Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19

IntroductionMannose-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.MethodsBlood 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.ResultsThe 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.DiscussionThe 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

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Estudo da associação dos polimorfismos nos genes interleucina - 8 (IL8), Interferon - γ (IFNG) e fator de crescimento transformante - B (TGFB) em pacientes com infecção crônica pelos vírus das hepatites B e C.

Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Resumo: Atualmente as hepatites virais são consideradas a maior pandemia mundial, tendo os vírus da Hepatite B e C, como os principais responsáveis pelo desenvolvimento de doenças hepáticas crônicas no mundo, constituindo significativo problema de saúde pública. As hepatites desencadeiam diferentes respostas imunológicas de caráter adaptativo e inato, contribuindo para o aumento ou queda na produção de citocinas que atuarão de forma a mediar os processos imunes e inflamatórios. A Interleucina-8 (IL-8), o Interferon-γ (IFN- γ) e o Fator de Crescimento Transformante-β (TGF-β), são citocinas que regulam o processo inflamatório, podendo estar envolvidas com a progressão das hepatopatias. O objetivo do estudo foi determinar as frequências dos polimorfismos nos genes IL8, IFNG e TGFβ, em pacientes portadores crônicos das hepatites B e C, buscando identificar possíveis associações com as infecções. O estudo foi do tipo transversal e analítico, sendo a população de estudo composta por pacientes portadores de hepatite B crônica(74), hepatite C crônica (101) e grupo controle (300). Foi utilizado o método de extração de DNA total a partir de células do sangue total periférico das amostras, posteriormente, os polimorfismos rs4073 (T>A) no gene IL8, rs2430561 (T>A) no gene IFNG e rs1800469 (C>T) no gene TGFβ, foram genotipados por meio da reação em cadeia mediada pela polimerase em tempo real (qPCR). As amostras de sangue de todos os participantes foram coletadas em tubos a vácuo com EDTA, e as amostras de plasma separadas por centrifugação, as quais foram submetidas a exames bioquímicos e sorológicos. As análises estatísticas foram realizadas no programa BioEstat 5.0 e os gráficos construídos no programa GraphPad Prisma 5.0, adotando como nível de significância pT no gene TGFβ, bem como, ausência de correlação entre os polimorfismos de IL-8, IFN-γ e TGF-β, com atividade inflamatória e estadiamento de fibrose. Foi observado, também, associação significativa entre os níveis de GGT e polimorfismo de IL-8 no grupo HBV, assim como, associação entre os níveis de AST e HBV-DNA com o polimorfismo de TGF-β. Associação significante foi encontrada entre os níveis de GGT e o polimorfismo de IL-8 em pacientes com HBV sem cirrose, e associação entre os níveis de AST e carga viral com o polimorfismo de TGF-β, em pacientes HCV cirróticos e HBV não cirróticos, respectivamente. Dessa maneira, conclui-se que: o polimorfismo de TGFβ influencia o status de manutenção das hepatites e não há influência dos polimorfismos no quadro inflamatório e na progressão da fibrose. Conclui-se também que, os polimorfismos de IL-8 e TGF-β influenciam os níveis das enzimas hepáticas em pacientes com HBV, assim com o polimorfismo de TGFβ influencia os níveis de HBV-DNA; o polimorfismo de IL-8 influencia os níveis de GGT em pacientes com HBV na ausência de cirrose hepática; e o polimorfismo de TGFβ influência os níveis de AST e carga viral, em pacientes com HCV não cirróticos e pacientes HBV não cirróticos, respectivamente

Chlamydia trachomatis serotype A infections in the Amazon region of Brazil: prevalence, entry and dissemination

INTRODUCTION: Chlamydia infection is associated with debilitating human diseases including trachoma, pneumonia, coronary heart disease and urogenital diseases. Serotypes of C. trachomatis show a fair correlation with the group of diseases they cause, and their distribution follows a well-described geographic pattern. Serotype A, a trachoma-associated strain, is known for its limited dissemination in the Middle East and Northern Africa. However, knowledge on the spread of bacteria from the genus Chlamydia as well as the distribution of serotypes in Brazil is quite limited. METHODS: Blood samples of 1,710 individuals from ten human population groups in the Amazon region of Brazil were examined for antibodies to Chlamydia using indirect immunofluorescence and microimmunofluorescence assays. RESULTS: The prevalence of antibodies to Chlamydia ranged from 23.9% (Wayana-Apalai) to 90.7% (Awa-Guaja) with a mean prevalence of 50.2%. Seroreactivity was detected to C. pneumoniae and to all serotypes of C. trachomatis tested; furthermore, we report clear evidence of the as-yet-undescribed occurrence of serotype A of C. trachomatis. CONCLUSIONS: Specific seroreactivity not only accounts for the large extent of dissemination of C. trachomatis in the Amazon region of Brazil but also shows an expanded area of occurrence of serotype A outside the epidemiological settings previously described. Furthermore, these data suggest possible routes of Chlamydia introduction into the Amazon region from the massive human migration that occurred during the 1,700s

