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Autoantibodies against type I IFNs in patients with life-threatening COVID-19
| File | Description | Size | Format | |
|---|---|---|---|---|
 abd4585_CombinedPDF_v7-compressed.pdf | Accepted version | 3.23 MB | Adobe PDF | View/Open |
| Title: | Autoantibodies against type I IFNs in patients with life-threatening COVID-19 |
| Authors: | Bastard, P Rosen, LB Zhang, Q Michailidis, E Hoffmann, H-H Zhang, Y Dorgham, K Philippot, Q Rosain, J Béziat, V Manry, J Shaw, E Haljasmägi, L Peterson, P Lorenzo, L Bizien, L Trouillet-Assant, S Dobbs, K De Jesus, AA Belot, A Kallaste, A Catherinot, E Tandjaoui-Lambiotte, Y Le Pen, J Kerner, G Bigio, B Seeleuthner, Y Yang, R Bolze, A Spaan, AN Delmonte, OM Abers, MS Aiuti, A Casari, G Lampasona, V Piemonti, L Ciceri, F Bilguvar, K Lifton, RP Vasse, M Smadja, DM Migaud, M Hadjadj, J Terrier, B Duffy, D Quintana-Murci, L Van de Beek, D Roussel, L Vinh, DC Tangye, SG Haerynck, F Dalmau, D Martinez-Picado, J Brodin, P Nussenzweig, MC Boisson-Dupuis, S Rodríguez-Gallego, C Vogt, G Mogensen, TH Oler, AJ Gu, J Burbelo, PD Cohen, JI Biondi, A Bettini, LR D'Angio, M Bonfanti, P Rossignol, P Mayaux, J Rieux-Laucat, F Husebye, ES Fusco, F Ursini, MV Imberti, L Sottini, A Paghera, S Quiros-Roldan, E Rossi, C Castagnoli, R Montagna, D Licari, A Marseglia, GL Duval, X Ghosn, J HGID Lab NIAID-USUHS Immune Response to COVID Group COVID Clinicians COVID-STORM Clinicians Imagine COVID Group French COVID Cohort Study Group Milieu Intérieur Consortium CoV-Contact Cohort Amsterdam UMC Covid-19 Biobank COVID Human Genetic Effort Tsang, JS Goldbach-Mansky, R Kisand, K Lionakis, MS Puel, A Zhang, S-Y Holland, SM Gorochov, G Jouanguy, E Rice, CM Cobat, A Notarangelo, LD Abel, L Su, HC Casanova, J-L |
| Item Type: | Journal Article |
| Abstract: | 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. |
| Issue Date: | 23-Oct-2020 |
| Date of Acceptance: | 16-Sep-2020 |
| URI: | http://hdl.handle.net/10044/1/85248 |
| DOI: | 10.1126/science.abd4585 |
| ISSN: | 1095-9203 |
| Publisher: | AAAS |
| Journal / Book Title: | Science |
| Volume: | 370 |
| Issue: | 6515 |
| Copyright Statement: | Accepted author version (to be embargoed until publication) © 2020 Owner. This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published i nScience 23 Oct 2020: Vol. 370, Issue 6515, eabd4585 DOI: 10.1126/science.abd4585 |
| Sponsor/Funder: | UKRI Future Leader's Fellowship |
| Keywords: | Adult Aged Aged, 80 and over Antibodies, Neutralizing Asymptomatic Infections Autoantibodies Betacoronavirus COVID-19 Case-Control Studies Coronavirus Infections Critical Illness Female Humans Immunoglobulin G Interferon Type I Interferon alpha-2 Male Middle Aged Pandemics Pneumonia, Viral SARS-CoV-2 HGID Lab NIAID-USUHS Immune Response to COVID Group COVID Clinicians COVID-STORM Clinicians Imagine COVID Group French COVID Cohort Study Group Milieu Intérieur Consortium CoV-Contact Cohort Amsterdam UMC Covid-19 Biobank COVID Human Genetic Effort Humans Pneumonia, Viral Coronavirus Infections Critical Illness Immunoglobulin G Interferon Type I Autoantibodies Case-Control Studies Adult Aged Aged, 80 and over Middle Aged Female Male Antibodies, Neutralizing Asymptomatic Infections Pandemics Betacoronavirus Interferon alpha-2 COVID-19 SARS-CoV-2 Adult Aged Aged, 80 and over Antibodies, Neutralizing Asymptomatic Infections Autoantibodies Betacoronavirus COVID-19 Case-Control Studies Coronavirus Infections Critical Illness Female Humans Immunoglobulin G Interferon Type I Interferon alpha-2 Male Middle Aged Pandemics Pneumonia, Viral SARS-CoV-2 General Science & Technology |
| Publication Status: | Published |
| Conference Place: | United States |
| Online Publication Date: | 2020-10-23 |
| Appears in Collections: | Department of Infectious Diseases Faculty of Medicine Imperial College London COVID-19 |