Facing the potential risk of recombination between SARS-CoV-2 variants and the ACE2-dependent MERS-related coronaviruses, we would like to investigate the serological cross-reactivity induced by COVID-19 vaccination or SARS-CoV-2 breakthrough infection against MERS-CoV and its two related ACE2-dependent coronaviruses, NeoCoV and PDF-2180 (Figure 1A). Here, ACE2 is linked to infection.