Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia.
Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia.
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DOI：
10.1084/jem.20220131
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发表时间：
2022-08-01
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在一个由112名因中度至危重COVID-19肺炎住院的儿童组成的国际队列中，我们发现12名儿童患有四种已知的I型干扰素免疫隐性先天性缺陷之一：X连锁TLR 7和常染色体IFNAR 1，STAT 2和TYK 2缺陷。I型干扰素（IFN）免疫的隐性或显性先天性缺陷可能是未接种疫苗的成人严重COVID-19肺炎的基础。未接种疫苗的儿童患COVID-19肺炎的风险远低于未接种疫苗的成年人，这一点仍然无法解释。在一个由112名儿童组成的国际队列中，（<16岁）因COVID-19肺炎住院，我们报告了12名儿童（10.7%）年龄1.5-13岁，（7名儿童）、重度（3名）和中度（2名）肺炎，以及15例已知的临床隐性和生化完全先天性I型IFN免疫缺陷中的4例：X连锁隐性TLR 7缺陷（7例儿童）和常染色体隐性IFNAR 1（1例）、STAT 2（1例）或TYK 2（3例）缺陷。缺乏IFNAR 1、STAT 2或TYK 2的成纤维细胞对SARS-CoV-2非常脆弱。在1,224例无肺炎的SARS-CoV-2良性感染儿童和成人（P = 1.2 × 10−11）中，没有发现这15种缺陷，这些缺陷具有重叠的年龄、性别、血缘和种族特征。I型IFN免疫的隐性完全缺陷可能是10%的儿童COVID-19肺炎住院的原因。
In an international cohort of 112 children hospitalized for moderate to critical COVID-19 pneumonia, we identified 12 children with one of four known recessive inborn errors of type I interferon immunity: X-linked TLR7 and autosomal IFNAR1, STAT2, and TYK2 deficiencies. 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.
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DOI：
10.1126/science.abj7965
发表时间：
2021-11-26
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Casanova JL;Abel L
通讯作者：
Abel L
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DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
DOI：
10.1084/jem.20220028
发表时间：
2022-06-06
期刊：
The Journal of experimental medicine
影响因子：
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64.8
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通讯作者：
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影响因子：
82.9
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通讯作者：
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