Antibody-Dependent Enhancement and the Critical Pattern of COVID-19: Possibilities and Considerations

Coronavirus disease 2019 (COVID-19), a pandemic infection with profound effects on human society, has challenged our ability to control viral infections. Although at the beginning of the COVID-19 outbreak, the epidemic seemed controllable in Southern Iran, the disease presented a critical pattern as of May 2020. After a few months of the emergence of COVID-19, its severity and mortality increased dramatically. It has been proposed that antibodies produced during previous exposure to local circulating human coronaviruses or possibly severe acute respiratory syndrome coronavirus 2 might contribute to the development of more severe and lethal presentations of COVID-19 possibly by triggering antibody-dependent enhancement. The binding of virions complexed with antibodies to Fcγ receptors on the target cells initiates receptor-mediated signaling events, leading to enhanced expression of inflammatory cytokines and suppression of intracellular antiviral responses at the transcriptome level, followed by endocytosis of the virus and subsequent activation of immune cells. The activated immune cells might accumulate in the lung and promote cytokine storm and lymphopenia. Furthermore, the formation of immune complexes can promote complement activation and subsequent tissue damage. Although there are currently no clinical data to support this hypothesis, a better understanding of these immunopathologic phenomena and their relation to the disease course and severity might give insights into the development of the most efficient prophylactic and therapeutic approaches. This review demonstrates the critical pattern of COVID-19 in Southern Iran and highlights the possible interplay of factors leading to this condition.