Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency
Authors: Campbell Tessa Mollie , Liu Zhiyong , Zhang Qian , Moncada-Velez Marcela , Covill Laura E. , Zhang Peng , Alavi Darazam Ilad , Bastard Paul , Bizien Lucy , Bucciol Giorgia , Lind Enoksson Sara , Jouanguy Emmanuelle , Karabela Şemsi Nur , Khan Taushif , Kendir-Demirkol Yasemin , Arias Andres Augusto , Mansouri Davood , Marits Per , Marr Nico , Migeotte Isabelle , Moens Leen , Ozcelik Tayfun , Pellier Isabelle , Sendel Anton , Şenoğlu Sevtap , Shahrooei Mohammad , Smith C.I. Edvard , Vandernoot Isabelle , Willekens Karen , Kart Yaşar Kadriye ,   COVID Human Genetic Effort, Abel Laurent , Aiuti Alessandro , Al-Muhsen Saleh , Al-Mulla Fahd , Anderson Mark S. , Andreakos Evangelos , Arias Andrés A. , Baris Feldman Hagit , Belot Alexandre , Biggs Catherine M. , Bogunovic Dusan , Bolze Alexandre , Bondarenko Anastasiia , Bousfiha Ahmed A. , Brodin Petter , Bryceson Yenan , Bustamante Carlos D. , Butte Manish J. , Casari Giorgio , Christodoulou John , Condino-Neto Antonio , Constantinescu Stefan N. , Cooper Megan A. , Dalgard Clifton L. , Desai Murkesh , Drolet Beth A. , El Baghdadi Jamila , Espinosa-Padilla Sara , Fellay Jacques , Flores Carlos , Franco José Luis , Froidure Antoine , Gregersen Peter K. , Grimbacher Bodo , Haerynck Filomeen , Hagin David , Halwani Rabih , Hammarström Lennart , Heath James R. , Henrickson Sarah E. , Hsieh Elena W.Y. , Husebye Eystein , Imai Kohsuke , Itan Yuval , Jarvis Erich D. , Karamitros Timokratis , Kisand Kai , Ku Cheng-Lung , Lau Yu-Lung , Ling Yun , Lucas Carrie L. , Maniatis Tom , Mansouri Davood , Maródi László , Meyts Isabelle , Milner Joshua D. , Mironska Kristina , Mogensen Trine H. , Morio Tomohiro , Ng Lisa F.P. , Notarangelo Luigi D. , Novelli Antonio , Novelli Giuseppe , O'Farrelly Cliona , Okada Satoshi , Okamoto Keisuke , Ozcelik Tayfun , Pan-Hammarström Qiang , Papadaki Maria , Pape Jean W. , Perez de Diego Rebeca , Perlin David S. , Pesole Graziano , Planas Anna M. , Prando Carolina , Pujol Aurora , Quintana-Murci Lluis , Ramaswamy Sathishkumar , Renia Laurent , Resnick Igor , Rodríguez-Gallego Carlos , Sancho-Shimizu Vanessa , Sediva Anna , Seppänen Mikko R.J. , Shahrooei Mohammed , Shcherbina Anna , Slaby Ondrej , Snow Andrew L. , Soler-Palacín Pere , Spaan András N. , Tancevski Ivan , Tangye Stuart G. , Tayoun Ahmad Abou , Turvey Stuart E. , Uddin K M Furkan , Uddin Mohammed J. , van de Beek Diederik , Vinh Donald C. , von Bernuth Horst , Wauters Joost , Zatz Mayana , Zawadzki Pawel , Su Helen C. , Casanova Jean-Laurent , Bergman Peter , Abel Laurent , Cobat Aurélie , Casanova Jean-Laurent , Meyts Isabelle , Bryceson Yenan T. 
Published: June 2022

Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients’ fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2–specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity.