Although leflunomide has been previously associated with increased risk of infection requiring hospitalization after adjustment for important confounders [32], it has provided some beneficials actions beyond rheumatic diseases [33], such as anti-viral properties both in vitro and in vivo, including patients with COVID-19 [34–39], through inhibitor action against the dihydroorotate dehydrogenase (DHODH). This evidence concerns the gene DHODH and rheumatic disorder.