X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19
Takaki Asano, Bertrand Boisson, Fanny Onodi, Daniela Matuozzo, Marcela Moncada‐Vélez, Majistor Raj Luxman Maglorius Renkilaraj, Peng Zhang, Laurent Meertens, Alexandre Bolze, Marie Materna, Sarantis Korniotis, Adrian Gervais, Estelle Talouarn, Benedetta Bigio, Yoann Seeleuthner, Kaya Bilgüvar, Yu Zhang, Anna‐Lena Neehus, Masato Ogishi, Simon J. Pelham, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, Pere Soler‐Palacín, Roger Colobrán, Andrea Martín-Nalda, Jacques G. Rivière, Yacine Tandjaoui-Lambiotte, Khalil Chaïbi, Mohammad Shahrooei, Ilad Alavi Darazam, Nasrin Alipour Olyaei, Davood Mansouri, Nevin Hatipoğlu, Figen Palabıyık, Tayfun Özçelık, Giuseppe Novelli, Antonio Novelli, Giorgio Casari, Alessandro Aiuti, Paola Carrera, Simone Bondesan, Federica Barzaghi, Patrizia Rovere-Querini, Cristina Tresoldi, José Luis Franco, Julian Rojas, Luis Felipe Reyes, Ingrid G. Bustos, Andrés A. Arias, Guillaume Morelle, Christèle Kyheng, Jesús Troya, Laura Planas‐Serra, Agatha Schlüter, Marta Gut, Aurora Pujol, Luís M. Allende, Carlos Rodríguez‐Gallego, Carlos Flores, Óscar Cabrera-Marante, Daniel E. Pleguezuelo, Rebeca Pérez de Diego, Sevgi Keleş, Gökhan Aytekіn, Özge Metin Akcan, Yenan T. Bryceson, Peter Bergman, Petter Brodin, Daniel Smole, Smith Rjh, Anna-Carin Norlin, Tessa M. Campbell, Laura Covill, Lennart Hammarström, Qiang Pan‐Hammarström, Hassan Abolhassani, Shrikant Mane, Nico Marr, Manar Ata, Fatima Al Ali, Taushif Khan, András N. Spaan, Clifton L. Dalgard, Paolo Bonfanti, Andrea Biondi, Sarah Tubiana, Charles Burdet, Robert L. Nussbaum, Amanda Kahn-Kirby, Andrew L. Snow, COVID Human Genetic Effort, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, NIAID-USUHS COVID Study Group, Jacinta Bustamante, Anne Puel, Stéphanie Boisson‐Dupuis
Abstract
The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.