Autoantibodies against type I IFNs in patients with life-threatening COVID-19

作者：Paul Bastard, Lindsey B. Rosen, Qian Zhang, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Yu Zhang, Karim Dorgham, Quentin Philippot, Jérémie Rosain, Vivien Béziat, Jérémy Manry, Elana Shaw, Liis Haljasmägi, Pärt Peterson, Lazaro Lorenzo, Lucy Bizien, Sophie Trouillet‐Assant, Kerry Dobbs, Adriana A. de Jesus, Alexandre Bélot, Anne Kallaste, Émilie Catherinot, Yacine Tandjaoui-Lambiotte, Jérémie Le Pen, Gaspard Kerner, Benedetta Bigio, Yoann Seeleuthner, Rui Yang, Alexandre Bolze, András N. Spaan, Ottavia M. Delmonte, Michael S. Abers, Alessandro Aiuti, Giorgio Casari, Vito Lampasona, Lorenzo Piemonti, Fabio Ciceri, Kaya Bilgüvar, Richard P. Lifton, Marc Vasse, David M. Smadja, Mélanie Migaud, Jérôme Hadjadj, Benjamin Terrier, Darragh Duffy, Lluís Quintana‐Murci, Diederik van de Beek, Lucie Roussel, Donald C. Vinh, Stuart G. Tangye, Filomeen Haerynck, David Dalmau, Javier Martínez‐Picado, Petter Brodin, Michel C. Nussenzweig, Stéphanie Boisson‐Dupuis, Carlos Rodríguez-Gallego, Guillaume Vogt, Trine H. Mogensen, Andrew J. Oler, Jingwen Gu, Peter D. Burbelo, Jeffrey I. Cohen, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angiò, Paolo Bonfanti, Patrick Rossignol, Julien Mayaux, Frédéric Rieux‐Laucat, Eystein S. Husebye, Francesca Fusco, Matilde Valeria Ursini, Luisa Imberti, Alessandra Sottini, Simone Paghera, Eugenia Quirós-Roldán, Camillo Rossi, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, Gian Luigi Marseglia, Xavier Duval, Jade Ghosn, HGID Lab, NIAID-USUHS Immune Response to COVID Group, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic Effort, John S. Tsang, Raphaela Goldbach‐Mansky, Kai Kisand, Michail S. Lionakis, Anne Puel, Shen‐Ying Zhang, Steven M. Holland, Guy Gorochov, Emmanuelle Jouanguy, Charles M. Rice, Aurélie Cobat, Luigi D. Notarangelo, Laurent Abel, Helen C. Su, Jean‐Laurent Casanova, Andrés A. Arias, Bertrand Boisson, Soraya Boucherit, Jacinta Bustamante, Marwa Chbihi, Jie Chen, Maya Chrabieh, Tatiana Kochetkov, Tom Le Voyer, Dana Liu, Yelena Nemirovskaya, Masato Ogishi, Dominick Papandrea, Cécile Patissier, Franck Rapaport, Manon Roynard, Natasha Vladikine, Mark Woollett, Peng Zhang, Anuj Kashyap, Li Ding, Marita Bosticardo, Qinlu Wang, Sebastian Ochoa, Hui Liu, Samuel D. Chauvin, Michael Stack, Galina Koroleva, Neha Bansal, Clifton L. Dalgard, Andrew L. Snow, 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, Marie‐Alexandra Alyanakian, Blanca Amador-Borrero, Zahir Amoura, Arnau Antolí, Şevket Arslan, Sophie Assant, Terese 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 Blázquez‐Gamero, Markéta Bloomfield, Mireia Bolívar-Prados, Raphaël Borie, Ahmed Aziz Bousfiha, Claire Bouvattier, Oksana Boyarchuk, Maria Rita Passos‐Bueno, Jacinta Bustamante, 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, Emilie Catherinot, Martin Chalumeau, Bruno Charbit, Matthew Pellan Cheng, Père Clavé, Bonaventura Clotet, Anna Codina, Fatih Çölkesen, Fatma Çölkesen, Roger Colobrán, Cloé Comarmond, Angelo Guido Corsico, David Dalmau, D.R. Darley, Nicolás Dauby, Stéphane Dauger, Loïc de Pontual, Amin Dehban, Geoffroy Delplancq, Alexandre Demoule, Antonio Di Sabatino, Jean‐Luc Diehl, Stephanie Dobbelaere, Sophie Durand, Waleed Eldars, Mohamed Elgamal, Marwa H. Elnagdy, Melike Emiroğlu, Emine Hafize Erdeniz, Selma Erol Aytekin, Romain Euvrard, Recep Evcen, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernández‐Arquero, Carlos Flores, Bruno François, Victòria Fumadó, Francesca Fusco, Blanca García‐Solis, Pascale Gaussem, Juana Gil-Herrera, Laurent Gilardin, Mònica Girona Alarcón, Mònica Girona‐Alarcón, Jean‐Christophe Goffard, Funda Gök, Rafaela González‐Montelongo, Antoine Guerder, Yahya Gül, Şükrü Nail Güner, Marta Gut, Jérôme