In the case that O-glycosylation plays a key role in the pathogenesis of coronavirus disease, as was discussed in a previous SARS-CoV infection and is predicted for the current SARS-CoV-2 or COVID-19, this would involve the formation of hybrid, serologically A-like, O-N-acetyl-d-galactosamine (GalNAc)α1-Ser/Thr-R, Tn (“T nouvelle”) structures. Although the angiotensin-converting-enzyme 2 (ACE2) protein, mediating the transferring enzymes, is defined as the primary SARSCoV receptor, the actual and/or additional binding between host and pathogen appears to occur via such an intermediate hybrid O-glycan, which is dominated by the pathogen’s hydrophile amino acid serine. The ABO(H) phenotype formation occurs on both the cell surfaces and plasma proteins in a molecular connection with humoral innate immunity, and in the blood group O(H) a pathogen becomes exposed to the highly anti-glycan-aggressive ABO(H) isoagglutinin activities, exerted by the ancestral, non-immune immunoglobulin M (IgM). In the non-O blood groups these activities are down-regulated by phenotypic glycosylation. These blood groups thus become a preferred target for the virus, whereas blood group O(H) individuals, lacking the AB phenotypedetermining enzymes, have the least molecular contact with the pathogen; they maintain the isoagglutinins and the power of ancestral IgM, considered the humoral spearhead of innate immunity.