Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome.

Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling. Methods: Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection. Results: Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Discussion: Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.

Undiagnosed sleep disorder breathing as a risk factor for critical COVID-19 and pulmonary consequences at the midterm follow-up.

INTRODUCTION: Patients with severe COVID-19 develops an acute respiratory distress syndrome (ARDS), requiring admission to the intensive care unit. COVID-19 also reports an increased prevalence of comorbidities, similar to patients with Sleep disorder breathing (SDB). OBJECTIVES: To evaluate the association between undiagnosed SDB and the risk of ARDS and pulmonary abnormalities in a cohort of patients' survivors of COVID-19 between 3 and 6 months after diagnosis. METHODS: Prospective cohort study of patients who developed ARDS during hospitalization due to COVID-19 compared with a control group of patients who had COVID-19 with mild to moderate symptoms. All patients were evaluated between the 12th and 24th week after SARS-CoV-2 infection. The evaluation includes persistent symptoms, lung diffusing capacity of carbon monoxide (DLCO), chest CT scan and home sleep apnea test. SDB was diagnosed by the respiratory disturbance index ≥5 ev/h. The association between SDB and ARDS, the hazards of lung impairment and the hazard ratios (HR) were analyzed. RESULTS: A total of 60 patients were included (ARDS: 34 patients, Control: 26 patients). The mean follow-up was 16 weeks (range 12-24). ARDS reported a high prevalence of SDB (79% vs. 38% in control group). A total of 35% reported DLCO impairment, and 67.6% abnormal chest CT. SDB was independently associated to ARDS, OR 6.72 (CI, 1.56-28.93), p < 0.01, and abnormal Chest CT, HR 17.2 (CI, 1.68-177.4, p = 0.01). Besides, ARDS, days in mechanical ventilation, male gender were also associated with an increased risk of abnormal chest CT. CONCLUSION: Undiagnosed SDB is prevalent and independently associated with ARDS. In addition, undiagnosed SDB increased the hazard of abnormal Chest CT in the midterm. STUDY REGISTER: ISRCTN16865246.

[Association between FTO gene rs9939609 and adiposity markers in Chilean children]. / Asociación entre el polimorfismo rs9939609 del gen FTO y marcadores de adiposidad en población infantil chilena.

INTRODUCTION: Obesity is considered a chronic inflammatory disease with an important genetic component. Although several studies have reported an association between the FTO (fat-mass associated gene) and adiposity in children, there is limited evidence in the Chilean population. OBJECTIVE: To deter mine the association between the polymorphism rs9939609 of the FTO gene and markers of adipo sity in Chilean children. PATIENTS AND METHOD: Cross-sectional study which included 361 children aged between 6 and 11 years (50% were girls). Between March and June 2008, clinical data and blood sample collection was carried out. The rs9939609 single-nucleotide polymorphism (SNP) of the FTO gene, was determined using the genomic DNA extracted from leukocytes, using the QIAamp DNA Blood Mini Kit (Qiagen GmbH, Hilden, Germany).The adiposity markers included were body mass index (BMI), waist circumference (WC), body fat, and WC/H index; which were later compared adjusted by sex, age, and Tanner stage. Linear regression analyses were conducted to detect the association between the polymorphism and obesity markers. RESULTS: After adjusting the models by age, sex, and Tanner stage, we found a significant association between the polymorphism and markers of adiposity. For each extra copy of the risk allele, we found an increase of 2.47 kg body weight (95% CI: 1.39-3.55); 1.06 kg/m2 BMI (95% CI: 0.56-1.54); 2.55 cm WC, (95% CI: 1.26-3.85); and 1.98% body fat (95% CI: 0.78-3.19). When converting adiposity markers to z-score, we found that WC/height index shows the strongest association with the risk allele FTO. CONCLUSION: This study supports the association between the rs9939609 SNP of the FTO gene and overall and central adiposity markers in Chilean children.

