceral leishmaniasis/HIV-co-infected patients (VL/HIV) accounts for around 8% of VL reported cases in Brazil. Relapses of Leishmania infection after anti-leishmanial treatment constitute a great challenge in the clinical practice because of the disease severity and drug resistance. We have shown that non-relapsing-VL/HIV (NR-) evolved with increase of CD4+ T-cell counts and reduction of activated CD4+ and CD8+ T cells after anti-leishmanial treatment. This immune profile was not observed in relapsing-VL/HIV patients (R-), indicating a more severe immunological compromising degree. Elevated activation status may be related to a deficient immune reconstitution and could help to explain the frequent relapses in VL/HIV co-infection. Our aim was to evaluate if this gain of T cells was related to changes in the peripheral TCRVß repertoire and inflammatory status, as well as the possible thymus involvement in the replenishment of these newly formed T lymphocytes. Methods: VL/HIV patients, grouped into non-relapsing (NR- = 6) and relapsing (R- = 12) were evaluated from the active phase up to 12 months post-treatment (mpt). HIV-infected patients (non-VL) and healthy subjects (HS) were included. The TCRVß repertoire was evaluated ex vivo by flow cytometry, whereas the plasmatic cytokine levels were assessed by Luminex assay. To evaluate the thymic output, DNA was extracted from PBMCs for TCR rearrangement excision circles (TREC) quantification by qPCR. Results: VL/HIV cases presented an altered mobilization profile (expansions or retractions) of the TCRVß families when compared to HS independent of the follow-up phase (p < 0.05). TCRVß repertoire on CD4+ T-cells was more homogeneous in the NR-VL/HIV cases, but heterogeneous on CD8+ T-cells, since different Vß-families were mobilized. NR-VL/HIV had the inflammatory pattern reduced after 6 mpt. Importantly, VL/HIV patients showed number of TREC copies lower than controls during all follow-up. An increase of recent thymic emigrants was observed in NR-VL/HIV individuals at 10 mpt compared to R- patients (p < 0.01), who maintained lower TREC contents than the HIV controls. Conclusions: VL/HIV patients that maintain the thymic function, thus generating new T-cells, seem able to replenish the T lymphocyte compartment with effector cells, then enabling parasite control.