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The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , Interferon-alfa , Interleucina-6 , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Transdução de Sinais/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND: Syphilis is a chronic infectious disease, and its prevalence has been described since the 15th century. Because of the high prevalence of this infection in Brazil, this study aimed to evaluate the prevalence of syphilis and its associated factors among adolescent and young women living in the city of Boa Vista, Roraima, Brazil. METHODS: The present study was cross-sectional, descriptive, analytical and quantitative. It involved 200 young and adolescent women. Laboratory tests were performed to diagnose syphilis, and a sociodemographic and epidemiological questionnaire was employed. RESULTS: In the studied sample, 10 women had a positive result for syphilis, characterizing a prevalence of 5% for infection with Treponema pallidum. There was a statistically significant association between a monthly family income of less than 1 minimum wage and syphilis (p = 0.0449) and between illicit drug use and syphilis (p = 0.0234). CONCLUSIONS: These results indicate the need for public health interventions, action plans, and the implementation of risk reduction strategies focused on this population.
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Introduction: Human T-lymphotropic virus 2 (HTLV-2) has been described for more than 30 years as an endemic infection in Brazilian indigenous populations, with its occurrence varying by age and sex, maintained mainly by sexual intercourse and mother-to-child transmission, favoring intrafamilial aggregation. Methods: The epidemiological scenario of HTLV-2 infection has been described among communities of the Amazon region of Brazil (ARB), with the number of retrospective positive blood samples increasing for more than 50 years. Results: Five publications were selected that showed the presence of HTLV-2 in 24 of 41 communities; the prevalence of infection was described among 5,429 individuals at five points in time. Among the Kayapó villages, the prevalence rates were described according to age and sex and reached up to 41.2%. Three communities (Asurini, Araweté, and Kaapor) were kept virus free for 27 to 38 years of surveillance. Low, medium and high prevalence levels of infection were defined, and two pockets of high endemicity were shown in the state of Pará, pointing to the Kikretum and Kubenkokrê Kayapó villages as the epicenter of HTLV-2 in the ARB. Discussion: The prevalence rates over the years have shown a decline among the Kayapó (from 37.8 to 18.4%) and an apparent change to a higher prevalence among females, but not during the first decade of life, usually associated with transmission from mother to child. Sociocultural and behavioral aspects, as well as public health policies directed toward sexually transmitted infections, might have positively influenced the decline in HTLV-2 infections.
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BACKGROUND: The COVID-19 pandemic has had a great impact on pregnant women due to the broad clinical spectrum of the disease. The present study investigated the profile of three biomarkers during hospital admission of pregnant women-D-dimer, C-reactive protein (CRP), and ferritin-and their correlation with the severity and outcome of COVID-19. METHODS: The cross-sectional study included 226 pregnant women hospitalized in the city of Belém, Pará, Northern Brazil, from April 2020 to July 2021. Epidemiological and laboratory data were obtained from medical records, and all pregnant women underwent RT-PCR molecular testing for the detection of SARS-CoV-2. RESULTS: In total, 121 (53.5%) were positive and 105 (46.5%) were negative for SARS-CoV-2 using RT-PCR. Most pregnant women (49.5%) with COVID-19 were between 26 and 34 years old, were residing in the interior of the state of Pará (51.2%), and were in the third gestational trimester (71.9%). In addition, 71.1% of them were admitted to the ward and 28.9% were admitted to the intensive care unit (ICU), with 90.9% surviving COVID-19. The concentrations of D-dimer (p = 0.0122) and ferritin (p ≤ 0.0001) were significantly higher among pregnant women with COVID-19, especially among those hospitalized in the ICU. CONCLUSION: Ferritin and D-dimer seem to serve as important biomarkers for the prognosis of COVID-19 in pregnant women, which was not observed for CRP.