Asociación entre el polimorfismo rs9939609 del gen FTO y marcadores de adiposidad en población infantil chilena / Association between FTO gene rs9939609 and adiposity markers in Chilean children

Resumen: Introducción: La obesidad es una enfermedad inflamatoria donde la genética determina cierto nivel de riesgo. Aun cuando existen estudios que reportan asociación entre polimorfismos de FTO (fat-mass associated gene) y adiposidad, existe limitada evidencia en población infantil chilena. Objetivo: determinar la asociación entre el polimorfismo rs9939609 del FTO y marcadores de adiposidad en población in fantil chilena. Pacientes y Método: Estudio de corte transversal incluyó 361 participantes (de 6 a 11 años; 50% niñas). Los datos clínicos y la recolección de muestras de sangre se realizaron entre marzo y junio de 2008. El polimorfismo SNP (rs9939609), del gen FTO, se determinó utilizando ADN genómico extraído de leucocitos, utilizando el Mini Kit QIAamp DNA Blood (Qiagen GmbH, Hilden, Alemania). Los marcadores de adiposidad estudiados fueron, índice de masa corporal (IMC), masa grasa, perímetro de cintura (PC) y razón cintura/talla, y se compararon ajustados por sexo, edad y estadio de Tanner. La asociación entre el polimorfismo estudiado y los marcadores de obesidad se realizó mediante análisis de regresión lineal. Resultados: Al ajustar los marcadores por sexo, edad y estadío de Tanner se observó una asociación significativa entre el polimorfismo e indicadores de adi posidad. Por cada copia extra del alelo de riesgo se encontró un aumento de 2,47 kg de peso corporal, (IC 95%: 1,39-3,55); 1,06 kg/m2 de IMC, (IC 95%: 0,56-1,54); 2,55 cm de PC, (IC 95%: 1,26-3,85) y 1,98% de masa grasa, (IC 95%: 0,78-3,19). Al convertir los marcadores de adiposidad a z-score, la razón perímetro de cintura/talla arrojó la mayor asociación con el alelo de riesgo de FTO. Conclu sión: Este estudio indica asociación entre el polimorfismo rs9939609 del gen FTO con marcadores de adiposidad general y central en población infantil en Chile.

Abstract: Introduction: Obesity is considered a chronic inflammatory disease with an important genetic component. Although several studies have reported an association between the FTO (fat-mass associated gene) and adiposity in children, there is limited evidence in the Chilean population. Objective: To deter mine the association between the polymorphism rs9939609 of the FTO gene and markers of adipo sity in Chilean children. Patients and Method: Cross-sectional study which included 361 children aged between 6 and 11 years (50% were girls). Between March and June 2008, clinical data and blood sample collection was carried out. The rs9939609 single-nucleotide polymorphism (SNP) of the FTO gene, was determined using the genomic DNA extracted from leukocytes, using the QIAamp DNA Blood Mini Kit (Qiagen GmbH, Hilden, Germany).The adiposity markers included were body mass index (BMI), waist circumference (WC), body fat, and WC/H index; which were later compared adjusted by sex, age, and Tanner stage. Linear regression analyses were conducted to detect the association between the polymorphism and obesity markers. Results: After adjusting the models by age, sex, and Tanner stage, we found a significant association between the polymorphism and markers of adiposity. For each extra copy of the risk allele, we found an increase of 2.47 kg body weight (95% CI: 1.39-3.55); 1.06 kg/m2 BMI (95% CI: 0.56-1.54); 2.55 cm WC, (95% CI: 1.26-3.85); and 1.98% body fat (95% CI: 0.78-3.19). When converting adiposity markers to z-score, we found that WC/height index shows the strongest association with the risk allele FTO. Conclusion: This study supports the association between the rs9939609 SNP of the FTO gene and overall and central adiposity markers in Chilean children.

Efecto del estado nutricional neonatal en la asociación entre polimorfismo rs9939609 del gen FTO y obesidad en niños chilenos de origen amerindio / Effects of neonatal undernutrition on the association of obesity with rs9939609 polymorphism of FTO gene among Amerindian children

The presence of A allele in FTO gene is associated with a higher risk of obesity. Aim: to investigate the effect of neonatal nutritional status on the association between FTO gene rs9939609 variant and obesity in a cohort of Chilean children with Amerindian ancestry. Material and Methods: using birth registries, the neonatal ponderal index of 238 obese and 136 normal weight children was calculated. Nutritional status of participants was determined using cutoff points proposed by the Center for Disease Control. FTO polymorphism was measured by real time polymerase chain reaction. Results: the presence of FTO A allele was associated with a higher risk of obesity (odds ratio (OR) 1.87 95 percent confidence intervals (CI) 1.14-3.06, p < 0.01). The effect of this allele was only significant among males. The risk of obesity associated with A allele presence was non-significantly higher among males with a neonatal ponderal index below percentile 10, as compared with their counterparts with a neonatal ponderal index above this value (OR 5.65 95 percent CI 0.87-60.4). A logistic regression analyzing the presence of A allele as a risk factor for obesity using neonatal nutritional status and gender as control variables, did not substantially change the results. Conclusions: there is a non-significant effect of neonatal undernutrition on the risk of obesity conferred by the presence of A allele of FTO gene...

