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Zika virus (ZIKV) infection was first associated with Central Nervous System (CNS) infections in Brazil in 2015, correlated with an increased number of newborns with microcephaly, which ended up characterizing the Congenital Zika Syndrome (CZS). Here, we investigated the impact of ZIKV infection on the functionality of iPSC-derived astrocytes. Besides, we extrapolated our findings to a Brazilian cohort of 136 CZS children and validated our results using a mouse model. Interestingly, ZIKV infection in neuroprogenitor cells compromises cell migration and causes apoptosis but does not interfere in astrocyte generation. Moreover, infected astrocytes lost their ability to uptake glutamate while expressing more glutamate transporters and secreted higher levels of IL-6. Besides, infected astrocytes secreted factors that impaired neuronal synaptogenesis. Since these biological endophenotypes were already related to Autism Spectrum Disorder (ASD), we extrapolated these results to a cohort of children, now 6-7 years old, and found seven children with ASD diagnosis (5.14 %). Additionally, mice infected by ZIKV revealed autistic-like behaviors, with a significant increase of IL-6 mRNA levels in the brain. Considering these evidence, we inferred that ZIKV infection during pregnancy might lead to synaptogenesis impairment and neuroinflammation, which could increase the risk for ASD.
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Astrócitos , Transtorno do Espectro Autista , Doenças Neuroinflamatórias , Sinapses , Infecção por Zika virus , Zika virus , Infecção por Zika virus/patologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/virologia , Infecção por Zika virus/complicações , Transtorno do Espectro Autista/virologia , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/patologia , Humanos , Animais , Camundongos , Zika virus/fisiologia , Feminino , Criança , Sinapses/metabolismo , Sinapses/patologia , Doenças Neuroinflamatórias/virologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/etiologia , Astrócitos/virologia , Astrócitos/metabolismo , Astrócitos/patologia , Masculino , Interleucina-6/metabolismo , Interleucina-6/genética , Gravidez , Fatores de Risco , Células-Tronco Pluripotentes Induzidas/virologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Brasil/epidemiologia , Modelos Animais de Doenças , NeurogêneseRESUMO
Este artigo teve como objetivo discutir os efeitos da covid-19 sobre os direitos humanos da população negra brasileira, questionando a própria concepção de direitos humanos, a partir de autores e autoras que discutem a necessidade de racializar este debate. Para a análise, utilizou-se a metodologia fenomenológica dialética. Concluiu-se que a lógica do "pretuguês" surge como uma racionalidade que tensiona a produção do direito e a atuação do Estado e das políticas públicas em prol dos direitos humanos dos povos da periferia. Concluiu-se também que o dilema pandêmico causado pela covid-19 pode ser uma base para se repensarem as consequências do racismo estrutural, considerando que somente a partir de uma mudança de postura estatal e com a ação dos movimentos sociais será possível a efetivação dos direitos humanos, em especial os da população negra.
This article aimed to discuss the effects of Covid-19 on the human rights of the black Brazilian population, questioning the concept of human rights itself from authors who discuss the need to racialize the debate. For analysis, it was used the dialectical phenomenological methodology. It is concluded that the logic of the "pretuguês" appears as a rationality that stresses the production of law and the performance of the State and public policies in favor of the human rights of the peoples of the periphery. It was also concluded that this pandemic dilemma caused by Covid-19 can be a basis for rethinking the consequences of structural racism, considering that only from a change in State posture and with the action of social movements will it be possible to enforce human rights, especially those of the black population.
