Respiratory infections and tuberculosis Infecciones respiratorias y tuberculosis Infeccions respiratòries i tuberculosi Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55–78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5–19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6–23) days versus 8 (4–15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65–0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU. This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z), the Bill and Melinda Gates Foundation (OPP1209135), Canadian Institutes of Health Research Coronavirus Rapid Research Funding Opportunity OV2170359, grants from Rapid European COVID-19 Emergency Response Research (Horizon 2020 project 101003589), the European Clinical Research Alliance on Infectious Diseases (965313), The Imperial National Institute for Health Research (NIHR) Biomedical Research Centre, and The Cambridge NIHR Biomedical Research Centre; and endorsed by the Irish Critical Care Clinical Trials Group, co-ordinated in Ireland by the Irish Critical Care Clinical Trials Network at University College Dublin and funded by the Health Research Board of Ireland (CTN-2014-12). Data and Material provision was supported by grants from: the NIHR (award CO-CIN-01), the Medical Research Council (grant MC_PC_19059), the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), Wellcome Trust (Turtle, Lance-fellowship 205228/Z/16/Z), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. This work was by Research Council of Norway grant number 312780, and a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner.
descriptionPublicationkeyboard_double_arrow_right Article 2021 Germany, Denmark, Spain, France, Spain, Norway European Centre for Disease Control and Prevention (ECDC)
Authors: Kimberley S. M. Benschop; Jan Albert; Andrés Antón; Cristina Andres; +76 Authors
Kimberley S. M. Benschop; Jan Albert; Andrés Antón; Cristina Andres; Maitane Aranzamendi; Brynja Armannsdottir; Jean-Luc Bailly; Fausto Baldanti; Guðrún Erna Baldvinsdóttir; Stuart Beard; Natasa Berginc; Sindy Böttcher; Soile Blomqvist; L. Bubba; Cristina Calvo; María Cabrerizo; Annalisa Cavallero; Cristina Celma; Ferruccio Ceriotti; Inês Costa; Simon Cottrell; Margarita Del Cuerpo; Jonathan Dean; Jennifer L. Dembinski; Sabine Diedrich; Javier Díez-Domingo; DagnyHaug Dorenberg; Erwin Duizer; Robert Dyrdak; Diana Fanti; Agnes Farkas; Susan Feeney; Jacky Flipse; Cillian De Gascun; Cristina Galli; Irina Georgieva; Laura Gifford; Raquel Guiomar; Mario Hönemann; Niina Ikonen; Marion Jeannoel; Laurence Josset; Kathrin Keeren; F. Xavier López-Labrador; Melanie Maier; James McKenna; Adam Meijer; Beatriz Mengual-Chuliá; Sofie Midgley; Audrey Mirand; Milagrosa Montes; Catherine Moore; Ursula Morley; Jean-Luc Murk; Lubomira Nikolaeva-Glomb; Sanela Numanovic; Massimo Oggioni; Paula Palminha; Elena Pariani; Laura Pellegrinelli; Antonio Piralla; Corinna Pietsch; Luis Pineiro; Nuria Rabella; Petra Rainetova; Sara Colonia Uceda Renteria; María Pilar Romero; Marijke Reynders; Lieuwe Roorda; Carita Savolainen-Kopra; Isabelle Schuffenecker; Aysa Soynova; Caroline Ma Swanink; Tina Uršič; Jaco J. Verweij; Jorgina Vila; Tytti Vuorinen; Peter Simmonds; Thea Kølsen Fischer; Heli Harvala;
Acute flaccid myelitis; Enterovirus D68; Surveillance Mielitis flàcida aguda; Enterovirus D68; Vigilància Mielitis flácida aguda; Enterovirus D68; Vigilancia We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe.
