St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.
J Exp Med. 2022 Aug 1;219(8). doi: 10.1084/jem.20220131. Epub 2022 Jun 16.
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.
I 型干扰素（IFN）先天性免疫的隐性或显性遗传缺陷可能导致未接种疫苗的成年人发生严重的 COVID-19 肺炎。而未接种疫苗的儿童患 COVID-19 肺炎的风险比未接种疫苗的成年人低得多，其原因仍不清楚。在一项针对 112 名因 COVID-19 肺炎住院的儿童（<16 岁）的国际队列研究中，我们报告了 12 名年龄在 1.5-13 岁的儿童患有严重（7 名）、重度（3 名）和中度（2 名）肺炎，其中 4 名患有已知的临床隐性和生化完整的 I 型 IFN 先天性免疫缺陷：X 连锁隐性 TLR7 缺陷（7 名）和常染色体隐性 IFNAR1（1 名）、STAT2（1 名）或 TYK2（3 名）缺陷。缺乏 IFNAR1、STAT2 或 TYK2 的成纤维细胞对 SARS-CoV-2 非常敏感。在 1224 名无肺炎的良性 SARS-CoV-2 感染儿童和成年人中（年龄、性别、血缘关系和种族特征重叠）未发现这些 15 种缺陷（P = 1.2×10-11）。I 型 IFN 免疫的隐性完全缺陷可能导致约 10%的儿童 COVID-19 肺炎住院病例。
