Increased enzymatic activity of ERAP1 and ERAP2 as selected for by the Black Death appears to have led to a hyperinflammatory response and self-reactivity (Klunk et al. 2022; Raja and Kuiper 2023); while reduced enzymatic activity of ERAP1 and ERAP2 has been implicated in hypoinflammation that hampers the immune response to infection, results in a reduction in pathogen clearance and activation of chronic inflammatory pathways (Yao et al. 2019). This evidence concerns the gene ERAP1 and infection.