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OBJECTIVES: Defense against respiratory viruses depends on an immune response present in the mucosa, as saliva IgA secretes antibodies. During the pandemic, such as influenza or SARS-CoV-2, most infected patients are asymptomatic but retain specific antibodies post-infection. The authors evaluated IgG and IgA antibodies against SARS-CoV-2 and influenza in the saliva of asymptomatic volunteers, validated with controls or vaccinated individuals. METHODS: The authors detected specific antibodies by validated conventional ELISA using natural SARS-CoV-2 antigens from infected Vero cells or capture-ELISA for influenza using natural antigens of the influenza vaccine. RESULTS: Saliva from influenza-vaccinated individuals had more IgA than paired serum, contrary to the findings for specific IgG. In COVID-19-vaccinated samples, specific IgA in saliva increased after vaccination, but IgG levels were high after the first dose. In saliva from the asymptomatic population (226), anti-Influenza IgG was found in 57.5% (130) of samples, higher than IgA, found in 35% (79) of samples. IgA results were similar for SARS-CoV-2, with IgA present in 30% (68) of samples, while IgG was less present, in 44.2% (100) of samples. The proportion of influenza IgG responders was higher than that for SARS-CoV-2 IgG, but both populations presented similar proportions of IgA responders, possibly due to variable memory B cell survival. For both viruses, the authors found an important proportion (> 10%) of IgA+IgG- samples, suggesting the occurrence of humoral immunity directed to the mucosa. CONCLUSION: Specific antibodies for respiratory viruses in saliva are found in either infection or vaccination and are a convenient and sensitive diagnostic tool for host immune response.
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COVID-19 , Vacinas contra Influenza , Chlorocebus aethiops , Animais , Humanos , SARS-CoV-2 , Células Vero , Imunoglobulina A , Imunoglobulina GRESUMO
The objective of this study was to determine the effect of pre-slaughter time about some blood constituents used as stress indicators in the evaluation of animal welfare in cattle. In the practice of ethology, animal welfare is assessed through physiological and behavioral indicators. For the determination of serum biomarkers of animal stress, a total of 180 animals was used, divided into two major groups according to the time of pre-slaughter. In the acceptable group, the animals had a pre-slaughter time up to 24 hours and in the not acceptable group the pre-slaughter time was greater than 24 h. These two groups were split up into three animal categories (males, females and castrated males). In this study, 30 samples were collected from each animal category of the two groups, acceptable and not acceptable, totaling 180 samples. Samples were separated for analysis of muscle enzymes creatine kinase and lactate dehydrogenase (CK and LDH), glucose and cortisol. Physiological values, regardless of the animal category and pre-slaughter time, were higher than the normal values of reference, expressing the prior management effect on animal welfare. The data clearly show a need to update and adapt the entire production chain to animal welfare practices, with the objective of producing competitive quality meat in the world market.(AU)
O objetivo do estudo foi avaliar o efeito do tempo de pré-abate sobre alguns constituintes sanguíneos utilizados como indicadores de estresse na avaliação do bem-estar animal em bovinos. Na prática da etologia, o bem-estar animal é avaliado por meio de indicadores fisiológicos e comportamentais. Para a determinação sérica de biomarcadores de estresse animal utilizaram-se 180 animais, divididos em dois grupos de acordo com o tempo de pré-abate: até 24 horas ou acima de 24 horas. Esses dois grupos subdividiram-se em três categorias animais (machos não-castrados, machos castrados ou fêmeas). Foram coletadas 30 amostras de cada categoria animal nos dois grupos, totalizando 180 amostras. Foram separadas amostras para análise de enzimas musculares creatina quinase e lactato desidrogenase (CK e LDH), glicose e cortisol. Os valores fisiológicos, independentemente da categoria animal e do tempo de pré-abate, foram superiores aos valores de referência, expressando o efeito do manejo prévio sobre o bem-estar dos animais. Os dados evidenciam claramente a necessidade de atualização e adequação de toda a cadeia produtiva às práticas de bem-estar animal, com o objetivo de produzir carne de qualidade competitiva no mercado mundial.(AU)
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Animais , Estresse Fisiológico , Bem-Estar do Animal , Bovinos/fisiologia , Comportamento Animal/fisiologia , Hidrocortisona/química , Creatina Quinase/química , Abate de Animais/métodos , L-Lactato Desidrogenase/químicaRESUMO
