Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency
Tessa M. Campbell, Zhiyong Liu, Qian Zhang, Marcela Moncada‐Vélez, Laura Covill, Peng Zhang, Ilad Alavi Darazam, Paul Bastard, Lucy Bizien, Giorgia Bucciol, Sara Lind Enoksson, Emmanuelle Jouanguy, Şemsi Nur Karabela, Taushif Khan, Yasemin Kendir-Demirkol, Andrés A. Arias, Davood Mansouri, Per Marits, Nico Marr, Isabelle Migeotte, Leen Moens, Tayfun Özçelık, Isabelle Pellier, Anton Sendel, Sevtap Şenoğlu, Mohammad Shahrooei, Smith Rjh, Isabelle Vandernoot, Karen Willekens, Kadriye Kart Yaşar, COVID Human Genetic Effort, Laurent Abel, Alessandro Aiuti, Saleh Al‐Muhsen, Fahd Al‐Mulla, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Hagit Baris Feldman, Alexandre Bélot, Catherine M. Biggs, Dusan Bogunovic, Alexandre Bolze, Анастасія Бондаренко, Ahmed Aziz Bousfiha, Petter Brodin, Yenan T. Bryceson, Carlos D. Bustamante, Manish J. Butte, Giorgio Casari, John Christodoulou, Antônio Condino‐Neto, Stefan N. Constantinescu, Megan A. Cooper, Clifton L. Dalgard, Murkesh Desai, Beth A. Drolet, Jamila El Baghdadi, Sara Elva Espinosa‐Padilla, Jacques Fellay, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Sarah E. Henrickson, Elena W.Y. Hsieh, Eystein S. Husebye, Kohsuke Imai, Yuval Itan, Erich D. Jarvis, Timokratis Karamitros, Kai Kisand, Cheng‐Lung Ku, YL Lau, Yun Ling, C. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O’Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan‐Hammarström, Maria Papadaki
Abstract
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.