Authors: Frauke Degenhardt; Simonas Juzenas; Jon Lerga-Jaso; Douglas Maya-Miles; +180 Authors
Frauke Degenhardt; Simonas Juzenas; Jon Lerga-Jaso; Douglas Maya-Miles; Florian Uellendahl-Werth; Hesham ElAbd; Malte C. Ruehlemann; Jatin Arora; Onur oezer; Ole Bernt Lenning; Ronny Myhre; Aaron Blandino Ortiz; Adolfo de Salazar; Aleksander Rygh Holten; Alena Mayer; Alessandro Cherubini; Alessandro Protti; Alessio Aghemo; Alessio Gerussi; Alexander Popov; Alfredo Ramirez; Alice Braun; Ana Barreira; Ana Lleo; Ana Teles; Anders Benjamin Kildal; Andrea Biondi; Andreas Glueck; Andreas Lind; Annalisa Cavallero; Anne Ma Dyrhol-Riise; Antonio Julià; Ariadna Rando-Segura; Aurora Solier; Beatriz Cortés; Beatriz Mateos; Beatriz Nafria-Jimenez; Carla Bellinghausen; Carsten Skurk; Christian Herr; Christoph D. Spinner; Christoph Lange; Cinzia Hu; Clara Lehmann; Claudio Cappadona; Covid Aachen Study; Cristina Sancho; Dag Arne Lihaug Hoff; Daniela Galimberti; Daniele Prati; David Haschka; David Pestaña; David Toapanta; Elena Azzolini; Eloisa Urrechaga; Emanuele Pontali; Enric Reverter; Enrique Navas; Erik Solligård; Ernesto Contro; Eunate Arana; Felix Garcia Sanchez; Ferruccio Ceriotti; Francesco Blasi; Francesco Malvestiti; Francisco Mesonero; Francisco Rodriguez-Frias; Frank Hanses; Giacomo Grasselli; Gianni Pezzoli; Giorgio Costantino; Giovanni Albano; Giuseppe Citerio; Giuseppe Lamorte; Holger Neb; Ilaria My; Isabel Hernández; Isabell Pink; Jan Cato Holter; Jan Kristian Damås; Janine Altmueller; Joan Ramon Badia; Joaquín Dopazo; Jonas Bergan; Jordi Barretina; Joern Walter; Juan Delgado; Julia Fazaal; Julia Kraft; Kari Risnes; Karina Banasik; Karl Erik Mueller; Kristian Tonby; Laura Izquierdo-Sanchez; Lauro Sumoy; Leonardo Terranova; Lindokuhle Nkambule; Lise Tuset Gustad; Lucia Garbarino; Luigi Santoro; Luis Téllez; Luisa Roade; Mahnoosh Ostadreza; Maider Intxausti; Manolis Kogevinas; Mar Riveiro-Barciela; Mari Niemi; Maria Grazia Valsecchi; Maria J G T Vehreschild; Maria Manunta; Mariella D'Angiò; Marina Elena Cazzaniga; Marit Mæhle Grimsrud; Marta Marquié; Massimo Castoldi; Mauro D'Amato; Max Augustin; Melissa Tomasi; Mercè Boada; M Seilmaier; Michael Joannidis; Michela Mazzocco; M.A. Rodríguez-Gandía; Natale Imaz Ayo; Natalia Blay; Natalia Chueca; Nicola Montano; Oliver A. Cornely; Oliver Witzke; Orazio Palmieri; Paola Faverio; Paolo Bonfanti; Pedro Castro; Philipp Schommers; Phillip Suwalski; Raúl de Pablo; Ricard Ferrer; Robert Bals; Roberta Gualtierotti; Rosa Nieto; Ruben Morilla; Salvatore Badalamenti; Sandra May; Sara Pigazzini; Sebastian J. Klein; Selina Rolker; Serena Pelusi; Sibylle Wilfling; Silvano Bosari; Stefan Schreiber; Stephan Ripke; Susanne Gjeruldsen Dudman; Thomas Eggermann; Thomas Illig; Thorsten Brenner; Ulf Landmesser; Ulrike Protzer; Valeria Rimoldi; Vegard Skogen; Verena Keitel; Verena Kopfnagel; Vicente Friaza; Wolfgang Poller; Xiaomin Wang; Yascha Khodamoradi; Anna Latiano; Siegfried Goerg; Florian Tran; Heinz Zoller; Bettina Heidecker; Kerstin U. Ludwig; Javier Fernández; Manuel Romero-Gómez; Agustín Albillos; Maria Buti; Luis Bujanda; Johannes R. Hov; Tobias L. Lenz; Rosanna Asselta; Rafael de Cid; Luca Valenti; Tom H. Karlsen; Mario Cáceres; Andre Franke;
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). 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. No
