The influence of ABO blood groups on COVID-19 susceptibility and severity: A molecular hypothesis based on carbohydrate-carbohydrate interactions

Abstract

The world is experiencing one of the most difficult moments in history with the COVID-19 pandemic, a disease caused by SARS-CoV-2, a new type of coronavirus. Virus infectivity is mediated by the binding of Spike transmembrane glycoprotein to specific protein receptors present on cell host surface. Spike is a homotrimer that emerges from the virion, each monomer containing two subunits named S1 and S2, which are related to cell recognition and membrane fusion, respectively. S1 is subdivided in domains S1A (or NTD) and S1B (or RBD), with experimental and in silico studies suggesting that the former binds to sialic acid-containing glycoproteins, such as CD147, whereas the latter binds to ACE2 receptor. Recent findings indicate that the ABO blood system modulates susceptibility and progression of infection, with type-A individuals being more susceptible to infection and/or manifestation of a severe condition. Seeking to understand the molecular mechanisms underlying this susceptibility, we carried out an extensive bibliographic survey on the subject. Based on this survey, we hypothesize that the correlation between the ABO blood system and susceptibility to SARS-CoV-2 infection can be presumably explained by the modulation of sialic acid-containing receptors distribution on host cell surface induced by ABO antigens through carbohydrate-carbohydrate interactions, which could maximize or minimize the virus Spike protein binding to the host cell. This model could explain previous sparse observations on the molecular mechanism of infection and can direct future research to better understand of COVID-19 pathophysiology.

Association between ABO blood groups and susceptibility to COVID-19: profile of age and gender in Iraqi patients

“…Although some inconsistent results have been reported, most studies agree that ABO blood groups are of particular significance with regard to their association with susceptibility to COVID-19, but the molecular mechanism underlying this association has not been well described. It has been hypothesized that the blood group impact on susceptibility to COVID-19 may depend on a differential clustering of the virus glycoprotein receptors on host cell surface, induced by ABO(H) determinants through interactions (carbohydrate-carbohydrate) with the glycan motif of these receptors, and this may interfere with the binding of virus and its entrance to target cells [40]. The carbohydrate structures of ABO(H) blood groups are not restricted to the surface of red blood cells, and other cells and tissues express these structures; for instance, lymphocytes, endothelial cells, platelets, gastric mucosa and bone marrow.…”

“…Similar to COVID-19, group A has been associated with severe malaria, while individuals with group O are less susceptible to the infection. Further, group A individuals are more likely to have debilitated aging than those of group O [40].…”

The Impact of ABO Blood Grouping on COVID-19 Vulnerability and Seriousness: A Retrospective Cross-Sectional Controlled Study among the Arab Community

“…For example, blood types A and AB predispose subjects to aggravated malaria, while type O causes resistance to several protozoal infections. Furthermore, this blood grouping system exhibit direct or indirect association with some cardiovascular conditions [10]. Recently, Groot et al reported that people with A, B, and AB blood types are more susceptible to thrombosis and myocardial infarction, while those bearing the O blood group are more prone to hypertension [11].…”

Transcriptomic Analysis of Respiratory Tissue and Cell Line Models to Examine Glycosylation Machinery during SARS-CoV-2 Infection

“…This enticed the attention of researchers in devising therapeutic strategies to curtail the virus infection [ 41 , 64 ]. Additionally, it has also been reported that infectious SARS virions harness host histo-blood group antigens on S proteins [ 65 ], which might presumably modulate the interaction with host cell glycoprotein receptors through carbohydrate–carbohydrate interactions [ 66 ]. The current transcriptomic based research analysis is aimed to generate a hypothetical view of the alteration in glycan machinery, which could be used to explain the relevance of glycosylation underlying the lung pathology and immune responses reported in COVID-19 subjects.…”