Presumably, the reduced antiviral defense due to the absence of KIR3DL1+HLA-Bw4+ and KIR3DL2+HLA-A3/11+ interactions coupled with exuberant hyperinflammatory response mediated by activating KIR2DS1 and 2DS5 arbitrate the development of severe COVID-19. This evidence concerns the gene KIR3DL1 and COVID-19.