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

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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Submitted on : Friday, October 29, 2021 - 12:46:40 PM
Last modification on : Thursday, January 27, 2022 - 3:41:00 AM

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Romain Lévy, Peng Zhang, Paul Bastard, Karim Dorgham, Isabelle Melki, et al.. Monoclonal antibody-mediated neutralization of SARS-CoV-2 in an IRF9-deficient child. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2021, 118 (45), pp.e2114390118. ⟨10.1073/pnas.2114390118⟩. ⟨hal-03408790⟩

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