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COVID-19 , Humanos , Feminino , Gravidez , Adulto , COVID-19/diagnóstico , COVID-19/epidemiologia , Gestantes , Proteína C-Reativa/análise , SARS-CoV-2 , Estudos Transversais , Ferritinas , Pandemias , Brasil/epidemiologia , Biomarcadores , Estudos RetrospectivosRESUMO
Introduction: Mannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19. Methods: Blood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively. Results: The frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed. Discussion: The results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19.
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COVID-19 , Lectina de Ligação a Manose , Humanos , Fator de Necrose Tumoral alfa/genética , Interleucina-6/genética , Citocinas/genética , Síndrome de COVID-19 Pós-Aguda , COVID-19/genética , Polimorfismo Genético , Lectina de Ligação a Manose/genéticaRESUMO
Interleukin-6 has been recognized as a major role player in COVID-19 severity, being an important regulator of the cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of the IL-6 pathway, namely IL6, IL6R, and IL6ST, may provide valuable prognostic/predictive markers for COVID-19. The present cross-sectional study genotyped three SNPs (rs1800795, rs2228145, and rs7730934) at IL6. IL6R and IL6ST genes, respectively, in 227 COVID-19 patients (132 hospitalized and 95 non-hospitalized). Genotype frequencies were compared between these groups. As a control group, published data on gene and genotype frequencies were gathered from published studies before the pandemic started. Our major results point to an association of the IL6 C allele with COVID-19 severity. Moreover, IL-6 plasmatic levels were higher among IL6 CC genotype carriers. Additionally, the frequency of symptoms was higher at IL6 CC and IL6R CC genotypes. In conclusion, the data suggest an important role of IL6 C allele and IL6R CC genotype on COVID-19 severity, in agreement with indirect evidence from the literature about the association of these genotypes with mortality rates, pneumonia, and heightening of protein plasmatic levels pro-inflammatory driven effects.
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COVID-19 , Interleucina-6 , Humanos , Interleucina-6/genética , Estudos Transversais , Receptores de Interleucina-6/genética , COVID-19/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Receptor gp130 de Citocina/genéticaRESUMO
The first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Brazil was diagnosed on February 26, 2020. Due to the important epidemiological impact of COVID-19, the present study aimed to analyze the specificity of IgG antibody responses to the S1, S2 and N proteins of SARS-CoV-2 in different COVID-19 clinical profiles. This study enrolled 136 individuals who were diagnosed with or without COVID-19 based on clinical findings and laboratory results and classified as asymptomatic or as having mild, moderate or severe disease. Data collection was performed through a semistructured questionnaire to obtain demographic information and main clinical manifestations. IgG antibody responses to the S1 and S2 subunits of the spike (S) protein and the nucleocapsid (N) protein were evaluated using an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions. The results showed that among the participants, 87.5% (119/136) exhibited IgG responses to the S1 subunit and 88.25% (120/136) to N. Conversely, only 14.44% of the subjects (21/136) displayed S2 subunit responses. When analyzing the IgG antibody response while considering the different proteins of the virus, patients with severe disease had significantly higher antibody responses to N and S1 than asymptomatic individuals (p ≤ 0.0001), whereas most of the participants had low antibody titers against the S2 subunit. In addition, individuals with long COVID-19 showed a greater IgG response profile than those with symptomatology of a short duration. Based on the results of this study, it is concluded that levels of IgG antibodies may be related to the clinical evolution of COVID-19, with high levels of IgG antibodies against S1 and N in severe cases and in individuals with long COVID-19.
