Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
by Qian Zhang, Paul Bastard, Zhiyong Liu, JĂ©rĂ©mie Le Pen, Marcela Moncada-Velez, Jie Chen, Masato Ogishi, Ira K. D. Sabli, Stephanie Hodeib, Cecilia Korol, JĂ©rĂ©mie Rosain, Kaya Bilguvar, Junqiang Ye, Alexandre Bolze, Benedetta Bigio, Rui Yang, AndrĂ©s Augusto Arias, Qinhua Zhou, Yu Zhang, Fanny Onodi, Sarantis Korniotis, LĂ©a Karpf, Quentin Philippot, Marwa Chbihi, Lucie Bonnet-Madin, Karim Dorgham, NikaĂŻa Smith, William M. Schneider, Brandon S. Razooky, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Leen Moens, Ji Eun Han, Lazaro Lorenzo, Lucy Bizien, Philip Meade, Anna-Lena Neehus, Aileen Camille Ugurbil, AurĂ©lien Corneau, Gaspard Kerner, Peng Zhang, Franck Rapaport, Yoann Seeleuthner, Jeremy Manry, Cecile Masson, Yohann Schmitt, Agatha SchlĂĽter, Tom Le Voyer, Taushif Khan, Juan Li, Jacques Fellay, Lucie Roussel, Mohammad Shahrooei, Mohammed F. 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 J. Oler, Miranda F. 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, Ĺžemsi Nur Karabela, Carlos RodrĂguez-Gallego, Giuseppe Novelli, Sami Hraiech, Yacine Tandjaoui-Lambiotte, Xavier Duval, CĂ©dric LaouĂ©nan, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic Effort, NIAID-USUHS/TAGC COVID Immunity Group, Andrew L. Snow, Clifton L. Dalgard, Joshua D. Milner, Donald C. Vinh, Trine H. Mogensen, Nico Marr, András N. Spaan, Bertrand Boisson, StĂ©phanie Boisson-Dupuis, Jacinta Bustamante, Anne Puel, Michael J. Ciancanelli, Isabelle Meyts, Tom Maniatis, Vassili Soumelis, Ali Amara, Michel Nussenzweig, Adolfo GarcĂa-Sastre, Florian Krammer, Aurora Pujol, Darragh Duffy, Richard P. Lifton, Shen-Ying Zhang, Guy Gorochov, Vivien BĂ©ziat, Emmanuelle Jouanguy, Vanessa Sancho-Shimizu, Charles M. Rice, Laurent Abel, Luigi D. Notarangelo, AurĂ©lie Cobat, Helen C. Su, Jean-Laurent Casanova, Giuseppe Foti, Giacomo Bellani, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Jorge Abad, Sergio Aguilera-Albesa, Ozge Metin Akcan, Ilad Alavi Darazam, Juan C. Aldave, Miquel Alfonso Ramos, Seyed Alireza Nadji, Gulsum Alkan, Jerome Allardet-Servent, Luis M. Allende, Laia Alsina, Marie-Alexandra Alyanakian, Blanca Amador-Borrero, Zahir Amoura, Arnau AntolĂ, Sevket Arslan, Sophie Assant, Terese Auguet, Axelle Azot, Fanny Bajolle, AurĂ©lie Baldolli, Maite Ballester, Hagit Baris Feldman, Benoit Barrou, Alexandra Beurton, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blazquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, CĂ©dric Bosteels, Ahmed A. Bousfiha, Claire Bouvattier, Oksana Boyarchuk, Maria Rita P. Bueno, Jacinta Bustamante, Juan JosĂ© Cáceres Agra, Semra Calimli, Ruggero Capra, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Martin Castelle, Francesco Castelli, MartĂn Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Martin Chalumeau, Bruno Charbit, Matthew P. Cheng, Père ClavĂ©, Bonaventura Clotet, Anna Codina, Fatih Colkesen, Fatma Çölkesen, Roger Colobran, CloĂ© Comarmond, David Dalmau, David Ross Darley, Nicolas Dauby, StĂ©phane Dauger, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Alexandre Demoule, Jean-Luc Diehl, Stephanie Dobbelaere, Sophie Durand, Waleed Eldars, Mohamed Elgamal, Marwa H. Elnagdy, Melike Emiroglu, Emine Hafize Erdeniz, Selma Erol Aytekin, Romain Euvrard, Recep Evcen, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Carlos Flores, Bruno Francois, Victoria FumadĂł, Francesca Fusco, Blanca Garcia Solis, Pascale Gaussem, Juana Gil-Herrera, Laurent Gilardin, Monica Girona Alarcon, Mònica Girona-AlarcĂłn, Jean-Christophe Goffard, Funda Gok, Rafaela González-Montelongo, Antoine Guerder, Yahya Gul, Sukru Nail Guner, Marta Gut, JĂ©rĂ´me Hadjadj, Filomeen Haerynck, Rabih Halwani, Lennart Hammarström, Nevin Hatipoglu, Elisa Hernandez-Brito, CathĂ©rine