Monoclonal antibody-mediated neutralization of SARS-CoV-2 in an IRF9-deficient child
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 Ye, Guy Gorochov, Qian Zhang, Jean‐Laurent Casanova
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.