Neutralizing Antibodies and Antibody-Dependent Enhancement in COVID-19: A Perspective

Antibody-dependent enhancement (ADE) is an alternative route of viral entry in the susceptible host cell. In this process, antiviral antibodies enhance the entry access of virus in the cells via interaction with the complement or Fc receptors leading to the worsening of infection. SARS-CoV-2 variants pose a general concern for the efficacy of neutralizing antibodies that may fail to neutralize infection, raising the possibility of a more severe form of COVID-19. Data from various studies on respiratory viruses raise the speculation that antibodies elicited against SARS-CoV-2 and during COVID-19 recovery could potentially exacerbate the infection through ADE at sub-neutralizing concentrations; this may contribute to disease pathogenesis. It is, therefore, of utmost importance to study the effectiveness of the anti-SARS-CoV-2 antibodies in COVID-19-infected subjects. Theoretically, ADE remains a general concern for the efficacy of antibodies elicited during infection, most notably in convalescent plasma therapy and in response to vaccines where it could be counterproductive.