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

TitleAutoantibodies against type I IFNs in patients with life-threatening COVID-19.
Publication TypeJournal Article
Year of Publication2020
AuthorsBastard, 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, AAlmeida, 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, LRachele, D'Angio, M, Bonfanti, P, Rossignol, P, Mayaux, J, Rieux-Laucat, F, Husebye, ES, Fusco, F, Ursini, MValeria, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Castagnoli, R, Montagna, D, Licari, A, Marseglia, GLuigi, Duval, X, Ghosn, J, 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
Corporate AuthorsHGID 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
JournalScience
Volume370
Issue6515
Date Published2020 10 23
ISSN1095-9203
KeywordsAdult, Aged, Aged, 80 and over, Antibodies, Neutralizing, Asymptomatic Infections, Autoantibodies, Betacoronavirus, Case-Control Studies, Coronavirus Infections, COVID-19, Critical Illness, Female, Humans, Immunoglobulin G, Interferon alpha-2, Interferon Type I, Male, Middle Aged, Pandemics, Pneumonia, Viral, SARS-CoV-2
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.
DOI10.1126/science.abd4585
Alternate JournalScience
PubMed ID32972996
PubMed Central IDPMC7857397
Grant ListUM1 HG006504 / HG / NHGRI NIH HHS / United States
P01 AI138938 / AI / NIAID NIH HHS / United States
U19 AI111825 / AI / NIAID NIH HHS / United States
U24 HG008956 / HG / NHGRI NIH HHS / United States
MR/S032304/1 / MR / Medical Research Council / United Kingdom
R01 AI091707 / AI / NIAID NIH HHS / United States
/ HH / Howard Hughes Medical Institute / United States
UL1 TR001866 / TR / NCATS NIH HHS / United States
R01 AI088364 / AI / NIAID NIH HHS / United States
K08 AI135091 / AI / NIAID NIH HHS / United States