Studies of genetic factors associated with severe COVID-19 in young adults have been limited in non-Caucasian populations. Here, we use whole exome sequencing to characterize the genetic landscape of severe COVID-19 in a well phenotyped cohort of otherwise healthy, young adults (N=55; mean age 34.1 ± SD 5.0 years) representing 16 countries in Asia, the Middle East, and North Africa. Our findings show enrichment of rare, likely deleterious missense and truncating variants in interferon-mediated and bacterial infection-susceptibility genes, when compared to control, mildly affected, or asymptomatic COVID-19 patients (N = 25), or to general populations representing Asia and the Middle East. Genetic variants tended to associate with mortality, intensive care admission, and ventilation support. Our findings confirm the association of interferon pathway genes with severe COVID-19 and highlight the importance of extending genetic studies to diverse populations given implications for pan-ethnic therapeutic and genetic screening options.

No abstract

No abstract