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

Paul Bastard (1, 2) , Lindsey B. 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 N. Spaan (2, 15) , Ottavia M. Delmonte (3) , Michael S. 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 P. 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 C. Vinh (27) , Stuart G. Tangye (28, 29) , Filomeen Haerynck (30) , David Dalmau (31, 32) , Javier Martinez-Picado (33, 34, 35) , Petter Brodin (36, 37) , Michel C. Nussenzweig (2, 38) , Stéphanie Boisson-Dupuis (1, 2) , Carlos Rodríguez-Gallego (39, 40) , Guillaume Vogt (41) , Trine H. Mogensen (42, 43) , Andrew J. Oler (3) , Jingwen Gu (3) , Peter D. 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, 49, 50, 51) , Julien Mayaux (52) , Frédéric Rieux-Laucat (20) , Eystein S. Husebye (53, 54, 36) , Francesca Fusco (55) , Matilde Valeria Ursini (55) , Luisa Imberti (56) , Alessandra Sottini (56) , Simone Paghera (56) , Eugenia Quiros-Roldan (57, 56) , Camillo Rossi (56) , Riccardo Castagnoli (58, 59) , Daniela Montagna (59, 58) , Amelia Licari (58, 59) , Gian Luigi Marseglia (58, 59) , Xavier Duval (60, 61, 62, 63) , Jade Ghosn (62, 61) , John S. Tsang (3) , Raphaela Goldbach-Mansky (3) , Kai Kisand (5) , Michail S. Lionakis (3) , Anne Puel (1, 2) , Shen-Ying Zhang (1, 2) , Steven M. Holland (3) , Guy Gorochov (4, 64) , Emmanuelle Jouanguy (1, 2) , Charles M. Rice (2) , Aurélie Cobat (1, 2) , Luigi D. Notarangelo (3) , Laurent Abel (1) , Jean-Christophe Richard (65, 66) , Helen Su (3) , Jean-Laurent Casanova (1, 2, 38, 67) , Christelle Tual (68) , Yazdan Yazdanpanah (61) , Sylvie van Der Werf (69)

1 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
2 Rockefeller University [New York]
3 NIAID-NIH - National Institute of Allergy and Infectious Diseases [Bethesda]
4 CIMI - Centre d'Immunologie et des Maladies Infectieuses
5 University of Tartu
6 HCL - Hospices Civils de Lyon
7 CIRI - Centre International de Recherche en Infectiologie
8 RAISE - Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon]
9 LIFe - Lyon Immunopathology Federation
10 Tartu University Hospital [Tartu, Estonia]
11 Hôpital Foch [Suresnes]
12 Hôpital Avicenne [AP-HP]
13 H&P - Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires
14 Helix [San Mateo, CA]
15 University Medical Center [Utrecht]
16 IRCCS Ospedale San Raffaele [Milan, Italy]
17 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
18 YSM - Yale School of Medicine [New Haven, Connecticut]
19 IThEM - U1140 - Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis
20 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
21 Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière]
22 UPCité - Université Paris Cité
23 Immunologie Translationnelle - Translational Immunology lab
24 Génétique Evolutive Humaine - Human Evolutionary Genetics
25 Collège de France - Chaire Génomique humaine et évolution
26 Amsterdam Neuroscience [Pays-Bas]
27 MUHC - McGill University Health Center [Montreal]
28 Garvan Institute of medical research
29 UNSW - University of New South Wales [Sydney]
30 Ghent University Hospital
31 Hospital Universitario Mutua de Terrassa
32 UB - Universitat de Barcelona
33 IGTP - Institut d’Investigació Germans Trias i Pujol = Germans Trias i Pujol Research Institute
34 Universitat de Vic-Universitat Central de Catalunya, España
35 ICREA - Institució Catalana de Recerca i Estudis Avançats
36 Karolinska Institutet [Stockholm]
37 Karolinska University Hospital [Stockholm]
38 HHMI - Howard Hughes Medical Institute [New York]
39 Hospital Universitario de Gran Canaria Dr Negrin
40 University Fernando Pessoa - UFP
41 CNRGH - Centre National de Recherche en Génomique Humaine
42 Aarhus University Hospital
43 Aarhus University [Aarhus]
44 NIH - National Institutes of Health [Bethesda]
45 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
46 Fondazione MBBM-Ospedale [Monza, Italie]
47 San Gerardo Hospital of Monza
48 CIC-P - Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]
49 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
50 INI-CRCT - Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
51 Cardiovascular & Renal Clinical Trialists - CRCT - French-Clinical Research Infrastructure Network - F-CRIN [Paris]
52 Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière]
53 UiB - University of Bergen
54 Haukeland University Hospital
55 CNR - Consiglio Nazionale delle Ricerche [Napoli]
56 Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia]
57 UniBs - Università degli Studi di Brescia = University of Brescia
58 UNIPV - Università degli Studi di Pavia = University of Pavia
59 Fondazione IRCCS Policlinico San Matteo
60 CIC - CHU Bichat
61 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
62 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
63 UFR Médecine UPCité - UFR Médecine [Santé] - Université Paris Cité
64 Service d'Immunologie [CHU Pitié-Salpétrière]
65 CREATIS - Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
66 MYRIAD - Modeling & analysis for medical imaging and Diagnosis
67 Service d'immuno-hématologie pédiatrique [CHU Necker]
68 CIC - Centre d'Investigation Clinique [Rennes]
69 CNRS-UMR3569 - Virologie

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against 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 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

Domains: Immunology; Genetics

Paul Bastard, Lindsey B. Rosen, Qian Zhang, Eleftherios Michailidis, Hans-Heinrich Hoffmann, et al.. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science, 2020, 370 (6515), pp.eabd4585. ⟨10.1126/science.abd4585⟩. ⟨pasteur-02958871⟩