Heijmans, MarĂa Soledad Holanda-Peña, Juan Pablo Horcajada, Levi Hoste, Eric Hoste, Sami Hraiech, Linda Humbert, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, MarĂa JesĂşs Arranz, Iolanda Jordan, Philippe Jorens, Fikret Kanat, Hasan Kapakli, Iskender Kara, Adem Karbuz, Kadriye Kart Yasar, Sevgi Keles, Yasemin Kendir Demirkol, Adam Klocperk, Zbigniew J. KrĂłl, Paul Kuentz, Yat Wah M. Kwan, Jean-Christophe Lagier, Bart N. Lambrecht, Yu-Lung Lau, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain LĂ©vy, Zhi Li, Agnes Linglart, Bart Loeys, JosĂ© M. Lorenzo-Salazar, CĂ©line Louapre, Catherine Lubetzki, Charles-Edouard Luyt, David C. Lye, Davood Mansouri, Majid Marjani, Jesus Marquez Pereira, Andrea Martin, David MartĂnez Pueyo, Javier Martinez-Picado, Iciar Marzana, Alexis Mathian, Larissa R. B. Matos, Gail V. Matthews, Julien Mayaux, Jean-Louis Mège, Isabelle Melki, Jean-François Meritet, Ozge Metin, Isabelle Meyts, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Abián Montesdeoca Melián, Antonio Morales Martinez, Pierre Morange, ClĂ©mence Mordacq, Guillaume Morelle, StĂ©phane Mouly, Adrián Muñoz-Barrera, Leslie Naesens, Cyril Nafati, JoĂŁo Farela Neves, Lisa F. P. Ng, Yeray Novoa Medina, Esmeralda Nuñez Cuadros, J. Gonzalo Ocejo-Vinyals, Zerrin Orbak, Mehdi Oualha, Tayfun Ă–zçelik, Qiang Pan-Hammarström, Christophe Parizot, Tiffany Pascreau, Estela Paz-Artal, Sandra Pellegrini, Rebeca PĂ©rez de Diego, AurĂ©lien Philippe, Quentin Philippot, Laura Planas-Serra, Dominique Ploin, Julien Poissy, GĂ©raldine Poncelet, Marie Pouletty, Paul Quentric, Didier Raoult, Anne-Sophie Rebillat, Ismail Reisli, Pilar Ricart, Jean-Christophe Richard, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora Blanch, Carlos Rodrigo, Carlos Rodriguez-Gallego, AgustĂ RodrĂguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Flore Rozenberg, Maria Yolanda Ruiz del Prado, Joan Sabater Riera, Oliver Sanchez, Silvia Sánchez-RamĂłn, Agatha Schluter, Matthieu Schmidt, Cyril E. Schweitzer, Francesco Scolari, Anna Sediva, Luis M. Seijo, Damien Sene, Sevtap Senoglu, Mikko R. J. Seppänen, Alex Serra Ilovich, Mohammad Shahrooei, Hans Slabbynck, David M. Smadja, Ali Sobh, Xavier Solanich Moreno, Jordi SolĂ©-Violán, Catherine Soler, Pere Soler-PalacĂn, Yuri Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Yacine Tandjaoui-Lambiotte, Jean-Luc Taupin, Simon J. Tavernier, Benjamin Terrier, Caroline Thumerelle, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Sophie Trouillet-Assant, JesĂşs Troya, Alessandra Tucci, Matilde Valeria Ursini, Yurdagul Uzunhan, Pierre Vabres, Juan Valencia-Ramos, Eva Van Braeckel, Stijn Van de Velde, Ana Maria Van Den Rym, Jens Van Praet, Isabelle Vandernoot, Hulya Vatansev, Valentina VĂ©lez-Santamaria, SĂ©bastien Viel, CĂ©dric Vilain, Marie E. Vilaire, Audrey Vincent, Guillaume Voiriot, Fanny Vuotto, Alper Yosunkaya, Barnaby E. Young, Fatih Yucel, Faiez Zannad, Mayana Zatz, Alexandre Belot, Christine Bole-Feysot, Stanislas Lyonnet, CĂ©cile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate, Laurent Abel, Claire Andrejak, 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-Cadiergues, Eric D’Ortenzio, Charlene Da Silveira, Marie-Pierre Debray, Dominique Deplanque, Diane Descamps, Mathilde DesvallĂ©es, Alpha Diallo, Alphonsine Diouf, CĂ©line Dorival, François Dubos, Xavier Duval, Philippine Eloy, Vincent VE Enouf, HĂ©lène Esperou, Marina Esposito-Farese, Manuel Etienne, Nadia Ettalhaoui, Nathalie Gault, Alexandre Gaymard, Jade Ghosn, Tristan Gigante, Isabelle Gorenne, JĂ©rĂ©mie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Salma Jaafoura, Ouifiya Kafif, Florentia Kaguelidou, Sabina Kali, Antoine Khalil, Coralie Khan, CĂ©dric LaouĂ©nan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, HervĂ© Le Nagard, François-Xavier Lescure, Yves LĂ©vy, Claire Levy-Marchal, Bruno Lina, Guillaume Lingas, Jean Christophe Lucet, Denis Malvy, Marina Mambert, France MentrĂ©, NoĂ©mie Mercier, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Marion Noret, Justine Pages, AurĂ©lie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadja, Ventzislava Petrov-Sanchez, Gilles Peytavin, Olivier Picone, Oriane PuĂ©chal, Manuel Rosa-Calatrava, BĂ©nĂ©dicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Caroline Semaille, Nassima Si Mohammed, Lysa Tagherset, Coralie Tardivon, Marie-Capucine Tellier, François TĂ©oulĂ©, Olivier Terrier, Jean-François Timsit, ThĂ©o Trioux, Christelle Tual, Sarah Tubiana, Sylvie van der Werf, NoĂ©mie Vanel, AurĂ©lie Veislinger, Benoit Visseaux, AurĂ©lie Wiedemann, Yazdan Yazdanpanah, Loubna Alavoine, Karine K. A. Amat, Sylvie Behillil, Julia Bielicki, Patricia Bruijning, Charles Burdet, Eric Caumes, Charlotte Charpentier, Bruno Coignard, Yolande Costa, Sandrine Couffin-Cadiergues, Florence Damond, Aline Dechanet, Christelle Delmas, Diane Descamps, Xavier Duval, Jean-Luc Ecobichon, Vincent Enouf, HĂ©lène EspĂ©rou, Wahiba Frezouls, Nadhira Houhou, Emila Ilic-Habensus, Ouifiya Kafif, John Kikoine, Quentin Le Hingrat, David Lebeaux, Anne Leclercq, Jonathan Lehacaut, Sophie Letrou, Bruno Lina, Jean-Christophe Lucet, Denis Malvy, Pauline Manchon, Milica Mandic, Mohamed Meghadecha, Justina Motiejunaite, Mariama Nouroudine, Valentine Piquard, Andreea Postolache, Caroline Quintin, Jade Rexach, LayidĂ© Roufai, Zaven Terzian, Michael Thy, Sarah Tubiana, Sylvie van der Werf, ValĂ©rie Vignali, Benoit Visseaux, Yazdan Yazdanpanah, Michiel van Agtmael, Anna Geke Algera, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Matthijs C. Brouwer, Sanne de Bruin, Marianna Bugiani, Esther Bulle, O. Chouchane, Alex Cloherty, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Bart Geerts, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. 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 Reijnders, Michiel Schinkel, Marcus J. Schultz, Alex Schuurman, Kim Sigaloff, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa Tsonas, Marc van der Valk, Denise Veelo, Alexander P.J. Vlaar, Heder de Vries, Michèle van Vugt, W. Joost Wiersinga, Dorien Wouters, A. H. (Koos) Zwinderman, Diederik van de Beek, Laurent Abel, Alessandro Aiuti, Saleh Al Muhsen, Fahd Al-Mulla, Mark S. Anderson, AndrĂ©s Augusto Arias, Hagit Baris Feldman, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish Butte, Giorgio Casari, Samya Chakravorty, John Christodoulou, Elizabeth Cirulli, Antonio Condino-Neto, Megan A. Cooper, Clifton L. Dalgard, Alessia David, Joseph L. DeRisi, Murkesh Desai, Beth A. Drolet, Sara Espinosa, Jacques Fellay, Carlos Flores, Jose Luis Franco, Peter K. Gregersen, Filomeen Haerynck, David Hagin, Rabih Halwani, Jim Heath, Sarah E. Henrickson, Elena Hsieh, Kohsuke Imai, Yuval Itan, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davoud Mansouri, Laszlo Marodi, Isabelle Meyts, Joshua Milner, Kristina Mironska, Trine Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O’Farrelly, Satoshi Okada, Tayfun Ozcelik, Rebeca Perez de Diego, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Laurent Renia, Alessandra Renieri, Carlos RodrĂguez-Gallego, Vanessa Sancho-Shimizu, Vijay Sankaran, Kelly Schiabor Barrett, Mohammed Shahrooei, Andrew Snow, Pere Soler-PalacĂn, András N. Spaan, Stuart Tangye, Stuart Turvey, Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Sara E. Vazquez, Donald C. Vinh, Horst von Bernuth, Nicole Washington, Pawel Zawadzki, Helen C. Su, 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 Lenardo, Justin Lack, Eric Karlins, Daniel M. Hupalo, John Rosenberger, Gauthaman Sukumar, Matthew D. Wilkerson, Xijun Zhang
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