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

• Main Authors: Zhang, Qian, Matuozzo, Daniela, Le Pen, Jérémie, Lee, Danyel, Moens, Leen, Asano, Takaki, Bohlen, Jonathan, Liu, Zhiyong, Moncada-Velez, Marcela, Kendir-Demirkol, Yasemin, Jing, Huie, Bizien, Lucy, Marchal, Astrid, Abolhassani, Hassan, Delafontaine, Selket, Bucciol, Giorgia, Bayhan, Gulsum Ical, Keles, Sevgi, Kiykim, Ayca, Hancerli, Selda, Haerynck, Filomeen, Florkin, Benoit, Hatipoglu, Nevin, Ozcelik, Tayfun, Morelle, Guillaume, Zatz, Mayana, Ng, Lisa F. P., Lye, David C., Young, Barnaby Edward, Leo, Yee Sin, Dalgard, Clifton L., Lifton, Richard P., Renia, Laurent, Meyts, Isabelle, Jouanguy, Emmanuelle, Hammarström, Lennart, Pan-Hammarström, Qiang, Boisson, Bertrand, Bastard, Paul, Su, Helen C., Boisson-Dupuis, Stéphanie, Abel, Laurent, Rice, Charles M., Zhang, Shen-Ying, Cobat, Aurélie, Casanova, Jean-Laurent
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Medicine; Pyogenic Bacterial-Infections; Simplex-Virus Encephalitis
• Online Access: https://hdl.handle.net/10356/163940
• Institution: Nanyang Technological University

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.