ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points

Abstract

The implication of the ABO blood group in COVID-19 disease was formulated early, at the beginning of the COVID-19 pandemic more than 2 years ago. It has now been established that the A blood group is associated with more susceptibility and severe symptoms of COVID-19, while the O blood group shows protection against viral infection. In this review, we summarize the underlying pathophysiology of ABO blood groups and COVID-19 to explain the molecular aspects behind the protective mechanism in the O blood group. A or B antigens are not associated with a different risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than that of other antigens. In this case, the cornerstone is natural anti-A and anti-B antibodies from the ABO system. They are capable of interfering with the S protein (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2; host cell receptor), thereby conferring protection to patients with sufficient antibodies (O blood group). Indeed, the titers of natural antibodies and the IgG isotype (specific to the O blood group) may be determinants of susceptibility and severity. Moreover, older adults are associated with a higher risk of bad outcomes due to the lack of antibodies and the upregulation of ACE2 expression during senescence. A better understanding of the role of the molecular mechanism of ABO blood groups in COVID-19 facilitates better prognostic stratification of the disease. Furthermore, it could represent an opportunity for new therapeutic strategies.

Keywords: ABO blood group; ACE2 (angiotensin converting enzyme 2); COVID-19; SARS-CoV-2 spike protein; anti-A antibody.

Figure 1

Molecular mechanism that explains the susceptibility and severity of COVID-19 disease depending on the ABO blood group. The presence of anti-A antibodies and probably anti-B antibodies inhibit the interaction between the S protein of the virus and the ACE2 on the cell surface in the O blood group (Left side). The absence of antibodies in the A blood group facilitates the entrance of SARS-CoV-2 into the host cell and the consequent viral infection (Right side). ACE2: angiotensin-converting enzyme 2. TMPRSS2: transmembrane protease serine subfamily member DC/L-SIGN; dendritic-cell-specific ICAM3-grabbing nonintegrin.; Natural antibodies bind glycosylated or carbohydrate epitopes in the S protein of SARS-CoV-2 (on top) or ACE2 (below).

Figure 2

Specific isotype of immunoglobulin in each ABO blood group, expression of natural antibodies and receptors in immunosuppressive situations, and their relationship with the infectious capacity of SARS-CoV-2. Ab: antibody. Rc: receptor. Ig: immunoglobulin. ACE2: angiotensin-converting enzyme 2. TMPRSS2: transmembrane protease serine subfamily member. N; normal expression.