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

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. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks. We tested whether rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only 1 rare pLOF mutation across these genes among 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.

Automated summary

The study found no evidence of association between rare pLOF variants in 13 candidate genes and severe COVID-19 outcomes. Only one rare pLOF mutation was identified across these genes among cases with severe COVID-19, and there was no enrichment of pLOFs in severe cases compared to controls or mild COVID-19 cases.