Background: The Brazilian tapir (Tapirus terrestris), considered the largest land mammal in South America, is a vulnerable species in terms of its degree of conservation. In captivity, its health is evaluated through behavioral and physical observation and laboratory exams, and in some cases, chemical restraint, to reduce stress. Dissociative anesthetics and sedatives are used for the sedation of these animals, and few studies have reported the use of dexmedetomidine and its effects when associated with other drugs in chemical containment protocols; therefore, this work reports its use, in conjunction with ketamine and midazolam, in a young Brazilian tapir. Case: A male Brazilian tapir, male, weighing 89 kg, 1 and a half year old, housed at CETAS in Rio Branco, Acre, was chemically restrained with dexmedetomidine (7 µg/kg), ketamine (1.5 mg/kg), and midazolam (0.2 mg/kg) for venous blood collection, oral and rectal mucosal swabs, and microchipping. The protocol was administered intramuscularly to the right triceps brachii, after physical restraint. After 5 min of application, the animal assumed sternal recumbency and presented reflux. After 15 min, the patient was placed in the right lateral decubitus position. During collection, heart rate (48 ± 10 bpm), respiratory frequency (29 ± 1 mpm), rectal temperature (38.1 ± 0.18°C), oxyhemoglobin saturation (97 ± 1%), and electrocardiographic tracing were recorded. The tapir showed deep sedation, immobility, good muscle relaxation, discreet medial palpebral reflex, and bilateral rotation of the eyeball. After 40 min of protocol administration, sedative reversal was performed intramuscularly with 14 µg/kg atipamezole. Five min after administration, the tapir showed signs of mild sedation. After 10 min, he assumed the quadrupedal position, remained in this position for 8 min, and gently resumed the sternal decubitus. After only 20 min, he resumed the quadrupedal position, with mild ataxia and good muscular and conscious tone. After 50 min, the patient was discharged from anesthesia. Discussion: Domestic horses are phylogenetically close to tapirs, so the choice of drugs and doses of the protocol used was based on their use in horses, and on studies carried out with tapirs as well. Despite being docile and passive, the tapir was not conditioned and did not allow the manipulation and collection of samples collaboratively; therefore, it was chemically contained. The physical restraint performed did not generate satisfactory immobilization of the tapir, resulting in agitation and stress and causing the needle to break. The reflux presented by the tapir minutes after sedation and at recovery was induced by dexmedetomidine, and only the undigested banana pieces were offered to the animal. Reflux plus stress from extensive fasting and suboptimal physical restraint was responsible for the change in the tapir's eating behavior, with possible stress gastritis 24 h after chemical restraint. Only one study reported the use of dexmedetomidine in tapirs, associated with continuous infusions of ketamine, midazolam and guaiacol glyceryl ether for moderate to long-term field procedures. Sedative reversal of dexmedetomidine by atipamezole reduced the recovery time and the risk of death from cardiorespiratory depression. The anesthetic combination used was effective, promoting immobility, muscle relaxation, and stability of the physical parameters evaluated, with rapid and gentle induction and an adequate level of sedation for the objective, good sedative reversal, and anesthetic recovery.
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Animais , Masculino , Perissodáctilos/fisiologia , Dexmedetomidina/administração & dosagem , Dexmedetomidina/análise , Animais Selvagens/fisiologiaRESUMO
Abstract Objectives: Defense against respiratory viruses depends on an immune response present in the mucosa, as saliva IgA secretes antibodies. During the pandemic, such as influenza or SARS-CoV-2, most infected patients are asymptomatic but retain specific antibodies post-infection. The authors evaluated IgG and IgA antibodies against SARS-CoV-2 and influenza in the saliva of asymptomatic volunteers, validated with controls or vaccinated individuals. Methods: The authors detected specific antibodies by validated conventional ELISA using natural SARS-CoV-2 antigens from infected Vero cells or capture-ELISA for influenza using natural antigens of the influenza vaccine. Results: Saliva from influenza-vaccinated individuals had more IgA than paired serum, contrary to the findings for specific IgG. In COVID-19-vaccinated samples, specific IgA in saliva increased after vaccination, but IgG levels were high after the first dose. In saliva from the asymptomatic population (226), anti-Influenza IgG was found in 57.5% (130) of samples, higher than IgA, found in 35% (79) of samples. IgA results were similar for SARS-CoV-2, with IgA present in 30% (68) of samples, while IgG was less present, in 44.2% (100) of samples. The proportion of influenza IgG responders was higher than that for SARS-CoV-2 IgG, but both populations presented similar proportions of IgA responders, possibly due to variable memory B cell survival. For both viruses, the authors found an important proportion (> 10%) of IgA+IgG- samples, suggesting the occurrence of humoral immunity directed to the mucosa. Conclusion: Specific antibodies for respiratory viruses in saliva are found in either infection or vaccination and are a convenient and sensitive diagnostic tool for host immune response.
