Autoantibodies against type I IFNs in patients with life-threatening COVID-19
Authors: Bastard Paul , Rosen Lindsey B. , Zhang Qian , Michailidis Eleftherios , Hoffmann Hans-Heinrich , Zhang Yu , Dorgham Karim , Philippot Quentin , Rosain Jérémie , Béziat Vivien , Manry Jérémy , Shaw Elana , Haljasmägi Liis , Peterson Pärt , Lorenzo Lazaro , Bizien Lucy , Trouillet-Assant Sophie , Dobbs Kerry , de Jesus Adriana Almeida , Belot Alexandre , Kallaste Anne , Catherinot Emilie , Tandjaoui-Lambiotte Yacine , Le Pen Jeremie , Kerner Gaspard , Bigio Benedetta , Seeleuthner Yoann , Yang Rui , Bolze Alexandre , Spaan András N. , Delmonte Ottavia M. , Abers Michael S. , Aiuti Alessandro , Casari Giorgio , Lampasona Vito , Piemonti Lorenzo , Ciceri Fabio , Bilguvar Kaya , Lifton Richard P. , Vasse Marc , Smadja David M. , Migaud Mélanie , Hadjadj Jérome , Terrier Benjamin , Duffy Darragh , Quintana-Murci Lluis , van de Beek Diederik , Roussel Lucie , Vinh Donald C. , Tangye Stuart G. , Haerynck Filomeen , Dalmau David , Martinez-Picado Javier , Brodin Petter , Nussenzweig Michel C. , Boisson-Dupuis Stéphanie , Rodríguez-Gallego Carlos , Vogt Guillaume , Mogensen Trine H. , Oler Andrew J. , Gu Jingwen , Burbelo Peter D. , Cohen Jeffrey I. , Biondi Andrea , Bettini Laura Rachele , D'Angio Mariella , Bonfanti Paolo , Rossignol Patrick , Mayaux Julien , Rieux-Laucat Frédéric , Husebye Eystein S. , Fusco Francesca , Ursini Matilde Valeria , Imberti Luisa , Sottini Alessandra , Paghera Simone , Quiros-Roldan Eugenia , Rossi Camillo , Castagnoli Riccardo , Montagna Daniela , Licari Amelia , Marseglia Gian Luigi , Duval Xavier , Ghosn Jade ,   HGID Lab,   NIAID-USUHS Immune Response to COVID Group,   COVID Clinicians,   COVID-STORM Clinicians,   Imagine COVID Group,   French COVID Cohort Study Group,   The Milieu Intérieur Consortium,   CoV-Contact Cohort,   Amsterdam UMC Covid-19 Biobank,   COVID Human Genetic Effort, Tsang John S. , Goldbach-Mansky Raphaela , Kisand Kai , Lionakis Michail S. , Puel Anne , Zhang Shen-Ying , Holland Steven M. , Gorochov Guy , Jouanguy Emmanuelle , Rice Charles M. , Cobat Aurélie , Notarangelo Luigi D. , Abel Laurent , Su Helen C. , Casanova Jean-Laurent , Arias Andrés Augusto , Boisson Bertrand , Boucherit Soraya , Bustamante Jacinta , Chbihi Marwa , Chen Jie , Chrabieh Maya , Kochetkov Tatiana , Le Voyer Tom , Liu Dana , Nemirovskaya Yelena , Ogishi Masato , Papandrea Dominick , Patissier Cécile , Rapaport Franck , Roynard Manon , Vladikine Natasha , Woollett Mark , Zhang Peng , Kashyap Anuj , Ding Li , Bosticardo Marita , Wang Qinlu , Ochoa Sebastian , Liu Hui , Chauvin Samuel D. , Stack Michael , Koroleva Galina , Bansal Neha , Dalgard Clifton L. , Snow Andrew L. , Abad Jorge , Aguilera-Albesa Sergio , Akcan Ozge Metin , Darazam Ilad Alavi , Aldave Juan C. , Ramos Miquel Alfonso , Nadji Seyed Alireza , Alkan Gulsum , Allardet-Servent Jerome , Allende Luis