However, in rare cases, pathogen-specific antibodies can augment virulence in a process termed ‘antibody-dependent enhancement’ (ADE) (Fig. 2). ADE can occur via two distinct mechanisms. First, pathogen-specific antibodies could increase infection by promoting virus uptake and replication in Fcγ receptor-expressing immune cells (for example, as is seen in dengue haemorrhagic virus infection of macrophages). With SARS-CoV and SARS-CoV-2 (ref.20), in vitro evidence amassed to date indicate that these non-lymphotropic coronaviruses are unable to productively replicate within haematopoietic cells21. Alternatively, ADE can be mediated via increased immune activation by Fc-mediated effector functions or immune complex formation22. In the case of respiratory virus infections, the resulting immune cascade can contribute to lung disease. While the hallmarks of severe COVID-19 have features that overlap with this type of ADE, there is currently no definitive evidence to show ADE occurs with SARS-CoV-2 infection22.