Need Help?
Copied to clipboard!

​​Rare Genetic Variants and Severe COVID-19 in Previously Healthy Admixed Latin American Adults​

This study investigates the contribution of rare genetic variants to the progression of severe COVID-19 in young and middle-aged adults without pre-existing health conditions. The cohort included 161 Brazilian patients aged 18 to 60 years who were hospitalized in intensive care units due to life-threatening SARS-CoV-2 infection. Whole-genome sequencing (WGS) was performed to detect rare variants, followed by a targeted prioritization of loci previously linked to severe COVID-19 outcomes. The analysis identified 104 rare and potentially deleterious variants across 79 genes, with ultra-rare alterations most frequently observed in MUC5AC, IFNA10, ZNF778, and PTOV1. Seventeen novel variants were discovered, several predicted to be pathogenic or indicating strong intolerance to loss-of-function (LoF) mutations. Clinically, carriers of prioritized rare variants showed an increased incidence of acute respiratory distress syndrome (ARDS) (p = 0.027, OR = 2.59), and those with variants in highly LoF-intolerant genes had a fourfold higher mortality risk (p = 0.0084, OR = 4.04).

This represents the first comprehensive genomic analysis of severe COVID-19 in a previously healthy Latin American population, emphasizing the relevance of identifying population-specific rare variants associated with disease severity.