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

Peter Arend
2020 figshare.com  
Infection does not mean disease because for uncountable reasons the invasion of a pathogen does not always lead to disease symptoms. The molecular biology of a virus infection pathogenesis determines the genetic target and the human phenotype-determining enzymes decide about the difference between infection and disease. In the case that O-glycosylation plays a key role in the pathogenesis of coronavirus infections, as was discussed already 14 years ago in a SARS-CoV virus infection and is
more » ... tly again predicted for SARS-CoV-2 or COVID-19, this would involve the formation of hybrid, serologically A-like, O-GalNAcα1-Ser/Thr-R, Tn ("T nouvelle") antigenic structures. Although the ACE2 (angiotensin-converting-enzyme 2) protein 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 TMPRSS2 (transmembrane protease serine subtype 2) host protease-mobilized, virus-encoded serine molecule gets 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 of the ABO blood group, while the phenotype-determining sugars become the final glycosidic target. Individuals with blood group A and B cannot respond with preformed innate antibodies to the synthesis of A-like/Tn structures due to phenotypic accommodation of plasma proteins but perform a further (blood group-A- and/or B-specific) hybrid binding, most likely causing autoimmune reactions. A first statistical study suggests that people with blood group A have a significantly higher risk for acquiring COVID-19, whereas people with blood group O have a significantly lower risk for the infection compared with non-O blood groups (Zhao, J. et al., 2020). SARS-Cov-2 (COVID-19) infections may be considered an evolutionary selective disease, contributing to the present-day world distribution of the huma [...]
doi:10.6084/m9.figshare.12019035.v210 fatcat:aamtg4htgjaahj6crfmrvc54fy