Monoclonal antibody-mediated neutralization of SARS-CoV-2 in an IRF9-deficient child

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 vir...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS 2021-11, Vol.118 (45), p.1-5, Article 2114390118
Hauptverfasser:	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
Format:	Artikel
Sprache:	eng
Schlagworte:	Antibodies, Monoclonal, Humanized - therapeutic use Antibodies, Neutralizing - therapeutic use Biological Sciences Blood groups Child, Preschool COVID-19 COVID-19 - therapy Female Gene expression Humans Immunocompromised Host Interferon Interferon-Stimulated Gene Factor 3, gamma Subunit - deficiency Interferon-Stimulated Gene Factor 3, gamma Subunit - genetics Leukocytes Life Sciences Microbiology and Parasitology Monoclonal antibodies Multidisciplinary Sciences Mutation Neutralization Respiratory tract Respiratory tract diseases SARS-CoV-2 - immunology Science & Technology Science & Technology - Other Topics Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Viral diseases Viral Load Viremia Virology Viruses
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Zusammenfassung:	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.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.2114390118