The coevolution of species drives diversity in animals and plants and contributes to natural selection, whereas in host–parasite coevolution, a parasite may complete an incomplete evolutionary/developmental function by utilizing the host cell’s machinery. Analysis of related older data suggests that Plasmodium falciparum (P. falciparum), the pathogen of malaria tropica, cannot survive outside its human host because it is unable to perform the evolutionarily first protein glycosylation of serologically A-like, O-GalNAcα1-Ser/Thr-R, Tn antigen (“T nouvelle”) formation, owing to its inability for synthesizing the amino sugar N-acetyl-d-galactosamine (GalNAc). This parasite breaks the species barrier via hijacking the host's physiological A-like/Tn formation through abundantly expressing serine residues and creating hybrid A-like/Tn structures, which in the human blood group O(H) are attacked by the germline-encoded nonimmune polyreactive immunoglobulin M (IgM), exerting the highly anti-A/B/H-aggressive isoagglutinin activities. These activities physiologically undergo the ABO(H) blood group phenotype formation, occurring on the surfaces of red blood cells (RBC), epithelial and endothelial cells and on plasma proteins by identical glycosylation, performed by the ABO(H)-allelic glycotransferases, phenotypically downregulating the anti-A/B/H-reactive IgM (isoagglutinin) activities in the non-O blood groups. ABO(H) phenotype diversity, this way glycosidically linked and molecularly connected to humoral immunity, becomes exposed to the evolution.

While the angiotensin converting enzyme 2 (ACE2) protein is defined as the primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, the viral serine molecule might be mobilized by the host's transmembrane protease serine subtype 2 (TMPRSS2) enzyme from the viral spike (S) protein and hijack the host’s N-acetyl-D-galactosamine (GalNAc) metabolism. The resulting hybrid, serologically A-like/Tn (T-nouvelle) structure potentially acts as a host–pathogen functional molecular bridge. In humans, this intermediate structure will hypothetically be replaced by ABO(H) blood group-specific, mucin-type structures, in the case of infection hybrid epitopes, implicating the phenotypically glycosidic accommodation of plasma proteins. The virus may, by mimicking the synthetic pathways of the ABO(H) blood groups, bind to the cell surfaces of the blood group O(H) by formation of a hybrid H-type antigen as the potential precursor of hybrid non-O blood groups, which does not affect the highly anti-glycan aggressive anti-A and anti-B isoagglutinin activities, exerted by the germline-encoded nonimmune immunoglobulin M (IgM). In the non-O blood groups, which have developed from the H-type antigen, these IgM activities are downregulated by phenotypic glycosylation, while adaptive immunoglobulins might arise in response to the hybrid A and B blood group structures, bonds between autologous carbohydrates and foreign peptides, suggesting the exertion of autoreactivity. The non-O blood groups thus become a preferred target for the virus, whereas blood group O(H) individuals, lacking the A/B phenotype-determining enzymes and binding the virus alone by hybrid H-type antigen formation, have the least molecular contact with the virus and maintain the critical anti-A and anti-B isoagglutinin activities, exerted by the ancestral IgM, which is considered the humoral spearhead of innate immunity.