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. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-022-01215-7.
【저자키워드】 COVID-19, critical pneumonia, multisystem inflammatory syndrome in children (MIS-C), inborn errors of immunity (IEI), primary immunodeficiency (PID), IFNAR1, 【초록키워드】 COVID-19 pneumonia, Cytokines, Immunity, Pneumonia, SARS-COV-2 infection, children, Sequencing, variant, interferons, virus, type I interferon, MIS-C, autoantibodies, type I interferons, type I IFNs, Genetic variant, IFNAR1, Critical, patients, IFNs, specific antibodies, IFNAR1 deficiency, Inflammatory, Plasma levels, candidate gene, Type I IFN, autoantibody, dysregulation, autosomal recessive, supplementary material, Exome, causes, syndrome, loss-of-function, homozygous, objective, raise, Result, detect, died, investigated, specific antibody, was performed, contribute, cause, underlie, Inborn error, Plasma level, 【제목키워드】 Child,