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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‐Vélez, 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 Bonnet‐Madin, 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, Anna‐Lena Neehus, Aileen 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, 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’Angiò, Paolo Bonfanti, Luisa Imberti, Alessandra Sottini, Simone Paghera, Eugenia Quirós-Roldán, Camillo Rossi, Andrew J. Oler, Miranda F. Tompkins, Camille Alba, Isabelle Vandernoot, Jean‐Christophe Goffard, Guillaume Smits, Isabelle Migeotte, Filomeen Haerynck, Pere Soler‐Palacín, Andrea Martín-Nalda, Roger Colobrán, Pierre‐Emmanuel Morange, Sevgi Keleş, Fatma Çölkesen, Tayfun Özçelık, Kadriye Kart Yaşar, Sevtap Şenoğlu, Şemsi̇ Nur Karabela, Carlos Rodríguez‐Gallego, Giuseppe Novelli, Sami Hraiech, Yacine Tandjaoui-Lambiotte, Xavier Duval, Cédric Laouenan, Andrew L. Snow, Clifton L. Dalgard, Joshua D. Milner, Donald C. Vinh, Trine H. Mogensen, Nico Marr, Bertrand Boisson, Stéphanie Boisson‐Dupuis, Jacinta Bustamante, Anne Puel, Michael J. Ciancanelli, Tom Maniatis, Vassili Soumelis, Ali Amara, Michel C. Nussenzweig, Adolfo García‐Sastre, Florian Krammer, Aurora Pujol, Darragh Duffy, Richard P. Lifton, Shen‐Ying Zhang, Guy Gorochov, Vivien Béziat, Emmanuelle Jouanguy, Vanessa Sancho‐Shimizu, Charles M. Rice, Luigi D. Notarangelo, Aurélie Cobat, Helen C. Su, Jean‐Laurent 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, Marie‐Alexandra Alyanakian, Blanca Amador-Borrero, Zahir Amoura, Arnau Antolí, Şevket Arslan, Sophie Trouillet‐Assant, 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, Cédric Bosteels, Claire Bouvattier, Oksana Boyarchuk, Maria Rita Passos‐Bueno, 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, 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, Funda Gök, Rafaela González‐Montelongo, Antoine Guerder, Yahya Gül, Şükrü Nail Güner, Jérôme Hadjadj, Rabih Halwani, Lennart Hammarström, Nevin Hatipoğlu, Elisa Hernández-Brito, Cathérine Heijmans, María Soledad 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, İskender Kara, Adem Karbuz, Yasemin Kendir Demirkol, Adam Klocperk, Zbigniew Król, Paul Kuentz, Jean‐Christophe Lagier, Bart N. Lambrecht, YL Lau, Fleur Le Bourgeois, Yee‐Sin Leo, Rafael León‐López, Daniel Leung, Michael Levin, Michaël Levy, Romain Lévy, Zhi Li, Agnès Linglart, Bart Loeys, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Charles‐Édouard Luyt, David Chien Lye, 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, Mehdi Mezidi, Maude Millereux, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Abián Montesdeoca Melián, Antonio Morales Martínez, C. Mordacq, Guillaume Morelle, Stéphane Mouly, Adrián Muñoz‐Barrera, Leslie Naesens, Cyril Nafati, João Farela Neves, Yeray Nóvoa Medina, Esmeralda Núñez Cuadros, J. Gonzalo Ocejo‐Vinyals, Zerrin Orbak, Mehdi Oualha, Qiang Pan‐Hammarström, Christophe Parizot, Tiffany Pascreau, Estela Paz‐Artal, Sandra Pellegrini, Rebeca Pérez de Diego, Aurélien Philippe, 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, Agustí Rodríguez‐Palmero, Carolina S. Romero, Anya Rothenbühler, Flore Rozenberg, María Yolanda Ruiz del Prado, Joan Sabater‐Riera, Silvia Sánchez‐Ramón, Matthieu Schmidt, Cyril Schweitzer, Francesco Scolari, Anna Šedivá, Luis Seijó, D. Sène, Mikko Seppänen, Alex Serra Ilovich, Hans Slabbynck, David M. Smadja, Ali Sobh, Jordi Solé‐Violán, Catherine Soler, Yuri Stepanovskiy, Annabelle Stoclin, Fabio Silvio Taccone, Jean‐Luc Taupin, Simon J. Tavernier, Benjamin Terrier, C. Thumerelle, Gabriele Tomasoni, Julie Toubiana, 