Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19

Host genetic factors related to COVID-19 susceptibility and outcomes are of great interest, as their identification could elucidate the mechanisms of SARS-CoV-2 infection and severity, thereby providing clues about potential therapeutic targets.

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. The Montreal Node of C3G recently published a paper where they identified only 1 rare pLOF mutation across these genes among 713 cases with severe COVID-19. They observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. They found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.

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Published: October 23, 2021