The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies
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- Jeremy Manry
- INSERM U1163
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- Paul Bastard
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163
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- Adrian Gervais
- INSERM U1163
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- Tom Le Voyer
- INSERM U1163
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- Jérémie Rosain
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM
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- Quentin Philippot
- INSERM U1163
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- Eleftherios Michailidis
- The Rockefeller University, Laboratory of Virology and Infectious Disease
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- Hans-Heinrich Hoffmann
- Laboratory of Virology and Infectious Disease, Rockefeller University
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- Shohei Eto
- Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Marina Garcia-Prat
- Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute
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- Lucy Bizien
- INSERM U1163
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- Alba Parra-Martínez
- Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute
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- Rui Yang
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University
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- Liis Haljasmägi
- University of Tartu
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- Mélanie Migaud
- INSERM U1163
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- Karita Särekannu
- Institute of Biomedicine and Translational Medicine, University of Tartu
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- Julia Maslovskaja
- Institute of Biomedicine and Translational Medicine, University of Tartu
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- Nicolas de Prost
- Hôpitaux Universitaires Henri Mondor
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- Yacine Tandjaoui-Lambiotte
- Avicenne Hospital, AP-HP, Bobigny, INSERM U1272, Hypoxia and Lung
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- Charles-Edouard Luyt
- Hôpital Pitié-Salpêtrière, Service de Médecine Intensive Réanimation, Institut de Cardiologie
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- Blanca Amador-Borrero
- Internal Medicine Department, Lariboisière Hospital AP-HP, Paris University
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- Alexandre Gaudet
- University of Lille, U1019-UMR9017, Center for Infection and Immunity of Lille
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- Julien Poissy
- University of Lille, U1019-UMR9017, Center for Infection and Immunity of Lille
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- Pascal Morel
- Etablissement Français Du Sang
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- Pascale Richard
- Etablissement Français Du Sang
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- Fabrice Cognasse
- Etablissement Français du Sang, Auvergne-Rhône-Alpes
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- Jesus Troya
- Department of Internal Medicine, Infanta Leonor University Hospital
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- Sophie Trouillet-Assant
- Hospices Civils de Lyon
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- Alexandre Belot
- Hospices Civils de Lyon
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- Kahina Saker
- Hospices Civils de Lyon
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- Pierre Garçon
- Intensive Care Unit, Grand Hôpital de l’Est Francilien Site de Marne-La-Vallée
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- Jacques G. Rivière
- Hospital Universitari Vall d'Hebron
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- Jean-Christophe Lagier
- Méditerranée Infection Foundation
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- Stéphanie Gentile
- Service d’Evaluation Médicale, Hôpitaux Universitaires de Marseille APHM
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- Lindsey Rosen
- National Institutes of Health
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- Elana Shaw
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health,
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- Tomohiro Morio
- Tokyo Medical and Dental University
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- Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima Universit
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- David Dalmau
- Hospital Universitari MútuaTerrassa; Fundació Docència i Recerca MutuaTerrassa, Terrasa; Universitat de Barcelona
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- Pierre-Louis Tharaux
- Institut National de la Santé et de la Recherche Médicale (INSERM)
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- Damien Sene
- Internal Medicine Department, Lariboisière Hospital AP-HP, Paris University
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- Alain Stepanian
- Service d’Hématologie Biologique, Hôpital Lariboisière, AP-HP and EA3518, Institut Universitaire d'Hématologie-Hôpital Saint Louis, Université Paris
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- Bruno Mégarbane
- Réanimation Médicale et Toxicologique, Hôpital Lariboisière (AP-HP), Université Paris-Diderot, INSERM Unité Mixte de Recherche Scientifique (UMRS) 1144
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- Vasiliki Triantafyllia
- Laboratory of Immunobiology, Center for Clinical, Experimental Surgery, and Translational Research, Biomedical Research Foundation of the Academy of Athens
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- Arnaud Fekkar
- INSERM U1163
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- James Heath
- Institute for Systems Biology
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- Jose Franco
- University of Antioquia
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- Juan-Manuel Anaya
- Universidad del Rosario
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- Jordi Solé-Violán
- Intensive Care Medicine, University Hospital of Gran Canaria Dr. Negrín, Canarian Health System
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- Luisa Imberti
- CREA Laboratory (AIL Center for Hemato-Oncologic Research), Diagnostic Department, ASST Spedali Civili di Brescia
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- Andrea Biondi
- Fondazione Tettamenti
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- Paolo Bonfanti
- Department of Infectious Diseases, San Gerardo Hospital, University of Milano Bicocca
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- Riccardo Castagnoli
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health,
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- Ottavia Delmonte
- Immune Deficiency Genetics Section, Laboratory of Host Defenses, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
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- Yu Zhang
- NIAID
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- Andrew Snow
- Uniformed Services University of the Health Sciences, Bethesda, MD
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- Steve Holland
- Division of Intramural Research (HNM2), National Institute of Allergy and Infectious Diseases
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- Catherine Biggs
- Department of Pediatrics, British Columbia Children’s Hospital, University of British Columbia
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- Marcela Moncada-Vélez
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University
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- Andrés Arias
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University
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- Lazaro Lorenzo
- Necker Medical School
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- Soraya Boucherit
- Necker Medical School
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- Dany Anglicheau
- CHU Necker
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- Anna Planas
- Spanish National Research Council
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- Filomeen Haerynck
- Ghent University Hospital
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- Sotirija Duvlis
- Faculty of Medical Sciences, University “Goce Delchev,” Štip, Republic of Northern Macedonia.
