Badla, Beshr AbdulazizHanifa, Mohamed SamerAl Suwaidi, HananNowotny, NorbertPopatia, RizwanaAlsheikh-Ali, AlawiLoney, TomTayoun, Ahmad Abou2024-03-272024-03-272023204-2023.167https://repository.mbru.ac.ae/handle/1/1442Abstract: Studies of genetic factors associated with severe COVID-19 in young adults have been limited in non-Caucasian populations. Here, we clinically characterize a case series of patients with COVID19, who were otherwise healthy, young adults (N= 55; mean age 34.1 ±SD 5.0 years) from 16 Asian, Middle Eastern, and North African countries. Using whole exome sequencing, we identify rare, likely deleterious variants afecting 16 immune-related genes in 17 out of 55 patients (31%), including 7 patients (41% of all carriers or 12.7% of all patients) who harbored multiple such variants mainly in interferon and toll-like receptor genes. Protein network analysis as well as transcriptomic analysis of nasopharyngeal swabs from an independent COVID-19 cohort (N= 50; 42% Asians and 22% Arabs) revealed that most of the altered genes, as identifed by whole exome sequencing, and the associated molecular pathways were signifcantly altered in COVID-19 patients. Genetic variants tended to be associated with mortality, intensive care admission, and ventilation support. Our clinical cases series, genomic and transcriptomic fndings suggest a possible role for interferon pathway genes in severe COVID-19 and highlight the importance of extending genetic studies to diverse populations to better understand the human genetics of disease.enCOVID‑19YoungAsianMiddle EasternPatientsGenetic determinants of severe COVID 19 in young Asian and Middle Eastern patients: a case seriesArticle