Abstract
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.
Funder
H2020 European Institute of Innovation and Technology
National Institutes of Health
Karolinska Institute
Publisher
Springer Science and Business Media LLC
Subject
Immunology,Immunology and Allergy
Cited by
49 articles.
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