Authors: Jenny Bertholet; Marianne C. Aznar; Cristina Garibaldi; David Thwaites; +13 Authors
Jenny Bertholet; Marianne C. Aznar; Cristina Garibaldi; David Thwaites; Eduard Gershkevitsh; Daniela Thorwarth; Dirk Verellen; Ben J.M. Heijmen; Coen W. Hurkmans; Ludvig Paul Muren; Kathrine Røe Redalen; Frank André Siebert; Marco Schwarz; Wouter van Elmpt; Dietmar Georg; Nuria Jornet; Catharine H. Clark;
Background and purpose The COVID-19 pandemic has imposed changes in radiotherapy (RT) departments worldwide. Medical physicists (MPs) are key healthcare professionals in maintaining safe and effective RT. This study reports on MPs experience during the first pandemic peak and explores the consequences on their work. Methods A 39-question survey on changes in departmental and clinical practice and on the impact for the future was sent to the global MP community. A total of 433 responses were analysed by professional role and by country clustered on the daily infection numbers. Results The impact of COVID-19 was bigger in countries with high daily infection rate. The majority of MPs worked in alternation at home/on-site. Among practice changes, implementation and/or increased use of hypofractionation was the most common (47% of the respondents). Sixteen percent of respondents modified patient-specific quality assurance (QA), 21% reduced machine QA, and 25% moved machine QA to weekends/evenings. The perception of trust in leadership and team unity was reversed between management MPs (towards increased trust and unity) and clinical MPs (towards a decrease). Changes such as home-working and increased use of hypofractionation were welcomed. However, some MPs were concerned about pressure to keep negative changes (e.g. weekend work). Conclusion COVID-19 affected MPs through changes in practice and QA procedures but also in terms of trust in leadership and team unity. Some changes were welcomed but others caused worries for the future. This report forms the basis, from a medical physics perspective, to evaluate long-lasting changes within a multi-disciplinary setting.
descriptionPublicationkeyboard_double_arrow_right Article 2021 France, Poland, Portugal, Denmark, Belgium, Norway, Spain, Norway, France, Switzerland European Respiratory Society (ERS)
Authors: Christian Jung; Bernhard Wernly; Jesper Fjølner; Raphael Romano Bruno; +24 Authors
Christian Jung; Bernhard Wernly; Jesper Fjølner; Raphael Romano Bruno; David M. Dudzinski; Antonio Artigas; Bernardo Bollen Pinto; Joerg C. Schefold; Georg Wolff; Malte Kelm; Michael Beil; Sviri Sigal; Peter Vernon van Heerden; Wojciech Szczeklik; Mirosław Czuczwar; Muhammed Elhadi; Michael Joannidis; Sandra Oeyen; Tilemachos Zafeiridis; Brian Marsh; Finn H. Andersen; Rui Moreno; Maurizio Cecconi; Susannah Leaver; Ariane Boumendil; Dylan W. de Lange; Bertrand Guidet; Hans Flaatten;
More than a year after the onset of the SARS-Cov-2 pandemic, treating patients with COVID-19 remains a challenge. By contrast to the rapid development of effective vaccines against SARS-Cov-2, the development of specific and effective therapeutics against COVID-19 remains largely unresolved. This secondary analysis of the COVIP study shows a higher 30-day-mortality in critically ill elderly COVID-19 patients who received steroids as part of their treatment.
