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 et al. · Proc Natl Acad Sci U S A · 2021

case_report · Level V

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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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