Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.

TitleInborn errors of type I IFN immunity in patients with life-threatening COVID-19.
Publication TypeJournal Article
Year of Publication2020
AuthorsZhang, Q, Bastard, P, Liu, Z, Le Pen, J, Moncada-Velez, M, Chen, J, Ogishi, M, Sabli, IKD, Hodeib, S, Korol, C, Rosain, J, Bilguvar, K, Ye, J, Bolze, A, Bigio, B, Yang, R, Arias, AAugusto, Zhou, Q, Zhang, Y, Onodi, F, Korniotis, S, Karpf, L, Philippot, Q, Chbihi, M, Bonnet-Madin, L, Dorgham, K, Smith, N, Schneider, WM, Razooky, BS, Hoffmann, H-H, Michailidis, E, Moens, L, Han, JEun, Lorenzo, L, Bizien, L, Meade, P, Neehus, A-L, Ugurbil, ACamille, Corneau, A, Kerner, G, Zhang, P, Rapaport, F, Seeleuthner, Y, Manry, J, Masson, C, Schmitt, Y, Schluter, A, Le Voyer, T, Khan, T, Li, J, Fellay, J, Roussel, L, Shahrooei, M, Alosaimi, MF, Mansouri, D, Al-Saud, H, Al-Mulla, F, Almourfi, F, Al-Muhsen, SZaid, Alsohime, FAH, Turki, SAl, Hasanato, R, van de Beek, D, Biondi, A, Bettini, LRachele, D'Angio', M, Bonfanti, P, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Oler, AJ, Tompkins, MF, Alba, C, Vandernoot, I, Goffard, J-C, Smits, G, Migeotte, I, Haerynck, F, Soler-Palacin, P, Martin-Nalda, A, Colobran, R, Morange, P-E, Keles, S, Çölkesen, F, Ozcelik, T, Yasar, KKart, Senoglu, S, Karabela, ŞNur, Rodríguez-Gallego, C, Novelli, G, Hraiech, S, Tandjaoui-Lambiotte, Y, Duval, X, Laouénan, C, Snow, AL, Dalgard, CL, Milner, JD, Vinh, DC, Mogensen, TH, Marr, N, Spaan, AN, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, MJ, Meyts, I, Maniatis, T, Soumelis, V, Amara, A, Nussenzweig, M, García-Sastre, A, Krammer, F, Pujol, A, Duffy, D, Lifton, RP, Zhang, S-Y, Gorochov, G, Béziat, V, Jouanguy, E, Sancho-Shimizu, V, Rice, CM, Abel, L, Notarangelo, LD, Cobat, A, Su, HC, Casanova, J-L
Corporate AuthorsCOVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic Effort, NIAID-USUHS/TAGC COVID Immunity Group
JournalScience
Volume370
Issue6515
Date Published2020 10 23
ISSN1095-9203
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Alleles, Asymptomatic Infections, Betacoronavirus, Child, Child, Preschool, Coronavirus Infections, COVID-19, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Infant, Interferon Regulatory Factor-7, Interferon Type I, Loss of Function Mutation, Male, Middle Aged, Pandemics, Pneumonia, Viral, Receptor, Interferon alpha-beta, SARS-CoV-2, Toll-Like Receptor 3, Young Adult
Abstract

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
DOI10.1126/science.abd4570
Alternate JournalScience
PubMed ID32972995
PubMed Central IDPMC7857407
Grant ListHHSN272201400008C / AI / NIAID NIH HHS / United States
UL1 TR001866 / TR / NCATS NIH HHS / United States
P01 AI138938 / AI / NIAID NIH HHS / United States
HHSN272201800048C / AI / NIAID NIH HHS / United States
R01 AI088364 / AI / NIAID NIH HHS / United States
U19 AI135972 / AI / NIAID NIH HHS / United States
U19 AI111825 / AI / NIAID NIH HHS / United States
75N93019C00051 / AI / NIAID NIH HHS / United States
UL1 TR001873 / TR / NCATS NIH HHS / United States
U24 HG008956 / HG / NHGRI NIH HHS / United States
R35 HL135834 / HL / NHLBI NIH HHS / United States
UM1 HG006504 / HG / NHGRI NIH HHS / United States
U19 AI142733 / AI / NIAID NIH HHS / United States
MR/S032304/1 / MR / Medical Research Council / United Kingdom
R01 AI091707 / AI / NIAID NIH HHS / United States