Significance Life-threatening COVID-19 pneumonia can be caused by rare inborn errors of type I interferon (IFN) immunity, or by autoantibodies neutralizing IFN-α2 or IFN-ω. In 2018, we reported a girl with critical influenza pneumonia due to inherited IRF9 deficiency, a component of the ISGF-3 transcription factor. We report the course of COVID-19 in the same patient. She was admitted on day 1 of upper respiratory tract infection with viremia. Administration of SARS-CoV-2–specific neutralizing monoclonal antibodies on day 2 prevented the development of pneumonia. SARS-CoV-2–specific monoclonal antibodies were sufficient to overcome a lack of ISGF-3– and IRF9-dependent type I and type III IFN immunity to the virus. They should be considered in selected children at high risk of life-threatening COVID-19. 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.
【저자키워드】 COVID-19, SARS-CoV-2, interferon, RNA-Seq, inherited primary immunodeficiency, 【초록키워드】 COVID-19 pneumonia, Immunity, Antiviral, Pneumonia, antibody, Influenza, children, monoclonal antibody, Infection, upper respiratory tract infection, interferons, respiratory tract infection, risk, SARS-CoV-2 virus, nasal, monoclonal antibodies, virus, type I interferon, clinical manifestations, Viremia, Casirivimab, Imdevimab, autoantibodies, response, Patient, IFN, Neutralizing, type I IFNs, respiratory, expression, Critical, upper respiratory tract, IFNs, Blood, SARS-CoV-2 neutralization, neutralizing monoclonal antibody, leukocytes, girl, Type III IFN, autoantibody, high risk, blood type, transcription factor, clinical manifestation, leukocyte, IRF9, deficiency, IFN-α2, influenza pneumonia, type I, IFN-stimulated genes, secretion, life-threatening, type I and III interferons, component, inherited deficiency, Course, selected, lack, caused, reported, peaked, overcome, prevented, IFN-stimulated gene, Significance, 【제목키워드】 neutralization,