Given these parallel findings, we aimed to evaluate the synergistic impact of KIR motifs, Neanderthal-inherited OAS1/2/3 variants, and other immune-related SNPs on COVID-19 symptomatology and severity.<h4>Methods</h4>In a cohort of 175 unvaccinated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals (65 asymptomatic, 47 mild-intermediate, 63 severe), we genotyped KIR/KIR-ligand motifs and variants in OAS1/2/3, IFITM3, DPP4, TLR7, and APOE. This evidence concerns the gene APOE and COVID-19.