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Monoclonal antibody-mediated neutralization of SARS-CoV-2 in an IRF9-deficient child.
Lévy, Romain; Zhang, Peng; Bastard, Paul; Dorgham, Karim; Melki, Isabelle; Hadchouel, Alice; Hartoularos, George C; Neven, Bénédicte; Castelle, Martin; Roy, Charlotte; Toin, Tom; Berteloot, Laureline; Bizien, Lucy; Abid, Hanène; Burgard, Marianne; Houhou-Fidouh, Nadhira; Rozenberg, Flore; Jouanguy, Emmanuelle; Ye, Chun Jimmie; Gorochov, Guy; Zhang, Qian; Casanova, Jean-Laurent.
  • Lévy R; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children 75015 Paris, France.
  • Zhang P; Imagine Institute, University of Paris, Paris 75015, France.
  • Bastard P; Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris 75015, France.
  • Dorgham K; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
  • Melki I; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
  • Hadchouel A; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children 75015 Paris, France.
  • Hartoularos GC; Imagine Institute, University of Paris, Paris 75015, France.
  • Neven B; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
  • Castelle M; Sorbonne Université, INSERM, Centre for Immunology and Microbial Infections-Paris, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris 75013, France.
  • Roy C; Imagine Institute, University of Paris, Paris 75015, France.
  • Toin T; Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris 75015, France.
  • Berteloot L; General Pediatrics, Infectious Disease and Internal Medicine Department, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris, Paris 75019, France.
  • Bizien L; Pediatric Pulmonary Department, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris 75015, France.
  • Abid H; Institut Necker-Enfants Malades, INSERM U1151, Paris 75015, France.
  • Burgard M; Institute for Human Genetics, University of California, San Francisco, CA 94143.
  • Houhou-Fidouh N; Imagine Institute, University of Paris, Paris 75015, France.
  • Rozenberg F; Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris 75015, France.
  • Jouanguy E; Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris 75015, France.
  • Ye CJ; Pediatric Pulmonary Department, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris 75015, France.
  • Gorochov G; Pediatric Pulmonary Department, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris 75015, France.
  • Zhang Q; Pediatric Radiology, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris 75015, France.
  • Casanova JL; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children 75015 Paris, France.
Proc Natl Acad Sci U S A ; 118(45)2021 11 09.
Article in English | MEDLINE | ID: covidwho-1493350
ABSTRACT
We describe an unvaccinated child at risk for life-threatening COVID-19 due to an inherited deficiency of IRF9, which governs ISGF-3-dependent responses to type I and III interferons (IFN). She was admitted, with a high nasal SARS-CoV-2 load on day 1 of upper respiratory tract infection. She was viremic on day 2 and received casirivimab and imdevimab. Her clinical manifestations and viremia disappeared on days 3 and 4, respectively. Circulating SARS-CoV-2 virus induced the expression of IFN-stimulated genes in leukocytes on day 1, whereas the secretion of blood type I IFNs, which peaked on day 4, did not. Antibody-mediated SARS-CoV-2 neutralization is, therefore, sufficient to overcome a deficiency of antiviral IFNs.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interferon-Stimulated Gene Factor 3, gamma Subunit / Antibodies, Monoclonal, Humanized / SARS-CoV-2 / COVID-19 Type of study: Case report / Prognostic study Limits: Child, preschool / Female / Humans Language: English Year: 2021 Document Type: Article Affiliation country: Pnas.2114390118

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interferon-Stimulated Gene Factor 3, gamma Subunit / Antibodies, Monoclonal, Humanized / SARS-CoV-2 / COVID-19 Type of study: Case report / Prognostic study Limits: Child, preschool / Female / Humans Language: English Year: 2021 Document Type: Article Affiliation country: Pnas.2114390118