EFECTO DE LA RAZA DEL TORO DE CARNE SOBRE LA CALIDAD ESPERMÁTICA DE SEMEN DESCONGELADO

Objetive: The objective of this work was to assess the effect of bull breed on sperm quality after thawing semen. Design/methodology/approach: 10 plastic straws of 0.5 ml of frozen semen from three different breeds of bull were used, which were purchased from a commercial company. The bull breeds used were Charolais, Brahman and Simbrah. The straws were thawed at 37 ° C for 40 seconds. Immediately afterwards motility, viability and acrosmosomal integrity (NAR) were assessed. Results: The results were for motility 75.0, 87.5 and 85.0%; for viability 74.5, 74.5 and 72.5%; and for NAR 97.1, 96.9 and 96.9% for the Charolais, Brahaman and Simbrah races, respectively. Limitations/implications: The straws used were obtained from a commercial company dedicated to the sale of frozen bovine semen. Findings/conclusions: The three bull breeds showed good sperm quality after thawing, which can be recommended to be used in artificial insemination without any problem.Objetivo: El objetivo de este trabajo fue valorar el efecto de la raza del toro sobre la calidad espermática del semen descongelado. Diseño/metodología/aproximación: Se utilizaron 10 pajillas plásticas de 0.5 ml de semen congelado de tres diferentes razas de toro, las cuales se adquirieron en una empresa comercial. Las razas de toro utilizadas fueron Charolais, Brahman y Simbrah. Las pajillas fueron descongeladas a 37°C durante 40 segundos. Inmediatamente después se valoró motilidad, viabilidad e integridad acrorosomal (NAR). Resultados: Los resultados fueron para motilidad 75.0, 87.5 y 85.0 %; para viabilidad 74.5, 74.5 y 72.5 %; y para NAR 97.1, 96.9 y 96.9% para las razas Charolais, Brahaman y Simbrah, respectivamente. Limitaciones/implicaciones: Las pajillas utilizadas se obtuvieron de una empresa comercial dedicada a la venta de semen congelado de bovino. Hallazgos/conclusiones: Las tres razas de toros mostraron buena calidad espermática después de la descongelación, las cuales pueden ser recomendadas para ser utilizadas en la inseminación artificial sin ningún problema

Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles

Background and Aims We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors. Approach and Results We analyzed serum metabolome from 1154 individuals with biopsy-proven NAFLD, and from four mouse models of NAFLD with impaired VLDL-triglyceride (TG) secretion, and one with normal VLDL-TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL-TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL-TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL-TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL-TG and VLDL-apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6, and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10-year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin-like phospholipase domain-containing protein 3 NAFLD risk allele were lower in subtype A. Conclusions Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.National Institutes of Health (R01DK123763, R01DK119437, HL151328, P30DK52574, P30DK56341, and UL1TR002345); Ministerio de Economía y Competitividad de España (SAF2017-88041-R); Ministerio de Economía y Competitividad de España for the Severo Ochoa Excellence Accreditation (SEV-2016-0644); CIBERehd (Biomedical Research Center in Hepatic and Digestive Diseases) and Netherlands Organization for Applied Scientific Research Program (PMC13 and PMC15); Spanish Carlos III Health Institute (PI15/01132 and PI18/01075); Miguel Servet Program (CON14/00129 and CPII19/00008); Fondo Europeo de Desarrollo Regional, CIBERehd, Department of Industry of the Basque Country (Elkartek: KK-2020/00008); La Caixa Scientific Foundation (HR17-00601); Liver Investigation: Testing Marker Utility in Steatohepatitis consortium funded by the Innovative Medicines Initiative Program of the European Union (777377), which receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA; Newcastle NIHR Biomedical Research Center; Czech Ministry of Health (RVO-VFN64165/2020); Fondo Nacional De Ciencia y Tecnología de Chile (1191145); and the Comisión Nacional de Investigación, Ciencia y Tecnología (AFB170005, CARE Chile UC); Agencia Nacional de Investigación y Desarrollo (ANID ACE 210009); European Union's Horizon 2020 Research and Innovation Program (825510)

Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID‑19

Background. COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. Methods. A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. Results. The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183–12.968], 0.025), viral RNA load (N1) (1.962 [1.244–3.096], 0.004); viral RNA load (N2) (2.229 [1.382–3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). Conclusions. SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.This work was supported by awards from the Canadian Institutes of Health Research, the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative (CIHR OV2 – 170357), Research Nova Scotia (DJK), Atlantic Genome/Genome Canada (DJK), Li-Ka Shing Foundation (DJK), Dalhousie Medical Research Foundation (DJK), the “Subvenciones de concesión directa para proyectos y programas de investigación del virus SARS‐CoV2, causante del COVID‐19”, FONDO–COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (AT) and fnally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la fnanciación de proyectos de investigación en enfermedad COVID-19” (GRS COVID 53/A/20) (CA). DJK is a recipient of the Canada Research Chair in Translational Vaccinology and Infammation. APT was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co-fnanced by the European Development Regional Fund (A Way to Achieve Europe programme). The funding sources did not play any role neither in the design of the study and collection, not in the analysis, in the interpretation of data or in writing the manuscript

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Mar Menor: una laguna singular y sensible. Evaluación científica de su estado.

