Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome.
J Clin Immunol
; 42(3): 471-483, 2022 04.
Article
en En
| MEDLINE
| ID: mdl-35091979
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Interferón Tipo I
/
COVID-19
Tipo de estudio:
Prognostic_studies
Límite:
Child, preschool
/
Humans
Idioma:
En
Revista:
J Clin Immunol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Suecia