Our findings of a genetic correlation of soluble ACE2 and additional evidence that genetically determined soluble ACE2 is associated with increased risk of COVID-19 severity are consistent with recent in vitro data that the secreted form of ACE2 plays a direct role in cell entry of SARS-CoV-2 through receptor-mediated endocytosis.50 Our results are also consistent with human genetic studies indicating that genetic variation in soluble ACE2 influences COVID-19 risk.42,51. This evidence concerns the gene ACE2 and COVID-19.