Probiotics as a Coadjuvant Factor in Active or Quiescent Inflammatory Bowel Disease of Adults—A Meta-Analytical Study

(1) Background: Inflammatory bowel diseases are pathologies of unknown etiology and auto-immune pathogenia. The use of probiotics is studied in order to increase the arsenal of treatments. The aim was to assess the efficacy of the probiotics in these diseases in the active or quiescent phases; (2) Methods: A systematic review with meta-analysis was performed by an exhaustive bibliographic search in Medline, Cinahl, Embase, Scopus, Web of Science, and Cochrane Library. The inclusion criteria were studies of more than 10 years, English/Spanish, clinical trials, and involving human beings. Relative risk was used to compare efficacy, which was meta-analyzed using a fixed effects model. Heterogeneity was evaluated with the Higgins I2 test; (3) Results: Nineteen studies were included in the systematic review and 17 in the meta-analysis, with a total of 1537 patients (nexperimental group = 762; nplacebo group = 775). There are significant remission differences in ulcerative colitis (relative risk (RR) = 0.81; 95% CI = 0.72–0.91; I2 = 32%; p = 0.16). However, no significant differences were found in the use of probiotics for the prevention of ulcerative colitis, and for the remission of Crohn’s disease; (4) Conclusions: There are data showing an additional beneficial effect of probiotics on active ulcerative colitis. More and better studies are needed which assess its possible therapeutic efficacy for quiescent ulcerative colitis and for Crohn’s disease

Control of Molecular weight and polydispersity in polyethylene/needle-like shaped clay nanocomposites obtained by in situ polymerization with metallocene catalysts

Producción CientíficaIn an effort to understand the influence of the shape and area of the nanoclay type used in the in situ polymerization process, two different types of clays (fibrillar and laminar) were employed to obtain nanocomposites. The preliminary results demonstrated that a needlelike shaped clay promotes higher molar mass and better mechanical properties compared with laminar clay. The ultra-high molecular weight of sepiolite/nanocomposites introduces significant problems with processability. Therefore, a new method of polymerization was designed to include two significant changes. The first change was related to the use of a non-isothermal temperature profile and the second to the addition of an additional amount of non-anchored co-catalyst leading to materials with higher fluidity.Ministerio de Economía y Competitivida

Long-term follow-up of certolizumab pegol in uveitis due to immune-mediated inflammatory diseases : multicentre study of 80 patients

Objectives To evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID). Methods Multicentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year. Results We studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet's disease (n=10), psoriatic arthritis (n=8), Crohn's disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1), Conclusions CZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

Transferencia de investigaciones virológicas a sectores educativos y generales de la comunidad

