The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

Jérémy Manry; Paul Bastard; Adrian Gervais; Tom Le Voyer; Jérémie Rosain; Quentin Philippot; Eleftherios Michailidis; Hans-Heinrich Hoffmann; Shohei Eto; Marina Garcia-Prat; Lucy Bizien; Alba Parra-Martínez; Rui Yang; Liis Haljasmägi; Mélanie Migaud; Karita Särekannu; Julia Maslovskaja; Nicolas de Prost; Yacine Tandjaoui-Lambiotte; Charles-Edouard Luyt; Blanca Amador-Borrero; Alexandre Gaudet; Julien Poissy; Pascal Morel; Pascale Richard; Fabrice Cognasse; Jesús Troya; Sophie Trouillet-Assant; Alexandre Belot; Kahina Saker; Pierre Garçon; Jacques G Rivière; Jean-Christophe Lagier; Stéphanie Gentile; Lindsey B Rosen; Elana Shaw; Tomohiro Morio; Junko Tanaka; David Dalmau; Pierre-Louis Tharaux; Damien Sene; Alain Stepanian; Bruno Mégarbane; Vasiliki Triantafyllia; Arnaud Fekkar; James R Heath; José Luis Franco; Juan-Manuel Anaya; Jordi Solé-Violán; Luisa Imberti; Andrea Biondi; Paolo Bonfanti; Riccardo Castagnoli; Ottavia M Delmonte; Yu Zhang; Andrew L Snow; Steven M Holland; Catherine M Biggs; Marcela Moncada-Vélez; Andrés Augusto Arias; Lazaro Lorenzo; Soraya Boucherit; Dany Anglicheau; Anna M Planas; Filomeen Haerynck; Sotirija Duvlis; Tayfun Ozcelik; Sevgi Keles; Ahmed A Bousfiha; Jalila El Bakkouri; Carolina Ramirez-Santana; Stéphane Paul; Qiang Pan-Hammarström; Lennart Hammarström; Annabelle Dupont; Alina Kurolap; Christine N Metz; Alessandro Aiuti; Giorgio Casari; Vito Lampasona; Fabio Ciceri; Lucila A Barreiros; Elena Dominguez-Garrido; Mateus Vidigal; Mayana Zatz; Diederik van de Beek; Sabina Sahanic; Ivan Tancevski; Yurii Stepanovskyy; Oksana Boyarchuk; Yoko Nukui; Miyuki Tsumura; Loreto Vidaur; Stuart G Tangye; Sonia Burrel; Darragh Duffy; Lluis Quintana-Murci; Adam Klocperk; Nelli Y Kann; Anna Shcherbina; Yu-Lung Lau; Daniel Leung; Matthieu Coulongeat; Julien Marlet; Rutger Koning; Luis Felipe Reyes; Angélique Chauvineau-Grenier; Fabienne Venet; Guillaume Monneret; Michel C Nussenzweig; Romain Arrestier; Idris Boudhabhay; Hagit Baris-Feldman; David Hagin; Joost Wauters; Isabelle Meyts; Adam H Dyer; Sean P Kennelly; Nollaig M Bourke; Rabih Halwani; Fatemeh Saheb Sharif-Askari; Karim Dorgham; Jérôme Sallette; Souad Mehlal Sedkaoui; Suzan AlKhater; Raúl Rigo-Bonnin; Francisco Morandeira; Lucie Roussel; Donald C Vinh; Christian Erikstrup; Antonio Condino-Neto; Carolina Prando; Anastasiia Bondarenko; András N Spaan; Laurent Gilardin; Jacques Fellay; Stanislas Lyonnet; Kaya Bilguvar; Richard P Lifton; Shrikant Mane; Mark S Anderson; Bertrand Boisson; Vivien Béziat; Shen-Ying Zhang; Evangelos Andreakos; Olivier Hermine; Aurora Pujol; Pärt Peterson; Trine H Mogensen; Lee Rowen; James Mond; Stéphanie Debette; Xavier de Lamballerie; Charles Burdet; Lila Bouadma; Marie Zins; Pere Soler-Palacin; Roger Colobran; Guy Gorochov; Xavier Solanich; Sophie Susen; Javier Martinez-Picado; Didier Raoult; Marc Vasse; Peter K Gregersen; Lorenzo Piemonti; Carlos Rodríguez-Gallego; Luigi D Notarangelo; Helen C Su; Kai Kisand; Satoshi Okada; Anne Puel; Emmanuelle Jouanguy; Charles M Rice; Pierre Tiberghien; Qian Zhang; Jean-Laurent Casanova; Laurent Abel; Aurélie Cobat; Danish CHGE

doi:10.1073/pnas.2200413119

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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

