The COVID-19 pandemic presents a significant challenge to the global health and the world economy, with humanity engaged in an extended struggle against the virus. Notable advancements have been achieved in the development of vaccines and therapeutic interventions, including the application of neutralizing antibodies (NAbs) and convalescent plasma (CP). While antibody-dependent enhancement (ADE) has not been observed in human clinical studies related to SARS-CoV-2, the potential for ADE remains a critical concern and challenge in addressing SARS-CoV-2 infections. Moreover, the causal relationship between ADE and viral characteristics remains to be clearly elucidated. Viruses that present with severe clinical manifestations of ADE have demonstrated the capacity to replicate in macrophages or other immune cells, or to alter the immunological status of these cells, which induces abortive infections characterized by systemic inflammation. In this review, we summarize experimental observations and clinical evidence concerning the ADE effect associated with coronaviruses. We critically examine the potential mechanisms through which coronaviruses mediate ADE, and propose strategies to mitigate this phenomenon in the context of viral infection treatment. Our aim is to offer informed recommendations for the containment of the COVID-19 pandemic and to strengthen the response to SARS-CoV-2, as well as to prepare for potential future coronavirus threats.© The author(s).