Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.

ABSTRACT:

Background

We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.

Methods

We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.

Results

No gene reached genome-wide significance. Under a recessive mode

SUBMITTER: Matuozzo D 

PROVIDER: S-EPMC10074346 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature