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

We describe an unvaccinated child at risk of life-threatening COVID-19 due to an inherited deficiency of IRF9, which governs ISGF-3-dependent responses to type I and III interferons. She was admitted, with a high nasal SARS-CoV-2 load, on day one of upper respiratory tract infection. She was viremic on day two and received casirivimab and imdevimab. Her clinical manifestations and viremia disappeared on days three and four, respectively. Circulating SARS-Cov-2 virus induced the expression of interferon-stimulated genes in leukocytes on day one, whereas the secretion of blood type I IFNs, which peaked on day four, did not. Antibody-mediated SARS-CoV-2 neutralization is, therefore, sufficient to overcome a deficiency of anti-viral interferons.