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- Robert Nussbaum
- Invitae (United States)
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- Tayfun Ozcelik
- Bilkent University
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- Sevgi Keles
- Necmettin Erbakan University, Meram Medical Faculty
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- Aziz Bousfiha
- Centre Hospitalier Universitaire Hassan II
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- Jalila El Bakkouri
- Clinical Immunology Unit, Department of Pediatric Infectious Disease, CHU Ibn Rushd and LICIA, Laboratoire d’Immunologie Clinique, Inflammation et Allergie, Faculty of Medicine and Pharmacy,
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- Carolina Ramirez-Santana
- Center for Autoimmune Disease Research, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
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- Stéphane Paul
- Centre International de Recherche en Infectiologie Lyon
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- Qiang Pan-Hammarstrom
- Karolinska Institute
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- Lennart Hammarstrom
- Karolinska Institute
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- Annabelle Dupont
- Université de Lille, INSERM, CHU de Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France.
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- Alina Kurolap
- Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.
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- Christine Metz
- Feinstein Institute for Medical Research
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- Alessandro Aiuti
- San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan
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- Giorgio Casari
- Vita-Salute San Raffaele University, and Clinical Genomics, IRCCS Ospedale San Raffaele, Milan, Italy.
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- Vito Lampasona
- IRCCS Ospedale San Raffaele
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- Fabio Ciceri
- Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
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- Lucila Barreiros
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
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- Elena Dominguez-Garrido
- Fundación Rioja Salud, Centro de Investigación Biomédica de La Rioja, Logroño, Spain.
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- Mateus Vidigal
- University of São Paulo, São Paulo, Brazil.
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- Mayana Zatz
- University of São Paulo, São Paulo, Brazil.
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- Diederik van de Beek
- Department of Neurology, Amsterdam Neuroscience, Amsterdam, Netherlands.
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- Sabina Sahanic
- Department of Internal Medicine II, Medical University Innsbruck
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- Ivan Tancevski
- Innsbruck Medical University
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- Yurii Stepanovskyy
- Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine.
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- Oksana Boyarchuk
- Department of Children’s Diseases and Pediatric Surgery, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine.
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- Yoko Nukui
- Department of Infection Control and Prevention, Medical Hospital, TMDU, Tokyo, Japan.
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- Miyuki Tsumura
- Hirosima University
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- Loreto Vidaur
- Intensive Care Medicine, Donostia University Hospital, Biodonostia Institute of Donostia, San Sebastián, Spain.
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- Stuart Tangye
- Garvan Institute
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- Sonia Burrel
- Sorbonne University
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- Darragh Duffy
- Translational Immunology Lab, Institut Pasteur
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- Lluis Quintana-Murci
- Institut Pasteur
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- Adam Klocperk
- Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, 15006 Prague
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- Nelli Kann
- Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
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- Anna Shcherbina
- Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
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- Yu-Lung Lau
- The University of Hong Kong
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- Daniel Leung
- Department of Paediatrics and Adolescent Medicine, University of Hong Kong, Hong Kong, China.
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- Matthieu Coulongeat
- Division of Geriatric Medicine, Tours University Medical Center, Tours, France.
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- Julien Marlet
- INSERM U1259, MAVIVH, Université de Tours, Tours, France.
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- Rutger Koning
- Department of Neurology, Amsterdam Neuroscience, Amsterdam, Netherlands.
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- Luis Reyes
- Department of Microbiology, Universidad de La Sabana, Chía, Colombia.
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- Angélique Chauvineau-Grenier
- Service de Biologie Médicale, CHI Robert Ballanger, Aulnay-sous-Bois, France.
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- Fabienne Venet
- Hospices Civils de Lyon
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- guillaume monneret
- Immunology department
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- Michel Nussenzweig
- Rockefeller University
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- Romain Arrestier
- Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
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- Idris Boudhabhay
- Department of Nephrology and Transplantation, Necker University Hospital, APHP, Paris, France. 58INEM, INSERM U1151–CNRS UMR 8253, Paris University, Paris, France.
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- Hagit Baris-Feldman
- Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.
