Open AccessInborn errors of type I IFN immunity in patients with life-threatening COVID-19
Author(s) -
Qian Zhang,
Paul Bastard,
Zhiyong Liu,
Jérémie Le Pen,
Marcela MoncadaVélez,
Jie Chen,
Masato Ogishi,
Ira K. D. Sabli,
Stephanie Hodeib,
Cecilia B. Korol,
Jérémie Rosain,
Kaya Bilgüvar,
Junqiang Ye,
Alexandre Bolze,
Benedetta Bigio,
Rui Yang,
Andrés A. Arias,
Qinhua Zhou,
Yu Zhang,
Fanny Onodi,
Sarantis Korniotis,
Léa Karpf,
Quentin Philippot,
Marwa Chbihi,
Lucie BonnetMadin,
Karim Dorgham,
Nikaïa Smith,
William M. Schneider,
Brandon S. Razooky,
Hans-Heinrich Hoffmann,
Eleftherios Michailidis,
Leen Moens,
Ji Eun Han,
Lazaro Lorenzo,
Lucy Bizien,
Philip Meade,
AnnaLeeehus,
Aileen Camille Ugurbil,
Aurélien Corneau,
Gaspard Kerner,
Peng Zhang,
Franck Rapaport,
Yoann Seeleuthner,
Jérémy Manry,
Cécile Masson,
Yohann Schmitt,
Agatha Schlüter,
Tom Le Voyer,
Taushif Khan,
Juan Li,
Jacques Fellay,
Lucie Roussel,
Mohammad Shahrooei,
Mohammed F. Alosaimi,
Davood Mansouri,
Haya AlSaud,
Fahd AlMulla,
Feras Almourfi,
Saleh Zaid Al-Muhsen,
Fahad Alsohime,
Saeed Al Turki,
Rana Hasanato,
Diederik van de Beek,
Andrea Biondi,
Laura Rachele Bettini,
Mariella D’Angiò,
Paolo Bonfanti,
Luisa Imberti,
Alessandra Sottini,
Simone Paghera,
Eugenia Quirós-Roldán,
Camillo Rossi,
Andrew J. Oler,
Miranda F. Tompkins,
Camille Alba,
Isabelle Vandernoot,
JeanChristophe Goffard,
Guillaume Smits,
Isabelle Migeotte,
Filomeen Haerynck,
Pere SolerPalacín,
Andrea Martín-Nalda,
Roger Colobrán,
PierreEmmanuel Morange,
Sevgi Keleş,
Fatma Çölkesen,
Tayfun Özçelık,
Kadriye Kart Yaşar,
Sevtap Şenoğlu,
Şemsi̇ Nur Karabela,
Carlos RodríguezGallego,
Giuseppe Novelli,
Sami Hraiech,
Yacine Tandjaoui-Lambiotte,
Xavier Duval,
Cédric Laouénan,
Andrew L. Snow,
Clifton L. Dalgard,
Joshua D. Milner,
Donald C. Vinh,
Trine H. Mogensen,
Nico Marr,
András N. Spaan,
Bertrand Boisson,
Stéphanie BoissonDupuis,
Jacinta Bustamante,
Anne Puel,
Michael J. Ciancanelli,
Isabelle Meyts,
Tom Maniatis,
Vassili Soumelis,
Ali Amara,
Michel C. Nussenzweig,
Adolfo Garcı́a-Sastre,
Florian Krammer,
Aurora Pujol,
Darragh Duffy,
Richard P. Lifton,
ShenYing Zhang,
Guy Gorochov,
Vivien Béziat,
Emmanuelle Jouanguy,
Vanessa SanchoShimizu,
Charles M. Rice,
Laurent Abel,
Luigi D. Notarangelo,
Aurélie Cobat,
Helen C. Su,
JeanLaurent Casanova,
Giuseppe Foti,
Giacomo Bellani,
Giuseppe Citerio,
Ernesto Contro,
Alberto Pesci,
Maria Grazia Valsecchi,
Marina Elena Cazzaniga,
Jorge Abad,
Sergio Aguilera,
Özge Metin Akcan,
Ilad Alavi Darazam,
Juan C. Aldave,
Miquel Alfonso Ramos,
Seyed Alireza Nadji,
Gülsüm Alkan,
Jérôme Allardet-Servent,
Luís M. Allende,
Laia Alsina,
MarieAlexandra Alyanakian,
Blanca Amador-Borrero,
Zahir Amoura,
Arnau Antolí,
Şevket Arslan,
Sophie TrouilletAssant,
Teresa Auguet,
Axelle Azot,
Fanny Bajolle,
Aurélie Baldolli,
Mayte Ballester,
Hagit Baris Feldman,
Benoı̂t Barrou,
Alexandra Beurton,
Agurtzane Bilbao,
Géraldine Blanchard-Rohner,
Ignacio Blanco,
Adeline Blandinières,
Daniel BlázquezGamero,
Markéta Bloomfield,
Mireia Bolívar-Prados,