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, Hülya Vatansev, Valentina Vélez-Santamaría, Sébastien Viel, Marie E. Vilaire, Audrey Vincent, Guillaume Voiriot, Fanny Vuotto, Alper Yosunkaya, Barnaby Edward Young, Fatih Yücel, Faı̈ez Zannad, Mayana Zatz, Alexandre Bélot, Christine Bôle‐Feysot, Stanislas Lyonnet, Patrick Nitschké, Aurore Pouliet, Yoann Schmitt, Frédéric Torès, Mohammed Zarhrate, 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, Mathilde Desvallées, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, 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, Samira Laribi, Minh Quan Lê, Soizic Le Mestre, Hervé Le Nagard, François‐Xavier Lescure, Yves Lévy, Claire Lévy‐Marchal, 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 Trioux, Christelle Tual, Sarah Tubiana, Sylvie van der Werf, Noémie Vanel, Aurélie Veislinger, Benoît Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanah, Loubna Alavoine, Karine K. A. Amat, Julia Bielicki, Patricia Bruijning‐Verhagen, Charles Burdet, Éric Caumes, Charlotte Charpentier, B. Coignard, Yolande Costa, Florence Damond, Aline Dechanet, Christelle Delmas, Jean-Luc Ecobichon, Wahiba Frezouls, Nadhira Houhou, Emila Ilic-Habensus, John Kikoine, David Lebeaux, Anne Leclercq, Jonathan Lehacaut, Sophie Letrou, Jean‐Christophe Lucet, Pauline Manchon, Milica Mandic, Mohamed Meghadecha, Justina Motiejūnaitė, Mariama Nouroudine, Valentine Piquard, Andreea Postolache, Caroline Quintin, Jade Rexach, Layidé Roufai, Zaven Terzian, Michaël Thy, Valérie Vignali, Michiel A. van Agtmael, Anna Geke Algera, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije K. Bomers, Lieuwe D. J. Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Matthijs C. Brouwer, Sanne de Bruin, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Paul Elbers, Lucas M. Fleuren, Suzanne E. Geerlings, Bart F. Geerts, Armand R. J. Girbes, 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, Frederique Paulus, Edgar J.G. 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, 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 Condino‐Neto, Megan A. Cooper, Alessia David, Joseph L. 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Bibliographic record
VenueScience · 2020
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunodeficiency and Autoimmune Disorders
Canadian institutionsMcGill University Health Centre
FundersNHLBI Division of Intramural ResearchNational Heart, Lung, and Blood InstituteUniformed Services University of the Health SciencesNational Center for Advancing Translational SciencesNational Human Genome Research InstituteNederlandse Organisatie voor Wetenschappelijk OnderzoekAgence Nationale de la RechercheGeorgia Clinical and Translational Science AllianceGeorge Mason UniversityLeidosFrederick National Laboratory for Cancer ResearchMercatus Center, George Mason UniversityRockefeller UniversityYale UniversitySt. Giles FoundationU.S. Department of DefenseAmerican Association for the Advancement of ScienceNational Institutes of HealthFisher Center for Alzheimer's Research FoundationNational Institute of Allergy and Infectious DiseasesHoward Hughes Medical InstituteBrigham and Women's Hospital
KeywordsCoronavirus disease 2019 (COVID-19)Immunity2019-20 coronavirus outbreakSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)MedicineImmunologyVirologyImmune systemInternal medicineInfectious disease (medical specialty)DiseaseOutbreak
Abstract
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
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.019
GPT teacher head0.247
Teacher spread0.228 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations2,395
Published2020
Admission routes1
Has abstractyes