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

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. DOI: 10.1084/jem.20220131, PMID: 35708626
Authors: Qian Zhang, Daniela Matuozzo, Jérémie Le Pen, Danyel Lee, Leen Moens, Takaki Asano, Jonathan Bohlen, Zhiyong Liu, Marcela Moncada-Velez, Yasemin Kendir-Demirkol, Huie Jing, Lucy Bizien, Astrid Marchal, Hassan Abolhassani, Selket Delafontaine, Giorgia Bucciol, Gulsum Ical Bayhan, Sevgi Keles, Ayca Kiykim, Selda Hancerli, Filomeen Haerynck, Benoit Florkin, Nevin Hatipoglu, Tayfun Ozcelik, Guillaume Morelle, Mayana Zatz, Lisa F P Ng, David Chien Lye, Barnaby Edward Young, Yee-Sin Leo, Clifton L Dalgard, Richard P Lifton, Laurent Renia, Isabelle Meyts, Emmanuelle Jouanguy, Lennart Hammarström, Qiang Pan-Hammarström, Bertrand Boisson, Paul Bastard, Helen C Su, Stéphanie Boisson-Dupuis, Laurent Abel, Charles M Rice, Shen-Ying Zhang, Aurélie Cobat, Jean-Laurent Casanova