Asociación entre polimorfismos del gen de adiponectina y estado nutricional en escolares de la comuna de Hualpén / Association between adiponectin gene polymorphisms and obesity in school age children from Hualpén, Chile

Background: Several genetic polymorphisms of adiponectin have been associated to metabolic diseases as obesity and co-morbidities. Aim: To investigate if there are associations between +45TG, +276GT, -11,377CG y -11,391GA adiponectin SNPs (single nucleotide polymorphism) with obesity in a Chilean children population. Material and Methods: A case-control study was performed in 241 obese and 126 normal weight children (7-11 years old) from the urban community of Hualpén, Biobío region. Children were classified as normal or obese, according to age and gender-specificpercentiles defined by Centerfor Disease Control and Prevention (CDC). The analysis of serum markers was carried out using commercial kits. Adiponectin polymorphisms were determined through a High Resolution Melting (HRM)-enabled real time PCR and by DNA fragment sequencing. Results: The observed allelic frequencies of the studied SNPs were over 11%. The 11,377CG polymorphism was associated with a high risk of obesity, calculated by the additive inheritance model (odds ratio = 1.389, 95% confidence interval: 1.001-1.929,p = 0.049). Conclusions: Obese school children of the Biobío Region, have an increased risk of carrying the susceptibility allele polymorphism 11377CG of adiponectin gene.

[Association between adiponectin gene polymorphisms and obesity in school age children from Hualpén, Chile]. / Asociación entre polimorfismos del gen de adiponectina y estado nutricional en escolares de la comuna de Hualpén.

BACKGROUND: Several genetic polymorphisms of adiponectin have been associated to metabolic diseases as obesity and co-morbidities. AIM: To investigate if there are associations between +45TG, +276GT, -11,377CG y -11,391GA adiponectin SNPs (single nucleotide polymorphism) with obesity in a Chilean children population. MATERIAL AND METHODS: A case-control study was performed in 241 obese and 126 normal weight children (7-11 years old) from the urban community of Hualpén, Biobío region. Children were classified as normal or obese, according to age and gender-specificpercentiles defined by Centerfor Disease Control and Prevention (CDC). The analysis of serum markers was carried out using commercial kits. Adiponectin polymorphisms were determined through a High Resolution Melting (HRM)-enabled real time PCR and by DNA fragment sequencing. RESULTS: The observed allelic frequencies of the studied SNPs were over 11%. The 11,377CG polymorphism was associated with a high risk of obesity, calculated by the additive inheritance model (odds ratio = 1.389, 95% confidence interval: 1.001-1.929,p = 0.049). CONCLUSIONS: Obese school children of the Biobío Region, have an increased risk of carrying the susceptibility allele polymorphism 11377CG of adiponectin gene.

FTO gene is related to obesity in Chilean Amerindian children and impairs HOMA-IR in prepubertal girls.

OBJECTIVE: The objective of this study was to investigate the allelic frequency of the fat mass and obesity-associated (FTO) gene (rs9939609) and its influences on obesity and metabolic risk biomarkers in a cohort of normal weight and obese Chilean children determining its ethnicity. METHODS: A total of 136 normal weight children and 238 obese children (between 6 and 11 yr old) from an urban setting were recruited for this case-control study. The children were classified as normal weight [body mass index (BMI) ≥ 5th and < 85th percentiles] or obese (BMI >95th percentile), according to the international age- and gender-specific percentiles defined by the Center for Disease Control and Prevention. The analysis of serum markers was carried out using commercial kits. The FTO polymorphism was determined through a high-resolution melting enabled real time polymerase chain reaction. Ethnicity was determined by analyzing mitochondrial DNA by the restriction fragment length polymorphism method. RESULTS: As much as 85% of the cohort was Amerindian. The minor A allele of rs9939609 was associated with obesity (odds ratio (OR): 1.422 [95% confidence interval (CI) 1.068-1.868] p = 0.015), calculated using an additive model. In sex-stratified analysis we found that the risk variant (A) of rs9939609 was associated with a higher homeostasis model of assessment for insulin (HOMA-IR) in prepubertal obese girls. In male carriers of the A allele, HOMA-IR showed no further deterioration than that already associated with obesity. CONCLUSIONS: In summary, we confirm the association of the FTO gene single-nucleotide polymorphism rs9939609 with obesity in Chilean Amerindian children. Furthermore we show an association between the risk allele (A) and insulin resistance-related markers in prepubertal obese girls.