Dengue Fever, COVID-19 (SARS-CoV-2), and Antibody-Dependent Enhancement (ADE): A Perspective

Abstract

SARS-CoV-2 pandemic and recurrent dengue epidemics in tropical countries have turned into a global health threat. While both virus-caused infections may only reveal light symptoms, they can also cause severe diseases. Here, we review the possible antibody-dependent enhancement (ADE) occurrence, known for dengue infections, when there is a second infection with a different virus strain. Consequently, preexisting antibodies do not neutralize infection, but enhance it, possibly by triggering Fcγ receptor-mediated virus uptake. No clinical data exist indicating such mechanism for SARS-CoV-2, but previous coronavirus infections or infection of SARS-CoV-2 convalescent with different SARS-CoV-2 strains could promote ADE, as experimentally shown for antibodies against the MERS-CoV or SARS-CoV spike S protein. © 2020 International Society for Advancement of Cytometry.

Keywords: 2019-nCoV; COVID-19; SARS-CoV-2; antibody-dependent enhancement; coronavirus.

Figure 1

Potential pathways of aggravation of SARS‐CoV‐2 infection by ADE. Initially, the spike protein of SARS‐CoV‐2 binds through the RBD to angiotensin‐converting enzyme 2 (ACE2) on the host cell surface for virus invasion. After some days, humoral responses develop against the virus, eliminating infection through allosteric and neutralizing antibodies (NAbs). After a second infection with the same SARS‐CoV‐2 strain virus destruction may occur, if the NAb titer is high enough. However, in case of a low NAb titer, ADE may be observed following binding of the SARS‐CoV‐2/antibody complex to ACE2, internalization of the complex and IgG induced stimulation. In addition, immunized patients may be re‐infected with a different SARS‐CoV‐2 strain, such as a RBD‐mutated strain. In this context, already existing Abs could bind with reduced affinity to mutated RBD, inducing low levels of SARS‐CoV‐2/antibody complexes, following by internalization through the ACE2 receptor and ADE . On the other hand, immunized patients re‐infected by an RBD‐mutated strain may present sufficient Ab blockade of the heterotypic SARS‐CoV‐2 strain. In this case, SARS‐CoV‐2 covered by Abs may connect to Fcγ receptors II (FcγRII) on the surface of B cells or other professional antigen‐presenting cells (APCs). This receptor mediates SARS‐CoV‐2 invasion into immune cells, further spreading viral infection into all organs and ADE. [Color figure can be viewed at wileyonlinelibrary.com]