Indeed, the titers of natural antibodies and the IgG isotype (specific to the O blood group) may be determinants of susceptibility and severity. 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). In this case, the cornerstone is natural anti-A and anti-B antibodies from the ABO system. 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 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. 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. 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. 5Intensive Care Service, Hospital Universitario Sanchinarro, HM Hospitales, Madrid, Spain.4Pharmacological Big Data Laboratory, Pharmacology, Faculty of Medicine, University of Valladolid, Valladolid, Spain.3Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain. Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain 1Haematology and Hemotherapy Service, University Clinical Hospital, Valladolid, Spain.Álvaro Tamayo-Velasco 1,2,3 * María Jesús Peñarrubia-Ponce 1 Francisco Javier Álvarez 2,4 Ignacio de la Fuente 1 Sonia Pérez-González 1 David Andaluz-Ojeda 5
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