<b>How evolution of blood group A is associated with reduced innate immunity and duplicates the host’s exposure to pathogens, as suggested by SARS-CoV-2 (COVID-19) infection.</b>

Although the ABO(H) blood group phenotypes of humans and great apes have evolved from a common ancestor that is thought to be blood group A, each phenotype has gone through its own unique enzymatic pathways and life history. After host-SARS-CoV-2 contact, a terminal serine of the viral spike protein gains access to host GalNAc pathways, leading to intermittent, hybrid GalNAc1α-<i>O-</i>Ser Tn T-"nouvelle") antigen formation, catalyzed by a host developmental UDP-GalNAc transferase and initiating SARS-CoV-2 (COVID 19) infection. In blood group A, the additional formation of a hybrid mucin type epitope A, catalyzed by the A-allelic transferase, doubles the host's exposure to pathogens through two genetically distinct bindings, neutralizing the innate anti-Tn/A reactivities of pre-existing poly-reactive IgM. This physiological protection against phenotypic autoimmunity and the formation of hybrid autoimmunity implies a reduction in innate immunity, which explain the increased susceptibility and severity of disease in blood group A individuals.<br>