Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia

ABSTRACT: Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5-13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinically recessive and biochemically complete inborn errors of type I IFN immunity: X-linked recessive TLR7 deficiency (7 children) and autosomal recessive IFNAR1 (1), STAT2 (1), or TYK2 (3) deficiencies. Fibroblasts deficient for IFNAR1, STAT2, or TYK2 are highly vulnerable to SARS-CoV-2. These 15 deficiencies were not found in 1,224 children and adults with benign SARS-CoV-2 infection without pneumonia (P = 1.2 × 10-11) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie ∼10% of hospitalizations for COVID-19 pneumonia in children.

• Autores: Moncada Vélez, Marcela; Zhang, Qian; Matuozzo, Daniela; Le Pen, Jérémie; Lee, Danyel; Moens, Leen; Asano, Takaki; Bohlen, Jonathan; Liu, Zhiyong; Kendir Demirkol, Yasemin; Jing, Huie; Bizien, Lucy; Marchal, Astrid; Abolhassani, Hassan; Delafontaine, Selket; Bucciol, Giorgia; Ical Bayhan, Gulsum; Keles, Sevgi; Kiykim, Ayca; Hancerli, Selda; Haerynck, Filomeen; Florkin, Benoit; Hatipoglu, Nevin; Ozcelik, Tayfun; Morelle, Guillaume; Zatz, Mayana; F P Ng, Lisa; Chien Lye, David; Young, Barnaby Edward; Leo, Yee-Sin; Dalgard, Clifton L.; P Lifton, Richard; Renia, Laurent; Meyts, Isabelle; Jouanguy, Emmanuelle; Hammarström, Lennart; Pan Hammarström, Qiang; Boisson, Bertrand; Bastard, Paul; C Su, Helen; Boisson Dupuis, Stéphanie; Abel, Laurent; M Rice, Charles; Zhang, Shen-Ying; Cobat, Aurélie; Casanova, Jean Laurent
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2022
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/41000
• Acceso en línea: https://hdl.handle.net/10495/41000
• Palabra clave: COVID-19; Inheritance Patterns; Patrón de Herencia; Interferon Type I; Interferón Tipo I; Pneumonia; Neumonía; SARS-CoV-2; https://id.nlm.nih.gov/mesh/D000086402; https://id.nlm.nih.gov/mesh/D000086382; https://id.nlm.nih.gov/mesh/D040582; https://id.nlm.nih.gov/mesh/D007370; https://id.nlm.nih.gov/mesh/D011014
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/