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

• DOI: 10.1073/pnas.2114390118
• Publication Date: 2021-10-26T20:35:12Z
• Authors: Romain Lévy; Peng Zhang; Paul Bastard; Karim Dorgham; Isabelle Melki; Alice Hadchouel; George C. Hartoul...; Bénédicte Neven; Martin Castelle; Charlotte Roy; Tom Toin; Laureline Berteloot; Lucy Bizien; Hanène Abid; Marianne Burgard; Nadhira Houhou-Fi...; Flore Rozenberg; Emmanuelle Jouanguy; Chun Jimmie Ye; Guy Gorochov; Qian Zhang; Jean-Laurent Casa...
• Keywords: 0301 basic medicine; SARS-CoV-2; COVID-19; interferon; Biological Sciences; Viral Load; Antibodies, Monoclonal, Humanized; Antibodies, Neutralizing; Interferon-Stimulated Gene Factor 3, gamma Subunit; 3. Good health; Immunocompromised Host; 03 medical and health sciences; inherited primary immunodeficiency; Child, Preschool; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; Mutation; Humans; Female; RNA-seq

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.