La educación es la única y verdadera herramienta válida, por excelencia, para lograr cambios positivos en la historia, en la política, en la salud o en cualquiera otro aspecto importante de la vida de los hombres. Entonces, deberíamos insistir en mejorar la calidad educativa de los ciudadanos y alumnos de todos los niveles, mejorando necesariamente la actualización de los saberes de los funcionarios, profesionales y docentes para que se inscriba en el discurso cotidiano. El desconocer, no prepararse, nos lleva a crisis sociales que inevitablemente incrementan flagelos como la pobreza, la pérdida de biodiversidad, las guerras, las epidemias, entre otros. Así, desde donde se produce y construye el conocimiento científico, la Universidad Nacional de Córdoba, Facultad de Ciencias Médicas y específicamente el Instituto de Virología "Dr. José María Vanella" también se promueve el objetivo de extensión comunitaria, brindando este proyecto a docentes, alumnos y comunidad en general de la provincia de Córdoba como servicio educativo y actualización. Las temáticas son variadas, los talleres convocan a la Divulgación científica y tecnológica de infecciones virales de importancia sanitaria su conocimiento, prevención y difusión, no solo para el sector educativo sino también para la comunidad en general. Las actividades son talleres, conferencias, laboratorios, jornadas de un día hasta dos semanas. Las metodologías aplicadas son charlas dialogadas, vídeos, dinámica de grupos, Hay evaluaciones de seguimiento a través de comentarios, relatos, encuestas. Todas las actividades de extensión del InViV cuentan con la aprobación de la Facultad Ciencias Médicas a través de las Res. Decanales anuales.Fil: Balangero, Marcos. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Gil, Pedro Ignacio: Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Gil, Pedro Ignacio: Universidad Nacional de Córdoba. Secretaría de Ciencia y Tecnología; ArgentinaFil: Frutos: María Cecilia: Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Frutos: María Cecilia: Universidad Nacional de Córdoba. Secretaría de Ciencia y Tecnología; ArgentinaFil: Díaz, Luis Adrián. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Ré, Viviana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Farias, Adrián Alejandro. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Spinsanti, Lorena. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Venezuela, Raúl Fernando. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Kiguen, Ana Ximena. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Konigheim, Brenda. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Pisano, María Belén. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil:Masachessi, Gisela. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Barril, Patricia Angélica. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Varella"; Argentina.Fil: Barril, Patricia Angelica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Estudios en Comunicación, Expresión y Tecnologías; Argentina.Fil: Castro, Gonzalo. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Batallán, Pedro Gonzalo. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Batallán, Pedro Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Estudios en Comunicación, Expresión y Tecnologías; Argentina.Fil: Quaglia, Agustín.Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Tauro, Laura Beatriz. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Tauro, Laura Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Estudios en Comunicación, Expresión y Tecnologías; Argentina.Fil: Flores, Fernando Sebastián. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Flores, Fernando Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Estudios en Comunicación, Expresión y Tecnologías; Argentina.Fil: Beranek, Mauricio. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Beranek, Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Estudios en Comunicación, Expresión y Tecnologías; Argentina.Fil: Maturano, Eduardo. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Rodríguez, Pamela Elizabeth. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Cámara, Jorge Augusto. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil, Albrieu Llinás, Guillermo. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil, Albrieu Llinás, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Estudios en Comunicación, Expresión y Tecnologías; Argentina.Fil: Adamo, María Pilar. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Ghietto, Lucía María. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Ghietto, Lucía María. Universidad Nacional de Córdoba. Secretaría de Ciencia y Tecnología; ArgentinaFil: Pedranti, Mauro Sebastián. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Giordano, Miguel Oscar. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Martínez, Laura Cecilia.Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Isa, Maria Beatriz. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Ascheri, Stella Maris. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Paredes, Norma Gladys. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Contigiani, Marta Silvia. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Benítez, Marta. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Theiler, Gerardo. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Augello, Marysol. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Fosatti, L. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; ArgentinaFil:Moreno, F. Colegio San Martín; Argentina.Fil:Marín, M. Colegio Nuestra Señora del Sagrado Corazón; Argentina.Fil: Carreras, G. Provincia de Córdoba. Ipem 323 de Villa Angelelli; Argentina.Fil: Navarro, A. Provincia de Córdoba. Ipem 323 de Villa Angelelli; Argentina.Fil: Fuentes, M. Provincia de Córdoba. Ipem 323 de Villa Angelelli; Argentina.Fil: Santiago, T. Provincia de Córdoba. Ipem 323 de Villa Angelelli; Argentina.Fil: Cámara, Alicia. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Paglini, María Gabriela. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Cuffini, Cecilia. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Gallego, Sandra Verónica.Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Aguilar, Javier. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Paván, Jorge. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Fil: Nates, Silvia Viviana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología "Dr. José María Vanella"; Argentina.Enfermedades Infecciosa

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 8

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, volumen 8, de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada de acceso abierto a todas las áreas del conocimiento, que cuenta con el esfuerzo de investigadores de varios países del mundo, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico que consoliden la transformación del conocimiento en diferentes escenarios, tanto organizacionales como universitarios, para el desarrollo de habilidades cognitivas del quehacer diario. La gestión del conocimiento es un camino para consolidar una plataforma en las empresas públicas o privadas, entidades educativas, organizaciones no gubernamentales, ya sea generando políticas para todas las jerarquías o un modelo de gestión para la administración, donde es fundamental articular el conocimiento, los trabajadores, directivos, el espacio de trabajo, hacia la creación de ambientes propicios para el desarrollo integral de las instituciones

