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Get Free AccessThe 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
Paul Bastard, Paul Bastard, Lindsey B. Rosen, Lindsey B. Rosen, Qian Zhang, Qian Zhang, Eleftherios Michailidis, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Hans-Heinrich Hoffmann, Yu Zhang, Yu Zhang, Karim Dorgham, Karim Dorgham, Quentin Philippot, Quentin Philippot, Jérémie Rosain, Jérémie Rosain, Vivien Béziat, Vivien Béziat, Jérémy Manry, Jérémy Manry, Elana Shaw, Elana Shaw, Liis Haljasmägi, Liis Haljasmägi, Pärt Peterson, Pärt Peterson, Lazaro Lorenzo, Lazaro Lorenzo, Lucy Bizien, Lucy Bizien, Sophie Trouillet‐Assant, Sophie Trouillet‐Assant, Kerry Dobbs, Kerry Dobbs, Adriana A. de Jesus, Adriana A. de Jesus, Alexandre Bélot, Alexandre Bélot, Anne Kallaste, Anne Kallaste, Émilie Catherinot, Émilie Catherinot, Yacine Tandjaoui-Lambiotte, Yacine Tandjaoui-Lambiotte, Jérémie Le Pen, Jérémie Le Pen, Gaspard Kerner, Gaspard Kerner, Benedetta Bigio, Benedetta Bigio, Yoann Seeleuthner, Yoann Seeleuthner, Rui Yang, Rui Yang, Alexandre Bolze, Alexandre Bolze, András N. Spaan, András N. Spaan, Ottavia M. Delmonte, Ottavia M. Delmonte, Michael S. Abers, Michael S. Abers, Alessandro Aiuti, Alessandro Aiuti, Giorgio Casari, Giorgio Casari, Vito Lampasona, Vito Lampasona, Lorenzo Piemonti, Lorenzo Piemonti, Fabio Ciceri, Fabio Ciceri, Kaya Bilgüvar, Kaya Bilgüvar, Richard P. Lifton, Richard P. Lifton, Marc Vasse, Marc Vasse, David M. Smadja, David M. Smadja, Mélanie Migaud, Mélanie Migaud, Jérôme Hadjadj, Jérôme Hadjadj, Benjamin Terrier, Benjamin Terrier, Darragh Duffy, Darragh Duffy, Diederik van de Beek, Diederik van de Beek, Lucie Roussel, Lucie Roussel, Donald C. Vinh, Donald C. Vinh, Stuart G. Tangye, Stuart G. Tangye, Filomeen Haerynck, Filomeen Haerynck, David Dalmau, David Dalmau, Javier Martínez‐Picado, Javier Martínez‐Picado, Petter Brodin, Petter Brodin, Michel C. Nussenzweig, Michel C. Nussenzweig, Stéphanie Boisson–Dupuis, Stéphanie Boisson–Dupuis, Carlos Rodríguez‐Gallego, Carlos Rodríguez‐Gallego, Guillaume Vogt, Guillaume Vogt, Trine H. Mogensen, Trine H. Mogensen, Andrew J. Oler, Andrew J. Oler, Jingwen Gu, Jingwen Gu, Peter D. Burbelo, Peter D. Burbelo, Jeffrey I. Cohen, Jeffrey I. Cohen, Andrea Biondi, Andrea Biondi, Laura Rachele Bettini, Laura Rachele Bettini, Mariella D’Angiò, Mariella D’Angiò, Paolo Bonfanti, Paolo Bonfanti, Patrick Rossignol, Patrick Rossignol, Julien Mayaux, Julien Mayaux, Frédéric Rieux‐Laucat, Frédéric Rieux‐Laucat, Eystein S. Husebye, Eystein S. Husebye, Francesca Fusco, Francesca Fusco, Matilde Valeria Ursini, Matilde Valeria Ursini, Luisa Imberti, Luisa Imberti, Alessandra Sottini, Alessandra Sottini, Simone Paghera, Simone Paghera, Eugenia Quirós-Roldán, Eugenia Quirós-Roldán, Camillo Rossi, Camillo Rossi, Riccardo Castagnoli, Riccardo Castagnoli, Daniela Montagna, Daniela Montagna, Amelia Licari, Amelia Licari, Gian Luigi Marseglia, Gian Luigi Marseglia, Xavier Duval, Xavier Duval, Jade Ghosn, Jade Ghosn, John S. Tsang, John S. Tsang, Raphaela Goldbach‐Mansky, Raphaela Goldbach‐Mansky, Kai Kisand, Kai Kisand, Michail S. Lionakis, Michail S. Lionakis, Anne Puel, Anne Puel, Shen‐Ying Zhang, Shen‐Ying Zhang, Steven M. Holland, Steven M. Holland, Guy Gorochov, Guy Gorochov, Emmanuelle Jouanguy, Emmanuelle Jouanguy, Charles M. Rice, Charles M. Rice, Aurélie Cobat, Aurélie Cobat, Luigi D. Notarangelo, Luigi D. Notarangelo, Laurent Abel, Laurent Abel, Helen C. Su, Helen C. Su, Jean‐Laurent Casanova, Jean‐Laurent Casanova, Andrés A. Arias, Andrés A. Arias, Bertrand Boisson, Bertrand Boisson (2020). Autoantibodies against type I IFNs in patients with life-threatening COVID-19. , 370(6515), DOI: https://doi.org/10.1126/science.abd4585.
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Type
Article
Year
2020
Authors
200
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1126/science.abd4585
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