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 2021 Nov 09

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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. Copyright © 2021 the Author(s). Published by PNAS.

Citation

Romain Lévy, Peng Zhang, Paul Bastard, Karim Dorgham, Isabelle Melki, Alice Hadchouel, George C Hartoularos, Bénédicte Neven, Martin Castelle, Charlotte Roy, Tom Toin, Laureline Berteloot, Lucy Bizien, Hanène Abid, Marianne Burgard, Nadhira Houhou-Fidouh, Flore Rozenberg, Emmanuelle Jouanguy, Chun Jimmie Ye, Guy Gorochov, Qian Zhang, Jean-Laurent Casanova. 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. 2021 Nov 09;118(45)