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 17

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 17 de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada, de acceso abierto a todas las áreas del conocimiento, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico. Con esta colección, se aspira contribuir con el cultivo, la comprensión, la recopilación y la apropiación social del conocimiento en cuanto a patrimonio intangible de la humanidad, con el propósito de hacer aportes con la transformación de las relaciones socioculturales que sustentan la construcción social de los saberes y su reconocimiento como bien público

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

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 GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 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 (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic ∼0.9-Mb inversion polymorphism 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, 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.Andre Franke and David Ellinghaus were supported by a grant from the German Federal Ministry of Education and Research (01KI20197), Andre Franke, David Ellinghaus and Frauke Degenhardt were supported by the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). David Ellinghaus 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). David Ellinghaus, Karina Banasik and Søren Brunak acknowledge the Novo Nordisk Foundation (grant NNF14CC0001 and NNF17OC0027594). Tobias L. Lenz, Ana Teles and Onur Özer were funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project numbers 279645989; 433116033; 437857095. Mareike Wendorff and Hesham ElAbd are supported by the German Research Foundation (DFG) through the Research Training Group 1743, "Genes, Environment and Inflammation". This project was supported by a Covid-19 grant from the German Federal Ministry of Education and Research (BMBF; ID: 01KI20197). Luca Valenti received funding from: Ricerca Finalizzata Ministero della Salute RF2016-02364358, 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). Andrea Biondi was supported by the grant from Fondazione Cariplo to Fondazione Tettamanti: "Biobanking of Covid-19 patient samples to support national and international research (Covid-Bank). This research was partly funded by a 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. IGTP is part of the CERCA Program / Generalitat de Catalunya. GCAT is supported by Acción de Dinamización del ISCIIIMINECO 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). Marta Marquié received research funding from ant PI19/00335 Acción Estratégica en Salud, integrated in the Spanish National RDI Plan and financed by ISCIIISubdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa").Beatriz Cortes is supported by national grants PI18/01512. Xavier Farre is supported by VEIS project (001-P-001647) (cofunded by European Regional Development Fund (ERDF), “A way to build Europe”). Additional data included in this study was obtained in part by the COVICAT Study Group (Cohort Covid de Catalunya) supported by IsGlobal and IGTP, EIT COVID-19 Rapid Response activity 73A and SR20-01024 La Caixa Foundation. Antonio Julià and Sara Marsal were supported by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36). Antonio Julià was also supported the by national grant PI17/00019 from the Acción Estratégica en Salud (ISCIII) and the FEDER. The Basque Biobank is a hospitalrelated 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. Mario Cáceres 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). Manuel Romero Gómez, Javier Ampuero Herrojo, Rocío Gallego Durán and Douglas Maya Miles 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". Jan Cato Holter reports grants from Research Council of Norway grant no 312780 during the conduct of the study. Dr. Solligård: 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). Philipp Koehler has received non-financial scientific grants from Miltenyi Biotec GmbH, 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).Oliver A. Cornely 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. Genotyping was performed by the Genotyping laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki. This work was supported by grants of the Rolf M. Schwiete Stiftung, the Saarland University, BMBF and The States of Saarland and Lower Saxony. Kerstin U. Ludwig 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. Frank Hanses was supported by the Bavarian State Ministry for Science and Arts. Part of the genotyping was supported by a grant to Alfredo Ramirez 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 Alfredo Ramirez. Philip Rosenstiel is supported by the DFG (CCGA Sequencing Centre and DFG ExC2167 PMI and by SH state funds for COVID19 research). Florian Tran is supported by the Clinician Scientist Program of the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). Christoph Lange and Jan Heyckendorf are supported by the German Center for Infection Research (DZIF). Thorsen Brenner, Marc M Berger, Oliver Witzke und Anke Hinney are supported by the Stiftung Universitätsmedizin Essen. Marialbert Acosta-Herrera was supported by Juan de la Cierva Incorporacion program, grant IJC2018-035131-I funded by MCIN/AEI/10.13039/501100011033. Eva C Schulte is supported by the Deutsche Forschungsgemeinschaft (DFG; SCHU 2419/2-1).N