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- David Hagin
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv
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- Joost Wauters
- Medical Intensive Care Unit, UZ Gasthuisberg & Laboratory for Clinical Infectious and Inflammatory Disorders, Depart-ment of Microbiology, Immunology and Transplantation, KU Leuven
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- Isabelle Meyts
- University Hospitals Leuven
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- Adam Dyer
- Department of Age-Related Healthcare, Tallaght University Hospital, Dublin, Ireland.
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- Sean Kennelly
- Department of Age-Related Healthcare, Tallaght University Hospital, Dublin, Ireland.
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- Nollaig Bourke
- Department of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin, Ireland.
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- Rabih Halwani
- SIMR
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- Fatemeh Sharif-Askari
- Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
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- Karim Dorgham
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMIParis UMRS 1135)
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- Jérôme Sallette
- Cerba HealthCare, Issy-les-Moulineaux, France.
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- Souad Mehlal-Sedkaoui
- Cerba HealthCare, Issy-les-Moulineaux, France.
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- Suzan AlKhater
- Department of Pediatrics, King Fahad Hospital of the University, Al Khobar, Saudi Arabia.
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- Raúl Rigo-Bonnin
- Department of Clinical Laboratory, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain.
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- Francisco Morandeira
- Department of Immunology, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain.
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- Lucie Roussel
- Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, Montréal, QC, Canada.
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- Donald Vinh
- The Research Institute of the McGill University Health Centre
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- Christian Erikstrup
- Aarhus University Hospital
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- Antonio Condino-Neto
- Institute of Biomedical Sciences, University of São Paulo
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- Carolina Prando
- Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil.
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- Anastasiia Bondarenko
- Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine.
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- András Spaan
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.
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- Laurent Gilardin
- Service de Médecine Interne, Hôpital universitaire Jean-Verdier AP-HP, Bondy, France.
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- Jacques Fellay
- École Polytechnique Fédérale de Lausanne
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- Stanislas Lyonnet
- Hôpital Necker-Enfants Malades
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- Kaya Bilguvar
- Yale University School of Medicine
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- Richard Lifton
- Laboratory of Human Genetics and Genomics, The Rockefeller University
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- Shrikant Mane
- Yale University School of Medicine
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- Mark Anderson
- Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
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- Bertrand Boisson
- Rockefeller University
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- Vivien Béziat
- INSERM U1163
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- Evangelos Andreakos
- Biomedical Research Foundation, Academy of Athens
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- Olivier Hermine
- Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) 1163
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- Aurora Pujol
- ICREA/ IDIBELL
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- Pärt Peterson
- Molecular Pathology Research Group, Institute of Biomedicine and Translational Medicine, University of Tartu
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- Trine Hyrup Mogensen
- Aarhus University
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- Lee Rowen
- Institute for Systems Biology, Seattle, WA, USA.
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- James Mond
- ADMA Biologics Inc., Ramsey, NJ, USA
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- Stéphanie Debette
- University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219
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- Xavier deLamballerie
- Aix-Marseille University
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- Charles Burdet
- INSERM CIC 1425, Paris, France.
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- Lila Bouadma
- APHP- Hôpital Bichat – Médecine Intensive et Réanimation des Maladies
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- Marie Zins
- Université de Paris, Université Paris-Saclay, UVSQ, INSERM UMS11, Villejuif, France.
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- Pere Soler-Palacin
- Vall d'Hebron University Hospital
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- Roger Colobran
- Hospital Universitari Vall d'Hebron (HUVH)
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- Guy Gorochov
- APHP Sorbonne universite
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- Xavier Solanich
- Department of Internal Medicine, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain.
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- Sophie Susen
- Université de Lille, INSERM, CHU de Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France.
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- Javier Martinez-Picado
- IrsiCaixa
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- Didier Raoult
- Aix Marseille Université; IHU Méditerranée Infection-MEPHI
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- Marc Vasse
- Service de Biologie Clinique and UMR-S 1176, Hôpital Foch, Suresnes, France.
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- Peter Gregersen
- Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
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- Carlos Rodríguez-Gallego
- Department of Immunology, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System, Las Palmas de Gran Canaria, Spain.
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- Lorenzo Piemonti
- IRCCS Ospedale San Raffaele , San Raffaele Diabetes Research Institute, Via Olgettina 60, 20132 Milan
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- Luigi Notarangelo
- NIAID/NIH
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- Helen Su
- NIAID, NIH
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- Kai Kisand
- University of Tartu
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- Satoshi Okada
- Hiroshima University Graduate School of Biomedical and Health Sciences
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- Anne Puel
- INSERM
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- Emmanuelle Jouanguy
- Rockefeller University
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- Charles Rice
- Rockefeller University
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- Qian Zhang
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.
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- Laurent Abel
- Necker Medical School
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- Aurélie Cobat
- INSERM
抄録
<jats:title>Abstract</jats:title> <jats:p>SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules.<jats:bold> </jats:bold>Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.</jats:p>