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. The gene discussed is HLA-A; the disease is COVID-19.