Though more and more is being learned about COVID-19, important questions remain. Chief amongst these is why some people with COVID-19 develop life-threatening critical illness, while others get by with few symptoms at all. While some risk factors have been identified on the basis of epidemiological studies– including age, sex, and pre-existing conditions – much variability remains unexplained. Previous studies have shown that the likelihood of developing critical illness from an infection is in part determined by our genetic makeup. Understanding the extent to which our genes determine infection outcome, as well as the specific genes involved in this process, stands to greatly enhance our understanding of COVID-19, and suggest new strategies in the development of novel therapeutics, vaccines, and public health interventions. The Genomics of Mortality in Critical Care (GenOMICC) study is a multi-national endeavour that seeks to expand our understanding of how human genetics affect the progression of COVID-19. We will analyze the genomes of patients admitted to the intensive care unit (ICU) with COVID-19, and compare these with healthy population controls. Using advanced computational analysis, we will be able to look at hundreds of thousands of subtle genetic variations across the population, to determine which of these are associated with outcomes. This analysis requires a very large cohort; by joining forces with international collaborators we will be able to achieve actionable results faster. The genetic variations identified will provide invaluable insights, and lead to new strategies that will accelerate our efforts in the fight against COVD-19.