Journal article

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Peer reviewed

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

Jérémy Manry, Paul Bastard, Adrian Gervais, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Shohei Eto, Marina Garcia-Prat, …

Proceedings of the National Academy of Sciences - PNAS, Vol.119(21), pp.e2200413119-e2200413119

24/05/2022

DOI: https://doi.org/10.1073/pnas.2200413119

PMID: 35576468

Abstract

Adult

Age Factors

Aged

Aged, 80 and over

Antibodies, Neutralizing - blood

Autoantibodies - blood

Autoimmunity

COVID-19 - immunology

COVID-19 - mortality

Female

Humans

Interferon Type I - immunology

Male

Middle Aged

Risk

SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y 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, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.

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Title: The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies
Creators - without role: Jérémy Manry - Inserm
Paul Bastard - Imagine Institute for Genetic Diseases
Adrian Gervais - Inserm
Tom Le Voyer - Imagine Institute for Genetic Diseases
Jérémie Rosain - Université Paris Cité
Quentin Philippot - Imagine Institute for Genetic Diseases
Eleftherios Michailidis - Rockefeller University
Hans-Heinrich Hoffmann - Rockefeller University
Shohei Eto - Hiroshima University
Marina Garcia-Prat - Vall d'Hebron Institut de Recerca
Lucy Bizien - Imagine Institute for Genetic Diseases
Alba Parra-Martínez - Vall d'Hebron Institut de Recerca
Rui Yang - Rockefeller University
Liis Haljasmägi - University of Tartu
Mélanie Migaud - Imagine Institute for Genetic Diseases
Karita Särekannu - University of Tartu
Julia Maslovskaja - University of Tartu
Nicolas de Prost - Université Paris-Est Créteil
Yacine Tandjaoui-Lambiotte - Assistance Publique – Hôpitaux de Paris
Charles-Edouard Luyt - Assistance Publique – Hôpitaux de Paris
Blanca Amador-Borrero - Hôpital Lariboisière
Alexandre Gaudet - Center for Infection and Immunity of Lille
Julien Poissy - Center for Infection and Immunity of Lille
Pascal Morel - Établissement Français du Sang
Pascale Richard - Établissement Français du Sang
Fabrice Cognasse - Jean Monnet University
Jesús Troya - Hospital Universitario Infanta Leonor
Sophie Trouillet-Assant - Inserm
Alexandre Belot - Hospices Civils de Lyon
Kahina Saker - Inserm
Pierre Garçon - Intensive Care Unit, Grand Hôpital de l’Est Francilien Site de Marne-La-Vallée, 77600 Jossigny, France
Jacques G Rivière - Vall d'Hebron Institut de Recerca
Jean-Christophe Lagier - Aix-Marseille University
Stéphanie Gentile - Aix-Marseille University
Lindsey B Rosen - National Institute of Allergy and Infectious Diseases
Elana Shaw - National Institute of Allergy and Infectious Diseases
Tomohiro Morio - Tokyo Medical and Dental University
Junko Tanaka - Hiroshima University
David Dalmau - Mútua Terrassa
Pierre-Louis Tharaux - Paris Cardiovascular Research Center
Damien Sene - Université Paris Cité
Alain Stepanian - Hôpital Lariboisière
Bruno Mégarbane - Hôpital Lariboisière
Vasiliki Triantafyllia - Academy of Athens
Arnaud Fekkar - Inserm
James R Heath - Institute for Systems Biology, Seattle, WA 98109
José Luis Franco - Universidad de Antioquia
Juan-Manuel Anaya - Universidad del Rosario
Jordi Solé-Violán - Instituto de Salud Carlos III
Luisa Imberti - Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Andrea Biondi - Azienda Ospedaliera San Gerardo
Paolo Bonfanti - University of Milano-Bicocca
Riccardo Castagnoli - National Institute of Allergy and Infectious Diseases
Ottavia M Delmonte - National Institute of Allergy and Infectious Diseases
Yu Zhang - National Institute of Allergy and Infectious Diseases
Andrew L Snow - Uniformed Services University of the Health Sciences