descriptionPublicationkeyboard_double_arrow_right Article 2021 Denmark, Belgium, Switzerland, Netherlands European Respiratory Society (ERS)
Authors: June K. Marthin; Jane S. Lucas; Mieke Boon; Carmen Casaulta; +20 Authors
June K. Marthin; Jane S. Lucas; Mieke Boon; Carmen Casaulta; Suzanne Crowley; Damien M.S. Destouches; Ernst Eber; Amparo Escribano; Eric G. Haarman; Claire Hogg; Bernard Maitre; Gemma Marsh; Vendula Martinu; Antonio Moreno-Galdó; Huda Mussaffi; Heymut Omran; Petr Pohunek; Bernhard Rindlisbacher; Phil Robinson; Deborah Snijders; Woolf T. Walker; Panayiotis K. Yiallouros; Helle Krogh Johansen; Kim G. Nielsen;
Introduction In primary ciliary dyskinesia (PCD) impaired mucociliary clearance leads to recurrent airway infections and progressive lung destruction, and concern over chronic airway infection and patient-to-patient transmission is considerable. So far, there has been no defined consensus on how to control infection across centres caring for patients with PCD. Within the BEAT-PCD network, COST Action and ERS CRC together with the ERN-Lung PCD core a first initiative has now been taken towards creating such a consensus statement. Methods A multidisciplinary international PCD expert panel was set up to create a consensus statement for infection prevention and control (IP&C) for PCD, covering diagnostic microbiology, infection prevention for specific pathogens considered indicated for treatment and segregation aspects. Using a modified Delphi process, consensus to a statement demanded at least 80% agreement within the PCD expert panel group. Patient organisation representatives were involved throughout the process. Results We present a consensus statement on 20 IP&C statements for PCD including suggested actions for microbiological identification, indications for treatment of Pseudomonas aeruginosa, Burkholderia cepacia and nontuberculous mycobacteria and suggested segregation aspects aimed to minimise patient-to-patient transmission of infections whether in-hospital, in PCD clinics or wards, or out of hospital at meetings between people with PCD. The statement also includes segregation aspects adapted to the current coronavirus disease 2019 (COVID-19) pandemic. Conclusion The first ever international consensus statement on IP&C intended specifically for PCD is presented and is targeted at clinicians managing paediatric and adult patients with PCD, microbiologists, patient organisations and not least the patients and their families. For the first time ever, an international consensus statement for infection prevention and control in PCD is presented. A total of 20 statements were developed in a collaboration of BEAT-PCD, COST Action, ERS CRC and ERN-LUNG PCD Core Network. https://bit.ly/3yuahKt
AG has received support by NordForsk Nordic Trial Alliance (NTA) grant, by Academy of Finland Fellow grant N. 323116 and the Academy of Finland for PREDICT consortium N. 340541. The Richards research group is supported by the Canadian Institutes of Health Research (CIHR) (365825 and 409511), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation (CFI), the NIH Foundation, Cancer Research UK, Genome Québec, the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS). TN is supported by a research fellowship of the Japan Society for the Promotion of Science for Young Scientists. GBL is supported by a CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship. JBR is supported by an FRQS Clinical Research Scholarship. Support from Calcul Québec and Compute Canada is acknowledged. TwinsUK is funded by the Welcome Trust, the Medical Research Council, the European Union, the National Institute for Health Research-funded BioResource and the Clinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. The Biobanque Québec COVID19 is funded by FRQS, Genome Québec and the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé. These funding agencies had no role in the design, implementation or interpretation of this study. The COVID19-Host(a)ge study received infrastructure support from the DFG Cluster of Excellence 2167 “Precision Medicine in Chronic Inflammation (PMI)” (DFG Grant: “EXC2167”). The COVID19-Host(a)ge study 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). Genotyping in COVID19-Host(a)ge was supported by a philantropic donation from Stein Erik Hagen. The COVID GWAs, Premed COVID-19 study (COVID19-Host(a)ge_3) was supported by "Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"and also by the Instituto de Salud Carlos III (CIBERehd and CIBERER). Funding comes from COVID-19-GWAS, COVID-PREMED initiatives. Both of them are supported by "Consejeria de Salud y Familias" of the Andalusian Government. DMM is currently funded by the the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018). The Columbia University Biobank was supported by Columbia University and the National Center for Advancing Translational Sciences, NIH, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Columbia University. The SPGRX study was supported by the Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150. The GEN-COVID study was funded by: the MIUR grant “Dipartimenti di Eccellenza 2018-2020” to the Department of Medical Biotechnologies University of Siena, Italy; the “Intesa San Paolo 2020 charity fund” dedicated to the project NB/2020/0119; and philanthropic donations to the Department of Medical Biotechnologies, University of Siena for the COVID-19 host genetics research project (D.L n.18 of March 17, 2020). Part of this research project is also funded by Tuscany Region “Bando Ricerca COVID-19 