Why Blood Group A Individuals Are at Risk Whereas Blood Group O Individuals Might Be Protected from SARS-CoV-2 (COVID-19) Infection: A Hypothesis Regarding How the Virus Invades the Human Body via Abo(H) Blood Group-Determining Carbohydrates

Abstract

Although the angiotensin-converting-enzyme 2 (ACE2) is defined as the primary SARS-CoV receptor, it is the history of the amino acid serine, suggesting the actual or additional binding via an intermediate hybrid O-glycan: the protease-mobilized, virus-encoded serine molecule may get access to the host's N-acetyl-D-galactosamine (GalNAc) metabolism and the resulting intermediate, hybrid A-like/Tn structure performs the adhesion of the virus to host cells primarily independent from the ABO(H) blood group. In humans, this genetically undefined structure may be replaced by blood group ABO(H)-specific, mucin-type hybrid epitopes. While the phenotype formation occurs in evolutionary connection with humoral innate immunity, in the blood group O(H), hybrid epitopes become exposed to the highly anti-glycan-aggressive ABO(H) isoagglutinin activities, exerted by the ancestral, nonimmune immunoglobulin M (IgM). In the non-O blood groups these IgM activities are downregulated by phenotypic glycosylation and the formation of adaptive IgG is excluded by clonal selection. The non-O blood groups thus become a preferred target for the virus, whereas blood group O(H) individuals, lacking the AB phenotype-determining 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.

Anti‐A and SARS‐CoV‐2: an intriguing association

“…This finding is similar to previous studies that reported ABO blood group association with SARS-CoV in 2003 [11] and with SARS-CoV-2, in 2020 [4,17,18]. One possible mechanism is that blood types A and B have sugars crucial to the O-glycosidic target, functioning as a possible site for binding the virus to the host [19].…”

“…Bold indicates statistical significant values (P < 0Á05). [ 12,19]. Genetic research also has increased in this area.…”

A longitudinal study of convalescent plasma (CCP) donors and correlation of ABO group, initial neutralizing antibodies (nAb), and body mass index (BMI) with nAb and anti‐nucleocapsid (NP) SARS‐CoV‐2 antibody kinetics: Proposals for better quality of CCP collections

“…Arend 60 recently proposed a different model for invasion, initially independent of the ABO group, via the formation of a hybrid A-like/Tn (T-nouvelle) structure (different from the specific blood group A epitope), acting as a functional bridge between the spike protein and host mobilization (via TMPRSS2), allowing viral invasion into the host's cell (initial invasion could be present both in group O and non-O individuals, via the host's GalNac metabolism pathway). After invasion, SARS-CoV-2 newly formed virions from group O individuals replace this initial pathway by mucin-type fucosylation and synthesis of hybrid H-type antigen, unaffected by innate anti-A/Tn or anti-B/Tn isoagglutinins, with a secondary IgG response and reduced viral binding because it happens only via the hybrid-H-type antigen since anti-A or -B/Tn isoagglutinins are preserved, explaining the protector effect on group O individuals.…”