Given the accessibility of MTHFR screening and the implications of thrombosis in COVID-19 patients, our review aimed to collate the data pertaining to (1) the association between hereditary MTHFR mutations and COVID-19 severity and thromboembolic events and (2) the link between MTHFR variants and adverse thrombotic events following COVID-19 vaccination. This evidence concerns the gene MTHFR and COVID-19.