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


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Zhang Q., Matuozzo D., Le Pen J., Lee D., Moens L., Asano T., ...More

Journal of Experimental Medicine, vol.219, no.8, 2022 (Peer-Reviewed Journal) identifier identifier

  • Publication Type: Article / Article
  • Volume: 219 Issue: 8
  • Publication Date: 2022
  • Doi Number: 10.1084/jem.20220131
  • Journal Name: Journal of Experimental Medicine
  • Journal Indexes: Science Citation Index Expanded, Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database

Abstract

© 2022 Zhang et al.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.