Raphaël Borie,
Cédric Bosteels,
Ahmed Aziz Bousfiha,
Claire Bouvattier,
Oksana Boyarchuk,
Maria Rita PassosBueno,
Juan José Cáceres Agra,
Semra Calimli,
Ruggero Capra,
Maria Carrabba,
Carlos Casasnovas,
Marion Caséris,
Martin Castelle,
Francesco Castelli,
Martín Castillo de Vera,
Mateus Vidigal de Castro,
Émilie Catherinot,
Martin Chalumeau,
Bruno Charbit,
Matthew P. Cheng,
Père Clavé,
Bonaventura Clotet,
Anna Codina,
Fatih Çölkesen,
Cloé Comarmond,
David Dalmau,
D.R. Darley,
Nicolás Dauby,
Stéphane Dauger,
Loïc de Pontual,
Amin Dehban,
Geoffroy Delplancq,
Alexandre Demoule,
JeanLuc Diehl,
Stephanie Dobbelaere,
Sophie Durand,
Waleed Eldars,
Mohamed Elgamal,
Marwa H. Elnagdy,
Melike Emiroğlu,
Emine Hafize Erdeniz,
Selma Erol Aytekin,
Romain Euvrard,
Recep Evcen,
Fabio Gavarini,
Laurence Faivre,
Antonin Falck,
Muriel Fartoukh,
Morgane Faure,
Miguel FernándezArquero,
Carlos Flores,
Bruno François,
Victòria Fumadó,
Francesca Fusco,
Blanca GarcíaSolis,
Pascale Gaussem,
Juana Gil-Herrera,
Laurent Gilardin,
Monica Girona Alarcon,
Mònica GironaAlarcón,
Funda Gök,
Rafaela GonzálezMontelongo,
Antoine Guerder,
Yahya Gül,
Şükrü Nail Güner,
Marta Gut,
Jérôme Hadjadj,
Rabih Halwani,
Lennart Hammarström,
Nevin Hatipoğlu,
Elisa Hernández-Brito,
Cathérine Heijmans,
M.S. Holanda Peña,
Juan Pablo Horcajada,
Levi Hoste,
Eric A. J. Hoste,
L. Humbert,
Alejandro Iglesias,
Antonio Íñigo-Campos,
Matthieu Jamme,
María J. Arranz,
Iolanda Jordán,
Philippe G. Jorens,
Fikret Kanat,
Hasan Kapaklı,
Iskender Kara,
Adem Karbuz,
Yasemin Kendir Demirkol,
Adam Klocperk,
Zbigniew Król,
Paul Kuentz,
Mike Yat Wah Kwan,
JeanChristophe Lagier,
Bart N. Lambrecht,
YL Lau,
Fleur Le Bourgeois,
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Rafael LeónLópez,
Daniel Leung,
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Agnès Linglart,
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Catherine Lubetzki,
CharlesÉdouard Luyt,
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Majid Marjani,
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Andrea MartínNalda,
David Martínez Pueyo,
Javier MartínezPicado,
Iciar Marzana,
Alexis Mathian,
Larissa R. B. Matos,
Gail Matthews,
Julien Mayaux,
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Isabelle Melki,
Jean–François Méritet,
Mehdi Mezidi,
Maude Millereux,
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Clotilde Mircher,
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Abián Montesdeoca Melián,
Antonio Morales Martínez,
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Christophe Parizot,
Tiffany Pascreau,
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Sandra Pellegrini,
Rebeca Pérez de Diego,
Aurélien Philippe,
Laura PlanasSerra,
Dominique Ploin,
Julien Poissy,
Géraldine Poncelet,
Marie Pouletty,
Paul Quentric,
Didier Raoult,
AnneSophie Rebillat,
İsmail Reisli,
Pilar Ricart,
JeanChristophe Richard,
Nadia Rivet,
Jacques G. Rivière,
Gemma Rocamora Blanch,
Carlos Rodrigo,
Agustí RodríguezPalmero,
Carolina S. Romero,
