@article{01GW9ZJRV1ZGYCN1R5E69M6JXF,
  abstract     = {{X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4–dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8–207.8, P < 0.001). The patients’ susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.}},
  articleno    = {{e20220170}},
  author       = {{García-García, Ana and Pérez de Diego, Rebeca and Flores, Carlos and Rinchai, Darawan and Solé-Violán, Jordi and Deyà-Martínez, Àngela and García-Solis, Blanca and Lorenzo-Salazar, José M. and Hernández-Brito, Elisa and Lanz, Anna-Lisa and Moens, Leen and Bucciol, Giorgia and Almuqamam, Mohamed and Domachowske, Joseph B. and Colino, Elena and Santos-Perez, Juan Luis and Marco, Francisco M. and Pignata, Claudio and Bousfiha, Aziz and Turvey, Stuart E. and Bauer, Stefanie and Haerynck, Filomeen and Ocejo-Vinyals, Javier Gonzalo and Lendinez, Francisco and Prader, Seraina and Naumann-Bartsch, Nora and Pachlopnik Schmid, Jana and Biggs, Catherine M. and Hildebrand, Kyla and Dreesman, Alexandra and Cárdenes, Miguel Ángel and Ailal, Fatima and Benhsaien, Ibtihal and Giardino, Giuliana and Molina-Fuentes, Agueda and Fortuny, Claudia and Madhavarapu, Swetha and Conway, Daniel H. and Prando, Carolina and Schidlowski, Laire and Martínez de Saavedra Álvarez, María Teresa and Alfaro, Rafael and Rodríguez de Castro, Felipe and Kindle, Gerhard and Mahlaoui, Nizar and Seidel, Markus G. and Vassilios, Lougaris and Seppänen, Mikko R.J. and Abel, Laurent and Aiuti, Alessandro and Al-Muhsen, Saleh and Al-Mulla, Fahd and Anderson, Mark S. and Andreakos, Evangelos and Arias, Andrés A. and Baris Feldman, Hagit and Belot, Alexandre and Biggs, Catherine M. and Bogunovic, Dusan and Bolze, Alexandre and Bondarenko, Anastasiia and Bousfiha, Ahmed A. and Brodin, Petter and Bryceson, Yenan and Bustamante, Carlos D. and Butte, Manish J. and Casari, Giorgio and Christodoulou, John and Condino-Neto, Antonio and Constantinescu, Stefan N. and Cooper, Megan A. and Dalgard, Clifton L. and Desai, Murkesh and Drolet, Beth A. and El Baghdadi, Jamila and Espinosa-Padilla, Sara and Fellay, Jacques and Flores, Carlos and Franco, José Luis and Froidure, Antoine and Gregersen, Peter K. and Grimbacher, Bodo and Hagin, David and Halwani, Rabih and Hammarström, Lennart and Heath, James R. and Henrickson, Sarah E. and Hsieh, Elena W.Y. and Husebye, Eystein and Imai, Kohsuke and Itan, Yuval and Jarvis, Erich D. and Karamitros, Timokratis and Kisand, Kai and Ku, Cheng-Lung and Lau, Yu-Lung and Ling, Yun and Lucas, Carrie L. and Maniatis, Tom and Mansouri, Davood and Meyts, Isabelle and Milner, Joshua D. and Mironska, Kristina and Mogensen, Trine H. and Morio, Tomohiro and Ng, Lisa F.P. and Notarangelo, Luigi D. and Novelli, Antonio and Novelli, Giuseppe and O’Farrelly, Cliona and Okada, Satoshi and Okamoto, Keisuke and Ozcelik, Tayfun and Pan-Hammarström, Qiang and Pape, Jean W. and Perez de Diego, Rebecca and Perlin, David S. and Pesole, Graziano and Planas, Anna M. and Prando, Carolina and Pujol, Aurora and Quintana-Murci, Lluis and Ramaswamy, Sathishkumar and Renia, Laurent and Resnick, Igor and Rodríguez-Gallego, Carlos and Sancho-Shimizu, Vanessa and Sediva, Anna and Seppänan, Mikko R.J. and Shahrooei, Mohammed and Shcherbina, Anna and Slaby, Ondrej and Snow, Andrew L. and Soler-Palacín, Pere and Spaan, András N. and Tancevski, Ivan and Tangye, Stuart G. and Tayoun, Ahmad Abou and Turvey, Stuart E. and Uddin, K M Furkan and Uddin, Mohammed J. and van de Beek, Diederik and Vinh, Donald C. and von Bernuth, Horst and Wauters, Joost and Zatz, Mayana and Zawadzki, Pawel and Su, Helen C. and Casanova, Jean-Laurent and Meyts, Isabelle and Hauck, Fabian and Puel, Anne and Bastard, Paul and Boisson, Bertrand and Jouanguy, Emmanuelle and Abel, Laurent and Cobat, Aurélie and Zhang, Qian and Casanova, Jean-Laurent and Alsina, Laia and Rodríguez-Gallego, Carlos and ESID Registry Working Party, [missing] and COVID Human Genetic Effort, [missing]}},
  issn         = {{0022-1007}},
  journal      = {{JOURNAL OF EXPERIMENTAL MEDICINE}},
  keywords     = {{Immunology,Immunology and Allergy}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{26}},
  publisher    = {{Rockefeller University Press}},
  title        = {{Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia}},
  url          = {{http://doi.org/10.1084/jem.20220170}},
  volume       = {{220}},
  year         = {{2023}},
}

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