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
in English
| MEDLINE | ID: covidwho-1653615
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Interferon Type I
/
COVID-19
Type of study:
Case report
/
Prognostic study
Topics:
Long Covid
/
Variants
Limits:
Child, preschool
/
Humans
Language:
English
Journal:
J Clin Immunol
Year:
2022
Document Type:
Article
Affiliation country:
S10875-022-01215-7
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