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