-This track shows variants associated with monogenic congenital defects of immunity to SARS-CoV-2, +This track shows variants associated with monogenic congenital defects of immunity to SARS-CoV-2, with incomplete or complete penetrance from the COVID Human Genetic Effort. This international consortium aims to detect rare or common monogenic inborn immunity errors (IEI) underlying severe forms of COVID-19 in previously healthy individuals, as well as rare or common monogenic variations that make certain individuals resistant to the infection by SARS-CoV2 itself despite repeated exposure.
-Rare variants were predicted to be loss-of-function (LOF) at 13 human loci known to govern +The major feature of the small set of variants in this track is that they are functionally tested +to be deleterious and genetically tested to be disease-causing. Specifically, +rare variants were predicted to be loss-of-function (LOF) at 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus in patients with life-threatening COVID-19 pneumonia, relative to subjects with asymptomatic or benign infection. These genetic defects display incomplete penetrance for influenza respiratory distress and only manifested clinically upon infection with the more virulent SARS-CoV-2.
Variant calls in 12 autosomal IFN-related genes from whole exome or genome data with a MAF lower than 0.001 (gnomAD v2.1.1) and experimental demonstration of loss-of-function (LOF) were considered for statistical analysis. Proportion of individuals carrying at least one pLOF variant was compared