Anya Rothenbühler,
Flore Rozenberg,
Maria Yolanda Ruiz del Prado,
Joan SabaterRiera,
Olivier Sanchez,
Silvia SánchezRamón,
Matthieu Schmidt,
Cyril Schweitzer,
Francesco Scolari,
Anna Šedivá,
Luis Seijó,
D. Sène,
Mikko Seppänen,
Alex Serra Ilovich,
Hans Slabbynck,
David M. Smadja,
Ali Sobh,
Xavier Solanich,
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Catherine Soler,
Yuri Stepanovskiy,
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Benjamin Terrier,
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Julie Toubiana,
Josep Trenado,
Jesús Troya,
Alessandra Tucci,
Matilde Valeria Ursini,
Y. Uzunhan,
P. Vabres,
Juan Valencia-Ramos,
Eva Van Braeckel,
Stijn Van de Velde,
Ana Maria Van Den Rym,
Jens Van Praet,
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Valentina Vélez-Santamaría,
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C Vilain,
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Niels van Mourik,
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Benedikt Preckel,
Jan M. Prins,
Jorinde Raasveld,
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Alex R. Schuurman,
Kim Sigaloff,
Marry R. Smit,
Cornelis Stijnis,
Willemke Stilma,
Charlotte E. Teunissen,
Patrick Thoral,
Anissa M. Tsonas,
Marc van der Valk,
Denise P. Veelo,
Alexander P. J. Vlaar,
Heder de Vries,
Michèle van Vugt,
W. Joost Wiersinga,
Dorien Wouters,
Aeilko H. Zwinderman,
Alessandro Aiuti,
Saleh Al Muhsen,
Mark S. Anderson,
Dusan Bogunovic,
Анастасія Бондаренко,
Petter Brodin,
Yenan T. Bryceson,
Carlos D. Bustamante,
Manish J. Butte,
Giorgio Casari,
Samya Chakravorty,
John Christodoulou,
Elizabeth T. Cirulli,
Antônio CondinoNeto,
Megan A. Cooper,
Alessia David,
Joseph L. DeRisi,
Murkesh Desai,
Beth A. Drolet,
Sara Espinosa,
José Luis Franco,
Peter K. Gregersen,
David Hagin,
Jim F. Heath,
Sarah E. Henrickson,
Elena W.Y. Hsieh,
Kohsuke Imai,
Yuval Itan,
Timokratis Karamitros,
Kai Kisand,
ChengLung Ku,
Yun Ling,
C. Lucas,
László Maródi,
Kristina Mironska,
Tomohiro Morio,
Antonio Novelli,
Cliona OʼFarrelly,
Satoshi Okada,
Anna M. Planas,
Carolina Prando,
Lluís QuintanaMurci,
Laurent Rénia,
Alessandra Renieri,
Vijay G. Sankaran,
Kelly M. Schiabor Barrett,
Mohammed Shahrooei,
Stuart G. Tangye,
Stuart E. Turvey,
K. M. Furkan Uddin,
Mohammed Uddin,
Sara E. Vazquez,
Horst von Bernuth,
Nicole L. Washington,
Paweł Zawadzki,
Jean-Laurent Casanova,
Huie Jing,
Wesley Tung,
Christopher R. Luthers,
Bradly M. Bauman,
Samantha Shafer,
Lixin Zheng,
Zinan Zhang,
Satoshi Kubo,
Samuel D. Chauvin,
Kazuyuki Meguro,
Elana Shaw,
Michael J. Lenardo,
Justin Lack,
Eric Karlins,
Daniel M. Hupalo,
J. K. Rosenberger,
Gauthaman Sukumar,
Matthew D. Wilkerson,
Xijun Zhang
Publication year - 2020
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.abd4570
Subject(s) - covid-19 , immunity , medicine , immunology , virology , immune system , infectious disease (medical specialty) , disease , outbreak
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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