Novel genes and sex differences in COVID-19 severity.

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

Beneficial effects of liraglutide on adipocytokines, insulin sensitivity parameters and cardiovascular risk biomarkers in patients with Type 2 diabetes: a prospective study.

AIMS: To evaluate the effects of liraglutide after 14 weeks of treatment on serum adipokines, insulin resistance index and cardiovascular risk biomarkers in overweight or obese T2DM patients unable to achieve glycemic control with metformin alone or in association with a sulfonylurea in daily clinical practice. METHODS: Prospective study in 59 consecutive overweight or obese (BMI≥25kg/m(2)) T2DM patients unable to achieve glycemic control (HbA1c>7%, 53mmol/mol) with metformin alone or in association with sulfonylurea that require initiation of liraglutide in progressive dose increase up to 1.8mg/day subcutaneously. Weight, body composition, blood pressure, glucose, HbA1c, C-peptide, insulin, plasma lipids, adipokines (leptin, adiponectin, resistin and visfatin) as well as cardiovascular biomarkers (IL-6 and TNF-a) levels were measured fasting at baseline and 14 weeks after liraglutide initiation. RESULTS: 14 weeks of liraglutide treatment significantly reduced HbA1c, BMI and total body fat mass by 0.9%, 1.4kg/m(2) and 0.5% respectively. Statistically significant lower insulin resistance and higher insulin secretion was found by HOMA-IR 8.4 (1.6) vs 4.6 (0.9)molmIU/L(2) and HOMA-B 48.2 (9.0) vs 87.6 (16.3)µIU/mmol. Statistically significantly higher levels of visfatin 6.3 (2.1) vs 6.8 (2.1)ng/ml and resistin 3.6 (2.0) vs 4.3 (2.3)ng/ml were also observed after treatment. Baseline visfatin was negatively correlated with basal fasting plasma glucose r=-0.360 (p<0.05). CONCLUSIONS: Liraglutide treatment for 14 weeks in daily clinical practice led to reduction of BMI and improvement of glucose control and insulin sensitivity and resistance parameters. Additionally, circulating levels of adipokines and pro-inflammatory factors could play an important role in GLP-1 treatment response.

Valoración del nivel de dependencia en pacientes ancianos tras un ingreso hospitalario / Assessment of the dependency level of elderly patients following hospitalization

Objetivo: valorar la existencia de modificaciones de la dependencia en el anciano después de un ingreso hospitalario en un Servicio de Medicina Interna y analizar su relación con las principales características sociodemográficas de estos pacientes. Material y métodos: estudio observacional descriptivo longitudinal (febrero2010-julio 2010) con medidas mediante el test de Barthel al ingreso y al alta. La muestra se seleccionó mediante muestreo no probabilístico, de series de casos consecutivos. Al ingreso se han recogido las variables edad, sexo, domicilio, centro de salud, fecha de ingreso, número de ingresos en el último año y duración de los mismos, residencia habitual, riesgo social, motivo de ingreso y el primer test de Barthel. Al alta se ha registrado la fecha, el lugar al que vuelve el anciano, el riesgo social, la necesidad o no de entregar informe de alta de Enfermería (por necesitar continuidad en los cuidados) y el segundo test de Barthel. Resultados: se analizaron 318 casos al ingreso, de los cuales se obtuvieron datos al alta en 157 pacientes (49,3%). La mediana de la estancia fue de nueve días con un rango intercuartílico de 5,5-15,0 días. El grupo analizado al alta presentó características similares al grupo inicial, por lo que puede considerarse (..) (AU)

Objective: to assess the existence of dependency changes in the elderly after hospitalization in an Internal Medicine department and to analyzeits relationship with key socio-demographic characteristics of these patients. Material and methods: observational, longitudinal, descriptive study (february 2010-july 2010) with measurements taken using the test of Barthel at admission and at discharge. The sample was selected using non-probability sampling, of consecutive case series. On admission variables included were age, sex, address, health center, date of admission, number of admissions in the last year and their duration, habitual residence, social risk, reason for admission and the first test of Barthel. At discharge the date, the place where elderly patient is returning to, social risk, whether or not to submit a nursing discharge report (for continuity of care purposes) and the second test of Barthel were all recorded. Results: 318 cases were analyzed on admission, of which discharge data were obtained in 157 patients (49,3%). Mean stay was nine days with an interquartile range of 5,5 to 15,0 days. The group analyzed at discharge showed similar characteristics to the original group, and can there forebe considered representative of it. We included 86 women (54,8%) and71 men (45,2%), with an overall mean age of 72,5 ± 17,5 years. The difference between the Barthel test at discharge and the Barthel tests at admission had a mean of 0,9 ± 18,6. There were 42 patients who improved(26,7%), 89 who remained stable (56,7%) and 26 whose scores worsened(16,6%). The multimorbidity of the elderly that causes a high number of hospital admissions is key to the interpretation of this outcome. Conclusions: a significant loss of dependency, and hence of quality of life, cannot be demonstrated in our elderly patients subjected to hospitalization (AU)

Relation of -55CT polymorphism of uncoupling protein 3 gene with fat mass and insulin resistance in morbidly obese patients.

Some studies have pointed to a role of uncoupling protein 3 (UCP3) in the regulation of whole-body energy homoeostasis and regulation of fat distribution. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene on fat mass and insulin resistance in morbidly obese patients. A population of 47 obese subjects (body mass index [BMI] >40 kg/m(2)) was selected randomly in a prospective way. A nutritional evaluation was performed. Dietary intake and exercise were recorded. The mean age was 48.2 +/- 15.4 years; and the BMI was 44.7 +/- 4.7 kg/m(2), with 10 men (21.3%) and 37 women (78.7%). Thirty-two (68.1%) had the genotype -55CC (wild-type group), and 15 patients (31.9%) had -55CT (mutant-type group). In the mutant-type group, insulin (20.6+/-10.8 vs 31.2 +/- 17.4 mIU/L, P < .05), homeostasis model assessment (5.3 +/- 2.7 vs 8.7 6.6, P < .05), weight (114.1 +/- 17.3 vs 122.8+/-19.1 kg, P < .05), BMI (44.1 +/- 4.6 vs 45.7 +/- 6.3 kg/m(2), P < .05), fat mass (56.3 +/- 11.4 vs 61.4 +/- 15.1 kg, P < .05), and waist circumference (124.8 +/- 12.5 vs 128.3 +/- 9.1 cm, P < .05) were higher than those in the wild-type group. Adiponectin levels were higher in wild-type group than mutant-type group (70.3 +/- 26.1 vs 30.5 +/- 32.5 ng/mL, P < .05). In conclusion, mutant-type group of -55CC UCP3 gene patients had higher weight, fat mass, and insulin resistance than wild-type group.