The results reported here seem to show that the DHF folic acid metabolite has a high affinity to bind to the ACE2 receptor, and that when DHF acts as a ligand, the RBD of the Wild type SARS-CoV-2 might not form a stable, low-energy complex with the ACE2 receptor and therefore cannot initiate infection of a host cell. However, the RBD for the Beta and Delta variants can form a high affinity complex with the ACE2 receptor, even when the DHF acts as a ligand. Therefore, this folic acid metabolite cannot prevent infection from these SARS-CoV-2 variants, which could explain the almost double increase in severe cases of COVID-19 due to the delta variant in pregnant women.