Steven M Holland - National Institute of Allergy and Infectious Diseases
Catherine M Biggs - British Columbia Children's Hospital
Marcela Moncada-Vélez - Rockefeller University
Andrés Augusto Arias - Universidad de Antioquia
Lazaro Lorenzo - Inserm
Soraya Boucherit - Inserm
Dany Anglicheau - Assistance Publique – Hôpitaux de Paris
Anna M Planas - Institut d'Investigacions Biomèdiques de Barcelona
Filomeen Haerynck - Ghent University Hospital
Sotirija Duvlis - Goce Delcev University
Tayfun Ozcelik - Bilkent University
Sevgi Keles - Necmettin Erbakan University
Ahmed A Bousfiha - Centre Hospitalier Universitaire Ibn Rochd
Jalila El Bakkouri - Centre Hospitalier Universitaire Ibn Rochd
Carolina Ramirez-Santana - Universidad del Rosario
Stéphane Paul - Inserm
Qiang Pan-Hammarström - Karolinska Institutet
Lennart Hammarström - Karolinska Institutet
Annabelle Dupont - Pasteur Institute of Lille
Alina Kurolap - Tel Aviv Sourasky Medical Center
Christine N Metz - Feinstein Institute for Medical Research
Alessandro Aiuti - IRCCS Ospedale San Raffaele
Giorgio Casari - Vita-Salute San Raffaele University
Vito Lampasona - Istituti di Ricovero e Cura a Carattere Scientifico
Fabio Ciceri - IRCCS Ospedale San Raffaele
Lucila A Barreiros - Universidade de São Paulo
Elena Dominguez-Garrido - Center for Biomedical Research of La Rioja
Mateus Vidigal - Universidade de São Paulo
Mayana Zatz - Universidade de São Paulo
Diederik van de Beek - Amsterdam Neuroscience
Sabina Sahanic - Innsbruck Medical University
Ivan Tancevski - Universität Innsbruck
Yurii Stepanovskyy - Shupyk National Healthcare University of Ukraine
Oksana Boyarchuk - I.Horbachevsky Ternopil National Medical University
Yoko Nukui - Tokyo Medical and Dental University Hospital
Miyuki Tsumura - Hiroshima University
Loreto Vidaur - Biogipuzkoa Health Research Institute
Stuart G Tangye - St Vincent's Clinic
Sonia Burrel - Institut Pierre Louis d‘Épidémiologie et de Santé Publique
Darragh Duffy - Université Paris Cité
Lluis Quintana-Murci - Institut Pasteur
Adam Klocperk - Charles University
Nelli Y Kann - Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Anna Shcherbina - Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Yu-Lung Lau - University of Hong Kong
Daniel Leung - University of Hong Kong
Matthieu Coulongeat - Division of Geriatric Medicine, Tours University Medical Center, 37044 Tours, France
Julien Marlet - Centre Hospitalier Universitaire de Tours
Rutger Koning - University of Amsterdam
Luis Felipe Reyes - Universidad de La Sabana
Angélique Chauvineau-Grenier - Service de Biologie Médicale, Centre Hospitalier Intercommunal Robert Ballanger, 93600 Aulnay-sous-Bois, France
Fabienne Venet - Hospices Civils de Lyon
Guillaume Monneret - Hospices Civils de Lyon
Michel C Nussenzweig - Rockefeller University
Romain Arrestier - Groupe de Recherche Clinique Cardiovascular and Respiratory Manifestations of Acute Lung Injury and Sepsis (CARMAS), Faculté de santé de Créteil, Université Paris Est Créteil, 94010 Créteil Cedex, France
Idris Boudhabhay - Institut Necker Enfants Malades
Hagit Baris-Feldman - Tel Aviv University
David Hagin - Tel Aviv Sourasky Medical Center
Joost Wauters - Medical Intensive Care Unit, University Hospitals Leuven, 3000 Leuven, Belgium
Isabelle Meyts - Department of Pediatrics, Jeffrey Modell Diagnostic and Research Network Center, University Hospitals Leuven, 3000 Leuven, Belgium
Adam H Dyer - Trinity College Dublin
Sean P Kennelly - Trinity College Dublin
Nollaig M Bourke - Trinity College Dublin
Rabih Halwani - King Saud University
Fatemeh Saheb Sharif-Askari - University of Sharjah
Karim Dorgham - Centre d'Immunologie et des Maladies Infectieuses
Jérôme Sallette - Cerba HealthCare, 92130 Issy-les-Moulineaux, France
Souad Mehlal Sedkaoui - Cerba HealthCare, 92130 Issy-les-Moulineaux, France
Suzan AlKhater - Imam Abdulrahman Bin Faisal University
