Data for this review were identified by searches of PubMed, and preprint servers, and references from relevant articles using the search terms “COVID-19”, “Heparin”, “Non-anticoagulant functions of heparin”, “Low molecular weight heparin”, “ARDS”, “Kidney dysfunction”, “Endothelial barrier dysfunction”, “Heparanase”, “Heparan sulphate”, “Viral entry”, ”Heparanase inhibition”, “Inflammation”, “Complement system”, and “Neutrophil extracellular traps”. This evidence concerns the gene HPSE and COVID-19.