Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Qian Zhang; Paul Bastard; Zhiyong Liu; Jérémie Le Pen; Marcela Moncada-Velez; Jie Chen; Masato Ogishi; Ira Sabli; Stephanie Hodeib; Cecilia Korol; Jérémie Rosain; Kaya Bilguvar; Junqiang Ye; Alexandre Bolze; Benedetta Bigio; Rui Yang; Andrés Augusto Arias; Qinhua Zhou; Yu Zhang; Fanny Onodi; Sarantis Korniotis; Léa Karpf; Quentin Philippot; Marwa Chbihi; Lucie Bonnet-Madin; Karim Dorgham; Nikaïa Smith; William Schneider; Brandon Razooky; Hans-Heinrich Hoffmann; Eleftherios Michailidis; Leen Moens; Ji Eun Han; Lazaro Lorenzo; Lucy Bizien; Philip Meade; Anna-Lena Neehus; Aileen Camille Ugurbil; Aurélien Corneau; Gaspard Kerner; Peng Zhang; Franck Rapaport; Yoann Seeleuthner; Jeremy Manry; Cecile Masson; Yohann Schmitt; Agatha Schlüter; Tom Le Voyer; Taushif Khan; Juan Li; Jacques Fellay; Lucie Roussel; Mohammad Shahrooei; Mohammed Alosaimi; Davood Mansouri; Haya Al-Saud; Fahd Al-Mulla; Feras Almourfi; Saleh Zaid Al-Muhsen; Fahad Alsohime; Saeed Al Turki; Rana Hasanato; Diederik van de Beek; Andrea Biondi; Laura Rachele Bettini; Mariella D’angio; Paolo Bonfanti; Luisa Imberti; Alessandra Sottini; Simone Paghera; Eugenia Quiros-Roldan; Camillo Rossi; Andrew Oler; Miranda Tompkins; Camille Alba; Isabelle Vandernoot; Jean-Christophe Goffard; Guillaume Smits; Isabelle Migeotte; Filomeen Haerynck; Pere Soler-Palacin; Andrea Martin-Nalda; Roger Colobran; Pierre-Emmanuel Morange; Sevgi Keles; Fatma Çölkesen; Tayfun Ozcelik; Kadriye Kart Yasar; Sevtap Senoglu; Şemsi Nur Karabela; Carlos Rodríguez Gallego; Giuseppe Novelli; Sami Hraiech; Yacine Tandjaoui-Lambiotte; Xavier Duval; Cédric Laouénan; Christelle Tual; Andrew Snow; Clifton Dalgard; Joshua Milner; Amsterdam UMC Covid-19 Biobank

doi:10.1126/science.abd4570

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Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Journal article

Open access

Peer reviewed

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Qian Zhang, Paul Bastard, Zhiyong Liu, Jérémie Le Pen, Marcela Moncada-Velez, Jie Chen, Masato Ogishi, Ira Sabli, Stephanie Hodeib, Cecilia Korol, …

Science (American Association for the Advancement of Science), Vol.370(6515), p.eabd4570

23/10/2020

DOI: https://doi.org/10.1126/science.abd4570

PMID: 32972995

Abstract

Human health and pathology

Infectious diseases

Life Sciences

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)– and interferon regulatory factor 7 (IRF7)–dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