Hadjadj, Filomeen Haerynck, Rabih Halwani, Lennart Hammarström, Nevin Hatipoğlu, Elisa Hernández-Brito, María Soledad Holanda-Peña, Juan Pablo Horcajada, Sami Hraiech, L. Humbert, Alejandro Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María J. Arranz, Iolanda Jordán, Fikret Kanat, Hasan Kapaklı, İskender Kara, Adem Karbuz, Kadriye Kart Yaşar, Sevgi Keleş, Yasemin Kendir Demirkol, Adam Klocperk, Zbigniew Król, Paul Kuentz, Yat Wah M. Kwan, Jean‐Christophe Lagier, YL Lau, Fleur Le Bourgeois, Yee‐Sin Leo, Rafael León‐López, Daniel Leung, Michael Levin, Michaël Levy, Romain Lévy, Zhi Li, Agnès Linglart, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Charles‐Édouard Luyt, David Chien Lye, Davood Mansouri, Majid Marjani, Jesus Marquez Pereira, Andrea Martín‐Nalda, David Martínez Pueyo, Javier Martínez‐Picado, Iciar Marzana, Alexis Mathian, Larissa R. B. Matos, Gail Matthews, Julien Mayaux, Jean‐Louis Mège, Isabelle Melki, Jean–François Méritet, Özge Metin Akcan, Isabelle Meyts, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Abián Montesdeoca Melián, Antonio Morales Martínez, Pierre‐Emmanuel Morange, C. Mordacq, Guillaume Morelle, Stéphane Mouly, Adrián Muñoz‐Barrera, Cyril Nafati, João Farela Neves, Lisa F. P. Ng, Yeray Nóvoa Medina, Esmeralda Núñez Cuadros, J. Gonzalo Ocejo‐Vinyals, Zerrin Orbak, Mehdi Oualha, Tayfun Özçelık, Qiang Pan‐Hammarström, Christophe Parizot, Tiffany Pascreau, Estela Paz‐Artal, Rebeca Pérez de Diego, Aurélien Philippe, Quentin Philippot, Laura Planas‐Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Marie Pouletty, Paul Quentric, Didier Raoult, Anne‐Sophie Rebillat, İsmail Reisli, Pilar Ricart, Jean‐Christophe Richard, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora Blanch, Carlos Rodrigo, Carlos Rodríguez‐Gallego, Agustí Rodríguez‐Palmero, Carolina S. Romero, Anya Rothenbühler, Flore Rozenberg, María Yolanda Ruiz del Prado, Joan Sabater‐Riera, Oliver Sanchez, Silvia Sánchez‐Ramón, Agatha Schlüter, Matthieu Schmidt, Cyril Schweitzer, Francesco Scolari, Anna Šedivá, Luis Seijó, D. Sène, Sevtap Şenoğlu, Mikko Seppänen, Alex Serra Ilovich, Mohammad Shahrooei, David M. Smadja, Ali Sobh, Xavier Solanich Moreno, Jordi Solé‐Violán, Catherine Soler, Pere Soler‐Palacín, Yuri Stepanovskiy, Annabelle Stoclin, Fabio Silvio Taccone, Yacine Tandjaoui-Lambiotte, Jean‐Luc Taupin, Simon J. Tavernier, Benjamin Terrier, C. Thumerelle, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Sophie Trouillet-Assant, Jesús Troya, Alessandra Tucci, Matilde Valeria Ursini, Y. Uzunhan, P. Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Hülya Vatansev, Valentina Vélez-Santamaría, Sébastien Viel, Cédric Vilain, Marie E. Vilaire, Audrey Vincent, Guillaume Voiriot, Fanny Vuotto, Alper Yosunkaya, Barnaby Edward Young, Fatih Yücel, Faı̈ez Zannad, Mayana Zatz, Alexandre Bélot, Giuseppe Foti, Giacomo Bellani, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Elena Cazzaniga, Christine Bôle‐Feysot, Stanislas Lyonnet, Cécile Masson, Patrick Nitschké, Aurore Pouliet, Yoann Schmitt, Frédéric Torès, Mohammed Zarhrate, Laurent Abel, Claire Andréjak, François Angoulvant, Delphine Bachelet, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, François Bompart, Lila Bouadma, Maude Bouscambert, Mireille Caralp, Minerva Cervantes-Gonzalez, Anissa Chair, Alexandra Coelho, Camille Couffignal, Sandrine Couffin-Cadièrgues, Éric D’Ortenzio, Charlène Da Silveira, Marie‐Pierre Debray, Dominique Deplanque, Diane Descamps, Mathilde Desvallées, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Xavier Duval, Philippine Eloy, Vincent Enouf, Hélène Espérou, Marina Esposito‐Farèse, Manuel Etienne, Nadia Ettalhaoui, Nathalie Gault, Alexandre Gaymard, Jade Ghosn, Tristan Gigante, Isabelle Gorenne, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Salma