Este libro recopila las aportaciones que equipos de investigación de la Universidad de Murcia, Universidad Politécnica de Cartagena, Instituto Geológico-Minero de España, Universidad de Alicante, el Instituto Español de Oceanografía y otros organismos hicieron en las Jornadas Científicas del Mar Menor, celebradas en diciembre de 2014.La información recogida en este libro se estructura en dos grandes bloques, uno de Biología y Ecología del Mar Menor (capítulos 1 al 8) y otro de Condiciones fisicoquímicas e impacto de actividades humanas en la laguna (capítulos 9 al 14). El primer bloque resume buena parte de los estudios ecológicos realizados en el Mar Menor, que han servido para mejorar su conocimiento y también para cambiar antiguas asunciones sobre la naturaleza y el funcionamiento de estos ecosistemas lagunares (Capítulo 1). El segundo capítulo muestra que esta laguna alberga en zonas someras de su perímetro hábitats fundamentales para mantener y conservar tanto especies migratorias como residentes, que es necesario conocer para paliar el impacto de las actividades humanas que les afectan. En este sentido la reducción de la carga de nutrientes y contaminantes orgánicos e inorgánicos que fluyen hacia el Mar Menor puede ayudar a preservar la laguna en mejores condiciones, bien sea tratando las escorrentías (plantas de tratamiento, humedales artificiales u otras técnicas) y recuperar este agua para uso agrícola o evitar su descarga en la laguna (Capítulo 3). Estas actuaciones serán clave para la conservación de especies emblemáticas como el caballito de mar (Capítulo 4) y reducir el impacto de las proliferaciones masivas de medusas que se producen en la laguna desde 1993 (Capítulo 5). En este mismo sentido los cambios acaecidos en la laguna han favorecido la incursión de invertebrados marinos alóctonos (Capítulo 6) y han afectado a la respuesta de la dinámica poblacional de las aves acuáticas a distintas escalas (Capítulo 7). Para completar este bloque se ofrece una perspectiva histórica de la importancia que ha tenido la investigación sobre acuicultura realizada en esta laguna, que ha servido de base para su gran desarrollo actual (Capítulo 8). El segundo bloque se inicia con una evaluación del origen y evolución del Mar Menor desde el punto de vista geológico, y evidencia su vulnerabilidad ante el deterioro que puede sufrir la desaparición de la barrera de cierre y/o su colmatación (Capítulo 9). En el Capítulo 10 se describe la relevancia que tiene la interacción de los acuíferos del Campo de Cartagena con la laguna, que se produce no sólo a nivel superficial sino también subterráneo. Esta interacción permite el acceso de nutrientes a la laguna, a pesar de la cierta capacidad de depuración de los humedales que le circundan, y también de metales traza por los aportes de residuos mineros (Capítulo 11). De hecho los metales traza están presentes en los sedimentos de la laguna, y su distribución se ha caracterizado en la columna sedimentaria relacionándola con la granulometría y el contenido de materia orgánica del sedimento (Capítulo 12). Posteriormente se describe la entrada de diversos contaminantes orgánicos, incluyendo pesticidas y fármacos a través de la rambla del Albujón, y su distribución estacional en agua y sedimento de la laguna (Capítulo 13). Este segundo bloque finaliza con el Capítulo 14 en el que se describe la bioacumulación de hidrocarburos aromáticos policíclicos, pesticidas y fármacos en moluscos y peces del Mar Menor, así como los efectos biológicos que la carga contaminante que accede a través de la rambla del Albujón produce en los organismos que allí habitan. El libro concluye con un breve epílogo redactado por los editores de este libro

Mar Menor: una laguna singular y sensible. Evaluación científica de su estado.

