Association of the IFNG +874T/A Polymorphism with Symptomatic COVID-19 Susceptibility.

Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, we investigated the associations of the TNF -308G/A and IFNG +874T/A polymorphisms with COVID-19. We analyzed the frequencies of the two polymorphisms in the control groups (CG: TNF -308G/A, n = 497; IFNG +874T/A, n = 397), a group of patients with COVID-19 (CoV, n = 222) and among the subgroups of patients with nonsevere (n = 150) and severe (n = 72) COVID-19. We found no significant difference between the genotypic and allelic frequencies of TNF -308G/A in the groups analyzed; however, both the frequencies of the high expression genotype (TT) (CoV: 13.51% vs. CG: 6.30%; p = 0.003) and the *T allele (CoV: 33.56% vs. CG: 24. 81%; p = 0.001) of the IFNG +874T/A polymorphism were higher in the COVID-19 group than in the control group, with no differences between the subgroups of patients with nonsevere and severe COVID-19. The *T allele of IFNG +874T/A (rs2430561) is associated with susceptibility to symptomatic COVID-19. These SNPs provided valuables clues about the potential mechanism involved in the susceptibility to developing symptomatic COVID-19.

Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α.

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.

Association of Polymorphisms of IL-6 Pathway Genes (IL6, IL6R and IL6ST) with COVID-19 Severity in an Amazonian Population.

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.

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.

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.

Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome.

The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort. A total of 317 patients diagnosed with COVID-19 were included; cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome). In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-α, and patients without comorbidities had higher levels of TNF-α, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05). Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies.

Carga de trabalho da enfermagem e a mortalidade de pacientes na unidades de terapia intensiva / Nursing workload and mortality of intensive care unit patients

Objetivo: Analisar a correlação entre a carga de trabalho da equipe de enfermagem, aferida pelo escore NAS (Nursing Activities Score) e a mortalidade predita pelo escore SAPS 3 dos pacientes internados em Unidade de Terapia Intensiva, verificando as correlações entre os profissionais de enfermagem atuantes na unidade segundo o preconizado pela RDC e o recomendado pelo escore NAS. Material e Métodos: Trata-se de um estudo de coorte realizado no período de setembro de 2014 a abril de 2015, com 270 pacientes. Utilizou-se o instrumento NAS e, posteriormente, foi submetido a análise estatística no BioEstat 5.3®. Resultados: A partir da análise dos resultados foi possível identificar que a sepse foi o principal diagnóstico. Houve correlação linear entre o NAS médio e o inicial dos pacientes internados com o índice prognóstico SAPS 3, com diferença estatisticamente significante entre o número de profissionais atuantes nas unidades e o número de profissionais de enfermagem dimensionados pelo NAS. Conclusão: Conclui-se que o NAS é uma ferramenta importante para dimensionar a carga de trabalho da equipe nas UTIs. (AU)

Objective: This study aims to analyze the correlation between the workload of the nursing team, measured by the NAS score (Nursing Activities Score) and the predicted mortality by SAPS 3 score of patients in the Intensive Care Unit and to investigate the correlations between nursing professionals working in the unit as recommended by the Resolution n° 7, from brazilian Ministério da Saúde Materials and Methods: A clinical cohort conducted during the period of September 2014 and April 2015, with 270 patientes. The NAS score was used and was later submitted to statistical analysis in the BioEstat 5.3®.Results: From the analysis of the results, it was possible to identify that the sepsis was the main diagnosis. There was linear correlation between the medium and initial NAS of the hospitalized patients with the SAPS score 3, with significant statistical diference between the number of working professionals in the units and the number of nursing professionals measured by the NAS. Conclusion : The NAS is an important tool for measuring the workload of the ICU teams. (AU)

Fila de espera para tratamento de pacientes com cardiopatia congênita: relato de um Centro de Referência Amazônico / Waiting for cardiac procedure in congenital heart disease: portrait of an Amazonian Hospital

As cardiopatias congênitas são importantes causas de morbimortalidade infantil e, em cerca de 50% dos casos, é necessária a intervenção cirúrgica no primeiro ano de vida. Estima-se alto défice de procedimentos na Região Norte do Brasil.Analisar o tempo de espera para realização de tratamento eletivo cirúrgico e/ou intervencionista de crianças portadoras de cardiopatias congênitas em um centro de referência cardiológico, e fazer considerações sobre as cardiopatias e suas formas de tratamento na referida instituição. Estudo analítico, de caráter transversal do período de janeiro de 2012 a outubro de 2014, de pacientes com idade igual ou inferior a 14 anos diagnosticados com cardiopatias congênitas que estavam na fila de tratamento cardíaco eletivo cirúrgico ou percutâneo. Das 407 crianças que aguardavam por tratamento, a faixa etária mais prevalente foi a de > 2 a 6 anos (34,0%). O tempo médio de espera, em meses, foi 23,1 ± 18,3, com mediana de 19. As cardiopatias mais frequentes foram comunicação interventricular (28,98%), persistência do canal arterial (18,42%) e comunicação interatrial (11,05%). A maioria das crianças (63,4%) não pertencia à região metropolitana. As intervenções percutâneas representaram somente 27,84% do total de cateterismos e 14,85% de todos os tratamentos cardíacos. Cerca de 60% do volume de cirurgias pediátricas ocorreu em crianças sem cadastro prévio no sistema, devido ao caráter de urgência. Grande parte das crianças que aguardam por procedimento cardíaco é procedente de fora da região metropolitana e tem malformações potencialmente tratáveis por cateterismo. É necessário aumentar a capacidade operacional do único centro de referência público do Estado, além de descentralizar o atendimento em alta complexidade cardiológica da região metropolitana

