Theoretical Explanation for the Rarity of Antibody-Dependent Enhancement of Infection (ADE) in COVID-19

Global vaccination against the SARS-CoV-2 virus has proved to be highly effective. However, the possibility of antibody-dependent enhancement of infection (ADE) upon vaccination remains underinvestigated. Here, we aimed to theoretically determine conditions for the occurrence of ADE in COVID-19. We developed a series of mathematical models of antibody response: model Ab-a model of antibody formation; model Cv-a model of infection spread in the body; and a complete model, which combines the two others. The models describe experimental data on SARS-CoV and SARS-CoV-2 infections in humans and cell cultures, including viral load dynamics, seroconversion times and antibody concentration kinetics. The modelling revealed that a significant proportion of macrophages can become infected only if they bind antibodies with high probability. Thus, a high probability of macrophage infection and a sufficient amount of pre-existing antibodies are necessary for the development of ADE in SARS-CoV-2 infection. However, from the point of view of the dynamics of pneumocyte infection, the two cases where the body has a high concentration of preexisting antibodies and a high probability of macrophage infection and where there is a low concentration of antibodies in the body and no macrophage infection are indistinguishable. This conclusion could explain the lack of confirmed ADE cases for COVID-19.