<b>How blood group A evolution involves reduced innate immunity and doubles the host's exposure to pathogens, as suggested by SARS-CoV-2 (COVID-19) infection. </b>— <b><i>Brief communication</i></b><b><i> </i></b><i>—</i>

While the ABO(H) blood group phenotypes of humans and great apes evolved from a common ancestor considered to be blood group A, each phenotype has undergone its own distinct enzymatic pathways and life history. After host-pathogen contact, a terminal serine of the viral spike protein gains access to host GalNAc pathways, leading to intermittent, hybrid Gal-NAc1α-O-Ser Tn T-"nouvelle") antigen formation catalyzed by a host 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 A-allelic transferase, then doubles the host's exposure to pathogens through two genetically distinct bindings, neutralising the innate anti-Tn/A reactivities of pre-existing poly-reactive IgM. This physiological protection against phenotypic autoimmunity and, in the event of infection, the formation of hybrid autoimmunity, implies a reduction in innate immunity and a doubling of pathogen exposure, explaining the increased susceptibility and severity of disease in blood group A.<br><br>