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COVID-19 , Humanos , Anticorpos Antivirais , Formação de Anticorpos , Imunoglobulina G , Proteínas do Nucleocapsídeo , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Glicoproteína da Espícula de CoronavírusRESUMO
CCR5Δ32 and SDF1-3'A polymorphisms were investigated in a cohort of viremia controllers, without the use of therapy, along with their influence on CD4+ T lymphocytes (TLs), CD8+ TLs, and plasma viral load (VL). The samples were analyzed from 32 HIV-1-infected individuals classified as viremia controllers 1 and 2 and viremia non-controllers, from both sexes, mostly heterosexuals, paired with 300 individuals from a control group. CCR5∆32 polymorphism was identified by PCR amplification of a fragment of 189 bp for the wild-type allele and 157 bp for the allele with the ∆32 deletion. SDF1-3'A polymorphism was identified by PCR, followed by enzymatic digestion (restriction fragment length polymorphism) with the Msp I enzyme. The relative quantification of gene expression was performed by real-time PCR. The distribution of allele and genotype frequencies did not show significant differences between the groups. The gene expression of CCR5 and SDF1 was not different between the profiles of AIDS progression. There was no significant correlation between the progression markers (CD4+ TL/CD8+ TL and VL) and the CCR5∆32 polymorphism carrier status. The 3'A allele variant was associated with a marked loss of CD4+ TLs and a higher plasma VL. Neither CCR5∆32 nor SDF1-3'A was associated with viremia control or the controlling phenotype.
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Síndrome da Imunodeficiência Adquirida , Quimiocina CXCL12 , Infecções por HIV , Receptores CCR5 , Feminino , Humanos , Masculino , Síndrome da Imunodeficiência Adquirida/genética , Biomarcadores , Brasil , Quimiocina CXCL12/genética , Progressão da Doença , Frequência do Gene , HIV-1 , Receptores CCR5/genética , ViremiaRESUMO
TNF-α is a Th1 cytokine profile active in the control of Mycobacterium tuberculosis infection, IL-10 is associated with persistence of bacterial infection. The aim of the study was to investigate the association of TNFA -308G/A and IL10 -819C/T polymorphisms and TNFA and IL10 gene expression levels with pulmonary and extrapulmonary tuberculosis (n = 200) and control (n = 200). The individuals were submitted to genotyping and quantification of gene expression performed by real-time quantitative polymerase chain reaction (qPCR). No association was observed between the frequencies of polymorphisms evaluated and pulmonary tuberculosis. The frequency of polymorphic genotypes for TNFA -308G/A were associated with the extrapulmonary tuberculosis (p = 0.0445). The levels of TNFA expression were lower in the pulmonary tuberculosis group than in the control (p = 0.0009). There was a positive correlation between the levels of TNFA and IL10 in patients with pulmonary tuberculosis (r = 0.560; p = 0.0103). Reduced levels of TNFA expression may promote the formation of an anti-inflammatory microenvironment, favoring the persistence of the bacillus in the host, contributing to the establishment of pulmonary tuberculosis.
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Interleucina-10 , Tuberculose Pulmonar , Humanos , Interleucina-10/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Brasil , Genótipo , Fator de Necrose Tumoral alfa/genética , Expressão Gênica , Frequência do GeneRESUMO
Antiretroviral therapy (ART) improves the quality of life of people living with HIV-1 (PLHIV) and reduces the mortality rate, but some individuals may develop metabolic abnormalities. This study evaluated changes in the nutritional status and biochemistry of PLHIV on antiretroviral therapy in a cohort that had not previously received ART and to follow up these individuals for 24 months after starting treatment. The initial cohort consisted of 110 individuals and ended with 42 people, assessed by a physical examination. A biochemical assay was performed using the colorimetric enzyme reaction technique, the proviral load was detected by qPCR and the quantification of the CD4/CD8 T lymphocytes was conducted by flow cytometry. PLHIV had increased levels of total cholesterol, LDL, triglycerides, ALT, urea and creatinine after 24 months of ART use (p < 0.05). In the assessment of the nutritional status, PLHIV had increased measures of Triciptal Skinfold, body mass index and arm circumference after the use of ART (p < 0.05). The viral load levels decreased and the CD4 levels increased after 24 months of ART use (p < 0.05). The change in the nutritional status in PLHIV on antiretroviral therapy seems to be a slow process, occurring in the long term, therefore, there is the need for a constant evaluation of these people to identify patients who need a nutritional intervention.