M. , Alsina Laia , Alyanakian Marie-Alexandra , Amador-Borrero Blanca , Amoura Zahir , Antolí Arnau , Arslan Sevket , Assant Sophie , Auguet Terese , Azot Axelle , Bajolle Fanny , Baldolli Aurélie , Ballester Maite , Feldman Hagit Baris , Barrou Benoit , Beurton Alexandra , Bilbao Agurtzane , Blanchard-Rohner Geraldine , Blanco Ignacio , Blandinières Adeline , Blazquez-Gamero Daniel , Bloomfield Marketa , Bolivar-Prados Mireia , Borie Raphael , Bousfiha Ahmed A. , Bouvattier Claire , Boyarchuk Oksana , Bueno Maria Rita P. , Bustamante Jacinta , Cáceres Agra Juan José , Calimli Semra , Capra Ruggero , Carrabba Maria , Casasnovas Carlos , Caseris Marion , Castelle Martin , Castelli Francesco , de Vera Martín Castillo , Castro Mateus V. , Catherinot Emilie , Chalumeau Martin , Charbit Bruno , Cheng Matthew P. , Clavé Père , Clotet Bonaventura , Codina Anna , Colkesen Fatih , Colkesen Fatma , Colobran Roger , Comarmond Cloé , Corsico Angelo G. , Dalmau David , Darley David Ross , Dauby Nicolas , Dauger Stéphane , de Pontual Loic , Dehban Amin , Delplancq Geoffroy , Demoule Alexandre , Di Sabatino Antonio , Diehl Jean-Luc , Dobbelaere Stephanie , Durand Sophie , Eldars Waleed , Elgamal Mohamed , Elnagdy Marwa H. , Emiroglu Melike , Erdeniz Emine Hafize , Aytekin Selma Erol , Euvrard Romain , Evcen Recep , Fabio Giovanna , Faivre Laurence , Falck Antonin , Fartoukh Muriel , Faure Morgane , Arquero Miguel Fernandez , Flores Carlos , Francois Bruno , Fumadó Victoria , Fusco Francesca , Solis Blanca Garcia , Gaussem Pascale , Gil-Herrera Juana , Gilardin Laurent , Alarcon Monica Girona , Girona-Alarcón Mónica , Goffard Jean-Christophe , Gok Funda , González-Montelongo Rafaela , Guerder Antoine , Gul Yahya , Guner Sukru Nail , Gut Marta , Hadjadj Jérôme , Haerynck Filomeen , Halwani Rabih , Hammarström Lennart , Hatipoglu Nevin , Hernandez-Brito Elisa , Holanda-Peña María Soledad , Horcajada Juan Pablo , Hraiech Sami , Humbert Linda , Iglesias Alejandro D. , Íñigo-Campos Antonio , Jamme Matthieu , Arranz María Jesús , Jordan Iolanda , Kanat Fikret , Kapakli Hasan , Kara Iskender , Karbuz Adem , Yasar Kadriye Kart , Keles Sevgi , Demirkol Yasemin Kendir , Klocperk Adam , Król Zbigniew J. , Kuentz Paul , Kwan Yat Wah M. , Lagier Jean-Christophe , Lau Yu-Lung , Le Bourgeois Fleur , Leo Yee-Sin , Lopez Rafael Leon , Leung Daniel , Levin Michael , Levy Michael , Lévy Romain , Li Zhi , Linglart Agnes , Lorenzo-Salazar José M. , Louapre Céline , Lubetzki Catherine , Luyt Charles-Edouard , Lye David C. , Mansouri Davood , Marjani Majid , Pereira Jesus Marquez , Martin Andrea , Pueyo David Martínez , Martinez-Picado Javier , Marzana Iciar , Mathian Alexis , Matos Larissa R. B. , Matthews Gail V. , Mayaux Julien , Mège Jean-Louis , Melki Isabelle , Meritet Jean-François , Metin Ozge , Meyts Isabelle , Mezidi Mehdi , Migeotte Isabelle , Millereux Maude , Mirault Tristan , Mircher Clotilde , Mirsaeidi Mehdi , Melián Abián Montesdeoca , Martinez Antonio Morales , Morange Pierre , Mordacq Clémence , Morelle Guillaume , Mouly Stéphane , Muñoz-Barrera Adrián , Nafati Cyril , Neves João Farela , Ng Lisa F. P. , Medina Yeray Novoa , Cuadros Esmeralda Nuñez , Ocejo-Vinyals J. Gonzalo , Orbak Zerrin , Oualha Mehdi , Özçelik Tayfun , Hammarström Qiang Pan , Parizot Christophe , Pascreau Tiffany , Paz-Artal Estela , de Diego Rebeca Pérez , Philippe Aurélien , Philippot Quentin , Planas-Serra Laura , Ploin Dominique , Poissy Julien , Poncelet Géraldine , Pouletty Marie , Quentric Paul , Raoult Didier , Rebillat Anne-Sophie , Reisli Ismail , Ricart Pilar , Richard Jean-Christophe , Rivet Nadia , Rivière Jacques G. , Blanch Gemma Rocamora , Rodrigo Carlos , Rodriguez-Gallego Carlos , Rodríguez-Palmero Agustí , Romero Carolina Soledad , Rothenbuhler Anya , Rozenberg Flore , Ruiz del Prado Maria Yolanda , Riera Joan Sabater , Sanchez Oliver , Sánchez-Ramón Silvia , Schluter Agatha , Schmidt Matthieu , Schweitzer Cyril E. , Scolari Francesco , Sediva Anna , Seijo Luis M. , Sene Damien , Senoglu Sevtap , Seppänen Mikko R. J. , Ilovich Alex Serra , Shahrooei Mohammad , Smadja David , Sobh Ali , Moreno Xavier Solanich , Solé-Violán Jordi , Soler Catherine , Soler-Palacín Pere , Stepanovskiy Yuri , Stoclin Annabelle , Taccone Fabio , Tandjaoui-Lambiotte Yacine , Taupin Jean-Luc , Tavernier Simon J. , Terrier Benjamin , Thumerelle Caroline , Tomasoni Gabriele , Toubiana Julie , Alvarez Josep Trenado , Trouillet-Assant Sophie , Troya Jesús , Tucci Alessandra , Ursini Matilde Valeria , Uzunhan Yurdagul , Vabres Pierre , Valencia-Ramos Juan , Van Den Rym Ana Maria , Vandernoot Isabelle , Vatansev Hulya , Vélez-Santamaria Valentina , Viel Sébastien , Vilain Cédric , Vilaire Marie E. , Vincent Audrey , Voiriot Guillaume , Vuotto Fanny , Yosunkaya Alper , Young Barnaby E. , Yucel Fatih , Zannad Faiez , Zatz Mayana , Belot Alexandre , Foti Giuseppe , Bellani Giacomo , Citerio Giuseppe , Contro Ernesto , Pesci Alberto , Valsecchi Maria Grazia , Cazzaniga Marina , Bole-Feysot Christine , Lyonnet Stanislas , Masson Cécile , Nitschke Patrick , Pouliet Aurore , Schmitt Yoann , Tores Frederic , Zarhrate Mohammed , Abel Laurent , Andrejak Claire , Angoulvant François , Bachelet Delphine , Basmaci Romain , Behillil Sylvie , Beluze Marine , Benkerrou Dehbia , Bhavsar Krishna , Bompart François , Bouadma Lila , Bouscambert Maude , Caralp Mireille , Cervantes-Gonzalez Minerva , Chair Anissa , Coelho Alexandra , Couffignal Camille , Couffin-Cadiergues Sandrine , D’ortenzio Eric , Da Silveira Charlene , Debray Marie-Pierre , Deplanque Dominique , Descamps Diane , Desvallées Mathilde , Diallo Alpha , Diouf Alphonsine , Dorival Céline , Dubos François , Duval Xavier , Eloy Philippine , Enouf Vincent V. E. , Esperou Hélène , Esposito-Farese Marina , Etienne Manuel , Ettalhaoui Nadia , Gault Nathalie , Gaymard Alexandre , Ghosn Jade , Gigante Tristan , Gorenne Isabelle , Guedj Jérémie , Hoctin Alexandre , Hoffmann Isabelle , Jaafoura Salma , Kafif Ouifiya , Kaguelidou Florentia , Kali Sabina , Khalil Antoine , Khan Coralie , Laouénan Cédric , Laribi Samira , Le Minh , Le Hingrat Quentin , Le Mestre Soizic , Le Nagard Hervé , Lescure François-Xavier , Lévy Yves , Levy-Marchal Claire , Lina Bruno , Lingas Guillaume , Lucet Jean Christophe , Malvy Denis , Mambert Marina , Mentré France , Mercier Noémie , Meziane Amina , Mouquet Hugo , Mullaert Jimmy , Neant Nadège , Noret Marion , Pages Justine , Papadopoulos Aurélie , Paul Christelle , Peiffer-Smadja Nathan , Petrov-Sanchez Ventzislava , Peytavin Gilles , Picone Olivier , Puéchal Oriane , Rosa-Calatrava Manuel , Rossignol Bénédicte , Rossignol Patrick , Roy Carine , Schneider Marion , Semaille Caroline , Mohammed Nassima Si , Tagherset Lysa , Tardivon Coralie , Tellier Marie-Capucine , Téoulé François , Terrier Olivier , Timsit Jean-François , Treoux Théo , Tual Christelle , Tubiana Sarah , van der Werf Sylvie , Vanel Noémie , Veislinger Aurélie , Visseaux Benoit , Wiedemann Aurélie , Yazdanpanah Yazdan , Abel Laurent , Alcover Andres , Aschard Hugues , Astrom Kalla , Bousso Philippe , Bruhns Pierre , Cumano Ana , Demangel Caroline , Deriano Ludovic , Di Santo James , Dromer Françoise , Eberl Gérard , Enninga Jost , Fellay Jacques , Gomperts-Boneca Ivo , Hasan Milena , Hercberg Serge , Lantz Olivier , Mouquet Hugo , Patin Etienne , Pellegrini Sandra , Pol Stanislas , Rausell Antonio , Rogge Lars , Sakuntabhai Anavaj , Schwartz Olivier , Schwikowski Benno , Shorte Spencer , Tangy Frédéric , Toubert Antoine , Touvier Mathilde , Ungeheuer Marie-Noëlle , Albert Matthew L. , Duffy Darragh , Quintana-Murci Lluis , Alavoine Loubna , Amat Karine K. A. , Behillil Sylvie , Bielicki Julia , Bruijning Patricia , Burdet Charles , Caumes Eric , Charpentier Charlotte , Coignard Bruno , Costa Yolande , Couffin-Cadiergues Sandrine , Damond Florence , Dechanet Aline , Delmas Christelle , Descamps Diane , Duval Xavier , Ecobichon Jean-Luc , Enouf Vincent , Espérou Hélène , Frezouls Wahiba , Houhou Nadhira , Ilic-Habensus Emila , Kafif Ouifiya , Kikoine John , Le Hingrat Quentin , Lebeaux David , Leclercq Anne , Lehacaut Jonathan , Letrou Sophie , Lina Bruno , Lucet Jean-Christophe , Malvy Denis , Manchon Pauline , Mandic Milica , Meghadecha Mohamed , Motiejunaite Justina , Nouroudine Mariama , Piquard Valentine , Postolache Andreea , Quintin Caroline , Rexach Jade , Roufai Layidé , Terzian Zaven , Thy Michael , Tubiana Sarah , van der Werf Sylvie , Vignali Valérie , Visseaux Benoit , Yazdanpanah Yazdan , van Agtmael Michiel , Algera Anna Geke , van Baarle Frank , Bax Diane , Beudel Martijn , Bogaard Harm Jan , Bomers Marije , Bos Lieuwe , Botta Michela , de Brabander Justin , Bree Godelieve , Brouwer Matthijs C. , de Bruin Sanne , Bugiani Marianna , Bulle Esther , Chouchane Osoul , Cloherty Alex , Elbers Paul , Fleuren Lucas , Geerlings Suzanne , Geerts Bart , Geijtenbeek Theo , Girbes Armand , Goorhuis Bram , Grobusch Martin P. , Hafkamp Florianne , Hagens Laura , Hamann Jorg , Harris Vanessa , Hemke Robert , Hermans Sabine M. , Heunks Leo , Hollmann Markus W. , Horn Janneke , Hovius Joppe W. , de Jong Menno D. , Koning Rutger , van Mourik Niels , Nellen Jeaninne , Paulus Frederique , Peters Edgar , van der Poll Tom , Preckel Benedikt , Prins Jan M. , Raasveld Jorinde , Reijnders Tom , Schinkel Michiel , Schultz Marcus J. , Schuurman Alex , Sigaloff Kim , Smit Marry , Stijnis Cornelis S. , Stilma Willemke , Teunissen Charlotte , Thoral Patrick , Tsonas Anissa , van der Valk Marc , Veelo Denise , Vlaar Alexander P. J. , de Vries Heder , van Vugt Michèle , Wiersinga W. Joost , Wouters Dorien , Zwinderman A. H. (Koos) , van de Beek Diederik , Abel Laurent , Aiuti Alessandro , Al Muhsen Saleh , Al-Mulla Fahd , Anderson Mark S. , Arias Andrés Augusto , Feldman Hagit Baris , Bogunovic Dusan , Bolze Alexandre , Bondarenko Anastasiia , Bousfiha Ahmed A. , Brodin Petter , Bryceson Yenan , Bustamante Carlos D. , Butte Manish , Casari Giorgio , Chakravorty Samya , Christodoulou John , Cirulli Elizabeth , Condino-Neto Antonio , Cooper Megan A. , Dalgard Clifton L. , DeRisi Joseph L. , Desai Murkesh , Drolet Beth A. , Espinosa Sara , Fellay Jacques , Flores Carlos , Franco Jose Luis , Gregersen Peter K. , Haerynck Filomeen , Hagin David , Halwani Rabih , Heath Jim , Henrickson Sarah E. , Hsieh Elena , Imai Kohsuke , Itan Yuval , Karamitros Timokratis , Kisand Kai , Ku Cheng-Lung , Lau Yu-Lung , Ling Yun , Lucas Carrie L. , Maniatis Tom , Mansouri Davoud , Marodi Laszlo , Meyts Isabelle , Milner Joshua D. , Mironska Kristina , Mogensen Trine , Morio Tomohiro , Ng Lisa F. P. , Notarangelo Luigi D. , Novelli Giuseppe , Novelli Antonio , O'Farrelly Cliona , Okada Satoshi , Ozcelik Tayfun , de Diego Rebeca Perez , Planas Anna M. , Prando Carolina , Pujol Aurora , Quintana-Murci Lluis , Renia Laurent , Renieri Alessandra , Rodríguez-Gallego Carlos , Sancho-Shimizu Vanessa , Sankaran Vijay , Barrett Kelly Schiabor , Shahrooei Mohammed , Snow Andrew , Soler-Palacín Pere , Spaan András N. , Tangye Stuart , Turvey Stuart , Uddin Furkan , Uddin Mohammed J. , van de Beek Diederik , Vazquez Sara E. , Vinh Donald C. , von Bernuth Horst , Washington Nicole , Zawadzki Pawel , Su Helen C. , Casanova Jean-Laurent 
Published: September 2020

The genetics underlying severe COVID-19

The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang
et al.
used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard
et al.
identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy individuals. Together, these studies identify a means by which individuals at highest risk of life-threatening COVID-19 can be identified.

Science
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