Toscana” grant to the Azienda Ospedaliero Universitaria Senese (CUP I49C20000280002). Authors are grateful to: the CINECA consortium for providing computational resources; the Network for Italian Genomes (NIG) (http://www.nig.cineca.it) for its support; the COVID-19 Host Genetics Initiative (https://www.covid19hg.org/); the Genetic Biobank of Siena, member of BBMRI-IT, Telethon Network of Genetic Biobanks (project no. GTB18001), EuroBioBank, and RD-Connect, for managing specimens. Genetics against coronavirus (GENIUS), Humanitas University (COVID19-Host(a)ge_4) was supported by Ricerca Corrente (Italian Ministry of Health), intramural funding (Fondazione Humanitas per la Ricerca). The generous contribution of Banca Intesa San Paolo and of the Dolce&Gabbana Fashion Firm is gratefully acknowledged. Data acquisition and sample processing was supported by COVID-19 Biobank, Fondazione IRCCS Cà Granda Milano; LV group was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, the European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- “Liver Investigation: Testing Marker Utility in Steatohepatitis”, Programme “Photonics” under grant agreement “101016726” for the project “REVEAL: Neuronal microscopy for cell behavioural examination and manipulation”, Fondazione Patrimonio Ca’ Granda “Liver Bible” PR-0361. DP was supported by Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, CV PREVITAL “Strategie di prevenzione primaria nella popolazione Italiana” Ministero della Salute, and Associazione Italiana per la Prevenzione dell’Epatite Virale (COPEV). Genetic modifiers for COVID-19 related illness (BeLCovid_1) was supported by the "Fonds Erasme". The Host genetics and immune response in SARS-Cov-2 infection (BelCovid_2) study was supported by grants from Fondation Léon Fredericq and from Fonds de la Recherche Scientifique (FNRS). The INMUNGEN-CoV2 study was funded by the Consejo Superior de Investigaciones Científicas. KUL is supported by the German Research Foundation (LU 1944/3-1) SweCovid is funded by the SciLifeLab/KAW national COVID-19 research program project grant to Michael Hultström (KAW 2020.0182) and the Swedish Research Council to Robert Frithiof (2014-02569 and 2014-07606). HZ is supported by Jeansson Stiftelser, Magnus Bergvalls Stiftelse. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping for the COMRI cohort was performed and funded by the Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland. These funding agencies had no role in the design, implementation or interpretation of this study. Background: There is considerable variability in COVID-19 outcomes amongst younger adults—and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. Method: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. Findings: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. Interpretation: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality—and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. CV PREVITAL “Strategie di prevenzione primaria nella popolazione Italiana” Ministero della Salute, and Associazione Italiana per la Prevenzione dell’Epatite Virale (COPEV) Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland Clinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS) CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) "Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia" “Intesa San Paolo 2020 charity fund” dedicated to the project NB/2020/0119 Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico SciLifeLab/KAW national COVID-19 research program project (KAW 2020.0182) Andalusian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018) Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150 Canadian Institutes of Health Research (CIHR) (365825 and 409511) Japan Society for the Promotion of Science for Young Scientists "Consejeria de Salud y Familias" of the Andalusian Government McGill Interdisciplinary Initiative in Infection and Immunity Ricerca Finalizzata Ministero della Salute RF-2016-02364358 National Institute for Health Research-funded BioResource Fondazione Patrimonio Ca’ Granda “Liver Bible” PR-0361 Swedish Research Council (2014-02569 and 2014-07606) Instituto de Salud Carlos III (CIBERehd and CIBERER) National Center for Advancing Translational Sciences Academy of Finland for PREDICT consortium N. 340541. Lady Davis Institute of the Jewish General Hospital MIUR grant “Dipartimenti di Eccellenza 2018-2020” Technical University of Munich, Munich, Germany Jeansson Stiftelser, Magnus Bergvalls Stiftelse Tuscany Region “Bando Ricerca COVID-19 Toscana” Consejo Superior de Investigaciones Científicas Ricerca Corrente (Italian Ministry of Health) Academy of Finland Fellow grant N. 323116 Fonds de la Recherche Scientifique (FNRS) German Research Foundation (LU 1944/3-1) Canadian Foundation for Innovation (CFI) Fondazione Humanitas per la Ricerca FRQS Clinical Research Scholarship Fondazione IRCCS Cà Granda Milano Network for Italian Genomes (NIG) COVID-19 Host Genetics Initiative Fonds de Recherche Québec Santé Public Health Agency of Canada NIH Grant Number UL1TR001873 Dolce&Gabbana Fashion Firm MyFirst Grant AIRC n.16888 COVID-PREMED initiatives Genetic Biobank of Siena Fondation Léon Fredericq “Photonics” “101016726” (CompLS grant 031L0165) Banca Intesa San Paolo Medical Research Counc (DFG Grant: “EXC2167”) King’s College London Columbia University Cancer Research UK CINECA consortium COVID-19 Biobank Stein Erik Hagen Compute Canada "Fonds Erasme" NIH Foundation European Union Genome Québec COVID-19-GWAS Calcul Québec Welcome Trust EuroBioBank RD-Connect