Este libro recopila las aportaciones que equipos de investigación de la Universidad de Murcia, Universidad Politécnica de Cartagena, Instituto Geológico-Minero de España, Universidad de Alicante, el Instituto Español de Oceanografía y otros organismos hicieron en las Jornadas Científicas del Mar Menor, celebradas en diciembre de 2014.La información recogida en este libro se estructura en dos grandes bloques, uno de Biología y Ecología del Mar Menor (capítulos 1 al 8) y otro de Condiciones fisicoquímicas e impacto de actividades humanas en la laguna (capítulos 9 al 14). El primer bloque resume buena parte de los estudios ecológicos realizados en el Mar Menor, que han servido para mejorar su conocimiento y también para cambiar antiguas asunciones sobre la naturaleza y el funcionamiento de estos ecosistemas lagunares (Capítulo 1). El segundo capítulo muestra que esta laguna alberga en zonas someras de su perímetro hábitats fundamentales para mantener y conservar tanto especies migratorias como residentes, que es necesario conocer para paliar el impacto de las actividades humanas que les afectan. En este sentido la reducción de la carga de nutrientes y contaminantes orgánicos e inorgánicos que fluyen hacia el Mar Menor puede ayudar a preservar la laguna en mejores condiciones, bien sea tratando las escorrentías (plantas de tratamiento, humedales artificiales u otras técnicas) y recuperar este agua para uso agrícola o evitar su descarga en la laguna (Capítulo 3). Estas actuaciones serán clave para la conservación de especies emblemáticas como el caballito de mar (Capítulo 4) y reducir el impacto de las proliferaciones masivas de medusas que se producen en la laguna desde 1993 (Capítulo 5). En este mismo sentido los cambios acaecidos en la laguna han favorecido la incursión de invertebrados marinos alóctonos (Capítulo 6) y han afectado a la respuesta de la dinámica poblacional de las aves acuáticas a distintas escalas (Capítulo 7). Para completar este bloque se ofrece una perspectiva histórica de la importancia que ha tenido la investigación sobre acuicultura realizada en esta laguna, que ha servido de base para su gran desarrollo actual (Capítulo 8). El segundo bloque se inicia con una evaluación del origen y evolución del Mar Menor desde el punto de vista geológico, y evidencia su vulnerabilidad ante el deterioro que puede sufrir la desaparición de la barrera de cierre y/o su colmatación (Capítulo 9). En el Capítulo 10 se describe la relevancia que tiene la interacción de los acuíferos del Campo de Cartagena con la laguna, que se produce no sólo a nivel superficial sino también subterráneo. Esta interacción permite el acceso de nutrientes a la laguna, a pesar de la cierta capacidad de depuración de los humedales que le circundan, y también de metales traza por los aportes de residuos mineros (Capítulo 11). De hecho los metales traza están presentes en los sedimentos de la laguna, y su distribución se ha caracterizado en la columna sedimentaria relacionándola con la granulometría y el contenido de materia orgánica del sedimento (Capítulo 12). Posteriormente se describe la entrada de diversos contaminantes orgánicos, incluyendo pesticidas y fármacos a través de la rambla del Albujón, y su distribución estacional en agua y sedimento de la laguna (Capítulo 13). Este segundo bloque finaliza con el Capítulo 14 en el que se describe la bioacumulación de hidrocarburos aromáticos policíclicos, pesticidas y fármacos en moluscos y peces del Mar Menor, así como los efectos biológicos que la carga contaminante que accede a través de la rambla del Albujón produce en los organismos que allí habitan. El libro concluye con un breve epílogo redactado por los editores de este libro.Versión del edito

Detailed stratified GWAS analysis for severe COVID-19 in four European populations