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Rabies transmitted by sylvatic populations has become an increasing concern in Brazil. A total of 113 participants with a history of contact with sylvatic populations were interviewed in 27 municipalities of Ceará State in northeast Brazil. Questionnaires included questions on knowledge, attitudes and practices (KAP) regarding sylvatic rabies. Most of the respondents (92%) knew about rabies and confirmed at least one species that transmitted the disease (79.6%). Of these respondents, 69% mentioned monkeys, and 67.2% mentioned dogs. However, 16% of the respondents listed an incorrect species. In general, knowledge on the symptoms and signs and on prevention measures was weak. The majority raised pets (93.8%), most commonly dogs and cats, and, of all the pets, 85.7% were claimed to be vaccinated against rabies. A total of 67.3% reported the appearance of free-living wild animals around their houses, mostly marmosets and wild canids; 18.3% reported that sylvatic populations had attacked animals or humans. Seventy-three percent had raised or still were raising wild animals as pets, mostly capuchin monkeys (79.5%) and marmosets (24.1%). This is the first KAP study on sylvatic rabies in Brazil. The data indicate important knowledge gaps and risk behavior within a high-risk population. There is a need for strengthening and improving sylvatic rabies surveillance and control, combined with the intensification of education and information campaigns.
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An unprecedented global health crisis has been caused by a new virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed experiments to test if a hypertonic saline solution was capable of inhibiting virus replication. Our data show that 1.2% NaCl inhibited virus replication by 90%, achieving 100% of inhibition at 1.5% in the nonhuman primate kidney cell line Vero, and 1.1% of NaCl was sufficient to inhibit the virus replication by 88% in human epithelial lung cell line Calu-3. Furthermore, our results indicate that the inhibition is due to an intracellular mechanism and not to the dissociation of the spike SARS-CoV-2 protein and its human receptor. NaCl depolarizes the plasma membrane causing a low energy state (high ADP/ATP concentration ratio) without impairing mitochondrial function, supposedly associated with the inhibition of the SARS-CoV-2 life cycle. Membrane depolarization and intracellular energy deprivation are possible mechanisms by which the hypertonic saline solution efficiently prevents virus replication in vitro assays.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent of coronavirus disease 2019 (COVID-19), is responsible for the worst pandemic of the 21st century. Like all human coronaviruses, SARS-CoV-2 originated in a wildlife reservoir, most likely from bats. As SARS-CoV-2 has spread across the globe in humans, it has spilled over to infect a variety of non-human animal species in domestic, farm, and zoo settings. Additionally, a broad range of species, including one neotropical monkey, have proven to be susceptible to experimental infection with SARS-CoV-2. Together, these findings raise the specter of establishment of novel enzootic cycles of SARS-CoV-2. To assess the potential exposure of free-living non-human primates to SARS-CoV-2, we sampled 60 neotropical monkeys living in proximity to Manaus and São José do Rio Preto, two hotspots for COVID-19 in Brazil. Our molecular and serological tests detected no evidence of SAR-CoV-2 infection among these populations. While this result is reassuring, sustained surveillance efforts of wildlife living in close association with human populations is warranted, given the stochastic nature of spillover events and the enormous implications of SARS-CoV-2 spillover for human health.
