Antibody Dependent Enhancement in COVID-19
Non-neutralizing but cross-reactive antibodies may lead to ADE and hence enhance the immunopathological state. ADE can occur through various pathways, the most important among which include endocytosis of antibody conjugated virus by the phagocytic cells (via Fc gamma receptor IIa (FcγRIIa) and enhanced antibody immune complex formation (Kulkarni, 2020). Virus uptake by the phagocytic cells induces robust propagation and hence may further aggravate the disease condition, while antibody immune complex formation may generate a high pro-inflammatory response. Experience from previous viral infections has shown that ADE may lead to worse disease outcome in some patients with the presence of non-neutralizing antibodies, reviewed by Lee W.S. et al. (2020). In vitro studies on monocytes and macrophages have shown ADE in SARS-CoV (Flipse et al., 2016). However, no definitive clinical data is available that indicates the occurrence of ADE during SARS-CoV or SARS-CoV-2 infection. Nevertheless, based on the substantial cross-reactivity between various epitope regions of CoVs, some patients may exhibit ADE due to the presence of cross-reactive but non-neutralizing antibodies from previous infections.