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.S.E.H. and C.A.S. partially supported genotyping through a philanthropic donation. A.F. and D.E. were supported by a grant from the German Federal Ministry of Education and COVID-19 grant Research (BMBF; ID:01KI20197); A.F., D.E. and F.D. were supported by the Deutsche Forschungsgemeinschaft Cluster of Excellence ‘Precision Medicine in Chronic Inflammation’ (EXC2167). D.E. was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences funding concept (CompLS grant 031L0165). D.E., K.B. and S.B. acknowledge the Novo Nordisk Foundation (NNF14CC0001 and NNF17OC0027594). T.L.L., A.T. and O.Ö. were funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project numbers 279645989; 433116033; 437857095. M.W. and H.E. are supported by the German Research Foundation (DFG) through the Research Training Group 1743, ‘Genes, Environment and Inflammation’. L.V. received funding from: Ricerca Finalizzata Ministero della Salute (RF-2016-02364358), Italian Ministry of Health ‘CV PREVITAL’—strategie di prevenzione primaria cardiovascolare primaria nella popolazione italiana; The European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- and for the project ‘REVEAL’; Fondazione IRCCS Ca’ Granda ‘Ricerca corrente’, Fondazione Sviluppo Ca’ Granda ‘Liver-BIBLE’ (PR-0391), Fondazione IRCCS Ca’ Granda ‘5permille’ ‘COVID-19 Biobank’ (RC100017A). A.B. was supported by a grant from Fondazione Cariplo to Fondazione Tettamanti: ‘Bio-banking of Covid-19 patient samples to support national and international research (Covid-Bank). This research was partly funded by an MIUR grant to the Department of Medical Sciences, under the program ‘Dipartimenti di Eccellenza 2018–2022’. This study makes use of data generated by the GCAT-Genomes for Life. Cohort study of the Genomes of Catalonia, Fundació IGTP (The Institute for Health Science Research Germans Trias i Pujol) IGTP is part of the CERCA Program/Generalitat de Catalunya. GCAT is supported by Acción de Dinamización del ISCIII-MINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026); the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529). M.M. received research funding from grant PI19/00335 Acción Estratégica en Salud, integrated in the Spanish National RDI Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (European Regional Development Fund (FEDER)-Una manera de hacer Europa’). B.C. is supported by national grants PI18/01512. X.F. is supported by the VEIS project (001-P-001647) (co-funded by the European Regional Development Fund (ERDF), ‘A way to build Europe’). Additional data included in this study were obtained in part by the COVICAT Study Group (Cohort Covid de Catalunya) supported by IsGlobal and IGTP, European Institute of Innovation & Technology (EIT), a body of the European Union, COVID-19 Rapid Response activity 73A and SR20-01024 La Caixa Foundation. A.J. and S.M. were supported by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36). A.J. was also supported by national grant PI17/00019 from the Acción Estratégica en Salud (ISCIII) and the European Regional Development Fund (FEDER). The Basque Biobank, a hospital-related platform that also involves all Osakidetza health centres, the Basque government’s Department of Health and Onkologikoa, is operated by the Basque Foundation for Health Innovation and Research-BIOEF. M.C. received Grants BFU2016-77244-R and PID2019-107836RB-I00 funded by the Agencia Estatal de Investigación (AEI, Spain) and the European Regional Development Fund (FEDER, EU). M.R.G., J.A.H., R.G.D. and D.M.M. are supported by the ‘Spanish Ministry of Economy, Innovation and Competition, the Instituto de Salud Carlos III’ (PI19/01404, PI16/01842, PI19/00589, PI17/00535 and GLD19/00100) and by the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018, COVID-Premed, COVID GWAs). The position held by Itziar de Rojas Salarich is funded by grant FI20/00215, PFIS Contratos Predoctorales de Formación en Investigación en Salud. Enrique Calderón’s team is supported by CIBER of Epidemiology and Public Health (CIBERESP), ‘Instituto de Salud Carlos III’. J.C.H. reports grants from Research Council of Norway grant no 312780 during the conduct of the study. E.S. reports grants from Research Council of Norway grant no. 312769. The BioMaterialBank Nord is supported by the German Center for Lung Research (DZL), Airway Research Center North (ARCN). The BioMaterialBank Nord is member of popgen 2.0 network (P2N). P.K. Bergisch Gladbach, Germany and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany. He is supported by the German Federal Ministry of Education and Research (BMBF). O.A.C. is supported by the German Federal Ministry of Research and Education and is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—CECAD, EXC 2030–390661388. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. This work was supported by grants of the Rolf M. Schwiete Stiftung, the Saarland University, BMBF and The States of Saarland and Lower Saxony. K.U.L. is supported by the German Research Foundation (DFG, LU-1944/3-1). Genotyping for the BoSCO study is funded by the Institute of Human Genetics, University Hospital Bonn. F.H. was supported by the Bavarian State Ministry for Science and Arts. Part of the genotyping was supported by a grant to A.R. from the German Federal Ministry of Education and Research (BMBF, grant: 01ED1619A, European Alzheimer DNA BioBank, EADB) within the context of the EU Joint Programme—Neurodegenerative Disease Research (JPND). Additional funding was derived from the German Research Foundation (DFG) grant: RA 1971/6-1 to A.R. P.R. is supported by the DFG (CCGA Sequencing Centre and DFG ExC2167 PMI and by SH state funds for COVID19 research). F.T. is supported by the Clinician Scientist Program of the Deutsche Forschungsgemeinschaft Cluster of Excellence ‘Precision Medicine in Chronic Inflammation’ (EXC2167). C.L. and J.H. are supported by the German Center for Infection Research (DZIF). T.B., M.M.B., O.W. und A.H. are supported by the Stiftung Universitätsmedizin Essen. M.A.-H. was supported by Juan de la Cierva Incorporacion program, grant IJC2018-035131-I funded by MCIN/AEI/10.13039/501100011033. E.C.S. is supported by the Deutsche Forschungsgemeinschaft (DFG; SCHU 2419/2-1).Peer reviewe