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COVID-19/epidemiologia , Monitoramento Epidemiológico/veterinária , Primatas/virologia , Alouatta/virologia , Animais , Animais Selvagens/virologia , Brasil/epidemiologia , COVID-19/veterinária , Callicebus/virologia , Callithrix/virologia , Pandemias , SARS-CoV-2/patogenicidade , Zoonoses Virais/transmissãoRESUMO
The risk of contamination and dissemination by SARS-CoV-2 has a strong link with nasal, oral and pharyngeal cavities. Recently, our research group observed the promising performance of an anionic phthalocyanine derivative (APD) used in a mouthwash protocol without photoexcitation; this protocol improved the general clinical condition of patients infected with SARS-CoV-2. The present two-arm study evaluated in vitro the antiviral activity and cytotoxicity of APD. Additionally, a triple-blind randomized controlled trial was conducted with 41 hospitalized patients who tested positive for COVID-19. All the included patients received World Health Organization standard care hospital treatment (non-intensive care) plus active mouthwash (experimental group AM/n = 20) or nonactive mouthwash (control group NAM/n = 21). The adjunct mouthwash intervention protocol used in both groups consisted one-minute gargling/rinsing / 5 times/day until hospital discharge. Groups were compared considering age, number of comorbidities, duration of symptoms prior admission and length of hospital stay (LOS). The associations between group and sex, age range, presence of comorbidities, admission to Intensive care unit (ICU) and death were also evaluated. The in vitro evaluation demonstrated that APD compound was highly effective for reduction of SARS-CoV-2 viral load in the 1.0 mg/mL (99.96%) to 0.125 mg/mL (92.65%) range without causing cytotoxicity. Regarding the clinical trial, the median LOS of the AM group was significantly shortened (4 days) compared with that of the NAM group (7 days) (p = 0.0314). Additionally, gargling/rinsing with APD was very helpful in reducing the severity of symptoms (no ICU care was needed) compared to not gargling/rinsing with APD (28.6% of the patients in the NAM group needed ICU care, and 50% of this ICU subgroup passed way, p = 0.0207). This study indicated that the mechanical action of the protocol involving mouthwash containing a compound with antiviral effects against SARS-CoV-2 may reduce the symptoms of the patients and the spread of infection. The use of APD in a mouthwash as an adjuvant the hospital COVID-19 treatment presented no contraindication and reduced the hospital stay period.Trial registration: The clinical study was registered at REBEC-Brazilian Clinical Trial Register (RBR-58ftdj).
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Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Isoindóis/uso terapêutico , Antissépticos Bucais/uso terapêutico , Adulto , Idoso , Animais , Antivirais/química , Brasil/epidemiologia , COVID-19/epidemiologia , Chlorocebus aethiops , Feminino , Humanos , Isoindóis/química , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Antissépticos Bucais/química , SARS-CoV-2/efeitos dos fármacos , Células VeroRESUMO
OBJECTIVE: To describe the neurological and neurodevelopmental outcomes of children with Congenital Zika Syndrome (CZS) associated microcephaly beyond 2 years of age. METHOD: We followed children with CZS-associated microcephaly in an outpatient clinic in Salvador, Brazil. Neurological and neurodevelopmental assessments were performed using the Hammersmith Infant Neurological Examination (HINE) and Bayley Scales of Infant and Toddler Neurodevelopment (Bayley-III) respectively. RESULTS: Of the 42 children included, 19 were male (45.2%); median (interquartile range) age at neurological evaluation was 28 (25-32) months, and 36 (85.7%) had severe microcephaly. HINE and Bayley-III results were completed for 35/42 (83.3%) and 33/42 (78.5%) children respectively. Bayley-III identified a severe developmental delay in 32/33 (97.0%) children while 1/33 (3.0%) had only a mild delay. In the multivariable analysis, we found that Bayley-III and HINE scores were correlated. Better HINE scores were associated with higher Bayley-III cognitive raw scores (ß = 0.29; CI 95% = 0.02-0.57) and motor raw scores (ß = 0.43; CI 95% = 0.04-0.82) after adjusting for head circumference, prematurity, and age at neurodevelopmental evaluation. Furthermore, we found that greater head circumference at follow up was associated with higher cognitive (ß = 1.27; CI 95% = 0.01-2.53) and motor raw scores (ß = 2.03; CI 95% = 0.25-3.81). CONCLUSION: Children with CZS-associated microcephaly demonstrate severe neurodevelopmental delays and slower growth rates than their peers over time. Still, they have remarkably heterogeneous neurodevelopmental profiles according to neurological exam scores which correlate with their long-term outcomes. We found that HINE scores effectively captured the heterogeneity of neurological capabilities among these children and could be predictive of cognitive and motor development progress.
