Browsing by Author "Bizien, Lucy"

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Open Access
Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia
(Rockefeller University Press, 2022-08-01) Özçelik, Tayfun; Zhang, Qian; Matuozzo, Daniela; Le Pen, Jérémie; 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; Hatipoğlu, Nevin; Morelle, Guillaume; Zatz, Mayana; Ng, Lisa F. P.; Lye, David Chien; 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, Laurenta; Rice, Charles M.; Zhang, Shen-Ying; Cobat, Aurélie; Casanova, Jean-Laurent
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. © 2022 Zhang et al.
Open Access
Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency
(Rockefeller University Press, 2022) Özçelik, Tayfun; Campbell, Tessa Mollie; Liu, Zhiyong; Zhang, Qian; Moncada-Velez, Marcela; Covill, Laura E.; Zhang, Peng; Darazam, Ilad Alavi; Bastard, Paul; Bizien, Lucy; Bucciol, Giorgia; Enoksson, Sara Lind; Jouanguy, Emmanuelle; Karabela, Şemsi Nur; Khan, Taushif; Kendir-Demirkol, Yasemin; Arias, Andres Augusto; Mansouri, Davood; Marits, Per; Marr, Nico; Migeotte, Isabelle; Moens, Leen; Pellier, Isabelle; Sendel, Anton; Shahrooei, Mohammad; Edvard Smith C.I.; Vandernoot, Isabelle; Willekens, Karen; Bergman, Peter; Abel, Laurent; Cobat, Aurélie; Casanova, Jean-Laurent; Meyts, Isabelle; Bryceson, Yenan T.
Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients’ fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza-and SARS-CoV-2–specific memory CD4+ and CD8+ Tcells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity. © 2022 Campbell et al.