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The varied clinical manifestations and outcomes in patients with SARS-CoV-2 infections implicate a role of host-genetics in the predisposition to disease severity. This role is supported by evidence that is now emerging, where initial reports identify common risk factors and rare genetic variants associated with high risk for severe/life-threatening COVID-19. We investigated the host genomes of individuals with severe/life-threatening COVID-19 at the structural variant level (500 bp – Mbps) to identify events that might provide insight into the inter-individual variability in clinical course and outcomes associated with SARS-CoV-2 infections and COVID-19 mortality.