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Deficiências do Desenvolvimento/diagnóstico , Microcefalia/diagnóstico , Microcefalia/epidemiologia , Infecção por Zika virus/diagnóstico , Brasil/epidemiologia , Cefalometria , Pré-Escolar , Deficiências do Desenvolvimento/fisiopatologia , Deficiências do Desenvolvimento/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/etiologia , Microcefalia/virologia , Exame Neurológico , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/fisiopatologia , Complicações Infecciosas na Gravidez/virologia , Zika virus/patogenicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/virologiaRESUMO
Crianças atingidas pelo racismo acabam por expressar a negação da identidade negra em virtude dos estigmas associados à negritude. A Psicologia Comunitária, utilizando como aporte teórico-metodológico a problematização e a conscientização, pode proporcionar a potencialização dos sujeitos por meio do resgate da memória histórica e da desconstrução dos estereótipos de inferioridade racial. O presente artigo apresenta uma experiência profissional de práticas grupais com crianças, cujo principal objetivo consistiu em propiciar o resgate da memória histórica da cultura negra por meio da contação de histórias, visando combater o racismo.
Children affected by racism end up expressing the denial of black identity because of the stigmas associated with blackness. Community Psychology, using problematization and awareness as a theoretical-methodological contribution, can provide the potentiation of subjects through the rescue of historical memory and the deconstruction of racial inferiority stereotypes. This article presents a professional experience of group practices with children whose main objective was to propitiate the rescue of the historical memory of the black culture through the storytelling, aiming at fighting racism.
Los niños afectados por el racismo terminan expresando la negación de la identidad negra debido a los estigmas asociados con la negrura. La Psicología Comunitaria, utilizando la problematización y la concienciación como una contribución teórico-metodológica, puede proporcionar la potenciación de los sujetos mediante el rescate de la memoria histórica y la deconstrucción de los estereotipos de inferioridad racial. Este artículo presenta una experiencia profesional de prácticas de grupo con niños cuyo objetivo principal era propiciar el rescate de la memoria histórica de la cultura negra a través del relato de historias, con el fin de luchar contra el racismo.
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Racismo , Psicologia Social , Identificação Social , Conscientização , CulturaRESUMO
This study aims to describe the sociodemographic determinants associated with exposure to Zika Virus (ZIKV) in pregnant women during the 2015-2016 epidemic in Salvador, Brazil. METHODS: We recruited women who gave birth between October 2015 and January 2016 to a cross-sectional study at a referral maternity hospital in Salvador, Brazil. We collected information on their demographic, socioeconomic, and clinical characteristics, and evaluated their ZIKV exposure using a plaque reduction neutralization test. Logistic regression was then used to assess the relationship between these social determinants and ZIKV exposure status. RESULTS: We included 469 pregnant women, of whom 61% had a positive ZIKV result. Multivariate analysis found that lower education (adjusted Prevalence Rate [aPR] 1.21; 95%CI 1.04-1.35) and food insecurity (aPR 1.17; 95%CI 1.01-1.30) were positively associated with ZIKV exposure. Additionally, age was negatively associated with the infection risk (aPR 0.99; 95%CI 0.97-0.998). CONCLUSION: Eve after controlling for age, differences in key social determinants, as education and food security, were associated with the risk of ZIKV infection among pregnant women in Brazil. Our findings elucidate risk factors that can be targeted by future interventions to reduce the impact of ZIKV infection in this vulnerable population.
