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

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

  • Science. 2020 Oct 23;370(6515):eabd4570. doi: 10.1126/science.abd4570.
Qian Zhang 1,  Paul Bastard # 2 3,  Zhiyong Liu # 1,  Jérémie Le Pen # 4,  Marcela Moncada-Velez # 1,  Jie Chen # 1,  Masato Ogishi # 1,  Ira K D Sabli # 5,  Stephanie Hodeib # 5,  Cecilia Korol # 2,  Jérémie Rosain # 2 3,  Kaya Bilguvar # 6,  Junqiang Ye # 7,  Alexandre Bolze # 8,  Benedetta Bigio # 1,  Rui Yang # 1,  Andrés Augusto Arias # 1 9 10,  Qinhua Zhou # 1,  Yu Zhang # 11 12,  Fanny Onodi 13,  Sarantis Korniotis 13,  Léa Karpf 13,  Quentin Philippot 2 3,  Marwa Chbihi 2 3,  Lucie Bonnet-Madin 14,  Karim Dorgham 15,  Nikaïa Smith 16,  William M Schneider 4,  Brandon S Razooky 4,  Hans-Heinrich Hoffmann 4,  Eleftherios Michailidis 4,  Leen Moens 17,  Ji Eun Han 1,  Lazaro Lorenzo 2 3,  Lucy Bizien 2 3,  Philip Meade 18,  Anna-Lena Neehus 2 3,  Aileen Camille Ugurbil 1,  Aurélien Corneau 19,  Gaspard Kerner 2 3,  Peng Zhang 1,  Franck Rapaport 1,  Yoann Seeleuthner 2 3,  Jeremy Manry 2 3,  Cecile Masson 20,  Yohann Schmitt 20,  Agatha Schlüter 21,  Tom Le Voyer 2 3,  Taushif Khan 22,  Juan Li 1,  Jacques Fellay 23 24 25,  Lucie Roussel 26,  Mohammad Shahrooei 27 28,  Mohammed F Alosaimi 29,  Davood Mansouri 30 31 32,  Haya Al-Saud 33,  Fahd Al-Mulla 34,  Feras Almourfi 33,  Saleh Zaid Al-Muhsen 35,  Fahad Alsohime 29,  Saeed Al Turki 36 37,  Rana Hasanato 29,  Diederik van de Beek 38,  Andrea Biondi 39,  Laura Rachele Bettini 39,  Mariella D'Angio' 39,  Paolo Bonfanti 40,  Luisa Imberti 41,  Alessandra Sottini 41,  Simone Paghera 41,  Eugenia Quiros-Roldan 42,  Camillo Rossi 43,  Andrew J Oler 44,  Miranda F Tompkins 45,  Camille Alba 45,  Isabelle Vandernoot 46,  Jean-Christophe Goffard 47,  Guillaume Smits 46,  Isabelle Migeotte 48,  Filomeen Haerynck 49,  Pere Soler-Palacin 50,  Andrea Martin-Nalda 50,  Roger Colobran 51,  Pierre-Emmanuel Morange 52,  Sevgi Keles 53,  Fatma Çölkesen 54,  Tayfun Ozcelik 55,  Kadriye Kart Yasar 56,  Sevtap Senoglu 56,  Şemsi Nur Karabela 56,  Carlos Rodríguez-Gallego 57 58,  Giuseppe Novelli 59,  Sami Hraiech 60,  Yacine Tandjaoui-Lambiotte 61 62,  Xavier Duval 63 64,  Cédric Laouénan 63 64 65,  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,  Andrew L Snow 66,  Clifton L Dalgard 45 67,  Joshua D Milner 68,  Donald C Vinh 26,  Trine H Mogensen 69 70,  Nico Marr 22 71,  András N Spaan 1 72,  Bertrand Boisson 1 2 3,  Stéphanie Boisson-Dupuis 1 2 3,  Jacinta Bustamante 1 2 3 73,  Anne Puel 1 2 3,  Michael J Ciancanelli 1 74,  Isabelle Meyts 17 75,  Tom Maniatis 7 76,  Vassili Soumelis 13 77,  Ali Amara 14,  Michel Nussenzweig 78 79,  Adolfo García-Sastre 18 80 81 82,  Florian Krammer 18,  Aurora Pujol 21,  Darragh Duffy 16,  Richard P Lifton # 83 84 85,  Shen-Ying Zhang # 1 2 3,  Guy Gorochov # 15,  Vivien Béziat # 1 2 3,  Emmanuelle Jouanguy # 1 2 3,  Vanessa Sancho-Shimizu # 5,  Charles M Rice # 4,  Laurent Abel # 1 2 3,  Luigi D Notarangelo # 11 12,  Aurélie Cobat # 1 2 3,  Helen C Su # 11 12,  Jean-Laurent Casanova # 86 2 3 79 87
Affiliations

Affiliation

  • # Contributed equally.
PMID: 32972995 DOI: 10.1126/science.abd4570
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.

Figures