Hence, the protection conferred by the HLA-A*02:01, B*18:01, DRB1*03:01 three-loci extended haplotype against severe SARS-Cov-2 in the Sardinian population seems to efficiently contrast the high risk of a severe and devastating clinical course of the infection predicted for carriers of the Neanderthal haplotype. This evidence concerns the gene HLA-DRB1 and COVID-19.