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

Paul Bastard 1, 2, * Lindsey Rosen 3 Qian Zhang 2 Eleftherios Michailidis 2 Hans-Heinrich Hoffmann 2 Yu Zhang 3 Karim Dorgham 4 Quentin Philippot 1 Jérémie Rosain 1 Vivien Béziat 1, 2 Jérémy Manry 1 Elana Shaw 3 Liis Haljasmägi 5 Pärt Peterson 5 Lazaro Lorenzo 1 Lucy Bizien 1 Sophie Trouillet-Assant 6, 7 Kerry Dobbs 3 Adriana Almeida de Jesus 3 Alexandre Belot 7, 8, 9 Anne Kallaste 10 Emilie Catherinot 11 Yacine Tandjaoui-Lambiotte 12, 13 Jeremie Le Pen 2 Gaspard Kerner 1 Benedetta Bigio 2 Yoann Seeleuthner 1 Rui Yang 2 Alexandre Bolze 14 András Spaan 2, 15 Ottavia Delmonte 3 Michael Abers 3 Alessandro Aiuti 16, 17 Giorgio Casari 16, 17 Vito Lampasona 16, 17 Lorenzo Piemonti 16, 17 Fabio Ciceri 16, 17 Kaya Bilguvar 18 Richard Lifton 18, 2 Marc Vasse 11 David Smadja 19 Mélanie Migaud 1 Jérome Hadjadj 20 Benjamin Terrier 21, 22 Darragh Duffy 23 Lluis Quintana-Murci 24, 25 Diederik van de Beek 26 Lucie Roussel 27 Donald Vinh 27 Stuart Tangye 28, 29 Filomeen Haerynck 30 David Dalmau 31, 32 Javier Martinez-Picado 33, 34, 35 Petter Brodin 36, 37 Michel Nussenzweig 2, 38 Stéphanie Boisson-Dupuis 1, 2 Carlos Rodríguez-Gallego 39, 40 Guillaume Vogt 41 Trine Mogensen 42, 43 Andrew Oler 3 Jingwen Gu 3 Peter Burbelo 44 Jeffrey Cohen 3 Andrea Biondi 45, 46 Laura Rachele Bettini 45, 46 Mariella d'Angio 45, 46 Paolo Bonfanti 47, 45 Patrick Rossignol 48 Julien Mayaux 49 Frédéric Rieux-Laucat 20 Eystein Husebye 50, 51, 36 Francesca Fusco 52 Matilde Valeria Ursini 52 Luisa Imberti 53 Alessandra Sottini 53 Simone Paghera 53 Eugenia Quiros-Roldan 54, 53 Camillo Rossi 53 Riccardo Castagnoli 55, 56 Daniela Montagna 56, 55 Amelia Licari 55, 56 Gian Luigi Marseglia 55, 56 Xavier Duval 57, 58, 59, 60 Jade Ghosn 60, 58 John Tsang 3 Raphaela Goldbach-Mansky 3 Kai Kisand 5 Michail Lionakis 3 Anne Puel 1, 2 Shen-Ying Zhang 1, 2 Steven Holland 3 Guy Gorochov 4, 61 Emmanuelle Jouanguy 1, 2 Charles Rice 2 Aurélie Cobat 1, 2 Luigi Notarangelo 3 Laurent Abel 1 Helen Su 3 Jean-Laurent Casanova 1, 2, 38, 62, *
* Corresponding author
1 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
IMAGINE - U1163 - Imagine - Institut des maladies génétiques
20 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
IMAGINE - U1163 - Imagine - Institut des maladies génétiques
Abstract : Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
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Paul Bastard, Lindsey Rosen, Qian Zhang, Eleftherios Michailidis, Hans-Heinrich Hoffmann, et al.. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science, American Association for the Advancement of Science, 2020, pp.eabd4585. ⟨10.1126/science.abd4585⟩. ⟨pasteur-02958871⟩

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