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Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Fatores Socioeconômicos , Infecção por Zika virus/economia , Infecção por Zika virus/epidemiologia , Adulto , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/economia , Fatores de RiscoRESUMO
BACKGROUND: Current evidence regarding COVID-19 convalescent plasma (CCP) transfusion practices is limited and heterogeneous. We aimed to determine the impact of the use of CCP transfusion in patients with previous circulating neutralizing antibodies (nAbs) in COVID-19. METHODS: Prospective cohort including 102 patients with COVID-19 transfused with ABO compatible CCP on days 0-2 after enrollment. Clinical status of patients was assessed using the adapted World Health Organization (WHO) ordinal scale on days 0, 5, and 14. The nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBank MT126808.1). The primary outcome was clinical improvement on day 14, defined as a reduction of at least two points on the adapted WHO ordinal scale. Secondary outcomes were the number of intensive care unit (ICU)-free days and the number of invasive mechanical ventilation-free days. RESULTS: Both nAbs of CCP units transfused (p < 0.001) and nAbs of patients before CCP transfusions (p = 0.028) were associated with clinical improvements by day 14. No significant associations between nAbs of patients or CCP units transfused were observed in the number of ICU or mechanical ventilation-free days. Administration of CCP units after 10 days of symptom onset resulted in a decrease in ICU-free days (p < 0.001) and mechanical ventilation-free days (p < 0.001). CONCLUSION: Transfusion of high titer nAbs CCP units may be a determinant in clinical strategies against COVID-19. We consider these data as useful parameters to guide future CCP transfusion practices.
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Anticorpos Neutralizantes/sangue , COVID-19/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Doadores de Sangue , COVID-19/sangue , COVID-19/imunologia , Estudos de Coortes , Feminino , Humanos , Imunização Passiva/métodos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Soroterapia para COVID-19RESUMO
BACKGROUND: Blood groups and anti-A isohemagglutinin may be involved in susceptibility to SARS-CoV-2 infection. MATERIALS AND METHODS: We retrospectively studied 268 COVID-19 convalescent plasma donors and 162 COVID-19 inpatients (total 430 subjects, confirmed by RT-PCR) and 2,212 healthy volunteer first-time blood donors as a control group. These were further divided into two groups: those with anti-A (blood types O and B) and those without it (types A and AB). Titres of nucleoproteins, and neutralizing SARS-CoV-2 antibody were measured in the convalescent plasma donors and inpatients. Multivariate logistic regression and non-parametric tests were applied. RESULTS: Persons having types O or B showed less infection prevalence than those of types A or AB (OR = 0·62, 95% CI 0·50-0·78; P < 0·001), but there was no difference when COVID-19 inpatients were analysed. Immunoglobulins M, G and A were lower in COVID-19 subjects of types O or B group than those of A or AB (0·16 vs. 0·19; P = 0·03, 2·11 vs. 2·55; P = 0·02, 0·23 vs. 0·32; P = 0·03, respectively). CONCLUSION: In this retrospective cohort, COVID-19 individuals were less likely to belong to blood types O and B, and also had lower SARS-CoV-2 antibody titres than A and AB individuals. COVID-19 severity did not associate with the blood groups.
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Sistema ABO de Grupos Sanguíneos/sangue , Anticorpos Antivirais/sangue , COVID-19/sangue , COVID-19/terapia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Hemaglutininas/imunologia , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Soroterapia para COVID-19RESUMO
Aerobic organisms require oxygen for energy. In the course of the infection, adaptation to hypoxia is crucial for survival of human pathogenic fungi. Members of the Paracoccidioides complex face decreased oxygen tensions during the life cycle stages. In Paracoccidioides brasiliensis proteomic responses to hypoxia have not been investigated and the regulation of the adaptive process is still unknown, and this approach allowed the identification of 216 differentially expressed proteins in hypoxia using iTRAQ-labelling. Data suggest that P. brasiliensis reprograms its metabolism when submitted to hypoxia. The fungus reduces its basal metabolism and general transport proteins. Energy and general metabolism were more representative and up regulated. Glucose is apparently directed towards glycolysis or the production of cell wall polymers. Plasma membrane/cell wall are modulated by increasing ergosterol and glucan, respectively. In addition, molecules such as ethanol and acetate are produced by this fungus indicating that alternative carbon sources probably are activated to obtain energy. Also, detoxification mechanisms are activated. The results were compared with label free proteomics data from Paracoccidioides lutzii. Biochemical pathways involved with acetyl-CoA, pyruvate and ergosterol synthesis were up-regulated in both fungi. On the other hand, proteins from TCA, transcription, protein fate/degradation, cellular transport, signal transduction and cell defense/virulence processes presented different profiles between species. Particularly, proteins related to methylcitrate cycle and those involved with acetate and ethanol synthesis were increased in P. brasiliensis proteome, whereas GABA shunt were accumulated only in P. lutzii. The results emphasize metabolic adaptation processes for distinct Paracoccidioides species.