Jaafoura, Ouifiya Kafif, Florentia Kaguelidou, Sabina Kali, Antoine Khalil, Coralie Khan, Cédric Laouenan, Samira Laribi, Minh Quan Lê, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François‐Xavier Lescure, Yves Lévy, Claire Lévy‐Marchal, Bruno Lina, Guillaume Lingas, Jean Christophe Lucet, Denis Malvy, Marina Mambert, France Mentré, Noémie Mercier, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Néant, Marion Noret, Justine Pages, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer‐Smadja, Ventzislava Petrov–Sanchez, Gilles Peytavin, Olivier Picone, Oriane Puéchal, Manuel Rosa‐Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Caroline Semaille, Nassima Si Mohammed, Lysa Tagherset, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean‐François Timsit, Théo Treoux, Christelle Tual, Sarah Tubiana, Sylvie van der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanah, Laurent Abel, Andrés Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James P. Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Serge Herçberg, Olivier Lantz, Hugo Mouquet, Étienne Patin, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie‐Noëlle Ungeheuer, Matthew L. Albert, Darragh Duffy, Lluís Quintana‐Murci, Loubna Alavoine, Karine K. A. Amat, Sylvie Behillil, Julia Bielicki, Patricia Bruijning‐Verhagen, Charles Burdet, Éric Caumes, Charlotte Charpentier, B. 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Brouwer, Sanne de Bruin, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Paul Elbers, Lucas M. Fleuren, Suzanne E. Geerlings, Bart F. Geerts, Theo Geijtenbeek, Armand R. J. Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura A. Hagens, Jörg Hamann, Vanessa Harris, Robert Hemke, Sabine Hermans, Leo Heunks, Markus W. Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Niels van Mourik, Jeaninne Nellen, Frederique Paulus, Edgar Peters, Tom van der Poll, Benedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom D. Y. Reijnders, Michiel Schinkel, Marcus J. Schultz, 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, Diederik van de Beek, Laurent Abel, Alessandro Aiuti, Saleh Al Muhsen, Fahd Al‐Mulla, Mark S. Anderson, Andrés A. Arias, Hagit Baris Feldman, Dusan Bogunovic, Alexandre Bolze, Анастасія Бондаренко, Ahmed Aziz Bousfiha, Petter Brodin, Yenan T. Bryceson, Carlos D. Bustamante, Manish J. Butte, Giorgio Casari, Samya Chakravorty, John Christodoulou, Elizabeth T. Cirulli, Antônio Condino‐Neto, Megan A. Cooper, Clifton L. Dalgard, Joseph L. DeRisi, Murkesh Desai, Beth A. Drolet, Sara Espinosa, Jacques Fellay, Carlos Flores, José Luis Franco, Peter K. Gregersen, Filomeen Haerynck, David Hagin, Rabih Halwani, Jim F. Heath, Sarah E. Henrickson, Elena W.Y. Hsieh, Kohsuke Imai, Yuval Itan, Timokratis Karamitros, Kai Kisand, Cheng‐Lung Ku, YL Lau, Yun Ling, C. Lucas, Tom Maniatis, Davoud Mansouri, László Maródi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Giuseppe Novelli, Antonio Novelli, Cliona O’Farrelly, Satoshi Okada, Tayfun Özçelık, Rebeca Pérez de Diego, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluís Quintana‐Murci, Laurent Rénia, Alessandra Renieri, Carlos Rodríguez-Gallego, Vanessa Sancho‐Shimizu, Vijay G. Sankaran, Kelly M. Schiabor Barrett, Mohammed Shahrooei, Andrew L. Snow, Pere Soler‐Palacín, András N. Spaan, Stuart G. Tangye, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed Uddin, Diederik van de Beek, Sara E. Vazquez, Donald C. Vinh, Horst von Bernuth, Nicole Washington, Paweł Zawadzki, Helen C. Su, Jean‐Laurent Casanova · 发表于：Science · 年份：2020 · DOI：10.1126/science.abd4585 · 被引用次数：2882 · 研究领域：SARS-CoV-2 and COVID-19 Research、Diabetes and associated disorders、COVID-19 Clinical Research Studies

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 , this issue p. eabd4570 , p. eabd4585 ; see also p. 404