The Genetic Profile and Serum Level of IL-8 Are Associated with Chronic Hepatitis B and C Virus Infection

The present study evaluated the IL8-251 A/T polymorphism in samples from 74 patients with chronic hepatitis B (HBV), 100 patients with chronic hepatitis C (HCV), and 300 healthy donors (CG). The correlations of this polymorphism with plasma IL-8 and disease stage were calculated. Polymorphisms were identified by real-time PCR. IL-8 was measured by enzyme-linked immunosorbent assay. The IL8-251 A/T genotype was not associated with susceptibility to infection by HBV or HCV. The wild-type allele (A) was associated with higher levels of inflammation (p = 0.0464) and fibrosis scores (p = 0.0016) in the HBV group, representing an increased risk for increased inflammatory activity (OR = 1.84; p = 0.0464) and for high fibrosis scores (OR = 2.63; p = 0.0016). Viral load was higher in HBV patients with polymorphic genotypes (TA and TT) at the IL8-251 A/T polymorphism than in those with the wild-type genotype (p = 0.0272 and p = 0.0464, respectively). Plasma IL-8 was higher among patients infected with HBV or HCV than in the control group (p = 0.0445 and p = 0.0001, respectively). The polymorphic genotype was associated with lower IL-8 than the wild-type genotype in the HBV group (p = 0.0239) and the HCV group (p = 0.0372). The wild-type genotype for IL8-251 A/T and high IL-8 were associated with a worse prognosis for infections; therefore, they may contribute to viral persistence and the development of more severe forms of chronic viral liver diseases

The TGFB1-509C/T polymorphism and elevated TGF-beta 1 levels are associated with chronic hepatitis C and cirrhosis

This work was supported by the Brazilian National Council for Sci-entific and Technological Development (CNPQ Nos. 480128/2013-8, 301869/2017-0 and 312979/2018-5) and by the Federal University of Par ́a (PROPESP/PAPQ/2020)Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil.Federal University of Pará. João de Barros Barreto Hospital. Belém, Pará, Brazil / Federal University of Pará. Institute of Health Sciences. School of Medicine. Belém, Pará, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Human Genetics. Belém, Pará, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil.The IFN-γ and TGF-β1 cytokines perform antagonistic activities in the immune response, and polymorphisms in these genes may induce changes in their plasma levels and influence the course of chronic Hepacivirus C (HCV) infection. The present study evaluated the IFNG +874A/T and TGFB1 -509 C/T polymorphisms in 99 samples from patients with chronic hepatitis C and in 300 samples from healthy donors, and the present study also investigated the association of cytokine plasma level with disease stage. Polymorphisms were identified by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of the IFNG +874A/T polymorphic allele was not associated with susceptibility to HCV infection, but it was associated with lower inflammatory activity (p = 0.0432). The frequency of the TGFB1 -509C/T polymorphic (TT) genotype was associated with HCV infection (p = 0.0062) and a higher risk of infection (OR = 2.0465; p = 0.0091). Plasma levels of IFN-γ were higher in TT genotype carriers among the control (p = 0.0012) and HCV groups (p = 0.0064) as well as in patients with fibrosis (p = 0.0346) and patients with a high degree of inflammatory activity (p = 0.0381). The highest TGF-β1 levels were found in HCV-infected (p = 0.0329) individuals and in TT genotype carriers. Patients with cirrhosis had higher TGF-β1 (p = 0.0400). IFN-γ and TGF-β1 levels showed a negative correlation (p = 0.0001). In conclusion, the TGFB1 -509C > T polymorphism is associated with a risk of developing chronic hepatitis C, leading to increased TGF-β1, which inhibits IFN-γ production, contributing to the progression to cirrhosi

Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19

National Council for Scientific and Technological Development (CNPQ #401235/2020-3); Fundação Amazônia de Amparo a Estudos e Pesquisa do Pará (FAPESPA #005/2020 and #006/2020), Secretaria de Estado de Ciência, Tecnologia e Educação Profissional e Tecnológica (#09/ 2021) and Universidade Federal do Pará (PAPQ/2022)Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Programa de Pós-Graduação em Virologia. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Programa de Pós-Graduação em Virologia. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Pesquisa Básica em Malária, Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Pesquisa Básica em Malária, Ananindeua, PA, Brasil / Federal University of Pará. Institute of Medical Sciences. School of Medicine. Belém, PA, Brazil.Belém Adventist Hospital. Belém, PA, Brazil.Belém Adventist Hospital. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Programa de Pós-Graduação em Virologia. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Programa de Pós-Graduação em Virologia. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.University of the State of Pará. Center of Biological and Health Sciences. Belém, PA, Brazil.University of the State of Pará. Center of Biological and Health Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.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