How blood group A might be a risk and blood group O be protected from coronavirus (COVID-19) infections (how the virus invades the human body via ABO(H) blood group carbohydrates).

When according to the numbers of Wikipedia (although they are disputed) in countries like Chile, Ecuador, Colombia, Simbabwe and Mexico 59 to 85 percent of the people have blood group O and these countries officially publish extremely low COVID-19 cases and death rates per 1 million inhabitants, this may not alone result from insufficient investigations but might suggest a lower susceptibility of blood group O to the disease. 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 <i>O</i>-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 currently again predicted for SARS-CoV-2 or COVID-19, this would involve the formation of hybrid, serologically A-like, <i>O</i>-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 <i>O</i>-glycan: the <em>TMPRSS2 host protease</em>-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 cannot respond with either acquired or innate antibodies to the synthesis of A-like hybrid structures due to clonal selection and phenotypic accommodation of plasma proteins but perform a further (blood group-A-specific) hybrid binding. 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. <i>et al., </i>2020). While these findings await confirmations, blood group O individuals, lacking the blood group-A-determining enzyme, may develop the least molecular contact with the virus and maintain the anti-A/Tn cross-reactive, complement-dependent isoagglutinin activity, which is exerted by the polyreactive, nonimmune immunoglobulin M (IgM), representing the humoral spearhead of innate immunity and a first line of defense.<b>Reference</b>: Zhao, J. <i>et al.</i> Relationship between the ABO Blood Group and the COVID-19 Susceptibility. <i>medRxiv</i> (2020) doi:10.1101/2020.03.11.20031096.<br>