Relevance of Antibody-Dependent Enhancement in COVID-19

Antibody-dependent enhancement (ADE) is a well-established mechanism of pathology in several viral diseases, but its relevance in COVID-19 is not yet recognized. Although several studies in humans have shown an association between antibody responses and disease severity, long term studies addressing the presence of antibodies before infection and their neutralization capacity are needed to establish ADE. Mechanistic studies have determined that the entry of SARS-CoV-2 into host cells can be mediated by immune complexes through Fcγ receptors or by favoring ACE2 conformation. However, the impact on viral replication is not clear. There is evidence for enhancing effects of immune complexes on Fcγ receptor-mediated effector mechanisms and cytokine secretion after modulation of cell signaling in immune cells, specially by antibodies with altered glycosylation, which points to ADE that can contribute to COVID-19 pathology. However, more studies are needed to determine the impact of antibodies both in naturally infected and vaccinated subjects, which can lead to their use as a prognostic marker and increase vaccine safety.