Here, in-depth analysis of the HLA and KIR genotypes and their interaction system in Chinese COVID-19 patients with different clinical presentations supports the notion that in addition to T-cell-mediated immunity, NK cell-mediated immune defense also plays a critical role in the anti-SARS-CoV-2 response, at least in an Asian population with a high number of detrimental HLA class I alleles in binding coronavirus peptides but with enhanced NK cell repertoires. This evidence concerns the gene KIR3DL1 and COVID-19.