Raúl Rigo-Bonnin - Department of Clinical Laboratory, Hospital Universitari de Bellvitge, The Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain
Francisco Morandeira - Department of Immunology, Hospital Universitari de Bellvitge, The Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain
Lucie Roussel - McGill University Health Centre
Donald C Vinh - McGill University Health Centre
Christian Erikstrup - Aarhus University Hospital
Antonio Condino-Neto - Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 05508-060 São Paulo, Brazil
Carolina Prando - Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, 80250-200 Curitiba, Brazil
Anastasiia Bondarenko - Shupyk National Healthcare University of Ukraine
András N Spaan - University Medical Center Utrecht
Laurent Gilardin - Centre de Recherche des Cordeliers
Jacques Fellay - SIB Swiss Institute of Bioinformatics
Stanislas Lyonnet - Université Paris Cité
Kaya Bilguvar - Department of Medical Genetics, Acibadem University School of Medicine, 34750 Istanbul, Turkey
Richard P Lifton - Yale University
Shrikant Mane - Yale University
Mark S Anderson - Pi
Bertrand Boisson - Rockefeller University
Vivien Béziat - Rockefeller University
Shen-Ying Zhang - Rockefeller University
Evangelos Andreakos - Biomedical Research Foundation of the Academy of Athens
Olivier Hermine - Ghent University Hospital
Aurora Pujol - Catalan Institution of Research and Advanced Studies (ICREA), 08010 Barcelona, Spain
Pärt Peterson - University of Tartu
Trine H Mogensen - Aarhus University
Lee Rowen - Institute for Systems Biology, Seattle, WA 98109
James Mond - ADMA Biologics
Stéphanie Debette - Department of Neurology, Institute of Neurodegenerative Diseases, Bordeaux University Hospital, F-33000 Bordeaux, France
Xavier de Lamballerie - Aix-Marseille University
Charles Burdet - Assistance Publique – Hôpitaux de Paris
Lila Bouadma - Assistance Publique – Hôpitaux de Paris
Marie Zins - Assistance Publique – Hôpitaux de Paris
Pere Soler-Palacin - Vall d'Hebron Institut de Recerca
Roger Colobran - Vall d'Hebron Institut de Recerca
Guy Gorochov - Assistance Publique – Hôpitaux de Paris
Xavier Solanich - Department of Internal Medicine, Hospital Universitari de Bellvitge, The Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain
Sophie Susen - University of Lille, INSERM, Centre Hospitalier Universitaire de Lille, Institut Pasteur de Lille, U1011-European Genomic Institute for Diabetes (EGID), F-59000 Lille, France
Javier Martinez-Picado - Centro de Investigación Biomédica en Red
Didier Raoult - Institut de Recherche pour le Développement
Marc Vasse - Hôpital Foch
Peter K Gregersen - Northwell Health
Lorenzo Piemonti - Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, 20132 Milan, Italy
Carlos Rodríguez-Gallego - Department of Immunology, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System, 35010 Las Palmas de Gran Canaria, Spain
Luigi D Notarangelo - National Institute of Allergy and Infectious Diseases
Helen C Su - University of Pennsylvania
Kai Kisand - University of Tartu
Satoshi Okada - Hiroshima University
Anne Puel - Rockefeller University
Emmanuelle Jouanguy - Rockefeller University
Charles M Rice - Rockefeller University
Pierre Tiberghien - Établissement Français du Sang
Qian Zhang - Rockefeller University
Jean-Laurent Casanova - Rockefeller University
Laurent Abel - Rockefeller University
Aurélie Cobat - Rockefeller University
Danish CHGE
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.119(21), pp.e2200413119-e2200413119
Grant note: ZIA AI001270 / Intramural NIH HHS R01 AI088364 / NIAID NIH HHS UL1 RR024143 / NCRR NIH HHS R01 AI163029 / NIAID NIH HHS
Identifiers: 9914534008331
Academic Unit: Imam Abdulrahman Bin Faisal University; King Saud University
Language: English
Resource Type: Journal article