Congenital heart disease is an important cause of morbidity and mortality in childhood, and in 50% of cases, surgery is required in the first year of life. A high deficit of surgical procedures is estimated in Northern Brazil. To analyze the waiting time for elective surgical treatment and/or intervention in children with congenital heart disease in a Cardiology referral center, and to make considerations about heart diseases and forms of treatment in that institution. A cross-sectional study of all patients aged less than 14 years, with a diagnosis of congenital heart disease that were waiting for elective surgical or percutaneous cardiac treatment. Among the 407 children with congenital heart defects, the most prevalent age group was > 2 to 6 years (34.0%). The average waiting time was 23.1 ± 18.3 months, with a median of 19. The most frequent heart disease was ventricular septal defect (28.98%), patent ductus arteriosus (18.42%) and atrial septal defect (11.05%). Most children (63.4%) were not from the metropolitan area. The percutaneous interventions represented only 27.84% of the catheterization procedures and 14,85% of all heart treatments. Approximately 60% of the pediatric surgeries occurred in children who were not previously registered due to urgency cases. Most of the children waiting for a cardiac procedure were not from the metropolitan area and had malformations potentially treatable by catheterization. It is necessary to increase the capacity of the single referral center in the state of Pará, as well as decentralize the high-complexity cardiological care in the metropolitan region

Waiting for Cardiac Procedure in Congenital Heart Disease: Portrait of an a Hospital in the Amazonian Region / Fila de Espera para Tratamento de Pacientes com Cardiopatia Congênita: Retrato de um Centro de Referência Amazônico

Congenital heart disease is an important cause of morbidity and mortality in childhood, and in 50% of cases, surgery is required in the first year of life. A high deficit of surgical procedures is estimated in Northern Brazil. Objective: To analyze the waiting time for elective surgical treatment and/ or intervention in children with congenital heart disease in a Cardiology referral center, and to make considerations about heart diseases and forms of treatment in that institution. Methods: A cross-sectional study of all patients aged less than 14 years, with a diagnosis of congenital heart disease that were waiting for elective surgical or percutaneous cardiac treatment. Results: Among the 407 children with congenital heart defects, the most prevalent age group was > 2 to 6 years (34.0%). The average waiting time was 23.1 ± 18.3 months, with a median of 19. The most frequent heart disease was ventricular septal defect (28.98%), patent ductus arteriosus (18.42%) and atrial septal defect (11.05%). Most children (63.4%) were not from the metropolitan area. The percutaneous interventions represented only 27.84% of the catheterization procedures and 14,85% of all heart treatments. Approximately 60% of the pediatric surgeries occurred in children who were not previously registered due to urgency cases. Conclusion: Most of the children waiting for a cardiac procedure were not from the metropolitan area and had malformations potentially treatable by catheterization. It is necessary to increase the capacity of the single referral center in the state of Pará, as well as decentralize the high-complexity cardiological care in the metropolitan region

As cardiopatias congênitas são importantes causas de morbimortalidade infantil e, em cerca de 50% dos casos, é necessária a intervenção cirúrgica no primeiro ano de vida. Estima-se alto défice de procedimentos na Região Norte do Brasil. Objetivo: Analisar o tempo de espera para realização de tratamento eletivo cirúrgico e/ou intervencionista de crianças portadoras de cardiopatias congênitas em um centro de referência cardiológico, e fazer considerações sobre as cardiopatias e suas formas de tratamento na referida instituição. Método: Estudo analítico, de caráter transversal do período de janeiro de 2012 a outubro de 2014, de pacientes com idade igual ou inferior a 14 anos diagnosticados com cardiopatias congênitas que estavam na fila de tratamento cardíaco eletivo cirúrgico ou percutâneo. Resultados: Das 407 crianças que aguardavam por tratamento, a faixa etária mais prevalente foi a de > 2 a 6 anos (34,0%). O tempo médio de espera, em meses, foi 23,1 ± 18,3, com mediana de 19. As cardiopatias mais frequentes foram comunicação interventricular (28,98%), persistência do canal arterial (18,42%) e comunicação interatrial (11,05%). A maioria das crianças (63,4%) não pertencia à região metropolitana. As intervenções percutâneas representaram somente 27,84% do total de cateterismos e 14,85% de todos os tratamentos cardíacos. Cerca de 60% do volume de cirurgias pediátricas ocorreu em crianças sem cadastro prévio no sistema, devido ao caráter de urgência. Conclusão: Grande parte das crianças que aguardam por procedimento cardíaco é procedente de fora da região metropolitana e tem malformações potencialmente tratáveis por cateterismo. É necessário aumentar a capacidade operacional do único centro de referência público do Estado, além de descentralizar o atendimento em alta complexidade cardiológica da região metropolitana