This study investigated the influence of single nucleotide polymorphisms (SNPs) in genes associated with the interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) on COVID-19 severity and their association with nonalcoholic fatty liver disease (MAFLD). This evidence concerns the gene OAS1 and metabolic dysfunction-associated steatotic liver disease.