Assuntos
Hipóxia/metabolismo , Paracoccidioides/metabolismo , Proteoma/metabolismo , Proteômica , Parede Celular/metabolismo , Ergosterol/biossíntese , Proteínas Fúngicas/genética , Proteínas Fúngicas/isolamento & purificação , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Glicólise , Humanos , Peróxido de Hidrogênio/metabolismo , Nitrogênio/metabolismo , Paracoccidioides/genética , Paracoccidioides/patogenicidade , VirulênciaRESUMO
INTRODUCTION: Little is known about the neutralizing (nAb) and binding antibody kinetics in COVID-19 convalescent plasma donors, especially during the first 100 days after disease onset. MATERIALS AND METHODS: A cohort of previously RT-PCR positive (detected by nasopharyngeal swab during the acute phase), male convalescent patients, all with mild symptoms, were enrolled in serial blood sample collection for a longitudinal nAb titers and anti-nucleocapsid (NP) antibodies (IgM, IgG and IgA) evaluation. NAbs were detected by a cytopathic effect-based virus neutralization test (CPE-based VNT), carried out with SARS-CoV-2 (GenBank: MT350282). RESULTS: A total of 78 male volunteers provided 316 samples, spanning a total of 4820 days of study. Although only 25% of donors kept nAb titers ≥160 within 100 days after the onset of disease, there was >75% probability of sustaining nAb titers ≥160 in volunteers whose initial nAb titer was ≥1280, weight ≥ 90 kg or obese, according to their body mass index (BMI), as evidenced by Kaplan-Meier analysis and Cox hazard regression (all p < .02). There was no correlation between the ABO group, ABO antibody titers and persistent high nAb titers. High IgG anti-NP (S/CO ≥5.0) is a good surrogate for detecting nAb ≥ 160, defined by the ROC curve (sensitivity = 90.5%; CI95%: 84.5%-94.7%). CONCLUSION: Selection of CCP donors for multiple collections based on initial high nAb titers (≥1280) or BMI ≥ 30 kg/m2 provides a simple strategy to achieve higher quality in CCP programs. High IgG anti-NP levels can also be used as surrogate markers for high nAb screening.
Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Doadores de Sangue , Segurança do Sangue , Índice de Massa Corporal , COVID-19/sangue , Nucleocapsídeo/sangue , SARS-CoV-2/metabolismo , Adolescente , Adulto , Feminino , Humanos , Cinética , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The efficacy of convalescent plasma (CP), an alternative for the treatment of COVID-19, depends on high titers of neutralizing antibodies (nAbs), but assays for quantifying nAbs are not widely available. Our goal was to develop a strategy to predict high titers of nAbs based on the results of anti-SARS-CoV-2 immunoassays and the clinical characteristics of CP donors. STUDY DESIGN AND METHODS: A total of 214 CP donors were enrolled and tested for the presence of anti-SARS-CoV-2 antibodies (IgG) using two commercial immunoassays: EUROIMMUN (ELISA) and Abbott (Chemiluminescence). Quantification of nAbs was performed using the Cytopathic Effect-based Virus Neutralization test. Three criteria for identifying donors with nAbs ≥ 1:160 were tested: - C1: Curve ROC; - C2: Conditional decision tree considering only the IA results and - C3: Conditional decision tree including both the IA results and the clinical variables. RESULTS: The performance of the immunoassays was similar referring to both S/CO and predictive value for identifying nAbs titers ≥1:160. Regarding the studied criteria for identifying CP donors with high nAbs titers: (a) C1 showed 76.1% accuracy if S/CO = 4.65, (b) C2 presented 76.1% accuracy if S/CO ≥4.57 and (c) C3 had 71.6% accuracy if S/CO was ≥4.57 or if S/CO was between 2.68-4.57 and the last COVID-19-related symptoms were recent (within 19 days). CONCLUSION: SARS-CoV-2 IgG immunoassays (S/CO) can be used to predict high anti-SARS-CoV-2 nAbs titers. This study has proposed different criteria for identifying donors with ≥1:160 nAbs titers, all with high efficacy.