[HTML][HTML] Inherited IFNAR1 deficiency in a child with both critical COVID-19 pneumonia and multisystem inflammatory syndrome
H Abolhassani, N Landegren, P Bastard… - Journal of clinical …, 2022 - Springer
Journal of clinical immunology, 2022•Springer
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 …
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 …
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.
Springer