Novel genes and sex differences in COVID-19 severity

[EN] 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.S

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Prediction models of health-related quality of life in different neck pain conditions: a cross-sectional study

Hector Beltran-Alacreu,1,2 Ibai L&oacute;pez-de-Uralde-Villanueva,1,2 C&eacute;sar Calvo-Lobo,3 Roy La Touche,1,2,4 Roberto Cano-de-la-Cuerda,5 Alfonso Gil-Mart&iacute;nez,1,2,4 David Fern&aacute;ndez-Ayuso,6 Josu&eacute; Fern&aacute;ndez-Carnero2,4,5 1Departamento de Fisioterapia, Centro Superior de Estudios Universitarios La Salle, Universidad Aut&oacute;noma de Madrid, Spain; 2Motion in Brains Research Group, Institute of Neuroscience and Movement Sciences (INCIMOV), Centro Superior de Estudios Universitarios La Salle, Universidad Auton&oacute;ma de Madrid, Spain; 3Nursing and Physical Therapy Department, Institute of Biomedicine (IBIOMED), Faculty of Health Sciences, Universidad de Le&oacute;n, Ponferrada, Le&oacute;n, Spain; 4Hospital La Paz Institute for Health Research, IdiPAZ, Madrid, Spain; 5Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, Alcorc&oacute;n, Madrid, Spain; 6&ldquo;San Juan de Dios&rdquo; School of Nursing and Physiotherapy, Pontifica de Comillas University, Madrid, Spain Purpose: The main aim of the study was to predict the health-related quality of life (HRQoL) based on physical, functional, and psychological measures in patients with different types of neck pain (NP). Materials and methods: This cross-sectional study included 202 patients from a primary health center and the physiotherapy outpatient department of a hospital. Patients were divided into four groups according to their NP characteristics: chronic (CNP), acute whiplash (WHIP), chronic NP associated with temporomandibular dysfunction (NP-TMD), or chronic NP associated with chronic primary headache (NP-PH). The following measures were performed: Short Form-12 Health Survey (SF-12), Neck Disability Index (NDI), visual analog scale (VAS), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BECK), and cervical range of movement (CROM). Results: The regression models based on the SF-12 total HRQoL for CNP and NP-TMD groups showed that only NDI was a significant predictor of the worst HRQoL (48.9% and 48.4% of the variance, respectively). In the WHIP group, the regression model showed that BECK was the only significant predictor variable for the worst HRQoL (31.7% of the variance). Finally, in the NP-PH group, the regression showed that the BECK, STAI, and VAS model predicted the worst HRQoL (75.1% of the variance). Conclusion: Chronic nonspecific NP and chronic NP associated with temporomandibular dysfunction were the main predictors of neck disability. In addition, depression, anxiety, and pain were the main predictors of WHIP or primary headache associated with CNP. Keywords: quality of life, neck pain, disability, depression, anxiet

Home parenteral nutrition in Spain 2011 and 2012; a report of the home and ambulatory artificial nutrition group nadya

OBJETIVE: To report the data of the Home Parenteral Nutrition (HPN) registry of the NADYA-SENPE working group for the years 2011 and 2012. METHODOLOGY: We compiled the data from the on-line registry introduced by reviewers of NADYA group responsible for monitoring of NPD introduced by since January 1, 2011 to december 31, 2012. Included fields were: age, sex, diagnosis and reason for HPN, access path, complications, beginning and end dates, complementary oral or enteral nutrition, activity level, autonomy degree, product and fungible material supply, withdrawal reason and intestinal transplant indication. RESULTS: Year 2010: 184 patients from 29 hospitals , representing a rate of 3.98 patients/million inhabitants/ year 2011, with 186 episodes were recorded NPD . During 2012, 203 patients from 29 hospitals , representing a rate of 4.39 patients/million inhabitants/year 2012 , a total of 211 episodes were recorded NPD . CONCLUSIONS: We observe an increase in registered patients with respect to previous years.Neoplasia remains as the main pathology since 2003. Although NADYA is consolidated registry and has been indispensable source of information relevant to the understanding of the progress of Home Artificial Nutrition in our country, there is ample room for improvement. Especially that refers to the registration of pediatric patients and the registration of complications.YesObjetivo: Comunicar los datos del registro de Nutrición Parenteral Domiciliaria (NPD) del grupo de trabajo NADYA-SENPE de los años 2011 y 2012. Material y métodos: Recopilación de los datos del registro “on-line” introducidos por los colaboradores del grupo NADYA responsables del seguimiento de la NPD desde el 1 de enero de 2011 al 31 de diciembre de 2012 dividido por años naturales. Resultados: Año 2010: Se registraron 184 pacientes, procedentes de 29 hospitales, lo que representa una tasa de 3,98 pacientes/millón habitantes/año 2011, con 186 episodios de NPD. Durante el año 2012 se registraron 203 pacientes, procedentes de 29 hospitales, lo que representa una tasa de 4,39 pacientes/millón habitantes/año 2012, con un total de 211 episodios de NPD. Conclusiones: Se observa un aumento progresivo de los pacientes registrados respecto a años anteriores. El principal grupo patológico sigue siendo oncológico ocupando el primer lugar desde 2003. Aunque el registro NADYA es un registro consolidado y ha sido y es fuente imprescindible de información relevante para el conocimiento de los avances de la Nutrición Artificial Domiciliaria en nuestro país, queda un amplio margen para la mejora. En especial lo que hace referencia al registro de pacientes pediátricos y al registro de las complicaciones