%0 Journal Article %T Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome %+ Department of Biosciences and Nutrition [Karolinska Insitutet, Sueden] (BioNut) %+ Iran University of Medical Sciences [Tehran, Iran] (IUMS) %+ Uppsala University %+ Department of medicine [Stockholm] %+ St. Giles Laboratory of Human Genetics of Infectious Diseases %+ Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163) %+ Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163) %+ Children’s Medical Center [Tehran, Liban] %+ Karolinska Institute %+ Sidra Medicine [Doha, Qatar] %+ Hamad Bin Khalifa University (HBKU) %+ Centre International de Recherche en Infectiologie (CIRI) %+ Service d'immunologie [Centre Hospitalier Lyon Sud - HCL] %+ Hôpital Femme Mère Enfant [CHU - HCL] (HFME) %+ Howard Hughes Medical Institute [New York] (HHMI) %+ Karolinska University Hospital [Stockholm] %A Abolhassani, Hassan %A Landegren, Nils %A Bastard, Paul %A Materna, Marie %A Modaresi, Mohammadreza %A Du, Likun %A Aranda-Guillén, Maribel %A Sardh, Fabian %A Zuo, Fanglei %A Zhang, Peng %A Marcotte, Harold %A Marr, Nico %A Khan, Taushif %A Ata, Manar %A Al-Ali, Fatima %A Pescarmona, Remi %A Belot, Alexandre %A Béziat, Vivien %A Zhang, Qian %A Casanova, Jean-Laurent %A Kämpe, Olle %A Zhang, Shen-Ying %A Hammarström, Lennart %A Pan-Hammarström, Qiang %Z Open access funding provided by Karolinska Institute. This work was supported by The European Union’s Horizon 2020 research and innovation program (ATAC, 101003650), the Center for Innovative Medicine at Karolinska Institutet, the Swedish Research Council, the Knut and Alice Wallenberg Foundation (KAW). The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), ANR grants (ANR-14-CE14-0008–01, ANR-18-CE15-0020–02, ANR-20-CE93-003, ANR-20-CO11-000,1 and ANR-21-COVR-0039), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), the European Union’s Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-Genomics), the Square Foundation, Grandir-Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Fondation du Souffle, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University of Paris. PB was supported by the French Foundation for Medical Research (FRM, EA20170638020). PB was supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). NM received funding from Sidra Medicine (SDR400048) and the Qatar National Research Fund (NPRP9-251–3-045). %< avec comité de lecture %@ 0271-9142 %J Journal of Clinical Immunology %I Springer Verlag %V 42 %N 3 %P 471-483 %8 2022-04 %D 2022 %R 10.1007/s10875-022-01215-7 %K COVID-19 %K critical pneumonia %K multisystem inflammatory syndrome in children (MIS-C) %K inborn errors of immunity (IEI) %K primary immunodeficiency (PID) %K IFNAR1 %Z Life Sciences [q-bio]/ImmunologyJournal articles %X Abstract Background Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. Objectives To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. Methods Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. Results We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1 , underlying autosomal recessive IFNAR1 deficiency. Conclusions Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients. %G English %L hal-03691612 %U https://u-paris.hal.science/hal-03691612 %~ INSERM %~ UNIV-ST-ETIENNE %~ ENS-LYON %~ HCL %~ CNRS %~ UNIV-LYON1 %~ OPENAIRE %~ CHLS %~ CIRI %~ UDL %~ UNIV-LYON %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SANTE %~ ANR %~ FRM