Given the key role of HLA-C molecules in antigen presentation to KIR receptors on NK cells, HLA-C*04:01 molecules with (i) a poor affinity to the SARS-CoV-2 peptides (26), (ii) a low cell surface expression ability [due to bearing HLA-C 3UTR’ target site that miR-148a binds (51)], (iii) and differential avidity to its cognate receptors (i.e. high for the inhibiting KIR (KIR2DL1) than the activating KIR [functional KIR2DS4 (52)], may cause NK cell hyporesponsiveness since the early phase of infection (49). The gene discussed is KIR2DS4; the disease is infection.