Loss-of-function mutations in IFNAR2 in COVID-19 severe infection susceptibility.
J Glob Antimicrob Resist
; 26: 239-240, 2021 09.
Article
in English
| MEDLINE | ID: covidwho-1309281
ABSTRACT
Recent COVID-19 (coronavirus disease 2019) host genetics studies suggest enrichment of mutations in genes involved in the regulation of type I and type III interferon (IFN) immunity in patients with severe COVID-19 infection. We performed whole-genome sequencing analysis of samples obtained from patients participating in the ongoing ODYSSEY phase 3 study of hospitalised patients with severe COVID-19 infection receiving supplemental oxygen support. We focused on burden testing of categories of rare and common loss-of-function (LOF) variants in all of the IFN pathway genes, specifically with MAF < 0.1% and MAF < 1%. In a model including LOF and missense variants (MAF < 1%), we report a significant signal in both INFAR1 and IFNAR2. We report carriers of rare variants in our COVID-19 cohort, including a stop-gain IFNAR2 (NM_000874exon9c.C966Ap.Y322X) amongst carriers of several other IFNAR rare nonsynonymous variants. Furthermore, we report an increased allelic frequency of common IFNAR2 variants in our data, reported also by the COVID-19 Host Genetics Initiative.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
J Glob Antimicrob Resist
Year:
2021
Document Type:
Article
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