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Title: Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
Creators - without role: Qian Zhang - Rockefeller University
Paul Bastard - Inserm
Zhiyong Liu - Rockefeller University
Jérémie Le Pen - Rockefeller University
Marcela Moncada-Velez - Rockefeller University
Jie Chen - Rockefeller University
Masato Ogishi - Rockefeller University
Ira Sabli
Stephanie Hodeib - Imperial College London
Cecilia Korol - Inserm
Jérémie Rosain - Inserm
Kaya Bilguvar - Yale School of Medicine
Junqiang Ye - Columbia University
Alexandre Bolze - Helix
Benedetta Bigio - Rockefeller University
Rui Yang - Rockefeller University
Andrés Augusto Arias - Rockefeller University
Qinhua Zhou - Rockefeller University
Yu Zhang - Office of Extramural Research
Fanny Onodi - Université Paris Cité
Sarantis Korniotis - Université Paris Cité
Léa Karpf - Université Paris Cité
Quentin Philippot - Imagine Institute for Genetic Diseases
Marwa Chbihi - Inserm
Lucie Bonnet-Madin - Université Paris Cité
Karim Dorgham - Centre d'Immunologie et des Maladies Infectieuses
Nikaïa Smith - Institut Pasteur
William Schneider - Rockefeller University
Brandon Razooky - Rockefeller University
Hans-Heinrich Hoffmann - Rockefeller University
Eleftherios Michailidis - Rockefeller University
Leen Moens - KU Leuven
Ji Eun Han - Rockefeller University
Lazaro Lorenzo - Inserm
Lucy Bizien - Imagine Institute for Genetic Diseases
Philip Meade - Icahn School of Medicine at Mount Sinai
Anna-Lena Neehus - Inserm
Aileen Camille Ugurbil - Rockefeller University
Aurélien Corneau - Sorbonne Université, UMS037, PASS, Plateforme de Cytométrie de la Pitié-Salpêtrière CyPS, Paris, France.
Gaspard Kerner - Inserm
Peng Zhang - Rockefeller University
Franck Rapaport - Rockefeller University
Yoann Seeleuthner - Inserm
Jeremy Manry - Inserm
Cecile Masson - Université Paris Cité
Yohann Schmitt
Agatha Schlüter - Centre for Biomedical Network Research on Rare Diseases
Tom Le Voyer - Inserm
Taushif Khan - Qatar Airways
Juan Li - Rockefeller University
Jacques Fellay - École Polytechnique Fédérale de Lausanne
Lucie Roussel - McGill University Health Centre
Mohammad Shahrooei
Mohammed Alosaimi - King Saud University
Davood Mansouri - Masih Daneshvari Hospital
Haya Al-Saud - King Abdulaziz City for Science and Technology
Fahd Al-Mulla - Dasman Diabetes Institute
Feras Almourfi - King Abdulaziz City for Science and Technology
Saleh Zaid Al-Muhsen - King Saud University
Fahad Alsohime - King Saud University
Saeed Al Turki - National Guard Health Affairs
Rana Hasanato - King Saud University
Diederik van de Beek - Amsterdam Neuroscience
Andrea Biondi - University of Milano-Bicocca
Laura Rachele Bettini - University of Milano-Bicocca
Mariella D’angio
Paolo Bonfanti - University of Milano-Bicocca
Luisa Imberti - Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Alessandra Sottini - Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Simone Paghera - Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Eugenia Quiros-Roldan - University of Brescia
Camillo Rossi - Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Andrew Oler - Computational Sciences
Miranda Tompkins - Uniformed Services University of the Health Sciences
Camille Alba - Uniformed Services University of the Health Sciences
Isabelle Vandernoot - Université Libre de Bruxelles
Jean-Christophe Goffard - Université Libre de Bruxelles
Guillaume Smits - Université Libre de Bruxelles
Isabelle Migeotte - Université Libre de Bruxelles
Filomeen Haerynck - Ghent University Hospital
Pere Soler-Palacin - Vall d'Hebron Institut de Recerca
Andrea Martin-Nalda - Vall d'Hebron Hospital Universitari
Roger Colobran - Vall d'Hebron Institut de Recerca
Pierre-Emmanuel Morange - Aix-Marseille University
Sevgi Keles - Necmettin Erbakan University
Fatma Çölkesen
Tayfun Ozcelik - Bilkent University
Kadriye Kart Yasar - Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi
Sevtap Senoglu - Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi
Şemsi Nur Karabela - Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi
Carlos Rodríguez Gallego
Giuseppe Novelli - University of Rome Tor Vergata
Sami Hraiech - Marseille Public University Hospital System
Yacine Tandjaoui-Lambiotte - Université Sorbonne Paris Nord
Xavier Duval - Université Paris Cité
Cédric Laouénan - Université Paris Cité
Christelle Tual - Centre d'Investigation Clinique [Rennes]
Andrew Snow - Uniformed Services University of the Health Sciences
Clifton Dalgard - Uniformed Services University of the Health Sciences
Joshua Milner - Columbia University
Amsterdam UMC Covid-19 Biobank
Publication Details: Science (American Association for the Advancement of Science), Vol.370(6515), p.eabd4570
Publisher: American Association for the Advancement of Science (AAAS)
Identifiers: 9918634908331
Academic Unit: King Abdulaziz City for Science & Technology; King Khalid University; King Saud University
Language: English
Resource Type: Journal article