| Title: |
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19 |
| Authors: |
Universitat Rovira i Virgili; Zhang 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 AA, 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 HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schlüter 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 SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, 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 JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Çölkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela ?N, Gallego CR, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouénan C,, Snow AL, Dalgard CL, Milner J, Vinh DC, Mogensen TH, Marr N, Spaan AN, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli M, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, García-Sastre A, Krammer F, Pujol A, Duffy D, Lifton R, Zhang SY, Gorochov G, Béziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC, Casanova JL COVID-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 |
| Source: |
Science; 10.1126/science.abd4570; Science. 370 (6515): 422-+ |
| Publisher Information: |
2020 |
| Document Type: |
Electronic Resource |
| Abstract: |
Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal 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 TLR3- and 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 define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway 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.Copyright © 2020, American Association for the Advancement of Science. |
| Index Terms: |
History and Philosophy of Science,Multidisciplinary,Multidisciplinary Sciences; Susceptibility; Nf-kappa-b; Herpes-simplex encephalitis; Deficiency; Zootecnia / recursos pesqueiros; Saúde coletiva; Química; Psychology; Psicología; Planejamento urbano e regional / demografia; Multidisciplinary sciences; Multidisciplinary; Medicina veterinaria; Medicina ii; Medicina i; Materiais; Interdisciplinar; History and philosophy of science; Geografía; Geociências; General o multidisciplinar; General medicine; Farmacia; Ensino; Engenharias iv; Engenharias iii; Engenharias ii; Engenharias i; Educação física; Economia; Direito; Ciencias sociales; Ciências biológicas iii; Ciências biológicas ii; Ciências biológicas i; Ciências ambientais; Ciências agrárias i; Ciência política e relações internacionais; Biotecnología; Biodiversidade; Astronomia / física; Antropologia / arqueologia; Administração pública e de empresas, ciências contábeis e turismo; Journal Publications |
| URL: |
http://hdl.handle.net/20.500.11797/imarina8681133 |
| Availability: |
Open access content. Open access content; info:eu-repo/semantics/openAccess |
| Other Numbers: |
RIV oai:urv.cat:imarina:8681133; 1443573646 |
| Contributing Source: |
UNIVERSITAT ROVIRA I VIRGILI BIBLIOTECA; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1443573646 |
| Database: |
OAIster |