Fig. 2.

Potential pathways of antibody-dependent enhancement of SARS-CoV-2 infection. SARS-CoV-2 is recognized by cross-reactive nonneutralizing antibodies obtained from previous infections with circulating human coronaviruses. Virus-antibody complexes bind to immune cells and initiate receptor-mediated signaling events, followed by endocytosis of the virus and subsequent activation of immune cells. The activated immune cells, notably inflammatory macrophages, accumulate in various organs and promote cytokine storm, tissue damage, and lymphopenia, which contribute to the development of more severe presentations of COVID-19. On the other hand, IL-6 and GM-CSF induce monocyte activation and differentiation to inflammatory macrophages. Furthermore, the formation and deposition of immune complexes in various organs can promote complement activation and subsequent tissue damage. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019.